bluuebunny/crossref_metadata_2025_split huggingface dataset:
Response to pembrolizumab in patients with mismatch repair deficient (dMMR) metastatic colorectal cancer (mCRC).
Authors: Leal Alexis Diane , Paludo Jonas , Finnes Heidi D. , Grothey Axel 
Published: March 2017

714 Background: Mismatch repair deficient (dMMR) colorectal cancer (CRC) has been shown to be responsive to blockade with anti-programmed death-1 (PD-1) antibodies. We describe a cohort of 17 patients with dMMR mCRC receiving treatment with pembrolizumab. Methods: Patients were identified through review of the Mayo Clinic electronic medical record (EMR) and chemotherapy administration records from May 2015 through September 2016. All patients with dMMR mCRC who received treatment with pembrolizumab were included. The EMR was reviewed to identify demographic, clinical, pathologic and treatment details. Overall survival (OS), progression free survival (PFS) and disease control rate (DCR=CR+PR+SD) are reported. Time to event analysis was calculated using the Kaplan-Meier method. Results: A total of 17 patients were included in this analysis; median age at diagnosis was 48.5 years (range 25-93); 59% were female. Most primary tumors were right sided (n=12; 71%), 4 (24%) were left sided and 1 (5%) was a tumor of unknown primary within the bowel. Thirteen (75%) patients received 2 or more lines of therapy prior to pembrolizumab (range 1-4). All patients received 2 mg/kg every 3 weeks, with the exception of two patients on a clinical trial; one who received 200 mg every 3 weeks, the other received 10 mg/kg every 2 weeks. The most common mutations (mut) identified were loss of MLH1 (9/12) and PMS2 (10/12), 4 patients had germline mut. KRAS mut was identified in 6/15 patients and only 1 patient had BRAF mut. Number of cycles of pembrolizumab ranged from 1 to 35, with 10 (59%) patients receiving 6 or more cycles. DCR at first assessment was 57%, with 7% CR and 50% PR. Median follow-up was 28 months (95% CI 18-55). Median OS was 103 months (95% CI NR-NR); 12-month OS was 88% and 24-month OS was 81%. Median OS post-PD-1 therapy was NR (95% CI 2-NR). Median PFS was 19 months (95% CI 5-19); 12-month PFS was 64% and 24-month PFS was 0%. At time of analysis, 11 patients remain on PD-1 therapy; 4 patients have died. Conclusions: Anti-PD1 blockade with pembrolizumab can provide long lasting benefit in dMMR mCRC, even in heavily pretreated patients.
Effect of adjuvant chemotherapy following pathologic complete response on long-term survival in rectal cancer: A propensity score matched analysis.
Authors: Mokdad Ali , Huerta Sergio , Minter Rebecca M , Mansour John C. , Choti Michael A. , Polanco Patricio 
Published: March 2017

717 Background: The role of adjuvant chemotherapy following resection in patients with rectal cancer that achieve pathologic complete response (pCR) after neoadjuvant therapy is unclear. Current data have been limited by small sample size series. This study examined the impact of adjuvant chemotherapy following pCR on overall survival in a national cohort of patients. Methods: Patients with rectal adenocarcinoma were identified in the National Cancer Data Base between 2006 and 2012. Those with locally advanced tumor (clinical stage II or III) that achieved pCR (defined as ypT0N0 in surgical specimens) after neoadjuvant chemoradiotherapy (nCRT) were included in the study. We matched by propensity score patients that received adjuvant chemotherapy (ACT) and patients that did not receive postoperative treatment (no-ACT) controlling for demographic as well as perioperative patient and tumor characteristics. Overall survival was compared using a Cox proportional hazards model. Results: We identified 2,543 patients (ACT: 732, no-ACT: 1,811 patients) with resected locally advanced rectal adenocarcinoma that achieved pCR after nCRT. Among patients that received ACT, 711 were matched with 711 patients in the no-ACT group. Adjuvant chemotherapy was associated with improved overall survival compared to no-ACT (hazard ratio[HR] = 0.46, 95% confidence interval [CI] = 0.29 – 0.75). Overall survivals at 1, 3, and 5 years in the ACT and no-ACT groups were 100% vs 98% (P=0.1), 98% vs 94% (P<0.01), and 94% vs 89% (P<0.01), respectively. In subgroup analyses, adjuvant chemotherapy improved overall survival in patients with clinical stage II (HR = 0.43, 95% CI = 0.22 – 0.85) as well as stage III tumor (OR = 0.50, 95% CI = 0.26 – 0.98). Among patients that received adjuvant chemotherapy, there was no difference in overall survival between single agent and multiagent regimens (HR = 1.37, 95% CI = 0.57 – 3.29). Conclusions: Adjuvant chemotherapy may providea small long-term survival benefit in patients with resected locally advanced rectal cancer and pCR after nCRT.
Cost effectiveness of maintenance bevacizumab in patients with metastatic colorectal cancer.
Authors: Lange Joel , Rajeev Rahul , Gamblin T. Clark , Turaga Kiran 
Published: March 2017

