bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variation in the use of adjuvant chemotherapy following neoadjuvant radiotherapy and surgery for rectal cancer in a publicly-insured health care system.
Authors: Bubis Lev , Mahar Alyson L. , Gupta Vaibhav , Jeong Yunni , Davis Laura , Li Qing , Karanicolas Paul Jack , Coburn Natalie 
Published: January 2019

854 Background: The efficacy of routine administration of adjuvant chemotherapy following sequential neoadjuvant chemoradiotherapy and surgery for rectal cancer is uncertain. This uncertainty may lead to practice pattern variations, with significant downstream discrepancies in oncological outcomes, patient-centered outcomes, and healthcare costs. The objective of this study, therefore, was to evaluate patient, disease, and health system factors associated with receipt of adjuvant chemotherapy following neoadjuvant radiotherapy and proctectomy. Methods: A retrospective cohort study of patients diagnosed with rectal cancer undergoing preoperative radiotherapy prior to proctectomy from January 1, 2010 to December 31, 2014 was performed using linked administrative healthcare databases. We compared the rate of chemotherapy administration (≥ 1 billing record) within 180 days of index rectal resection by healthcare administrative region in Ontario, Canada (2014 population: 13.4 million). Multivariable logistic regression models were constructed to assess patient, disease, and health system factors associated with differences in receipt of adjuvant chemotherapy. Results: We studied 1668 patients treated with preoperative radiotherapy and proctectomy, of whom 67% received chemotherapy within 180 days after surgery. The rate of adjuvant chemotherapy administration varied among health regions from 54% to 93%. On multivariable analysis, health region of residence, younger patient age, lower baseline comorbidity burden, and pathological nodal involvement were significant predictors of receipt of adjuvant chemotherapy. Conclusions: There is significant variation in receipt of adjuvant chemotherapy for patients receiving preoperative radiotherapy followed by proctectomy in Ontario. This variability is associated with patient, disease, and health system-related factors. Identifying the drivers of variability in cancer care practice may help to provide a basis for understanding and addressing discrepancies in clinical, patient-centered, and economic outcomes in healthcare systems.
PROX: Primary resistance to oxaliplatin containing regimen in the first line treatment of metastatic colorectal carcinoma—Retrospective analysis.
Authors: Machado Larissa , Felismino Tiago , De Brito Sales Diogo , Morbeck Diogo , Karani Amanda , Diniz Lara Azevedo , Cunha Ingrid Hariman Fonseca , Souza Virgilio , Begnami Maria Dirlei , Macedo Mariana Petaccia , Carraro Dirce Maria , Mello Celso Lopes 
Published: January 2019

855 Background: The rate of primary resistance to modern first line (FL) chemotherapy regimen in the treatment of metastatic colorectal cancer (mCRC) is low. Progression Disease (PD) to FOLFOX in the FL is less than 15% in most trials. Prognostic factors associated with worse outcome in mCRC have been identified. However, primary resistance to Oxaliplatin (PROX) containing regimen is not well understood, as well as the role of salvage therapy in further lines of treatment. The aim of the study was to analyze clinical and pathological characteristics of patients with PROX. Methods: A retrospective, single center study included patients that presented PD in the first response evaluation with an Oxaliplatin containing regimen in the FL treatment of mCRC. We also evaluated the Overall Survival (OS) and progression free survival (PFS) of these patients to second and third line. Clinical and pathological variables were analyzed and correlated with (OS). Results: A total of 55 patients were inclued. Median age these cohort was 57 years. Female/Male rate was 42%/58%. Mucinous component was 27%. Right and Left colon was 27% and 66%, respectively. BRAF mutation (2/16 pts). Wild type KRAS was 44%. Synchronic metastasis was 75%. Ressection of metastasis was performed in 20%. Liver limeted disease was found in 45%. Main chemotherapy regimen containing oxaliplatin was FOLFOX (78%) in first line. Bevacizumab, Cetuximab and Panitumumab were used in 21.8%, 9%, 1.8%, respectively. OS was 9.4 months. PFS in second line 3.8 months (47 pts) and third line 3.5 months (18 pts). The only variable associated with longer survival was resection of metastasis (25.6 x 8.6 months, p=0.039). Conclusions: No clinical and pathological variable were able to predict primary resistance to Oxaliplatin containing regimen. However, we found a higher proportion of mucinous subtype. Patients submitted to resection of metastasis had almost three fold the survival of patient that did not underwent surgery. Refractory patients have a very short survival. Further lines of treatment are not able to rescue these patients. Further studies focusing in patients with primary resistance to chemotherapy in first line are needed.
A phase II trial of first-line FOLFIRINOX for patients with advanced gastroesophageal adenocarcinoma.
Authors: Park Haeseong , Wang-Gillam Andrea , Suresh Rama , Rigden Caron E. , Amin Manik A. , Tan Benjamin R. , Pedersen Katrina , Lim Kian-Huat , Trikalinos Nikolaos , Navo Katherine , Morton Ashley , Schrumpf Lindsey , Marquez Samantha , Trinkaus Kathryn , Lockhart A. Craig 
Published: January 2019

