Impact of Second-line Combination Chemotherapy on Post-progression Survival in Metastatic and Recurrent Pancreatic Cancer

Impact of Second-line Combination Chemotherapy on Post-progression Survival in Metastatic and Recurrent Pancreatic Cancer | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Impact of Second-line Combination Chemotherapy on Post-progression Survival in Metastatic and Recurrent Pancreatic Cancer Takafumi Mie, Masato Ozaka, Takeshi Okamoto, Tsuyoshi Takeda, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5965079/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 11 Jun, 2025 Read the published version in International Journal of Clinical Oncology → Version 1 posted 5 You are reading this latest preprint version Abstract Background: This study aimed to evaluate the efficacy of the second-line combination chemotherapy (CC) for patients with metastatic or recurrent pancreatic cancer. Methods: We retrospectively analyzed consecutive patients with metastatic or recurrent pancreatic cancer, who received second-line chemotherapy after disease progression on first-line modified FOLFIRINOX (mFFX) or gemcitabine with nab-paclitaxel (GnP) between January 2014 and March 2023 at our hospital. Overall survival (OS), progression free survival (PFS), and post-progression survival (PPS) were compared between first-line mFFX and GnP. Additionally, OS, PFS, and PPS for second-line treatment with CC and single-agent chemotherapy (SAC) were compared using propensity score matching (PSM). Results: A total of 457 patients (mFFX / GnP: 122 / 335) were included. Median OS and PPS of mFFX and GnP were 15.5 months vs. 15.0 months (p = 0.73) and 7.7 months vs. 7.2 months (p = 0.37), respectively. After PSM, median OS and median PPS were significantly longer in the CC group than in the SAC group (OS: 16.3 months vs. 12.8 months, p < 0.01; PPS: 8.0 months vs. 5.5 months, p < 0.01). There was no difference in first-line PFS between the two groups (7.1 months vs. 6.4 months, p = 0.74). Performance status at the beginning of first-line treatment, and carbohydrate antigen 19-9 level, Glasgow prognostic score at the end of first-line treatment, and second-line CC were independently associated with OS. Conclusion: Second-line CC achieved longer PPS and OS than SAC. To improve OS, it was important to receive second-line CC. pancreatic cancer chemotherapy post-progression survival FOLFIRINOX gemcitabine with nab-paclitaxel Figures Figure 1 Figure 2 Figure 3 Introduction Pancreatic cancer (PC) is one of the cancers with the poorest prognoses, and approximately 80% of patients are diagnosed with unresectable PC (URPC) [1]. Chemotherapy is the standard of care for patients with URPC, and gemcitabine with nab-paclitaxel (GnP) and modified FOLFIRINOX (mFFX) are most commonly used as first-line treatment [2-4]. We previously reported that there was no difference in overall survival (OS) and progression-free survival (PFS) between GnP and mFFX [5]. The efficacy of S-IROX (S-1, irinotecan and oxaliplatin combination therapy) was reported from Japan, and S-IROX was expected as first-line treatment option alternative to GnP or mFFX [6]. Recently, the phase II/III trial was conducted to compare the OS between GnP, mFFX and S-IROX as first-line treatment for patients with metastatic and recurrent PC, and mFFX and S-IROX failed to demonstrate superiority over GnP [7]. While there was no difference in PFS between the three regimens, post-progression survival (PPS) tended to be longer with GnP than with mFFX or S-IROX. While a correlation between PPS and OS has been proposed [8], reports on PPS and efficacy of second-line treatment in patients with URPC are limited. First-line gemcitabine-based chemotherapy is generally followed by 5-fluorouracil (5-FU)-based chemotherapy, and vice versa. It remains unclear whether single-agent chemotherapy (SAC) or combination chemotherapy (CC) is more effective as second-line treatment after GnP or mFFX. Therefore, we conducted a retrospective study to evaluate PPS after first-line GnP or mFFX in the real-world setting. Patients and methods Patients We retrospectively analyzed consecutive patients with metastatic or recurrent PC registered on our prospectively registered database. Those treated with GnP or mFFX as first-line treatment between January 2014 and March 2023 at our institution and received second-line chemotherapy after disease progression were included. Patients with recurrent PC were excluded if recurrence occurred during or within six months after completion of adjuvant chemotherapy. This study was conducted in accordance with the Declaration of Helsinki and the master protocol at our institution (2023-GB-077), which was approved by the Institutional Review Board of our hospital. Due to the retrospective nature of the study, informed consent for participation was waived. Treatment Both first-line and second-line treatment regimens were selected based on the discretion of the physician. When the first-line treatment was GnP, 5-FU-based chemotherapy was selected as second-line treatment. When the first-line treatment was mFFX, gemcitabine-based chemotherapy was selected as second-line treatment. Subsequent treatment was classified into CC (mFFX, GnP, irinotecan plus 5-FU and leucovorin (5-FU/LV), oxaliplatin plus 5-FU/LV, nanoliposomal irinotecan (nal-IRI) plus 5-FU/LV, nal-IRI plus S-1, S-IROX) and SAC (gemcitabine alone or S-1 alone). While CC was generally selected as second-line treatment, SAC was selected when deemed more appropriate based on the patient's age, performance status, or general conditions. Evaluations Baseline data before first-line treatment included age, sex, Eastern Cooperative Oncology Group performance status (ECOG PS), laboratory data, disease status (metastatic or recurrent), tumor location (head or body/tail), and metastatic site (liver, lung, distant lymph node, or peritoneum). Data obtained at the end of the first-line treatment included age, ECOG PS, and laboratory data. Assessed laboratory data included complete blood count, albumin, C-reactive protein (CRP), carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9). Glasgow prognostic score (GPS) was divided into the following categories according to albumin and CRP: patients with both hypoalbuminenia (albumin 1.0 mg/dL) were scored as 2; patients with only one of these biochemical abnormalities were scored as 1; and patients with neither of these abnormalities were scored as 0 [9]. Follow-up computed tomography was conducted every 8-12 weeks to assess efficacy of treatment. PFS was measured from the first day of first-line chemotherapy to the time of disease progression. OS was measured from the first day of first-line chemotherapy to the time of death or last follow-up. PPS was measured from the day of disease progression with first-line treatment to the time of death or last follow-up. First, PFS, OS and PPS were analyzed using the Kaplan-Meier method and the log-rank test for comparisons of first-line treatment between GnP and mFFX. Second, PFS, OS and PPS were analyzed for comparison of subsequent treatment between CC, and SAC with and without propensity score matching (PSM). Statistical analysis Continuous variables are presented as medians (range) and were compared using the Mann-Whitney U test. Categorical variables are described as absolute numbers (proportions) and were analyzed using the chi-squared or Fisher’s exact test. A pvalue < 0.05 was considered statistically significant. The following variables were assessed by univariate analysis to identify factors affecting OS: age (≥ 65 years vs. < 65 years), ECOG PS before first-line and the end of first-line (0 vs. 1/2), regimen of first-line (GnP vs. mFFX), CA19-9 before first-line and the end of first-line (≥ 1000 U/mL vs. < 1000 U/mL), GPS before first-line and the end of first-line (0 vs. 1/2), and second-line treatment (CC vs. SAC). Factors in the univariate analysis with a p value < 0.05 were included in multivariate logistic regression analysis, and hazard ratios (HR) with 95% confidence intervals (CI) were calculated. When the factors of the same category (ECOG PS, GPS, and CA19-9 before first-line vs. at the end of first-line) overlapped, the factor with the lowest HR was selected in multivariate analysis. PSM in a one-to-one ratio with a caliper width equal to 0.2 was applied to create comparable cohorts of patients receiving second-line treatment with CC and SAC. PSM was calculated with factors including age, ECOG PS, CEA level and CA19-9 level of the end of first-line treatment; sex, and disease status (metastatic or recurrent). The final analysis was conducted using follow-up data up to April 30, 2024. All statistical analyses were performed with EZR ver. 1.64 (Saitama Medical Center, Jichi Medical University, Saitama, Japan) [10]. Results Patient characteristics and treatment outcomes compared between GnP and mFFX A total of 955 consecutive patients with metastatic or recurrent PC were treated with GnP or mFFX as first-line treatment between January 2014 and March 2023. Recurrence during adjuvant chemotherapy or within six months after adjuvant chemotherapy completion was occurred in 131 cases, first-line treatment was terminated due to reasons other than disease progression in 211 cases, 10 cases remained on first-line treatment, and 146 cases received second-line treatment other than chemotherapy or best supportive care. Finally, 457 cases were analyzed in this study. Of these, 335 patients were treated with GnP and 122 patients were treated with mFFX. Patient characteristics before first-line treatment are shown in Table 1. Patients in the GnP group were older, had poorer ECOG PS, were more likely to be recurrent cases, and were less likely to have liver metastases than those in the mFFX group. The outcomes of the GnP group and the mFFX group were comparable, with no significant differences in median OS (15.0 months and 15.5 months; p = 0.73), median PFS (6.7 months and 6.5 months), or median PPS (7.2 months and 7.7 months; p = 0.37) (Figure 1). Details of second-line treatment are shown in Table 2. CC was more frequently selected in the mFFX group than in the GnP group (61.5% vs. 91.8%, p < 0.01). Post-progression survival based on choice of second-line treatment When comparing outcomes based on choice of second-line treatment, median OS and median PPS in the CC group were better than those in the SAC group (OS, 16.6 months vs. 12.8 months, p < 0.01; PPS, 8.8 months vs. 5.1 months, p < 0.01). Median PFS of first-line therapy was similar between groups (6.7 months vs. 6.5 months, p = 0.45) (Figure 2). Table 3 shows univariate and multivariate analyses of factors affecting OS. Multivariate analysis revealed that ECOG PS at the beginning of first-line treatment, CA19-9 level, and GPS at the end of first-line treatment, and second-line CC were independent prognostic factors for OS. The choice of first-line regimen (GnP or mFFX) did not significantly affect OS. Comparison of combination and single-agent chemotherapy using propensity score matching Table 4 shows a comparison of characteristics before first-line treatment and at the end of first-line treatment between the CC group and the SAC group, with and without PSM. After PSM, there were no differences in age, ECOG PS, CA19-9 level before first-line treatment and at the end of first-line treatment between groups. There was no difference in median PFS of first-line treatment between the two groups (7.1 months vs. 6.4 months, p = 0.74). However, median OS (16.3 months vs. 12.8 months, p < 0.01) and median PPS (8.0 months vs. 5.5 months, p < 0.01) were significantly longer in the CC group than in the SAC group (Figure 3). Discussion In this study, we found that second-line CC achieved longer PPS and OS than SAC in patients with metastatic or recurrent PC, although the efficacy of GnP and mFFX as first-line treatment were similar. For first-line treatment, FFX and GnP demonstrated superiority over gemcitabine monotherapy in URPC [2,3], but evidence comparing the efficacy of the two regimens is scarce. We previously reported that there was