718 Background: Observation alone after initial treatment of unresectable metastatic colorectal cancer is often anxiety provoking for physician and patient alike. The CAIRO 3 trial suggested the efficacy of maintenance capecitabine and bevacizumab in improving overall survival for such patients. We hypothesized that the cost effectiveness for maintenance capecitabine and bevacizumab would be worse than accepted population thresholds. Methods: Data from the CAIRO-3 trial was used to populate a semi-markov model, in which patients transitioned between different disease and complication based states. Transition probabilities were extratcted from the trial. Costs were determined from a thirs payer persective from the Medicare part B ASP drug pricing file. Utility was converted from the global quality of life scale. Incremental cost effectiveness ratios were calculated. Results: Cost of the maintenance arm after 10 cycles was $108,848 with a gain in 14.93 quality adjusted life months, while the quality adjusted life months gained at no cost in the observation arm was 13.67. This yielded an ICER of $1,036,648/QALY. Two way sensitivity analyses demonstrated dominance of observation across a wide range of parameters unless the cost per cycle was < $6250. Conclusions: Maintenance capecitabine and bevacizumab is not cost effective and is higher than the willingness to pay threshold for any developed nation. Reducing drug pricing is the only way to financially support the argument for this treatment strategy.
Nationwide incidence, treatment, and outcomes of patients 80 years and older with rectal adenocarcinomas: Analysis of 5,076 patients.
Authors: Cassidy Richard John , Cheng En , Switchenko Jeffrey M. , Jiang Renjian , Jhaveri Jaymin , Tanenbaum Daniel G , Gillespie Theresa Wicklin , McDonald Mark William , Landry Jerome C 
Published: March 2017

723 Background: Elderly patients have been underrepresented in randomized clinical trials of rectal cancer, and the value and tolerance of treatment options in this population remain unclear. We used the National Cancer Data Base (NCDB) to assess the incidence, treatment patterns, and overall survival (OS) outcomes of patients 80 years or older with newly diagnosed non-metastatic rectal adenocarcinomas. Methods: 5076 patients 80 years and older diagnosed with non-metastatic rectal adenocarcinomas from 2004 to 2013 were identified. Univariable and multivariable (MVA) analysis were performed to identify patient, tumor, and treatment characteristics associated with receipt of standard of care therapy (SOCT) and factors predictive of OS. SOCT was defined as surgical resection for Stage I patients and receipt of neoadjuvant therapy followed by surgical resection for Stage II/III patients. Kaplan-Meier curves were generated to assess the effect of stage and treatment received on overall survival. Results: At presentation, 935 (18.5%) were TXN0, 1557 (30.8%) were Stage I, 1552 (30.6%) were Stage II, and 1,032 (20.1%) were Stage III. The rates of patients receiving no therapy were: 29.6% for TXN0, 22.6% for Stage I, 16.5% for Stage II, and 12.2% for Stage III. The rates of patients not receiving SOCT were: 22.6% for Stage I, 51.4% for Stage II and 39.4% for Stage III cases. Survival was significantly worse for patients not receiving standard of care therapy: Stage I (52.1% receiving SOCT vs. 7.6% not receiving SOCT; p < 0.01), Stage II (49.8% receiving SOCT vs. 14.5% not receiving SOCT; p < 0.01), and Stage III (47.5% receiving SOCT vs. 10.2% not receiving SOCT; p < 0.01). On MVA of patient, tumor, and treatment variables, receipt of SOCT was associated with improved OS for the entire cohort (p < 0.01) and when examined by stage (p < 0.01). Conclusions: In this nationwide sample of patient’s ≥ 80 years old with rectal cancer, there was a high rate of patients receiving no therapy. Those that did receive standard therapy achieved reasonable outcomes, suggesting avoidance of guideline care in this population should not be advised.
Current alignment between the practice patterns of gastrointestinal (GI) cancer clinical investigators (CI) and general medical oncologists (MO) in the treatment of metastatic GI cancers.
Authors: Love Neil , Kelly Gloria , Miller Kirsten , Paley Douglas , Moss Jonathan , Ziel Kathryn 
Published: March 2017

