bluuebunny/crossref_metadata_2025 huggingface dataset:
A national survey: Are oncology caregivers getting what they want?
Authors: Patel Kamal , Lis Christopher G. , Rodeghier Mark , Rogers Mark , Gupta Digant
Published: February 2017

91

Background: More than 65 million people will serve as caregivers and about 1.6 million new cancer cases will be diagnosed in the US in 2013. These staggering numbers serve as the impetus on evaluating the quality of medical care. To this end, we conducted a national cancer survey to evaluate caregiver experience with service quality. Methods: An online survey was conducted among a national random sample of 1000 cancer caregivers in Aug-Sept 2012. Importance of 15 service quality items was measured on a 5-point Likert scale ranging from “not at all important” to “extremely important”. Caregiver experience with those 15 service quality items was captured as a yes/no response. Caregiver satisfaction was measured on a 5-point Likert scale ranging from “completely dissatisfied” to “completely satisfied”. Results: The top 3 areas of gaps between importance and experience were ‘having a specific individual to coordinate care’ (33%, p<.01), ‘after-treatment care and support’ (25%, p < 0.01) and ‘providing a comforting and stress-free environment’ (25%, p < 0.01). Among respondents who rated these areas as very/extremely important, only 45%, 63% and 64% experienced it, respectively. Conclusions: These national findings illustrate that information on caregiver satisfaction can be useful for healthcare managers in the exercise of quality assurance and identification of unmet needs. [Table: see text]
Assessing cancer clinic visit time as a marker of quality care.
Authors: Hamel Lauren M. , Eggly Susan , Penner Louis , Chapman Robert , Vichich Jennifer , Tkatch Rifky , Albrecht Terrance Lynn
Published: February 2017

95

Background: The uses of patient time and clinic space in outpatient cancer clinics can be indicators of efficiency and quality of cancer care. Inefficient use of these can have deleterious effects on clinic flow, patient satisfaction, physician/staff morale, and treatment adherence. We tested a unique method of assessing patient time and clinic space in cancer clinics as a measure of cancer care quality. Methods: We video recorded patient occupancy in exam rooms in two outpatient cancer clinics (n = 53) using an IRB-approved, custom-designed unobtrusive recording system (Albrecht et al. 2005) and analyzed use of time. Coders assessed: Patient Occupancy Time (total time in the exam room; POT); Patient Wait Time (time spent in the exam room prior to seeing the oncologist; PWT); and Physician-Patient Interaction Time (PPIT). POT was compared with Scheduled Occupancy Time (from clinic records; SOT) to obtain measures of Discrepancy in Occupancy Time (difference in scheduled exam room time and actual time the patient spent in the exam room; DiOT). Results: Mean POT across both clinics was 82.0 minutes (SD = 36.2), mean PWT was 24.8 minutes (SD = 26.0), and mean PPIT was 31.4 (SD = 14.9) minutes. SOT was only available for Clinic A in which case mean DiOT was 42.6 minutes with a range of 3.5 to 146.5 minutes. Only three cases used the room for less time than originally scheduled. SOT was unrelated to POT, PWT, and PPIT. DiOT was unrelated to PPIT. Conclusions: This method of objectively measuring cancer clinic time can help inform interventions to improve clinic efficiency. We found wait times were lengthy, suggesting an inefficient use of time and space. Importantly, there was no consistent relationship between scheduled and actual time spent in the exam room, reflecting an inefficient use of resources and potential inaccuracy in using scheduled time as a valid measure of quality. [Table: see text]
Predicting survival in stomach cancer: The role of quality-of-life assessment.
Authors: Braun Donald Peter , Gupta Digant , Staren Edgar Donald
Published: February 2017

100

Background: Although assessment of quality of life (QoL) with validated instruments has been increasing in the clinical oncology community, there is little data examining its prognostic significance in stomach cancer. We investigated the association between baseline QoL and survival in stomach cancer. Methods: A consecutive case series of 129 stomach cancer patients treated between Jan 2001 and Dec 2009. QoL was evaluated at baseline using EORTC-QLQ-C30 which incorporates 1 global, 5 functional and 8 symptom scales. Scores range from 0-100 with higher scores in global/functional scales and lower scores in symptom scales indicating better QoL. Patient survival was defined as the time between the date of first patient visit and the date of death from any cause/date of last contact. Cox regression was performed to evaluate the prognostic significance of QoL. Results: Mean age at diagnosis was 60.9 years. 61 patients were newly diagnosed and received their first cancer treatment at our hospital, while 68 were previously treated elsewhere. Stage at diagnosis was I, 12; II, 11; III, 17; and IV, 89. Median overall survival was 8.4 months (95% CI: 5.9-10.7 months). QoL scales predictive of survival upon univariate analysis were global (p=0.001), physical (p=0.002) and fatigue (p=0.02). Upon multivariate analyses, after adjusting for age, gender, stage, and treatment history, global (HR=0.84; 95%CI=0.74, 0.93; p=0.001), physical (HR=0.83; 95%CI=0.73, 0.93; p=0.001) and fatigue (HR=1.10; 95%CI=1.02, 1.18; p=0.02) scales were significantly associated with survival, such that patients with higher (better) global and physical scores and lower (better) fatigue scores had better survival. For both newly diagnosed and previously treated patients, global and physical scales were significantly predictive of survival. Conclusions: Baseline QoL elements that reflect specific functional and symptomatic attributes provide useful prognostic information in stomach cancer. Significantly, this held true for global and physical function for both newly diagnosed and previously treated patients. Such determinations should be considered when designing clinical trials with survival endpoints and may aid decision-making in clinical practice.
The impact of modified Glasgow prognostic score on survival in patients with gastric cancer.
Authors: Goto Hironobu , Tokunaga Masanori , Makuuchi Rie , Tanizawa Yutaka , Bando Etsuro , Kawamura Taiichi , Kinugasa Yusuke , Tsubosa Yasuhiro , Kanemoto Hideyuki , Uesaka Katsuhiko , Terashima Masanori
Published: February 2017