89 Background: Standard first-line regimens for patients with metastatic gastroesophageal adenocarcinomas have an approximate 40% objective response rate (ORR). FOLFIRINOX has been used in first line therapy in other GI cancers (i.e pancreatic and CRC) with impressive efficacy signals. Methods: This is a phase II study of first line combination chemotherapy with fluorouracil (5-FU), irinotecan, and oxaliplatin in patients with advanced gastric, esophageal, or gastroesophageal junction adenocarcinoma (NCT01928290). Starting doses were 5-FU 400mg/m2 bolus followed by 2400 mg/m2 over 46 hours with leucovorin 400 mg/m2, irinotecan 180 mg/m2, and oxaliplatin 85 mg/m2. Trastuzumab was administered as 6 mg/kg loading dose then 4 mg/kg every 14 days if patients had HER2+ cancer. The primary endpoint was overall response rate (ORR). Secondary endpoints included progression free survival (PFS), overall survival (OS), time to progression (TTP), clinical benefit rate (CBR), and duration of response. Enrollment of 41 patients with HER2- disease was planned to reach one-sided = 0.10 and power 0.90 with goal of detecting true ORR60%. No enrollment goal was planned for HER2+. Results: From Nov 2013 to July 2017, 58 patients were enrolled, 25 out of 58 (43%) had HER2+ disease. Forty-nine patients were evaluable for response as they completed at least one restaging scan. ORR was 78% (38/49) in all patients, 67% (18/27) in HER2-, 91% (20/22) in HER2+. One patient (2%) had complete response, 37 (76%) had partial response, 7 (14%) had stable disease > 6 months; therefore, CBR was 92%. Median PFS is 11.9 months, median OS is 17.4 months and median follow up time 16.1 months. 41 (83.7%) had dose modification or delay during treatment. There were no unexpected toxicities. Conclusions: FOLFIRINOX with or without trastuzumab showed remarkable ORR and PFS in patients with advanced gastroesophageal adenocarcinoma in the first-line setting. This regimen may be a reasonable therapeutic option for patients with preserved performance status. Further investigation in larger population is warranted. Clinical trial information: NCT01928290.
Associations of PD-1 and PD-L1 expression with mismatch repair status and prognosis in chemoradiotherapy-naïve esophageal and gastric adenocarcinoma.
Authors: Svensson Maria , Borg David , Zhang Cheng , Hedner Charlotta , Nodin Bjorn , Uhlen Mathias , Mardinoglu Adil , Leandersson Karin , Jirstrom Karin 
Published: January 2019

9 Background: Although neoadjuvant and/or adjuvant treatment enhances survival in patients with resectable esophageal and gastric (EG) cancer, the prognosis remains poor and there is a great need to identify novel treatment strategies and suitable biomarkers. Expression of programmed death ligand 1 (PD-L1) is, together with mismatch repair (MMR) status, a putative biomarker of response to immune-modulating therapies, but their prognostic value in EG cancer remains unclear. Therefore, the aim of this study was to examine the expression of PD-L1 in tumour cells (TC) and tumour-infiltrating immune cells (TIC), and the receptor PD-1 in TIC, in EG adenocarcinoma. Particular attention was given to their relationship with MMR status, and prognosis. Methods: PD-L1 and PD-1 expression in TC and/or TIC was assessed by immunohistochemistry (IHC) on tissue microarrays with primary tumours from a retrospective consecutive cohort of 174 patients with chemoradiotherapy-naïve resected EG adenocarcinoma. MMR status was determined by IHC. The prognostic value of PD-L1 and PD-1 was also examined at the mRNA level in 354 cases of gastric adenocarcinoma in The Cancer Genome Atlas. Results: PD-1 expression was not associated with MMR status, but PD-L1 expression in TC and TIC was significantly associated with MMR deficiency (p < 0.001 for both). Neither TC PD-L1 nor MMR status was prognostic. However, high PD-1 (10%) and PD-L1 ( > 50%) expression in TIC was significantly associated with a prolonged OS, the latter independently of other prognostic factors and MMR status (hazard ratio = 0.39, 95% confidence interval 0.15-0.99). Moreover, the prognostic value was only evident in MMR proficient tumours, and similar in esophageal and gastric tumours. At the transcript level, PD-L1 expression was not prognostic, but high PD-1 expression was significantly associated with a prolonged OS in gastric adenocarcinoma (p = 0.012). Conclusions: High expression of PD-L1 but not PD-1 is significantly associated with MMR deficiency in EG cancer. High PD-L1 expression in TIC but not in TC, or high PD-1 expression in TIC, signifies a prolonged survival, in particular in MMR proficient tumours.
Nivolumab safety profile in Asian and Western patients with chemotherapy-refractory (CTx-R) advanced gastric/gastroesophageal junction (adv G/GEJ) cancer from the ATTRACTION-2 and CheckMate-032 trials.
Authors: Chau Ian , Chen Li-Tzong , Kang Yoon-Koo , Satoh Taroh , Kato Ken , Chung Hyun Cheol , Kang Won Ki , Chao Yee , Chen Jen-Shi , Ott Patrick Alexander , Le Dung T. , Zhao Huanyu , Jimenez-Exposito Maria Jesus , Janjigian Yelena Yuriy , Boku Narikazu 
Published: January 2019

