The effect of neoadjuvant chemoradiation therapy in resectable pancreatic cancer was independent of intratumoral vascularization

The effect of neoadjuvant chemoradiation therapy in resectable pancreatic cancer was independent of intratumoral vascularization | 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 The effect of neoadjuvant chemoradiation therapy in resectable pancreatic cancer was independent of intratumoral vascularization Tomomi Yasue, Reiko Ashida, Ryoji Takada, Kenji Ikezawa, Kazuyoshi Ohkawa, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5140786/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 19 Jul, 2025 Read the published version in BMC Gastroenterology → Version 1 posted 6 You are reading this latest preprint version Abstract Aim Contrast-enhanced harmonic endoscopic ultrasound (CH-EUS) has promising potential in the diagnosis of pancreatic tumors, assessment of fibrosis, and prediction of chemotherapy efficacy. We hypothesize that radiation therapy might reduce variations in chemotherapeutic efficacy caused by fibrosis-induced blood flow disparities, as we explored the relationship between CH-EUS patterns and the efficacy of neoadjuvant chemoradiotherapy (NACRT) in resectable pancreatic cancer (PC). Methods Patients with resectable PC who underwent CH-EUS followed by NACRT were retrospectively analyzed. The CH-EUS enhancement pattern was evaluated in the vascular and perfusion phases and classified according to vascularity: Group A, hypovascular in both phases; Group B, isovascular and hypovascular in the vascular and perfusion phases, respectively; and Group C, isovascular in both phases. The relationships between the CH-EUS vascular pattern and the histological response according to the Evans classification to NACRT, recurrence-free survival (RFS) and overall survival (OS) were evaluated. Results Of the 48 enrolled patients, 31, 11, and 6 were classified into Groups A, B, and C, respectively. There was no significant difference in histopathological differentiation or the efficacy of NACRT among the groups. In addition, there was no significant difference between the groups in terms of median RFS or OS, although it was longer than previously reported. Conclusion The histopathological efficacy of NACRT for resectable PC did not differ significantly on the basis of enhancement pattern observed on CH-EUS. NACRT may provide additional therapeutic benefit independent of blood flow considerations. chemoradiation CH-EUS EUS neoadjuvant therapy pancreatic cancer Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction The incidence of pancreatic cancer (PC) has been increasing in recent years. However, the 5-year survival rate is only 10% despite the recent development of new chemotherapies [ 1 ]. Therefore, a multidisciplinary approach such as chemoradiation therapy is mandatory to improve this very poor prognosis. It has been suggested that the reason for the poor prognosis in PC is strong fibrotic changes that reduce the permeability of anticancer drugs and suppress immune activity. The desmoplastic reaction generates excessively high interstitial fluid pressure and induces vascular collapse, which presents significant barriers to perfusion, diffusion, and convection of therapeutic agents [ 2 , 3 ]. Chemotherapeutic agents for pancreatic cancer have been shown to be poorly delivered to tumors in mouse models due to poor tumor vascularization, and this poor vascularity correlates with a highly dense fibrosclerotic stroma within the tumor [ 4 ]. The effects of fibrotic changes can be visualized via contrast-enhanced computed tomography (CE-CT), magnetic resonance imaging (MRI), and endoscopic ultrasound (EUS) [ 5 ]. EUS has the ability to obtain tissue for histopathological diagnosis and therefore can play a crucial role in the differential diagnosis process of pancreatic tumors, including mass-forming chronic pancreatitis, autoimmune pancreatitis, and pancreatic adenocarcinoma [ 6 ]. Contrast-enhanced harmonic EUS (CH-EUS), which uses second-generation contrast agents, can be used to generate perfusion images depicting the microvasculature of the target. For decades, CH-EUS has shown promising results for the differential diagnosis of pancreatic tumors [ 7 – 12 ], and several studies have reported that the enhancement pattern of CH-EUS reflects the degree of fibrosis in pancreatic masses [ 13 , 14 ]. Yamashita et al. reported that evaluating intratumoral vascular flow via CH-EUS could be useful for predicting the efficacy of chemotherapy in patients with unresectable PC treated with gemcitabine or S1 monotherapy [ 15 ]. Zhou et al. reported that in patients with locally advanced PC, the survival time was significantly longer in those with iso-enhancement than in those with hypovascular enhancement in the arterial phase on CE-US [ 16 ]. Emori et al. reported that in patients with unresectable PC treated with first-line gemcitabine and nab-paclitaxel, both PFS and OS were significantly longer in those who had iso-enhancement in both the early and late phases on CH-EUS [ 17 ]. These findings suggest that pancreatic cancers with an isovascular pattern on CH-EUS may have increased blood flow and a potentially more favorable response to chemotherapy than those with a hypovascular pattern. On the other hand, although preoperative neoadjuvant chemoradiation therapy (NACRT) is a promising option for the multimodal treatment of PC [ 18 , 19 ], prior to our study, no studies had investigated the relationship between contrast enhancement patterns on CH-EUS and the efficacy of NACRT for resectable pancreatic cancer. Therefore, we hypothesized that the addition of radiotherapy might mitigate differences in chemotherapeutic efficacy resulting from variations in blood flow due to the degree of fibrosis. To investigate this, we conducted a retrospective study to assess the relationship between CH-EUS patterns and the efficacy of NACRT for resectable pancreatic cancer, with a specific focus on evaluating the additional impact of radiotherapy. Methods Study design Patients who underwent CH-EUS prior to NACRT between August 2011 and January 2015 were included in the study. The selection criteria were as follows: 1) pathologically confirmed diagnosis of pancreatic adenocarcinoma before the initiation of preoperative chemoradiation therapy; 2) resectable or borderline resectable pancreatic cancer; 3) suitable for preoperative chemoradiation therapy; and 4) performance status (PS) of 0–1. Resectable and borderline resectable PC was defined as follows: 1) no evidence of distant disease (M0) ; 2) no evidence of tumor abutment greater than 180 degree of the circumstance of the superior mesenteric artery (SMA), celiac axis (CA), or common hepatic artery (CHA) ; 3) no evidence of cancer invasion into the confluent point of right colic vein to the superior mesenteric vein (SMV); and 4) no evidence of occlusion of the SMV and portal vein (PV) without an appropriate option for venous resection and reconstruction. The primary endpoint was the relationship between the histopathological efficacy of NACRT and the vascular pattern on CH-EUS. The secondary endpoints were the relationships between the CH-EUS vascular pattern and histological differentiation, recurrence-free survival (RFS), and overall survival (OS) in patients who underwent NACRT. This study was conducted retrospectively at a single institution in accordance with the Declaration of Helsinki, and the protocol was approved by the Osaka International Cancer Institute Institutional Review Board (No. 20134). EUS procedure and classification of contrast patterns CH-EUS was performed via a linear type echo endoscope (GF-UCT260; Olympus Corporation, Tokyo, Japan) with an ultrasound observation system (ProSound SSD α-10, ALOKA, Tokyo, Japan) under conscious sedation. EUS was performed at the time of initial diagnosis. For CH-EUS, a 0.015 mL/kg bolus of contrast agent (Sonazoid; Daiichi-Sankyo, Tokyo) containing perfluorobutane microbubbles was administered, followed by a 10 mL flush of saline solution. The vascularity of the pancreatic tumor was apparent at 10–15 seconds after the injection of Sonazoid into a peripheral vein, peaked at approximately 20 seconds, and was observed for 120 seconds [ 20 ]. Relatively large vascular irregularities were evaluated in the “vascular phase”, defined as approximately 20 seconds after injection. In the “perfusion phase”, defined as 40–60 seconds after injection, the enhancement of capillaries in the mass was evaluated in comparison with that of the surrounding pancreatic parenchyma. Kappa values were calculated to assess interobserver variability at each phase and for each assessment of intratumoral vascularity on CH-EUS. Kappa values were interpreted according to the Fleiss kappa index, with 95% CI, via the jackknife method. The kappa value results were interpreted as follows: 0.00-0.20, poor agreement; 0.21–0.40, fair agreement; 0.41–0.60, moderate agreement; 0.61–0.80, substantial agreement; and 0.81-1.00, almost perfect agreement [ 21 , 22 ]. Intratumoral vascularity was then classified into three patterns according to the enhancement observed in each phase, as follows. Group A included patients who were hypovascular in both the vascular and perfusion phases. Group B included patients who were isovascular in the vascular phase and hypovascular in the perfusion phase. Group C was isovascular in both the vascular and perfusion phases. The images of each pattern are shown in Fig. 1 . Preoperative treatment and subsequent surgery All patients were treated preoperatively with chemoradiation therapy shown in supplementary Fig. 1. For systemic chemotherapy, gemcitabine (1000 mg/m 2 ) monotherapy was administered to 41 patients on days 1, 8, and 15 of each 28-day as two cycles with concurrent radiotherapy followed by one cycle gemcitabine chemotherapy alone. S-1 (80 mg/ m 2 ) monotherapy was administered to 5 patients for 4 weeks at 2-week intervals as one cycle with concurrent radiotherapy followed by another cycle of S-1 chemotherapy alone. Two patients were administered a combination of gemcitabine (1000 mg/m 2 ) and nab-PTX (125 mg/m 2 ) on day 1 and 8 of each 15 days as one cycle and 2cycle as total with concurrent radiotherapy after 2 cycles of gemcitabine plus nab-PTX induction chemotherapy. Three-dimensional radiation was delivered at a total radiation dose of 50 Gy in daily fractions of 2 Gy and total of 25 fractions, 5 times per week. After completing NACRT, restaging of the PC was performed and pancreatectomy was performed in patients who showed no signs of disease progression, such as manifestation of distant metastases, during NACRT. Surveillance after surgery After surgical resection of the PC, standard postoperative follow-up with a focus on surveillance for tumor relapse was performed in all patients as follows. 1) Monthly physical examination and routine laboratory tests, including evaluation of tumor markers such as carbohydrate antigen 19 − 9 (CA19-9) and carcinoembryonic antigen (CEA). Routine postsurgical imaging studies (chest and abdominal CE-CT, abdominal ultrasound, or MRI) were performed every 3 months for 3 years after surgery. 