104

Background: Modified Glasgow Prognostic Score (mGPS), based on serum C-reactive protein (CRP) and albumin-levels, was reported to be a good prognosticator for survival in patients with lung cancer. However, the role of mGPS in gastric cancer is still controversial. The aim of this study is to clarify the significance of mGPS as a prognosticator in patients with gastric cancer. Methods: This study included 1,062 patients who underwent gastrectomy for gastric cancer at Shizuoka Cancer Center between September 2002 and December 2006. Patients who received neoadjuvant chemotherapy, and those who had other cancers were excluded from the analysis. mGPS is defined by serum CRP level and serum albumin level. Patients with serum CRP level of 1.0mg/dl or lower were classified to mGPS 0 irrespective to the serum albumin level. Patients with elevated serum CRP level (>1.0mg/dl) were classified to mGPS1 or mGPS2 according to the serum albumin level (mGPS1, albumin≥3.5g/dl; mGPS2, albumin<3.5g/dl). We compared relationships between mGPS and clinicopathological characteristics of patients, the incidence of intra-abdominal infectious complications (Clavien-Dindo grade II or more severe), and overall survival. Results: There were 712 male and 350 female patients. The median age was 65 years old. The number of patients classified to the mGPS0, mGPS1, and mGPS2 group were 970 (91.3%), 59 (5.6%), and 33 (3.1%), respectively. The incidences of intra-abdominal infectious complications were 27.1% in mGPS1, and 24.3% in mGPS2, and were significantly higher than that in mGPS0 (9.5%, P< 0.001). Overall five-year survival rates were 74.6% in mGPS0, 61.4% in mGPS1, and 34.6% in mGPS2. The overall survival was significantly worse in patients with mGPS2 than those with mGPS0 or mGPS1 (P<0.001). Conclusions: mGPS was correlated with the incidence of intra-abdominal infectious complications. In addition, mGPS was found to be a prognosticator for survival in patients with gastric cancer. Preoperative nutritional support may lead to reduced incidence of surgical complications and improved survival outcome after gastrectomy in patients with gastric cancer.
Impact of pathologic complete response to preoperative docetaxel-based chemotherapy on disease-free survival in esophagogastric adenocarcinoma.
Authors: Lorenzen Sylvie , Homann Nils , Al-Batran Salah-Eddin , Lordick Florian , Schuster Tibor , Peschel Christian , Pauligk Claudia , Thuss-Patience Peter C.
Published: February 2017

123

Background: The aim of this study was to evaluate the impact of pathologic complete response (pCR) on outcome in patients with gastric or esophagogastric junction (EGJ) adenocarcinoma after treatment with preoperative docetaxel/platin /fluoropyrimidine based chemotherapy. Methods: This analysis of a prospective database identified patients who received at least one cycle of preoperative docetaxel/platin/fluoropyrimidine-based chemotherapy for at least T3/4 and N+ disease. An association of pretreatment clinicopathologic factors and pCR was investigated. Overall survival, disease-free survival and disease-specific survival were analyzed according to the achievement of a pCR. Results: A total of 120 patients received preoperative docetaxel-based chemotherapy and underwent subsequent resection of the primary tumor. 15 pts (13%) had distant metastases (M1) at initial diagnosis. 18 patients achieved a pCR in the primary (15%). Median follow-up was 41.1months. The median DFS and OS for the whole population was 24.1 and 48.6 months, respectively. DFS was significantly prolonged in pCR compared to non-pCR patients (HR 2.65, 95% CI 1.1- to 6.2; 3-year DFS probability: 71.8%±10.7 and 37.7%±5.1, respectively, P-value log-rank test=0.018). For patients with a pCR the median DFS was not reached and for those without pCR the median DFS was 22.1 months. Patients with a pCR showed an almost 50% decreased risk of death compared to non-pCR patients (HR 0.53; 95%CI 0.23 to 1.23; P=0.131). Disease-specific survival (DSS) was significantly longer in pCR vs. non-pCR patients (HR 0.188, 95%CI 0.046-to 0.77; P= 0.021). Two clinicopathological parameters were identified as predictors of pCR: tumor localization in the EGJ (p=0.019) and intestinal tumor type according to Laurén’s classification (p=0.042). Conclusions: The analysis confirms that pCR to neoadjuvant chemotherapy is a predictor of favourable patient outcome in patients with gastric or EGJ adenocarcinoma. Tumor location in the EGJ and intestinal histology represent factors significantly associated with the achievement of pCR.
Neoadjuvant DCF in resectable esophageal cancer: Single-center experience.
Authors: Noronha Vanita , Gulia Seema , Joshi Amit , Prabhash Kumar
Published: February 2017