90 Background: Nivolumab (NIVO) monotherapy demonstrated a survival benefit and durable responses in pts with CTx-R adv G/GEJ cancer (Boku N et al ESMO 2017; Janjigian Y et al ASCO 2017). Here we describe the safety profile of NIVO in Asian (A) and Western (W) pts with CTx-R adv G/GEJ who had received ≥ 2 prior CTx in the ATTRACTION-2 and CheckMate-032 trials, respectively. Methods: The safety population included pts who received ≥ 1 dose of study drug at the data cutoff of August 2016 for ATTRACTION-2 and March 2016 for CheckMate-032. TRAEs, serious TRAEs, and select TRAEs (sTRAE; with a potential immune-related etiology) were assessed. sTRAEs were managed using protocol-specified algorithms, which included corticosteroids as immune-modulating treatment (tx). Time to onset and resolution of sTRAEs were also assessed. Results: Median duration of NIVO tx was 1.9 mo in A and 2.3 mo in W pts. TRAEs (any grade) were reported in 43% of A and 64% of W pts; grade 3–4 TRAEs (A pts:10%; W pts:14%), serious TRAEs (A pts:10%; W pts:7%) and TRAEs leading to discontinuation (≤ 3% of pts in both groups) were infrequent. Most sTRAEs were grade 1–2 (Table) and occurred within the first 3 mo of NIVO tx. In A and W pts, median time to resolution of sTRAEs ranged from 3–19 wk. For those sTRAEs that required tx with immune-modulating agents, the median time to resolution of most sTRAEs ranged from 3–35 wk. Conclusions: NIVO demonstrated an acceptable safety profile in both A and W pts with CTx-R adv G/GEJ cancers with no clinically meaningful racial differences. Most sTRAEs were grade 1–2 in both cohorts and manageable using the recommended tx algorithms. Clinical trial information: NCT02267343 ATTRACTION-2 and NCT01928394 CheckMate 032. [Table: see text]
Postoperative chemotherapy in patients who are pN+ following neoadjuvant chemoradiation for locally advanced esophageal cancer.
Authors: Francis Samual , Nevala-Plagemann Christopher Duane , Cavalieri Courtney Christine , Lloyd Shane , Garrido-Laguna Ignacio 
Published: January 2019

