bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disparities in receipt of radiotherapy and survival by age, sex, and race among patients with nonmetastatic squamous cell carcinoma of the anus.
Authors: Baughman Doug , Ghimire Krishna Bilas , Shah Binay Kumar 
Published: February 2017

721 Background: Combination chemoradiotherapy is the standard of care for treatment of non-metastatic squamous cell carcinoma of the anus (SCCA). This population-based study evaluated disparities in receipt of radiotherapy (RT) and its effect on survival in patients with localized and regional SCCA in the United States. Methods: The Surveillance, Epidemiology, and End Results (SEER) 18 database was used to identify patients with localized and regional SCCA diagnosed between 1998 and 2008. We used univariate and multivariate logistic regression to model the relationships between receipt of RT and age, sex, marital status, stage, and race. Relative survival rates were calculated and compared using two sample z-tests. A Cox proportional hazards model was used to find adjusted hazard ratios (HR). Results: A total of 3,971 patients with localized or regional SCCA as the only primary malignancy were included in the study, of which 3,278 (82.6%) received RT. After adjusting for covariates, those 65 years and older (adjusted OR 0.82, p=0.029) were less likely to receive RT. Females were more likely to receive RT compared to males (adjusted OR 1.54, p<0.001). We found no difference in receipt of RT by race. Comparisons of 1- and 5-year relative survival rates showed lower survival for blacks (p-value <0.01 at 1-year and <0.0001 at 5-years), those 65 years and older, and males. A 1-year survival disparity was found for those not receiving RT (p-value <0.0001 at 1-year), but no difference was observed at 5-years. A Cox proportional hazards model adjusting for all covariates showed greater hazard for blacks (adjusted HR 1.36, p=0.001), those not receiving RT (adjusted HR 1.23, p=0.03), patients 65 years or older, and males. Conclusions: This population based study identified older patients as less likely to receive RT and females as more likely to receive RT. Survival analysis identified blacks, males, older patients, and those not receiving RT as having lower rates of survival.
Impact of total lymph node count on staging and survival after neoadjuvant chemoradiation therapy for rectal cancer.
Authors: Hall Matthew David , Schultheiss Timothy E. , Wong Jeffrey Y.C. , Chen Yi-Jen 
Published: February 2017

736 Background: Neoadjuvant chemoradiation therapy (CRT) results in fewer retrieved lymph nodes at the time of surgery for rectal cancer. The extent of optimal regional nodal dissection is based on guidelines developed before neoadjuvant CRT was commonly used. The purpose of this study is to assess the impact of the number of dissected and positive lymph nodes on overall survival (OS) for rectal cancer patients treated with neoadjuvant CRT. Methods: Treatment data were obtained by structured query on all patients with rectal adenocarcinoma (2000-2013) in the National Oncology Data Alliance, a proprietary database of merged tumor registries. Eligible patients were treated with neoadjuvant CRT followed by surgery and had complete data on the number of positive and dissected lymph nodes and dates of treatment. The relationships between number of lymph nodes examined and OS were separately analyzed in patients with 0, exactly 1, or any number of positive nodes. Results: The median number of lymph nodes examined was 11 (interquartile range 6-16). In 4,581 evaluable patients, there was a significant improvement in OS with the examination of more lymph nodes. Number of positive lymph nodes, number of lymph nodes dissected, age, gender, grade, marital status, and race were significant predictors of OS on multivariate analysis. On subset analysis, patients with 0, exactly 1, and any number of positive nodes were found to have better OS with increasing number of lymph nodes dissected up to eight. Increasing overall mortality was observed in patients with 0, 1, 2-4, 5-7, and ≥8 positive lymph nodes. The Kaplan-Meier curves showed a clear statistically significant difference in OS in patients divided into these five nodal groupings (p<0.0001). Conclusions: Patients with eight or more lymph nodes examined had the greatest improvement in OS in rectal cancer patients treated with neoadjuvant CRT. This should be considered the threshold for an adequate lymph node sampling in this population. A five-tier nodal grouping was found to best forecast prognosis based on the number of positive lymph nodes identified.
Predictive factors and prognostic significance of tumor regression grade in rectal cancer.
