Survival Benefit after Shifting from Upfront Surgery to Neoadjuvant Treatment in Borderline Resectable Pancreatic Cancer.

According to the 2016 National Comprehensive Cancer Network (NCCN) guidelines, patients with borderline resectable pancreatic cancer (BRPC) should receive chemotherapy as the first-line treatment. This study examined the real-world survival benefits of modifying BRPC treatment guidelines. Patients treated for BRPC at a single institution from 2013 to 2015 (pre-guideline group) and 2017 to 2019 (post-guideline group) were retrospectively reviewed. According to the treatment method used, patients were classified into upfront surgery (US), surgery after neoadjuvant treatment (NAT), and chemotherapy only (CO) groups. Overall survival (OS) was compared according to period and treatment type. Factors associated with OS were analyzed using a Cox regression model. Among the 165 patients, 63 were in the pre-guideline group and 102 patients were in the post-guideline group. The median OS was significantly improved in the post-guideline group compared to the pre-guideline group (29 vs. 13 months, p < 0.001). According to the treatment method, the median OS of the NAT group was significantly longer than that of the US and CO groups (40 vs. 16 vs. 15 months, respectively, p < 0.001). In multivariate analysis, tumor size, differentiation, NAT, and perineural invasion were significant prognostic factors. NAT is an important treatment option for BRPC and increased patient survival in the real world.

Safety and efficacy of adjuvant chemoradiation therapy with capecitabine after resection of pancreatic ductal adenocarcinoma: a retrospective review.

PURPOSE: To evaluate clinical outcomes and safety of adjuvant chemoradiation therapy (CRT) with capecitabine after resection of pancreatic adenocarcinoma at a single institution. PATIENTS AND METHODS: A retrospective analysis of patients undergoing adjuvant CRT with capecitabine after resection of pancreatic ductal adenocarcinoma between 2004 and 2007 yielded a total of 55 patients. Capecitabine was administered at 850 mg/m(2) twice daily every day per week radiotherapy (45 Gy in 25 fractions) over the 5 weeks. Sixteen percent of patients (N=9) went on to receive gemcitabine. RESULTS: Of 55 patients, 42 had curative (R0) resection and 13 had incomplete resection (R1). Median overall survival (OS) and progression free survival were 18.3 and 8.0 months for all patients, respectively. Patients receiving additional gemcitabine after adjuvant CRT with capecitabine showed better OS and progression free survival than those not receiving additional gemcitabine (P<0.05). In multivariate analysis, lymphovascular invasion (present vs. absent) and addition gemcitabine therapy (yes vs. no) were significant independent prognostic factors for OS (P<0.05). Local recurrence was observed in 10 patients, and distant recurrence in 26 patients, synchronously accounting for 6 recurrences. Ten patients (18.2%) had severe grade 3 toxicities. CONCLUSIONS: Capecitabine-based CRT after resection of pancreatic adenocarcinoma showed favorable outcomes and tolerable toxicity profiles.

Relationship of polymorphism of the tandem repeat sequence in the thymidylate synthase gene and the survival of stage III colorectal cancer patients receiving adjuvant 5-flurouracil-based chemotherapy.

BACKGROUND: The aim of this study was to determine whether the different polymorphisms in the thymidylate synthase (TS) gene, novel G>C single nucleotide polymorphism (SNP) and variable number of tandem repeat (VNTR), may be related with disease-free survival (DFS) in patients with stage III colorectal cancer receiving adjuvant chemotherapy. METHODS: The study included 201 patients with pathologic TNM stage III colon cancer who received adjuvant 5-fluorouracil (5-FU)-based chemotherapy after surgery. DNA was extracted from fresh tumor tissue and sequenced. Patients with TS genotypes of 2R3G, 3C3G, or 3G3G were assigned to a high expression group, and those with 2R2R, 2R3C, or 3C3C, to a low expression group. RESULTS: Frequencies of the TS tandem repeat polymorphisms among the tumor genotypes were 6.0% in 2R2R, 25.4% in 2R3R, and 68.7% in 3R3R. The low expression group included 52 patients (25.9%), and the high expression group included 149 patients (74.1%). Groups classified according to possession of VNTR, SNP, and low- or high-expression genotypes did not differ significantly in DFS. In multivariate analysis, only tumor stage showed significant prognostic value (hazard ratio (HR) 2.05, 95% CI = 1.24-3.37, P = 0.005). CONCLUSIONS: TS polymorphisms do not predict clinical outcome of colorectal cancer patients treated with adjuvant 5-FU-based chemotherapy.

