bluuebunny/crossref_metadata_2025 huggingface dataset:
Formation of an international quality improvement collaborative for palliative care: The Global Palliative Care Quality Alliance (GPCQA).
Authors: Kamal Arif , Nicolla Jonathan , Friedman Fred , Stinson Charles S. , Patel Laura , Swetz Keith Mark , Strand Jacob , Portman Diane G. , Thirlwell Sarah , Groninger Hunter , Tuch Howard , Twaddle Martha , Kennedy William , Kyler Andy , Matthews Loretta , Candell Greg , Baker Karen , Anwar Zeba , Abernethy Amy Pickar , Bull Janet
Published: February 2017

91

Background: Formal mechanisms to share data on quality remain immature in specialty palliative care. As the field grows, infrastructure that promotes collaboration among academic and community-based practice will be required to foster comparisons and benchmarking of data to inform areas for quality improvement. Further, such relationships will create a palliative care “quality improvement laboratory”, where proposed guidelines and best practices can be developed, implemented, and tested. Methods: We set out to bring together specialty palliative care practices with a shared vision for collaborative quality improvement. We modeled our approach after the Institute for Healthcare Improvement Breakthrough Series alongside our Rapid Learning Quality Improvement paradigm. We use a set of common data collection procedures, across an electronic point-of-care platform called Quality Data Collection Tool (QDACT), alongside a centralized data registry. Further, we meet and discuss challenges and issues, compare best practices, and brainstorm new projects through biweekly conference calls. Results: We have created a multi-institutional collaboration for quality assessment and improvement in specialty palliative care. Termed the Global Palliative Care Quality Alliance, we have brought together 11 academic and community organizations, both general and oncology-specific, across six states to study various areas of quality practice. Short-term, we will conduct rapid-cycling quality improvement projects addressing National Quality Forum domains for quality palliative care, including documentation of spiritual assessment and timely advance care planning. Long-term, we aim to study the link between quality measure adherence and outcomes and further align our initiatives with those of other large consortia, like the Palliative Care Research Cooperative and Palliative Care Quality Network. Conclusions: Collaborative quality improvement is needed in specialty palliative care across a national platform. Developing the infrastructure to perform standardized quality improvement is achievable across multiple palliative care settings.
Processes of discontinuing chemotherapy for metastatic non-small cell lung cancer at the end of life.
Authors: Pirl William F. , Greer Joseph A. , Irwin Kelly , Lennes Inga Tolin , Jackson Vicki A. , Park Elyse R. , Fujisawa Daisuke , Wright Alexi A. , Temel Jennifer S.
Published: February 2017

96

Background: Administration of chemotherapy close to death is widely recognized as poor quality care. The goals of this study were to describe the processes of how chemotherapy is discontinued and examine their relationships with timing before death, hospice referrals, and terminal hospitalizations. Methods: We reviewed electronic health records of a prospective cohort of 151 patients with newly diagnosed metastatic non-small cell lung cancer (NSCLC) who participated in a randomized trial of early palliative care. Chemotherapy treatment during the final regimen was qualitatively analyzed, identifying categories of discontinuation processes. We then quantitatively investigated predictors and outcomes of the discontinuation process categories. Results: 144 patients had died, with 81 and 48 receiving intravenous (IV) and oral chemotherapy as final regimens, respectively. Five discontinuation processes were identified: definitive decisions; deferred decisions (breaks); disruptions for radiation therapy; disruptions due to hospitalizations; and no decisions. For patients receiving IV chemotherapy, definitive decisions were least frequent (19.7%), while disruptions due to hospitalizations were most frequent (27.2%). The different processes occurred at significantly different times before death; and often hospice referrals occurred months after chemotherapy discontinuation. Deferred decisions, or “breaks,” occurred at the longest interval before death, but definitive decisions resulted in greatest hospice utilization. Among patients receiving oral chemotherapy, 83.3% were switched from IV to oral as their final regimen, sometimes concurrent with or even after hospice referral. Conclusions: Patients with metastatic NSCLC stop their final chemotherapy regimen via different processes, which significantly vary in time before death and in subsequent end-of-life care.
A phase I/II study of DHP107, a novel oral paclitaxel formulation, in patients with advanced solid tumors (phase I) and gastric cancer (phase II).
Authors: Ryu Min-Hee , Ryoo Baek-Yeol , Kim Tae Won , Kim Sung-Bae , Lim Hyeong-Seok , Bae Kyun-Seop , Park Sook Ryun , Jo Yeong-Woo , Cho Hyun Ju , Kang Yoon-Koo
Published: February 2017