Authors: Ogundimu Oluwabunmi , Ramjeesingh Ravi , Ren Kevin , Qu Melody Xuan Lu , Hurlbut David , Biagi James Joseph , Mahmud Aamer 
Published: February 2017

739 Background: Several systems describe tumour regression grade (TRG) after neo-adjuvant chemo-radiotherapy (nCRT) in rectal cancer; however, there is lack of literature on factors predicting TRG and its prognostic significance when comparing two TRG systems. Methods: Chart review of 187 patients (pts) diagnosed with rectal cancer managed at our institution identified clinical T3 or T4 and/ or node positive adenocarcinoma who completed nCRT between 2005-2011. Assessment of TRG post-nCRT in 104 pts was determined using College of American Pathologists (CAP) and Modified Rectal Cancer Regression Grade (mRCRG) scoring systems. Logistic regression model was used to identify factors associated with TRG. Overall survival (OS) was estimated using Kaplan-Meier method, log-rank test to compare groups and Cox proportional hazard model to estimate hazard ratio. Results: Median age of 103 eligible pts was 64 (range [r] 31-88) and 70% were male. Median pre-nCRT tumour size was 4 cm (r 0.5-12). 61% tumours were distal. Radiation dose (RD) was >54 Gy in 57%, 50.4 Gy in 40%, and 45 Gy in 3% patients. 71% received concomitant 5 FU; 12% capecitabine and 17% according to clinical trials prior to radical surgery. Median time between completion of nCRT and surgery was 49 days. CAP scoring was 0 (21%), 1 (7%), 2 (19%), and 3 (53%) whereas mRCRG scoring was 1 (31%), 2 (21%), and 3 (48%). With median follow up 5.04 years (yr), 5 yr OS was 65%. OS was 77% for CAP 0 and 1 vs. 59% for CAP 2 and 3 (p=0.0483, HR2.4); mRCRG 1 and 2 OS was 75% vs 54% for mRCRG 3 (p= 0.0060, HR2.6). >30% reduction in pre-nCRT tumour occurred in 63% of CAP 1, 2, and 3 cases. Age (≥65 yr), higher RD and higher pre-op CEA were associated with mRCRG grade 3 (p=0.0339, 0.0415, and 0.0760 respectively). Tumour size, location, grade, type of chemotherapy, or gender were not predictive of TRG. Conclusions: Favorable TRG post-nCRT is associated with a statistically significant OS advantage. Younger age and RD escalation are associated with favorable TRG. CAP and mRCRG scoring systems of TRG were comparable for prognosis. nCRT leads to a significant cytoreduction in 63% of non-complete responders. TRG may have a future role in decisions on surgery, organ sparing, adjuvant chemotherapy, surveillance and patient counseling.
Association of morphologic response with progression free survival in patients with metastatic colorectal cancer treated with bevacizumab-based chemotherapy: HGCSG0802.
Authors: Yuki Satoshi , Nakatsumi Hiroshi , Hayashi Hideyuki , Fukushima Hiraku , Kato Takashi , Meguro Takashi , Nakamura Michio , Iwanaga Ichiro , Eto Kazunori , Sato Atsushi , Okuda Hiroyuki , Oba Ayane , Miyagishima Takuto , Muto Osamu , Yabusaki Satoshi , Miyamoto Noriyuki , Kudo Kohsuke , Sakamoto Naoya , Sakata Yuh , Komatsu Yoshito 
Published: February 2017

743 Background: It was reported that an optimal morphologic response to preoperative chemotherapy was associated with better overall survival (OS) in patients (pts) with colorectal liver metastases (CLM). We investigated association of morphologic response with progression free survival (PFS) in pts with unresectable CLM from HGCSG0802 observational cohort study in pts with mCRC treated with first-line bevacizumab (BV)-based chemotherapy. Methods: The objective of HGCSG0802 was to evaluate PFS, OS, time to treatment failure (TTF), response rate (RR), safety, etc. The key eligibility criteria were evaluable lesions, older than 20 years old, ECOG PS 0-2. Pts with CLM underwent contrast-enhanced CT at the start and every 8-weeks of BV-based chemotherapy. In this analysis, three blinded, independent radiologists evaluated images for morphologic response, based on metastases changing from heterogeneous masses with ill-defined margins into homogeneous hypoattenuating lesions with sharp borders. Association of morphologic response and pts characteristics, RR, and PFS were evaluated. PFS was analyzed with Kaplan-Meier method, log-rank test, and Cox proportional hazards model. Results: Of 108 pts (the full analysis set), 73 pts with CLM were evaluable for morphologic criteria. Eighteen pts (24.7%) had optimal morphologic response (OR), 31 (42.5%) had incomplete (IR), and 24 (32.9%) had no response (NR). The pts characteristics between those with OR, IR and NR were generally balanced. The median TTF was 7.2 months in NR versus 7.2 months in IR versus 6.8 months in OR (HR (OR/NR) = 0.91, HR (OR/IR) = 0.90; p = 0.93). RR was 77.8% in OR versus 64.5% in IR and 58.3% in NR (p = 0.528). The median PFS was 8.3 months in NR versus 8.5 months in IR versus 9.1 months in OR (HR (OR/NR) = 0.72, HR (OR/IR) = 1.04; p = 0.420). Conclusions: In this analysis, morphologic response might not be a prognostic marker in first-line BV-based chemotherapy in pts with CLM.