724 Background: CI with an interest in specific cancers amass a unique body of knowledge and relevant experiences that may make their practice patterns different from those of MO. This initiative sought to document and compare the stated management approaches of CI and MO. Methods: InMay 2016, as part of a continuing medical education (CME) project, 31 CI elected to complete a 78-item survey assessing their usual treatments for various metastatic colorectal, gastric and pancreatic cancer clinical scenarios. A stipend was provided for participation. On June 4, 2016, 13 clinical questions from the CI survey were posed to 140 MO, 103 US-based and 37 non-US-based, prior to a CME symposium on GI cancers. Responses of the groups were compared. Results: For 10 out of 13 questions, there was relative concordance between CI and MO responses. However,for 3 there was considerable variation (see Table). Conclusions: Although CI and MO approach the care of many patients with GI cancers in a similar manner, important and noteworthy variations exist. These findings indicate that the documentation and comparison of treatment recommendations could be a novel strategy to elucidate misalignment between CI and MO and impel either or both to rethink current approaches. Additional work is needed to validate these findings and understand potential implications and applications. [Table: see text]
Predictability of survival outcome by early tumor shrinkage (ETS) at 8 weeks with cutoff value of 20% in metastatic colorectal cancer (mCRC) patients treated with mFOLFOX6 plus bevacizumab (bev) or FOLFIRI plus bev as first-line chemotherapy (1st-CTx): Validation in the phase III WJOG4407G trial.
Authors: Sakamaki Kentaro , Kito Yosuke , Izawa Naoki , Tsuda Takashi , Morita Satoshi , Yamazaki Kentaro , Boku Narikazu , Muro Kei , Hyodo Ichinosuke 
Published: March 2017

