bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting acute small-bowel toxicity in patients with rectal cancer treated with neoadjuvant chemoradiation: A comparison of peritoneal space versus small-bowel loop contouring techniques.
Authors: Banerjee Robyn , Chakraborty Santam , Nygren Ian , Sinha Richie 
Published: February 2017

673 Background: In lieu of contouring individual small bowel loops, the peritoneal space (PS) has been suggested as a possible surrogate volume for predicting small bowel toxicity. A dose-volume relationship for the PS has not been firmly established. The aim of this study was to determine whether contours of the PS better predict significant acute small bowel toxicity in neoadjuvant rectal cancer patients when compared with contours of individual small bowel loops. Methods: A standardized contouring method was developed for the PS and retrospectively applied to the radiation treatment plans of sixty-seven patients treated with neoadjuvant chemoradiotherapy for rectal cancer. All patients had locally advanced disease, no evidence of metastases, and received concurrent radiation and infusional 5-Fluorourocil chemotherapy. Dose-volume histogram (DVH) data was extracted and analyzed against patient toxicity. Receiver operating characteristic analysis and logistic regression was carried out for both contouring methods. Results: Grade ≥ 3 small bowel toxicity occurred in 16% (11/67) of patients. Volumes of the contoured small bowel loops correlated with grade ≥ 3 toxicity at each 5 Gray (Gy) dose level from 5 to 45 Gy, with the greatest area under the curve (AUC) measuring .964 (p=.000) associated with the volume receiving at least 25 Gy (V25). Volumes of the contoured PS predicted toxicity from 5 to 40 Gy, with the greatest AUC also at the V25 and measuring .896 (p=.000). Logistic regression analysis demonstrated a less than 15% risk of acute grade ≥ 3 toxicity was associated with a V25 of 215 cc for the small bowel and 710 cc for the PS. Conclusions: DVH analysis of peritoneal space volumes predicts grade ≥ 3 small bowel toxicity in neoadjuvant rectal cancer patients, suggesting the peritoneal space is a reasonable surrogate for contouring individual small bowel loops. However, contouring individual small bowel loops is a more sensitive method for predicting toxicity at each dose increment. For both contouring methods, the greatest sensitivity for predicting toxicity was associated with the volume receiving at least 25 Gy (V25).
Assessment of safety of bevacizumab (bev) use for metastatic colorectal cancer (mCRC) in elderly patients treated at the Centre Hospitalier de l’Université de Montréal (CHUM): A retrospective study.
Authors: Otte Francois-Xavier Bicharh , Aubin Francine , Tehfe Mustapha Ali , Letourneau Richard , Lougnarath Rasmy , Richard Carole S. , Soulieres Denis , Charpentier Danielle , Biron Guy , Ayoub Jean-Pierre M. 
Published: February 2017

677 Background: A 2004 randomized study showed a meaningful improvement in survival with bev added to chemotherapy (CT) for patients with mCRC. This combination is now widely used and generally well tolerated although adverse events (AEs) are described associated with the use of bev, some of which may be increased in incidence in an elderly population. In this study, we assessed these AEs in a population of elderly patients treated with bev in a major center in Montréal. Methods: Patients with mCRC who received bev at our institution outside a clinical trial were retrieved from the pharmacy registry. Medical records were sought from patients who qualified for the inclusion criteria: ≥ 65 years, bev therapy at 5mg/kg every two weeks, combination with CT, period 2007-2011. A retrospective analysis of specific AEs was done and grade according to NCI-CTC (version 4.0) was assessed: febrile neutropenia, hypertension, proteinuria, diarrhea, venous thromboembolic event (VTE), arterial thromboembolic event (ATE), bleeding and gastrointestinal perforation. Results: 47 patients received a total of 486 cycles of bev. Out of these cycles, 210 were given with FOLFOX, 199 with FOLFIRI and 77 with other combinations. Median age of the patients was 69 years. 3 episodes of febrile neutropenia were noted. Grade 3 or 4 arterial hypertension occurred in 4 patients of which 2 had to definitively stop bev. Grade 3 proteinuria was reported with definitive cessation of bev in 2 patients. Grade 3 or 4 diarrhea was observed in 2 cases. We reported 1 cerebral ATE leading to discontinuation of bev and grade 2 VTE in two patients. One grade 5 gastrointestinal perforation was reported. No major bleeding was noted. Conclusions: The number of adverse events observed in this population of elderly patients is comparable to other studies. Thus, age should not be an exclusion criteria for treatment with bev and CT.
A phase I/II study of capecitabine (Cape), oxaliplatin (Ox), panitumumab (Pmab), and external beam radiation therapy (RT) for patients with esophagogastric carcinoma (EC).
Authors: Czito Brian G. , Willett Christopher , Palta Manisha , McCall Shannon , Gee Nathan , Hurwitz Herbert , Coleman R Edward , Zafar Yousuf , Kennedy-Newton Paula , Uronis Hope 
Published: February 2017