101

Background: Paclitaxel has been proven to be effective and widely used in various types of cancers. DHP107 is a novel oral paclitaxel formulation. In the previous first-in-human study, DHP107 showed no DLTs at a single dose-escalating schedule and was reported safe and feasible in patients with advanced malignancies. This study was conducted to determine 1) recommended dose (RD) for multiple dosing of DHP107 in patients with metastatic solid tumor and 2) efficacy in patients with advanced gastric cancer (AGC). Methods: In phase I study, standard 3 + 3 dose escalation scheme was used, and the planned dose of DHP107 was 150 mg/m2 bid at level 1, 200 mg/m2 bid at level 2, and 250 mg/m2 bid at level 3 on days 1, 8, and 15, every 4 weeks. In phase II study planned by Simon’s optimal two stage design (P0=0.05, P1=0.25, α=0.05, and β=0.2), DHP107 was administered at the RD in patients with AGC refractory to first-line chemotherapy containing fluoropyrimidine and platinum. Results: In the phase I study, no dose-limiting toxicity (DLT) was observed at level 1 (n=3) and at level 2 (n=6). At level 3, 2 out of 4 patients showed a DLT (one grade 4 neutropenia over 7 days and one febrile neutropenia). At additional dose level 2A (225 mg/m2 bid), 2 out of 4 patients experienced febrile neutropenia. Finally, the RD of DHP107 was determined as level 2 (200 mg/m2 bid). In PK analysis, 200 mg/m2 bid of DHP107 showed similar AUC, Cmax and half-life to i.v. paclitaxel at 80 mg/m2. Out of the 11 patients enrolled in the phase II study, 3 patients achieved a confirmed partial response (27%; 95% C.I. 0-59%). Grade 3/4 adverse events with frequency > 5% included neutropenia (27.3%), stomatitis (18.2%), anemia (9.1%), and febrile neutropenia (9.1%). There was no treatment-related death. Conclusions: RD of DHP107 was determined as 200 mg/m2 bid. At the RD, DHP107 was generally well tolerated and showed anti-tumor activity comparable to i.v. paclitaxel as a second-line chemotherapy in AGC. Based on these results, a phase III study to compare DHP107 with i.v. paclitaxel is currently ongoing in AGC. This study was supported by DAEHWA Pharmaceutical Co. and Gangwon Institute for Regional Program Evaluation by Korean government.
Distribution and timing of distant metastasis (DM) after definitive therapy for patients with esophageal and esophagogastric junction (E-EGJ) cancer.
Authors: Shiozaki Hironori , Sudo Kazuki , Wadhwa Roopma , Hofstetter Wayne Lewis , Skinner Heath D. , Komaki Ritsuko , Lee Jeffrey H. , Weston Brian , Bhutani Manoop S. , Maru Dipen M. , Blum Mariela A. , Ajani Jaffer A.
Published: February 2017

105

Background: For localized E-EGJ cancer patients, the preferred therapy is chemoradiation (CRT) followed by surgery (TMT). Definitive CRT (BMT) has been also established for the patients who do not qualify for surgery. Distribution and timing of distant metastasis has not been described. Methods: Between 2002 and 2013, 629 patients with localized E-EGJ cancer who underwent TMT or BMT were reviewed the distribution and timing of DM over time. Overall survival (OS) was estimated by the Kaplan-Meier method. Results: The median follow-up time was 37.2 months (interquartile range: 17.8-65.0) among patients with data that were censored. Among 356 patients with TMT, 33% (119) developed DM as their first relapse. Among 273 patients with BMT, 40% (109) developed DM. Following TMT and BMT, 91% and 96% of DM were diagnosed within 2 years of treatment, respectively. The 7 most common anatomic sites of DM were: lung (20% of DM for TMT and 17% of DM for BMT), distant lymph node (13% and 20%), liver (14% and 11%), peritoneum (10% and 13%), bone (6% and 11%), brain (8% and 8%) and pleura (7% and 5%). The median OS from DM were 10.2 months (95% CI: 7.8-12.7) for TMT patients and 7.8 months (95% CI: 5.7-9.9) for BMT patients. The median OS of patients with pleura metastasis was the shortest (1.5 months [95% CI: 1.0-2.1] for TMT and 3.5 months [95% CI: 3.3-3.6]) for BMT. Conclusions: After TMT and BMT, 33% and 40% of patients had DM and most DM occurred within 2 years (91% and 96%). Common sites of DM sites are lung, distant lymph node and liver. The risk factors associated with DM need to be elucidated. Supported by UT M. D. Anderson Cancer Center Multidisciplinary Research G rants, CA138671, CA172741, CA129926 from NCI (JAA) and Generous Donors. [Table: see text]
Trastuzumab with triple chemotherapy (DOC) in patients with advanced gastroesophageal cancer: A phase I dose-finding trial.
Authors: Schoennemann Katrine R. , Yilmaz Mette K. N. , Baeksgaard Lene , Jensen Helle Anita , Vestermark Lene Weber , Hansen Tine Plato , Pfeiffer Per
Published: February 2017

108

Background: Trastuzumab (T) improves efficacy of doublet chemotherapy (TOGA trial) in HER2 positive patients with advanced gastro-esophageal (GE) cancer but safety and efficacy with triple chemotherapy is presently unknown. We initiated a dose-finding trial to establish a safe 4 drug combination of docetaxel (D), short-time infusion of oxaliplatin (O), continuously capecitabine (C) and trastuzumab (T). Methods: This phase I, dose-finding trial was approved by the local etic committee. All pts had histologically confirmed GE adenocarcinoma. Therapy was given day 1 with escalating doses of D (42mg/m2 to 51 mg/m2 as a 60 minutes infusion), O (100 mg/m2 as a 30 minutes infusion) and C (1,250 mg/m2/day continuously). DOC was repeated every 3 weeks for a maximum of 6 courses. T was given as a loading dose (8 mg/kg) followed by 6 mg/kg every 3 weeks until PD or unacceptable toxicity. Toxicity was evaluated according to NCIC-CTC 3.0. DLT was evaluated after the first course and defined as non-haematological toxicity grade ≥ 3, neutropenia grade 4 more than 7 days or febrile neutropenia. Response was evaluated by the investigator according to RECIST 1.0 every 9th weeks. Data was updated September 1, 2013. Results: From May 2010 to October 2012 we included 11 pts. Median age was 62years (range 32-73), 5/11 pts had PS 0, all pts had metastatic disease. Neutropenia grade 3-4 was observed in two pts, one had febrile neutropenia grade 3 after four courses. Two pts had grade 3 vomiting, fatigue, or nausea, respectively and one patient had diarrhoea grade 3. Only one pt developed a DLT (grade 3 vomiting, nausea and fatigue). Dose-intensity, after six courses, in all 11 pts was: D = 89%, O= 88% C = 81% and T = 100%. Median number of DOC was 6; all pts continued T to a median of 12 courses and one pt is presently receiving T. Partial response was obtained in 9 pts (81%). Progression free survival was 8.8 months and overall survival was 16.5 months. Five pts are presently alive. Conclusions: DOC-T in HER2 positive GE pts is safe and easily administered in an out-patient setting. The recommended doses for further evaluation are: D 51 mg/m2, O 100 mg/m2, C 1,250 mg/m2. Efficacy is very promising and deserves evaluation in larger trials. Clinical trial information: NCT01295086.
Long-term outcome of endoscopic submucosal dissection for early gastric cancer compared to surgical resection.
Authors: Sim Eun Hui , Kim Byung-Wook , Kim Ji Hee , Kim Jin-Jo
Published: February 2017