no difference in OS and PFS between mFFX and GnP, and the outcomes in this study were also comparable between the two groups [5]. Recently, the NAPOLI 3 trial demonstrated the superiority of nal-IRI in combination with 5-fluorouracil, leucovorin, and oxaliplatin (NALIRIFOX) over GnP with respect to OS [11]. In the GENERATE trial conducted in Japan, mFFX and S-IROX did not achieve the superiority over GnP [7]. Median OS was reported 11.1 months with NALIRIFOX and 9.2 months with GnP in NAPOLI 3 trial, but 14.0 months with mFFX, 13.6 months with S-IROX, and 17.1 months with GnP in the GENERATE trial. The large difference in numerical OS between the two studies makes it difficult to consider NALIRIFOX as the clear first choice for first-line treatment. However, as the GENERATE trial had not been fully published and available data was limited, comparisons should be interpreted with caution. For second-line treatment, there was no established regimen following mFFX and GnP, but CC was selected whenever possible. Following mFFX, GnP was often selected as second-line CC, which was reported to have OS from second-line initiation of 7.2–9.8 months [12-14]. The NAPOLI 1 trial showed the survival benefits of nal-IRI plus 5-FU/LV over 5-FU/LV following GnP [15]. On the other hand, the efficacy of mFFX after GnP has also been reported [16]. It remains unclear whether mFFX or nal-IRI plus 5-FU/LV is the more effective regimen after GnP. There were few reports comparing the outcomes of mFFX and nal-IRI plus 5-FU/LV following GnP, which showed no differences in OS between the two groups (9.7–11.8 in the mFFX group and 7.4–9.5 in the nal-IRI plus 5-FU/LV group) [17-19]. In fact, it remains unclear whether CC is really more effective than SAC in second-line treatment following mFFX or GnP. One report found that longer OS and PFS were achieved with GnP than with gemcitabine monotherapy following mFFX [20]. Two reports comparing mFFX and S1 following GnP both reported comparable OS between groups although one reported better PFS with second-line mFFX [21,22]. However, these reports must be interpreted with caution due to selection bias based on patient characteristics, including age and ECOG PS. Fukahori et al. compared CC and SAC following mFFX or GnP using PSM, finding no differences in PFS or OS [23]. However, that report had a small sample size after PSM and did not include patients receiving second-line nal-IRI plus 5-FU/LV. Recently, Imaoka et al. used the inverse probability of treatment weighting method to demonstrate longer OS with nal-IRI plus 5-FU/LV than with S-1 monotherapy as second-line treatment [24]. In the GENERATE trial, GnP achieved longer numerical OS compared with mFFX and S-IROX, , although the difference was not statistically significant [7]. PFS was similar among the three groups, but PPS was tended to be better in the GnP group, which was reflected in the difference in OS. In this study, there were no differences in OS, PFS, and PPS between first-line mFFX and GnP. OS and PPS were longer in the CC group than the SAC group, but second-line PFS was comparable between the two groups (Figure 2). As multivariate analysis revealed that CA19-9 level, ECOG PS, and GPS were independent prognostic factors in addition to second-line CC, we performed PSM analysis to reduce the effects of confounders. After controlling for CA19-9 level, ECOG PS, and GPS at the beginning and end of first-line treatment, CC maintained its significant advantage over SAC. A key finding in this study is that CC achieved significant OS prolongation despite no difference in first-line PFS between groups. While OS and PPS may have been affected by unmeasurable confounding factors, this study suggests that second-line CC has the potential to improve OS relative to second-line SAC. Further consideration on how to prepare patients for second-line CC is warranted. This study has several limitations. First, it was a retrospective cohort study conducted at a single center. Second, first-line treatment differed between the CC and SAC groups, However, we believe the impact on our results was limited, given the similar OS, PFS, and PPS achieved with first-line GnP and mFFX in this study. Third, there was no established strategy to select and start the subsequent treatment after first-line chemotherapy. Fourth, third-line and subsequent treatment was not evaluated. Fifth, this study only included patients refractory to first-line mFFX or GnP. Finally, PFS, adverse events, and reasons for termination of second-line treatment were not evaluated in this study. Although PSM was employed to minimize the effect of associated selection bias, residual selection bias might still be present. In conclusion, second-line CC achieved longer PPS and OS compared to second-line SAC. Appropriate management during first-line treatment is desirable to ensure that the patients remain fit for second-line CC following disease progression on first-line treatment. Abbreviations CA 19-9: carbohydrate antigen 19-9 CC: combination chemotherapy CEA: carcinoembryonic antigen CI: confidence interval CRP: C-reactive protein ECOG PS: Eastern Cooperative Oncology Group performance status FFX: FOLFIRINOX 5-FU/LV: 5-fluorouracil and leucovorin GnP: gemcitabine with nab-paclitaxel GPS: Glasgow prognostic score HR: hazard ratio mFFX: modified FOLFIRINOX nal-IRI: nanoliposomal irinotecan NALIRIFOX: nanoliposomal irinotecan in combination with fluorouracil, leucovorin, and oxaliplatin OS: overall survival PC: pancreatic cancer PFS: progression-free survival PPS: post-progression survival PSM: propensity score matching SAC: single-agent chemotherapy S-IROX: S-1, irinotecan and oxaliplatin combination therapy URPC: unresectable pancreatic cancer Declarations Author contributions: All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Takafumi Mie, Takeshi Okamoto and Masato Ozaka. The first draft of the manuscript was written by Takafumi Mie and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Conflict of Interest Statement: The authors declare that they have no conflict of interest. Data availability statements : The data that support the findings of this study are not openly available due to reasons of sensitivity and are available from the corresponding author upon reasonable request. Data are located in controlled access data storage at Cancer Institute Hospital of Japanese Foundation for Cancer Research. References Ilic M, Ilic I (2016) Epidemiology of pancreatic cancer. 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Sci Rep 13 (1):19399. doi:10.1038/s41598-023-46924-0 Imaoka H, Ikeda M, Kobayashi S, Ohba A, Ueno M, Suzuki Y, Tsumura H, Kimura N, Kawaguchi S, Kawamoto Y, Nakachi K, Tsuji K, Kobayashi N, Ashida R, Okano N, Umemoto K, Murohisa G, Hosokawa A, Asagi A, Nebiki H, Suzuki R, Terashima T, Shibata R, Kawata K, Doi T, Ohyama H, Kitano Y, Shioji K, Okuyama H, Naganuma A, Negoro Y, Sakamoto Y, Shimizu S, Morizane C, Ueno M, Furuse J, Nagano H, Japan Oncology Network in H, Pancreas (2024) Efficacy of liposomal irinotecan + 5-FU/LV vs. S-1 in gemcitabine-refractory metastatic pancreatic cancer: a real-world study using inverse probability of treatment weighting. J Gastroenterol. doi:10.1007/s00535-024-02186-9 Tables Table 1. Patient characteristics GnP (n = 335) mFFX (n = 122) p value Age (yr) Median (range) 67 (39–82) 61 (34–76) < 0.01 Sex, n (%) Male 168 (50.1%) 73 (59.8%) 0.07 Female 167 (49.9%) 49 (40.2%) ECOG PS, n (%) 0 257 (76.7%) 112 (91.8%) < 0.01 1 76 (22.7%) 10 (8.2%) 2 2 (0.6%) 0 (0%) White blood cell count (/mm3) Median (range) 5800 (2600–17300) 5400 (2800–20600) 0.08 Neutrophil count (/mm3) Median (range) 3730 (1070–10550) 3290 (1230–14010) 0.02 Hemoglobin (g/dL) Median (range) 12.6 (8.4–17.0) 12.7 (8.5–16.2) 0.76 Albumin (g/dl) Median (range) 4.0 (2.5–4.6) 3.8 (2.4–5.2) < 0.01 CRP (mg/dl) Median (range) 0.21 (0.01–12.52) 0.20 (0.01–17.09) 0.81 CEA (ng/mL) Median (range) 5.9 (0.8–16984.4) 4.3 (0.5–8154.2) 0.05 CA19-9 (U/mL) Median (range) 1274.4 (2–50000) 711.9 (2–50000) 0.14 GPS, n (%) Low (0) 243 (72.5%) 81 (66.4%) 0.20 High (1, 2) 92 (27.5%) 41 (33.6%) Disease status, n (%) Metastatic 273 (81.5%) 111 (91.0%) 0.01 Recurrent 62 (18.5%) 11 (9.0%) Tumor location, n (%) * Head 103 / 273 (37.7%) 50 / 111 (45.0%) 0.21 Body and tail 170 / 273 (62.3%) 61 / 111 (55.0%) Metastatic site, n (%) † Liver 199 (59.4%) 86 (70.5%) 0.04 Lung 54 (16.1%) 17 (13.9%) 0.66 Distant lymph nodes 99 (29.6%) 34 (27.9%) 0.82 Peritoneum 87 (26.0%) 30 (24.6%) 0.81 Number of metastatic sites, n (%) Median (range) 1 (1–5) 1 (1–4) 0.81 GnP, gemcitabine with nab-paclitaxel; mFFX, modified FOLFIRINOX; ECOG, Eastern Cooperative Oncology Group; PS, performance status; CRP, C-reactive protein; CEA, carcinoembryonic antigen; CA19-9, carbohydrate antigen 19-9; GPS, Glasgow prognostic score *; Recurrent cases were excluded. †; Including cases with metastasis to multiple sites. Table 2. Second-line treatment First-line treatment GnP (n = 335) mFFX (n = 122) p value Combination chemotherapy 206 (61.5%) 112 (91.8%) < 0.01 mFFX 138 (41.2%) mFOLFIRI 5 (1.5%) mFOLFOX 1 (0.3%) nal-IRI plus 5-FU/LV 56 (16.7%) 2 (1.6%) nal-IRI plus S-1 1 (0.3%) GnP 109 (89.3%) S-IROX 5 (1.5%) 1 (0.8%) Single-agent chemotherapy 129 (38.5%) 10 (8.2%) < 0.01 Gemcitabine 6 (4.9%) S-1 129 (38.5%) 4 (3.3%) GnP, gemcitabine with nab-paclitaxel; mFFX, modified FOLFIRINOX; mFOLFIRI, modified FOLFIRI; mFOLFOX, modified FOLFOX; nal-IRI, nanoliposomal irinotecan; 5-FU/LV, fluorouracil and leucovorin; S-IROX, S-1 and irinotecan plus oxaliplatin combination therapy Table 3. Factors influencing overall survival Univariate Multivariate HR (95% CI) p value HR (95% CI) p value Age (beginning of first-line treatment) 0.98 65 ref ECOG PS (beginning of first-line treatment) < 0.01 0 ref ref First-line regimen 0.73 mFFX 1.04 (0.83–1.31) GnP ref GPS (beginning of first-line treatment) < 0.01 Low (0) 0.67 (0.54–0.83) High (1 or 2) ref CA19-9 (beginning of first-line treatment) < 0.01 < 1000 0.61 (0.50–0.75) ≥ 1000 ref CA19-9 (end of first-line treatment) < 0.01 < 0.01 < 1000 0.60 (0.49–0.73) 0.66 (0.54–0.81) ≥ 1000 ref ref ECOG PS (end of first-line treatment) 0 ref GPS (end of first-line treatment) < 0.01 < 0.01 Low (0) 0.57 (0.47–0.70) 0.61 (0.50–0.75) High (1 or 2) ref ref Combination chemotherapy as second-line treatment < 0.01 < 0.01 Yes 0.60 (0.49–0.75) 0.63 (0.51–0.78) No ref ref HR, hazard ratio; CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group performance status; mFFX, modified FOLFIRINOX; GnP, gemcitabine with nab-paclitaxel; GPS, Glasgow prognostic score; CA19-9, carbohydrate antigen 19-9 Table 4. Comparison of patient characteristics between second-line combination and single-agent chemotherapy before and after propensity score matching Before PSM After PSM Single-agent chemotherapy (n = 139) Combination chemotherapy (n = 318) p value Single-agent chemotherapy (n = 97) Combination chemotherapy (n = 97) p value Before first-line chemotherapy Age (yr) Median (range) 71 (44–82) 63 (34–81) < 0.01 69 (44–80) 68 (50–81) 0.23 Sex, n (%) Male 60 (43.2%) 181 (56.9%) < 0.01 48 (49.5%) 52 (53.6%) 0.67 Female 79 (56.8%) 137 (43.1%) 49 (50.5%) 45 (46.4%) ECOG PS, n (%) 0 100 (71.9%) 269 (84.6%) < 0.01 75 (77.3%) 71 (73.2%) 0.62 1 39 (38.1%) 47 (14.8%) 22 (22.7%) 25 (25.8%) 2 0 2 (0.6%) 0 (0%) 1 (1.0%) First-line regimen, n (%) mFFX 10 (7.2%) 112 (35.2%) < 0.01 7 (7.2%) 23 (23.7%) < 0.01 GnP 129 (92.8%) 206 (64.8%) 90 (92.8%) 74 (76.3%) White blood cell count (/mm3) Median (range) 5700 (2600–11000) 5800 (2700–20600) 0.25 5600 (2600–10900) 5300 (2700–9700) 0.92 Neutrophil count (/mm3) Median (range) 3690 (1200–9570) 3690 (1070–14010) 0.35 3440 (1200–7830) 3540 (1070–8340) 0.74 Hemoglobin (g/dL) Median (range) 12.4 (8.4–17.0) 12.7 (8.5–17.0) 0.04 12.4 (8.4–17.0) 12.7 (9.4–17.0) 0.26 Albumin (g/dl) Median (range) 3.9 (2.6–4.6) 3.9 (2.4–5.2) 0.62 3.9 (2.6–4.6) 3.9 (2.9–4.5) 0.37 CRP (mg/dl) Median (range) 0.17 (0.01–5.92) 0.22 (0.01–17.09) 0.23 0.17 (0.01–5.49) 0.19 (0.01–10.82) 0.55 CEA (ng/mL) Median (range) 6.0 (0.8–209.5) 5.2 (0.5–16984.4) 0.84 5.7 (0.8–118.1) 5.4 (0.7–8154.2) 0.52 CA19-9 (U/mL) Median (range) 2039.5 (2–50000) 704.2 (2–50000) 0.02 1523.9 (2–50000) 982.7 (2–50000) 0.30 GPS, n (%) Low (0) 95 (68.3%) 229 (72.0%) 0.44 68 (70.1%) 73 (75.3%) 0.52 High (1, 2) 44 (31.7%) 89 (28.0%) 29 (29.9%) 24 (24.7%) Disease status, n (%) Metastatic 110 (79.1%) 274 (86.2%) 0.07 76 (78.4%) 78 (80.4%) 0.86 Recurrent 29 (20.9%) 44 (13.8%) 21 (21.6%) 19 (19.6%) Tumor location, n (%) * Head 35 / 110 (31.8%) 118 / 274 (43.1%) < 0.05 28 / 76 (36.8%) 40 / 78 (51.3%) 0.08 Body and tail 75 / 110 (68.2%) 156 / 274 (56.9%) 48 / 76 (63.2%) 38 / 78 (48.7%) Metastatic site, n (%) † Liver 85 (61.2%) 200 (62.9%) 0.75 62 (63.9%) 55 (56.7%) 0.38 Lung 23 (16.5%) 48 (15.1%) 0.68 12 (12.4%) 20 (20.6%) 0.18 Distant lymph nodes 43 (30.9%) 90 (28.3%) 0.58 33 (34.0%) 24 (24.7%) 0.21 Peritoneum 33 (23.7%) 84 (26.4%) 0.56 22 (22.7%) 24 (24.7%) 0.87 Number of metastatic sites, n (%) 1 (1–5) 1 (1–5) 0.44 1 (1–5) 1 (1–4) 0.43 At the end of first-line chemotherapy Age (yr) Median (range) 72 (45–83) 63 (34–82) < 0.01 70 (45–80) 69 (51–82) 0.22 ECOG PS, n (%) 0 60 (43.2%) 238 (74.8%) < 0.01 57 (58.8%) 51 (52.6%) 0.47 1 70 (50.4%) 77 (24.2%) 40 (41.2%) 45 (46.4%) 2 9 (6.4%) 3 (1.0%) 0 (0%) 1 (1.0%) White blood cell count (/mm3) Median (range) 4900 (1300–14600) 4420 (1200–23100) 0.17 4700 (1370–14600) 4600 (1370–11100) 0.78 Neutrophil count (/mm3) Median (range) 3050 (570–11660) 2630 (400–16400) 0.04 2900 (570–11500) 2740 (880–11590) 0.71 Hemoglobin (g/dL) Median (range) 10.1 (7.7–15.0) 10.9 (6.3–14.7) < 0.01 10.3 (7.7–15.0) 10.5 (7.4–14.2) 0.29 Albumin (g/dl) Median (range) 3.5 (1.7–4.3) 3.7 (2.4–4.5) < 0.01 3.5 (2.2–4.3) 3.6 (2.5–4.4) 0.16 CRP (mg/dl) Median (range) 0.43 (0.01–20.37) 0.35 (0.01–24.53) 0.59 0.43 (0.01–12.33) 0.38 (0.01–11.22) 0.98 CEA (ng/mL) Median (range) 7.6 (1.1–276.4) 6.5 (0.7–12369.6) 0.29 7.0 (1.1–276.4) 7.2 (0.8–12369.6) 0.86 CA19-9 (U/mL) Median (range) 2125.0 (2–50000) 818.7 (2–50000) 0.99 High (1, 2) 73 (52.5%) 126 (39.6%) 46 (47.4%) 46 (47.4%) PSM, propensity score matching; ECOG PS, Eastern Cooperative Oncology Group performance status; mFFX, modified FOLFIRINOX; GnP, gemcitabine with nab-paclitaxel; CRP, C-reactive protein; CEA, carcinoembryonic antigen; CA19-9, carbohydrate antigen 19-9; GPS, Glasgow prognostic score *; Recurrent cases were excluded. †; Including cases with metastasis to multiple sites. Cite Share Download PDF Status: Published Journal Publication published 11 Jun, 2025 Read the published version in International Journal of Clinical Oncology → Version 1 posted Editorial decision: Accept 17 May, 2025 Reviewers agreed at journal 20 Apr, 2025 Reviewers invited by journal 19 Apr, 2025 Editor assigned by journal 17 Apr, 2025 First submitted to journal 14 Apr, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5965079","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":445246948,"identity":"746ef552-f185-4afd-9a3e-7b306e0f8835","order_by":0,"name":"Takafumi 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1","display":"","copyAsset":false,"role":"figure","size":80919,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of overall survival (a), progression-free survival (b), and post-progression survival (c) between first-line GnP and mFFX therapy.\u003c/p\u003e\n\u003cp\u003eGnP, gemcitabine with nab-paclitaxel; mFFX, modified FOLFIRINOX; CI, confidence interval\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-5965079/v1/a703b08dafc7696a14e5e94f.png"},{"id":81693127,"identity":"a859e1ce-809e-4ea2-8d87-4e2a816749ce","added_by":"auto","created_at":"2025-04-30 11:46:31","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":98349,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of overall survival (a), progression-free survival of first-line chemotherapy (b), and post-progression survival (c) between second-line combination chemotherapy (CC) and single-agent chemotherapy (SAC) before propensity score matching (PSM).\u003c/p\u003e\n\u003cp\u003eCI, confidence interval\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-5965079/v1/039a9bdb20787550b5246992.png"},{"id":81690587,"identity":"01570a2d-fd1d-4155-8a21-40eeb5ffcfab","added_by":"auto","created_at":"2025-04-30 11:30:31","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":99012,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of overall survival (a), progression-free survival (b), and post-progression survival of first-line chemotherapy (c) between second-line combination chemotherapy (CC) and single-agent chemotherapy (SAC) after propensity score matching (PSM).\u003c/p\u003e\n\u003cp\u003eCI, confidence interval\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-5965079/v1/38e0c83fd2a6a7ce76f2f1e9.png"},{"id":84726784,"identity":"409eb2c3-b01a-46c7-9fcb-bc4f70cec299","added_by":"auto","created_at":"2025-06-16 16:08:16","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1120819,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5965079/v1/4f5ace03-77d4-436b-9fd2-b5fdc891404f.pdf"}],"financialInterests":"","formattedTitle":"Impact of Second-line Combination Chemotherapy on Post-progression Survival in Metastatic and Recurrent Pancreatic Cancer","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePancreatic cancer (PC) is one of the cancers with the poorest prognoses, and approximately 80% of patients are diagnosed with unresectable PC (URPC) [1]. Chemotherapy is the standard of care for patients with URPC, and gemcitabine with nab-paclitaxel (GnP) and modified FOLFIRINOX (mFFX) are most commonly used as first-line treatment [2-4]. We previously reported that there was no difference in overall survival (OS) and progression-free survival (PFS) between GnP and mFFX [5]. The efficacy of S-IROX (S-1, irinotecan and oxaliplatin combination therapy) was reported from Japan, and S-IROX was expected as first-line treatment option alternative to GnP or mFFX [6]. Recently, the phase II/III trial was conducted to compare the OS between GnP, mFFX and S-IROX as first-line treatment for patients with metastatic and recurrent PC, and mFFX and S-IROX failed to demonstrate superiority over GnP [7]. While there was no difference in PFS between the three regimens, post-progression survival (PPS) tended to be longer with GnP than with mFFX or S-IROX.\u003c/p\u003e\n\u003cp\u003eWhile a correlation between PPS and OS has been proposed [8], reports on PPS and efficacy of second-line treatment in patients with URPC are limited. First-line gemcitabine-based chemotherapy is generally followed by 5-fluorouracil (5-FU)-based chemotherapy, and vice versa. It remains unclear whether single-agent chemotherapy (SAC) or combination chemotherapy (CC) is more effective as second-line treatment after GnP or mFFX. Therefore, we conducted a retrospective study to evaluate PPS after first-line GnP or mFFX in the real-world setting.\u003c/p\u003e"},{"header":"Patients and methods","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003ePatients\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe retrospectively analyzed consecutive patients with metastatic or recurrent PC registered on our prospectively registered database. Those treated with GnP or mFFX as first-line treatment between January 2014 and March 2023 at our institution and received second-line chemotherapy after disease progression were included. Patients with recurrent PC were excluded if recurrence occurred during or within six months after completion of adjuvant chemotherapy. This study was conducted in accordance with the Declaration of Helsinki and the master protocol at our institution (2023-GB-077), which was approved by the Institutional Review Board of our hospital. Due to the retrospective nature of the study, informed consent for participation was waived.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eTreatment\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBoth first-line and second-line treatment regimens were selected based on the discretion of the physician. When the first-line treatment was GnP, 5-FU-based chemotherapy was selected as second-line treatment. When the first-line treatment was mFFX, gemcitabine-based chemotherapy was selected as second-line treatment. Subsequent treatment was classified into CC (mFFX, GnP, irinotecan plus 5-FU and leucovorin (5-FU/LV), oxaliplatin plus 5-FU/LV, nanoliposomal irinotecan (nal-IRI) plus 5-FU/LV, nal-IRI plus S-1, S-IROX) and SAC (gemcitabine alone or S-1 alone). While CC was generally selected as second-line treatment, SAC was selected when deemed more appropriate based on the patient's age, performance status, or general conditions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eEvaluations\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBaseline data before first-line treatment included age, sex, Eastern Cooperative Oncology Group performance status (ECOG PS), laboratory data, disease status (metastatic or recurrent), tumor location (head or body/tail), and metastatic site (liver, lung, distant lymph node, or peritoneum). Data obtained at the end of the first-line treatment included age, ECOG PS, and laboratory data. Assessed laboratory data included complete blood count, albumin, C-reactive protein (CRP), carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9). Glasgow prognostic score (GPS) was divided into the following categories according to albumin and CRP: patients with both hypoalbuminenia (albumin \u0026lt; 3.5g/dL) and elevated CRP level (\u0026gt; 1.0 mg/dL) were scored as 2; patients with only one of these biochemical abnormalities were scored as 1; and patients with neither of these abnormalities were scored as 0 [9].\u003c/p\u003e\n\u003cp\u003eFollow-up computed tomography was conducted every 8-12 weeks to assess efficacy of treatment. PFS was measured from the first day of first-line chemotherapy to the time of disease progression. OS was measured from the first day of first-line chemotherapy to the time of death or last follow-up. PPS was measured from the day of disease progression with first-line treatment to the time of death or last follow-up. First, PFS, OS and PPS were analyzed using the Kaplan-Meier method and the log-rank test for comparisons of first-line treatment between GnP and mFFX. Second, PFS, OS and PPS were analyzed for comparison of subsequent treatment between CC, and SAC with and without propensity score matching (PSM).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eStatistical analysis\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eContinuous variables are presented as medians (range) and were compared using the Mann-Whitney U test. Categorical variables are described as absolute numbers (proportions) and were analyzed using the chi-squared or Fisher’s exact test. A pvalue \u0026lt; 0.05 was considered statistically significant. The following variables were assessed by univariate analysis to identify factors affecting OS: age (≥ 65 years vs. \u0026lt; 65 years), ECOG PS before first-line and the end of first-line (0 vs. 1/2), regimen of first-line (GnP vs. mFFX), CA19-9 before first-line and the end of first-line (≥ 1000 U/mL vs. \u0026lt; 1000 U/mL), GPS before first-line and the end of first-line (0 vs. 1/2), and second-line treatment (CC vs. SAC). Factors in the univariate analysis with a p value \u0026lt; 0.05 were included in multivariate logistic regression analysis, and hazard ratios (HR) with 95% confidence intervals (CI) were calculated. When the factors of the same category (ECOG PS, GPS, and CA19-9 before first-line vs. at the end of first-line) overlapped, the factor with the lowest HR was selected in multivariate analysis.\u003c/p\u003e\n\u003cp\u003ePSM in a one-to-one ratio with a caliper width equal to 0.2 was applied to create comparable cohorts of patients receiving second-line treatment with CC and SAC. PSM was calculated with factors including age, ECOG PS, CEA level and CA19-9 level of the end of first-line treatment; sex, and disease status (metastatic or recurrent). The final analysis was conducted using follow-up data up to April 30, 2024. All statistical analyses were performed with EZR ver. 1.64 (Saitama Medical Center, Jichi Medical University, Saitama, Japan) [10].