2) Routine laboratory tests and imaging studies were performed 2 to 3 times per year thereafter. Recurrence of PC was identified on the basis of the findings of the imaging studies and the clinical manifestations. Additional examinations such as positron emission tomography-computed tomography (PET-CT) were also performed to investigate the recurrence of PC when clinically indicated. Cytological/histopathological confirmation of recurrence was not strictly needed. Pathology assessment of resected samples All resected samples were fixed in 10% formalin for 48–72 hours at room temperature. The entire specimen was serially sectioned at 3- to 4-mm intervals according to the pathological tumor node metastasis (pTNM) classification and the guidelines [ 23 ]. In the present study, an R1 resection margin was defined as the presence of viable tumor cells within 1 mm of the superior mesenteric artery margin, posterior margin, or portal groove margin. Pancreatic transection margins with focal high-grade dysplasia (PanIN 3) were also considered positive. Definitions The tumor reduction ratio was calculated from CE-CT or CH-EUS as (tumor size before CRT minus tumor size after CRT)/(tumor size before CRT). The histopathological response to NACRT was evaluated via the Evans classification (a histological grading system of the percentage of tumor cells destroyed after chemoradiation), as follows: Grade I, little (< 10%) or no tumor cell destruction; Grade IIa, destruction of 10–50% of tumor cells; Grade IIb, destruction of 51–90% of tumor cells; Grade III, few (< 10%) viable-appearing tumor cells; and Grade IV, no viable tumor cells [ 24 ]. Statistical analysis Intratumoral vascularity was compared among pattern groups A, B, and C by Fisher’s exact test. RFS and OS were measured from the first day of NACRT to the date of disease recurrence or death, respectively, and were estimated using the Kaplan–Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazards model to determine variables significantly associated with prognosis. After the hazard ratio (HR) and its 95% confidence interval (CI) were calculated, multivariate analysis was performed on the factors that were significant in the univariate analysis to identify factors independently associated with RFS and OS. P-values < 0.05 were considered statistically significant. Statistical analysis was performed with EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan). Results Population and tumor characteristics Among the 65 patients who were diagnosed with PC between August 2011 and January 2015, 9 had upfront surgery, and 56 had NACRT for resectable PC after assessment for potential resectability. Among these patients, 1 patient developed distant metastasis during NACRT, and 7 failed NACRT due to severe adverse events. Therefore, a total of 48 patients (26 males, 22 females) were included in this retrospective study (Fig. 2 ). The mean patient age was 66.2 years (range, 47–82 years). Twenty-four (50%) tumors were located in the head of the pancreas, and 24 (50%) were in the body or tail. The mean tumor size was 20.1 ± 7.2 cm (range, 8–35 cm). Regarding the pattern of tumor vascularity, there were 31 patients in Group A, 11 patients in Group B, and 6 patients in Group C. Kappa values were calculated to assess the interobserver variability of the visual tumor enhancement pattern on CH-EUS, with a kappa value of 0.98 taken to indicate almost perfect agreement. The patient demographics and clinical characteristics are listed in Table 1 . There was no significant difference between the groups in terms of age, sex, Eastern Cooperative Oncology Group performance status scale score, tumor location, tumor size before NACRT, CEA, CA19-9, or first-line chemotherapy. Table 1 Patient demographics and preoperative clinical characteristics Vascularity Vascular phase / Perfusion phase Total (n = 48) Group A Group B Group C p-value Hypo a / Hypo (n = 31) Iso b / Hypo (n = 11) Iso / Iso (n = 6) Sex Female 22 (46%) 14 (45%) 4 (36%) 4 (67%) 0.519 Male 26 (54%) 17 (55%) 7 (64%) 2 (33%) Age, years 65≤ 27 (56%) 19 (61%) 4 (36%) 4 (67%) 0.327 65> 21 (44%) 12 (39%) 7 (64%) 2 (33%) ECOG performance status 0–1 48 (100%) 31 (100%) 11 (100%) 6 (100%) 1.000 2≤ 0 (0%) 0 (0%) 0 (0%) 0 (0%) Tumor location Head 24 (50%) 17 (55%) 4 (36%) 3 (50%) 0.585 Body/tail 24 (50%) 14 (45%) 7 (64%) 3 (50%) Tumor size before preoperative CRT c 20 mm> 27 (56%) 14 (45%) 8 (73%) 5 (83%) 0.143 20 mm≤ 21 (44%) 17 (55%) 3 (27%) 1 (17%) CA19-9 37 IU/mL> 19 (40%) 11 (35%) 6 (55%) 2 (45%) 0.240 37 IU/mL≤ 29 (60%) 20 (65%) 5 (45%) 4 (55%) CEA 5.0 ng/mL> 42 (88%) 26 (84%) 10 (91%) 6 (100%) 0.831 5.0 ng/mL≤ 6 (12%) 5 (16%) 1 (9%) 0 (0%) Initial chemotherapy Gemcitabine 41 (86%) 25 (81%) 10 (91%) 6 (100%) 1.000 Gemcitabine + nab-paclitaxel 5 (10%) 4 (13%) 1 (9%) 0 (0%) S-1 2 (4%) 2 (6%) 0 (0%) 0 (0%) a Hypo Hypovascular, b Iso Isovascular, c CRT chemoradiation therapy, ECOG Eastern Cooperative Oncology Group, CA19-9 carbohydrate antigen 19 − 9, CEA carcinoembryonic antigen NACRT and subsequent surgery Among the 56 patients who receiced NACRT for potentially resectable PC, 48/56 completed NACRT. One patient developed distant metastases in the liver and lung. Seven patients failed NACRT due to severe adverse events, such as anaphylaxis to gemcitabine. After NACRT and reassessment for resectability, 28/48 patients underwent pancreaticoduodenectomy, 19/48 underwent distal pancreatectomy, and 1/48 underwent total pancreatectomy. There was no patient mortality during the perioperative period. R0 resection was completed in 29/31 (94%) patients in Group A, in 11/11 (100%) in Group B, and in 6/6 (100%) in Group C (no significant difference). Pathology specimens Table 2 lists the histopathological variables according to vascular pattern group in patients who underwent pancreatectomy after NACRT. There was no significant difference in the reduction ratio, Evans classification, or histological grade among the groups. With respect to the effectiveness of NACRT, three patients achieved complete remission (CR) (Group A, n = 2; Group B, n = 1). Representative imaging findings of CR patients are shown in Fig. 3 . The Evans classification grades of the 48 patients were as follows: grade lV, n = 3; grade lll, n = 9; grade llb, n = 22; grade lla, n = 11; and grade l, n = 3. There was no significant difference between the groups in terms of the vascular pattern. Table 2 Histological variables after NACRT Vascularity Vascular phase / Perfusion phase Total (n = 48) Group A Group B Group C p-value Hypo / Hypo (n = 31) Iso / Hypo (n = 11) Iso / Iso (n = 6) Reduction ratio of tumor < 0 9 (19%) 6 (19%) 2 (18%) 1 (17%) 0.783 0≤, < 30 19 (40%) 13 (42%) 5 (45%) 1 (17%) 30≤ 20 (41%) 12 (39%) 4 (36%) 4 (66%) Evans's classification Grade 1 3 (6%) 1 (3%) 2 (18%) 0 (0%) 0.282 Grade 2a 11 (23%) 8 (26%) 2 (18%) 1 (17%) Grade 2b 22 (46%) 16 (52%) 2 (18%) 4 (66%) Grade 3 9 (19%) 4 (13%) 4 (36%) 1 (17%) Grade 4 3 (6%) 2 (6%) 1 (9%) 0 (0%) Histological Differentiation Unevaluable, CIS 7 (15%) 6 (19%) 1 (9%) 0 (0%) 0.314 Well 13 (27%) 5 (16%) 4 (36%) 4 (67%) Moderate 24 (50%) 17 (55%) 5 (41%) 2 (33%) Poorly 4 (8%) 3 (10%) 1 (9%) 0 (0%) RFS and OS The seven-year median RFS and OS for each group are shown in Fig. 4 . The five-year and seven-year median RFS times were 24.2 months in Group C and 55.9 months in Group A (not yet reached in Group B). The five-year median OS was 34.1 months in Group C (not yet reached in Groups A and B). The seven-year median OS was 47.7 months in Group C and 65.5 months in Group A (not yet reached in Group B). There was no significant difference between the groups in terms of median RFS or OS. Discussion NACRT represents a pivotal component of the multidisciplinary approach to treating pancreatic cancer PC. Our institution has extensively documented the efficacy of NACRT for resectable PC since 2009 [ 18 , 19 , 25 , 26 ]. NACRT presents a range of benefits: first, it exerts a potent local therapeutic effect, potentially facilitating downstaging and enabling R0 resection by mitigating the risk of local recurrence. Second, it enhances the immune response by stimulating the release of neoantigens through radiation. Third, NACRT aids in identifying previously undetected distant metastases during treatment, thus sparing patients from unnecessary surgery. Given that the primary challenge in PC treatment lies in the fibrotic alterations caused by desmoplastic reactions, which compromise drug permeability and the immune response, local radiation therapy has emerged as particularly advantageous and may increase the efficacy of systemic chemotherapy in managing micrometastases. CH-EUS provides intricate insights into tumor vascularity and has proven invaluable in the differential diagnosis of solid pancreatic lesions. A recent meta-analysis revealed pooled estimates of CH-EUS sensitivity and specificity of 93% (95% CI, 0.90–0.95) and 80% (95% CI, 0.75–0.85), respectively [ 10 ]. EUS offers several advantages over alternative imaging modalities for assessing intratumoral vascularity in PCs. Notably, it surpasses US and CT in terms of tumor detection accuracy, particularly in cases of smaller pancreatic cancers (< 2 cm in diameter) [ 27 , 28 ]. Furthermore, the advent of second-generation ultrasound contrast agents such as Sonazoid enables the acquisition of microvascular images, with EUS outperforming CT in identifying intratumoral microvessels [ 12 , 29 ]. Contrast-enhanced ultrasound (CE-US) has also proven instrumental in evaluating fibrotic changes in PCs. For example, Zhou et al. demonstrated that CE-US iso-enhancement in the early phase is correlated with increased tumor angiogenesis and minimal fibrosis [ 16 ]. In a comparison of surgical samples, Numata et al. reported that the CE-US findings in PC are influenced by interstitial histological features associated with tumor growth [ 13 ]. Yamashita et al. reported that evaluating intratumoral vessel flow via CH-EUS could be useful for predicting the efficacy of chemotherapy in patients with unresectable PC who are treated with gemcitabine or S1 monotherapy [ 15 ]. Zhou et al. reported that in patients with locally advanced PC, the survival time was significantly longer in those who demonstrated iso-enhancement than in those with hypovascular enhancement in the arterial phase on CE-US [ 16 ]. Emori et al. reported that in patients with unresectable PC who were treated with first-line gemcitabine and nab-paclitaxel, both PFS and OS were significantly longer in those who had iso-enhancement in both the early and late phases on CH-EUS [ 17 ]. These results suggest that PCs that show an isovascular pattern on CH-EUS have greater blood flow and will have a better response to chemotherapy than those with a hypovascular pattern. However, to the best of our knowledge, no previous study has investigated the relationship between the pattern of contrast enhancement on CH-EUS and the efficacy of NACRT for resectable PC. In our study, three distinct contrast-enhancement patterns were identified. Group A exhibited