120

Background: Endoscopic submucosal dissection (ESD) is now accepted as an alternative to surgery for the treatment of early gastric cancer (EGC). However, long-term clinical outcome of ESD for EGC compared to surgical resection has not been evaluated. The aim of this study is to evaluate the clinical outcome of ESD for EGC compared to surgical resection. Methods: A retrospective analysis was performed in 152 patients who underwent ESD or surgical resection for EGC according to Gotoda’s extended criteria from 2006 and 2008 in Incheon St. Mary’s Hospital and Seoul St. Mary’s Hospital, The Catholic University of Korea. Overall survival and recurrence rates were compared between the two groups. Results: A total of 56 patients underwent surgical gastrectomy and 96 patients underwent ESD. The medial follow-up was 76 months in surgical resection group and 71 months in ESD group. Metachronous recurrences including dysplasia were found in 9 patients in ESD group and none in surgical resection group (P=0.001). There was no significant difference between the groups in overall survival. Conclusions: Gotoda’s extended criteria for ESD might be acceptable for the treatment of EGC considering the oval survival. However, meticulous surveillance program should be established because metachronous recurrence is more common after ESD.
A phase II study of weekly nab-paclitaxel in combination with cisplatin as neoadjuvant chemotherapy in patients (pts) with locally advanced esophageal squamous cell carcinoma (SCC).
Authors: Yun Fan , Zhou Xinming , Jiang Youhua , Chen Qixun , Huang Zhiyu , Gong Lei , Yu Haifeng , Yang Haiyan , Liu Jinshi , Mao Weimin
Published: February 2017

122

Background: This phase II study was aimed to define the pathological response rate and safety of combining weekly nab-paclitaxel and cisplatin as neoadjuvant chemotherapy in pts with locally advanced esophageal SCC. Methods: Pts with resectable locally advanced thoracic esophageal SCC staged by EUS, CT and/or PET-CTscan. All pts received nab-paclitaxel (100 mg/m2, d1, d8, d22 and d29) and cisplatin (75 mg/m2, d1 and d22) as neoadjuvant chemotherapy, followed by esophagectomy.Postoperation: 2 cycles of adjuvant chemotherapy with same regimen was given in 4-6 weeks after the resection.The primary endpoint was pathological response rate. The second endpoints included R0 resection rate,down-staging rate, 3 years overall survival (OS) and disease-free survival (DFS). Results: From 01/2011 to 10/2012, 35 pts were enrolled. 31 male:4 females; IIA/IIB/IIIA/IIIB/IIIC in 3 (8.6%), 5 (14.3%),10 (28.6%), 8 (22.9%) and 9 (25.7%) pts. 30/35 pts went to surgery (85.7%). 30 had R0 resection (100%). Pathological complete response (pCR) was achieved in 4 pts (13.3%). Near pCR (microfoci of tumor cells on the primary tumor without lymph nodal metastases) in 2 pt (6.7%). Down-staging was observed in 19 of 30 patiens (63.3%). 5 pts did not going to surgery: 2 for progressive disease, 3 for refused. 24/30 pts (80.0%) received adjuvant chemotherapy, 7 pts (23.3%) received adjuvant chemoradiotherapy. Grade 3/4 toxicities in 35 evaluable pts during chemotherapy were as follow: neutropenia (11.4%), anemia (8.6%), thrombocytopenia (5.7%), nausea/vomiting (14.3%), neutropenia fever (8.6%), asthenia (20.0%). Surgical complications: 1 anastomotic leaks (3.3%). No treatment-related death. At a median follow up of 12 months (8~20mos), 29 pts were all disease-free survival. Conclusions: In pts with locally advanced esophageal SCC, weekly nab-paclitaxel and cisplatin as neoadjuvant chemotherapy achieved a high pathological response rate and R0 resection rate. The toxicity was well tolerated. Evaluation of nab-paclitaxel and cisplatin in randomized trials was warranted. Clinical trial information: NCT01258192.
Molecular profiling in gastric cancer: Examining potential targets for chemotherapy.
Authors: Miura John Thomas , Jayakrishnan Thejus T. , Eastwood Daniel , Johnston Fabian McCartney , Tsai Susan , Christians Kathleen K. , Turaga Kiran , Gamblin T. Clark
Published: February 2017

131

Background: Current NCCN guidelines recommend perioperative epirubicin (E), cisplatin (C), and 5-fluorouracil (F) along with other triple agent derivations as first line therapeutic approaches for operable gastric adenocarcinoma (GC). In this study, we utilized molecular profiling to evaluate expression of chemotherapy targeted biomarkers associated with ECF therapy for GC. Methods: Surgically obtained GC specimens were analyzed by immunohistochemistry for TOP2A, ERCC1, and TS expression (Caris Life Sciences, Phoenix) from 2009-2012. Actionable gene targets were analyzed for mutually exclusive or simultaneous expression. Results: A total of 230 GC specimens were analyzed. The median age of patients was 61 (IQR: 50-72) years with the majority being male (n= 139, 60%). IHC actionable targets included: 60% (n=138) high TOP2A, 55% (n=127) negative ERCC1, and 63% (n=145) negative TS, indicating potential benefit from E, C and F respectively. When analyzing for simultaneous expression profiles of the three genes, only 24 % (n=55) of patients had gene expression levels that suggested sensitivity to all three agents (ECF). Moreover, biomarker results of 6.5% (n=15) of patients demonstrated a potential complete lack of sensitivity to first line ECF therapy. Overall, 61% (n=140) of patients had molecular profiles that indicated sensitivity to two or more agents. Conclusions: Biomarker analysis of GC suggests that there is potential for TOP2A, ERCC1and TS to define patients who have the greatest likelihood of deriving benefit from ECF therapy. 93.5% of patients had the biomarker profile that predicted sensitivity to at least one of these agents. Prospective controlled studies are required to validate the role of TOP2A, TS and ERCC1 in routine management of GC patients.
A prospective observational study on chemotherapy-induced nausea and vomiting for esophageal cancer patients in Japan.
Authors: Yamamoto Sachiko , Ishihara Ryu , Yoshida Naoya , Shimada Hideaki , Noguchi Tsuyoshi , Miyazaki Tatsuya , Yoshikawa Takaki , Yasuda Takushi , Nakajima Yasuaki , Kitagawa Yuko , Baba Hideo , Aiba Keisuke
Published: February 2017