\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003ePatient characteristics and treatment outcomes compared between GnP and mFFX\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 955 consecutive patients with metastatic or recurrent PC were treated with GnP or mFFX as first-line treatment between January 2014 and March 2023. Recurrence during adjuvant chemotherapy or within six months after adjuvant chemotherapy completion was occurred in 131 cases, first-line treatment was terminated due to reasons other than disease progression in 211 cases, 10 cases remained on first-line treatment, and 146 cases received second-line treatment other than chemotherapy or best supportive care. Finally, 457 cases were analyzed in this study. Of these, 335 patients were treated with GnP and 122 patients were treated with mFFX. Patient characteristics before first-line treatment are shown in Table 1. Patients in the GnP group were older, had poorer ECOG PS, were more likely to be recurrent cases, and were less likely to have liver metastases than those in the mFFX group.\u003c/p\u003e\n\u003cp\u003eThe outcomes of the GnP group and the mFFX group were comparable, with no significant differences in median OS (15.0 months and 15.5 months; p = 0.73), median PFS (6.7 months and 6.5 months), or median PPS (7.2 months and 7.7 months; p = 0.37) (Figure 1).\u003c/p\u003e\n\u003cp\u003eDetails of second-line treatment are shown in Table 2. CC was more frequently selected in the mFFX group than in the GnP group (61.5% vs. 91.8%, p \u0026lt; 0.01).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003ePost-progression survival based on choice of second-line treatment\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWhen comparing outcomes based on choice of second-line treatment, median OS and median PPS in the CC group were better than those in the SAC group (OS, 16.6 months vs. 12.8 months, p \u0026lt; 0.01; PPS, 8.8 months vs. 5.1 months, p \u0026lt; 0.01). Median PFS of first-line therapy was similar between groups (6.7 months vs. 6.5 months, p = 0.45) (Figure 2).\u003c/p\u003e\n\u003cp\u003eTable 3 shows univariate and multivariate analyses of factors affecting OS. Multivariate analysis revealed that ECOG PS at the beginning of first-line treatment, CA19-9 level, and GPS at the end of first-line treatment, and second-line CC were independent prognostic factors for OS. The choice of first-line regimen (GnP or mFFX) did not significantly affect OS.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eComparison of combination and single-agent chemotherapy using propensity score matching\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 4 shows a comparison of characteristics before first-line treatment and at the end of first-line treatment between the CC group and the SAC group, with and without PSM. After PSM, there were no differences in age, ECOG PS, CA19-9 level before first-line treatment and at the end of first-line treatment between groups. There was no difference in median PFS of first-line treatment between the two groups (7.1 months vs. 6.4 months, p = 0.74). However, median OS (16.3 months vs. 12.8 months, p \u0026lt; 0.01) and median PPS (8.0 months vs. 5.5 months, p \u0026lt; 0.01) were significantly longer in the CC group than in the SAC group (Figure 3).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, we found that second-line CC achieved longer PPS and OS than SAC in patients with metastatic or recurrent PC, although the efficacy of GnP and mFFX as first-line treatment were similar.\u003c/p\u003e\n\u003cp\u003eFor first-line treatment, FFX and GnP demonstrated superiority over gemcitabine monotherapy in URPC [2,3], but evidence comparing the efficacy of the two regimens is scarce. We previously reported that there was no difference in OS and PFS between mFFX and GnP, and the outcomes in this study were also comparable between the two groups [5]. Recently, the NAPOLI 3 trial demonstrated the superiority of nal-IRI in combination with 5-fluorouracil, leucovorin, and oxaliplatin (NALIRIFOX) over GnP with respect to OS [11]. In the GENERATE trial conducted in Japan, mFFX and S-IROX did not achieve the superiority over GnP [7]. Median OS was reported 11.1 months with NALIRIFOX and 9.2 months with GnP in NAPOLI 3 trial, but 14.0 months with mFFX, 13.6 months with S-IROX, and 17.1 months with GnP in the GENERATE trial. The large difference in numerical OS between the two studies makes it difficult to consider NALIRIFOX as the clear first choice for first-line treatment. However, as the GENERATE trial had not been fully published and available data was limited, comparisons should be interpreted with caution.\u003c/p\u003e\n\u003cp\u003eFor second-line treatment, there was no established regimen following mFFX and GnP, but CC was selected whenever possible. Following mFFX, GnP was often selected as second-line CC, which was reported to have OS from second-line initiation of 7.2–9.8 months [12-14]. The NAPOLI 1 trial showed the survival benefits of nal-IRI plus 5-FU/LV over 5-FU/LV following GnP [15]. On the other hand, the efficacy of mFFX after GnP has also been reported [16]. It remains unclear whether mFFX or nal-IRI plus 5-FU/LV is the more effective regimen after GnP. There were few reports comparing the outcomes of mFFX and nal-IRI plus 5-FU/LV following GnP, which showed no differences in OS between the two groups (9.7–11.8 in the mFFX group and 7.4–9.5 in the nal-IRI plus 5-FU/LV group) [17-19]. In fact, it remains unclear whether CC is really more effective than SAC in second-line treatment following mFFX or GnP. One report found that longer OS and PFS were achieved with GnP than with gemcitabine monotherapy following mFFX [20]. Two reports comparing mFFX and S1 following GnP both reported comparable OS between groups although one reported better PFS with second-line mFFX [21,22]. However, these reports must be interpreted with caution due to selection bias based on patient characteristics, including age and ECOG PS. Fukahori et al. compared CC and SAC following mFFX or GnP using PSM, finding no differences in PFS or OS [23]. However, that report had a small sample size after PSM and did not include patients receiving second-line nal-IRI plus 5-FU/LV. Recently, Imaoka et al. used the inverse probability of treatment weighting method to demonstrate longer OS with nal-IRI plus 5-FU/LV than with S-1 monotherapy as second-line treatment [24].\u003c/p\u003e\n\u003cp\u003eIn the GENERATE trial, GnP achieved longer numerical OS compared with mFFX and S-IROX, , although the difference was not statistically significant [7]. PFS was similar among the three groups, but PPS was tended to be better in the GnP group, which was reflected in the difference in OS. In this study, there were no differences in OS, PFS, and PPS between first-line mFFX and GnP. OS and PPS were longer in the CC group than the SAC group, but second-line PFS was comparable between the two groups (Figure 2). As multivariate analysis revealed that CA19-9 level, ECOG PS, and GPS were independent prognostic factors in addition to second-line CC, we performed PSM analysis to reduce the effects of confounders. After controlling for CA19-9 level, ECOG PS, and GPS at the beginning and end of first-line treatment, CC maintained its significant advantage over SAC. A key finding in this study is that CC achieved significant OS prolongation despite no difference in first-line PFS between groups. While OS and PPS may have been affected by unmeasurable confounding factors, this study suggests that second-line CC has the potential to improve OS relative to second-line SAC. Further consideration on how to prepare patients for second-line CC is warranted.\u003c/p\u003e\n\u003cp\u003eThis study has several limitations. First, it was a retrospective cohort study conducted at a single center. Second, first-line treatment differed between the CC and SAC groups, However, we believe the impact on our results was limited, given the similar OS, PFS, and PPS achieved with first-line GnP and mFFX in this study. Third, there was no established strategy to select and start the subsequent treatment after first-line chemotherapy. Fourth, third-line and subsequent treatment was not evaluated. Fifth, this study only included patients refractory to first-line mFFX or GnP. Finally, PFS, adverse events, and reasons for termination of second-line treatment were not evaluated in this study. Although PSM was employed to minimize the effect of associated selection bias, residual selection bias might still be present.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; In conclusion, second-line CC achieved longer PPS and OS compared to second-line SAC. Appropriate management during first-line treatment is desirable to ensure that the patients remain fit for second-line CC following disease progression on first-line treatment.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCA 19-9: carbohydrate antigen 19-9\u003c/p\u003e\n\u003cp\u003eCC: combination chemotherapy\u003c/p\u003e\n\u003cp\u003eCEA: carcinoembryonic antigen\u003c/p\u003e\n\u003cp\u003eCI: confidence interval\u003c/p\u003e\n\u003cp\u003eCRP: C-reactive protein\u003c/p\u003e\n\u003cp\u003eECOG PS: Eastern Cooperative Oncology Group performance status\u003c/p\u003e\n\u003cp\u003eFFX: FOLFIRINOX\u003c/p\u003e\n\u003cp\u003e5-FU/LV: 5-fluorouracil and leucovorin\u003c/p\u003e\n\u003cp\u003eGnP: gemcitabine with nab-paclitaxel\u003c/p\u003e\n\u003cp\u003eGPS: Glasgow prognostic score\u003c/p\u003e\n\u003cp\u003eHR: hazard ratio\u003c/p\u003e\n\u003cp\u003emFFX: modified FOLFIRINOX\u003c/p\u003e\n\u003cp\u003enal-IRI: nanoliposomal irinotecan\u003c/p\u003e\n\u003cp\u003eNALIRIFOX: nanoliposomal irinotecan in combination with fluorouracil, leucovorin, and oxaliplatin\u003c/p\u003e\n\u003cp\u003eOS: overall survival\u003c/p\u003e\n\u003cp\u003ePC: pancreatic cancer\u003c/p\u003e\n\u003cp\u003ePFS: progression-free survival\u003c/p\u003e\n\u003cp\u003ePPS: post-progression survival\u003c/p\u003e\n\u003cp\u003ePSM: propensity score matching\u003c/p\u003e\n\u003cp\u003eSAC: single-agent chemotherapy\u003c/p\u003e\n\u003cp\u003eS-IROX: S-1, irinotecan and oxaliplatin combination therapy\u003c/p\u003e\n\u003cp\u003eURPC: unresectable pancreatic cancer\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor contributions:\u003c/strong\u003e All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Takafumi Mie, Takeshi Okamoto and Masato Ozaka. The first draft of the manuscript was written by Takafumi Mie and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConflict of Interest Statement:\u003c/strong\u003e The authors declare that they have no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statements\u003c/strong\u003e: The data that support the findings of this study are not openly available due to reasons of sensitivity and are available from the corresponding author upon reasonable request. Data are located in controlled access data storage at Cancer Institute Hospital of Japanese Foundation for Cancer Research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cbr\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003e Ilic M, Ilic I (2016) Epidemiology of pancreatic cancer. World J Gastroenterol 22 (44):9694\u0026ndash;9705. doi:10.3748/wjg.v22.i44.9694\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouarn Y, Adenis A, Raoul JL, Gourgou-Bourgade S, de la Fouchardiere C, Bennouna J, Bachet JB, Khemissa-Akouz F, Pere-Verge D, Delbaldo C, Assenat E, Chauffert B, Michel P, Montoto-Grillot C, Ducreux M, Groupe Tumeurs Digestives of U, Intergroup P (2011) FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. 