729 Background: We reported that ETS at 8 weeks with cutoff value of 20% is the best candidate for predicting overall survival (OS) in mCRC patients who received 1st-CTx in the retrospective study (Kito, ESMO, 2015), where ETS was estimated by the tumor growth inhibition model (Claret, JCO, 2013). The objective of the study was to validate our proposed evaluation time and cutoff value for ETS in the phase III WJOG4407G trial which showed equivalent efficacy of mFOLFOX6+bev and FOLFIRI+bev as 1st-CTx for mCRC (Yamazaki, Ann Oncol, 2016). Methods: Tumor shrinkage ratio (TSR), which is the relative change in the sum of the longest diameters of target lesions according to the RECIST between before and during 1st-CTx, was calculated using actually measured tumor size data. Cutoff values of TSR for ETS and allowance ranges for measurement time of tumor size were evaluated. The association between ETS and OS was investigated by Cox regression model. In multivariate analyses, the general prognostic factors of mCRC, such as ECOG performance status (PS), prior history of adjuvant chemotherapy (AC), baseline tumor size (bTS), serum alkaline phosphatase (ALP) and white blood cell (WBC), were adjusted. Results: Of 402 enrolled patients, 305 patients had tumor size data measured within 8 +- 2 weeks. Patient characteristics were: mFOLFOX6+bev/FOLFIRI+bev 153/152; PS 0/1 244/61; AC Yes/No 49/256; median bTS 79 mm (range 10-512); median ALP 274 IU/L (110-1,200); median WBC 6400/mm3(3,030–12,000). In multivariate analyses, ETS at 8 weeks with cutoff value of 20% was most significantly associated with OS showing hazard ratio (HR) of 0.53 (95%CI: 0.38-0.74, p < 0.001). Moreover, HR of ETS was 0.47 (95%CI: 0.33-0.67, p < 0.001) in using the data during 8 +- 1 weeks (n = 257), while HR was 1.03 (95%CI: 0.41-2.62, p = 0.95) in using the data earlier or later than 8 +- 1 weeks (6 to 7 or 9 to 10 weeks) (n = 48). Conclusions: This analysis supported that ETS with cutoff value of 20% using data within 8 +- 1 weeks is optimal for predicting OS in mCRC patients who received 1st-CTx. Clinical trial information: UMIN000001396.
Impact of cyclophilin A on survival in gastric cancer patients who received platinum-based chemotherapy.
Authors: Maeng Chi Hoon , Baek Sun Kyung , Sung Ji-Youn , Kim Si-Young 
Published: March 2017

73 Background: Cyclophilin A (CypA), which is a protein that mediates protein folding and trafficking, has known to be associated with cancer progression and drug resistance such as cisplatin. However, the actual effect in cancer patients has not been elucidated. Methods: We collected clinical data from the cohort of 289 gastric cancer patients. Subjects were selected as following criteria: 1) adjuvant or first-line palliative chemotherapy containing platinum, 2) available FFPE tissue for immunohistochemical stain for CypA. We divided the population into two groups; Group A was patients who received adjuvant chemotherapy and Group P was those of palliative chemotherapy-treated group. The score of CypA immunohistochemistry was calculated depending on the intensity of stain and the percentage of stained cells. We performed survival analysis based on CypA expression. Results: 1) Group A (N = 147) Patients with lower expression of CypA ( < vs. ≥ median IHC score) showed significantly worse progression-free survival (PFS, 2.4 years vs NR, p = 0.043), and overall survival (OS, 3.4 months vs. NR, p = 0.002). In subgroup analysis, level of CypA expression discriminated PFS significantly in patients with age less than 65, poorly differentiated histology, signet ring cell type, and OS for those with use of oxaliplatin, age less than 65, stage III, poorly differentiated histology, diffuse type of Lauren classification, and signet ring cell type favoring higher expression of CypA. 2) Group P (N = 142) There was no relationship between expression level of CypA and PFS/OS in patients with palliative settings. However, in patients who were treated with oxaliplatin-containing chemotherapy, lower expression of CypA showed worse OS (8.3 vs 11.1 months, p = 0.003) Conclusions: Lower level of CypA expression was associated with worse PFS and OS in patients with adjuvant setting, especially in case of advanced stage, and high grade histology. Although CypA did not have significant effect on survivals in palliative chemotherapy-received patients, those who received oxaliplatin showed worse OS with lower CypA.
Utilization of minimally invasive versus open colectomy for colon cancer and perioperative/short-term oncologic outcomes: Are we there yet?
Authors: Smith Jillian K. , Esnaola Nestor F. 
Published: March 2017