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Background: Chemotherapy-induced nausea and vomiting (CINV) is still one of the major problems in cancer treatment. However detailed profile of CINV in patients with esophageal cancer is not known. Prospective multi-center observational study was conducted to assess the current status of CINV in Japan. Methods: Between May 2011 and December 2012, 193 patients with esophageal cancer who underwent systemic chemotherapy with high (HEC) or moderate emetogenic agents (MEC) were registered. Antiemetic drugs (5-HT3 receptor antagonists, dexamethasone and NK1receptor antagonist) were used to suppress CINV. Occurrence and severity of CINV were assessed with a diary provided to the patients prior to chemotherapy. Acute phase (within 24 hours from the start of chemotherapy) and late phase CINV (24 hours or later) were assessed separately. Multivariate logistic regression analysis was conducted to identify the predictive factors for acute and late phase CINV. Results: Of 193 patients 165 were male and 28 were female. Median age was 66 (range 40-84). HEC and MEC were administered in 180 and 13 patients, respectively. Acute phase nausea and vomiting were observed in 9 (4.7%) and 7 (3.6%) of 193 patients, respectively. Late-phase nausea and vomiting were observed in 75 (38.9%) and 18 (9.3%) of 193 patients, respectively. Risk factors for acute phase nausea, acute phase vomiting, late phase nausea and late-phase vomiting were assessed separately. By multivariate analysis for late-phase vomiting, younger age (Odds ratio 0.523 [every 10 years]; 95%CI 0.278-0.986; p=0.045) and male gender (Odds ratio 5.796; 95%CI 1.806-18.603; p=0.003) were independent predictive factors. By multivariate analyses for acute phase nausea, acute phase vomiting and late-phase nausea, no independent predictive factor was identified. Conclusions: Acute phase CINV was effectively suppressed by antiemetic drugs, while late phase CINV was not sufficiently suppressed. Further intervention to suppress late phase CINV should be considered, especially in high-risk patients. Clinical trial information: UMIN000005971.
Comparison of outcomes for the elderly patients treated with single agent versus doublet regimen as first-line chemotherapy for recurrent or metastatic gastric cancer.
Authors: Sun Der Sheng , Ko Yoon Ho , Jeon Eun Kyoung , Won Hye Sung , Shim Byoung Young , Roh Sang Young , Park Ji Chan , KIM Hoon Kyo , Hong Young Seon , Park Suk Young
Published: February 2017

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Background: Gastric cancer (GC) is a second leading cause of death in Korean elderly cancer patients. Palliative chemotherapy would be an option of treatment in inoperable elderly GC patients for gaining survival time. We analysed the differences between single and doublet first line palliative chemotherapy in elderly GC patients. Methods: More than 70-year-old GC patients treated in the hospitals of the Catholic university of Korea were analysed. Baseline characteristics, first-line chemotherapy regimen, treatment responses, toxicities, time to progression (TTP) and overall survival (OS) were evaluated. Results: From 2005 to 2012, 178 GC patients above 70 years had been treated with palliative chemotherapy with single or doublet regimen. The median age were 77 years (range 70-89) in single regimen group (SG, 70 patients) and 73 years (range 70-81) in doublet regimen group (DG, 108 patients). TS-1 or capecitabine was used in SG, and platinum combined with 5FU or taxane was the most common regimen in DG. The most common response in both group was stable disease. Median relative dose intensity was 92.4% (range 50~100%) in SG and 83.5% (range 43~100%) in DG. Median TTP in SG was 4.40 months (95% CI, 2.85-5.95) and 4.10 months in DG (95% CI, 2.62-5.57, P=0.295). Median OS was 6.90 months (95% CI, 4.20-9.59) in SG, 8.20 months (95% CI, 5.96-10.43, p=0.918) in DG. Hematologic (P=0.03) and non-hematologic toxicities (p=0.061) were more frequent in DG. The common causes to terminate chemotherapy were disease progression in SG and decreased performance status in DG. Conclusions: No significant differences were observed in TTP and OS in both groups, but treatment related hematologic toxicity of SG was less than DG. Single agent treatment would be considered as the option of first line palliative chemotherapy in the elderly more than 70 years.
Carboplatin and paclitaxel as first-line treatment of unresectable or metastatic esophageal or gastric cancer.
Authors: Prithviraj Gopi Kesaria , Baksh Kathryn Anissa , Fulp William J. , Meredith Ken , Hoffe Sarah E. , Shridhar Ravi , Almhanna Khaldoun
Published: February 2017

