Impact of Sarcopenia During Induction Treatment in Patients with Unresectable Locally Advanced Pancreatic Cancer: A Scoring Model for indication of Conversion Surgery

Impact of Sarcopenia During Induction Treatment in Patients with Unresectable Locally Advanced Pancreatic Cancer: A Scoring Model for indication of Conversion Surgery | 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 Sarcopenia During Induction Treatment in Patients with Unresectable Locally Advanced Pancreatic Cancer: A Scoring Model for indication of Conversion Surgery Sho Uemura, Masayuki Tanaka, Minoru Kitago, Hiroshi Yagi, Yuta Abe, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5706477/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Chemotherapeutic advances have increased opportunities for conversion surgery (CS) of unresectable locally advanced (UR-LA) pancreatic cancer (PC). However, the optimal indications for CS remain unclear. We aimed to identify predictive factors of prognosis in UR-LA PC, and evaluate indication for CS using these factors including sarcopenia. Methods In this retrospective study, we reviewed consecutive patients with UR-LA PC who had received chemo(radio)therapy as an initial treatment between 2015 and 2023. We examined relevant clinical variables and CT findings at initial diagnosis and at 6 months after starting treatment. Results Ten of the 41 patients had undergone CS. Tumor size at 6 months, clinical lymph node metastasis at diagnosis, and changes in sarcopenia over 6 months were associated with overall survival (OS) (multivariate analysis: hazard ratio = 3.25, 2.79 and 3.51, respectively). Each of these factors was assigned a value of 1, resulting in a scoring system ranging from 0 to 3 points. There was a significant difference in OS between the patients who scored 0 points and those who scored 1 to 3 points (median OS: 30.3 months v.s. 17.3 months, P = 0.013). CS was associated with better OS among patients who scored 0 (not reached v.s. 25.5 months, P = 0.039). Conclusions Change in sarcopenia is a novel predictor of the prognosis of patients with UR-LA PC. Patients with favorable scores in our simple scoring model, which incorporates three prognostic factors identified by the current analysis, may achieve better survival after CS than that achieved induction therapy alone. chemotherapy conversion surgery sarcopenia scoring model unresectable locally advanced pancreatic cancer Figures Figure 1 Figure 2 Figure 3 BACKGROUND Pancreatic cancer (PC) has one of the worst survival rates of cancers worldwide. At initial presentation, only 10–20% of patients present with resectable disease, the majority having distant metastases (50–60%) or locally advanced disease (20–30%) [ 1 ]. Multidisciplinary treatments combining surgical resection and chemo(radio)therapy have been implemented with the aim of improving the survival of patients with unresectable PC [ 2 , 3 ]. Development of multidisciplinary treatments has enabled to perform conversion surgery (CS) for highly selected patients with UR-LA PC [ 4 , 5 , 6 ]. Several articles have reported impacts of resectability and curative resection on the prognosis of patients who undergo CS after induction therapy [ 7 , 8 ]. Although CS reportedly improves survival, the optimal indications for this procedure remain unclear [ 9 ]. Hence, in clinical practice, decisions for CS of UR-LA PC after induction treatment have been made on a highly individualized basis. It has recently been demonstrated that sarcopenia, which is loss of muscle mass with age, is associated with poor short-and long-term outcomes in various types of malignancies, including PC [ 10 , 11 ]. An association between sarcopenia and unfavorable prognosis in patients with unresectable PC has been reported [ 12 ]. However, that series lacked evidence regarding the impact of change of sarcopenia status during chemotherapy on clinical outcomes. Therefore, the aims of this study were to investigate predictors of prognosis in all patients with UR-LA PC, and to establish a novel guide which may support decision-making for CS. METHODS Study Design and Participants We retrospectively reviewed data of 41 consecutive patients with UR-LA PC cases who had chemo(radio)therapy between January 2015 and December 2023 at the Department of Surgery, Keio University Hospital. We allocated the patients to two groups: those who had undergone pancreatectomy (CS group) and those who had not (C[R]Tx group). UR-LA PC was defined according to the NCCN guidelines [ 13 ]. This study was approved by the Ethics Committee of the Keio University School of Medicine (Approval number: 20140389). The most commonly administered regimens of chemo(radio)therapy were gemcitabine plus nab-paclitaxel (GnP) or folinic acid, fluorouracil, irinotecan, and oxaliplatin (FFX), with or without radiotherapy. Decisions on this therapy were based on patient age, general condition, doctor preference and clinical study. In the present study, we evaluated relevant clinical variables at initial diagnosis and at 6 months after commencing treatment. At least 6 months of induction treatment was generally planned for patients with newly diagnosed UR-LA PC. For all patients undergoing CS, the clinical variables were evaluated immediately before surgery. Patient Surveillance During Chemo(radio)therapy From the time of initial diagnosis and commencement of chemo(radio)therapy, patients were basically reevaluated every 3 months during treatment by clinical examination, measurement of CA19-9 serum levels, and computed tomography (CT). The imaging data were transferred to a computer workstation to assess the psoas muscle area. Cross-sectional areas of the right and left psoas muscles at the middle level of the third lumbar vertebra were automatically measured using SYNAPSE VINCENT software (Fuji Film, Tokyo, Japan). The measured psoas muscle area was normalized for height using the following equation: normalized psoas muscle area, defined as the psoas muscle mass index (PMI, cm 2 /m 2 ) = measured psoas muscle area (cm 2 ) / height (m 2 ). Indications for Conversion Surgery The surgical indications for UR-LA PC patients were discussed by a multidisciplinary team of surgeons, oncological physicians, and radiologists. The general surgical indications were: (1) no tumor progression on imaging, (2) declining or stable CA19-9 levels; and (3) technically resectable disease (including the consideration of venous and arterial resections). The final decisions concerning performing CS on patients who did not fulfil all of these criteria were made by the multidisciplinary team. Outcomes Study variables included patient characteristics and laboratory data. Normal CA19-9 serum levels were defined as ≦ 37 U/mL at the relevant assessment point. Tumor size was defined as the maximum tumor diameter on axial CT slices. Clinical lymph node metastasis was defined as nodes having a short axis of 10mm or more on CT images or showing increased uptake on PET-CT. Inflammation-based prognostic scores, which indicate the nutritional status and predict prognosis, such as the Modified Glasgow Prognostic Score (mGPS), controlling nutritional status (CONUT), the prognostic nutritional index (PNI), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR), were calculated [ 14 , 15 , 16 , 17 , 18 ]. All continuous variables were divided by the appropriate cut-off value to convert them to categorical variables. The primary endpoint of this study was determination of predictive factors of overall survival (OS) in patients with UR-LA PC. Statistical Analysis All analyses were performed using SPSS software (Version.29; IBM Corp., Armonk, NY, USA). OS was defined as the time from the date of initiation of chemo(radio)therapy to the date of death from any cause and was calculated using Kaplan-Meier survival analysis. Data were censored if the patient had been alive at the time of the analysis or had been lost to follow-up. The optimal cutoff points for continuous variables for OS were determined by using a minimum P -value approach [ 19 ]. All possible cutoff points were examined by means of the log-rank test. The value with the minimum P -value was considered to be the optimal cutoff point. We performed univariate analyses using Cox proportional hazard regression models to select variables likely related to OS among all candidate factors. Factors with P < 0.05 according to univariate analysis were used in the multivariate analysis with Cox proportional hazard regression models to identify independent prognostic factors. In order to establish the optimal indications for CS, a scoring model was created using the hazard ratios (HRs) for OS of the significant predictors according to multivariable Cox regression. These scores were scaled down to 1, as previously reported [ 9 ]. P < 0.05 was considered to denote statistical significance. RESULTS Baseline Patient Characteristics and Survival Outcomes Forty-one patients with UR-LA PC who had chemo(radio)therapy as the initial treatment were identified (Table 1 ). Preoperative CA19-9 serum levels were not available for two of these patients (5%). The median data of following variables were worse at 6 months after starting treatment: CA19-9, tumor size, PMI, mGPS, CONUT, PNI, NLR, and PLR. Surgery was scheduled on 14 patients (34%) and CS on 10 (24%). Four patients underwent palliative or explorative surgery, due to two peritoneal disseminations, one cytology-positive peritoneal washings, and one increased local