68 Background: EC is commonly managed with concurrent chemoradiotherapy, with or without surgical resection. The optimal combination and dose of agents is the subject of continued investigation. This study examines chemotherapeutic agents with known efficacy in EC in combination with the EGFR inhibitor panitumumab. Methods: Eligible pts received RT (1.8 Gy qd to 50.4 Gy) combined with concurrent chemotherapy. Dose-level (DL) 1 was cape (625 mg/m2/bid RT days), ox (40 mg/m2 weekly X 6 weeks), and pmab (3.6 mg/kg, weeks 1, 3 and 5). Chemotherapy doses were escalated barring dose limiting toxicity (DLT). The primary endpoint was defining the maximally tolerated dose with this combination. Secondary endpoints included toxicity and radiographic/pathologic response rates. Results: Twenty-nine pts were enrolled. Twenty-five had adenocarcinoma, 24 (83%) were cN+ and 9 (31%) had M1a/b disease. DLT was not encountered in DL 1. Two of 6 patients at DL 2 (cape 825 mg/m2/bid RT days, ox 50 mg/m2 weekly, pmab 4.8 mg/kg, weeks 1, 3 and 5) developed DLT (one hospitalization due to dehydration; one with drug reaction requiring hospitalization). Twenty additional pts were enrolled at DL1. Primary toxicities were EGFR-rash, esophagitis, nausea/vomiting and fatigue. On repeat endoscopy, 16 (55%) had CR, 10 (35%) PR and 2 (7%) SD. Using PERCIST criteria, 12 (41%), 11 (38%), 2 (7%) and 3 (10%) had CR, PR, SD and PD response on restaging PET, respectively. Twenty pts underwent esophagectomy, revealing Gr 0 response (no residual disease) in 9 (45%), Gr 1 (single/microscopic cells) in 3 (15%), Gr 2 (fibrosis > gross disease) in 4 (20%) and Gr 3 (gross residual > fibrosis or no evident response) in 4 (20%). Seven pts (35%) experienced anastomotic leak (2 requiring reoperation and 3 stent placement). Conclusions: Concurrent chemoradiotherapy utilizing capecitabine, oxaliplatin, panitumumab is reasonably well-tolerated and associated with high rates of radiographic, endoscopic and pathologic response. Postoperative anastomotic leak rates were higher than expected. Further study of this regimen in the operative and nonoperative settings is warranted.
Patterns of care according to treatment intent for metastatic colorectal cancer (mCRC): A two-year review of routine practice.
Authors: Field Kathryn Maree , Desai Jayesh , Tie Jeanne , Kosmider Suzanne , Bae Susie , McKendrick Joseph James , Harold Michael , Gibbs Peter 
Published: February 2017

682 Background: Cure is potentially achievable in select patients (pts) with mCRC with limited metastatic disease to liver and/or lung. To date the peri-operative strategies undertaken by oncologists in routine practice for such pts have not been well documented. Methods: A clinical database recording information on all pts diagnosed with mCRC since July 2009 from 5 hospitals was analysed. Management strategies where a curative-intent resection had occurred; was planned; or was a potential option were compared with those managed with palliative intent. Results: Status at the time of first review regarding systemic chemotherapy (CT) was documented for 280 pts. 11 (4%) had already undergone curative-intent resection; 31 (11%) had a resection planned; 27 (10%) were considered potentially resectable if their response to treatment was good; and 207 (74%) were treated with palliative intent. No pts already resected or planned for resection were >ECOG 1, compared with 11% (3/27) potentially resectable and 17% (36/207) palliative pts. CT was delivered in 9 (82%) already-resected, 26 (84%) planned for resection, 26 (96%) potentially-resectable and 159 (77%) palliative-intent pts. Combination CT was the dominant strategy, although 7 of 11 (66%) already-resected pts received single agent treatment. No already-resected pts received bevacizumab with CT, compared with 27% (n=14) of planned or potentially-curative pts and 55% (n=88) of those treated with palliative intent. At the time of analysis 13 pts (42%) with a planned resection and 8 (30%) considered potentially curative have had surgery, while 3 (1.4%) where treatment was initially considered palliative have had curative-intent surgery. Conclusions: Treatment strategies for pts with mCRC differ significantly based on the treatment intent, and may be affected by surgical preference and referral pattern. Bevacizumab was less likely to be used for already-resected pts and the use of single agent therapy in this group was also not uncommon. Many pts initially considered resectable do not ultimately undergo resection, whereas occasional ‘palliative’ pts may become resectable, confirming the importance of continued consideration of this option.
Pathologic complete response to standard preoperative chemoradiation in patients with locally advanced rectal cancer.
Authors: Naseem Madiha , Murray Joshua , Simmons Christine E. , Baxter Nancy , Burnstein Marcus J. , Brezden-Masley Christine 
Published: February 2017