Phase II trial of irinotecan plus s-1 (IRIS) with cetuximab (IRIS/Cet) as second-line treatment in patients with KRAS wild-type metastatic colorectal cancer (mCRC): HGCSG0902—Comparison of administration interval in cetuximab treatment.
Authors: Komatsu Yoshito , Yuki Satoshi , Nakatsumi Hiroshi , Hosokawa Ayumu , Nakamura Michio , Muto Osamu , Meguro Takashi , Iwanaga Ichiro , Hatanaka Kazuteru , Tsuji Yasushi , Sato Atsushi , Eto Kazunori , Furukawa Kouichi , Onodera Manabu , Tateyama Miki , Takahashi Yasuo , Dazai Masayoshi , Yokoyama Sachio , Honda Takuya , Sakata Yuh ,   HGCSG
Published: February 2017

746 Background: HGCSG0902 is the multicenter phase II study to investigate the safety and efficacy of IRIS/Cet as second-line treatment in patients with KRAS wild type mCRC. RR was 33.3% (95% CI, 20.8%-45.9%), therefore primary endpoint was met (Muto et al. ESMO 2014 ). Here we report an exploratory analysis of outcomes based on administration interval of Cet (every week [EW] vs bi-weekly [BW]). Methods: Eligibility includes histologically confirmed colorectal cancer, previously received oxaliplatin-contained chemotherapy, PS: 0-1, EGFR positive and KRAS WT. Pts. received S-1 80-120 mg/day p.o. on days 1-14 and irinotecan 100 mg/m2 on days 1 and 15 repeated every 28 days. Cet was administrated 400 mg/m2 as loading dose and continued 250 mg/m2 every week or 500 mg/m2 bi-weekly. The primary endpoint was RR and the secondary endpoints were disease control rate, PFS, OS and safety. To compare with EW and BW, Fisher’s exact test was used in terms of patient characteristics, AE, RR, and Log-rank test was used in terms of PFS, OS, and TTF. Results: Between March 2010 and September 2013, 58 pts were enrolled. One patient was not administered (57 pts were safety analysis set), and 3 pts were ineligible (54 pts were efficacy analysis set). Based on each physician choice, 34 pts. of EW and 23 of BW were included in the full safety analysis set. RR was 34.4% in the EW group and 31.8% in the BW group (p=1.000). Median PFS was 4.2 months (95% CI 3.5−4.9) in the EW group and 6.1 months (4.1-8.1) in the BW group (HR 0.752, 95% CI 0.413−1.372, p=0.350). The most common non-hematological adverse events of grade 3 or higher were diarrhea (23.5% in the EW group vs. 52.2% in the BW group: p=0.005) and stomatitis (2.9% in the EW group vs. 30.4% in the BW group: p=0.046), these were significantly more common in the BW group. Conclusions: IRIS/Cet appeared to be highly effective with RR and PFS in the both treatment schedule, and also had met the primary endpoint. Diarrhea and stomatitis were significantly more common in the BW group. Therefore, in case of treatment with IRIS, cetuximab should be administered weekly. Clinical trial information: 000004882.