invasion that was found intraoperatively. Comparisons between the CS and C[R]Tx groups revealed that no significant differences in terms of CA19-9 at diagnosis and at 6 months. The CS group had significantly smaller tumor sizes at 6 months (15 mm vs. 33 mm, P = 0.030) and greater PMI at 6 months (5.46 cm 2 /m 2 vs. 4.76 cm 2 /m 2 , P = 0.025). The median OS was longer in the CS than C[R]Tx group (35.9 months vs. 15.7 months, P = 0.006) (Fig. 1 .). Table 1 Patient background of all patients and according to resection status Parameter Patients N = 41 CS group N = 10 C[R]Tx group N = 31 P Age (years), median (range) 69 (42–86) 72 (57–77) 69 (42–86) 0.988 Male gender, n (%) 24 (58.5) 8 (80.0) 16 (51.6) 0.096 Body mass index (kg/㎡), median (range) 21.7 (16.8–30.6) 22.2 (19.1–29.3) 20.6 (16.8–30.6) 0.115 Chemotherapy regimen Gemcitabine base, n (%) 35 (85.4) 9 (90.0) 26 (83.9) 0.644 5-FU base, n (%) 5 (12.2) 1 (10.0) 4 (12.9) 0.813 RTx, n (%) 17 (41.5) 4 (40.0) 13 (41.9) 0.917 Clinical lymph node metastasis at diagnosis, n (%) 11 (26.8) 2 (20.0) 9 (29.0) 0.586 CA19-9 (U/ml) at diagnosis, median (range) 104 (2-5831) 49 (12–742) 115 (2-5831) 0.492 after 6 months, median (range) 48 (2-20548) 19 (7–90) 76 (2-20548) 0.402 Tumor size (mm) at diagnosis, median (range) 34 (14–100) 33 (15–45) 34 (14–100) 0.629 after 6 months, median (range) 30 (7-100) 15 (11–37) 33 (7-100) 0.030 PMI (cm 2 /m 2 ) at diagnosis, median (range) 5.27 (3.37–8.06) 6.07 (4.01–8.06) 5.18 (3.37–7.90) 0.120 after 6 months, median (range) 4.95 (2.13–7.68) 5.46 (3.84–7.68) 4.76 (2.13–7.27) 0.025 mGPS, (0/1/2) at diagnosis 33/7/1 8/2/0 25/5/1 0.883 after 6 months 19/12/10 9/1/0 10/11/10 0.112 CONUT, (normal/mild/moderate/severe) at diagnosis 14/22/5/0 5/2/3/0 9/20/2/0 0.969 after 6 months 5/12/18/6 4/4/2/0 1/8/16/6 0.106 PNI at diagnosis, median (range) 47.2 (37.1–55.8) 50.9 (41.2–52.8) 45.6 (37.1–55.8) 0.249 after 6 months, median (range) 42.2 (29.2–52.0) 46.3 (38.9–50.7) 39.3 (29.2–52.0) 0.229 NLR at diagnosis, median (range) 2.8 (1.1–7.5) 2.7 (1.4–5.2) 2.9 (1.1–7.5) 0.651 after 6 months, median (range) 3.7 (0.7–17.3) 3.7 (1.2–7.5) 3.6 (0.7–17.3) 0.056 PLR at diagnosis, median (range) 172.5 (91.0-387.0) 127.4 (93.9-288.1) 179.6 (91.0-387.0) 0.235 after 6 months, median (range) 241.3 (46.4–1168.0) 232.8 (99.2-344.7) 244.5 (46.4–1168.0) 0.234 Abbreviations: CS, conversion surgery; C[R]Tx, chemo(radio)therapy; 5-FU, 5-fluorouracil; CA19-9, carbohydrate antigen 19 − 9; PMI, psoas muscle mass index; mGPS, modified Glasgow Prognostic Score; CONUT, controlling nutritional status; PNI, prognostic nutritional index; NLR, neutrophil-lymphocyte ratio; PLR, platelet-lymphocyte ratio; RTx, radiation therapy Defining Cut-off Points According to a minimum P -value approach by the log-rank test, in which every possible cut-off point for each continuous variable for OS was assessed, continuous variables were converted to dichotomous variables by using the relevant cut-off points. The best cut-off point for tumor size at 6 months was 35mm ( P < 0.001) and that for rate of change of PMI during the first 6 months was 1.10 ( P < 0.001). Univariate and Multivariate Analysis of Survival According to univariate analysis, tumor size at 6 months, normalization of CA19-9 serum levels, clinical lymph node metastasis at diagnosis, rate of change in PMI during the first 6 months, and CS were significantly associated with OS ( P < 0.001, P = 0.002, P = 0.047, P < 0.001, and P = 0.011, respectively). Among these five factors, multivariate analysis revealed that tumor size at 6 months, clinical lymph node metastasis at diagnosis, and rate of change of PMI during the first 6 months were significantly relevant to OS ( P = 0.019, P = 0.036, P = 0.039, respectively) (Table 2 ). Table 2 Results of univariate and multivariate analysis of predictors of overall survival Variables Univariate analysis Multivariate analysis P Hazard ratio 95%CI P Tumor size at 6 months (mm) < 0.001 3.247 1.211–8.702 0.019 ≧ 35 < 35 CA19-9 serum levels normalized 0.002 1.956 0.713–5.369 0.193 No Yes Clinical lymph node metastasis at diagnosis 0.047 2.785 1.067–7.267 0.036 Yes No Change rate of PMI during 6 months < 0.001 3.514 1.065–11.589 0.039 ≧ 1.10 < 1.10 Conversion Surgery 0.011 0.405 0.119–1.371 0.146 Yes No Abbreviation: PMI, psoas muscle mass index Predictive Model and Effect of Resection among Cases with Favorable Prognostic Scores In the multivariate analysis, the HRs for OS of tumor size at 6 months, clinical lymph node metastasis, and rate of change of PMI during the first 6 months were 3.25, 2.79, and 3.51, respectively (Table 2 ). Consequently, a score of 1 was assigned to each factor identified by multivariate analysis, resulting in scores ranging from 0 to 3 points. According to this scoring system, 14 patients (34%) scored no points and 27 patients (66%) scored 1 to 3 points (Table 3 ). There was a significant difference in OS between patients who scored no points and those who scored 1 to 3 points (median OS: 30.3 months vs. 17.3 months, P = 0.013) (Fig. 2 ). Four of the patients (29%) who had undergone CS scored no points. Among the patients who scored no points, CS was associated with better OS (median OS: not reached vs. 25.5 months, P = 0.039) (Fig. 3 a). In contrast, among the patients who scored 1 to 3 points, CS was not associated with a better OS (median OS: 23.2 months vs. 13.2 months, P = 0.183) (Fig. 3 b). Table 3 Patient distribution according to model scores for the prognosis of UR-LA PC Score N (%) 0 14 (34) 1 11 (27) 2 11 (27) 3 5 (12) Abbreviations: UR-LA, unresectable locally advanced; PC, pancreatic cancer DISCUSSION In this study, tumor size at 6 months, clinical lymph node metastasis at diagnosis, and rate of change of PMI during the first 6 months after initial treatment were identified as independent predictors of survival in patients with initially UR-LA PC and received chemo(radio)therapy. Furthermore, we established a simple prognostic scoring model comprised of these three factors. Although CS did not prolong prognosis in patients with unfavorable scores (1, 2, or 3 points), it was associated with prolongation of OS in those with favorable scores. Predictive factors of the prognosis of patients who undergo induction treatment followed by CS for UR-LA PC have been controversial over the past decade [ 20 ]. With advances in multidisciplinary treatments for UR-LA PC, several prognostic factors, such as normalization of CA19-9 levels after induction treatment, tumor shrinkage, and CS have been reported [ 8 , 21 ]. Additionally, sarcopenia, as a poor prognostic factor, has been paid attention to [ 12 , 22 ]. Although several studies have reported indication for CS, no association between sarcopenia and CS has been reported. In the present study, we identified these three factors as being significantly associated with prognosis. Tumor size after induction treatment as a predictor of resectability and OS has been reported in several articles [ 9 , 22 , 23 ]. And, regional lymph node metastasis has been shown to be associated with poor prognoses in patients with resectable, borderline resectable, and UR-LA PC [ 24 , 25 , 26 ]. Progression of sarcopenia has been reported to impair patient’s tolerance to chemotherapy [ 27 , 28 ], so that its dose reductions or discontinuation are often needed. Deterioration in skeletal muscle mass during neoadjuvant therapy has been linked to poor prognoses in patients with resectable and borderline resectable PC, but not reported in those with UR-LA PC [ 27 , 29 ]. Thus, rate of change of PMI may reflect prognosis, even in those with UR-LA PC, supporting its use as an indication for CS. Using the findings of univariate and multivariate analyses, we established a scoring system that utilizes weighted values derived from the HRs for the prognosis of UR-LA PC. As the indications for CS remains unclear, two recent reports have focused on the optimal timing for CS in patients with UR-LA PC by creating scoring systems based on prognostic factors [ 9 , 30 ]. However, one of these studies did not include a control group without CS [ 9 ], and the other included patients with UR-M in the analysis [ 30 ]. Neither of these reports mentioned sarcopenia. In contrast with these studies, our study included all consecutive patients with UR-LA PC and evaluated indication for CS with prognostic factors, including sarcopenia. Although multiple reports have demonstrated that CS improved the survival of UR-LA PC patients [ 8 , 20 , 21 , 30 ], the true impact of CS has remained unclear because of a lack of patients who had a good responses to induction treatment, but did not purposely undergo CS. In this study, we found that CS was associated with significantly improved outcomes in patients with the favorable prognostic scores (no points), whereas CS did not prolong prognosis in those with the unfavorable scores (1, 2, or 3 points). Although CS was not an independent prognostic factor, our results imply that performing oncologic resection in patients with no points may further enhance survival outcomes. Hence, CS can provide additional benefits in selected patients with UR-LA PC and setting a boundary between scores of 0 and 1 may lead to better decision-making concerning implementing CS. This study had several limitations. First, it was a small, retrospective, single institution study. However, this is the first to examine the relationship between sarcopenia and CS among patients with UR-LA PC. Second, although the