hypovascular contrast-enhancement in both the vascular and perfusion phases, which was indicative of poor intratumoral blood flow due to fibrotic changes. Conversely, Group C showed persistent contrast enhancement in both phases, suggesting relatively robust intratumoral blood flow. No correlation between the enhancement pattern and histological differentiation of resected samples was observed, despite previous indications that poorly differentiated PC and anaplastic carcinoma tend to exhibit reduced fibrosis [ 13 ]. Notably, the hypovascular pattern observed in some cases may be attributed to necrotic changes within the tumor. Despite challenges in evaluating histological differentiation post-NACRT due to extensive tumor eradication, pretreatment assessment via endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) revealed findings typical of pancreatic cancer, such as irregular internuclear distances, clear nucleoli and protruding nuclei. Notably, there were no discernible differences in stromal sample status among the various Evans classifications. According to Zhou et al, the iso-enhancement pattern on CEUS indicates abundant tumor angiogenesis, evenly distributed throughout the lesion, and low-grade fibrosis, whereas the hypo-enhancement pattern is associated with sparse, heterogeneously distributed tumor angiogenesis and relatively high fibrosis [ 16 ]. However, distinguishing between preexisting fibrotic stroma and NACRT-induced fibrotic changes is difficult, and the relationship between contrast enhancement patterns and treatment-induced fibrosis was not investigated in our study. Nevertheless, among the Group A patients predicted to be less likely to respond to preoperative chemotherapy in previous reports, 19% had responses corresponding to Grade 3 or 4 according to the Evans classification. The addition of radiotherapy may be expected to have an additive effect on chemotherapy efficacy, regardless of intratumoral blood flow assessed by CH-EUS. In contrast to previous studies, our findings revealed no significant difference in RFS or OS based on contrast-enhancement patterns [ 30 ]. Additionally, the completion of postoperative adjuvant therapy did not impact OS or RFS (Supplementary Tables 1, 2). Remarkably, the median OS surpassed historical data for neoadjuvant chemotherapy for resectable PC, irrespective of CH-EUS contrast patterns [ 31 , 32 ]. These results suggest that the addition of radiotherapy to preoperative chemotherapy may confer additional local therapeutic benefits independent of intratumoral blood flow. Notably, OS may be influenced by factors such as subsequent anticancer therapies or patient characteristics, as emphasized by Yamashita et al.'s evaluation of chemotherapy efficacy in resectable pancreatic cancer patients treated with neoadjuvant chemotherapy (NAC) [ 33 ]. While our study has certain limitations, including its single-center retrospective design and variability in chemotherapy and adjuvant therapy regimens, and the relatively small sample size, the observed additive effect of radiotherapy underscores the potential therapeutic benefits of NACRT regardless of tumor blood flow. Future prospective multicenter studies are warranted to validate these findings conclusively. In summary, our study suggests that NACRT may mitigate variations in chemotherapeutic efficacy associated with fibrosis-induced blood flow disparities, potentially contributing to improved prognostic outcomes. Conclusion NACRT may provide additional therapeutic benefits regardless of the extent of intratumoral blood flow, potentially extending its prognostic benefits. Declarations Conflicts of interest The authors have no relevant financial disclosures or conflicts of interest to declare. Ethics approval and consent to participate The protocol of this study was approved by the Osaka International Cancer Institute, Institutional Review Board (IRB No. 20134). It strictly followed the Declaration of Helsinki and other relevant guidelines. All the patients signed written informed consent to use their clinical data. Consent for publication Not applicable. Funding Declaration This study was supported in part by a grant from The Osaka Foundation for the Prevention of Cancer and Lifestyle-related Diseases (Public Interest Incorporated Foundation). Author Contribution RA designed the research; RA, RT, KI, KO, HA, and HT performed the procedures and surgery; TT performed the radiation therapy; SN performed the pathological assessment; RA and TY analyzed the data; TY drafted the paper; YD and HE revised the draft and approved the final draft. All the authors have read and approved the final manuscript. References Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021. 2021, 71(1):7–33. Neesse A, Michl P, Frese KK, Feig C, Cook N, Jacobetz MA, Lolkema MP, Buchholz M, Olive KP, Gress TM, et al. Stromal biology and therapy in pancreatic cancer. Gut. 2011;60(6):861–8. Provenzano PP, Cuevas C, Chang AE, Goel VK, Von Hoff DD, Hingorani SR. Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma. Cancer Cell. 2012;21(3):418–29. Olive KP, Jacobetz MA, Davidson CJ, Gopinathan A, McIntyre D, Honess D, Madhu B, Goldgraben MA, Caldwell ME, Allard D, et al. 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Ohigashi H, Ishikawa O, Eguchi H, Takahashi H, Gotoh K, Yamada T, Yano M, Nakaizumi A, Uehara H, Tomita Y, et al. Feasibility and efficacy of combination therapy with preoperative full-dose gemcitabine, concurrent three-dimensional conformal radiation, surgery, and postoperative liver perfusion chemotherapy for T3-pancreatic cancer. Ann Surg. 2009;250(1):88–95. Eguchi H, Takeda Y, Takahashi H, Nakahira S, Kashiwazaki M, Shimizu J, Sakai D, Isohashi F, Nagano H, Mori M, et al. A Prospective, Open-Label, Multicenter Phase 2 Trial of Neoadjuvant Therapy Using Full-Dose Gemcitabine and S-1 Concurrent with Radiation for Resectable Pancreatic Ductal Adenocarcinoma. Ann Surg Oncol. 2019;26(13):4498–505. Yamabe A, Irisawa A, Bhutani MS, Shibukawa G, Fujisawa M, Sato A, Yoshida Y, Arakawa N, Ikeda T, Igarashi R, et al. Efforts to improve the diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration for pancreatic tumors. Endoscopic ultrasound. 2016;5(4):225–32. Tawada K, Yamaguchi T, Kobayashi A, Ishihara T, Sudo K, Nakamura K, Hara T, Denda T, Matsuyama M, Yokosuka O. Changes in tumor vascularity depicted by contrast-enhanced ultrasonography as a predictor of chemotherapeutic effect in patients with unresectable pancreatic cancer. Pancreas. 2009;38(1):30–5. Kitano M, Kudo M, Yamao K, Takagi T, Sakamoto H, Komaki T, Kamata K, Imai H, Chiba Y, Okada M, et al. Characterization of small solid tumors in the pancreas: the value of contrast-enhanced harmonic endoscopic ultrasonography. Am J Gastroenterol. 2012;107(2):303–10. Uesaka K, Boku N, Fukutomi A, Okamura Y, Konishi M, Matsumoto I, Kaneoka Y, Shimizu Y, Nakamori S, Sakamoto H, et al. Adjuvant chemotherapy of S-1 versus gemcitabine for resected pancreatic cancer: a phase 3, open-label, randomised, non-inferiority trial (JASPAC 01). Lancet (London England). 2016;388(10041):248–57. Ye M, Zhang Q, Chen Y, Fu Q, Li X, Bai X, Liang T. Neoadjuvant chemotherapy for primary resectable pancreatic cancer: a systematic review and meta-analysis. HPB: official J Int Hepato Pancreato Biliary Association. 2020;22(6):821–32. Versteijne E, van Dam JL, Suker M, Janssen QP, Groothuis K, Akkermans-Vogelaar JM, Besselink MG, Bonsing BA, Buijsen J, Busch OR, et al. Neoadjuvant Chemoradiotherapy Versus Upfront Surgery for Resectable and Borderline Resectable Pancreatic Cancer: Long-Term Results of the Dutch Randomized PREOPANC Trial. J Clin oncology: official J Am Soc Clin Oncol. 2022;40(11):1220–30. Yamashita Y, Ashida R, Kojima F, Okada KI, Kawai M, Yamazaki H, Tamura T, Kawaji Y, Tamura T, Hatamaru K, et al. Utility of contrast-enhanced harmonic endoscopic ultrasonography for prediction of pathological response after neoadjuvant chemotherapy in patients with pancreatic cancer. Pancreatology. 2023;23(8):1014–9. Additional Declarations No competing interests reported. Supplementary Files SupplementaryTable1.xlsx SupplementaryTable2.xlsx SupplementaryFigure1.pptx Supplementary Fig.1 Regimen of preoperative chemoradiation therapy. Cite Share Download PDF Status: Published Journal Publication published 19 Jul, 2025 Read the published version in BMC Gastroenterology → Version 1 posted Editorial decision: Revision requested 19 May, 2025 Reviews received at journal 16 May, 2025 Reviewers agreed at journal 04 May, 2025 Reviewers invited by journal 31 Mar, 2025 Submission checks completed at journal 31 Mar, 2025 First submitted to journal 25 Mar, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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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-5140786","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":436184186,"identity":"087b0581-4516-4ebc-b33d-35542887adc0","order_by":0,"name":"Tomomi Yasue","email":"","orcid":"","institution":"Osaka Habikino Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Tomomi","middleName":"","lastName":"Yasue","suffix":""},{"id":436184187,"identity":"81d36e32-fd52-4350-8c22-a4360ddbb641","order_by":1,"name":"Reiko Ashida","email":"data:image/png;base64,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","orcid":"","institution":"Wakayama Medical University","correspondingAuthor":true,"prefix":"","firstName":"Reiko","middleName":"","lastName":"Ashida","suffix":""},{"id":436184188,"identity":"12b420ba-9fa8-43bd-8726-f3b765acfb2d","order_by":2,"name":"Ryoji Takada","email":"","orcid":"","institution":"Osaka International Cancer Institute","correspondingAuthor":false,"prefix":"","firstName":"Ryoji","middleName":"","lastName":"Takada","suffix":""},{"id":436184189,"identity":"99e681a5-950a-43e0-bab1-61a4a7c888b5","order_by":3,"name":"Kenji Ikezawa","email":"","orcid":"","institution":"Osaka International Cancer Institute","correspondingAuthor":false,"prefix":"","firstName":"Kenji","middleName":"","lastName":"Ikezawa","suffix":""},{"id":436184190,"identity":"e6bc020b-d409-4f46-8118-dbc519d8cc88","order_by":4,"name":"Kazuyoshi Ohkawa","email":"","orcid":"","institution":"Osaka International Cancer Institute","correspondingAuthor":false,"prefix":"","firstName":"Kazuyoshi","middleName":"","lastName":"Ohkawa","suffix":""},{"id":436184191,"identity":"9ef61f4f-b007-4bd6-8964-0f6d9092ba51","order_by":5,"name":"Shigenori Nagata","email":"","orcid":"","institution":"Osaka International Cancer Institute","correspondingAuthor":false,"prefix":"","firstName":"Shigenori","middleName":"","lastName":"Nagata","suffix":""},{"id":436184192,"identity":"58eb22a1-78f1-481c-ada9-25ecc569b003","order_by":6,"name":"Teruki Teshima","email":"","orcid":"","institution":"Osaka Heavy Ion Therapy Center","correspondingAuthor":false,"prefix":"","firstName":"Teruki","middleName":"","lastName":"Teshima","suffix":""},{"id":436184193,"identity":"36a8e1a1-95d4-4779-bd78-5a2fde7c305b","order_by":7,"name":"Hirofumi Akita","email":"","orcid":"","institution":"Osaka University Graduate