733 Background: Randomized controlled trials (RCTs) in highly-selected patient populations demonstrated equivalent outcomes following minimally invasive colectomy (MIC) versus (vs) open colectomy (OC) for colon cancer. The purpose of this study was to evaluate utilization of MIC and compare perioperative/short-term oncologic outcomes after MIC vs OC in a large, generalizable, national sample. Methods: We identified adult patients with invasive colon adenocarcinoma who underwent elective surgical resection between 2010 and 2012 using the National Cancer Data Base. Univariate associations between patient/tumor/facility/treatment characteristics and surgical approach were analyzed using chi-square tests. Multivariable logistic regression was used to identify independent predictors of receipt of MIC, as well as to evaluate independent associations between surgical approach and outcomes. Results: Among 111,372 patients identified, 48,393 (43.5%) underwent MIC; the proportion who underwent MIC increased between 2010 (37.8%) and 2012 (49%; p < 0.001). High education level (adjusted odds ratio [aOR] 1.13) and increasing income level (aOR 1.09-1.36) were independently associated with receipt of MIC, whereas black race (aOR 0.85), Medicare (aOR 0.86)/Medicaid (aOR 0.67)/uninsured status (aOR 0.57), non-metropolitan residence (aOR 0.92), and community (aOR 0.63) or other (aOR 0.58) cancer programs were independently associated with potential underuse. Mean length of stay was shorter following MIC vs OC (6.07 vs 7.68 days; p < 0.001). Use of MIC was independently associated with reduced 30-day (aOR 0.6) and 90-day (aOR 0.62) mortality, as well as lower rate of positive surgical margins (aOR 0.69) and higher rate of regional lymph nodes examined > = 12 (aOR 1.14). Conclusions: This study confirms that MIC is associated with favorable perioperative/short-term oncologic outcomes (compared to OC), as demonstrated in RCTs. Although utilization of MIC for colon cancer continues to rise, implementation studies are warranted to enhance access to optimal surgical care and eradicate persistent disparities in receipt of MIC among historically underserved populations.
Comparative analysis of survival in colon cancer undergoing sentinel lymph node mapping versus conventional surgery based on number of positive lymph nodes.
Authors: Ramanathan Sabarina , Saha Sukamal , Mukkamala Suresh , Hicks Michael , Knight Patrick , Mazzaferro Daniel , Siva Thushy , Bajaj Vinay , Hutcherson Lori , Chang Avian , Livert David , Oza Rajen 
Published: March 2017

734 Background: Unlike in breast cancer or melanoma, resection during sentinel lymph node mapping (SLNM) in colon cancer (CCa) includes regional lymphadenectomy including SLNs and non SLNs. However, SLNM often identifies micrometastases which can be missed by conventional (Conv) surgery and pathologic examination. It is unknown whether this impacts survival or recurrence. Hence, a retrospective analysis was undertaken to study overall (OS) and disease -specific (DSS) survival between patients (pts) undergoing SLNM vs Conv surgery based on the number of +veLNs. Methods: SLNM was done by subserosal injection with blue dye followed by segmental resection including regional lymphadenectomy. All SLNs were ultrastaged and other nodes were examined by conv. methods with H&E. Results: There are 309 pts in SLNM (GpA) vs 499 pts in Conv surgery (GpB); with average no. of lymph nodes (LNs) and +ve LNs 17.3/1.6 vs 14.4/2.49 respectively. For GpA, success rate was 99.6% and the average no of SLN was 3. Of the pts in GpA vs GpB, 1+ve LN were found in 38% vs 27%, 2+ve LNs in 10% vs 16%, and > 2 LNs in 53% vs 57%, respectively. Comparing 5 years OS between GpA vs GpB, for 1+ve LN was 62.8% vs 52.38%, for 2 +ve LNs 72.7% vs 48.65% and for > 2 +ve LNs 35% vs 33.33%, respectively. Similarly, DSS for 1 +veLN was 54.4% vs 47.6%, 2+ve LNs 40% vs 40.54% and > 2+ve LNs, 30.4% vs 25.76%, respectively(Table1.). Conclusions: Compared to Conv surgery, SLNM identified higher no. of LNs per pt with high success rate. Five-year OS and DSS also are better in SLNM vs Conv surgery for all +ve LN gps. Hence, SLNM in CCa may have prognostic value. A larger multicenter trial needs to be done to validate such data. [Table: see text]
Efficacy and safety of regorafenib compared to TAS-102 for metastatic colorectal cancer: A systematic review and network meta-analysis.
Authors: Kinupe Abrahao Ana Beatriz , Ko Yoo-Joung , Chan Kelvin K. , Berry Scott R. 
Published: March 2017