duration of this study was approximately 6 months based on the previous reports, the optimal duration of induction treatment for CS varied widely. [ 30 , 31 , 32 ]. Third, clinical parameters were basically evaluated at 6 months after commencing treatment. However, the variations in timing of evaluation of clinical parameters in patients who undertook CS or selected best supportive care within 6 months may have contributed to a risk of bias. Fourth, induction treatment regimens were not standardized. This may lead to the heterogeneity of morphologic response by various agents. Lastly, though previous studies have reported that CS may be associated with prolongation of survival [ 8 , 20 , 21 , 30 ], we did not identify it as an independent prognostic factor in the present study, possibly due to our suboptimal indication for CS. Consequently, our analysis was focused on the additional benefits of CS. However, due to the small number of patients in the favorable group, multivariate analysis could not be performed, necessitating further validation in future study. CONCLUSIONS In this study, we identified prognostic indicators in patients with UR-LA PC, and established a simple scoring model that incorporated the three identified factors. Stratification according to this scoring system may be useful in predicting survival outcomes and may be valuable in guiding the indications for CS. Patients with favorable scores are considered candidates for CS and can achieve excellent survival times. Declarations ACKNOWLEDGEMENT We would like to thank Dr Trish Reynolds, MBBS, FRACP, from Edanz (http://www.edanz.com/) for English language editing. Authors’ contributions SU, MT, and MK conceived and designed this study. SU and MT drafted the manuscript. HY, YA, YH, SH, YN, and YK analyzed the data and critically revised the manuscript. All authors were involved in data interpretation and drafting the manuscript and have read and approved the final version of the manuscript. Disclosure of ethical statements This study was approved by the Ethics Committee of the Keio University School of Medicine (Approval number: 20140389). Conflict of interest Dr. Kitagawa has received grants and has been involved in lectures for TAIHO PHARMACEUTICAL CO., LTD., CHUGAI PHARMACEUTICAL CO., LTD., DAIICHI SANKYO COMPANY, LIMITED, Takeda Pharmaceutical Company Limited, Nippon Kayaku Co., Ltd., and MSD K.K. Additionally, he has been involved in lectures for Yakult Honsha Co., Ltd. and has received a grant from Kyouwa Hakkou Kirin Co., Ltd. Disclaimer The funding source had no role in the design, practice, or analysis of this study. References Vincent A, Herman J, Schulick R et al (2011) Pancreat cancer Lancet 378(9791):607–620 Von Hoff DD, Ervin T, Arena FP et al (2013) Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 369(18):1691–1703 Loehrer PJ, Sr., Feng Y, Cardenes H et al (2011) Gemcitabine alone versus gemcitabine plus radiotherapy in patients with locally advanced pancreatic cancer: an Eastern Cooperative Oncology Group trial. J Clin Oncol 29(31):4105–4112 Suker M, Beumer BR, Sadot E et al (2016) FOLFIRINOX for locally advanced pancreatic cancer: a systematic review and patient-level meta-analysis. Lancet Oncol 17(6):801–810 Yamada S, Fujii T, Yokoyama Y et al (2018) Phase I study of chemoradiotherapy using gemcitabine plus nab-paclitaxel for unresectable locally advanced pancreatic cancer. Cancer Chemother Pharmacol 81(5):815–821 Nitsche U, Wenzel P, Siveke JT et al (2015) Resectability After First-Line FOLFIRINOX in Initially Unresectable Locally Advanced Pancreatic Cancer: A Single-Center Experience. Ann Surg Oncol 22(Suppl 3):S1212–1220 Hackert T (2018) Surgery for Pancreatic Cancer after neoadjuvant treatment. Ann Gastroenterol Surg 2(6):413–418 Satoi S, Yamamoto T, Yamaki S et al (2020) Surgical indication for and desirable outcomes of conversion surgery in patients with initially unresectable pancreatic ductal adenocarcinoma. Ann Gastroenterol Surg 4(1):6–13 Tanaka M, Heckler M, Mihaljevic AL et al (2023) Induction Chemotherapy with FOLFIRINOX for Locally Advanced Pancreatic Cancer: A Simple Scoring System to Predict Effect and Prognosis. Ann Surg Oncol 30(4):2401–2408 Chindapasirt J (2015) Sarcopenia in Cancer Patients. Asian Pac J Cancer Prev 16(18):8075–8077 Otten L, Stobäus N, Franz K et al (2019) Impact of sarcopenia on 1-year mortality in older patients with cancer. Age Ageing 48(3):413–418 Salinas-Miranda E, Deniffel D, Dong X et al (2021) Prognostic value of early changes in CT-measured body composition in patients receiving chemotherapy for unresectable pancreatic cancer. Eur Radiol 31(11):8662–8670 Tempero MA, Malafa MP, Al-Hawary M et al (2021) Pancreatic Adenocarcinoma, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 19(4):439–457 Pinato DJ, North BV, Sharma R (2012) A novel, externally validated inflammation-based prognostic algorithm in hepatocellular carcinoma: the prognostic nutritional index (PNI). Br J Cancer 106(8):1439–1445 Miyata T, Yamashita YI, Higashi T et al (2018) The Prognostic Impact of Controlling Nutritional Status (CONUT) in Intrahepatic Cholangiocarcinoma Following Curative Hepatectomy: A Retrospective Single Institution Study. World J Surg 42(4):1085–1091 Lin G, Liu Y, Li S et al (2016) Elevated neutrophil-to-lymphocyte ratio is an independent poor prognostic factor in patients with intrahepatic cholangiocarcinoma. Oncotarget 7(32):50963–50971 Chen Q, Dai Z, Yin D et al (2015) Negative impact of preoperative platelet-lymphocyte ratio on outcome after hepatic resection for intrahepatic cholangiocarcinoma. Med (Baltim) 94(13):e574 Okuno M, Ebata T, Yokoyama Y et al (2016) Evaluation of inflammation-based prognostic scores in patients undergoing hepatobiliary resection for perihilar cholangiocarcinoma. J Gastroenterol 51(2):153–161 Prado CM, Lieffers JR, McCargar LJ et al (2008) Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study. Lancet Oncol 9(7):629–635 Seufferlein T, Hammel P, Delpero JR et al (2019) Optimizing the management of locally advanced pancreatic cancer with a focus on induction chemotherapy: Expert opinion based on a review of current evidence. Cancer Treat Rev 77:1–10 Tanaka M, Heckler M, Mihaljevic AL et al (2019) CT response of primary tumor and CA19-9 predict resectability of metastasized pancreatic cancer after FOLFIRINOX. Eur J Surg Oncol 45(8):1453–1459 Asama H, Ueno M, Kobayashi S et al (2022) Sarcopenia: Prognostic Value for Unresectable Pancreatic Ductal Adenocarcinoma Patients Treated With Gemcitabine Plus Nab-Paclitaxel. Pancreas 51(2):148–152 Michelakos T, Pergolini I, Castillo CF et al (2019) Predictors of Resectability and Survival in Patients With Borderline and Locally Advanced Pancreatic Cancer who Underwent Neoadjuvant Treatment With FOLFIRINOX. Ann Surg 269(4):733–740 Klaiber U, Schnaidt ES, Hinz U et al (2021) Prognostic Factors of Survival After Neoadjuvant Treatment and Resection for Initially Unresectable Pancreatic Cancer. Ann Surg 273(1):154–162 Morales-Oyarvide V, Rubinson DA, Dunne RF et al (2017) Lymph node metastases in resected pancreatic ductal adenocarcinoma: predictors of disease recurrence and survival. Br J Cancer 117(12):1874–1882 Medrano J, Garnier J, Ewald J et al (2020) Patient outcome according to the 2017 international consensus on the definition of borderline resectable pancreatic ductal adenocarcinoma. Pancreatology 20(2):223–228 Sandini M, Patino M, Ferrone CR et al (2018) Association Between Changes in Body Composition and Neoadjuvant Treatment for Pancreatic Cancer. JAMA Surg 153(9):809–815 Takaichi S, Tomimaru Y, Kobayashi S et al (2023) Change Impact of Body Composition During Neoadjuvant Chemoradiotherapy in Patients with Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma Undergoing Pancreatectomy. Ann Surg Oncol 30(4):2458–2468 Choi MH, Yoon SB (2022) Sarcopenia in pancreatic cancer: Effect on patient outcomes. World J Gastrointest Oncol 14(12):2302–2312 Ushida Y, Inoue Y, Oba A et al (2022) Optimizing Indications for Conversion Surgery Based on Analysis of 454 Consecutive Japanese Cases with Unresectable Pancreatic Cancer Who Received Modified FOLFIRINOX or Gemcitabine Plus Nab-paclitaxel: A Single-Center Retrospective Study. Ann Surg Oncol 29(8):5038–5050 Williams JL, Kadera BE, Nguyen AH et al (2016) CA19-9 Normalization During Pre-operative Treatment Predicts Longer Survival for Patients with Locally Progressed Pancreatic Cancer. J Gastrointest Surg 20(7):1331–1342 Takano N, Yamada S, Sonohara F et al (2021) The impact of early tumor shrinkage on conversion surgery and the survival in patients with unresectable locally advanced pancreatic cancer. Surg Today 51(7):1099–1107 Additional Declarations No competing interests reported. 