124

Background: Despite improvement in surgical techniques and peri-operative care, the 5 yr OS in esophageal cancer is 10%. RCTs comparing NACT to surgery alone have demonstrated a significant increase in median survival from 13 months to 17 months. We aimed at studying impact of DCF NACT. Methods: Retrospective analysis of prospective database of patients with locally advanced esophageal cancer. All patients had ECOG performance status of 0 to 1, with no uncontrolled comorbidities. Chemotherapy consisted of 3 cycles of standard DCF (Docetaxel 75 mg/m2 on day1, Cisplatin 75 mg/m2 on day 1 and 5 fluorouracil 750mg/m2 as a continuous intravenous infusion for 5 days) with growth factors and prophylactic antibiotics were administered. Following chemotherapy, a restaging scan was performed. If disease was deemed resectable, surgery was performed. Patients were followed up after surgery and then 3-monthly. Toxicity was graded according to CTCAE v.4.03, response was calculated as per RECIST 1.1 and statistics were by simple percentages. OS and PFS calculated by Kaplan–Meier method. Results: Between February 2010 and April 2012, there were 22 patients who received neoadjuvant DCF chemotherapy. Male to female ratio 1.2. Median age 44.5 years (range: 32- 63 yrs). 20 patients had squamous histology and 2 had adenocarcinoma. Middle one third of esophagus was the primary site in 54.5%. Response rate: CR-32%, PR-55%, SD-9% and PD-4.5%. 16 (73%) patients underwent R0 resections, 1-R1 resection, 3-R2 resection, 1 was deemed unresectable preoperatively and treated with chemo-radiotherapy and 1 had CR but surgery was postponed due to hyperthyroidism. 7 patients (31.8%) had pathologic complete remission. Toxicities grade (3/ 4) included neutropenia (77.3%), febrile neutropenia (86.4%), diarrhea (45.5%), hyponatremia (45.5%), fatigue (18.2%), and mucositis (13.5%). Dose reduction due to toxicities was done in 50% patients. At a median follow up period of 13 months (range 4-31 months), the PFS is 81.8% and OS is 90.9%. Conclusions: Response rate to DCF is 87%, with a pathologic CR rate of 32%. The complete responders appear to have a durable benefit; all remain disease free at the last date of follow up. Our initial data looks promising but follow up period is short.
Efficacy and safety of endoscopic submucosal dissection for superficial squamous esophageal neoplasia: A systematic review and meta-analysis of the literature.
Authors: Kim Joon Sung , Kim Byung-Wook , Ji Jeong-Seon , Lee Bo-In , Choi Hwang
Published: February 2017

127

Background: The number of ESD candidates with esophageal neoplasia has increased with the recent development of endoscopy. Increasing number of studies has recently reported the application of endoscopic submucosal dissection (ESD) for treatment of esophageal lesions. However, most of these series were retrospective and single center studies that included only a relatively small number of cases. The aim of this systematic review and meta-analysis was to assess the efficacy and safety of ESD for esophageal lesions. Methods: Comprehensive literature searches were performed on studies that reported ESD for the removal of esophageal dysplasia or esophageal squamous cell carcinoma. MEDLINE, EMBASE and the Cochrane Library were searched using the primary keywords “endoscopic submucosal dissection”, “esophagus” and “esophageal”. Statistical analyses were executed by the aid of Comprehensive Meta-analysis software version 2. Results: A total of 17 studies were identified. Meta-analysis revealed pooled estimates of complete cure en bloc resection as 89.7% (95%CI 85%-93%; I2 =54.6%) and pooled estimates of en bloc resection as 96% (95%CI;93%-98%; I2=21.2). The pooled estimates of complications of ESD such as bleeding, perforation and stenosis were 2%, 5%, 12%, respectively. Subgroup analysis was performed by grouping studies into two groups. Complete cure en bloc resection was 92.4% for studies from Japan and 81.6% for studies from other countries than Japan. Conclusions: ESD appeared to be an extremely effective technique to achieve complete cure en bloc resection of superficial squamous esophageal neoplasia. The very low rate of complications also shows the potential safety of this approach. However, the resection rates were statistically different for studies from Japan and for studies from other countries. Standardization of techniques and equipment may be needed before ESD can be widely accepted for treatment of superficial squamous esophageal neoplasms.
Retrospective study regarding the efficacy of second- or higher-line chemotherapy (CT) of patients in advanced or recurrent gastric cancer (ARGC) after the failure of S-1 or S-1 combination chemotherapy (S+α).
Authors: Kobayashi Kazuma , Negoro Yuji , Hata Yasuhiro , Morita Sojiro , Aiba Keisuke , Tsuji Akihito
Published: February 2017