School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Hirofumi","middleName":"","lastName":"Akita","suffix":""},{"id":436184194,"identity":"80830c2f-7e66-434a-90f4-9d9112706667","order_by":8,"name":"Hidenori Takahashi","email":"","orcid":"","institution":"Yamaguchi University Graduate School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Hidenori","middleName":"","lastName":"Takahashi","suffix":""},{"id":436184195,"identity":"482862d8-8c41-4d99-9ed7-72960d77fd83","order_by":9,"name":"Yuichiro Doki","email":"","orcid":"","institution":"Osaka University Graduate School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yuichiro","middleName":"","lastName":"Doki","suffix":""},{"id":436184196,"identity":"79398bb1-b77c-4b23-a526-ebdf6c4b7c62","order_by":10,"name":"Hidetoshi Eguchi","email":"","orcid":"","institution":"Osaka University Graduate School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Hidetoshi","middleName":"","lastName":"Eguchi","suffix":""}],"badges":[],"createdAt":"2024-09-24 01:08:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5140786/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5140786/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12876-025-04108-2","type":"published","date":"2025-07-19T16:05:28+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":79745442,"identity":"e8f49bd3-cc51-43dc-add5-e484cb57a6d3","added_by":"auto","created_at":"2025-04-02 08:43:17","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":166611,"visible":true,"origin":"","legend":"\u003cp\u003eClassification of patterns on CE-EUS: \u003cstrong\u003ea, b\u003c/strong\u003e Group A: combination of hypovascular patterns in the vascular phase (a) and in the perfusion phase (b). \u003cstrong\u003ec, d\u003c/strong\u003e Group B: The combination of the isovascular pattern in the vascular phase (c) and the hypovascular pattern in the perfusion phase (d). \u003cstrong\u003ee, f\u003c/strong\u003e Group C: The combination of the isovascular pattern in the vascular phase (e) and in the perfusion phase (f).\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-5140786/v1/2460601f42cfcc181d894366.png"},{"id":79745441,"identity":"5852678c-c6e5-432f-90ca-b76bc896199e","added_by":"auto","created_at":"2025-04-02 08:43:17","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":83899,"visible":true,"origin":"","legend":"\u003cp\u003eSixty-five patients were diagnosed with resectable PC. Nine patients did not receive preoperative treatment, and 48 patients ultimately completed NACRT.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-5140786/v1/ba994f98a75153e8cda50634.png"},{"id":79747260,"identity":"cecc8c61-8737-4de4-86c4-ff85bfff3bb0","added_by":"auto","created_at":"2025-04-02 08:59:17","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":273394,"visible":true,"origin":"","legend":"\u003cp\u003eCase of complete remission by NACRT: \u003cstrong\u003ea\u003c/strong\u003eCE-CT before starting initial treatment. \u003cstrong\u003eb,c\u003c/strong\u003e Conventional B-mode image (\u003cstrong\u003eb\u003c/strong\u003e) and contrast-enhanced harmonic image (\u003cstrong\u003ec\u003c/strong\u003e) in the vascular phase on CH-EUS before NACRT. \u003cstrong\u003ed\u003c/strong\u003e Pancreatic ductal adenocarcinoma samples collected by EUS-FNA before NACRT (Papanicolaou staining, 400x). \u003cstrong\u003ee\u003c/strong\u003e CE-CT after NACRT. \u003cstrong\u003ef\u003c/strong\u003e Postoperative pancreatic tissue (hematoxylin-eosin (HE) staining, 40x).\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-5140786/v1/a6d6d0343f40824656d9d3e6.png"},{"id":79745446,"identity":"2553e26c-16ff-4276-be53-4ab9c2e56f1f","added_by":"auto","created_at":"2025-04-02 08:43:17","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":157291,"visible":true,"origin":"","legend":"\u003cp\u003eProbability of seven-year survival after NACRT in patients with resectable PC: \u003cstrong\u003ea \u003c/strong\u003eKaplan-Meier curve for recurrence-free survival (RFS) after NACRT according to the vascularity pattern. The RFS ratio did not differ significantly among Group A, B, and C (p=0.717).\u003cstrong\u003e b\u003c/strong\u003e Kaplan-Meier curve for overall survival after NACRT according to the vascularity pattern. The overall survival ratio did not differ significantly among Group A, B, and C (p=0.783).\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-5140786/v1/e739f275515e14ce397a9eeb.png"},{"id":87220625,"identity":"fe6dcd66-5528-4dd9-912d-affc8c6f6378","added_by":"auto","created_at":"2025-07-21 16:12:54","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1809821,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5140786/v1/3c4a1e98-cbd9-4b3e-adc9-ca7650ad8f77.pdf"},{"id":79745448,"identity":"c01b098a-60bc-4134-abb7-49e31cbe1611","added_by":"auto","created_at":"2025-04-02 08:43:17","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":12251,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTable1.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-5140786/v1/84587d999ac3381b8ad7d025.xlsx"},{"id":79746017,"identity":"fc44926e-1a54-415e-996e-9ff5f2f95d14","added_by":"auto","created_at":"2025-04-02 08:51:17","extension":"xlsx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":12311,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTable2.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-5140786/v1/2772e9f47c3d6c3103834ea6.xlsx"},{"id":79746020,"identity":"dc2e0735-dc5d-444a-8e54-228641485005","added_by":"auto","created_at":"2025-04-02 08:51:17","extension":"pptx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":57025,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplementary Fig.1\u003c/strong\u003e Regimen of preoperative chemoradiation therapy.\u003c/p\u003e","description":"","filename":"SupplementaryFigure1.pptx","url":"https://assets-eu.researchsquare.com/files/rs-5140786/v1/63ff400d2aef86ec9dae7459.pptx"}],"financialInterests":"No competing interests reported.","formattedTitle":"The effect of neoadjuvant chemoradiation therapy in resectable pancreatic cancer was independent of intratumoral vascularization","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe incidence of pancreatic cancer (PC) has been increasing in recent years. However, the 5-year survival rate is only 10% despite the recent development of new chemotherapies [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Therefore, a multidisciplinary approach such as chemoradiation therapy is mandatory to improve this very poor prognosis.\u003c/p\u003e \u003cp\u003eIt has been suggested that the reason for the poor prognosis in PC is strong fibrotic changes that reduce the permeability of anticancer drugs and suppress immune activity. The desmoplastic reaction generates excessively high interstitial fluid pressure and induces vascular collapse, which presents significant barriers to perfusion, diffusion, and convection of therapeutic agents [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Chemotherapeutic agents for pancreatic cancer have been shown to be poorly delivered to tumors in mouse models due to poor tumor vascularization, and this poor vascularity correlates with a highly dense fibrosclerotic stroma within the tumor [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The effects of fibrotic changes can be visualized via contrast-enhanced computed tomography (CE-CT), magnetic resonance imaging (MRI), and endoscopic ultrasound (EUS) [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. EUS has the ability to obtain tissue for histopathological diagnosis and therefore can play a crucial role in the differential diagnosis process of pancreatic tumors, including mass-forming chronic pancreatitis, autoimmune pancreatitis, and pancreatic adenocarcinoma [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eContrast-enhanced harmonic EUS (CH-EUS), which uses second-generation contrast agents, can be used to generate perfusion images depicting the microvasculature of the target. For decades, CH-EUS has shown promising results for the differential diagnosis of pancreatic tumors [\u003cspan additionalcitationids=\"CR8 CR9 CR10 CR11\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], and several studies have reported that the enhancement pattern of CH-EUS reflects the degree of fibrosis in pancreatic masses [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eYamashita et al. reported that evaluating intratumoral vascular flow via CH-EUS could be useful for predicting the efficacy of chemotherapy in patients with unresectable PC treated with gemcitabine or S1 monotherapy [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Zhou et al. reported that in patients with locally advanced PC, the survival time was significantly longer in those with iso-enhancement than in those with hypovascular enhancement in the arterial phase on CE-US [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Emori et al. reported that in patients with unresectable PC treated with first-line gemcitabine and nab-paclitaxel, both PFS and OS were significantly longer in those who had iso-enhancement in both the early and late phases on CH-EUS [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThese findings suggest that pancreatic cancers with an isovascular pattern on CH-EUS may have increased blood flow and a potentially more favorable response to chemotherapy than those with a hypovascular pattern. On the other hand, although preoperative neoadjuvant chemoradiation therapy (NACRT) is a promising option for the multimodal treatment of PC [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], prior to our study, no studies had investigated the relationship between contrast enhancement patterns on CH-EUS and the efficacy of NACRT for resectable pancreatic cancer. Therefore, we hypothesized that the addition of radiotherapy might mitigate differences in chemotherapeutic efficacy resulting from variations in blood flow due to the degree of fibrosis. To investigate this, we conducted a retrospective study to assess the relationship between CH-EUS patterns and the efficacy of NACRT for resectable pancreatic cancer, with a specific focus on evaluating the additional impact of radiotherapy.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design\u003c/h2\u003e \u003cp\u003ePatients who underwent CH-EUS prior to NACRT between August 2011 and January 2015 were included in the study. The selection criteria were as follows: 1) pathologically confirmed diagnosis of pancreatic adenocarcinoma before the initiation of preoperative chemoradiation therapy; 2) resectable or borderline resectable pancreatic cancer; 3) suitable for preoperative chemoradiation therapy; and 4) performance status (PS) of 0\u0026ndash;1. Resectable and borderline resectable PC was defined as follows: 1) no evidence of distant disease (M0) ; 2) no evidence of tumor abutment greater than 180 degree of the circumstance of the superior mesenteric artery (SMA), celiac axis (CA), or common hepatic artery (CHA) ; 3) no evidence of cancer invasion into the confluent point of right colic vein to the superior mesenteric vein (SMV); and 4) no evidence of occlusion of the SMV and portal vein (PV) without an appropriate option for venous resection and reconstruction.