bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tolerability and clinical outcomes in elderly patients with advanced pancreatic cancer treated with FOLFIRINOX.
Authors: Yamamoto Taikan , Sunakawa Yu , Kubota Yutaro , Tagawa Teppei , Kaga Yasuhiro , Ikusue Toshikazu , Uto Yu , Kitahara Yu , Toshima Hirokazu , Kobayashi Kouji , Hisamatsu Atsushi , Ichikawa Wataru , Sekikawa Takashi , Shimada Ken , Sasaki Yasutsuna 
Published: February 2017

404 Background: FOLFIRINOX, a combination chemotherapy of 5-FU, oxaliplatin, and irinotecan, has contributed to the overall survival (OS) benefit of advanced pancreatic cancer (PC), of which a major concern is severe toxicity such as neutropenia and diarrhea. Some elderly patients (pts) with PC need such an intensive chemotherapy in practical treatment; however, tolerability and efficacy for the regimen in the elderly are not well known. We report a retrospective analysis for toxicity and efficacy of FOLFIRINOX treatment in elderly pts with advanced PC. Methods: We analyzed pts with unresectable/metastatic PC, ECOG performance status 0 or 1, neutrocyte over 1500/mm3, and hemoglobin over 9g/dl, who received FOLFIRINOX as 1st- or 2nd-line therapy between November 2012 and July 2015 in 3 institutes of Showa University, Japan. All pts were divided into two groups, elderly group with pts 65 years of age or older and younger group with pts under 65 years old, then were compared in the toxicity and efficacy of FOLFIRINOX treatment. Results: Fifty-nine pts (median age: 62 years) were enrolled in this study: elderly and younger groups included 26 pts (median age: 70 years) and 33 pts (median age: 57 years), respectively. Severe neutropenia with grade 4 was numerically more frequent in the elderly group compared to the younger group (54% vs. 36%, p = 0.17). However, rate of febrile neutropenia was similar between the groups: 3 (12%) pts for the elderly group and 2 (6%) pts for the younger group. There was no difference in frequency of any grade toxicities, and no FOLFIRINOX treatment-related death was observed in both groups. Response rate was 14% (5/26) for the elderly group and 33% (11/33) for the younger group, with no significant difference (p = 0.22). Median progression-free survival (PFS) and OS were comparable between the elderly and younger groups (5.3 months vs. 5.4 months, log-rank p = 0.47 for PFS; not-reached vs. 10.7 months, long-rank p = 0.49 for OS). Conclusions: Our study suggests that FOLFIRINOX treatment is tolerable and active for the elderly pts with advanced PC, although frequency of severe neutropenia is higher in the elderly compared to the younger pts.
Local effect and gastrointestinal toxicity for carbon-ion radiotherapy in patients with unresectable locally advanced pancreatic cancer.
Authors: Shinoto Makoto , Shioyama Yoshiyuki , Suefuji Hiroaki , Matsunobu Akira , Toyama Shingo , Kudo Sho 
Published: February 2017

410 Background: Carbon-ion radiotherapy (CIRT) is a unique external radiotherapy that has an excellent dose conformity and higher biological effectiveness compared to conventional radiotherapy. The sensitivity of the organs in upper abdomen has limited the radiation dose to levels that are ineffective against pancreatic cancer, which has extreme radioresisnatnce. We investigated effectiveness and gastrointestinal (GI) toxicity of CIRT. Methods: From April 2014 to June 2015, 41 patients with pancreatic cancer were treated with definitive CIRT. 26 patients who were confirmed as unresectable locally advanced pancreatic cancer pathologically and by imaging techniques were included in this retrospective analysis. 15 patients were excluded because of resectable disease (n = 3), borderline disease (n = 4), no cell evidence (n = 11). CIRT was performed with 55.2 Gy (RBE) at 12 fractions. The maximal absolute dose with covered 2cm3 of the organ (D2) was restricted under 46 Gy (RBE). All patients were followed up using CT, FDG-PET and upper gastrointestinal endoscopy at least every six months. Anti-tumor effect was evaluated using CT and FDG-PET according to RECIST. If FDG accumulation was negative or equal to normal pancreatic tissue after CIRT, it was defined CR even no decreasing in seize on CT. GI toxicity was evaluated using CTCAE. Results: Tumor location were head in 7, head-body in 2, body-tail in 16. Median tumor size was 35mm (range 21-50). In all patients, sequential and/or concurrent chemotherapy was performed. The median follow-up period was 7.7 months. Local effect using CT criteria was CR in 0, PR in 2, SD in 22, and PD in 2. The evaluation adding FDG-PET criteria was CR in 12, PR in 4, SD in 8, and PD in 2. Two patients who were SD by CT and CR by FDG-PET performed tumor resection and were revealed pCR. The actual incidence of gastric ulcer/bleeding was 15% (n = 4). Only one patient (4%) received blood transfusion because of grade 3 gastric ulcer. The other patients experienced grade 1/2 gastric ulcer. There was no duodenal ulcer. Conclusions: CIRT were effective and well tolerated under the restriction of D2 < 46 Gy (RBE). FDG-PET was useful for the evaluation of local effect after CIRT.
Nab-paclitaxel plus gemcitabine followed by radiotherapy with concurrent 5-FU in locally advanced unresectable pancreatic cancer: A Western Australian experience.
Authors: Dean Andrew Peter , Spry Nigel , McGrath Alycea 
Published: February 2017