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Jpn J Clin Oncol 52 (12):1399\u0026ndash;1407. doi:10.1093/jjco/hyac145\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Tezuka S, Ueno M, Kobayashi S, Hamaguchi T, Yamachika Y, Oishi R, Nagashima S, Fukushima T, Morimoto M, Shin M (2022) Nal-IRI/5-FU/LV versus modified FOLFIRINOX and FOLFIRI as second-line chemotherapy for unresectable pancreatic cancer: A single center retrospective study. Pancreatology 22 (6):789\u0026ndash;796. doi:10.1016/j.pan.2022.06.004\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Park HS, Kang B, Chon HJ, Im HS, Lee CK, Kim I, Kang MJ, Hwang JE, Bae WK, Cheon J, Park JO, Hong JY, Kang JH, Kim JH, Lim SH, Kim JW, Kim JW, Yoo C, Choi HJ (2021) Liposomal irinotecan plus fluorouracil/leucovorin versus FOLFIRINOX as the second-line chemotherapy for patients with metastatic pancreatic cancer: a multicenter retrospective study of the Korean Cancer Study Group (KCSG). ESMO Open 6 (2):100049. doi:10.1016/j.esmoop.2021.100049\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Zaibet S, Hautefeuille V, Auclin E, Lievre A, Tougeron D, Sarabi M, Gilabert M, Wasselin J, Edeline J, Artru P, Bechade D, Morin C, Ducoulombier A, Taieb J, Pernot S (2022) Gemcitabine\u0026thinsp;+\u0026thinsp;Nab-paclitaxel or Gemcitabine alone after FOLFIRINOX failure in patients with metastatic pancreatic adenocarcinoma: a real-world AGEO study. Br J Cancer 126 (10):1394\u0026ndash;1400. doi:10.1038/s41416-022-01713-w\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Hino K, Nishina T, Numata Y, Asagi A, Inoue T, Yoshimatsu M, Sakaguchi C, Nakasya A, Nishide N, Kajiwara T, Terao T, Nadano S, Marui K, Okujima Y, Kokubu M, Imamura Y, Kanemitsu K, Koizumi M, Kumagi T, Hiasa Y, Hyodo I (2022) Clinical Outcomes of S-1 Monotherapy and Modified FOLFIRINOX Therapy after Gemcitabine plus Nab-paclitaxel Therapy in Unresectable Pancreatic Cancer. Intern Med 61 (15):2255\u0026ndash;2261. doi:10.2169/internalmedicine.8736-21\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Ikezawa K, Kiyota R, Takada R, Daiku K, Maeda S, Imai T, Abe Y, Kai Y, Yamai T, Fukutake N, Nakabori T, Ashida R, Uehara H, Tabuchi T, Katayama K, Ohkawa K (2021) Efficacy and safety of modified fluorouracil/leucovorin plus irinotecan and oxaliplatin (mFOLFIRINOX) compared with S-1 as second-line chemotherapy in metastatic pancreatic cancer. JGH Open 5 (6):679\u0026ndash;685. doi:10.1002/jgh3.12555\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Fukahori M, Okabe Y, Shimokawa M, Otsuka T, Koga F, Ueda Y, Nakazawa J, Komori A, Otsu S, Arima S, Makiyama A, Taguchi H, Honda T, Ushijima T, Miwa K, Shibuki T, Nio K, Ide Y, Ureshino N, Mizuta T, Mitsugi K, Shirakawa T (2023) Efficacy of second-line chemotherapy after treatment with gemcitabine plus nab-paclitaxel or FOLFIRINOX in patients with metastatic pancreatic cancer. Sci Rep 13 (1):19399. doi:10.1038/s41598-023-46924-0\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Imaoka H, Ikeda M, Kobayashi S, Ohba A, Ueno M, Suzuki Y, Tsumura H, Kimura N, Kawaguchi S, Kawamoto Y, Nakachi K, Tsuji K, Kobayashi N, Ashida R, Okano N, Umemoto K, Murohisa G, Hosokawa A, Asagi A, Nebiki H, Suzuki R, Terashima T, Shibata R, Kawata K, Doi T, Ohyama H, Kitano Y, Shioji K, Okuyama H, Naganuma A, Negoro Y, Sakamoto Y, Shimizu S, Morizane C, Ueno M, Furuse J, Nagano H, Japan Oncology Network in H, Pancreas (2024) Efficacy of liposomal irinotecan\u0026thinsp;+\u0026thinsp;5-FU/LV vs. S-1 in gemcitabine-refractory metastatic pancreatic cancer: a real-world study using inverse probability of treatment weighting. J Gastroenterol. doi:10.1007/s00535-024-02186-9\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1. Patient characteristics\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"688\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 219px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003eGnP\u003cbr\u003e\u0026nbsp;(n = 335)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003emFFX\u003cbr\u003e\u0026nbsp;(n = 122)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003ep value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 219px;\"\u003e\n \u003cp\u003eAge (yr)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003eMedian (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e67 (39\u0026ndash;82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e61 (34\u0026ndash;76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e\u0026lt; 0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 219px;\"\u003e\n \u003cp\u003eSex, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e168 (50.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e73 (59.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 219px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e167 (49.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e49 (40.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 219px;\"\u003e\n \u003cp\u003eECOG PS, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e257 (76.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e112 (91.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e\u0026lt; 0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 219px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e76 (22.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e10 (8.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 219px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e2 (0.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 219px;\"\u003e\n \u003cp\u003eWhite blood cell count (/mm3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003eMedian (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e5800 (2600\u0026ndash;17300)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e5400 (2800\u0026ndash;20600)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 219px;\"\u003e\n \u003cp\u003eNeutrophil count (/mm3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003eMedian (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e3730 (1070\u0026ndash;10550)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e3290 (1230\u0026ndash;14010)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 219px;\"\u003e\n \u003cp\u003eHemoglobin (g/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003eMedian (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e12.6 (8.4\u0026ndash;17.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e12.7 (8.5\u0026ndash;16.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.76\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 219px;\"\u003e\n \u003cp\u003eAlbumin (g/dl)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003eMedian (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e4.0 (2.5\u0026ndash;4.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e3.8 (2.4\u0026ndash;5.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e\u0026lt; 0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 219px;\"\u003e\n \u003cp\u003eCRP (mg/dl)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003eMedian (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e0.21 (0.01\u0026ndash;12.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e0.20 (0.01\u0026ndash;17.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.81\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 219px;\"\u003e\n \u003cp\u003eCEA (ng/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003eMedian (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e5.9 (0.8\u0026ndash;16984.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e4.3 (0.5\u0026ndash;8154.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 219px;\"\u003e\n \u003cp\u003eCA19-9 (U/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003eMedian (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e1274.4 (2\u0026ndash;50000)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e711.9 (2\u0026ndash;50000)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 219px;\"\u003e\n \u003cp\u003eGPS, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003eLow (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e243 (72.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e81 (66.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.20\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 219px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003eHigh (1, 2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e92 (27.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e41 (33.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 219px;\"\u003e\n \u003cp\u003eDisease status, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003eMetastatic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e273 (81.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e111 (91.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 219px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003eRecurrent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e62 (18.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e11 (9.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 219px;\"\u003e\n \u003cp\u003eTumor location, n (%)\u0026nbsp;*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003eHead\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e103 / 273 (37.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e50 / 111 (45.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.21\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 219px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003eBody and tail\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e170 / 273 (62.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e61 / 111 (55.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 219px;\"\u003e\n \u003cp\u003eMetastatic site, n (%)\u0026nbsp;\u0026dagger;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003eLiver\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e199 (59.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e86 (70.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 219px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003eLung\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e54 (16.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e17 (13.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.66\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 219px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003eDistant lymph nodes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e99 (29.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e34 (27.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.82\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 219px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003ePeritoneum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e87 (26.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e30 (24.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.81\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 219px;\"\u003e\n \u003cp\u003eNumber of metastatic sites, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003eMedian (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e1 (1\u0026ndash;5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e1 (1\u0026ndash;4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.81\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 219px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eGnP, gemcitabine with nab-paclitaxel; mFFX, modified FOLFIRINOX; ECOG, Eastern Cooperative Oncology Group; PS, performance status; CRP, C-reactive protein; CEA, carcinoembryonic antigen; CA19-9, carbohydrate antigen 19-9; GPS,\u0026nbsp;Glasgow prognostic score\u003c/p\u003e\n\u003cp\u003e*; Recurrent cases were excluded.\u003c/p\u003e\n\u003cp\u003e\u0026dagger;; Including cases with metastasis to multiple sites.\u003c/p\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003eTable 2. Second-line treatment\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"524\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 229px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 197px;\"\u003e\n \u003cp\u003e\u003cu\u003eFirst-line treatment\u003c/u\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 229px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003eGnP\u003cbr\u003e\u0026nbsp;(n = 335)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003emFFX\u003cbr\u003e\u0026nbsp;(n = 122)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003ep value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 229px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCombination chemotherapy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e206 (61.5%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e112 (91.8%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt; 0.01\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 229px;\"\u003e\n \u003cp\u003emFFX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e138 (41.