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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-5706477","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":396062872,"identity":"442b09f2-c9ba-4e37-a91e-c083ca1c011f","order_by":0,"name":"Sho Uemura","email":"","orcid":"","institution":"Keio University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Sho","middleName":"","lastName":"Uemura","suffix":""},{"id":396062873,"identity":"eb9d45ad-3ee0-4838-b011-135b7b9186eb","order_by":1,"name":"Masayuki Tanaka","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAwklEQVRIiWNgGAWjYDADfh4GhgMMDGwkaJHsIVmLwRliVeq2H3/4gXFHnd3mM4cPHvjAwJdHUIvZmRxjCcYzh5O3nW1LODiDga2YsJYDOQwSjG0Hks3O8xgc5mFgS2wgqOX888c/GNvqko37+T8QqeVGghnQFmY7A94eBmK1vDGzAPolQeLMMYODMwyI8cv59Mc3gCFmz9+T/PjDh4pjhEMMBJj/NjBA3WNwLIEoLQyMDQz2UGYNkVpGwSgYBaNgJAEAOJxAdfZhZosAAAAASUVORK5CYII=","orcid":"","institution":"Keio University School of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Masayuki","middleName":"","lastName":"Tanaka","suffix":""},{"id":396062876,"identity":"59bcc926-8e4a-4a8a-843b-b64ebd8004f7","order_by":2,"name":"Minoru Kitago","email":"","orcid":"","institution":"Keio University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Minoru","middleName":"","lastName":"Kitago","suffix":""},{"id":396062877,"identity":"a2712d79-c876-49c1-a62b-3b3c0e0cdead","order_by":3,"name":"Hiroshi Yagi","email":"","orcid":"","institution":"Keio University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Hiroshi","middleName":"","lastName":"Yagi","suffix":""},{"id":396062878,"identity":"200d3602-249e-4229-a053-a9ac4a3775b2","order_by":4,"name":"Yuta Abe","email":"","orcid":"","institution":"Keio University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yuta","middleName":"","lastName":"Abe","suffix":""},{"id":396062879,"identity":"9727b258-1599-456d-94e6-df8fbdd37370","order_by":5,"name":"Yasushi Hasegawa","email":"","orcid":"","institution":"Keio University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yasushi","middleName":"","lastName":"Hasegawa","suffix":""},{"id":396062880,"identity":"9a234429-5ad4-49c8-b83a-36c8e209e7a5","order_by":6,"name":"Shutaro Hori","email":"","orcid":"","institution":"Keio University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Shutaro","middleName":"","lastName":"Hori","suffix":""},{"id":396062881,"identity":"a8ab0e46-2529-4eab-86f2-3252eb16bc84","order_by":7,"name":"Yutaka Nakano","email":"","orcid":"","institution":"Keio University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yutaka","middleName":"","lastName":"Nakano","suffix":""},{"id":396062882,"identity":"476c91af-da42-4b53-a24d-0f54968e32e4","order_by":8,"name":"Yuko Kitagawa","email":"","orcid":"","institution":"Keio University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yuko","middleName":"","lastName":"Kitagawa","suffix":""}],"badges":[],"createdAt":"2024-12-24 13:23:06","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5706477/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5706477/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":72739458,"identity":"318bb74a-921b-4bd1-bb8c-ae807d4be60a","added_by":"auto","created_at":"2025-01-01 09:24:02","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":222321,"visible":true,"origin":"","legend":"\u003cp\u003eOverall survival of all patients who had versus had not undergone CS. There was a significant difference (\u003cem\u003eP\u003c/em\u003e = 0.006).\u003c/p\u003e\n\u003cp\u003eAbbreviation: CS, Conversion surgery\u003c/p\u003e","description":"","filename":"Figure1TIFF.tiff.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5706477/v1/346b01c361731a81cba32c6b.jpg"},{"id":72739460,"identity":"b1e10166-beda-48ae-b930-2549b68d6aec","added_by":"auto","created_at":"2025-01-01 09:24:02","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":202679,"visible":true,"origin":"","legend":"\u003cp\u003eOverall survival in patients who scored no points (A) versus those who scored 1 to 3 points (B). There was a significant difference (\u003cem\u003eP\u003c/em\u003e= 0.013).\u003c/p\u003e","description":"","filename":"Figure2TIFF.tiff.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5706477/v1/589002bbe2266fdfbfe67eb8.jpg"},{"id":72739461,"identity":"021c2311-3050-416f-99ff-cd71915bca81","added_by":"auto","created_at":"2025-01-01 09:24:02","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":491634,"visible":true,"origin":"","legend":"\u003cp\u003eEffect of CS in patients with favorable versus unfavorable prognostic scores. (a) Overall survival of patients with scores of 0 who had versus had not undergone CS. There was a significant difference (\u003cem\u003eP\u003c/em\u003e= 0.039). (b) Overall survival of patients with scores of 1 to 3 who had versus had not undergone CS. There wasn’t a significant difference (\u003cem\u003eP\u003c/em\u003e = 0.183).\u003c/p\u003e\n\u003cp\u003eAbbreviation: CS, Conversion surgery\u003c/p\u003e","description":"","filename":"Figure3aTIFF.tiff.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5706477/v1/e647bebf002e26f32195669d.jpg"},{"id":79099143,"identity":"c42fb2c8-fcaf-4e32-9f10-97a8569bcd56","added_by":"auto","created_at":"2025-03-24 11:47:10","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1806017,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5706477/v1/863c49c5-90ec-4d71-8d9a-2969bcb5ecf3.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Impact of Sarcopenia During Induction Treatment in Patients with Unresectable Locally Advanced Pancreatic Cancer: A Scoring Model for indication of Conversion Surgery","fulltext":[{"header":"BACKGROUND","content":"\u003cp\u003ePancreatic cancer (PC) has one of the worst survival rates of cancers worldwide. At initial presentation, only 10\u0026ndash;20% of patients present with resectable disease, the majority having distant metastases (50\u0026ndash;60%) or locally advanced disease (20\u0026ndash;30%) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Multidisciplinary treatments combining surgical resection and chemo(radio)therapy have been implemented with the aim of improving the survival of patients with unresectable PC [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDevelopment of multidisciplinary treatments has enabled to perform conversion surgery (CS) for highly selected patients with UR-LA PC [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Several articles have reported impacts of resectability and curative resection on the prognosis of patients who undergo CS after induction therapy [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Although CS reportedly improves survival, the optimal indications for this procedure remain unclear [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Hence, in clinical practice, decisions for CS of UR-LA PC after induction treatment have been made on a highly individualized basis.\u003c/p\u003e \u003cp\u003eIt has recently been demonstrated that sarcopenia, which is loss of muscle mass with age, is associated with poor short-and long-term outcomes in various types of malignancies, including PC [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. An association between sarcopenia and unfavorable prognosis in patients with unresectable PC has been reported [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. However, that series lacked evidence regarding the impact of change of sarcopenia status during chemotherapy on clinical outcomes.\u003c/p\u003e \u003cp\u003eTherefore, the aims of this study were to investigate predictors of prognosis in all patients with UR-LA PC, and to establish a novel guide which may support decision-making for CS.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design and Participants\u003c/h2\u003e \u003cp\u003eWe retrospectively reviewed data of 41 consecutive patients with UR-LA PC cases who had chemo(radio)therapy between January 2015 and December 2023 at the Department of Surgery, Keio University Hospital. We allocated the patients to two groups: those who had undergone pancreatectomy (CS group) and those who had not (C[R]Tx group). UR-LA PC was defined according to the NCCN guidelines [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. This study was approved by the Ethics Committee of the Keio University School of Medicine (Approval number: 20140389).\u003c/p\u003e \u003cp\u003eThe most commonly administered regimens of chemo(radio)therapy were gemcitabine plus nab-paclitaxel (GnP) or folinic acid, fluorouracil, irinotecan, and oxaliplatin (FFX), with or without radiotherapy. Decisions on this therapy were based on patient age, general condition, doctor preference and clinical study. In the present study, we evaluated relevant clinical variables at initial diagnosis and at 6 months after commencing treatment. At least 6 months of induction treatment was generally planned for patients with newly diagnosed UR-LA PC. For all patients undergoing CS, the clinical variables were evaluated immediately before surgery.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003ePatient Surveillance During Chemo(radio)therapy\u003c/h3\u003e\n\u003cp\u003eFrom the time of initial diagnosis and commencement of chemo(radio)therapy, patients were basically reevaluated every 3 months during treatment by clinical examination, measurement of CA19-9 serum levels, and computed tomography (CT).\u003c/p\u003e \u003cp\u003eThe imaging data were transferred to a computer workstation to assess the psoas muscle area. Cross-sectional areas of the right and left psoas muscles at the middle level of the third lumbar vertebra were automatically measured using SYNAPSE VINCENT software (Fuji Film, Tokyo, Japan). The measured psoas muscle area was normalized for height using the following equation: normalized psoas muscle area, defined as the psoas muscle mass index (PMI, cm\u003csup\u003e2\u003c/sup\u003e/m\u003csup\u003e2\u003c/sup\u003e)\u0026thinsp;=\u0026thinsp;measured psoas muscle area (cm\u003csup\u003e2\u003c/sup\u003e) / height (m\u003csup\u003e2\u003c/sup\u003e).