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Purpose: To explore genomic biomarkers in rectal cancer by performing whole-exome sequencing., Materials and Methods: Pre-chemoradiation (CRT) biopsy and post-CRT surgical specimens were obtained from 27 patients undergoing neoadjuvant CRT followed by definitive resection. Exomes were sequenced to a mean coverage of 30×. Somatic single-nucleotide variants (SNVs) and insertions/deletions (indels) were identified. Tumor mutational burden was defined as the number of SNVs or indels. Mutational signatures were extracted and fitted to COSMIC reference signatures. Tumor heterogeneity was quantified with a mutant-allele tumor heterogeneity (MATH) score. Genetic biomarkers and frequently occurred copy number alterations (CNAs) were compared between pre- and post-CRT specimens. Their associations with tumor regression grade (TRG) and clinical outcomes were explored., Results: Top five mutated genes were APC, TP53, NF1, KRAS, and NOTCH1 for pre-CRT samples and APC, TP53, NF1, CREBBP, and ATM for post-CRT samples. Several gene mutations including RUNX1, EGFR, and TP53 in pre-CRT samples showed significant association with clinical outcomes, but not with TRG. However, no such association was found in post-CRT samples. Discordance of driver mutation status was found between pre- and post-CRT samples. In tumor mutational burden analysis, higher number of SNVs or indels was associated with worse treatment outcomes. Six single-base substitution (SBS) signatures identified were SBS1, SBS30, SBS29, SBS49, SBS3, and SBS44. The MATH score decreased after CRT on paired analysis. Less than half of CNAs frequent in post-CRT samples were present in pre-CRT samples., Conclusion: Pre- and post-CRT samples showed different genomic landscape. Potential genetic biomarkers of pre-CRT samples found in the current analysis call for external validation., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: Despite curative resection, the 5-year survival for patients with resectable pancreatic cancer is less than 20%. Recurrence occurs both locally and at distant sites and effective multimodality adjuvant treatment is needed., Materials and Methods: Patients with curatively resected stage IB-IIB pancreatic adenocarcinoma were eligible. Treatment consisted of chemotherapy with gemcitabine 1,000 mg/m2 on days 1 and 8 and cisplatin 60 mg/m2 on day 1 every 3 weeks for two cycles, followed by chemoradiotherapy (50.4 Gy/28 fx) with weekly gemcitabine (300 mg/m2/wk), and then gemcitabine 1,000 mg/m2 on days 1 and 8 every 3 weeks for four cycles. The primary endpoint was 1-year disease-free survival rate. The secondary endpoints were disease-free survival, overall survival, and safety., Results: Seventy-four patients were enrolled. One-year disease-free survival rate was 57.9%. Median disease-free and overall survival were 15.0 months (95% confidence interval [CI], 11.6 to 18.4) and 33.0 months (95% CI, 21.8 to 44.2), respectively. At the median follow-up of 32 months, 57 patients (77.0%) had recurrence including 11 patients whose recurrence was during the adjuvant treatment. Most of the recurrences were systemic (52 patients). Stage at the time of diagnosis (70.0% in IIA, 51.2% in IIB, p=0.006) were significantly related with 1-year disease-free survival rate. Toxicities were generally tolerable, with 53 events of grade 3 or 4 hematologic toxicity and four patients with febrile neutropenia., Conclusion: Adjuvant gemcitabine and cisplatin chemotherapy followed by chemoradiotherapy with gemcitabine and maintenance gemcitabine showed efficacy and good tolerability in curatively resected pancreatic cancer.