140

Background: Survival in patients with metastatic esophageal and gastric cancer is dismal. No standard treatment has been established. Carboplatin/paclitaxel is active in both advanced gastric and esophageal cancer. Here we present the data of our single center retrospective analysis. Methods: Between 1998-2013, a total of 134 patients with metastatic esophageal and gastric adenocarcinoma treated with carboplatin/paclitaxel (carboplatin predominantly AUC 5 and paclitaxel predominantly 175 mg/m2) every 3 weeks as first-line therapy were identified. Baseline characteristics, response to therapy, toxicities, and survival in this patient population were evaluated. Overall survival was defined as date from biopsy to death or last follow-up and progression-free survival was defined at time from cycle 1 to death, progression, or last follow-up. Kaplan-Meier curves were fit to estimate overall and progression-free survival. Results: Of the 134 patients evaluated, the median age at diagnosis was 65 years. Overall response rate (ORR) was 62.6% (complete response (CR)- 11%, partial response (PR)- 28%, stable disease (SD)-33%). Median overall survival from date of initial diagnosis was 1.29 years (95% confidence interval [CI] 1.06-1.5). Median progression-free survival from date of initiation of carboplatin and paclitaxel was 0.44 years (95% CI 0.34-0.5). Grade III toxicity occurred in 18.7% of patients. The most common grade III toxicity was neuropathy, present in 3.7% of total study population. Conclusions: In patients with metastatic or unresectable esophageal or gastric cancer, the combination of carboplatin and paclitaxel is well tolerated with comparable overall survival and progression-free survival to existing regimens in this population.
A phase I dose escalation study to evaluate safety and tolerability of cabazitaxel (Cbz) as a single agent in patients (pts) with advanced gastric adenocarcinoma who have failed prior chemotherapy (CT) regimens (GASTANA).
Authors: Kang Yoon-Koo , Ryoo Baek-Yeol , Yoon Shinkyo , Shen Lin , Lee Jooyun , Wei Chenlu , Zhou Yu , Ryu Min-Hee
Published: February 2017

141

Background: Cbz showed antitumor activity in a CT-resistant human gastric cancer xenograft model. The Phase I GASTANA study aimed to determine the safety profile of Cbz in pts with advanced gastric adenocarcinoma who failed prior CT regimens. Methods: Asian pts with metastatic gastric adenocarcinoma failing 2 prior CT regimens received Cbz (single agent, Day 1 of every 3-week cycle) in a standard 3+3 dose escalation design. Dose levels (DL) were 20 mg/m2 (DL 1), 25 mg/m2 (DL 2) and 15 mg/m2 (DL -1). Treatment continued until disease progression or unacceptable toxicity. Prophylactic G-CSF was not permitted at cycle 1. Results: Fifteen pts were evaluable for dose-limiting toxicities (DLTs) at cycle 1. All pts were heavily pretreated (median of 2 prior anticancer regimens), and 11 had prior taxane exposure.At DL 1, no DLTs occurred in any of the first 3 pts. At DL 2, 4 pts were enrolled as 1 pt discontinued prematurely, with only 1 DLT (Grade [Gr] 4 febrile neutropenia [FN]) observed. However, all 4 pts at DL 2 experienced FN, and so 3 more pts were enrolled at DL 1 to further explore safety at this lower DL. Two DLTs (Gr 4 neutropenia > 7 days) occurred in these additional 3 pts. In response, DL -1 was opened, with no DLTs observed in the 6 pts enrolled. The median numbers of cycles were 5 (DL 1), 1.5 (DL 2) and 3 (DL -1). Frequent Gr 3/4 toxicities (safety population, N = 16) included neutropenia (63%) and FN (38%). Best overall responses included 1 partial response (6.3%; DL -1) and 8 stable disease (50%). Conclusions: Due to the unexpectedly high incidence of neutropenia-related complications compared with pts with other cancer types, a further Phase II study of Cbz was put on hold pending further data in pts with gastric cancer. The frequent occurrence of neutropenic complications with Cbz in this study may be attributed in part to the heavily pretreated nature of the pts and the accumulated toxicity of prior taxane therapy. Also, prophylactic G-CSF use after cycle 1 was not mandatory in pts with dose interruptions due to neutropenia, which may have increased the rate of neutropenic complications in subsequent cycles. Clinical trial information: NCT01497964.
Adjuvant chemotherapy after trimodality therapy in locally advanced esophageal cancer.
Authors: Yerramilli Divya , Sohal Davendra , Teitelbaum Ursina R. , Wissel Paul Stephen , Damjanov Nevena , Giantonio Bruce J. , O'Dwyer Peter J. , Plastaras John Peter , Ben-Josef Edgar , Metz James M. , Kucharczuk John , Williams Noel , Apisarnthanarax Smith
Published: February 2017

144

Background: The benefit of adjuvant chemotherapy after preoperative chemoradiation and surgery is unclear in patients with locally advanced esophageal cancer. We studied the toxicities and clinical outcomes in patients treated with or without adjuvant chemotherapy (CTX) after trimodality therapy. Methods: Records of patients with T3+ or N+ esophageal cancer who received preoperative chemoradiation followed by surgical resection from 2003-2013 were reviewed. Patients with postoperative deaths or poor performance status within 3 months after surgery were excluded (n = 13). Tolerability and hematologic toxicities of adjuvant CTX were recorded. Clinical outcomes of patients treated with adjuvant CTX were compared with a cohort of patients who received no further therapy (NFT). Results: Of the 81 trimodality patients included in the study, 53 received CTX and 28 received NFT after surgery. Median follow-up time was 23 months. FOLFOX (34%), cisplatin/5-FU (15%), 5-FU/LV (15%), ECF (13%), and carboplatin/paclitaxel (9%) were the most commonly used adjuvant regimens. Multiple rationales for adjuvant CTX were cited, including pathologic nodal status (32%), favorable pathologic response (61%), and provider preference (51%). Grade III/IV hematologic toxicity occurred in 11% of the CTX group: leukopenia (8%/2%), neutropenia (4%/4%), and thrombocytopenia (2%/0%). Two patients in the CTX group did not complete their prescribed CTX, which was discontinued after 1 cycle. Patient and clinical characteristics between CTX and NFT patients were well-balanced, except for pathologic complete response (pCR) rates (CTX 25% vs. NFT 50%, p=0.03). Three-year OS and DFS were similar between CTX and NFT patients (74% vs 70%, 60% vs. 64%, respectively). In patients who achieved pCR (33% overall), adjuvant CTX was associated with an improved 3-yr OS (86% vs. 62%), but the difference did not reach statistical significance (p=0.22). Distant failures occurred in 11% of the CTX group and 18% of the NFT group. Conclusions: Adjuvant CTX after trimodality therapy in esophageal cancer is feasible and well-tolerated with encouraging clinical outcomes. Further studies are needed to define the role of adjuvant CTX in these patients.
Phase I study of concomitant pemetrexed and cisplatin plus radiation in patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) carcinomas.
Authors: Babiker Hani M. , Kovoor Andrew I. , Green Myke R. , Dragovich Tomislav , Brown Thomas David , Elquza Emad
Published: February 2017