430 Background: The optimal management of patients with locally advanced unresectable pancreatic cancer is unclear. In the metastatic setting, superior response rates have been seen with nab-paclitaxel plus gemcitabine compared to gemcitabine alone. We investigate the efficacy and safety of nab-paclitaxel plus gemcitabine followed by radical radiotherapy with concurrent 5-FU in patients with locally advanced unresectable pancreatic adenocarcinoma. Methods: A retrospective review was conducted of all patients with locally advanced unresectable pancreatic cancer treated with nab-paclitaxel plus gemcitabine, the majority proceeding to radical radiotherapy with concurrent 5-FU, at two large Western Australian metropolitan hospitals from January 2009 to December 2014. Charts were reviewed to obtain patient characteristics, efficacy and tolerability. Kaplan-Meier analysis was utilised to obtain survival curves. Results: Forty-two patients were identified as having locally advanced unresectable pancreatic adenocarcinoma, receiving nab-paclitaxel plus gemcitabine to a mean number of 5 cycles, the majority requiring dose reductions. Of these, thirty proceeded to radical radiotherapy; the majority receiving 3DCRT, 54 Gy, with concurrent 5-FU. Seven had sufficient response to therapy to be offered radical resection. Six went on to radical resection, all with R0 or close resection margins (2 with complete response). Median length of stay following surgery was 18 days, and there were no perioperative deaths. The median survival for patients proceeding with surgery was 30 months. Median survival was 23 months for those treated with chemoradiotherapy, and 10 months with chemotherapy alone. Conclusions: This retrospective investigation demonstrates that nab-paclitaxel plus gemcitabine followed by radical radiotherapy with concurrent 5-FU is a tolerable treatment option with encouraging results for patients with locally advanced unresectable pancreatic cancer. The R0 resection rate in patients that had adequate response to allow for radical resection is promising. Further studies are warranted.
The effect of postoperative morbidity on long-term survival after curative resection for extra-hepatic biliary tumors: A multi-institution analysis from the U.S. Extrahepatic Biliary Malignancy Consortium.
Authors: Jin Linda , Krasnick Bradley , Davidson Jesse , Ethun Cecilia Grace , Pawlik Timothy M. , Poultsides George A. , Tran Thuy , Idrees Kamran , Isom Chelsea A , Weber Sharon M. , Salem Ahmed I. , Scoggins Charles Raben , Shen Perry , Mogal Harveshp , Schmidt Carl Richard , Beal Eliza W , Hatzaras Ioannis , Maithel Shishir Kumar , Fields Ryan C. 
Published: February 2017