\u003c/p\u003e \u003cp\u003eThe primary endpoint was the relationship between the histopathological efficacy of NACRT and the vascular pattern on CH-EUS. The secondary endpoints were the relationships between the CH-EUS vascular pattern and histological differentiation, recurrence-free survival (RFS), and overall survival (OS) in patients who underwent NACRT. This study was conducted retrospectively at a single institution in accordance with the Declaration of Helsinki, and the protocol was approved by the Osaka International Cancer Institute Institutional Review Board (No. 20134).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eEUS procedure and classification of contrast patterns\u003c/h3\u003e\n\u003cp\u003eCH-EUS was performed via a linear type echo endoscope (GF-UCT260; Olympus Corporation, Tokyo, Japan) with an ultrasound observation system (ProSound SSD α-10, ALOKA, Tokyo, Japan) under conscious sedation.\u003c/p\u003e \u003cp\u003eEUS was performed at the time of initial diagnosis. For CH-EUS, a 0.015 mL/kg bolus of contrast agent (Sonazoid; Daiichi-Sankyo, Tokyo) containing perfluorobutane microbubbles was administered, followed by a 10 mL flush of saline solution. The vascularity of the pancreatic tumor was apparent at 10\u0026ndash;15 seconds after the injection of Sonazoid into a peripheral vein, peaked at approximately 20 seconds, and was observed for 120 seconds [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Relatively large vascular irregularities were evaluated in the \u0026ldquo;vascular phase\u0026rdquo;, defined as approximately 20 seconds after injection. In the \u0026ldquo;perfusion phase\u0026rdquo;, defined as 40\u0026ndash;60 seconds after injection, the enhancement of capillaries in the mass was evaluated in comparison with that of the surrounding pancreatic parenchyma. Kappa values were calculated to assess interobserver variability at each phase and for each assessment of intratumoral vascularity on CH-EUS. Kappa values were interpreted according to the Fleiss kappa index, with 95% CI, via the jackknife method. The kappa value results were interpreted as follows: 0.00-0.20, poor agreement; 0.21\u0026ndash;0.40, fair agreement; 0.41\u0026ndash;0.60, moderate agreement; 0.61\u0026ndash;0.80, substantial agreement; and 0.81-1.00, almost perfect agreement [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIntratumoral vascularity was then classified into three patterns according to the enhancement observed in each phase, as follows. Group A included patients who were hypovascular in both the vascular and perfusion phases. Group B included patients who were isovascular in the vascular phase and hypovascular in the perfusion phase. Group C was isovascular in both the vascular and perfusion phases. The images of each pattern are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003ePreoperative treatment and subsequent surgery\u003c/h3\u003e\n\u003cp\u003eAll patients were treated preoperatively with chemoradiation therapy shown in supplementary Fig.\u0026nbsp;1. For systemic chemotherapy, gemcitabine (1000 mg/m\u003csup\u003e2\u003c/sup\u003e) monotherapy was administered to 41 patients on days 1, 8, and 15 of each 28-day as two cycles with concurrent radiotherapy followed by one cycle gemcitabine chemotherapy alone. S-1 (80 mg/ m\u003csup\u003e2\u003c/sup\u003e) monotherapy was administered to 5 patients for 4 weeks at 2-week intervals as one cycle with concurrent radiotherapy followed by another cycle of S-1 chemotherapy alone. Two patients were administered a combination of gemcitabine (1000 mg/m\u003csup\u003e2\u003c/sup\u003e) and nab-PTX (125 mg/m\u003csup\u003e2\u003c/sup\u003e) on day 1 and 8 of each 15 days as one cycle and 2cycle as total with concurrent radiotherapy after 2 cycles of gemcitabine plus nab-PTX induction chemotherapy. Three-dimensional radiation was delivered at a total radiation dose of 50 Gy in daily fractions of 2 Gy and total of 25 fractions, 5 times per week.\u003c/p\u003e \u003cp\u003eAfter completing NACRT, restaging of the PC was performed and pancreatectomy was performed in patients who showed no signs of disease progression, such as manifestation of distant metastases, during NACRT.\u003c/p\u003e\n\u003ch3\u003eSurveillance after surgery\u003c/h3\u003e\n\u003cp\u003eAfter surgical resection of the PC, standard postoperative follow-up with a focus on surveillance for tumor relapse was performed in all patients as follows. 1) Monthly physical examination and routine laboratory tests, including evaluation of tumor markers such as carbohydrate antigen 19\u0026thinsp;\u0026minus;\u0026thinsp;9 (CA19-9) and carcinoembryonic antigen (CEA). Routine postsurgical imaging studies (chest and abdominal CE-CT, abdominal ultrasound, or MRI) were performed every 3 months for 3 years after surgery. 2) Routine laboratory tests and imaging studies were performed 2 to 3 times per year thereafter.\u003c/p\u003e \u003cp\u003eRecurrence of PC was identified on the basis of the findings of the imaging studies and the clinical manifestations. Additional examinations such as positron emission tomography-computed tomography (PET-CT) were also performed to investigate the recurrence of PC when clinically indicated. Cytological/histopathological confirmation of recurrence was not strictly needed.\u003c/p\u003e\n\u003ch3\u003ePathology assessment of resected samples\u003c/h3\u003e\n\u003cp\u003eAll resected samples were fixed in 10% formalin for 48\u0026ndash;72 hours at room temperature. The entire specimen was serially sectioned at 3- to 4-mm intervals according to the pathological tumor node metastasis (pTNM) classification and the guidelines [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. In the present study, an R1 resection margin was defined as the presence of viable tumor cells within 1 mm of the superior mesenteric artery margin, posterior margin, or portal groove margin. Pancreatic transection margins with focal high-grade dysplasia (PanIN 3) were also considered positive.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eDefinitions\u003c/h2\u003e \u003cp\u003eThe tumor reduction ratio was calculated from CE-CT or CH-EUS as (tumor size before CRT minus tumor size after CRT)/(tumor size before CRT). The histopathological response to NACRT was evaluated via the Evans classification (a histological grading system of the percentage of tumor cells destroyed after chemoradiation), as follows: Grade I, little (\u0026lt;\u0026thinsp;10%) or no tumor cell destruction; Grade IIa, destruction of 10\u0026ndash;50% of tumor cells; Grade IIb, destruction of 51\u0026ndash;90% of tumor cells; Grade III, few (\u0026lt;\u0026thinsp;10%) viable-appearing tumor cells; and Grade IV, no viable tumor cells [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eIntratumoral vascularity was compared among pattern groups A, B, and C by Fisher\u0026rsquo;s exact test. RFS and OS were measured from the first day of NACRT to the date of disease recurrence or death, respectively, and were estimated using the Kaplan\u0026ndash;Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazards model to determine variables significantly associated with prognosis. After the hazard ratio (HR) and its 95% confidence interval (CI) were calculated, multivariate analysis was performed on the factors that were significant in the univariate analysis to identify factors independently associated with RFS and OS. P-values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered statistically significant. Statistical analysis was performed with EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003ePopulation and tumor characteristics\u003c/h2\u003e \u003cp\u003eAmong the 65 patients who were diagnosed with PC between August 2011 and January 2015, 9 had upfront surgery, and 56 had NACRT for resectable PC after assessment for potential resectability. Among these patients, 1 patient developed distant metastasis during NACRT, and 7 failed NACRT due to severe adverse events. Therefore, a total of 48 patients (26 males, 22 females) were included in this retrospective study (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The mean patient age was 66.2 years (range, 47\u0026ndash;82 years). Twenty-four (50%) tumors were located in the head of the pancreas, and 24 (50%) were in the body or tail. The mean tumor size was 20.1\u0026thinsp;\u0026plusmn;\u0026thinsp;7.2 cm (range, 8\u0026ndash;35 cm).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eRegarding the pattern of tumor vascularity, there were 31 patients in Group A, 11 patients in Group B, and 6 patients in Group C. Kappa values were calculated to assess the interobserver variability of the visual tumor enhancement pattern on CH-EUS, with a kappa value of 0.98 taken to indicate almost perfect agreement. The patient demographics and clinical characteristics are listed in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. There was no significant difference between the groups in terms of age, sex, Eastern Cooperative Oncology Group performance status scale score, tumor location, tumor size before NACRT, CEA, CA19-9, or first-line chemotherapy.\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 demographics and preoperative clinical characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"16\"\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 \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c14\" colnum=\"14\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c15\" colnum=\"15\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c16\" colnum=\"16\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" morerows=\"1\" nameend=\"c2\" namest=\"c1\" rowspan=\"2\"\u003e \u003cp\u003eVascularity\u003c/p\u003e \u003cp\u003eVascular phase / Perfusion phase\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" morerows=\"1\" nameend=\"c5\" namest=\"c3\" rowspan=\"2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;48)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003eGroup A\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c11\" namest=\"c9\"\u003e \u003cp\u003eGroup B\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c14\" namest=\"c12\"\u003e \u003cp\u003eGroup C\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" morerows=\"1\" nameend=\"c16\" namest=\"c15\" rowspan=\"2\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003eHypo\u003csup\u003ea\u003c/sup\u003e/ Hypo\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;31)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c11\" namest=\"c9\"\u003e \u003cp\u003eIso\u003csup\u003eb\u003c/sup\u003e/ Hypo\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;11)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c14\" namest=\"c12\"\u003e \u003cp\u003eIso / Iso\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;6)\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\u003eSex\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 \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c16\" namest=\"c16\"\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\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(46%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(45%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e(36%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e(67%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.519\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c16\" namest=\"c16\"\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\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(54%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(55%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e(64%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e(33%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c16\" namest=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAge, years\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 \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c16\" namest=\"c16\"\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\u003e65\u0026le;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(56%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(61%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e(36%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e(67%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.327\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c16\" namest=\"c16\"\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\u003e65\u0026gt;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(44%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(39%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e(64%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e(33%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c16\" namest=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eECOG performance status\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 \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c16\" namest=\"c16\"\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\u003e0\u0026ndash;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e(100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e(100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c16\" namest=\"c16\"\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\u003e2\u0026le;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e(0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e(0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c16\" namest=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eTumor location\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 \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c16\" namest=\"c16\"\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\u003eHead\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(50%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(55%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e(36%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e(50%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.585\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c16\" namest=\"c16\"\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\u003eBody/tail\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(50%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(45%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e(64%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e(50%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c16\" namest=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eTumor size before preoperative CRT\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c16\" namest=\"c16\"\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\u003e20 mm\u0026gt;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(56%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(45%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e(73%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e(83%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.143\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c16\" namest=\"c16\"\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\u003e20 mm\u0026le;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(44%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(55%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e(27%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e(17%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c16\" namest=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eCA19-9\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 \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c16\" namest=\"c16\"\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\u003e37 IU/mL\u0026gt;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(40%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(35%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e(55%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e(45%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.240\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c16\" namest=\"c16\"\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\u003e37 IU/mL\u0026le;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(60%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(65%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e(45%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e(55%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c16\" namest=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eCEA\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 \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c16\" namest=\"c16\"\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\u003e5.0 ng/mL\u0026gt;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(88%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(84%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e(91%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e(100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.831\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c16\" namest=\"c16\"\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\u003e5.0 ng/mL\u0026le;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(12%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(16%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e(9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e(0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c16\" namest=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eInitial chemotherapy\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 \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c16\" namest=\"c16\"\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\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(86%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(81%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e(91%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e(100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c16\" namest=\"c16\"\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\u0026thinsp;+\u0026thinsp;nab-paclitaxel\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(10%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(13%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e(9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e(0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c16\" namest=\"c16\"\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\u003eS-1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e(0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e(0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c16\" namest=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"16\" nameend=\"c16\" namest=\"c1\"\u003e \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e\u003cem\u003eHypo\u003c/em\u003e Hypovascular, \u003csup\u003eb\u003c/sup\u003e\u003cem\u003eIso\u003c/em\u003e Isovascular, \u003csup\u003ec\u003c/sup\u003e\u003cem\u003eCRT\u003c/em\u003e chemoradiation therapy, ECOG Eastern Cooperative Oncology Group, CA19-9 carbohydrate antigen 19\u0026thinsp;\u0026minus;\u0026thinsp;9, CEA carcinoembryonic antigen\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eNACRT and subsequent surgery\u003c/h2\u003e \u003cp\u003eAmong the 56 patients who receiced NACRT for potentially resectable PC, 48/56 completed NACRT. One patient developed distant metastases in the liver and lung. Seven patients failed NACRT due to severe adverse events, such as anaphylaxis to gemcitabine. After NACRT and reassessment for resectability, 28/48 patients underwent pancreaticoduodenectomy, 19/48 underwent distal pancreatectomy, and 1/48 underwent total pancreatectomy. There was no patient mortality during the perioperative period. R0 resection was completed in 29/31 (94%) patients in Group A, in 11/11 (100%) in Group B, and in 6/6 (100%) in Group C (no significant difference).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003ePathology specimens\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e lists the histopathological variables according to vascular pattern group in patients who underwent pancreatectomy after NACRT. There was no significant difference in the reduction ratio, Evans classification, or histological grade among the groups. With respect to the effectiveness of NACRT, three patients achieved complete remission (CR) (Group A, n\u0026thinsp;=\u0026thinsp;2; Group B, n\u0026thinsp;=\u0026thinsp;1). Representative imaging findings of CR patients are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. The Evans classification grades of the 48 patients were as follows: grade lV, n\u0026thinsp;=\u0026thinsp;3; grade lll, n\u0026thinsp;=\u0026thinsp;9; grade llb, n\u0026thinsp;=\u0026thinsp;22; grade lla, n\u0026thinsp;=\u0026thinsp;11; and grade l, n\u0026thinsp;=\u0026thinsp;3. There was no significant difference between the groups in terms of the vascular pattern.