145

Background: For the treatment of esophageal and GEJ carcinomas, weekly cisplatin (20-30 mg/m2 weekly; total dose approximately 100 mg/m2) has demonstrated efficacy and tolerability. Pemetrexed (PEM) in combination with carboplatin and concomitant radiation has also shown activity for treatment of esophageal or lung carcinomas on a tri-weekly schedule, despite tolerability when administered weekly. This is the first phase I trial sought to establish the MTD of bi-weekly PEM in combination with weekly cisplatin and radiation in patients with locally advanced/metastatic esophageal and GEJ carcinomas. Methods: This is a phase I single institution, open-label dose-escalation trial (Fibonacci 3+3). Patients with stage III/IV esophageal cancer received PEM on weeks 1, 3, and 5 at doses of 300, 500, 750 mg/m2 concurrently with weekly cisplatin (20 mg/m2) and 28 daily fractions of radiation (total 50.4 Gy). If 1 or fewer DLTs were observed, the next cohort of patients received an escalated dose. If two or more patients develop DLTs, then dose escalation halted. Primary endpoint was to determine MTD; secondary endpoints included tolerability and preliminary anti-tumor activity using RECIST (Version 1.0). Results: 8 patients enrolled; median age was 72 (range 56-81); 50% were male; ECOG range was 0-2; 50% of patients had adenocarcinoma (AC), remaining patients had squamous cell carcinoma (SCC); 63% and 37% of patients were stage III and IV, respectively. Dose-escalation proceeded to 750 mg/m2 dose. The MTD was determined to be 500 mg/m2 bi-weekly following grade 4 dehydration and esophagitis at 750 mg/m2. DLTs observed were grade 4 thrombosis and grade 3 neutropenia at 300 and 500 mg/m2, respectively. Complete response was observed in 50% of patients (75% stage III SCC), partial response in 25% of patients (100% Stage IV AC), and disease progression in 1 patient (Stage III AC). 38% of patients proceeded to surgery. Conclusions: The combination of bi-weekly pemetrexed 500 mg/m2 and weekly cisplatin concomitantly with radiation demonstrates efficacy in patients with advanced or metastatic GEJ carcinomas with manageable safety profile. Clinical trial information: NCT00701857.
Can induction chemotherapy improve dysphagia in locally advanced esophageal/GEJ cancer?
Authors: Won Elizabeth , Ilson David H. , Herrera Jessica , Janjigian Yelena Yuriy , Ku Geoffrey Yuyat , Rizk Nabil P. , Sarkaria Inderpal S. , Adusumili Prasad S. , Rusch Valerie W. , Bains Manjit S.
Published: February 2017

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Background: Dysphagia is one of the most common presenting symptoms in esophageal cancer (EC) and can lead to significant nutritional decline, which is associated with increased toxicity and poor outcomes. Invasive feeding tubes or endoscopic stents are frequently used to improve nutrition in this setting. We evaluated the role of induction chemotherapy prior to concurrent chemoradiation as presurgical treatment in improving dysphagia. Methods: Retrospective analysis of 4 prospective studies conducted at MSKCC with induction chemotherapy followed by concurrent chemoradiation and surgery in locally advanced esophageal/GEJ cancer. Regimens included cisplatin/paclitaxel, cisplatin/irinotecan, and cisplatin/irinotecan/bevacizumab. Dysphagia was graded prospectively using a validated dysphagia scale. Response of dysphagia and nutritional status to induction chemotherapy was evaluated. Results: Of 161 patients (pts) undergoing induction chemotherapy, [median age 59(21-76), KPS 90 (70-100), 77% adenocarcinoma], 121 (76%) had dysphagia, with 59(37%) having grade 2 dysphagia or higher (20% Stage II, 80% Stage III). 6(4%) required EGD dilatation/stent and none required feeding tube placement prior to treatment. 22% patients had>10% body weight loss prior to treatment and average weight loss in all pts was 4.3kg. After induction chemotherapy, 104 (64%) had improvement in dysphagia. This was associated with a weight gain in 42% of pts. Only 7(4%) had worsening dysphagia after induction chemotherapy: 4/7 required feeding tubes (2% of all pts), 2/7 underwent endoscopic dilatation or stent (1% of all pts). 6/7 of these pts with worsening dysphagia had poor short term outcomes after induction treatment: 2/7 progressive disease, 3/7 unresectable at surgery, 1/7 post-operative death. Conclusions: Induction chemotherapy prior to concurrent chemoradiation for locally advanced esophageal cancer can effectively improve swallowing and nutritional status, while mitigating need for feeding tubes or stents in patients with significant dysphagia. Post-induction dysphagia may be prognostic and merits further investigation.
Incidence and prognostic significance of HER2 overexpression in gastric cancer (GC): A monoinstitutional retrospective analysis.
Authors: De Vita Ferdinando , Orditura Michele , Fabozzi Alessio , Laterza Maria Maddalena , Ventriglia Jole , Savastano Beatrice , Giordano Guido , Petrillo Angelica , Marano Luigi , Di Martino Natale , Morgillo Floriana , Martinelli Erika , Troiani Teresa , Ciardiello Fortunato
Published: February 2017