435 Background: Surgical resection is the cornerstone of curative therapy for extrahepatic biliary tumors (EHBTs) Postoperative complications (POCs) can negatively impact survival after oncologic resection. We evaluated the impact of POCs on survival after resection of EHBTs. Methods: We analyzed 914 patients from ten institutions of the U.S. Extrahepatic Biliary Malignancy Consortium who underwent curative resection for gallbladder adenocarcinoma (n=389), hilar (n=295) and distal (n=294) cholangiocarcinoma between 1998 and 2015. POCs were graded using the modified Clavien-Dindo system. Overall survival (OS) probabilities were estimated using the method of Kaplan and Meier and analyzed using multivariate Cox regression. Results: Median follow-up was 20 months. The median age was 66 years, and the overall complication rate was 54%. Complication rates were significantly higher in patients with distal or hilar cholangiocarcinoma (62%) when compared with gallbladder cancer (41%, p<0.001). For all cancer types, patients who experienced POCs had lower 5-year OS when compared with those who did not (18% vs 28%, p<0.001). On multivariate Cox regression, POC remained an independent predictor for decreased OS (HR 1.5, 95% CI 1.3-1.9, p<0.001; Table). Among patients who experienced POCs, survival did not differ by greatest Clavien grade of complication experienced (p=0.89), however patients who had 2 or more POCs did have decreased long term survival when compared with patients with only a single POC (HR 1.5, 95% CI 1.2-1.8, p=0.001). Conclusions: POCs adversely affect long-term outcomes after curative resection for extra-hepatic biliary tumors. While any complication grade did not have a significant impact on long-term survival, increasing number of POCs did significantly worsen the prognosis for OS. [Table: see text]
Second-line chemotherapy (CTx) outcomes in advanced biliary cancers (ABC): A retrospective multicenter analysis.
Authors: Lowery Maeve Aine , Goff Laura Williams , Jordan Emmet , Wang Rui , Bocobo Andrea Grace , Chou Joanne F. , O'Reilly Eileen Mary , Harding James J. , Kemeny Nancy E. , Capanu Marinela , Griffin Ann , McGuire Joseph P. , Venook Alan P. , Abou-Alfa Ghassan K. , Kelley Robin Kate 
Published: February 2017

437 Background: While gemcitabine in combination with platinum has been well established as first line systemic therapy for ABC, there remains no standard of care regimen in the second line setting. We evaluated current practice and outcomes for second line chemotherapy in patients with ABC across three geographically diverse, large US academic medical centers. Methods: 198 pts who received second line chemotherapy for ABC after 1/1/11 were identified from institutional databases following IRB approval. Records were reviewed for demographic, treatment and response data. Overall survival (OS) was calculated from start of second line chemotherapy and estimated using Kaplan-Meier methods. Results: Median follow up among survivors was 5 months and median OS for all patients from start of second line therapy was 11 months (mo) (95% CI 8.8-13.1): intrahepatic (61.1%): 13.4 mo (95%CI: 10.7-17.8); extrahepatic (14.1%): 6.8 mo (95%CI: 5-11); and gallbladder (24.8%): 9.4 mo (95%CI: 7.2-12.3). Median duration of second line chemotherapy was 2.2 mo (range 0-32.5). 103 pts (52%) received ≥ 3 lines of chemotherapy. Median OS from start of first line of gemcitabine plus cisplatin or oxaliplatin was 22.4 mo (95% CI 17.9 – 25.5). Conclusions: In highly selected pts with ABC treated at academic medical centers, survival following progression on first line chemotherapy was higher than previously reported, and patients received multiple lines of treatment. This multicenter collaboration provides a contemporary benchmark to inform the hypotheses and design of future clinical trials of second line chemotherapy in ABC. [Table: see text]
Treatment of borderline resectable (BR) and locally advanced (LA) pancreatic cancer in the era of FOLFIRINOX and gemcitabine plus nab-paclitaxel: A multi-institutional study.
Authors: Idrees Kamran , Parikh Alexander A. , Postlewait Lauren McLendon , Weber Sharon M. , Cho Clifford Suhyun , Salem Ahmed I. , Martin Robert C. G. , Scoggins Charles Raben , Kim Hong Jin , Carr Jacquelyn , Stuart Heather , Xia Brent , Ahmed Syed , Abbott Daniel Erik , Maithel Shishir Kumar , Kooby David A. , Merchant Nipun B. 
Published: February 2017