Background: Laparoscopic surgery has been widely used for rectal cancer; however, its long-term outcomes remain controversial. This study aimed to assess the long-term oncological safety of laparoscopic surgery for rectal cancer using 10-year follow-up data of the Comparison of Open versus laparoscopic surgery for mid or low REctal cancer After Neoadjuvant chemoradiotherapy (COREAN) trial., Methods: The COREAN trial is a, open-label, non-inferiority, randomised controlled trial. Eligible participants were aged 18-80 years, had cT3N0-2M0 middle or low rectal cancer with lesions located within 9 cm of the anal verge, and had been treated with preoperative chemoradiotherapy. Patients were randomly assigned (1:1) to open or laparoscopic surgery with a computer-generated random allocation sequence with a random permuted block design. Neither patients nor clinicians were masked to treatment assignment. Open or laparoscopic total mesorectal excision was done 6-8 weeks after the administration of preoperative concurrent chemoradiotherapy (fluoropyrimidines alone, doublet therapy, or triplet therapy) at a dose of 50·5 Gy over 5·5 weeks. Postoperative adjuvant chemotherapy was administered for 4 months. The primary endpoint of 3-year disease-free survival was published previously. Here, we report 10-year overall survival, disease-free survival, and local recurrence. Analyses were done in the modified intention-to-treat population of all participants who were randomly assigned and provided follow-up data. This study is registered with ClinicalTrials.gov, NCT00470951., Findings: Of the 340 patients enrolled in the COREAN trial between April 4, 2006, and Aug 26, 2009 (170 patients in each group), two patients in the laparoscopic surgery group moved abroad and were lost to follow-up, so were not included in this 10-year analysis. The median duration of follow-up was 143 months (IQR 122-156). No differences were observed in 10-year overall survival (74·1% [95% CI 66·8-80·0] in the open surgery group vs 76·8% [69·6-82·5] in the laparoscopic surgery group; p=0·44), 10-year disease-free survival (59·3% [51·1-66·5] vs 64·3% [56·0-71·5]; p=0·20), or 10-year local recurrence (8·9% [5·2-15·0] vs 3·4% [1·4-7·9]; p=0·050) between the open surgery and laparoscopic surgery groups at 10 years after surgery. The stratified hazard ratios, adjusted for ypT and ypN classification and tumour regression grade, for open surgery versus laparoscopic surgery were 0·94 (95% CI 0·63-1·43) for overall survival, 1·05 (0·74-1·49) for disease-free survival, and 2·22 (0·78-6·34) for local recurrence., Interpretation: The 10-year follow-up of the COREAN trial confirms the long-term oncological safety of laparoscopic surgery in patients with rectal cancer treated with preoperative chemoradiotherapy. Similar to open surgery, laparoscopic surgery does not compromise long-term survival outcomes in rectal cancer when performed by well trained surgeons., Funding: National Cancer Center, Goyang, South Korea., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background/aims: Although many studies have reported the promising effect of neoadjuvant treatment for borderline resectable pancreatic cancer (BRPC) to increase resectability, only a few studies have recommended the use of first-line chemotherapeutic agents as neoadjuvant treatment for BRPC. The current study compared clinical outcomes between gemcitabine and FOLFIRINOX (5-fluorouracil, leucovorin, oxaliplatin, and irinotecan) in patients with BRPC., Methods: In this single-center retrospective study, 100 BRPC patients treated with neoadjuvant chemotherapy and resection from 2008 to 2018 were reviewed. Clinical outcomes included overall survival, resectability, and recurrence patterns after gemcitabine or FOLFIRINOX treatment., Results: For neoadjuvant chemotherapy, gemcitabine was administered to 34 patients and FOLFIRINOX to 66. Neoadjuvant radiotherapy was administered to 27 patients (79.4%) treated with gemcitabine and 19 (28.8%) treated with FOLFIRINOX (p<0.001). The 2- and 5-year survival rates (YSRs) were significantly higher after FOLFIRINOX (2YSR, 72.2%; 5YSR, 46.0%) than after gemcitabine (2YSR, 58.4%; 5YSR, 19.1%; p=0.041). The margin negative rate was comparable (gemcitabine, 94.1%; FOLFIRINOX, 92.4%; p=0.753), and the tumor size change in percentage showed only a marginal difference (gemcitabine, 20.5%; FOLFIRINOX, 29.0%; p=0.069). Notably, the metastatic recurrence rate was significantly lower in the FOLFIRINOX group (n=20, 52.6%) than in the gemcitabine group (n=22, 78.6%; p=0.001). The rate of adverse events after chemotherapy was significantly higher with FOLFIRINOX than with gemcitabine (43.9%, 20.6%, respectively; p=0.037)., Conclusions: FOLFIRINOX provided more clinical and oncological benefit than gemcitabine, with significantly higher overall survival and lower cumulative recurrence rates in BRPC. However, since FOLFIRINOX causes more adverse effects, the regimen should be individualized based on patient's general condition and clinical status.