686 Background: Pathologic complete response (pCR) is associated with lower rates of recurrences and longer disease-free survival rates in locally advanced rectal cancer (LARC) patients. The purpose of this study was to evaluate clinical outcomes of neoadjuvant chemoradiation and pCR among these patients. Methods: A retrospective chart review was performed for all patients treated for LARC between August 2005 and May 2011 at St. Michael's Hospital, Toronto. Patients were stratified into pCR and no-pCR groups and compared with respect to tumor size, nodal status, and treatment characteristics. Descriptive statistics were calculated for all variables of interest. Chi-square and t-tests were conducted to test for associations between categorical and continuous variables respectively. Disease free survival was calculated as the time between diagnosis and recurrence date, censored at last follow up. Results: A total of 92 patient charts were reviewed; 21 patients had metastatic carcinoma and were excluded from analysis. 63.4% (45/71) were male, with a mean age of 61.2 years and median follow up of 15 months. 12.7% (9/71) of patients achieved a pCR, while the remaining 87.35% (62/71) were no-pCR. All pCR patients received and completed standard pre-operative chemotherapy-radiotherapy. 73.4% (52/71) of the patients had complications from chemoradiotherapy. Furthermore, there was a significant association between having a significant response to treatment and achieving a pCR; where 78% (7/9) of pCR patients had a significant response to treatment. Overall, 4/71 patients had a local recurrence, 22.2% (2/9) pCR and 3.2% (2/62) no-pCR. Those with no-pCR had a recurrence at 1 and 2.2 years post diagnosis, while those with pCR had a recurrence at 3.7 years. Conclusions: This study suggests that patients undergoing standard pre-operative chemoradiotherapy are likely to have a significant response and achieve a pCR. Based on this study, although a pCR does not prevent the risk of recurrence, it delays the onset of local recurrence. Longer follow-up is required to determine if these results are robust and to develop future studies to improve efficacy of treatment delivery in LARC patients.
Surgical treatment of colorectal liver metastasis after neoadjuvant chemotherapy.
Authors: Zegarac Milan , Nikolic Srdjan , Djurisic Igor , Buta Marko 
Published: February 2017

688 Background: Liver is typical place for metastasis for patients with colorectal carcinoma. During the period of disease, 50% of patients with colorectal carcinoma will get liver metastases, 20% of the will have synchronous and 30% metachronous. Surgical resection is modality of choice in treatment for liver metastases in colorectal carcinoma. Applying neoadjuvant chemotherapy in patients with colorectal cancer liver metastases, which are primarily nonresectable or potentially resectable, it is possible to transform in resectable state. The goal of treatment is R0 liver resection and putting the patient in the NED stage of disease. Methods: All patients received protocol for potentially resectable metastase- FOLFOX-bevacizumab. The assessment was conducted on the basis of angioCT and NMR. With all patients liver resection procedures and RFA were applied. Results: During the period from June 2007 to December 2009 in 40 patients with nonresectable or potentially resectable metastases the neoadjuvant HT FOLFOX-bevacizumab was applied on average for three months. The patients were operated 6 weeks after the last application of bevacizumab, because of the possibility of intraoperative bleeding. The number of metastases ranged from 1 to 6. With 17 patients lobar resection was performed, and with 10 patients segmental resection was performed. With another 11 patients metastasectomy was performed, while RFA was performed with 2 patients. 3 years survival is 57.5%. Conclusions: By applying neoadjuvant HT and bevacizumab with patients suffering from colorectal cancer liver metastases as the only existing metastases, it is possible to significantly reduce metastases, and thereby resection as well. With this approach time without disease and survival are increased.
A phase I evaluation of vandetanib plus paclitaxel, carboplatin, 5-fluorouracil, and XRT induction therapy followed by surgery for previously untreated locally advanced cancer of the esophagus and GE junction.
Authors: Astsaturov Igor A. , Meyer Joshua E. , Cheng Jonathan D. , Olszanski Anthony J. , Dushkin Holly , Berger Adam C. , Davey Monica , Cohen Steven J. , Burtness Barbara , Scott Walter Joseph 
Published: February 2017