451 Background: FOLFIRINOX or Gemcitabine+nab-Paclitaxel (Gem/nPac) has superior overall survival (OS) compared with gemcitabine alone in pts with Stage 4 pancreatic cancer (PC). Based on these results, FOLFIRINOX or Gem/nPac has been utilized in neoadjuvant (NA) setting for BR and LA PC. This report describes our multi-institutional experience with NA treatment with FOLFIRINOX or Gem/nPac followed by surgical resection. Methods: Pts with BR and LA PC who received NA FOLFIRINOX or Gem/nPac and underwent surgical resection between 2011 and 2015 at 7 high volume pancreas centers were reviewed. Pre-operative chemoradiation therapy (pCXRT) was administered selectively based on radiographic response (RR). Near-complete (minimal residual disease) or complete pathologic response (PR) was categorized as marked PR. Results: 86 pts received either NA FOLFIRINOX (69%) or Gem/nPac therapy (31%) for BR (67%), LA (32%) PC. pCXRT was administered in 71% of pts. Pts received a median of 4 cycles of FOLFIRINOX (range 1-28) and 3 cycles of Gem/nPac (range 2-13). No grade 4-5 toxicities were noted. The majority of pts underwent pancreaticoduodenectomy (84%) and vascular resection was performed in 53% - 40 with venous resection and 6 with arterial resection. R0 resection rate was 86% with no difference between two treatment groups (p = 0.9). Reduction in CA 19-9 or RR did not correlate with pathological response (p = 0.8). A marked PR was seen in 12 pts – 13.6% vs. 15.4% for FOLFIRINOX and Gem/nPac, respectively (p = 0.8). Adjuvant chemotherapy or CXRT was administered in 44% of pts. With a median follow up of 20 months (mo), OS was 27.4 mo with median OS in marked PR was 53 vs. 25 mo in moderate PR/non-responders (p = 0.04). Recurrence was noted in 45 pts – 49% had distant recurrence, 20% had local recurrence and 31% had both. Conclusions: Neoadjuvant FOLFIRINOX or Gem/nPac therapy in conjunction with aggressive surgical resection in BR and select LA PDAC pts result in significant long-term survival especially in marked pathologic responders. Further, optimization of treatment protocols in the neoadjuvant and adjuvant setting is warranted since recurrence rates are high.
Results of the phase Ib portion of a phase I/II trial of the indoleamine 2,3-dioxygenase pathway (IDO) inhibitor indoximod plus gemcitabine/nab-paclitaxel for the treatment of metastatic pancreatic cancer.
Authors: Bahary Nathan , Garrido-Laguna Ignacio , Wang-Gillam Andrea , Nyak-Kapoor Asha , Kennedy Eugene , Vahanian Nicholas N. , Link Charles J. 
Published: February 2017

452 Background: IDO is a tryptophan-catabolizing enzyme that plays a key role in the normal regulation of peripheral immune tolerance. Tumors also employ this mechanism to induce a state of immunosuppression. In cancer, IDO mediates an acquired immune tolerance towards tumors, allowing evasion of immune mediated destruction. Indoximod is a broad IDO pathway inhibitor, as it has been shown to potentially interfere with multiple targets within the IDO pathway. Pre-clinical models have demonstrated synergy between indoximod and chemotherapy. The combination of gemcitabine (Gem) and nab-paclitaxel (Nab) is a current SOC for first line treatment of metastatic pancreas cancer. This trial is designed to determine the potential for benefit of combination therapy with indoximod and Gem / Nab for to patients with metastatic pancreatic cancer. Methods: Indoximod was escalated (600mg/1000mg/1200mg PO twice daily continuous dosing) in combination with Gem / Nab (1000mg/m2 / 125mg/m2 q week x 3 per 4 week cycle) in a 3+3 design. Patients were first line metastatic pancreatic cancer or minimum 6 months from adjuvant chemo and / or radiation following previous resection. Treatment continues until progression or toxicity. Primary endpoints for Phase 1 include safety, toxicity, and determination of a Phase 2 dose. The prospective collection of tumor samples for exploration of biomarkers is built into the trial. Results: 15 patients were required to successfully dose escalate the Phase 1 study to 1200 mg twice daily. Two patients were replaced in the lowest dose cohort after rapid deterioration due to underlying disease during the regimen limiting toxicity (RLT) window. One RLT was observed during the study (ascites Grade 3) at the highest dose cohort. The most common AE’s (all Grade 1 or 2) occurring in ≥ 4 subjects, regardless of attribution, were nausea, fatigue, peripheral edema, peripheral neuropathy, alopecia. Conclusions: Indoximod and Gem / Nab were well tolerated in a clinical trial setting. The Phase 2 dose was set at 1200 mg twice daily and Phase 2 enrollment (target 80 patients) is ongoing. Updated results will be presented. Clinical trial information: NCT02077881.
Accuracy of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in predicting node positivity and metastatic disease in patients with gastrointestinal malignancies.
Authors: Doepker Matthew , Baughen Kabisa , Brown Richard H. , Kucera Steven , Lee Justin , Shridhar Ravi , Meredith Kenneth 
Published: February 2017