Background: Despite the widespread use of neoadjuvant chemoradiotherapy, there is no prognostic surrogate marker established in locally advanced rectal cancer., Objective: This study evaluated the role of neoadjuvant rectal score as a prognostic factor to stratify individual-level risks of survival and tumor recurrence., Design: This is a retrospective study., Settings: This study was conducted at the Seoul National University Hospital., Patients: A total of 397 patients who underwent chemoradiotherapy plus total mesorectal excision were analyzed., Interventions: There was no intervention., Main Outcome Measures: Harrell C statistic and receiver operating characteristic analysis, as well as Cox regression analysis, were used to assess the prognostic strength., Results: The low (<8), intermediate (8-16), and high (>16) neoadjuvant rectal score groups included 91 (23%), 208 (52%), and 98 patients (25%). A high neoadjuvant rectal score was independently associated with inferior overall survival and disease-free survival (p = 0.011 and 0.008). Regarding the prognostic models adjusted for neoadjuvant rectal score (I) and ypT/N stage (II), the c-index was higher in model I (0.799 and 0.787, p = 0.009 for overall survival; 0.752 and 0.743, p = 0.093 for disease-free survival). The predictive ability of the neoadjuvant rectal score was superior to tumor regression grade, ypT, and ypN in the receiver operating characteristic analyses (p < 0.05 for all). Adjuvant chemotherapy was associated with better overall and disease-free survival (p = 0.003 and 0.052) in the high neoadjuvant rectal score group., Limitations: Potential selection bias attributed to the retrospective study design was a limitation., Conclusions: We verified the applicability of the neoadjuvant rectal score to stratify the relapse risk at the individual level for patients with stage II/III rectal cancer undergoing neoadjuvant chemoradiotherapy. Additional studies are needed to validate the usability of neoadjuvant rectal score levels as a determinant of adjuvant strategy. See Video Abstract at http://links.lww.com/DCR/B354. ESTRATIFICACIÓN DE RIESGO UTILIZANDO LA PUNTUACIÓN RECTAL NEOADYUVANTE EN LA ERA DE LA QUIMIORRADIOTERAPIA NEOADYUVANTE: VALIDACIÓN CON DATOS DE RESULTADOS A LARGO PLAZO: A pesar del uso generalizado de la quimiorradioterapia neoadyuvante, no existe un marcador subrogado pronóstico establecido en el cáncer de recto localmente avanzado.Este estudio evaluó el papel de la puntuación rectal neoadyuvante como factor pronóstico para estratificar los riesgos a nivel individual de supervivencia y recurrencia tumoral.Este es un estudio retrospectivo.Este estudio se realizó en el Hospital de la Universidad Nacional de Seúl.Se analizaron un total de 397 pacientes que se sometieron a quimiorradioterapia más escisión mesorrectal total.No hubo intervención.El análisis estadístico C de Harrell y las características operativas del receptor, así como el análisis de regresión de Cox, se utilizaron para evaluar la fuerza pronóstica.Los grupos de puntaje rectal neoadyuvante bajo (<8), intermedio (8-16) y alto (> 16) incluyeron 91 (23%), 208 (52%) y 98 (25%) pacientes, respectivamente. Una puntuación rectal neoadyuvante alta se asoció independientemente con una supervivencia general y una supervivencia libre de enfermedad inferiores (p = 0.011 y 0.008, respectivamente). Con respecto a los modelos pronósticos ajustados por la puntuación rectal neoadyuvante (I) y el estadio ypT/N (II), el índice c fue mayor en el modelo I (0.799 y 0.787, p = 0.009 para la supervivencia general; 0.752 y 0.743, p = 0.093 para supervivencia libre de enfermedad). La capacidad predictiva de la puntuación rectal neoadyuvante fue superior al grado de regresión tumoral, ypT y ypN en los análisis de características operativas del receptor (p <0.05 para todos). La quimioterapia adyuvante se asoció con una mejor supervivencia global y libre de enfermedad (p = 0.003 y 0.052, respectivamente) en el grupo de puntaje rectal neoadyuvante alto.El sesgo de selección potencial debido al diseño retrospectivo del estudio fue la limitación.Verificamos la aplicabilidad de la puntuación rectal neoadyuvante para estratificar el riesgo de recurrencia a nivel individual para pacientes con cáncer rectal en estadio II/III sometidos a quimiorradioterapia neoadyuvante. Se necesitan más estudios para validar la usabilidad de los niveles de puntuación rectal neoadyuvante como determinante de la estrategia adyuvante. Consulte Video Resumen en http://links.lww.com/DCR/B354.