Definitive chemoradiation therapy with capecitabine in locally advanced pancreatic cancer.

We evaluated safety and efficacy of concurrent chemoradiotherapy (CCRT) with capecitabine in patients with locally advanced pancreatic cancer (LAPC). Between January 2004 and January 2008, 39 patients with LAPC treated with capecitabine CCRT were reviewed. Capecitabine was administered at 850 mg/m twice daily every day with 5 days per week radiotherapy (1.8 Gy fractions) over the 5 weeks. Thirty-seven (94.8%) patients completed CCRT. Of the 36 evaluable patients, 15 (41.7%) and 13 (36.1%) patients achieved partial response and stable disease, and eight (28.6%) among them received gemcitabine-based post-CCRT chemotherapy without dose reduction or delay. The overall survival was 14.3 months [95% confidence interval (CI): 10.6-17.9 months]. Median progression-free survival was 11.1 months for all patients, and 7.9 months for those patients who had not received post-CCRT chemotherapy. Eight patients (21.6%) had severe grade 3 toxicities, seven (18.9%) with gastrointestinal toxicity, and one (2.7%) with hematologic toxicity. Prognostic factors for survival were serum albumin (P = 0.014; relative risk: 3.4; 95% CI: 1.4-9.7), and adjuvant gemcitabine treatment (P=0.005; relative risk: 3.5; 95% CI: 1.2-10.6). Combined therapy with capecitabine CCRT was well tolerated and seems to be a promising regimen, in terms of response, survival, and adverse effects.

Prognostic factors and adjuvant chemoradiation therapy after pancreaticoduodenectomy for pancreatic adenocarcinoma.

BACKGROUND: The aim of this study was to determine prognostic factors for survival after resection of pancreatic adenocarcinoma (PC) and to compare outcomes after surgery alone versus surgery plus adjuvant therapy. METHODS: We performed a retrospective review of 219 patients who underwent pancreaticoduodenectomy for PC with curative intent between 1995 and 2007. Data were collected prospectively. Postoperative adjuvant chemoradiation therapy (CRT) consisted of fluorouracil or gemcitabine-based chemotherapy; the median radiation dose was 45 Gy. RESULTS: The 3- and 5-year overall survival (OS) rates were 24.3% and 14.2%, respectively. Median OS was 14.0 months [95% confidence interval (CI), 12-16 months]. Patients with metastatic lymph nodes experienced improved median survival (16 vs 10 months; P < 0.001) and 3-year OS (3-year OS 28% vs 8%) after adjuvant CRT compared with those who had no CRT. Patients who underwent non-curative resection had the same effect (median OS, 13 vs 8 months; P = 0.037). Lymph node metastasis and non-curative resection showed no significance on multivariate analysis. Poor differentiation [risk ratio (RR) = 2.10; P < 0.001] and tumor size >3 cm (RR = 1.57; P = 0.018) were found to be adverse prognostic factors; adjuvant CRT had borderline significance (RR = 0.70; P = 0.087). CONCLUSIONS: Adjuvant CRT benefited a subset of patients with resected PC, particularly those with lymph node metastasis and those undergoing non-curative resection. Multivariate analysis demonstrated that patients with tumors larger than 3 cm and poor differentiation had poor prognosis.

Impact of E2F-1 expression on clinical outcome of gastric adenocarcinoma patients with adjuvant chemoradiation therapy.