735 Background: Recent studies have shown regorafenib and TAS-102 (TAS) to be superior to placebo (P) in refractory metastatic colorectal cancer (mCRC). However, no studies have directly compared both drugs. Giving the lack of therapeutic options for these patients,, a systematic review to compare the efficacy and safety of regorafenib compared with TAS was performed, using indirect comparison methods. Methods: A systematic review using PubMed, Medline, Embase, Scopus and Cochrane database to identify published and unpublished studies up to November 2015 for randomized controlled trials (RCTs) for patients with metastatic colorectal cancer, involving regorafenib or TAS was performed. Data including overall survival (OS), progression-free survival (PFS) and toxicity were extracted. Pairwise direct meta-analyses (regorafenib versus placebo and TAS versus placebo) and indirect comparison (regorafenib versus TAS) using network meta-analyses methods (R package “netmeta”) to preserve randomization were performed using random effects. Results: 914 citations were initially identified among which 3 RCTs fulfilled eligibility criteria (CORRECT, CONCUR and RECOURSE trials) involving 1.764 patients (regorafenib: 641, TAS: 534, Placebo: 589). Subgroups of patients (1.659) who had not received prior regorafenib or TAS-102 were used to performed meta-analyses for efficacy. In indirect comparison, there were no statically differences observed between regorafenib and TAS-102 in overall survival (HR 0.96 95% CI 0.56-1.55 p = 0.082) and progression-free survival (HR HR 0.85 95% CI 0.40-1.80 p = 0.0182). In addition, there were no differences in objective response rate and disease control between both drugs. However, regorafenib has statistically more all grade toxicity (risk difference (RD) 0.31 CI 0.25-0.38 p = 0.001) and toxicity grade 3-5 (RD 0.22 CI 0.13-0.31 p < 0.001) compared to TAS. Conclusions: In this indirect comparison, regorafenib and TAS appeared to have similar efficacy. However, regorafenib has more toxicity compared to TAS. Post-approval real world data focusing on the comparative toxicity of regorafenib and TAS is warranted.
Utilization of systemic therapy options in the routine treatment of metastatic colorectal cancer.
Authors: Delahunty Rachel Lee , Lee Margaret , Wong Hui-Li , McKendrick Joseph James , Lee Belinda , Kosmider Suzanne , Cooray Prasad , Ananda Sumitra , Tran Ben , Tie Jeanne , Desai Jayesh , Gibbs Peter , Wong Rachel 
Published: March 2017

738 Background: In the treatment of metastatic colorectal cancer (mCRC), exposure to all three active cytotoxic agents; 5-fluorouracil/capecitabine (FP), irinotecan (Ir) and oxaliplatin (Ox), and the biologic agents, bevacizumab (Bev) and cetuximab and panitumumab (EGFR-I) improves outcomes. The current uptake of systemic agents for mCRC in a community setting in Australia is poorly described. Methods: The ACCORD database was interrogated to determine demographics, treatments and outcomes for all patients diagnosed with mCRC between 1/01/2011 and 1/01/2015 at 6 Melbourne centres (3 public and 3 private). Results: 865 patients were identified: median age was 68 years. 68% were ECOG 0-1, 60% had de novo metastatic disease. RAS status was known in 59%, of whom 48% were RAS wild-type (WT). At the time of analysis 69% of all patients had received systemic treatment with 51% receiving treatment second line and beyond; 65% RAS WT, 57% RASm, 16% RAS-Unk. See Table. Metastasectomy was performed in 29% of patients of whom 38% remain disease-free. With a median follow-up of 31.3 months 46% of patients remain alive. The median overall survival was 25 months for all patients(unresected;17.6 months, resected: not reached). Conclusions: A high proportion of patients receiving routine clinical care in the community setting do not receive any systemic therapy and few patients receive all available active agents. Despite this, the overall survival of patients with mCRC in this community-based cohort was 25 months and in-line with clinical trial data. [Table: see text]