PEPCOL: A randomized noncomparative phase II study of PEP02 (MM-398) or irinotecan in combination with leucovorin and 5-fluorouracil as second-line therapy in patients with unresectable metastatic colorectal cancer—A GERCOR Study.
Authors: Chibaudel Benoist , Maindrault-Goebel Frederique , André Thierry , Bachet Jean Baptiste , Louvet Christophe , Khalil Ahmed , Dupuis Olivier Jean Marie , Hammel Pascal , Garcia Marie Line , Bennamoun Mostefa , Brusquant David , Arbaud Claire , Wang Yi-Wen , Yeh Grace , Bonnetain Franck , De Gramont Aimery ,   GERCOR, Groupe Coopérateur Multidisciplinaire en Oncologie
Published: February 2017

751 Background: PEP02 is a highly stable nanoliposomal irinotecan. This randomized non-comparative phase II (PEPCOL) study evaluated the efficacy and safety of PEP02 (MM-398) or irinotecan in combination with LV/5-FU in the second-line treatment of metastatic colorectal cancer (mCRC). (EudraCT 2010-020468-39A, NCT01375816). Methods: Patients with unresectable mCRC who had failed one prior oxaliplatin-based first-line therapy were randomly assigned to FUPEP (PEP02 80 mg/m² d1, folinic acid (FA) 400 mg/m² d1, 5-FU 2,400 mg/m² d1-2) or FOLFIRI (FOLFIRI1: irinotecan 180 mg/m² d1, FA 400 mg/m² d1, 5-FU bolus 400 mg/m² d1, 5-FU infusion 2,400 mg/m² d1-2; or modified FOLFIRI3: irinotecan 90 mg/m² d1 and 3, FA 400 mg/m² d1, 5-FU infusion 2,400 mg/m² d1-2). Bevacizumab q2w (5 mg/kg) was allowed in both arms as of June 2012 (TML study report). The primary endpoint was the objective tumor response (OR). Results: Fifty-five patients were randomized (FUPEP, n=28; FOLFIRI, n=27). In the evaluable population (n=50), OR rate were 16.7% (n=4/24) and 11.5% (n=3/26) in the FUPEP and the FOLFIRI arms, respectively. Most common grade 3-4 adverse events reported in the respective FUPEP and the FOLFIRI arms were diarrhea (21% vs 33%), neutropenia (11% vs 30%), mucositis (11% vs 11%), and alopecia (G2: 25% vs 26%). Conclusions: FUPEP regimen exhibits promising tumor response and safety profile, and can be combined with bevacizumab, for oxaliplatin-pretreated patients. Hence PEP02 (MM-398) may provide a new second-line treatment option for mCRC. Based on the safety profile of the FUPEP regimen in this PEPCOL study, it was added as the third arm to the positive phase III metastatic pancreatic cancer (NAPOLI-1) study. Clinical trial information: NCT01375816.
A prospective study of XELIRI plus bevacizumab as the first-line therapy in Japanese patients with unresectable or recurrent colorectal cancer (KSCC1101).