Background: This study was conducted to identify patients who may benefit from adjuvant chemoradiotherapy (CRT) for positive or close resection margin (RM) after curative resection of pancreatic adenocarcinoma., Methods: From 2004 to 2015, total of 472 patients with pancreatic adenocarcinoma underwent curative resection. After excluding patients with RM > 2 mm or unknown, remaining 217 patients were retrospectively analyzed. Forty-six (21.2%) patients were treated with adjuvant chemotherapy alone (CTx; mainly gemcitabine-based), 142 (65.4%) with adjuvant CRT (mainly upfront), and 29 (13.4%) patients didn't receive any adjuvant therapy (noTx group)., Results: Locoregional recurrence rate was significantly lower in the CRT group (43.7%) than in the CTx group (71.7%) or noTx group (65.5%) (p = 0.001). Significant survival benefits of CRT over CTx (HR 0.602, p = 0.020 for overall survival (OS); HR 0.599, p = 0.016 for time to any recurrence (TTR)) were demonstrated in multivariate analysis. CRT group had more 5-year survivors than other groups. In the subgroup analysis, such benefits of adjuvant CRT over CTx was observed only in patients with head tumor & vascular RM > 0.5 mm, but not in patients with body/tail tumor or vascular RM ≤ 0.5 mm. In the CRT group, radiation dose≥54 Gy was significantly associated with better TTR and OS., Conclusions: Adjuvant CRT could improve TTR and OS compared to adjuvant CTx alone in patients with close RM under 2 mm. Radiation dose escalation may be beneficial when feasible. Modern CRT regimen-based randomized evidence is needed for these high-risk patients., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Objective: To evaluate outcomes and toxicity profiles after re-irradiation in patients with pelvic recurrence of anorectal cancer., Methods: 25 anorectal cancer patients who received re-irradiation for pelvic recurrence between 2005 and 2015 were included. For initial treatment, all patients underwent surgical resection and preoperative or postoperative radiotherapy., Results: The median follow-up duration was 21.5 months (range, 2.9-84.4). After a median of 43.3 months (range, 11.7-218.5), patients received re-irradiation with a median dose of 45 Gy (range, 36-60). The equivalent dose in 2 Gy fractions (EQD2) of re-irradiation-calculated using α/β = 10 Gy-ranged from 34.5 to 84.0 Gy (median, 46.4). Surgical resection was performed for 11 patients, and 14 patients received concurrent chemotherapy with re-irradiation. The 3-year local progression-free survival was 29.7%. The 3-year overall survival was 49.7%. Concurrent chemotherapy with re-irradiation and re-irradiation doses >50 Gy EQD2 α/β=10 were significant prognostic factors for local progression free survival and overall survival according to multivariate analysis. 90% (9 of 10) of patients with symptoms had improvement after re-irradiation. Among 23 patients available for evaluation of late toxicity, 12 developed late toxicities. There were no Grade 4 late toxicities, and 6 patients had Grade 3 late toxicities (small bowel obstruction, bowel perforation and fistula)., Conclusion: Re-irradiation for pelvic recurrence of anorectal cancer improved symptoms of patients but the rate of late toxicity was high. Further investigation for patient selection is required., Advances in Knowledge: Re-irradiation could be considered as a possible option for pelvic recurrence of anorectal cancer in selected patients.

Background: To develop and compare delta-radiomics signatures from 2- (2D) and 3-dimensional (3D) features that predict treatment outcomes following preoperative chemoradiotherapy (CCRT) and surgery for locally advanced rectal cancer., Methods: In total, 101 patients (training cohort, n = 67; validation cohort, n = 34) with locally advanced rectal adenocarcinoma between 2008 and 2015 were included. We extracted 55 features from T2-weighted magnetic resonance imaging (MRI) scans. Delta-radiomics feature was defined as the difference in radiomics feature before and after CCRT. Signatures were developed to predict local recurrence (LR), distant metastasis (DM), and disease-free survival (DFS) from 2D and 3D features. The least absolute shrinkage and selection operator regression was used to select features and build signatures. The delta-radiomics signatures and clinical factors were integrated into Cox regression analysis to determine if the signatures were independent prognostic factors., Results: The radiomics signatures for LR, DM, and DFS were developed and validated using both 2D and 3D features. Outcomes were significantly different in the low- and high-risk patients dichotomized by optimal cutoff in both the training and validation cohorts. In multivariate analysis, the signatures were independent prognostic factors even when considering the clinical parameters. There were no significant differences in C-index from 2D vs. 3D signatures., Conclusions: This is the first study to develop delta-radiomics signatures for rectal cancer. The signatures successfully predicted the outcomes and were independent prognostic factors. External validation is warranted to ensure their performance.

Background: There are only limited data on the failure patterns after surgical resection for duodenal cancer, and the role of adjuvant chemoradiotherapy (CRT) also remains controversial. In this study, the treatment outcomes of surgery alone were compared to those of surgery plus adjuvant CRT for duodenal cancer., Methods: Between January 1991 and February 2013, a total of 47 patients with duodenal cancer had pancreaticoduodenectomy, and their age ranged from 31 to 80 (median 62). Twenty-five patients (53%) underwent surgery alone, while 22 (47%) underwent surgery plus adjuvant CRT. Postoperative radiotherapy with concomitant 5-fluorouracil was given to tumor bed and regional lymph nodes up to 40-55.4 Gy. Median duration of follow-up was 31 months (range 6-286) for all patients and 90 months (range 14-286) for survivors., Results: CRT (+) group included more patients with advanced nodal stage and overall stage group (p = 0.003 and 0.002, respectively). The 5-year overall survival rates were not different between CRT (-) and CRT (+) groups (50.1 vs. 46.7%, p = 0.794). CRT (+) group achieved a superior 5-year loco-regional relapse-free survival rate compared with CRT (-) group, but the difference did not reach a statistical significance (80.1 vs. 68.4%, p = 0.267). On multivariate analysis, however, the addition of CRT was the only favorable prognosticator predicting loco-regional relapse-free survival (p = 0.046). Two patients experienced grade 3 neutropenia during CRT., Conclusions: Adjuvant CRT after pancreaticoduodenectomy was correlated with an improved loco-regional control in duodenal cancer. Considering the high loco-regional recurrence in surgery alone group, CRT may be considered as adjuvant treatment.