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Background: HER2 overexpression in GC is reported in 20% of cases; it is considered a negative prognostic factor with a positive predictive value of response to trastuzumab. We reviewed our case records analyzing its clinical significance. Methods: We retrospectively collected the data for patients (pts.) with histologically confirmed GC and tumor specimens. Results: From June 2011 to December 2012 we analyzed HER2 status in 76 pts with metastatic GC. (M/F 50/26, median age 64 years, ECOG performance status 0/1/2 = 59/12/5, G1/G2/G3 = 6.6%/22.4%/71%). In 36.8% of pts. gastric body was the primary tumor site. HER-2 overexpression was observed in 13 pts (17.1%). HER2-positive group had the following characteristics: M/F = 10/3, median age 63 years; Lauren’s histotype: 75% intestinal and 25% diffuse; G1/G2/G3 = 15.4%/30.8%/53.8%; T3-T4 tumors and N+ disease were observed in 46.1% respectively; the primary tumor site was: proximal 38.4%, distal 61.6%. 46.1% of pts with metastatic disease received a first line CT with a median progression free survival (mPFS) of 5 months (range, 3-7) and a median overall survival (mOS) of 9 months (range, 3-23). In HER2-negative group, (N= 63, M/F = 40/23, median age 64 years), 92.1% of pts. Lauren’s histotype: 45.5% intestinal and 54.5% diffuse; G1/G2/G3 = 4.8%/20.6%/74.6%; metastatic disease: 55.5%. T3-T4 tumors were assessed in 65.1% of pts and N+ disease in 61.9%. The primary tumor location was: proximal 38.1%, distal 61.9%. 57.1% with advanced disease received a first line CT with a mPFS of 5.5 months (range, 2-30) and a mOS of 10 months (range, 2-67). No statistically significant differences for mPFS (p: 0.08) and mOS (p: 0.06) were observed between HER2 positive and HER2 negative metastatic patients. Conclusions: According to our experience, HER2 overexpression doesn’t seem to correlate with a worse prognosis. In particular, it is not correlated with a worse histology and higher stage at diagnosis. Furthermore, no differences in terms of mPFS and mOS were observed between HER2 positive and HER2 negative metastatic pts.
A comparison of proton and photon radiotherapy in reducing cardiac exposure for patients receiving radiation therapy for distal and esophagogastric junction cancer.
Authors: Ling Ted Chen-Tai , Slater Jerry Monroe , Mifflin Rachel , Nookala Prashanth , Grove Roger , Ly Anh , Patyal Baldev , Slater Jerry D. , Yang Gary
Published: February 2017

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Background: Recent studies indicate that radiation exposure to heart may have a greater impact on perioperative cardiac morbidities than do other clinical factors. The purpose of this study is to investigate dose distributions of proton and photon treatment plans in patients (pts) with distal and esophagogastric junction (GEJ) carcinoma, focusing specifically on dose reduction to cardiac structures. Methods: Ten pts between 2010 and 2013 were included in this study. Three separate plans were generated for each patient: 3D proton plan, 3D photon plan, and Intensity modulated radiotherapy (IMRT) photon plan. The clinical target volume (CTV) consisted of the pre-operative extent of tumor plus a 10mm manual expansion in all directions. The planning target volume (PTV) was generated by a further expansion on the CTV ranging from 10-15mm. A dose of 50.4Gy given in 28 fractions was delivered to the PTV. All plans were optimized to allow 90% isodose coverage of at least 95% of the PTV. Dose-volume histograms were calculated and analyzed in order to compare plans between the three modalities. ANOVA and two-tailed paired t-tests were performed for all data parameters. Results: The 3D proton plans showed decreased dose to partial volumes of the entire heart, arteries, valves, atria, and ventricles in comparison to both the IMRT and 3D photon plans (see Table). The IMRT plans showed decreased dose delivered to the LAD artery, pericardium, and atria in comparison to the 3D photon plans (see Table). Conclusions: For pts receiving radiation therapy for distal esophageal and GEJ cancer, proton plans are technically feasible with adequate coverage while resulting in lower dose to cardiac structures. This may result in decreased cardiac toxicity and less complications in a multimodality setting. [Table: see text]
Skeletal muscle loss after total gastrectomy, exacerbated by adjuvant chemotherapy.
Authors: Fujitani Kazumasa , Yamaoka Yusuke , Tsujinaka Toshimasa , Yamamoto Kazuyoshi , Hirao Motohiro , Sekimoto Mitsugu
Published: February 2017

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Background: Skeletal muscle loss is associated with physical disability, nosocomial infections, postoperative complications, and decreased survival. Preventing the loss of skeletal muscle mass after gastrectomy may lead to improved outcomes. The aims of this study were to assess changes in skeletal muscle mass after total gastrectomy (TG) and to clarify the clinical factors affecting significant loss of skeletal muscle after TG. Methods: One hundred and two patients undergoing TG for primary gastric cancer underwent abdominal computed tomography (CT) before and 1 year after TG to precisely quantify postoperative changes in skeletal muscle and adipose tissue. Univariate and multivariate logistic regression analyses identified clinical factors contributing to significant loss of skeletal muscle after TG. Results: At 1 year after TG, the mass of both skeletal muscle and adipose tissue was reduced by 6.20±6.80% and 65.8±36.1% of the preoperative values, respectively, and 26 patients (25.5%) showed a significant loss of skeletal muscle of more than 10%. Adjuvant chemotherapy with S-1 for ≥6 months (hazard ratio 26.75, 95% confidence interval 3.511 to 203.9) was identified as the single independent risk factor for a significant loss of skeletal muscle. Conclusions: Skeletal muscle loss was exacerbated by extended adjuvant chemotherapy after TG. Further research should identify appropriate nutritional interventions for maintaining skeletal muscle mass and leading to improved outcomes.
Survival difference in octogenarians with resectable gastric GIST: Surgery versus nonsurgical management.
Authors: Chauhan Dhaval , Burnett Atuhani S. , Rajab Taufiek Konrad , Ernst Philip , McCain Donald A. , Mokashi Suyog A.
Published: February 2017