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 229px;\"\u003e\n \u003cp\u003emFOLFIRI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e5 (1.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 229px;\"\u003e\n \u003cp\u003emFOLFOX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e1 (0.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 229px;\"\u003e\n \u003cp\u003enal-IRI plus 5-FU/LV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e56 (16.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e2 (1.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 229px;\"\u003e\n \u003cp\u003enal-IRI plus S-1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e1 (0.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 229px;\"\u003e\n \u003cp\u003eGnP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e109 (89.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 229px;\"\u003e\n \u003cp\u003eS-IROX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e5 (1.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e1 (0.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 229px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSingle-agent chemotherapy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e129 (38.5%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e10 (8.2%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt; 0.01\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 229px;\"\u003e\n \u003cp\u003eGemcitabine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e6 (4.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 229px;\"\u003e\n \u003cp\u003eS-1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e129 (38.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e4 (3.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 229px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eGnP, gemcitabine with nab-paclitaxel; mFFX, modified FOLFIRINOX; mFOLFIRI, modified FOLFIRI; mFOLFOX, modified FOLFOX; nal-IRI, nanoliposomal irinotecan; 5-FU/LV, fluorouracil and leucovorin; S-IROX, S-1 and irinotecan plus oxaliplatin combination therapy\u003c/p\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003eTable 3. Factors influencing overall survival\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"830\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 284px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 185px;\"\u003e\n \u003cp\u003eUnivariate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 189px;\"\u003e\n \u003cp\u003eMultivariate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 284px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 14.075%;\"\u003e\n \u003cp\u003eHR (95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.4451%;\"\u003e\n \u003cp\u003ep value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003eHR (95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003ep value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 284px;\"\u003e\n \u003cp\u003eAge (beginning of first-line treatment)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.075%;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.4451%;\"\u003e\n \u003cp\u003e0.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 284px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e\u0026lt; 65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.075%;\"\u003e\n \u003cp\u003e1.00 (0.82\u0026ndash;1.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.4451%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 284px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e\u0026gt; 65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.075%;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.4451%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 284px;\"\u003e\n \u003cp\u003eECOG PS (beginning of first-line treatment)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 14.075%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 8.4451%;\"\u003e\n \u003cp\u003e\u0026lt; 0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e\u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 284px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.075%;\"\u003e\n \u003cp\u003e0.53 (0.40\u0026ndash;0.60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.4451%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e0.57 (0.44\u0026ndash;0.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 284px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e\u0026gt; 0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.075%;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.4451%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 284px;\"\u003e\n \u003cp\u003eFirst-line regimen\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 14.075%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 8.4451%;\"\u003e\n \u003cp\u003e0.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 284px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003emFFX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.075%;\"\u003e\n \u003cp\u003e1.04 (0.83\u0026ndash;1.31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.4451%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 284px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003eGnP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.075%;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.4451%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 284px;\"\u003e\n \u003cp\u003eGPS (beginning of first-line treatment)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 14.075%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 8.4451%;\"\u003e\n \u003cp\u003e\u0026lt; 0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 284px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003eLow (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.075%;\"\u003e\n \u003cp\u003e0.67 (0.54\u0026ndash;0.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.4451%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 284px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003eHigh (1 or 2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.075%;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.4451%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 284px;\"\u003e\n \u003cp\u003eCA19-9 (beginning of first-line treatment)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 14.075%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 8.4451%;\"\u003e\n \u003cp\u003e\u0026lt; 0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 284px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e\u0026lt; 1000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.075%;\"\u003e\n \u003cp\u003e0.61 (0.50\u0026ndash;0.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.4451%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 284px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e\u0026ge; 1000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.075%;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.4451%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 284px;\"\u003e\n \u003cp\u003eCA19-9 (end of first-line treatment)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 14.075%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 8.4451%;\"\u003e\n \u003cp\u003e\u0026lt; 0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e\u0026lt; 0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 284px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e\u0026lt; 1000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.075%;\"\u003e\n \u003cp\u003e0.60 (0.49\u0026ndash;0.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.4451%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e0.66 (0.54\u0026ndash;0.81)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 284px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e\u0026ge; 1000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.075%;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.4451%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 284px;\"\u003e\n \u003cp\u003eECOG PS (end of first-line treatment)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 14.075%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 8.4451%;\"\u003e\n \u003cp\u003e\u0026lt; 0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 284px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.075%;\"\u003e\n \u003cp\u003e0.55 (0.44\u0026ndash;0.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.4451%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 284px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e\u0026gt; 0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.075%;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.4451%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 284px;\"\u003e\n \u003cp\u003eGPS (end of first-line treatment)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 14.075%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 8.4451%;\"\u003e\n \u003cp\u003e\u0026lt; 0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e\u0026lt; 0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 284px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003eLow (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.075%;\"\u003e\n \u003cp\u003e0.57 (0.47\u0026ndash;0.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.4451%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e0.61 (0.50\u0026ndash;0.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 284px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003eHigh (1 or 2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.075%;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.4451%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 284px;\"\u003e\n \u003cp\u003eCombination chemotherapy as second-line treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 14.075%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 8.4451%;\"\u003e\n \u003cp\u003e\u0026lt; 0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e\u0026lt; 0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 284px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.075%;\"\u003e\n \u003cp\u003e0.60 (0.49\u0026ndash;0.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.4451%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e0.63 (0.51\u0026ndash;0.78)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 284px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.075%;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.4451%;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHR, hazard ratio; CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group performance status; mFFX, modified FOLFIRINOX; GnP, gemcitabine with nab-paclitaxel; GPS, Glasgow prognostic score; CA19-9, carbohydrate antigen 19-9\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003eTable 4. Comparison of patient characteristics between second-line combination and single-agent chemotherapy before and after propensity score matching\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"1002\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 159px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 326px;\"\u003e\n \u003cp\u003e\u003cu\u003eBefore PSM\u003c/u\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e\u003cu\u003e\u0026nbsp;\u003c/u\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 332px;\"\u003e\n \u003cp\u003e\u003cu\u003eAfter PSM\u003c/u\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 159px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003eSingle-agent chemotherapy\u003cbr\u003e\u0026nbsp;(n = 139)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003eCombination\u0026nbsp;\u003c/p\u003e\n \u003cp\u003echemotherapy\u0026nbsp;\u003cbr\u003e\u0026nbsp;(n = 318)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003ep value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003eSingle-agent chemotherapy\u0026nbsp;\u003cbr\u003e\u0026nbsp;(n = 97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003eCombination\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;chemotherapy\u003cbr\u003e\u0026nbsp;(n = 97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003ep value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 159px;\"\u003e\n \u003cp\u003eBefore first-line\u0026nbsp;\u003c/p\u003e\n \u003cp\u003echemotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 159px;\"\u003e\n \u003cp\u003eAge (yr)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003eMedian (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e71 (44\u0026ndash;82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e63 (34\u0026ndash;81)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026lt; 0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e69 (44\u0026ndash;80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e68 (50\u0026ndash;81)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.23\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 159px;\"\u003e\n \u003cp\u003eSex, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e60 (43.