Purpose: To evaluate the prognostic value of matrix metalloproteinase-9 (MMP-9) in patients with extrahepatic bile duct (EHBD) cancer undergoing surgical resection and adjuvant radiotherapy., Methods: Between January 2000 and August 2006, patients who underwent complete resection followed by adjuvant radiotherapy for EHBD cancer were enrolled in this study. The expression of MMP-9 was assessed with immunohistochemical staining. The prognostic values of the MMP-9 expression and other clinicopathologic factors were evaluated in univariate and multivariate analyses., Results: Sixty-six patients were included in this study. All received radiotherapy with a median dose of 40 Gy (range, 40-56), and 61 patients received concomitant fluoropyrimidine chemotherapy. MMP-9 was highly expressed in 33 patients (50.0%). MMP-9 expression was significantly associated with locoregional recurrence-free survival (LRRFS) and overall survival (OS) but not with distant metastasis-free survival (DMFS). The 5-year LRRFS and OS rates were 50.8% versus 86.5% (p = .0281), and 23.3% versus 68.1% (p = .0087) in patients with low and high expression of MMP-9, respectively. Among the clinicopathologic factors, tumor location was associated with DMFS and OS (p = .0292 and .0003, respectively). Nodal stage and histologic differentiation showed significant association with DMFS (p = .0277 and .0060, respectively). Based on multivariate analysis for OS, tumor location was the only significant prognostic factor (p = .0021), while MMP-9 expression showed marginal significance (p = .0633)., Conclusion: MMP-9 expression is a useful prognostic factor for predicting LRRFS and OS in patients with EHBD cancer after surgical resection and adjuvant radiotherapy., (Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Purpose: To evaluate chemoradiotherapy (CRT)-induced changes in the expression levels of programmed death-ligand 1 (PD-L1) and CD8 + tumor-infiltrating lymphocytes (TILs) and prognostic associations in rectal cancer., Methods and Materials: We performed a paired analysis using pre-CRT biopsies and the corresponding post-CRT resected tissues of 123 rectal cancer patients undergoing preoperative CRT followed by surgery between 2005 and 2012. Immunohistochemistry of PD-L1 and CD8 was analyzed for the specimens., Results: The expression levels of PD-L1 and density of CD8 + TILs increased after CRT (P<.001 for both). With cutoffs using each median value, sustained higher expression of PD-L1 at pre- and post-CRT (high-to-high) was associated with less increase in the density of CD8 + TILs (P=.020). Patients representing sustained high-to-high PD-L1 expression had poorer overall survival and disease-free interval on univariate Kaplan-Meier analysis (P=.018 and .029, respectively), with inferior disease-free interval in low-to-low density CD8 + TILs (P=.010). On multivariate analysis, 2 subgroups with high baseline PD-L1 expression level, the high-to-low and high-to-high alterations, showed worse overall survival (hazard ratio 8.34, 95% confidence interval 1.85-37.53 and hazard ratio 11.03, 95% confidence interval 2.33-52.29, respectively), with the highest mortality risk observed in the high-to-high group., Conclusions: This study verified the CRT-induced immunologic shift toward increases in PD-L1 expression and density of CD8 + TILs in rectal cancer patients. The alteration profiles of checkpoint-related molecules identified the patients with poor prognosis, suggesting potential candidates who can benefit from combining CRT and checkpoint inhibitors., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: To evaluate the prognostic significance of phosphorylated Akt (p-Akt), phosphorylated mammalian target of rapamycin (p-mTOR), and total phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expressions in patients undergoing adjuvant chemoradiotherapy (CRT) for proximal extrahepatic bile duct (EHBD) cancer., Methods: Sixty-three patients with proximal EHBD cancer who underwent curative resection followed by adjuvant CRT were enrolled into this study. Postoperative radiotherapy was delivered to tumor bed and regional lymph nodes up to a median of 40 Gy (range, 40 to 54 Gy). Fifty-nine patients also received fluoropyrimidine chemotherapy as a radiosensitizer. p-Akt, p-mTOR, and PTEN expression were assessed with immunohistochemical staining on the tissue microarray., Results: p-Akt, p-mTOR, and PTEN were expressed in 23 (36.5%), 17 (27.0%), and 24 patients (38.1%), respectively. p-Akt expression was associated with distant metastasis and overall survival (OS), but not with locoregional recurrence. The 5-year distant metastasis-free and OS rates were 25.8% versus 58.2% (P=0.007), and 27.5% versus 50.2% (P=0.0167) in patients with negative and positive expression, respectively. On multivariate analysis, nodal involvement was the only significant prognosticator predicting inferior distant metastasis-free survival (P=0.0105), whereas p-Akt expression had a borderline significance (P=0.0541). As for OS, p-Akt expression was a marginally significant prognosticator (P=0.0635), whereas other risk factors lost the statistical significance., Conclusion: p-Akt expression tended to be associated with a favorable prognosis in patients undergoing curative resection followed by adjuvant CRT for proximal EHBD cancer.