\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\u003eHistological variables after NACRT\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"16\"\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 \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c14\" colnum=\"14\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c15\" colnum=\"15\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c16\" colnum=\"16\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" morerows=\"1\" nameend=\"c2\" namest=\"c1\" rowspan=\"2\"\u003e \u003cp\u003eVascularity\u003c/p\u003e \u003cp\u003eVascular phase / Perfusion phase\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" morerows=\"1\" nameend=\"c5\" namest=\"c3\" rowspan=\"2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;48)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c9\" namest=\"c6\"\u003e \u003cp\u003eGroup A\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c12\" namest=\"c10\"\u003e \u003cp\u003eGroup B\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c15\" namest=\"c13\"\u003e \u003cp\u003eGroup C\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c16\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c9\" namest=\"c6\"\u003e \u003cp\u003eHypo / Hypo\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;31)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c12\" namest=\"c10\"\u003e \u003cp\u003eIso / Hypo\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;11)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c15\" namest=\"c13\"\u003e \u003cp\u003eIso / Iso\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;6)\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\u003eReduction ratio of tumor\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 \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\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\u003e\u0026lt;\u0026thinsp;0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(19%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(19%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e(18%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e(17%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.783\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\u003e0\u0026le;, \u0026lt;\u0026thinsp;30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(40%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(42%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e(45%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e(17%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\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\u003e30\u0026le;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(41%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(39%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e(36%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e(66%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eEvans's classification\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 \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\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\u003eGrade 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e(18%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e(0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e0.282\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\u003eGrade 2a\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(23%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(26%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e(18%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e(17%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\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\u003eGrade 2b\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(46%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(52%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e(18%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e(66%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\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\u003eGrade 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(19%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(13%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e(36%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e(17%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\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\u003eGrade 4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e(9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e(0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eHistological Differentiation\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 \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\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\u003eUnevaluable, CIS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(15%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(19%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e(9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e(0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e0.314\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\u003eWell\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(27%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(16%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e(36%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e(67%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\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\u003eModerate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(50%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(55%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e(41%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e(33%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\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\u003ePoorly\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(10%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e(9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e(0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eRFS and OS\u003c/h2\u003e \u003cp\u003eThe seven-year median RFS and OS for each group are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. The five-year and seven-year median RFS times were 24.2 months in Group C and 55.9 months in Group A (not yet reached in Group B). The five-year median OS was 34.1 months in Group C (not yet reached in Groups A and B). The seven-year median OS was 47.7 months in Group C and 65.5 months in Group A (not yet reached in Group B). There was no significant difference between the groups in terms of median RFS or OS.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eNACRT represents a pivotal component of the multidisciplinary approach to treating pancreatic cancer PC. Our institution has extensively documented the efficacy of NACRT for resectable PC since 2009 [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. NACRT presents a range of benefits: first, it exerts a potent local therapeutic effect, potentially facilitating downstaging and enabling R0 resection by mitigating the risk of local recurrence. Second, it enhances the immune response by stimulating the release of neoantigens through radiation. Third, NACRT aids in identifying previously undetected distant metastases during treatment, thus sparing patients from unnecessary surgery. Given that the primary challenge in PC treatment lies in the fibrotic alterations caused by desmoplastic reactions, which compromise drug permeability and the immune response, local radiation therapy has emerged as particularly advantageous and may increase the efficacy of systemic chemotherapy in managing micrometastases.\u003c/p\u003e \u003cp\u003eCH-EUS provides intricate insights into tumor vascularity and has proven invaluable in the differential diagnosis of solid pancreatic lesions. A recent meta-analysis revealed pooled estimates of CH-EUS sensitivity and specificity of 93% (95% CI, 0.90\u0026ndash;0.95) and 80% (95% CI, 0.75\u0026ndash;0.85), respectively [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. EUS offers several advantages over alternative imaging modalities for assessing intratumoral vascularity in PCs. Notably, it surpasses US and CT in terms of tumor detection accuracy, particularly in cases of smaller pancreatic cancers (\u0026lt;\u0026thinsp;2 cm in diameter) [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Furthermore, the advent of second-generation ultrasound contrast agents such as Sonazoid enables the acquisition of microvascular images, with EUS outperforming CT in identifying intratumoral microvessels [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Contrast-enhanced ultrasound (CE-US) has also proven instrumental in evaluating fibrotic changes in PCs. For example, Zhou et al. demonstrated that CE-US iso-enhancement in the early phase is correlated with increased tumor angiogenesis and minimal fibrosis [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. In a comparison of surgical samples, Numata et al. reported that the CE-US findings in PC are influenced by interstitial histological features associated with tumor growth [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eYamashita et al. reported that evaluating intratumoral vessel flow via CH-EUS could be useful for predicting the efficacy of chemotherapy in patients with unresectable PC who are treated with gemcitabine or S1 monotherapy [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Zhou et al. reported that in patients with locally advanced PC, the survival time was significantly longer in those who demonstrated iso-enhancement than in those with hypovascular enhancement in the arterial phase on CE-US [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Emori et al. reported that in patients with unresectable PC who were treated with first-line gemcitabine and nab-paclitaxel, both PFS and OS were significantly longer in those who had iso-enhancement in both the early and late phases on CH-EUS [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThese results suggest that PCs that show an isovascular pattern on CH-EUS have greater blood flow and will have a better response to chemotherapy than those with a hypovascular pattern. However, to the best of our knowledge, no previous study has investigated the relationship between the pattern of contrast enhancement on CH-EUS and the efficacy of NACRT for resectable PC.\u003c/p\u003e \u003cp\u003eIn our study, three distinct contrast-enhancement patterns were identified. Group A exhibited hypovascular contrast-enhancement in both the vascular and perfusion phases, which was indicative of poor intratumoral blood flow due to fibrotic changes. Conversely, Group C showed persistent contrast enhancement in both phases, suggesting relatively robust intratumoral blood flow. No correlation between the enhancement pattern and histological differentiation of resected samples was observed, despite previous indications that poorly differentiated PC and anaplastic carcinoma tend to exhibit reduced fibrosis [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Notably, the hypovascular pattern observed in some cases may be attributed to necrotic changes within the tumor.\u003c/p\u003e \u003cp\u003eDespite challenges in evaluating histological differentiation post-NACRT due to extensive tumor eradication, pretreatment assessment via endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) revealed findings typical of pancreatic cancer, such as irregular internuclear distances, clear nucleoli and protruding nuclei. Notably, there were no discernible differences in stromal sample status among the various Evans classifications. According to Zhou et al, the iso-enhancement pattern on CEUS indicates abundant tumor angiogenesis, evenly distributed throughout the lesion, and low-grade fibrosis, whereas the hypo-enhancement pattern is associated with sparse, heterogeneously distributed tumor angiogenesis and relatively high fibrosis [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. However, distinguishing between preexisting fibrotic stroma and NACRT-induced fibrotic changes is difficult, and the relationship between contrast enhancement patterns and treatment-induced fibrosis was not investigated in our study. Nevertheless, among the Group A patients predicted to be less likely to respond to preoperative chemotherapy in previous reports, 19% had responses corresponding to Grade 3 or 4 according to the Evans classification. The addition of radiotherapy may be expected to have an additive effect on chemotherapy efficacy, regardless of intratumoral blood flow assessed by CH-EUS.