74 Background: Vandetanib (Vb) is an oral inhibitor that selectively targets VEGFR2, VEGFR3, RET and EGFR. Preclinical models indicate synergy with radiation and chemotherapy. We report the final results from an open-label phase I study of pre-operative Vb with carboplatin, paclitaxel, 5FU and radiation in pts with operable esophageal and GE junction (GEJ) carcinomas. Methods: Pts with operable PET/CT and EUS-staged carcinoma of the esophagus and GEJ received once daily Vb with concomitant RT (1.8 Gy/d, total 45 Gy) plus carboplatin AUC5 (d1 and 29), paclitaxel (50 mg/m2, d1,8,15,22,29), and 5-FU (CI 225 mg/m2, M-F, 5 wks). The primary objective was the safety, tolerability and the maximum tolerated dose of Vb in this combination. Planned dose escalations of Vb: 100, 200 and 300 mg daily with a “3+3” design. Results: Nine male pts (median age 58 (35-77), stage II, T2-3N0 (2 pts), III, T2-3N+ (7 pts)) were accrued between 03/2009 and 08/2010 at Fox Chase Cancer Center: 2/9 pts had esophageal squamous carcinoma (SCC) and 7/9 pts had adenocarcinoma including GEJ (2 pts). All patients completed the planned induction chemoradiation and underwent esophagectomy with curative intent. Of 3 initial pts at Vb 100 mg, one with SCC died on day 99 from GI hemorrhage which was considered treatment-related. Three more pts received Vb 100 mg and 3 pts received Vb 200 mg daily. Dose limiting toxicities (DLT) occurred in 2/3 pts receiving Vb 200 mg (esophago-gastric anastomotic leak, and diarrhea requiring Vb dose reduction). Grade 3 non-hematological toxicities included diarrhea (2), anorexia (1), abdominal pain (1), hyponatremia (1), AST/ALT (1), depression (1). Dose escalation to 300 mg Vb was not attempted. 5/9 pts had a pathologic complete response (no tumor seen, 56%), 5/9 remain disease free with median followup of 23 months (13-31). 3 pts had distant recurrences at 322, 334 and 561 days. Conclusions: Targeting VEGFR/RET/EGFR with Vb at 100 mg daily in combination with induction chemoradiotherapy for operable esophageal and GEJ cancer is well tolerated and with promising clinical activity warranting further phase II evaluation.
Survival differences between preoperative and postoperative radiation in esophageal cancer treated with combined modality therapy: A SEER analysis.
Authors: Wojcieszynski Andrzej Pawel , Milby Abigail Berman , Plastaras John Peter , Metz James M. , Apisarnthanarax Smith 
Published: February 2017

78 Background: The effect of radiation therapy (RT) sequencing with surgery on clinical outcomes for locally advanced esophageal cancer patients is unclear. We hypothesized that RT given prior to surgery has superior survival outcomes compared to RT delivered after surgery. Methods: Patients with the following inclusion criteria were identified within 17 Surveillance, Epidemiology, and End Results (SEER) registries from 1988-2006: adenocarcinoma or squamous cell carcinoma of the esophagus, esophagectomy, and RT. Data on demographics, tumor characteristics, and survival outcomes were extracted and compared between patients receiving preoperative and those receiving postoperative RT. Cox regression univariate and multivariate analyses were performed to identify parameters that were associated with cause-specific (CSS) and overall survival (OS). Results: A total of 2,579 patients met the defined criteria. Of these patients, 1,689 received preop RT and 890 received postop RT. Patients receiving preop RT compared to postop RT had improved 5-yr CSS (41% vs. 31%, p<0.0001) and OS (33% vs. 23%, p<0.0001). On univariate analysis, RT sequence, histology, T stage, nodal status, number lymph nodes examined, age, gender, marital status, race, and county income were significant independent predictors of OS. On multivariate analysis ( table ), preop RT continued to remain statistically significant for OS (HR 0.88; p = 0.034). Conclusions: Preoperative RT is associated with superior overall and cause-specific survival compared to postoperative RT and should be the preferred approach in combination with surgery for locally advanced esophageal cancer. [Table: see text]
Three, two, or one drug chemotherapy for frail or elderly patients with advanced gastroesophageal cancer (321GO): A feasibility study.
Authors: Hall Peter S. , Lord Simon , Collinson Michelle , Marshall Helen , Jones Marc , Olivier Catherine , Howard Helen , Seligman Jenny , Swinson Daniel , Roy Rajarshi , Dent Jo , Cheeseman Sue , Last Kim William , Seymour Matthew T. 
Published: February 2017