Authors: Hanazono Koichi , Emi Yasunori , Tsuji Akihito , Kishihara Fumiaki , Oki Eiji , Hamanoue Masahiro , Baba Hideo , Natsugoe Shoji , Ogata Yutaka , Sakai Kenji , Maehara Yoshihiko ,   Kyushu Study Group of Clinical Cancer (KSCC)
Published: February 2017

752 Background: XELIRI plus bevacizumab (Bev) might be one of the standard therapies for metastatic colorectal cancer (mCRC). However, there was no clinical practice data in Japan. This study was designed to evaluate the efficacy and safety of XELIRI plus Bev in clinical practice in Japanese mCRC patients (pts.). Methods: This was a multicenter, single-arm, open-label prospective study. The major inclusion criteria were previously untreated mCRC; presence of measurable lesions; age ≥20 years; ECOG performance status (PS) of 0–2; and adequate organ function. Pts received Bev 7.5 mg/kg day 1 and XELIRI (irinotecan 200 mg/m2 day 1 plus capecitabine 800 mg/m2 bid d1-14) q3w. This schedule was repeated until unacceptable toxicity or disease progression occurred. The primary endpoint was RECIST-confirmed objective response rate (ORR). A sample size of 35 was planned for a threshold ORR of 30% and expected value of 53%, with one-sided alpha of 0.05 and beta of approximately 0.2. Results: A total of 36 pts (male/female, 23/13; median age, 65.0 years (range 44.0-80.0); PS 0/1/2, 31/5/0) were enrolled in this study from July 2011 to September 2012. One patient did not fulfill the eligibility criteria and one withdrew the informed consent before the start of protocol treatment. Thirty-four pts were assessed for response; CR 0, PR 18, SD 9, PD 4, and NE 3. The confirmed ORR was 52.9% (90% CI, 37.7-67.8%). Median PFS was 9.6 months (95% CI, 5.1-11.1 months) and mOS was 23.0 months (95% CI, 11.3-NE months). mTTF was 5.3 months (95% CI, 3.2-8.3 months). The most common grade 3/4 adverse events were neutropenia 31.4%, anemia 20.0%, thrombocytopenia 5.7%, hyponatremia 20.0%, anorexia 20.0%, diarrhea 22.8%, fatigue 0.0%, hypertension 2.9%, hand-foot syndrome 0.0%, and bleeding 0.0%. Conclusions: First-line treatment of XELIRI + Bev showed a promising response rate and an acceptable tolerability profile in the clinical practice in Japanese mCRC pts. Clinical trial information: UMIN000006070.
Exploratory analysis of a prognosis predictive formula for metastatic colorectal cancer treated with chemotherapy.
Authors: Tanaka Mamoru , Kusaba Hitoshi , Mukaide Satomi , Kishimoto Junji , Kumagai Hozumi , Makiyama Akitaka , Shirakawa Tsuyoshi , Oda Hisanobu , Komoda Masato , Mitsugi Kenji , Akashi Koichi , Baba Eishi 
Published: February 2017

757 Background: Progression free survival (PFS) has been recognized as a surrogate outcome in the therapy for metastatic or recurrent colorectal cancer (mCRC). As molecular targeted therapies have become to be widely used, new surrogate outcome such as early tumor shrinkage (ETS; the relative change in the sum of longest diameters of target lesions at week 8 compared to baseline) and deepness of response (DpR; the relative change in the sum of longest diameters of target lesions at the nadir compared to baseline) are proposed. However, their validity has not been fully proven. We conducted to develop a new prognosis predictive formula consisting of the three factors, DpR, ETS and PFS, in the first-line chemotherapy of mCRC. Methods: We retrospectively evaluated mCRC patients who started any chemotherapy from 2005 to 2010. Estimated ETS (eETS), instead of ETS, was defined as the estimated relative change of target lesions at week 8 calculated from first image assessment. DpR was defined as above. Predictive formulae of prognosis were examined by single and multiple regression analysis. Results: 63 patients were enrolled. KRAS status were as follows; wild type; 33, mutant; 17, unknown; 13. Chemotherapies were performed as follows; oxaliplatin-based plus bevacizumab; 34, irinotecan-based plus bevacizumab; 6, oxaliplatin-based plus anti-EGFR antibody; 2, oxaliplatin-based; 17, irinotecan-based; 4. Median of DpR, eETS, PFS and overall survival (OS) were 26.5%, 15.4%, 236 days and 571 days, respectively. PFS showed a correlation with OS (r2= 0.434), while DpR and eETS were less correlated with OS (r2= 0.228, 0.082). PFS and eETS were thus chosen as variables for the prediction formula of prognosis. However, the present formula did not show an apparent increased R2 value compared with the formula consisted of PFS alone (adjusted R2= 0.442 vs 0.425), indicating that the present formula could not provide more accurate prediction. In the stratified subgroups according to treatment regimen and KRAS status, the formula did not show remarkable change in R2 value. Conclusions: The present formulae including DpR and eETS does not have superior predicting potential to PFS alone for prognosis of the whole mCRC patients.
The study of efficacy and safety of chemotherapy plus bevacizumab with oxaliplatin stop-and-go strategy in first-line treatment for metastatic colorectal cancer.