\u003c/p\u003e\n\u003ch3\u003eIndications for Conversion Surgery\u003c/h3\u003e\n\u003cp\u003eThe surgical indications for UR-LA PC patients were discussed by a multidisciplinary team of surgeons, oncological physicians, and radiologists. The general surgical indications were: (1) no tumor progression on imaging, (2) declining or stable CA19-9 levels; and (3) technically resectable disease (including the consideration of venous and arterial resections). The final decisions concerning performing CS on patients who did not fulfil all of these criteria were made by the multidisciplinary team.\u003c/p\u003e\n\u003ch3\u003eOutcomes\u003c/h3\u003e\n\u003cp\u003eStudy variables included patient characteristics and laboratory data. Normal CA19-9 serum levels were defined as ≦\u0026thinsp;37 U/mL at the relevant assessment point. Tumor size was defined as the maximum tumor diameter on axial CT slices. Clinical lymph node metastasis was defined as nodes having a short axis of 10mm or more on CT images or showing increased uptake on PET-CT. Inflammation-based prognostic scores, which indicate the nutritional status and predict prognosis, such as the Modified Glasgow Prognostic Score (mGPS), controlling nutritional status (CONUT), the prognostic nutritional index (PNI), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR), were calculated [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. All continuous variables were divided by the appropriate cut-off value to convert them to categorical variables.\u003c/p\u003e \u003cp\u003eThe primary endpoint of this study was determination of predictive factors of overall survival (OS) in patients with UR-LA PC.\u003c/p\u003e\n\u003ch3\u003eStatistical Analysis\u003c/h3\u003e\n\u003cp\u003eAll analyses were performed using SPSS software (Version.29; IBM Corp., Armonk, NY, USA). OS was defined as the time from the date of initiation of chemo(radio)therapy to the date of death from any cause and was calculated using Kaplan-Meier survival analysis. Data were censored if the patient had been alive at the time of the analysis or had been lost to follow-up. The optimal cutoff points for continuous variables for OS were determined by using a minimum \u003cem\u003eP\u003c/em\u003e-value approach [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. All possible cutoff points were examined by means of the log-rank test. The value with the minimum \u003cem\u003eP\u003c/em\u003e-value was considered to be the optimal cutoff point. We performed univariate analyses using Cox proportional hazard regression models to select variables likely related to OS among all candidate factors. Factors with \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 according to univariate analysis were used in the multivariate analysis with Cox proportional hazard regression models to identify independent prognostic factors. In order to establish the optimal indications for CS, a scoring model was created using the hazard ratios (HRs) for OS of the significant predictors according to multivariable Cox regression. These scores were scaled down to 1, as previously reported [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered to denote statistical significance.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eBaseline Patient Characteristics and Survival Outcomes\u003c/h2\u003e \u003cp\u003eForty-one patients with UR-LA PC who had chemo(radio)therapy as the initial treatment were identified (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Preoperative CA19-9 serum levels were not available for two of these patients (5%). The median data of following variables were worse at 6 months after starting treatment: CA19-9, tumor size, PMI, mGPS, CONUT, PNI, NLR, and PLR. Surgery was scheduled on 14 patients (34%) and CS on 10 (24%). Four patients underwent palliative or explorative surgery, due to two peritoneal disseminations, one cytology-positive peritoneal washings, and one increased local invasion that was found intraoperatively. Comparisons between the CS and C[R]Tx groups revealed that no significant differences in terms of CA19-9 at diagnosis and at 6 months. The CS group had significantly smaller tumor sizes at 6 months (15 mm vs. 33 mm, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.030) and greater PMI at 6 months (5.46 cm\u003csup\u003e2\u003c/sup\u003e/m\u003csup\u003e2\u003c/sup\u003e vs. 4.76 cm\u003csup\u003e2\u003c/sup\u003e/m\u003csup\u003e2\u003c/sup\u003e, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.025). The median OS was longer in the CS than C[R]Tx group (35.9 months vs. 15.7 months, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.006) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatient background of all patients and according to resection status\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePatients N\u0026thinsp;=\u0026thinsp;41\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCS group N\u0026thinsp;=\u0026thinsp;10\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eC[R]Tx group N\u0026thinsp;=\u0026thinsp;31\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAge (years), median (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e69 (42\u0026ndash;86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e72 (57\u0026ndash;77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e69 (42\u0026ndash;86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.988\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMale gender, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 (58.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (80.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e16 (51.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.096\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eBody mass index (kg/㎡), median (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21.7 (16.8\u0026ndash;30.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22.2 (19.1\u0026ndash;29.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e20.6 (16.8\u0026ndash;30.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.115\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eChemotherapy regimen\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGemcitabine base, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35 (85.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (90.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e26 (83.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.644\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5-FU base, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (12.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (10.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4 (12.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.813\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eRTx, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (41.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (40.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13 (41.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.917\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eClinical lymph node metastasis at diagnosis, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (26.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (20.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9 (29.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.586\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eCA19-9 (U/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eat diagnosis, median (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e104 (2-5831)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e49 (12\u0026ndash;742)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e115 (2-5831)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.492\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eafter 6 months, median (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48 (2-20548)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19 (7\u0026ndash;90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e76 (2-20548)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.402\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eTumor size (mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eat diagnosis, median (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34 (14\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e33 (15\u0026ndash;45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e34 (14\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.629\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eafter 6 months, median (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30 (7-100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15 (11\u0026ndash;37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e33 (7-100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.030\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003ePMI (cm\u003csup\u003e2\u003c/sup\u003e/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eat diagnosis, median (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.27 (3.37\u0026ndash;8.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.07 (4.01\u0026ndash;8.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.18 (3.37\u0026ndash;7.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.120\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eafter 6 months, median (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.95 (2.13\u0026ndash;7.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.46 (3.84\u0026ndash;7.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.76 (2.13\u0026ndash;7.