Purpose: The optimal treatment strategy for locally advanced pancreatic cancer (LAPC), particularly the role of concurrent chemoradiotherapy (CCRT), remains debatable. We compared the clinical outcomes of CCRT and palliative chemotherapy alone (CA) in patients with unresectable LAPC., Materials and Methods: Patients with LAPC who were consecutively treated between 2003 and 2010 were included. Resectability was evaluated according to National Comprehensive Cancer Network ver. 1.2012. The clinical outcomes for each treatment group (CCRT vs. CA) were evaluated retrospectively., Results: Sixty-three patients (58.9%) and 44 patients (41.1%) were treated with CCRT and CA, respectively. The CCRT cohort included patients who were treated with CCRT with or without chemotherapy backbone (CCRT alone, induction chemotherapy-CCRT, CCRT-maintenance chemotherapy, and induction-CCRT-maintenance chemotherapy). Median progression-free survival (PFS) and overall survival (OS) of all patients were 7.2 months and 13.1 months. PFS of the CCRT and CA groups was 9.0 months and 4.4 months, respectively (p=0.020). OS of the CCRT and CA groups was 15.4 months and 9.3 months, respectively (p=0.011). In multivariate analysis, the adjusted hazard ratio of CCRT was 0.536 (p=0.003) for OS and 0.667 (p=0.078) for PFS. Although the pattern of failure was similar in the CCRT and CA groups, the times to both local and distant failure were significantly longer in the CCRT group., Conclusion: In patients with unresectable LAPC, those who underwent CCRT during their entire treatment courses had longer OS than patients treated with chemotherapy alone.

This population-based study evaluated the survival impact of postoperative radiotherapy (PORT) in left-sided pancreatic cancer. The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients with surgically resected left-sided pancreatic adenocarcinoma from 2004 to 2010. Propensity score matching was conducted to compare PORT and non-PORT groups. A total of 445 patients were identified, and PORT was performed in 180 (40 %) patients. In the unmatched population, there were no significant differences in overall survival (OS) (P = 0.197) and cause-specific survival (CSS) (P = 0.379) between the PORT and non-PORT groups. After propensity score matching, the patients treated with PORT had longer median OS (P = 0.012) and CSS (P = 0.039) than the non-PORT group. In propensity-adjusted multivariate analysis, non-receipt of PORT was a poor prognostic factor in OS (hazard ratio [HR] 1.39, 95 % confidence interval [CI] 1.08-1.79), and CSS (HR 1.31, 95 % CI 1.01-1.71). The log odds of positive lymph nodes (LOODS) (≥-0.73) was also associated with worse OS (P = 0.003) and CSS (P = 0.001). In left-sided pancreatic cancer, considering the addition of PORT is a reasonable option as in pancreatic head cancer. The LOODS was suggested as a strong predictive indicator of the patients' prognoses.

Background: Current nodal staging system for extrahepatic bile duct (EHBD) cancer is controversial. The number of metastatic lymph nodes (mLN) and lymph node ratio (LNR) has been studied for the assessment of the nodal status in many other gastrointestinal cancers, but there are few studies on assessing the prognostic impact of these parameters in EHBD cancer., Methods: We retrospectively reviewed 239 consecutive patients who underwent curative resection followed by adjuvant chemoradiotherapy for adenocarcinoma of EHBD from 1995 to 2009 in our institution. The prognostic value of the number of mLN and LNR was evaluated by adjusting for other known factors. Optimal cutoff points were determined using maximally selected chi-square test., Results: Lymph node metastasis was found in 77 (32 %) patients. Univariate analysis for overall survival (OS) revealed both the number of mLN (0 vs. 1-3 vs. ≥4; p < 0.001) and LNR (<0.2 vs. ≥0.2; p < 0.001) as significant prognosticators. Multivariate analysis demonstrated that the number of mLN was an independent prognostic factor, whereas LNR was not. The estimated 5-year OS was 48.7 % for patients with negative nodes, 33.4 % for patients with 1-3 mLN, and 9.1 % for patients with 4 or more mLN (p < 0.001)., Conclusions: The number of mLN is a powerful parameter to predict survival in the EHBD cancer, which is more reliable than LNR. As for many other gastrointestinal cancers, further classification of node positive patients based on the number of mLN seems to be useful and may provide precise information.