Authors: Takano Nao , Nakayama Goro , Kodera Yasuhiro 
Published: February 2017

761 Background: In metastatic colorectal cancer (mCRC), the benefit of the molecular targeted drugs added to chemotherapy has been reported and a combination therapy of capecitabine (CAP) and oxaliplatin (CapeOX) plus bevacizumab (BEV) is an established first-line therapy for mCRC. However, the management of the cumlateve neurotoxicity of oxaliplatin still remains. We evaluated the efficacy and safety of CapeOX plus BEV with oxaliplatin stop and go strategy. Methods: Two prospective clinical trials of previously untreated unresectable mCRC were analyzed. Fifty four patients were treated with CapeOX plus BEV with oxaliplatin stop and go strategy (CCOG-0902). They were treated 4 cycles of CapeOX plus BV therapy followed by maintenance therapy of 8 cycles of Capecitabine plus BV and oxaliplatin reintroduction was scheduled after maintenance therapy or upon tumor progression. On the other group, forty seven patients were treated with mFOLFOX6 plus BEV (CCOG-0801). Progression free survival (PFS), overall survival (OS), response rate (RR), disease control rate (DCR), relative dose intensity (RDI), and frequency of peripheral sensory neuropathy (PSN) were evaluated. Results: Patient characteristics were balanced between the two groups. The median RDI of oxaliplatin in CCOG-0902 group was significantly higher, 92% than in CCOG-0801 group, 80%. RR and DCR were 61.5% and 96.3% respectively, in CCOG-0902 group, compared with 61.7% and 89.4% respectively, in CCOG-0801 group. Median PFS was 13.6 and 30.5 months, respectively, compared with 11.7 and 31.6 months, respectively, in CCOG-0801 group (p=not significant). The frequency of peripheral sensory neuropathy (PSN) was 19.0% (>Grade3: 1.9%) of patients in CCOG-0902 group compared with 72.3% (>grade 3: 17.0%) in CCOG-0801 group. Conclusions: CapeOX plus BV with oxaliplatin stop and go strategy could have same efficacy as continuing oxaliplatin with avoiding PSN. Clinical trial information: UMIN000006478.
Neoadjuvant chemoradiation (CRT) with or without panitumumab (Pan) in patients with K-ras unmutated, locally advanced rectal cancer (LARC): Final results of a randomized multicenter phase II trial (SAKK 41/07).
Authors: Helbling Daniel , Bodoky Gyorgy , Gautschi Oliver , Hayoz Stefanie , Bosman Fred , Madlung Axel , Gloor Beat , Burkhard Roger , Rauch Daniel , Winterhalder Ralph C. , Saletti Piercarlo , Widmer Lukas , Borner Markus M. , Baertschi Daniela , Yan Pu , Koeberle Dieter 
Published: February 2017

762 Background: We conducted a randomized phase II multicenter trial evaluate the anti-epidermal growth factor receptor (EGFR) panitumumab (P) in combination with CRT with standard-dose capecitabine as neoadjuvant treatment for wild-type KRAS LARC. Methods: Patients with wild-type KRAS, T3-4 and/or N+ LARC were randomly assigned to receive CRT either with or without P (6 mg/kg). The primary end-point was pathological near-complete or complete tumor response (pNC/CR), defined as grade 3 (pNCR) or 4 (pCR) histological regression by Dworak classification (DC). Secondary end-points were pathological response, R0-resection, sphincter preservation, downstaging, time to local relapse, time to distant failure and disease-free survival (DFS). Results: Patients with wild-type KRAS, T3-4 and/or N+ LARC were randomly assigned to receive CRT either with or without P (6 mg/kg). The primary end-point was pathological near-complete or complete tumor response (pNC/CR), defined as grade 3 (pNCR) or 4 (pCR) histological regression by Dworak classification (DC). Secondary end-points were pathological response, R0-resection, sphincter preservation, downstaging, time to local relapse, time to distant failure and disease-free survival (DFS). Conclusions: An addition of panitumumab to neoadjuvant CRT in patients with KRAS wild-type LARC resulted in a high pNC/CR rate, mostly grade 3 DC. Up to date no local recurrence occurred and DFS compared favorably to other trials. Clinical trial information: NCT00814619.