97 Background: Esophageal cancer survival rates have improved since the widespread adoption of neoadjuvant chemoradiation therapy (CRT) followed by esophagectomy for patients who present with locally advanced disease. Unfortunately, overall prognosis for these patients remains poor. In this study, we sought to assess the effect of additional adjuvant chemotherapy in patients who have positive lymph nodes (pN+) following surgery. Methods: Using the National Cancer Database we retrospectively identified all patients with locally advanced esophageal cancer who received neoadjuvant CRT from 2004 to 2014. We then identified patients within this dataset who were found to be pN+ following neoadjuvant chemoradiation and esophagectomy and categorized them as having received adjuvant chemotherapy versus no additional chemotherapy. Survival analysis was performed using Kaplan-Meier estimation and propensity score matching. Results: 2,045 patients were identified as being pN+ following neoadjuvant CRT. Within this group, 14% received adjuvant chemotherapy. The 1, 5, and 8 year overall survival (OS) of patients receiving adjuvant therapy was 87%, 30%, and 21% compared to 76%, 23%, and 16% in those receiving neoadjuvant therapy alone, respectively (p = 0.0017). After a propensity score matched analysis, median OS was found to be significantly longer in the those receiving neoadjuvant CRT plus adjuvant chemotherapy compared to neoadjuvant CRT alone (27.8 months vs 22.2 months; HR 0.78; 95% CI, 0.62 to 0.97; p = 0.032). Conclusions: While not currently the standard of care, our data suggests that adjuvant chemotherapy may improve survival in patients with locally advanced esophageal cancer who are found to be pN+ following surgery. Additional prospective studies are needed to confirm this finding.
Impact of adjuvant chemotherapy with S-1 on survival in patients with type 4 and large type 3 gastric cancer.
Authors: Omori Hayato , Kaji Sanae , Makuuchi Rie , Irino Tomoyuki , Tanizawa Yutaka , Bando Etsuro , Kawamura Taiichi , Terashima Masanori 
Published: January 2019

98 Background: The prognosis of patients with linitis plastica (type 4) and large ulcero-invasive-type (type 3) gastric cancer is reported to be extremely poor. In stage II/III gastric cancer, adjuvant chemotherapy with S-1 is a standard treatment in Japan. However, the efficacy of postoperative chemotherapy with S-1 in these types of patients with dismal prognosis is unknown. The aim of this study is to evaluate the impact of adjuvant chemotherapy with S-1 on survival in type 4 and large type 3 gastric cancer patients. Methods: A total of 152 patients with clinically resectable type 4 and large type 3 gastric cancer who underwent R0 or R1 surgery from 2002 to 2014 were included. The survival outcome between patents with surgery alone and patients who received adjuvant S-1 was compared using a 1:1 propensity score matching method. Results: Patients with adjuvant S-1 were significantly younger (67 vs 74 y, p = 0.009), had higher incidence of T4 (90 vs 62%, p < 0.001), N2-3 (84 vs 63%, p = 0.008), and cytology positive (52 vs 29%, p = 0.006) than in surgery alone patients. Before matching, median survival time (MST) was not different in surgery alone (n = 52) and adjuvant S-1 (n = 100) (31.3 vs 35.8 months, p = 0.41). Propensity score matching yielded 48 patients (24 patients in each group). After matching, baseline characteristics were well balanced between the two groups. Survival in patients with adjuvant S-1 was significantly better than in surgery alone patients (MST: 50.3 vs 15.4 months, p = 0.002). Cox proportional hazard analysis revealed adjuvant S-1 treatment was selected as independent prognostic factor (HR: 0.38, 95%CI: 0.18-0.76, p = 0.006), as well as lavage cytology (HR: 3.9, 95%CI: 1.8-8.9, p < 0.001). Conclusions: Adjuvant chemotherapy with S-1 may have a strong impact on survival in type 4 and large type 3 gastric cancer patients. The efficacy of this treatment will be further demonstrated in the future clinical trials.
Survival of second-line irinotecan-based chemotherapy in early relapse patients with gastric cancer after adjuvant chemotherapy: Exploratory subgroup analysis of TRICS trial.
Authors: Nishikawa Kazuhiro , Murotani Kenta , Fujitani Kazumasa , Inagaki Hiroshi , Akamaru Yuske , Tokunaga Shinya , Takagi Masakazu , Tamura Shigeyuki , Sugimoto Naotoshi , Shigematsu Tadashi , Yoshikawa Takaki , Ishiguro Tohru , Nakamura Masato , Miyashita Yumi , Morita Satoshi , Tsuburaya Akira , Sakamoto Junichi , Tsujinaka Toshimasa 
Published: January 2019