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.025\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003emGPS, (0/1/2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eat diagnosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33/7/1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8/2/0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25/5/1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.883\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eafter 6 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19/12/10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9/1/0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10/11/10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.112\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eCONUT, (normal/mild/moderate/severe)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eat diagnosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14/22/5/0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5/2/3/0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9/20/2/0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.969\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eafter 6 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5/12/18/6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4/4/2/0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1/8/16/6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.106\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003ePNI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eat diagnosis, median (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e47.2 (37.1\u0026ndash;55.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50.9 (41.2\u0026ndash;52.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e45.6 (37.1\u0026ndash;55.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.249\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eafter 6 months, median (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42.2 (29.2\u0026ndash;52.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e46.3 (38.9\u0026ndash;50.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e39.3 (29.2\u0026ndash;52.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.229\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eNLR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eat diagnosis, median (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.8 (1.1\u0026ndash;7.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.7 (1.4\u0026ndash;5.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.9 (1.1\u0026ndash;7.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.651\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eafter 6 months, median (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.7 (0.7\u0026ndash;17.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.7 (1.2\u0026ndash;7.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.6 (0.7\u0026ndash;17.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.056\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003ePLR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eat diagnosis, median (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e172.5 (91.0-387.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e127.4 (93.9-288.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e179.6 (91.0-387.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.235\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eafter 6 months, median (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e241.3 (46.4\u0026ndash;1168.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e232.8 (99.2-344.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e244.5 (46.4\u0026ndash;1168.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.234\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eAbbreviations: CS, conversion surgery; C[R]Tx, chemo(radio)therapy; 5-FU, 5-fluorouracil; CA19-9, carbohydrate antigen 19\u0026thinsp;\u0026minus;\u0026thinsp;9; PMI, psoas muscle mass index; mGPS, modified Glasgow Prognostic Score; CONUT, controlling nutritional status; PNI, prognostic nutritional index; NLR, neutrophil-lymphocyte ratio; PLR, platelet-lymphocyte ratio; RTx, radiation therapy\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eDefining Cut-off Points\u003c/h3\u003e\n\u003cp\u003eAccording to a minimum \u003cem\u003eP\u003c/em\u003e-value approach by the log-rank test, in which every possible cut-off point for each continuous variable for OS was assessed, continuous variables were converted to dichotomous variables by using the relevant cut-off points. The best cut-off point for tumor size at 6 months was 35mm (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and that for rate of change of PMI during the first 6 months was 1.10 (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eUnivariate and Multivariate Analysis of Survival\u003c/h2\u003e \u003cp\u003eAccording to univariate analysis, tumor size at 6 months, normalization of CA19-9 serum levels, clinical lymph node metastasis at diagnosis, rate of change in PMI during the first 6 months, and CS were significantly associated with OS (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.047, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001, and \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.011, respectively). Among these five factors, multivariate analysis revealed that tumor size at 6 months, clinical lymph node metastasis at diagnosis, and rate of change of PMI during the first 6 months were significantly relevant to OS (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.019, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.036, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.039, respectively) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eResults of univariate and multivariate analysis of predictors of overall survival\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUnivariate analysis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e \u003cp\u003eMultivariate analysis\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHazard ratio\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e95%CI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTumor size at 6 months (mm)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.247\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.211\u0026ndash;8.702\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.019\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e≧\u0026thinsp;35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCA19-9 serum levels normalized\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.956\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.713\u0026ndash;5.369\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.193\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eClinical lymph node metastasis at diagnosis\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.047\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.785\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.067\u0026ndash;7.267\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.036\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eChange rate of PMI during 6 months\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.514\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.065\u0026ndash;11.589\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.039\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e≧\u0026thinsp;1.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;1.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eConversion Surgery\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.011\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.405\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.119\u0026ndash;1.371\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.146\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eAbbreviation: PMI, psoas muscle mass index\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003ePredictive Model and Effect of Resection among Cases with Favorable Prognostic Scores\u003c/h2\u003e \u003cp\u003eIn the multivariate analysis, the HRs for OS of tumor size at 6 months, clinical lymph node metastasis, and rate of change of PMI during the first 6 months were 3.25, 2.79, and 3.51, respectively (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Consequently, a score of 1 was assigned to each factor identified by multivariate analysis, resulting in scores ranging from 0 to 3 points. According to this scoring system, 14 patients (34%) scored no points and 27 patients (66%) scored 1 to 3 points (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). There was a significant difference in OS between patients who scored no points and those who scored 1 to 3 points (median OS: 30.3 months vs. 17.3 months, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.013) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Four of the patients (29%) who had undergone CS scored no points. Among the patients who scored no points, CS was associated with better OS (median OS: not reached vs. 25.5 months, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.039) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea). In contrast, among the patients who scored 1 to 3 points, CS was not associated with a better OS (median OS: 23.2 months vs. 13.2 months, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.183) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eb).