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e181 (56.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026lt; 0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e48 (49.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e52 (53.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.67\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 159px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e79 (56.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e137 (43.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e49 (50.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e45 (46.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 159px;\"\u003e\n \u003cp\u003eECOG PS, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e100 (71.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e269 (84.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026lt; 0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e75 (77.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e71 (73.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.62\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 159px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e39 (38.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e47 (14.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e22 (22.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e25 (25.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 159px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e2 (0.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e1 (1.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 159px;\"\u003e\n \u003cp\u003eFirst-line regimen, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003emFFX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e10 (7.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e112 (35.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026lt; 0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e7 (7.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e23 (23.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e\u0026lt; 0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 159px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003eGnP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e129 (92.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e206 (64.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e90 (92.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e74 (76.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 159px;\"\u003e\n \u003cp\u003eWhite blood cell count (/mm3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003eMedian (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e5700 (2600\u0026ndash;11000)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e5800 (2700\u0026ndash;20600)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e0.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e5600 (2600\u0026ndash;10900)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e5300 (2700\u0026ndash;9700)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.92\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 159px;\"\u003e\n \u003cp\u003eNeutrophil count (/mm3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003eMedian (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e3690 (1200\u0026ndash;9570)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e3690 (1070\u0026ndash;14010)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e0.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e3440 (1200\u0026ndash;7830)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e3540 (1070\u0026ndash;8340)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.74\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 159px;\"\u003e\n \u003cp\u003eHemoglobin (g/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003eMedian (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e12.4 (8.4\u0026ndash;17.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e12.7 (8.5\u0026ndash;17.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e12.4 (8.4\u0026ndash;17.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e12.7 (9.4\u0026ndash;17.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.26\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 159px;\"\u003e\n \u003cp\u003eAlbumin (g/dl)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003eMedian (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e3.9 (2.6\u0026ndash;4.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e3.9 (2.4\u0026ndash;5.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e0.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e3.9 (2.6\u0026ndash;4.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e3.9 (2.9\u0026ndash;4.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.37\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 159px;\"\u003e\n \u003cp\u003eCRP (mg/dl)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003eMedian (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e0.17 (0.01\u0026ndash;5.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e0.22 (0.01\u0026ndash;17.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e0.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e0.17 (0.01\u0026ndash;5.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e0.19 (0.01\u0026ndash;10.82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.55\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 159px;\"\u003e\n \u003cp\u003eCEA (ng/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003eMedian (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e6.0 (0.8\u0026ndash;209.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e5.2 (0.5\u0026ndash;16984.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e0.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e5.7 (0.8\u0026ndash;118.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e5.4 (0.7\u0026ndash;8154.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.52\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 159px;\"\u003e\n \u003cp\u003eCA19-9 (U/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003eMedian (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e2039.5 (2\u0026ndash;50000)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e704.2 (2\u0026ndash;50000)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e1523.9 (2\u0026ndash;50000)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e982.7 (2\u0026ndash;50000)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.30\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 159px;\"\u003e\n \u003cp\u003eGPS, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003eLow (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e95 (68.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e229 (72.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e0.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e68 (70.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e73 (75.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.52\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 159px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003eHigh (1, 2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e44 (31.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e89 (28.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e29 (29.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e24 (24.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 159px;\"\u003e\n \u003cp\u003eDisease status, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003eMetastatic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e110 (79.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e274 (86.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e76 (78.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e78 (80.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.86\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 159px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003eRecurrent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e29 (20.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e44 (13.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e21 (21.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e19 (19.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 159px;\"\u003e\n \u003cp\u003eTumor location, n (%)\u0026nbsp;*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003eHead\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e35 / 110 (31.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e118 / 274 (43.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026lt; 0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e28 / 76 (36.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e40 / 78 (51.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 159px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003eBody and tail\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e75 / 110 (68.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e156 / 274 (56.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e48 / 76 (63.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e38 / 78 (48.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 159px;\"\u003e\n \u003cp\u003eMetastatic site, n (%)\u0026nbsp;\u0026dagger;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003eLiver\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e85 (61.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e200 (62.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e62 (63.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e55 (56.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.38\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 159px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003eLung\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e23 (16.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e48 (15.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e0.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e12 (12.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e20 (20.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 159px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003eDistant lymph nodes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e43 (30.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e90 (28.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e33 (34.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e24 (24.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.21\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 159px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003ePeritoneum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e33 (23.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e84 (26.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e0.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e22 (22.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e24 (24.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.87\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 159px;\"\u003e\n \u003cp\u003eNumber of metastatic\u0026nbsp;\u003c/p\u003e\n \u003cp\u003esites, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e1 (1\u0026ndash;5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e1 (1\u0026ndash;5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e0.