99 Background: Second-line chemotherapy (SLC) was reported to improve the survival of advanced gastric cancer (AGC). The TRICS trial which a randomized phase III study of second-line irinotecan plus cisplatin versus irinotecan alone in patients with AGC refractory to S-1 monotherapy, revealed that both irinotecan based chemotherapies were effective with favorable long-term survivals and generally well tolerated. Eligible patients included patients with recurrence within 6 months after the completion of adjuvant therapy with S-1 (early relapse cases), or patients with tumor progression after first-line S-1 for an advanced cancer (progressive cases), in this trial. However, it is unclear whether survivals in early relapse cases were different from these in progressive cases or not. Methods: A total of 168 patients registered to the TRICS trial were classified as early relapse group (n = 111) or progressive group (n = 57), and 168 (irinotecan plus cisplatin, early relapse 56/83, 67%; irinotecan alone, 55/85, 65%) and 163 (55/81, 68%; 53/82, 65%) patients were analyzed for survival. Adjusted OS and adjusted PFS were constructed adjusted Kaplan-Meier curve with inverse probability weight, and were estimated by inverse probability of treatment weighting method (IPTW). Results: In baseline characteristics, PS 0 were more frequently seen in early relapse group than in progressive group (86% vs 72%, p = 0.0328), and median age of early relapse group was younger than progressive group (66 vs 72, p = 0.0162). The median OS was 13.9 months in early relapse group and 10.0 months in progressive group (HR:0.746, p = 0.1019). The adjusted median OS was 14.0 months in early relapse group and 10.6 months in progressive group (IPTW HR:0.864, p = 0.1019). Early relapse group showed better trends in PFS compared to the progressive group (4.7M vs 3.6M, HR: 0.650, p = 0.0149). The adjusted median PFS was 4.8 months in early relapse group and 3.7 months in progressive group (IPTW HR:0.673, p = 0.0008). Conclusions: Irinotecan based chemotherapies were effective especially in early relapse cases after adjuvant therapy with S-1, in second-line setting of AGC.
CheckMate 649: A randomized, multicenter, open-label, phase III study of nivolumab (NIVO) + ipilimumab (IPI) or nivo + chemotherapy (CTX) versus CTX alone in patients with previously untreated advanced (Adv) gastric (G) or gastroesophageal junction (GEJ) cancer.
Authors: Moehler Markus H. , Janjigian Yelena Yuriy , Adenis Antoine , Aucoin Jean-Sebastien , Boku Narikazu , Chau Ian , Cleary James M. , Feeney Kynan , Franke Fabio A. , Mendez Guillermo Ariel , Schenker Michael , Li Mingshun , Hitre Erika , Couture Felix , Karamouzis Michalis , Etienne Pierre-Luc , Ajani Jaffer A. 
Published: January 2019

TPS192 Background: Pts with adv G/GEJ cancer have an OS of ≈ 1 y, indicating an unmet medical need for new first-line treatments. Expression of PD-L1 is observed in up to 40% of pts with G/GEJ cancer and is associated with poor prognosis. In the randomized phase 3 ATTRACTION-2 study, NIVO demonstrated superior overall survival vs placebo with a 38% reduction of the risk of death (median OS, 5.3 vs 4.1 mo; HR, 0.62 P< 0.0001) and increased the OS rate at 12 mo (27% vs 12%; Boku N et al ESMO 2017) in pts with adv CTX-R (≥ 2 lines) G/GEJ cancer. In the phase 1/2 CheckMate-032 study in pts with CTX-R G/GEJ/esophageal cancer (79% ≥ 2 prior Tx lines), NIVO 1 mg/kg + IPI 3 mg/kg had a manageable safety profile and resulted in 24% ORR (40% ORR in pts with PD-L1+ tumors), a median OS of 6.9 mo, and a 35% OS rate at 12 mo (Janjigian Y et al ASCO 2017). In the phase 1 CheckMate-012 trial, NIVO + CTX had clinical activity and manageable safety in pts with NSCLC (Rizvi NA et al J Clin Oncol 2016). These positive results support investigation of NIVO, NIVO + IPI, and NIVO + CTX in earlier lines of treatment for G/GEJ cancer. The open-label, phase 3 CheckMate 649 trial will evaluate NIVO + IPI and NIVO + CTX vs CTX alone as first-line treatment for pts with adv G/GEJ cancer (NCT02872116). Methods: 1266 pts aged ≥ 18 y with untreated, inoperable adv/metastatic G/GEJ cancer (histologically confirmed adenocarcinoma) regardless of PD-L1 status will be randomized to receive either NIVO + IPI, NIVO + CTX (capecitabine/oxaliplatin [XELOX] or fluorouracil/leucovorin/oxaliplatin [FOLFOX]), or investigator choice of XELOX or FOLFOX. Tumor tissue for determination of PD-L1 status (Dako assay) must be provided from ≤ 6 mo before study treatment. No prior systemic treatment, including HER2 inhibitors, are allowed. Pts with known HER2+ status, suspected autoimmune disease, grade > 1 peripheral neuropathy, or active infection are excluded. Primary endpoint is OS in pts with PD-L1+ (≥ 1%) tumors. Other endpoints include OS in all pts; PFS and time to symptom deterioration in all pts and in pts with PD-L1+ tumors; and safety. Clinical trial information: NCT02872116.