129

Background: At the 2007 ASCO meeting, two RCTs from Japan showed that S-1 (S) and S-1/CDDP (S+P) therapy now are an accepted standard 1st-line chemotherapeutic regimens for ARGC. Today in Japan, S+α are the mainstay CTs for ARGC. However, it is important to acquire a longer survival for ARGC and therefore development of a 2nd or higher line CT after S+α failure is thus required. At the 2012 ASCO meeting, WJOG4007G trial showed that weekly PTX was regarded as a temporary standard 2nd-line CT for ARGC after the failure of S+P. However, some clinical questions to appropriate 2nd-line CT have been unsolved. The present study set out to identify the factors, which make it appropriate to perform the CT after S+α failure, and to examine the validity of this treatment. Methods: Sixty-one pts with ARGC who failed to sufficiently respond to S+α therapy between Dec. 2004 and May 2010 were retrospectively reviewed. Results: The patient characteristics were: mean age, 63.8 y.o.; sex, M/F=42/19; patient status: unresectable: 35, non-curative operation: 17 and postoperative recurrence: 9. The initial CT regimens consisted of S: 32, S+α: 29. The 2nd-line CT regimens included Taxanes (TA): 40, CPT-11 (IRI): 20, S+α: 1. The median number of 2nd or higher treatment courses was 2 (1-6). The RR of 2nd-line CT was 24.6%. The mTTF and MST since the 2nd-line CT was administered were 112 days and 311 days, respectively. The transition rate to 3rd-line was 65.6%. The OS since the S+α administration significantly correlated with the TTF of S+α (p<0.001), while the OS since the 2nd-line CT administration (2nd OS) was independent of the TTF of S+α. The 2nd OS did not correlate with either the specific type of 2nd-line CT. However, the 2nd OS of pts receiving both TA and IRI was significantly longer than ones only either TA or IRI (p=0.0012). Conclusions: The findings of this study suggest that the addition of a 2nd or higher line CT is expected to result in a longer survival for pts with ARGC, even when the anti-tumor effect was deemed to be insufficient following the S+α therapy, and that the strategy of using all available agents in the treatment course of ARGC might be needed.
A retrospective study of neoadjuvant DCF (docetaxel, cisplatin, 5-fluorouracil) for locally advanced gastric or gastro-esophageal junction adenocarcinoma (GC).
Authors: Castellanos Raquel , Ernani Vinicius , Bayraktar Ulas Darda , Portelance Lorraine , Montero Alberto J. , Rocha Lima Caio Max S. , Hosein Peter Joel
Published: February 2017

138

Background: Perioperative chemotherapy (chemo) with ECF (epirubicin/cisplatin/5-fluorouracil) plus surgery improved survival over surgery alone in GC in the MAGIC trial. Herein we report our experience using DCF in the perioperative setting in patients (pts) with locally advanced GC. Methods: We conducted a retrospective IRB-approved study of pts with potentially resectable locally advanced GC who were treated with DCF with neoadjuvant intent. Pts received 3 cycles of preoperative (pre-op) DCF every 3 weeks, followed by surgery, then 3 cycles of postoperative (post-op) DCF. Patients with a poor pathologic response could be changed to radiation (RT) or an alternate chemo regimen postop. Results: A total of 41 pts were identified, 24 with gastric and 17 with GEJ adenocarcinoma. All pts received at least 1 cycle of DCF and 78% received at least 3 cycles pre-op. Five pts progressed during neoadjuvant DCF, 4 were unresectable by CT after neoadjuvant DCF and 2 were lost to follow-up. The remaining 30 pts had surgery with curative intent. Post-op, 2 pts were lost to follow-up, 12 received DCF (with 6 of these also receiving RT), 11 received a different chemo regimen due to a poor response to neoadjuvant DCF (including 6 pts who also received RT). Two pts received post-op RT only. The median PFS was 16.8 months (95% CI 7.7 - 25.9) and the median OS was 26.9 months (95% CI 18.7–35.1). The PFS was longer for pts who had a radiological or pathological response to neoadjuvant DCF (log rank p = 0.005 and 0.02 respectively) and for pts who received DCF post-op (log rank p = 0.005). Among pts who did not receive DCF post-op, there was no survival difference between the pts who were switched to an alternative chemo or chemoRT regimen post-op compared to those who received no further therapy. The most common chemo-related adverse events were anemia (27% grade 3 or 4), nausea/vomiting (17% G3 or 4), and febrile neutropenia (12%). Conclusions: The DCF regimen is well tolerated in locally advanced GC. Patients who do not have a good response (either radiologic or pathologic) to pre-op DCF appear to have a poor prognosis regardless of the post-op treatment given.
Phase II trial of sorafenib (S) and erlotinib (E) in unresectable pancreas cancer (UPC): Final results and correlative findings.
Authors: Cardin Dana Backlund , Goff Laura Williams , Chan Emily , Holloway Melanie , McClanahan Pamela , Shyr Yu , Li Chung-I , Meyer Krista , Grigorieva Julia , Berlin Jordan
Published: February 2017