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e1 (1\u0026ndash;5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e1 (1\u0026ndash;4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.43\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 159px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 159px;\"\u003e\n \u003cp\u003eAt the end of\u0026nbsp;\u003c/p\u003e\n \u003cp\u003efirst-line chemotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 159px;\"\u003e\n \u003cp\u003eAge (yr)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003eMedian (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e72 (45\u0026ndash;83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e63 (34\u0026ndash;82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026lt; 0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e70 (45\u0026ndash;80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e69 (51\u0026ndash;82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.22\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 159px;\"\u003e\n \u003cp\u003eECOG PS, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e60 (43.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e238 (74.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026lt; 0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e57 (58.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e51 (52.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.47\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 159px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e70 (50.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e77 (24.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e40 (41.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e45 (46.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 159px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e9 (6.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e3 (1.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e1 (1.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 159px;\"\u003e\n \u003cp\u003eWhite blood cell count (/mm3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003eMedian (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e4900 (1300\u0026ndash;14600)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e4420 (1200\u0026ndash;23100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e4700 (1370\u0026ndash;14600)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e4600 (1370\u0026ndash;11100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.78\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 159px;\"\u003e\n \u003cp\u003eNeutrophil count (/mm3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003eMedian (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e3050 (570\u0026ndash;11660)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e2630 (400\u0026ndash;16400)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e2900 (570\u0026ndash;11500)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e2740 (880\u0026ndash;11590)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.71\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 159px;\"\u003e\n \u003cp\u003eHemoglobin (g/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003eMedian (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e10.1 (7.7\u0026ndash;15.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e10.9 (6.3\u0026ndash;14.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026lt; 0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e10.3 (7.7\u0026ndash;15.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e10.5 (7.4\u0026ndash;14.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.29\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 159px;\"\u003e\n \u003cp\u003eAlbumin (g/dl)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003eMedian (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e3.5 (1.7\u0026ndash;4.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e3.7 (2.4\u0026ndash;4.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026lt; 0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e3.5 (2.2\u0026ndash;4.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e3.6 (2.5\u0026ndash;4.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 159px;\"\u003e\n \u003cp\u003eCRP (mg/dl)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003eMedian (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e0.43 (0.01\u0026ndash;20.37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e0.35 (0.01\u0026ndash;24.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e0.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e0.43 (0.01\u0026ndash;12.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e0.38 (0.01\u0026ndash;11.22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.98\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 159px;\"\u003e\n \u003cp\u003eCEA (ng/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003eMedian (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e7.6 (1.1\u0026ndash;276.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e6.5 (0.7\u0026ndash;12369.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e0.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e7.0 (1.1\u0026ndash;276.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e7.2 (0.8\u0026ndash;12369.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.86\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 159px;\"\u003e\n \u003cp\u003eCA19-9 (U/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003eMedian (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e2125.0 (2\u0026ndash;50000)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e818.7 (2\u0026ndash;50000)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026lt; 0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e1140.3 (2\u0026ndash;50000)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e797.3 (2\u0026ndash;50000)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 159px;\"\u003e\n \u003cp\u003eGPS, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003eLow (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e66 (47.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e192 (60.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e51 (52.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e51 (52.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e\u0026gt; 0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 159px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003eHigh (1, 2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e73 (52.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e126 (39.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e46 (47.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e46 (47.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 159px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 130px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 131px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 131px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 131px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 131px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePSM, propensity score matching; ECOG PS, Eastern Cooperative Oncology Group performance status; mFFX, modified FOLFIRINOX; GnP, gemcitabine with nab-paclitaxel; CRP, C-reactive protein; CEA, carcinoembryonic antigen; CA19-9, carbohydrate antigen 19-9; GPS,\u0026nbsp;Glasgow prognostic score\u003c/p\u003e\n\u003cp\u003e*; Recurrent cases were excluded.\u003c/p\u003e\n\u003cp\u003e\u0026dagger;; Including cases with metastasis to multiple sites.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"international-journal-of-clinical-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijco","sideBox":"Learn more about [International Journal of Clinical Oncology](http://link.springer.com/journal/10147)","snPcode":"10147","submissionUrl":"https://www.editorialmanager.com/ijco/default2.aspx","title":"International Journal of Clinical Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"pancreatic cancer, chemotherapy, post-progression survival, FOLFIRINOX, gemcitabine with nab-paclitaxel","lastPublishedDoi":"10.21203/rs.3.rs-5965079/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5965079/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e This study aimed to evaluate the efficacy of the second-line combination chemotherapy (CC) for patients with metastatic or recurrent pancreatic cancer.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e We retrospectively analyzed consecutive patients with metastatic or recurrent pancreatic cancer, who received second-line chemotherapy after disease progression on first-line modified FOLFIRINOX (mFFX) or gemcitabine with nab-paclitaxel (GnP) between January 2014 and March 2023 at our hospital. Overall survival (OS), progression free survival (PFS), and post-progression survival (PPS) were compared between first-line mFFX and GnP. Additionally, OS, PFS, and PPS for second-line treatment with CC and single-agent chemotherapy (SAC) were compared using propensity score matching (PSM).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e A total of 457 patients (mFFX / GnP: 122 / 335) were included. Median OS and PPS of mFFX and GnP were 15.5 months vs. 15.0 months (p = 0.73) and 7.7 months vs. 7.2 months (p = 0.37), respectively. After PSM, median OS and median PPS were significantly longer in the CC group than in the SAC group (OS: 16.3 months vs. 12.8 months, p \u0026lt; 0.01; PPS: 8.0 months vs. 5.5 months, p \u0026lt; 0.01). There was no difference in first-line PFS between the two groups (7.1 months vs. 6.4 months, p = 0.74). Performance status at the beginning of first-line treatment, and carbohydrate antigen 19-9 level, Glasgow prognostic score at the end of first-line treatment, and second-line CC were independently associated with OS.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e Second-line CC achieved longer PPS and OS than SAC. To improve OS, it was important to receive second-line CC.\u003c/p\u003e","manuscriptTitle":"Impact of Second-line Combination Chemotherapy on Post-progression Survival in Metastatic and Recurrent Pancreatic Cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-30 11:30:26","doi":"10.21203/rs.3.rs-5965079/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Accept","date":"2025-05-18T00:24:50+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2025-04-20T07:35:10+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-20T01:43:35+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-04-17T04:56:17+00:00","index":"","fulltext":""},{"type":"submitted","content":"International Journal of Clinical Oncology","date":"2025-04-14T11:35:34+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"international-journal-of-clinical-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijco","sideBox":"Learn more about [International Journal of Clinical Oncology](http://link.springer.com/journal/10147)","snPcode":"10147","submissionUrl":"https://www.editorialmanager.com/ijco/default2.aspx","title":"International Journal of Clinical Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"447c7c31-9c15-4ff8-b294-d681dd462d51","owner":[],"postedDate":"April 30th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-06-16T16:07:09+00:00","versionOfRecord":{"articleIdentity":"rs-5965079","link":"https://doi.org/10.1007/s10147-025-02796-0","journal":{"identity":"international-journal-of-clinical-oncology","isVorOnly":false,"title":"International Journal of Clinical Oncology"},"publishedOn":"2025-06-11 15:58:05","publishedOnDateReadable":"June 11th, 2025"},"versionCreatedAt":"2025-04-30 11:30:26","video":"","vorDoi":"10.1007/s10147-025-02796-0","vorDoiUrl":"https://doi.org/10.1007/s10147-025-02796-0","workflowStages":[]},"version":"v1","identity":"rs-5965079","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5965079","identity":"rs-5965079","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}