Background and Purpose: The Korean Radiation Oncology Group evaluated the significance of carcinoembryonic antigen (CEA) levels both as a predictor of tumor response after CRT and as a prognosticator for recurrence-free survival., Methods and Materials: 1804 rectal cancer patients, staged cT3-4N0-2M0, participated in a multicenter study. The patients were administered preoperative radiation of 50.4 Gy in 28 fractions with 5-FU or capecitabine, followed by total mesorectal excision. Patients with elevated CEA levels (>5 ng/mL) were matched at a 1 (n=595):1 (n=595) ratio with patients with normal CEA (⩽5 ng/mL). The tumor response after CRT and the recurrence-free survival (RFS) rates were evaluated and compared between two arms., Results: An elevated CEA level (p<0.001) was determined to be a significant negative predictor of downstaging after CRT. The downstaging rate was 42.9% for normal CEA and 23.4% for elevated CEA. A multivariate analysis also revealed that cT (p=0.021) and cN classification (p=0.001), tumor size (p=0.002), and tumor location from the anal verge (p=0.006) were significant predictors for tumor downstaging. The 5-year RFS rates were significantly higher for the normal CEA arm than for the elevated CEA arm (74.2 vs. 63.5%, p<0.001)., Conclusions: Elevated CEA (>5 ng/mL) is a negative predictor of tumor downstaging after CRT and also has a negative impact on RFS in rectal cancer., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objectives: To compare the treatment outcome of surgery alone with that of surgery followed by adjuvant chemoradiotherapy (CRT) for duodenal cancer., Methods: Between January 1991 and December 2002, 24 patients with duodenal cancer underwent pancreaticoduodenectomy. There were 14 males and 10 females, and median age was 61 years (range, 33-75). Nine patients received adjuvant CRT, and 15 did not. Postoperative radiotherapy was delivered up to 40 Gy at 2 Gy/fraction with a 2-week planned rest. Intravenous 5-fluorouracil (500 mg/m/d) was given on days 1 to 3 of each split course. Median follow-up period was 32 months (range, 5-170)., Results: Nodal stage and stage group were more advanced in CRT (+) group (P=0.0894 and 0.0361, respectively). However, other patient and tumor characteristics were similar in each group. Five-year overall survival rates of CRT (-) and CRT (+) group were 47% and 30%, respectively (P=0.3799). Five-year locoregional relapse-free survival rates of CRT (-) and CRT (+) group were 64% and 80%, respectively (P=0.4188). On multivariate analysis, patients treated with adjuvant CRT had better locoregional relapse-free survival with borderline significance (P=0.0750). No patient suffered grade 3 or higher toxicity during CRT., Conclusions: Adjuvant CRT is feasible and may enhance locoregional control in advanced-staged duodenal cancer after curative resection.

Purpose: To analyse the outcome of adjuvant chemoradiotherapy for periampullary adenocarcinoma and the impact of tumour location as a prognosticator., Methods and Materials: Between January 1991 and December 2002, 147 patients with periampullary cancer underwent adjuvant chemoradiotherapy after pancreaticoduodenectomy. Postoperative radiotherapy was delivered to tumour bed and regional lymph nodes up to 40 Gy at 2 Gy/fraction with a two-week planned rest. Intravenous 5-fluorouracil (500 mg/m(2)/day) was given on days 1-3 of each split course. The median follow-up period was 82 months in survivors., Results: Tumour >2 cm and margin-positivity were more common in patients with pancreatic cancer than nonpancreatic periampullary cancers (p<0.0001 and 0.0780, respectively). According to the tumour location, 5-year overall survival rates of ampulla of Vater, distal common bile duct, duodenal and pancreatic head cancers were 53.0%, 50.3%, 37.5%, and 13.0%, respectively (p<0.0001). On multivariate analysis, pancreatic location (p<0.0001) and nodal involvement (p=0.0123) were associated with inferior overall survival., Conclusion: Regardless of its advanced histologic features, pancreatic location itself was an adverse prognostic factor affecting overall survival.