462 Background: Accurate predictors of node positivity and metastatic disease for patients with gastrointestinal (GI) malignancies are currently lacking. Neutrophil-lymphocyte ratio (NLR), and platelet lymphocyte ratio (PLR) have been introduced as a possible prognostic scoring system. We sought to evaluate the accuracy of NLR and PLR in predicting advanced disease in patients with GI malignancies. Methods: We queried a prospective GI oncology database to identify 116 patients. NLR and PLR were calculated from complete blood counts before and after neoadjuvant therapy (NT) and pre-operatively in patients not treated with NT. The associations between NLR and PLR and the clinicopathologic parameters were assessed via χ2 or Fisher’s exact tests where appropriate. All the tests were two-sided, and p < 0.05 was considered statistically significant. Results: We identified 49(42.2%) esophageal, 34 (29.3%) pancreatic, 14 (12.1%) colorectal, 13 (11.2%) gastric, and 6(5.2%) biliary cancers. There were 36 (31%) LN-, 52 (44.8%) LN+, and 28 (24.2%) patients with metastatic disease. The median NLR for LN – patients was 1.78 (0.2-4.5) and for LN + and metastatic patients was 4.48 (2.38-24.1) p < 0.00001. The median PLR for LN– patients was 123 (66-207) and for LN+ and metastatic patients was 212 (112-2185) p < 0.00001. The sensitivity (SENS), specificity (SPEC), positive predictive value (PPV) and negative predictive value (NPV) for a NLR > 2.25 was 98.8%, 72.2%, 89%, and 96% respectively with an overall accuracy of 91%. The SENS, SPEC, PPV, and NPV for PLR > 140 was 95%, 78%, 90%, and 88% respectively with an overall accuracy of 90%. Utilizing both NLR > 2.25 and PLR > 140 the SENS, SPEC, PPV and NPV was 95%, 89%, 95%, and 89% respectively and the overall accuracy was 93%. Conclusions: NLR and PLR can be used to identify patients with node positivity and metastatic disease. Individually, NLR has a higher sensitivity and NPV while PLR has a higher specificity and PPV. However, the combination of NLR and PLR has the highest accuracy of predicting advanced disease among all gastrointestinal malignancies.
The incidence of secondary pelvic tumors after previous (chemo)radiation for rectal cancer.
Authors: Rombouts Anouk J.M. , Hugen Niek , Elferink Marloes A. G. , Feuth Ton , Poortmans Philip M. , Nagtegaal Iris D. , de Wilt Johannes H.W. 
Published: February 2017

491 Background: The aim of this study was to analyze the association between radiotherapy (RT) for rectal cancer and the development of second primary tumors. Methods: Data on all surgically treated, non-metastasized primary rectal cancer patients diagnosed between 1989 and 2007 were retrieved from a population-based cancer registry and retrospectively reviewed. To estimate the cumulative incidence of a second tumor, Fine and Gray’s competing risk model was used with death as a competing event. Standardized incidence ratios (SIR’s) were calculated for comparison with the incidence of primary tumors in the general population, taking in account sex, age and calendar year. Results: The cohort consisted of 29,214 patients of which 15,454 patients had undergone (chemo)RT. Median follow-up was 6.2 years (range 0-24). 3655 patients were diagnosed with at least one second primary tumor of which 808 patients had pelvic tumors. The SIR for any second tumor was 1.14 (95% confidence interval [CI] 1.10-1.17), resulting in 23.3/10,000 excess cases per year. RT reduced the cumulative incidence of second pelvic tumors compared to patients who received no RT (SHR 0.70, 95% CI 0.61-0.81). Second pelvic tumors were more common in patients who underwent post-operative RT than in patients who underwent pre-operative RT (SHR 1.37, 95% CI 1.10-1.70). Organ-specific analyses showed that second prostate tumors were less common in patients who received RT compared to patients who received no RT (SHR = 0.51, 95% CI 0.43-0.62). RT also reduced the risk for a second primary tumor in the rectum(sigmoid) compared to patients who did not receive RT (SHR 0.59 95% CI 0.37-0.94). Patients who received post-operative RT had higher chances of developing a second rectum(sigmoid) tumor then patients who received pre-operative RT (SHR 2.25, 95% CI 1.07-4.73). Patients without RT had worse overall survival than patients who received RT (hazard ratio 1.22, 95% CI 1.19-1.26). Conclusions: In this nationwide study, patients with previous rectal cancer had a slightly increased chance of developing another primary tumor compared with the general population. We found a protective effect of RT on the development of secondary pelvic tumors, predominantly for prostate cancer.