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Background: Surgical resection of gastric GIST (Gastro-Intestinal Stromal Tumor) in octogenarians is a morbid procedure. There is limited data in literature about the survival of octogenarians after resection of gastric GIST. In this study we focused on the outcome in terms of survival in octogenarians with resectable gastric GIST. Methods: Our study demonstrates that octagenarians as a whole do not experience a survival benefit from surgical resection for HCC. Subgroup analysis, however, may ultimately identify benefit in specific disease stages or patients with fewer comorbidities. Results: The mean survival in the patient group undergoing surgery was 31.30 months and the mean survival in the patients opting for non-surgical management was 33.89 months. The survival benefit in avoiding surgery in this population was 2.59 months with a p-value of <0.0001 and a confidence interval of 1.35 to 3.83 months. Conclusions: The mean survival in the patient group undergoing surgery was 31.30 months and the mean survival in the patients opting for non-surgical management was 33.89 months. The survival benefit in avoiding surgery in this population was 2.59 months with a p-value of <0.0001 and a confidence interval of 1.35 to 3.83 months.
Neutrophil-to-lymphocyte ratio for predicting palliative chemotherapy outcomes in advanced pancreatic cancer patients.
Authors: Xue Peng , Kanai Masashi
Published: February 2017

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Background: Several previous studies reported neutrophil-to-lymphocyte ratio (NLR) could be a promising prognostic factor for patients with cancer. We aimed to determine the prognostic value of NLR in patients with advanced pancreatic cancer (APC) following palliative chemotherapy. Methods: We retrospectively reviewed 253 consecutive APC patients receiving palliative chemotherapy between January 2006 and December 2012. We classified the patients according to the pretreatment NLR values (≤5 or >5) into two groups and investigated the difference in treatment outcomes, including time to treatment failure (TTF) and overall survival (OS); and also analyzed the impact of NLR kinetics after one cycle of chemotherapy on the treatment outcomes. Results: A total of 213 patients had pretreatment NLR values of ≤5 (group A), while 40 patients had an NLR of >5 (group B). TTF and OS were significantly shorter in group B than in group A (3.1 vs. 6.0 months and 8.8 vs. 12.8 months, respectively). After adjustment for putative prognostic factors, including distant metastasis, status of recurrent/unresectable disease, pretreatment carbohydrate antigen 19-9 levels, carcinoembryonic antigen levels, and C-reactive protein levels, using the Cox regression model, elevated pretreatment NLR remained an independent poor prognostic factor for OS (hazard ratio, 1.95; 95% confidence interval, 1.29–2.95; P <0.01). In addition, patients in group B whose NLR dropped to ≤5 before the second cycle of chemotherapy showed longer TTF and OS compared with those whose NLR remained at >5. Conclusions: Our results support the idea that NLR can be a promising prognostic and predictive marker for APC patients receiving palliative chemotherapy.
Postoperative CA19-9 and Glasgow prognostic score to predict early recurrence and poor prognosis in pancreatic cancer patients undergoing adjuvant chemotherapy after surgery.
Authors: Katayama Yusuke , Morinaga Soichiro , Murata Ippei , Asari Masahiro , Numata Koji , Sawazaki Sho , Godai Teni , Higuchi Akio , Shiozawa Manabu , Rino Yasushi , Masuda Munetaka , Akaike Makoto
Published: February 2017

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Background: Despite proven benefit of adjuvant chemotherapy in pancreatic cancer patients, earlyrecurrenceoccursinaconsiderablerate. Therefore, outcomeprediction in these patients remains a challenge. The aim of this study was to determine whether Glasgow Prognostic Score (GPS) and CA19-9 could predict early recurrence in patients undergoing adjuvant chemotherapy after surgery. Methods: 67 pancreatic ductal adenocarcinoma (PDAC) patients underwent curative resection and received adjuvant chemotherapy with gemcitabine after surgery at Kanagawa Cancer Center between 2007 and 2012.The GPS, CA19-9(measured prior to adjuvant therapy) and other clinicopathological factors were retrospectively reviewed. The GPS was calculated from CRP and albumin as follows: patients with both an elevated CRP level (>0.5mg/dl) and hypoalbuminemia (<3.5g/dl) were allocated a score of 2, patients with only one of these biochemical abnormalities were allocated a score of 1, and patients with neither of these abnormalities were allocated a score of 0. Patients were divided to high and low CA19-9 group with cutoff points of 180 U/ml, on the basis of several RCT trials. Univariate and multivariate analyses were performed to identify clinicopathological variables associated with early recurrence (within 6 months after surgery), disease free survival (DFS), and overall survival (OS). Results: Postoperative elevated GPS and CA19-9 were independent risk factors for early recurrence. Positive/negative predictive value (PPV/NPV) were 0.86/0.54 in GPS and 0.84/0.69 in CA19-9 respectively, and in combination use, the PPV/NPV increased to 0.88/0.82. Additionally, the elevated GPS and CA19-9 were independently associated with worse DFS (GPS GHR1.95, 95%CI 1.03-3.69, p=0.042)(CA19-9 GHR5.03, 95%CI 2.05-12.3, p<0.001)and OS (GPS; HR5.29, 95%CI 2.14-13.1, p<0.01, CA19-9 GHR4.79, 95%CI 1.99-11.5, p<0.001). Conclusions: Our results show the potential utility of GPS and CA19-9 as a predictor of early recurrence and prognostic factor in pancreatic cancer.