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatient distribution according to model scores for the prognosis of UR-LA PC\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eScore\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (34)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (27)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (27)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (12)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eAbbreviations: UR-LA, unresectable locally advanced; PC, pancreatic cancer\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eIn this study, tumor size at 6 months, clinical lymph node metastasis at diagnosis, and rate of change of PMI during the first 6 months after initial treatment were identified as independent predictors of survival in patients with initially UR-LA PC and received chemo(radio)therapy. Furthermore, we established a simple prognostic scoring model comprised of these three factors.\u003c/p\u003e \u003cp\u003eAlthough CS did not prolong prognosis in patients with unfavorable scores (1, 2, or 3 points), it was associated with prolongation of OS in those with favorable scores.\u003c/p\u003e \u003cp\u003ePredictive factors of the prognosis of patients who undergo induction treatment followed by CS for UR-LA PC have been controversial over the past decade [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. With advances in multidisciplinary treatments for UR-LA PC, several prognostic factors, such as normalization of CA19-9 levels after induction treatment, tumor shrinkage, and CS have been reported [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Additionally, sarcopenia, as a poor prognostic factor, has been paid attention to [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Although several studies have reported indication for CS, no association between sarcopenia and CS has been reported.\u003c/p\u003e \u003cp\u003eIn the present study, we identified these three factors as being significantly associated with prognosis. Tumor size after induction treatment as a predictor of resectability and OS has been reported in several articles [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. And, regional lymph node metastasis has been shown to be associated with poor prognoses in patients with resectable, borderline resectable, and UR-LA PC [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Progression of sarcopenia has been reported to impair patient\u0026rsquo;s tolerance to chemotherapy [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e], so that its dose reductions or discontinuation are often needed. Deterioration in skeletal muscle mass during neoadjuvant therapy has been linked to poor prognoses in patients with resectable and borderline resectable PC, but not reported in those with UR-LA PC [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Thus, rate of change of PMI may reflect prognosis, even in those with UR-LA PC, supporting its use as an indication for CS.\u003c/p\u003e \u003cp\u003eUsing the findings of univariate and multivariate analyses, we established a scoring system that utilizes weighted values derived from the HRs for the prognosis of UR-LA PC. As the indications for CS remains unclear, two recent reports have focused on the optimal timing for CS in patients with UR-LA PC by creating scoring systems based on prognostic factors [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. However, one of these studies did not include a control group without CS [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], and the other included patients with UR-M in the analysis [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Neither of these reports mentioned sarcopenia. In contrast with these studies, our study included all consecutive patients with UR-LA PC and evaluated indication for CS with prognostic factors, including sarcopenia.\u003c/p\u003e \u003cp\u003eAlthough multiple reports have demonstrated that CS improved the survival of UR-LA PC patients [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e], the true impact of CS has remained unclear because of a lack of patients who had a good responses to induction treatment, but did not purposely undergo CS. In this study, we found that CS was associated with significantly improved outcomes in patients with the favorable prognostic scores (no points), whereas CS did not prolong prognosis in those with the unfavorable scores (1, 2, or 3 points). Although CS was not an independent prognostic factor, our results imply that performing oncologic resection in patients with no points may further enhance survival outcomes. Hence, CS can provide additional benefits in selected patients with UR-LA PC and setting a boundary between scores of 0 and 1 may lead to better decision-making concerning implementing CS.\u003c/p\u003e \u003cp\u003eThis study had several limitations. First, it was a small, retrospective, single institution study. However, this is the first to examine the relationship between sarcopenia and CS among patients with UR-LA PC. Second, although the duration of this study was approximately 6 months based on the previous reports, the optimal duration of induction treatment for CS varied widely. [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Third, clinical parameters were basically evaluated at 6 months after commencing treatment. However, the variations in timing of evaluation of clinical parameters in patients who undertook CS or selected best supportive care within 6 months may have contributed to a risk of bias. Fourth, induction treatment regimens were not standardized. This may lead to the heterogeneity of morphologic response by various agents. Lastly, though previous studies have reported that CS may be associated with prolongation of survival [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e], we did not identify it as an independent prognostic factor in the present study, possibly due to our suboptimal indication for CS. Consequently, our analysis was focused on the additional benefits of CS. However, due to the small number of patients in the favorable group, multivariate analysis could not be performed, necessitating further validation in future study.\u003c/p\u003e"},{"header":"CONCLUSIONS","content":"\u003cp\u003eIn this study, we identified prognostic indicators in patients with UR-LA PC, and established a simple scoring model that incorporated the three identified factors. Stratification according to this scoring system may be useful in predicting survival outcomes and may be valuable in guiding the indications for CS. Patients with favorable scores are considered candidates for CS and can achieve excellent survival times.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eACKNOWLEDGEMENT\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to thank Dr Trish Reynolds, MBBS, FRACP, from Edanz (http://www.edanz.com/) for English language editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSU, MT, and MK conceived and designed this study. SU and MT drafted the manuscript. HY, YA, YH, SH, YN, and YK analyzed the data and critically revised the manuscript. All authors were involved in data interpretation and drafting the manuscript and have read and approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDisclosure of ethical statements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Ethics Committee of the Keio University School of Medicine (Approval number: 20140389).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDr. Kitagawa has received grants and has been involved in lectures for TAIHO PHARMACEUTICAL CO., LTD., CHUGAI PHARMACEUTICAL CO., LTD., DAIICHI SANKYO COMPANY, LIMITED, Takeda Pharmaceutical Company Limited, Nippon Kayaku Co., Ltd., and MSD K.K. Additionally, he has been involved in lectures for Yakult Honsha Co., Ltd. and has received a grant from Kyouwa Hakkou Kirin Co., Ltd.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDisclaimer\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe funding source had no role in the design, practice, or analysis of this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eVincent A, Herman J, Schulick R et al (2011) Pancreat cancer Lancet 378(9791):607\u0026ndash;620\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVon Hoff DD, Ervin T, Arena FP et al (2013) Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 369(18):1691\u0026ndash;1703\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLoehrer PJ, Sr., Feng Y, Cardenes H et al (2011) Gemcitabine alone versus gemcitabine plus radiotherapy in patients with locally advanced pancreatic cancer: an Eastern Cooperative Oncology Group trial. J Clin Oncol 29(31):4105\u0026ndash;4112\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSuker M, Beumer BR, Sadot E et al (2016) FOLFIRINOX for locally advanced pancreatic cancer: a systematic review and patient-level meta-analysis. Lancet Oncol 17(6):801\u0026ndash;810\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYamada S, Fujii T, Yokoyama Y et al (2018) Phase I study of chemoradiotherapy using gemcitabine plus nab-paclitaxel for unresectable locally advanced pancreatic cancer. Cancer Chemother Pharmacol 81(5):815\u0026ndash;821\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNitsche U, Wenzel P, Siveke JT et al (2015) Resectability After First-Line FOLFIRINOX in Initially Unresectable Locally Advanced Pancreatic Cancer: A Single-Center Experience. Ann Surg Oncol 22(Suppl 3):S1212\u0026ndash;1220\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHackert T (2018) Surgery for Pancreatic Cancer after neoadjuvant