97 Background: The median age of death from gastroesophageal (GO) cancer is 77 years. Palliative chemotherapy can improve survival and quality of life. Current standard combination regimens have been developed in trials involving patients of median age under 65 years with predominantly good performance status (PS). In light of audit and survey evidence of widespread use of arbitrarily modified chemotherapy schedules in frail and elderly patients, better evidence is needed to guide treatment. Based on our experience with the MRC FOCUS trial in colorectal cancer, 321GO aimed to test the feasibility of a randomised trial comparing chemotherapy in frail and elderly patients with advanced GO cancer. Methods: Patients with advanced GO cancer considered unfit for full-dose 3-drug chemotherapy, were randomly allocated (1:1:1) to 3, 2 or 1 drug chemotherapy at 80% dose of standard regimens with EOX: epirubicin 40mg/m2 d1, oxaliplatin 104mg/m2 d1, capecitabine 500mg/m2 bd x21d, OX: oxaliplatin 104mg/m2 d1, capecitabine 500mg/m2 bd x21d or X: capecitabine 1000mg/m2 bd d1-14, then 7 day rest. The primary endpoint for feasibility required 45 patients to be recruited over 18 months. Secondary endpoints included tolerability, treatment benefit and compliance with detailed health and quality of life (QoL) assessment. Results: 55 patients were recruited over an average of 18 months for each of the six recruiting centres; 17 to EOX, 19 to OX and 18 to X. The median age was 75. 37 (66%) patients were of WHO PS 0 or 1 and 18 (33%) were of PS 2. After 6-weeks, 12 (71%), 9 (47%) and 9 (50%) patients in the EOX, OX and X arms had experienced a treatment delay, dose reduction, grade 3 toxicity or stopped treatment. Treatment benefit (no radiological progression or clinical deterioration) at 12 weeks was seen in 8 (47%), 11 (58%) and 3 (16%) patients for EOX, OX and X respectively. Compliance with baseline health and QoL assessment was 98% at baseline and 69% at 12 weeks. Conclusions: A phase III trial randomising frail or elderly patients with advanced GO cancer to alternative chemotherapy regimens is feasible. EOX was associated with greater toxicity compared with OX; X offered no improvement in tolerability over OX.
Long-term cardiopulmonary mortality after radiation for locally advanced esophageal cancer.
Authors: Milby Abigail Berman , Wojcieszynski Andrzej Pawel , Apisarnthanarax Smith , Metz James M. , Plastaras John Peter 
Published: February 2017

99 Background: Radiation (RT) is considered an integral component of trimodality therapy for locally-advanced esophageal carcinoma to improve locoregional control and potentially survival. However, the long-term risk of cardiopulmonary mortality (CPM) is not well-understood in this population. Methods: Patients age 20-85 with esophageal carcinoma with T3, T4 or node positive (N+) disease who underwent esophagectomy were identified within 17 Surveillance, Epidemiology, and End Results registries from 1988-2006. Patients with metastatic disease or <6 mo follow up were excluded. CPM was calculated for patients receiving vs not receiving RT and compared by the Kaplan-Meier method. The log-rank test was used for univariate associations and Cox proportional hazards model was used for multivariate analysis (MVA). Results: A total of 4,079 patients met the defined selection criteria of whom 2,408 were treated with RT, and 1,671 were not. Median age was 62.2 yrs (22-84) and follow-up was 22 mos (6-248). There was no significant difference in CPM in patients who received RT versus those who did not (p=0.8). At 10 yr, the majority of deaths were from esophageal cancer (73 with vs 78% without RT) compared to CPM (13.7 with vs 11.6% without RT). On univariate analysis ( table ), age <60, diagnosis era, and histology were significant independent predictors of CPM. On MVA, age <60 (HR 0.36) and diagnosis era (0.63 for 1994-2000 and 0.55 for 2000-2006) remained statistically significant for CPM. Conclusions: RT for esophageal cancer is not associated with an increased long-term risk of CPM in the overall population. Older age and earlier diagnosis era predict for CPM. Although survival in esophageal cancer is dominated by cancer deaths, advances in RT are still needed to prevent excess treatment-related mortality. [Table: see text]