191

Background: The MAP kinase pathway plays a central role in PC pathogenesis. Blockade of this pathway at multiple levels using S and E is attractive mechanistically. S also targets VEGF receptors. Evidence suggests that dual blockade of both EGFR and VEGF pathways has potential for additive, if not synergistic, effects. This phase II trial was designed to evaluate the efficacy of the combination of S and E in patients (pts) with UPC. An exploratory correlative study analyzing pre-treatment serum samples using a proteomic mass-spectrometry test (VeriStrat), previously shown to correlate with outcomes in lung cancer pts treated with E or the combination of E and S, was performed to evaluate the possible clinical utility of the test in pts with UPC. Methods: Pts with UPC received S 400mg daily along with E 150mg daily as primarily second-line therapy (first-line was allowed). Primary endpoint was 8-week progression free survival (PFS) rate. Pre-treatment serum sample analysis by proteomic test was done blinded to clinical and outcome data; the endpoints were PFS and overall survival (OS). Difference between groups was assessed using log-rank p values; hazard ratios (HR) were obtained from Cox proportional hazards models. Results: Thirty-seven pts received study drugs and were included in the survival analysis. Eight-week PFS rate 0.47 (95% CI 0.32-0.67) did not meet the primary endpoint of a rate of ≥ 0.70. Thirty two pts were included in the correlative analysis. VeriStrat “Good” pts had superior PFS and OS compared to VeriStrat “Poor” pts (Table). Conclusions: This study did not meet the primary endpoint and this drug combination will not be further pursued. In this small retrospective analysis the proteomic classification was significantly associated with clinical outcomes (PFS and OS), meriting further evaluation. This will include a companion study to an ongoing phase I study evaluating gemcitabine, erlotinib and dasatinib in UPC (NCT01660971). Clinical trial information: NCT00837876. [Table: see text]
Phase II/III clinical trial with VEGFR2-epitope peptide and gemcitabine for patients with locally advanced, metastatic, or unresectable pancreatic cancer: Pegasus-PC study.
Authors: Yamaue Hiroki , Tani Masaji , Miyazawa Motoki , Yamao Kenji , Mizuno Nobumasa , Okusaka Takuji , Ueno Hideki , Boku Narikazu , Fukutomi Akira , Ishii Hiroshi , Ohkawa Shinichi , Furukawa Masayuki , Maguchi Hiroyuki , Ikeda Masafumi , Nishio Kazuto , Ohashi Yasuo , Tsunoda Takuya
Published: February 2017

223

Background: Gemcitabine is a key drug for treating pancreatic cancer; however, with the limitation in clinical benefits, the development of another potent therapeutic was strongly called for. VEGF-receptor 2 (VEGFR2: Flk-1 and KDR) is an essential target for tumor angiogenesis, and we have executed a phase I clinical trial using gemcitabine and VEGFR2-peptide (Cancer Sci 2010). Based on promising phase I trial results, a multicenter, randomized, placebo-controlled, double-blind phase II/III clinical trial has been conducted (UMIN000001664). Methods: The eligibility criteria are: locally advanced, metastatic, or unresectable pancreatic cancer. Patients were allocated to either VEGFR2 peptide (OTS102) + gemcitabine group or placebo + gemcitabine in 2:1 ratio by dynamic allocation method. The primary endpoint was overall survival. The Harrington-Fleming test, with the weight proportional to cumulative death probability, was used for the statistical analysis under the time-lagged effect of immunotherapy. Sample size was estimated presuming the effects will be observed from the time point of 50% cumulative survival rate. Assuming a type I error alpha (two-sided) level of 5% and a power of 80% or more for 50%-60% reduction of hazard, sample size necessary was estimated as 100 patients for the active group and 50 patients for the placebo group. Results: No statistically significant survival time prolongation was observed in OTS102 add-on group (p = 0.92). However, the three-month landmark analysis revealed significant interaction between the treatment and reports of indurations or ulcerations (p = 0.005) in add-on group, and if patients survived for over three months, grade 1-2 patients had better survival than grade 0 (1-year survival: 47%(23/49) and 22%(9/44), respectively) in add-on group. Conclusions: Despite the lack of survival time prolongation by OTS102 add-on to gemcitabine therapy, patients experienced injection site indurations or ulcerations may have better survival, suggesting new prognostic factors for VEGFR2-epitope peptide. Our results indicate the possibility of epitope peptide used in cocktail therapies. Clinical trial information: UMIN000001664.
Palliative reoperation for recurrent periampullary adenocarcinoma: Primum non nocere?
Authors: Boone Brian A. , Moser Arthur J. , Mock Brady K. , Johnson Paul J. , Dvorchik Igor , Zeh Herbert J. , Marsh J. Wallis
Published: February 2017

257

Background: A majority of patients with periampullary cancer develop local or metastatic recurrence despite successful R0 resection. Many of these patients present with unresectable, symptomatic recurrence and selective surgical palliation is often considered. While the literature has addressed palliative surgery in primary periampullary cancer, no study has evaluated outcomes in recurrent disease. We examined the outcomes of surgical palliation for recurrent periampullary cancer. Methods: This is a retrospective study of patients who underwent palliative reoperation for recurrent periampullary cancer from 1990-2011. Morbidity and mortality was followed to 90 days. Complications were graded according to the Clavien-Dindo classification. Kaplan Meier was used to evaluate survival. Results: Fourteen patients underwent palliative reoperation following successful primary resection for periampullary adenocarcinoma. Indications for reoperation were small bowel obstruction (n=10, 71%), gastric outlet obstruction (2, 14.3%), spinal compression (1, 7.1%) and symptomatic pleural effusion (1, 7.1%). For patients undergoing abdominal reoperation, 2 (17%) underwent incomplete resection, 5 (42%) underwent bypass and 5 (42%) underwent lysis of adhesions. Median estimated blood loss was 100 mL. Median length of stay was 12 days. Postoperative complications affected 8 (57%) patients, with 75% ≥ Grade 3 complications. 3 (38%) patients died during their operative stay. 30 day and 90 day postoperative mortality were 43% and 86% respectively. Median survival was 45 days (range: 4-100). There was improved median survival in patients with an interval of more than 9 months prior to undergoing reoperation (57 vs. 11 days, p <0.05). There was no difference in survival based on pancreatic versus ampullary cancer (45 vs. 43 days, p=0.096), or local versus metastatic site of recurrence (57 vs. 34 days, p=0.30). Conclusions: Palliative reoperation for periampullary cancer recurrence is associated with high morbidity and dismal survival. Non-operative palliation should be strongly considered in patients who have undergone prior resection and present with symptomatic recurrence.
Safety and efficacy of resin 90Y-microspheres in 548 patients with colorectal liver metastases progressing on systemic chemotherapy.
Authors: Kennedy Andrew S. , Ball David , Cohen Steven J. , Cohn Michael , Coldwell Douglas M. , Drooz Alain , Ehrenwald Edward , Kanani Samir , Rose Steven C. , Nutting Charles W. , Moeslein Fred M , Savin Michael , Schirm Sabine , Putnam Samuel G. , Sharma Navesh K , Wang Eric
Published: February 2017