Objectives: To analyze the outcome of adjuvant chemoradiotherapy for patients with extrahepatic bile duct (EHBD) cancer, and to identify the prognostic factors for these patients., Methods: Between January 1995 and December 2002, 86 patients with adenocarcinoma of EHBD underwent curative resection followed by adjuvant chemoradiotherapy. There were 59 male and 27 female patients, and median age was 59 years (range, 34 to 73 y). Postoperative radiotherapy was delivered to tumor bed and regional lymph nodes up to 40 Gy at 2 Gy/fraction with a 2-week planned rest. Intravenous 5-fluorouracil (500 mg/m(2)/d) was given on day 1 to 3 of each split course. The median follow-up period was 83 months for survivors., Results: Forty-eight patients failed the treatment: locoregional recurrence in 20, distant metastasis in 38, and both locoregional and distant relapses in 10 patients. Five-year locoregional relapse-free survival rate was 70.3%. On multivariate analysis, resection margin status was the only significant prognosticator (P=0.0299). Five-year distant metastasis-free survival rate was 53.6%. Three or more involved lymph nodes had an adverse impact on distant metastasis-free survival (P=0.0334). Five-year overall survival rate was 44.7%, and poorly differentiated tumor was associated with inferior overall survival (P=0.0297)., Conclusions: Adjuvant chemoradiotherapy after curative resection can achieve a long-term survival in patients with EHBD cancer. Resection margin status, number of involved lymph nodes, and histologic differentiation are associated with locoregional relapse, distant metastasis, and overall survival, respectively. Distant metastasis was the major pattern of failure, possibly due to the increased locoregional control by use of adjuvant chemoradiotherapy. Intensification of systemic treatment is warranted.

Purpose: To analyze the outcome of adjuvant chemoradiotherapy for patients with distal common bile duct (CBD) cancer who underwent curative surgery, and to identify the prognostic factors for these patients., Methods and Materials: Between January 1991 and December 2002, 38 patients with adenocarcinoma of the distal CBD underwent curative resection followed by adjuvant chemoradiotherapy. There were 27 men and 11 women, and the median age was 60 years (range, 34-73). Adjuvant radiotherapy was delivered to the tumor bed and regional lymph nodes up to 40 Gy at 2 Gy/fraction with a 2-week planned rest. Intravenous 5-fluorouracil (500 mg/m(2)/day) was given on day 1 to day 3 of each split course. The median follow-up period was 39 months., Results: The 5-year overall survival rate of all patients was 49.1%. On univariate analysis, only histologic differentiation (p = 0.0005) was associated with overall survival. Tumor size (< or =2 cm vs. >2 cm) had a marginally significant impact on the treatment outcome (p = 0.0624). However, there was no difference in overall survival rates between T3 and T4 tumors (p = 0.6189), for which the main determinants were pancreatic and duodenal invasion, respectively. On multivariate analysis, histologic differentiation (p = 0.0092) and tumor size (p = 0.0046) were independent risk factors for overall survival., Conclusions: Long-term survival can be expected in patients with distal CBD cancer undergoing curative surgery and adjuvant chemoradiotherapy. Histologic differentiation and tumor size were significant prognostic factors predicting overall survival, whereas duodenal invasion was not. This finding suggests the need for further refinement in tumor staging., (Copyright 2010 Elsevier Inc. All rights reserved.)

Aims and Background: To evaluate the influence of radiation therapy target volume on the treatment outcome of adjuvant chemoradiotherapy for pancreatic cancer after curative resection., Methods: Between February 1987 and July 2001, 70 patients treated with curative resection and adjuvant chemoradiotherapy for pancreatic adenocarcinoma were analyzed. There were 49 males and 21 females, with a median age of 57 years. Whipple's operation was performed in 44 patients, pylorus-preserving pancreaticoduodenectomy in 14, distal pancreatectomy in 9, and subtotal pancreatectomy in 3. Postoperative adjuvant radiotherapy was given up to 40 Gy at 2 Gy per fraction with a two-week planned rest. Intravenous 5-fluorouracil (500 mg/m2/day) was given on days 1 to 3 of each split course of radiotherapy. Until 1991, whole pancreas or preoperative tumor volume and retroperitoneal lymph nodes were irradiated (extended field, n=14). Thereafter, the target volume included the retroperitoneal lymph nodes and the involved pancreatic resection margin (limited field, n=56). The median follow-up period of all the patients was 16 months (range, 2-99)., Results: The overall 2- and 5-year survival rate of all patients was 29.7% and 14.0%, respectively. According to the radiotherapy target volume, the median survival time was 14 months in the extended field group and 16 months in the limited field group (P = 0.65)., Conclusions: From the viewpoint of the target volume of radiotherapy, a limited field did not worsen the treatment outcome, although the survival rate was poor in both groups.