\u003c/p\u003e \u003cp\u003eIn contrast to previous studies, our findings revealed no significant difference in RFS or OS based on contrast-enhancement patterns [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Additionally, the completion of postoperative adjuvant therapy did not impact OS or RFS (Supplementary Tables\u0026nbsp;1, 2). Remarkably, the median OS surpassed historical data for neoadjuvant chemotherapy for resectable PC, irrespective of CH-EUS contrast patterns [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. These results suggest that the addition of radiotherapy to preoperative chemotherapy may confer additional local therapeutic benefits independent of intratumoral blood flow. Notably, OS may be influenced by factors such as subsequent anticancer therapies or patient characteristics, as emphasized by Yamashita et al.'s evaluation of chemotherapy efficacy in resectable pancreatic cancer patients treated with neoadjuvant chemotherapy (NAC) [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWhile our study has certain limitations, including its single-center retrospective design and variability in chemotherapy and adjuvant therapy regimens, and the relatively small sample size, the observed additive effect of radiotherapy underscores the potential therapeutic benefits of NACRT regardless of tumor blood flow. Future prospective multicenter studies are warranted to validate these findings conclusively.\u003c/p\u003e \u003cp\u003eIn summary, our study suggests that NACRT may mitigate variations in chemotherapeutic efficacy associated with fibrosis-induced blood flow disparities, potentially contributing to improved prognostic outcomes.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eNACRT may provide additional therapeutic benefits regardless of the extent of intratumoral blood flow, potentially extending its prognostic benefits.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eConflicts of interest\u003c/h2\u003e \u003cp\u003eThe authors have no relevant financial disclosures or conflicts of interest to declare.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e \u003cp\u003e The protocol of this study was approved by the Osaka International Cancer Institute, Institutional Review Board (IRB No. 20134). It strictly followed the Declaration of Helsinki and other relevant guidelines. All the patients signed written informed consent to use their clinical data.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication\u003c/strong\u003e \u003cp\u003eNot applicable.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eDeclaration\u003c/p\u003e \u003cp\u003eThis study was supported in part by a grant from The Osaka Foundation for the Prevention of Cancer and Lifestyle-related Diseases (Public Interest Incorporated Foundation).\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eRA designed the research; RA, RT, KI, KO, HA, and HT performed the procedures and surgery; TT performed the radiation therapy; SN performed the pathological assessment; RA and TY analyzed the data; TY drafted the paper; YD and HE revised the draft and approved the final draft. All the authors have read and approved the final manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSiegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021. 2021, 71(1):7\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNeesse A, Michl P, Frese KK, Feig C, Cook N, Jacobetz MA, Lolkema MP, Buchholz M, Olive KP, Gress TM, et al. Stromal biology and therapy in pancreatic cancer. Gut. 2011;60(6):861\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eProvenzano PP, Cuevas C, Chang AE, Goel VK, Von Hoff DD, Hingorani SR. Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma. Cancer Cell. 2012;21(3):418\u0026ndash;29.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOlive KP, Jacobetz MA, Davidson CJ, Gopinathan A, McIntyre D, Honess D, Madhu B, Goldgraben MA, Caldwell ME, Allard D, et al. Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer. Sci (New York NY). 2009;324(5933):1457\u0026ndash;61.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHata H, Mori H, Matsumoto S, Yamada Y, Kiyosue H, Tanoue S, Hongo N, Kashima K. Fibrous stroma and vascularity of pancreatic carcinoma: correlation with enhancement patterns on CT. Abdom Imaging. 2010;35(2):172\u0026ndash;80.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKitano M, Kamata K, Imai H, Miyata T, Yasukawa S, Yanagisawa A, Kudo M. Contrast-enhanced harmonic endoscopic ultrasonography for pancreatobiliary diseases. Dig endoscopy: official J Japan Gastroenterological Endoscopy Soc. 2015;27(Suppl 1):60\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eImazu H, Uchiyama Y, Matsunaga K, Ikeda K, Kakutani H, Sasaki Y, Sumiyama K, Ang TL, Omar S, Tajiri H. 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Contrast harmonic echo-endoscopic ultrasound improves accuracy in diagnosis of solid pancreatic masses. \u003cem\u003eClinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association\u003c/em\u003e 2010, 8(7):629\u0026ndash;634.e621-622.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYamashita Y, Shimokawa T, Ashida R, Napol\u0026eacute;on B, Lisotti A, Fusaroli P, Gincul R, Dietrich CF, Omoto S, Kitano M. Comparison of endoscopic ultrasonography with and without contrast enhancement for characterization of pancreatic tumors: a meta-analysis. Endoscopy Int open. 2022;10(4):E369\u0026ndash;77.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKitano M, Sakamoto H, Kudo M. Endoscopic ultrasound: contrast enhancement. Gastrointest Endosc Clin N Am. 2012;22(2):349\u0026ndash;58.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKitano M, Sakamoto H, Kudo M. 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HPB: official J Int Hepato Pancreato Biliary Association. 2020;22(6):821\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVersteijne E, van Dam JL, Suker M, Janssen QP, Groothuis K, Akkermans-Vogelaar JM, Besselink MG, Bonsing BA, Buijsen J, Busch OR, et al. Neoadjuvant Chemoradiotherapy Versus Upfront Surgery for Resectable and Borderline Resectable Pancreatic Cancer: Long-Term Results of the Dutch Randomized PREOPANC Trial. J Clin oncology: official J Am Soc Clin Oncol. 2022;40(11):1220\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYamashita Y, Ashida R, Kojima F, Okada KI, Kawai M, Yamazaki H, Tamura T, Kawaji Y, Tamura T, Hatamaru K, et al. Utility of contrast-enhanced harmonic endoscopic ultrasonography for prediction of pathological response after neoadjuvant chemotherapy in patients with pancreatic cancer. Pancreatology. 2023;23(8):1014\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-gastroenterology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmge","sideBox":"Learn more about [BMC Gastroenterology](http://bmcgastroenterol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmge/default.aspx","title":"BMC Gastroenterology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"chemoradiation, CH-EUS, EUS, neoadjuvant therapy, pancreatic cancer","lastPublishedDoi":"10.21203/rs.3.rs-5140786/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5140786/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eAim\u003c/h2\u003e \u003cp\u003eContrast-enhanced harmonic endoscopic ultrasound (CH-EUS) has promising potential in the diagnosis of pancreatic tumors, assessment of fibrosis, and prediction of chemotherapy efficacy. We hypothesize that radiation therapy might reduce variations in chemotherapeutic efficacy caused by fibrosis-induced blood flow disparities, as we explored the relationship between CH-EUS patterns and the efficacy of neoadjuvant chemoradiotherapy (NACRT) in resectable pancreatic cancer (PC).\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003ePatients with resectable PC who underwent CH-EUS followed by NACRT were retrospectively analyzed. The CH-EUS enhancement pattern was evaluated in the vascular and perfusion phases and classified according to vascularity: Group A, hypovascular in both phases; Group B, isovascular and hypovascular in the vascular and perfusion phases, respectively; and Group C, isovascular in both phases. The relationships between the CH-EUS vascular pattern and the histological response according to the Evans classification to NACRT, recurrence-free survival (RFS) and overall survival (OS) were evaluated.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eOf the 48 enrolled patients, 31, 11, and 6 were classified into Groups A, B, and C, respectively. There was no significant difference in histopathological differentiation or the efficacy of NACRT among the groups. In addition, there was no significant difference between the groups in terms of median RFS or OS, although it was longer than previously reported.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe histopathological efficacy of NACRT for resectable PC did not differ significantly on the basis of enhancement pattern observed on CH-EUS. NACRT may provide additional therapeutic benefit independent of blood flow considerations.\u003c/p\u003e","manuscriptTitle":"The effect of neoadjuvant chemoradiation therapy in resectable pancreatic cancer was independent of intratumoral vascularization","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-02 08:43:12","doi":"10.21203/rs.3.rs-5140786/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-05-19T07:42:27+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-16T15:55:19+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"53085654117686770712368920739625280355","date":"2025-05-04T13:45:51+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-03-31T07:37:26+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-03-31T07:13:44+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Gastroenterology","date":"2025-03-25T14:41:05+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-gastroenterology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmge","sideBox":"Learn more about [BMC Gastroenterology](http://bmcgastroenterol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmge/default.aspx","title":"BMC Gastroenterology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"286f6880-bc2e-4e13-80af-6b4d3392cac8","owner":[],"postedDate":"April 2nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-07-21T16:11:26+00:00","versionOfRecord":{"articleIdentity":"rs-5140786","link":"https://doi.org/10.1186/s12876-025-04108-2","journal":{"identity":"bmc-gastroenterology","isVorOnly":false,"title":"BMC Gastroenterology"},"publishedOn":"2025-07-19 16:05:28","publishedOnDateReadable":"July 19th, 2025"},"versionCreatedAt":"2025-04-02 08:43:12","video":"","vorDoi":"10.1186/s12876-025-04108-2","vorDoiUrl":"https://doi.org/10.1186/s12876-025-04108-2","workflowStages":[]},"version":"v1","identity":"rs-5140786","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5140786","identity":"rs-5140786","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}