264

Background: 90Y-microspheres (radioembolization) are administered via the hepatic artery following failure of one or more lines of fluoropyrimidine-based systemic chemotherapy, with or without biologic agents in colorectal carcinoma metastatic (mCRC) to the liver. Methods: A retrospective review of consecutively treated patients with mCRC from July 2002 to December 2011 at 11 U.S. institutions was conducted. Data on background characteristics, prior chemotherapy, surgery/ablation, radiotherapy, vascular procedures, 90Y treatment (SIR-Spheres; Sirtex Medical), subsequent adverse events (grade 3+) and survival were documented. Median follow-up was 8.5 mo. (IQR 4.3–15.6). Trends in the occurrence of adverse events for patients receiving 1, 2, or 3+ lines of systemic chemotherapy were evaluated by Fisher’s Exact. Kaplan Meier estimates compared the overall survival of patients across lines of chemotherapy. Results: A total of 548 patients were included; majority were male (61%), Caucasian (66%), mean age 61 years; received median of 2 (range 1–6) lines of chemotherapy prior to 90Y therapy. Median tumor/liver ratio at 90Y therapy was 15% (IQR 23%). Median 90Y activity administered was 1.18 GBq (IQR 0.48). Hospital stay duration was <24 hours for most cases (97.8%). The most common adverse events (grade 3+) following 90Y therapy included: abdominal pain 6.6% (n=36), GI ulceration 1.8% (10), nausea 1.5% (8), vomiting 1.6% (9), fatigue 6.0% (33), ascites 3.5% (19), hyperbilirubinemia 5.7% (31) and anorexia 1.1% (6). A comparison of 1, 2 and 3+ lines of chemotherapy versus grade 3+ adverse events to 3 months post-90Y therapy revealed no significant difference (p>0.05). Corresponding median survivals (95% CI) were 13.0 (10.5–14.6), 9.0 (7.8–11.0) and 8.1 (6.4–9.3) months, respectively (p<0.0001). Conclusions: 90Y microsphere therapy appears to have a favorable risk/benefit ratio in patients with mCRC who have failed prior systemic chemotherapy. These data show a clinically relevant survival benefit for 90Y therapy in patients not responding to chemotherapy, including those heavily pre-treated (3+ lines).
Effect of upregulation of ANGPT2 by DARPP-32 on angioenesis in gastric cancer.
Authors: Chen Zheng , Zhu Shoumin , Hong Jun , Belkhiri Abbes , El-Rifai Wael
Published: February 2017

34

Background: Gastric cancer is the second most frequent cause of cancer-related death worldwide. We have previously shown that Dopamine and cAMP regulated phosphoprotein MW 32 kDa (DARPP-32) and its truncated form (t-DARPP) are overexpressed in two-thirds of gastric adenocarcinomas. Angiopoietin 2 (ANGPT2) -TIE2 signaling is a secreted protein that acts as a key regulator of adult vascular homeostasis and blood vessel formation. Methods: The expression of DARPP-32 in the multi-step carcinogenesis cascade was examined using IHC analysis on 533 samples. ANGPT2 mRNA level was detected by real-time quantitative polymerase chain reaction (PCR) in 30 gastric cancer tissue samples and 30 normal gastric tissues. DARPP-32 and t-DARPP were over expressed using stable and transient expression in AGS and MKN-28 gastric cancer cell lines, lacking endogenous DARPP-32 to investigate the induction of ANGPT2 by DARPP-32 and t-DARPP. Results: We found that ANGPT2 was higher expressed in cancer samples than normal tissues from RT-PCR. We also found gastric cancer tissue samples expressed higher DARPP-32 and t-DARPP mRNA than normal gastric tissues. Over expression of DARPP-32 and t-DARPP led to a significant increase of the mRNA and protein levels of ANGPT2 as compared to empty vector control. Consistent with these findings, the condition media from DARPP-32 and t-DARRP expressing cells showed high levels of secreted ANGPT-2. TNF-α treatment induced the levels of ANGPT2 further in DARPP-32 and t-DARPP expressing cells as compared to control. Of note, this increase in NF-κB activity was significantly higher in DARPP-32 and t-DARPP expressing cells as compared to control. To confirm the angiogenic potential, we used condition media from DARPP-32 and t-DARPP expressing AGS cells and demonstrated its ability to stimulate tube formation on human umbilical vein endothelial cells (HUVEC) models than the condition medium from control cells. Conclusions: Our results suggest that DARPP-32 and t-DARPP over expression may participate in the angiogenesis of gastric cancer. The in vitro studies indicate that DARPP-32 and t-DARPP play a role in up regulation of ANGPT2 in gastric cancer cells by enhancing the TNF-α induced activation of NF-κB signaling pathway.
Real-world comparative economics of a 12-gene assay for prognosis in stage II colon cancer.
Authors: Alberts Steven R. , Yu Tiffany , Behrens Robert J. , Renfro Lindsay Anne , Srivastava Geetika , Soori Gamini S. , Dakhil Shaker R. , Mowat Rex Bradford , Kuebler J. Phillip , Kim George P. , Mazurczak Miroslaw , Hornberger John C.
Published: February 2017