PURPOSE: There are no reliable prognostic markers that identify gastric cancer patients who may benefit from adjuvant chemoradiation therapy. E2F-1 was shown to be associated with radiosensitivity and chemosensitivity in certain tumor types. Therefore, we analyzed expression and prognostic significance of E2F-1 along with thymidylate synthase (TS) in R(0)-resected gastric adenocarcinoma patients, who underwent adjuvant chemoradiation therapy with 5-fluorouracil (5-FU) and leucovorin. EXPERIMENTAL DESIGN: The chemosensitivity to 5-FU and radiosensitivity were tested in three E2F-1-overexpressed gastric cancer cell lines in vitro. The expressions of TS and E2F-1 were analyzed in 467 R(0)-resected primary gastric cancer patients, who received adjuvant chemoradiation therapy with 5-FU and leucovorin using tissue microarray. RESULTS: The E2F-1 immunopositivity rate was 22.2% (103 of 465 samples) with a cutoff value of 5% immunoreactivity, whereas the TS-positive expression occurred in 19.0% of the 463 tumors tested. Using stepwise Cox proportional hazards regression modeling, multivariate analyses showed that the E2F-1 immunopositivity predicted more favorable survival as compared with the E2F-1 immunonegativity with borderline statistical significance [P = 0.050, hazard ratio (HR) = 0.702, 95% confidence interval, 0.487, 1.013]. However, the E2F-1 immunopositivity did not retain its statistical significance at multivariate analysis for predicting disease-free survival (data not shown, P = 0.270), but stage was the only influential factor for disease-free survival in stages IB to IV (M(0)) patients (P < 0.001). TS immunopositivity did not influence survival (P = 0.459) or disease-free survival (P = 0.447). CONCLUSION: E2F-1 is a potentially novel independent prognostic factor that may identify gastric cancer patients who will likely benefit from adjuvant chemoradiation therapy following curative resection.

Missing effect of glutamine supplementation on the surgical outcome after pancreaticoduodenectomy for periampullary tumors: a prospective, randomized, double-blind, controlled clinical trial.

BACKGROUND: The effect of glutamine (Gln) supplementation in patients undergoing a major operation has not been conclusively established. This study was designed to elucidate the effect of Gln supplementation on the surgical outcome after a pancreaticoduodenectomy (PD) for periampullary tumors. METHODS: A prospective, randomized, double-blind, and controlled clinical trial was undertaken for patients who underwent a classical PD or a pylorus-preserving PD for periampullary tumors. The Gln and control groups received isonitrogenous amino acid, with a 0.2 g/kg per day Gln regimen administered to the Gln group. The surgical outcome was compared in light of length of postoperative hospital stay, nutritional and chemical profiles, and complication rate between the Gln and control groups. RESULTS: Sixty of the consecutive 143 patients who were admitted to undergo operation for periampullary tumors were enrolled in our study; 32 were in the Gln group and 28 in the control group. The two groups were comparable prior to and during the operation. The median length of the postoperative hospital stay and the postoperative nutritional and chemical profiles were not different between two groups. The overall and PD-related complication rates of the Gln group (37.5% and 25.0%) and the control group (28.6% and 14.3%) were not statistically different. CONCLUSIONS: No significant beneficial effect of Gln supplementation with a low-dose parenteral regimen was demonstrated on the surgical outcome after a PD for periampullary tumors. Therefore, we should be prudent in using Gln as a routine pharmacologic supplement to the standard nutrition in patients who undergo major operations.

An observational study suggesting clinical benefit for adjuvant postoperative chemoradiation in a population of over 500 cases after gastric resection with D2 nodal dissection for adenocarcinoma of the stomach.

PURPOSE: The role of adjuvant chemoradiotherapy (CRT) in D2-resected gastric-cancer patients has not been defined yet. We investigated the effect of postoperative chemoradiotherapy on the relapse rate and survival rate of patients with D2-resected gastric cancer. METHODS AND MATERIALS: From August 1995 to April 2001, 544 patients received postoperative CRT after curative D2 resection. During the same period of time, 446 patients received surgery without further adjuvant treatment. The adjuvant CRT consisted of 400 mg/m2 of fluorouracil plus 20 mg/m2 of leucovorin for 5 days, followed by 4,500 cGy of radiotherapy for 5 weeks, with fluorouracil and leucovorin on the first 4 and the last 3 days of radiotherapy. Two 5-day cycles of fluorouracil and leucovorin were given 4 weeks after the completion of radiotherapy. RESULTS: The median duration of overall survival was significantly longer in the CRT group than in the comparison group (95.3 months vs. 62.6 months), which corresponds to a hazard ratio for death of 0.80 (p = 0.0200) or a reduction of 20% in the risk of death in the CRT group. The 5-year survival rates were consistently longer in the CRT group at Stages II, IIIA, IIIB, and IV than those in the comparison group. The CRT was associated with increases in the median duration of relapse-free survival (75.6 months vs. 52.7 months; hazard ratio for relapse, 0.80, p = 0.0160). CONCLUSION: Our results highly suggest that the postoperative chemoradiotherapy in D2-resected gastric-cancer patients can prolong survival and decrease recurrence.