treatment. Ann Gastroenterol Surg 2(6):413\u0026ndash;418\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSatoi S, Yamamoto T, Yamaki S et al (2020) Surgical indication for and desirable outcomes of conversion surgery in patients with initially unresectable pancreatic ductal adenocarcinoma. Ann Gastroenterol Surg 4(1):6\u0026ndash;13\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTanaka M, Heckler M, Mihaljevic AL et al (2023) Induction Chemotherapy with FOLFIRINOX for Locally Advanced Pancreatic Cancer: A Simple Scoring System to Predict Effect and Prognosis. Ann Surg Oncol 30(4):2401\u0026ndash;2408\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChindapasirt J (2015) Sarcopenia in Cancer Patients. Asian Pac J Cancer Prev 16(18):8075\u0026ndash;8077\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOtten L, Stob\u0026auml;us N, Franz K et al (2019) Impact of sarcopenia on 1-year mortality in older patients with cancer. Age Ageing 48(3):413\u0026ndash;418\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSalinas-Miranda E, Deniffel D, Dong X et al (2021) Prognostic value of early changes in CT-measured body composition in patients receiving chemotherapy for unresectable pancreatic cancer. Eur Radiol 31(11):8662\u0026ndash;8670\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTempero MA, Malafa MP, Al-Hawary M et al (2021) Pancreatic Adenocarcinoma, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 19(4):439\u0026ndash;457\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePinato DJ, North BV, Sharma R (2012) A novel, externally validated inflammation-based prognostic algorithm in hepatocellular carcinoma: the prognostic nutritional index (PNI). Br J Cancer 106(8):1439\u0026ndash;1445\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMiyata T, Yamashita YI, Higashi T et al (2018) The Prognostic Impact of Controlling Nutritional Status (CONUT) in Intrahepatic Cholangiocarcinoma Following Curative Hepatectomy: A Retrospective Single Institution Study. World J Surg 42(4):1085\u0026ndash;1091\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLin G, Liu Y, Li S et al (2016) Elevated neutrophil-to-lymphocyte ratio is an independent poor prognostic factor in patients with intrahepatic cholangiocarcinoma. Oncotarget 7(32):50963\u0026ndash;50971\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen Q, Dai Z, Yin D et al (2015) Negative impact of preoperative platelet-lymphocyte ratio on outcome after hepatic resection for intrahepatic cholangiocarcinoma. Med (Baltim) 94(13):e574\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOkuno M, Ebata T, Yokoyama Y et al (2016) Evaluation of inflammation-based prognostic scores in patients undergoing hepatobiliary resection for perihilar cholangiocarcinoma. J Gastroenterol 51(2):153\u0026ndash;161\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePrado CM, Lieffers JR, McCargar LJ et al (2008) Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study. Lancet Oncol 9(7):629\u0026ndash;635\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSeufferlein T, Hammel P, Delpero JR et al (2019) Optimizing the management of locally advanced pancreatic cancer with a focus on induction chemotherapy: Expert opinion based on a review of current evidence. Cancer Treat Rev 77:1\u0026ndash;10\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTanaka M, Heckler M, Mihaljevic AL et al (2019) CT response of primary tumor and CA19-9 predict resectability of metastasized pancreatic cancer after FOLFIRINOX. Eur J Surg Oncol 45(8):1453\u0026ndash;1459\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAsama H, Ueno M, Kobayashi S et al (2022) Sarcopenia: Prognostic Value for Unresectable Pancreatic Ductal Adenocarcinoma Patients Treated With Gemcitabine Plus Nab-Paclitaxel. Pancreas 51(2):148\u0026ndash;152\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMichelakos T, Pergolini I, Castillo CF et al (2019) Predictors of Resectability and Survival in Patients With Borderline and Locally Advanced Pancreatic Cancer who Underwent Neoadjuvant Treatment With FOLFIRINOX. Ann Surg 269(4):733\u0026ndash;740\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKlaiber U, Schnaidt ES, Hinz U et al (2021) Prognostic Factors of Survival After Neoadjuvant Treatment and Resection for Initially Unresectable Pancreatic Cancer. Ann Surg 273(1):154\u0026ndash;162\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMorales-Oyarvide V, Rubinson DA, Dunne RF et al (2017) Lymph node metastases in resected pancreatic ductal adenocarcinoma: predictors of disease recurrence and survival. Br J Cancer 117(12):1874\u0026ndash;1882\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMedrano J, Garnier J, Ewald J et al (2020) Patient outcome according to the 2017 international consensus on the definition of borderline resectable pancreatic ductal adenocarcinoma. Pancreatology 20(2):223\u0026ndash;228\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSandini M, Patino M, Ferrone CR et al (2018) Association Between Changes in Body Composition and Neoadjuvant Treatment for Pancreatic Cancer. JAMA Surg 153(9):809\u0026ndash;815\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTakaichi S, Tomimaru Y, Kobayashi S et al (2023) Change Impact of Body Composition During Neoadjuvant Chemoradiotherapy in Patients with Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma Undergoing Pancreatectomy. Ann Surg Oncol 30(4):2458\u0026ndash;2468\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChoi MH, Yoon SB (2022) Sarcopenia in pancreatic cancer: Effect on patient outcomes. World J Gastrointest Oncol 14(12):2302\u0026ndash;2312\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUshida Y, Inoue Y, Oba A et al (2022) Optimizing Indications for Conversion Surgery Based on Analysis of 454 Consecutive Japanese Cases with Unresectable Pancreatic Cancer Who Received Modified FOLFIRINOX or Gemcitabine Plus Nab-paclitaxel: A Single-Center Retrospective Study. Ann Surg Oncol 29(8):5038\u0026ndash;5050\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWilliams JL, Kadera BE, Nguyen AH et al (2016) CA19-9 Normalization During Pre-operative Treatment Predicts Longer Survival for Patients with Locally Progressed Pancreatic Cancer. J Gastrointest Surg 20(7):1331\u0026ndash;1342\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTakano N, Yamada S, Sonohara F et al (2021) The impact of early tumor shrinkage on conversion surgery and the survival in patients with unresectable locally advanced pancreatic cancer. Surg Today 51(7):1099\u0026ndash;1107\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"chemotherapy, conversion surgery, sarcopenia, scoring model, unresectable locally advanced pancreatic cancer","lastPublishedDoi":"10.21203/rs.3.rs-5706477/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5706477/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eChemotherapeutic advances have increased opportunities for conversion surgery (CS) of unresectable locally advanced (UR-LA) pancreatic cancer (PC). However, the optimal indications for CS remain unclear. We aimed to identify predictive factors of prognosis in UR-LA PC, and evaluate indication for CS using these factors including sarcopenia.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003e In this retrospective study, we reviewed consecutive patients with UR-LA PC who had received chemo(radio)therapy as an initial treatment between 2015 and 2023. We examined relevant clinical variables and CT findings at initial diagnosis and at 6 months after starting treatment.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eTen of the 41 patients had undergone CS. Tumor size at 6 months, clinical lymph node metastasis at diagnosis, and changes in sarcopenia over 6 months were associated with overall survival (OS) (multivariate analysis: hazard ratio\u0026thinsp;=\u0026thinsp;3.25, 2.79 and 3.51, respectively). Each of these factors was assigned a value of 1, resulting in a scoring system ranging from 0 to 3 points. There was a significant difference in OS between the patients who scored 0 points and those who scored 1 to 3 points (median OS: 30.3 months v.s. 17.3 months, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.013). CS was associated with better OS among patients who scored 0 (not reached v.s. 25.5 months, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.039).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eChange in sarcopenia is a novel predictor of the prognosis of patients with UR-LA PC. Patients with favorable scores in our simple scoring model, which incorporates three prognostic factors identified by the current analysis, may achieve better survival after CS than that achieved induction therapy alone.\u003c/p\u003e","manuscriptTitle":"Impact of Sarcopenia During Induction Treatment in Patients with Unresectable Locally Advanced Pancreatic Cancer: A Scoring Model for indication of Conversion Surgery","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-01 09:23:58","doi":"10.21203/rs.3.rs-5706477/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7692051d-0ac9-4c65-893d-b9f0f2d21c2c","owner":[],"postedDate":"January 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-03-24T11:38:55+00:00","versionOfRecord":[],"versionCreatedAt":"2025-01-01 09:23:58","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5706477","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5706477","identity":"rs-5706477","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}