391

Background: Prior economic analysis of a 12-gene assay (Oncotype DX), compared with patterns of care reported in the NCCN database of patients with stage II, T3, DNA mismatch repair proficient (MMR-P) colon cancer, predicted that the assay would save medical costs and improve patient well-being (Hornberger et al., Value Health, 2012). This study assessed the validity of those findings with actual adjuvant chemotherapy (aCT) recommendations. Methods: Outcomes and costs were estimated for patients with stage II, T3, MMR-P colon cancer using a Markov model. A study of 141 patients from 17 sites in the Mayo Clinic Cancer Research Consortium collected data on aCT recommended before and after knowledge of the 12-gene assay results (Srivastava et al. abstract). Quality-adjusted life years (QALY) and medical resource use after recurrence were computed using guideline-validated state-transition probability estimation methods. Risk of progression and incidence of adverse events with different aCT regimens were based on published literature. Drug and administration costs for aCT were obtained from 2012 Medicare fee schedules. One-way sensitivity analyses were conducted to evaluate parameter influence on economic impact. Results: After receiving the 12-gene assay results, physician recommendations in favor of aCT decreased 22% (95% CI 11%-32%; McNemar test p<0.001) from 73 (52%) to 42 (30%) patients. Oxaliplatin aCT and 5-FU monotherapy recommendations each declined 11%. Average aCT costs decreased $5,738 for drugs, $668 for administration, and $3,268 for adverse events management. Overall, average total direct medical costs decreased $4,203. The net effect on average patient well-being was a gain of 0.083 QALYs. Total medical costs are most influenced by change in aCT recommendations, 5-FU monotherapy efficacy, and oxaliplatin drug acquisition cost. Savings are expected to persist even if the cost of oxaliplatin dropped by >75% due to generic substitution. Conclusions: The 12-gene assayhas been shown to alter aCT recommendations for patients with stage II, T3, MMR-P colon cancer. This study provides real-world confirmation that these changes in aCT reduce direct medical costs and improve patient well-being.
Randomized phase II study of erlotinib (ERL) in two different schedules with concomitant modified XELOX in the first-line treatment of metastatic colorectal cancer (mCRC): Correlation with serial serum levels of amphiregulin (AMR) and transforming growth factor receptor-alpha (TGFa).
Authors: Chan Anthony T. C. , Chan Stephen Lam , Ho Wing Ming , Lau Wilson , Mo Frankie , Hui Edwin P. , Chan Charles , Poon Annette , Dattatray Rasalkar , Wong S. C. Cesar , To Ka Fai , King Ann Dorothy , Ahuja Anil Tejbhan , Ma Brigette
Published: February 2017

425

Background: This study evaluated the feasibility of combining XELOX with erlotinib in a 2 different schedules, and the prognostic significance of serum AMR and TGFa in previously untreated mCRC. Methods: Eligible patients (Pt) were randomized to the ‘continuous’ arm (Arm CON) [ERL 100mg daily D1-21, oxaliplatin (Ox) 130mg/m2 D1, capecitabine (Xe) 825mg/m2 bd D1-14, q3w], or the ‘intermittent’ arm (Arm INT) [ERL 150mg daily at alternate day on D 1-14, then 150mg daily on D15-21, Ox 130mg/m2 on D1, Xe 750mg/m2bd on D1-14, in a q3w]. Serum levels of AMR, TGFa and CEA were determined serially. KRAS mutation was determined from archived tumors. Results: 60 pts were randomized and there was no difference in the baseline characteristics between the 2 arms. Of the 58 pts evaluated for response, the overall response rates (ORR) were 56.3% (Arm CON) and 66.3% (Arm INT). At a median follow-up of 2.8 yrs, the median overall survival (OS) of pts in Arm CON and Arm INT were 9 m (95% CI: 7.2-18m) and 10.3m (95% CI: 7.2-15.6 m) respectively. KRAS mutation (n = 44 tumors) status did not predict ORR or survival. Gr 3-4 toxicities occurred in 53.3% (Arm CON) and 46.7% (Arm INT) of pts. Multivariate analysis showed that elevated baseline serum TGFa and AMR were independent predictors of inferior PFS and OS, respectively. Post-treatment drop in serum TGFa was associated with shorter OS and PFS, while a drop in serum TGFa and a rise in serum AMR were associated with inferior PFS and OS, respectively. Conclusions: Although there was no statistical difference in the toxicity and efficacy of the 2 arms, the ORR from XELOX and intermittent ERL compared favorably with historic control. KRAS mutation status was not predictive. Serum TGFa and AMR have prognostic significance in this cohort and further prospective studies are warranted. Clinical trial information: NCT01243047.
Assessment of the quality of the pathological evaluation of total mesorectal excision specimens: Differences in evaluation between local pathologists and a review committee in the context of an improvement project.
Authors: Demetter Pieter , Vandendael Tamara , Sempoux Christine , Ectors Nadine , Cuvelier Claude , Nagy Nathalie , Hoorens Anne , Jouret-Mourin Anne ,   PROCARE
Published: February 2017

481

Background: Data on quality control of the pathologic evaluation of total mesorectal excision specimens are scarce. Differences between evaluation by local pathologists participating in PROCARE, a Belgian improvement project on rectal cancer, and a review panel were assessed. Methods: Based on photographic material and histopathology slides, a review committee of pathologists with a particular interest in colorectal pathology re-evaluated the mesorectal plane, the circumferential resection margin (CRM), the tumour differentiation grade, the (y)pT stage and the tumour regression grade (according to Dworak) in 444 cases (354 low anterior resection and 90 abdomino-perineal resection specimens). Results: The surgical plane was reported in 89% and the CRM in 88% of cases by the local pathologist. The median number of lymph nodes harvested in patients undergoing long-course neoadjuvant radiochemotherapy was 11, whereas this was 14 in the other patients. The review committee downgraded the surgical plane of 17% of patients from (intra)mesorectal to intramuscular, and upgraded it in 27% from intramuscular to (intra)mesorectal. Tumour differentiation grade, T stage and tumour regression grade differed between local pathologists and review committee in 15%, 10% and 38%, respectively. T stage was upgraded in 8% of cases, mainly from T2 to T3. Tumour regression was judged by the review panel to be less advanced in 15% of cases. Conclusions: Acknowledging some shortcomings (comparison between a photographical evaluation and an evaluation on a fresh specimen), this study gives a realistic view of clinical practice. There are differences in interpretation with regard to macroscopic and microscopic analysis of TME specimens. These findings indicate a need for more objective and reproducible criteria in histopathology. Being aware of this is a first step for improvement.
High pathologic response rate of hepatic colorectal cancer metastases (HCRM) following neoadjuvant bevacizumab (Bev)-based treatment (tx).
Authors: Pietrantonio Filippo , Coppa Jorgelina Clara , Miceli Rosalba , Milione Massimo , Perrone Federica , Fanetti Giuseppe , Christian Cotsoglou , Melotti Flavia , Di Bartolomeo Maria , Mazzaferro Vincenzo , Mariani Luigi , Pellegrinelli Alessio , Bertan Claudia , Biondani Pamela , De Braud Filippo G.
Published: February 2017

529

Background: Pathologic response of HCRM to neoadjuvant tx is associated to better outcome. In retrospective analyses Bev-based tx improved tumor regression grade (TRG), while cetuximab (Cmab) increased RECIST response and R0 resections in prospective studies. The aim of this analysis was to assess the effect of Bev vs Cmab-based tx in terms of HCRM pathological response and outcome. Methods: Fifty-eight pts with HCRM were resected at National cancer Institute of Milan from 2007 to 2012 following Bev (n=30) or Cmab (n=28) based neoadjuvant tx. Pathological response was classified from TRG 1 for pathological complete response (pCR), to TRG5 for no response; TRG 1-3, for histological response; TRG 4-5 for scarce/no response (Rubbia-Brandt L, Ann Oncol 2007). Results: KRAS missing in 9 pts (3 Bev/6 Cmab), mutated in 18 pts (60%) in Bev vs 4 (14%) in Cmab group.Median number of resected metastases: 4.6 vs 3.9; mean TRG: 2.9 (2.2-4) in Bev vs 3.8 (3-5) in Cmab group (p=0.04 at Kruskal-Wallis test). Pathological response rate was higher for Bev vs Cmab (70% vs 39%; p=0.037 at Chi-square test). Bev also increased pCRs (20% vs 0%, p=0.024 at Fisher’s test). With generalized estimating equation for all resected nodules, mean TRG was lower in Bev vs Cmab group: 2.6 (2-4) vs 3.7 (3-4), p<0.001. At univariate analysis, no PFS and OS difference was observed according to tx. Multivariable Cox models shown below: Conclusions: Bev-based tx obtained an excellent pathological response rate, despite the high proportion of KRAS mutated tumors, and further prospective confirmation of these data is planned. [Table: see text]
Patient-reported outcomes from a phase III multicenter, randomized, double-blind, placebo-controlled trial of gefitinib versus placebo in esophageal cancer progressing after chemotherapy: Cancer Oesophagus Gefitinib (COG).
Authors: Dutton Susan J. , Blazeby Jane M. , Petty Russell D. , Mansoor Wasat , Thompson Joyce , Harrison Mark , Abbas Haider , Dahle-Smith Asa , Chatterjee Anirban , Falk Stephen , Garcia-Alonso Angel , Fyfe David Walter , Hubner Richard , Gamble Tina , Peachey Lynnda , Harvey Christine , Julier Patrick , Jankowski Janusz , Midgley Rachel , Ferry David R. ,   COG Collaborative Group
Published: February 2017

6

Background: There are no randomised trials of 2nd line chemotherapy for esophageal cancer. The phase III COG trial of gefitinib versus placebo in patients with esophageal cancer progressing after chemotherapy did not show significant overall survival (OS) benefit, however the trial incorporated patient reported outcomes (PRO) using validated tools. The PRO data are therefore critical to inform practice and the initial results are presented here. Methods: Adults with measurable/evaluable metastatic esophageal or types I/II junctional adeno or squamous cell carcinoma progressing after prior chemotherapy, with performance status 0-2 were randomised 1:1 to 500mg gefitinib (G) or placebo (P), treated until progression. Primary outcome: OS. Secondary outcomes include safety, PFS, PRO (assessed by EORTC QLQ-C30 and EORTC QLQ-OG25 at baseline 4, 8 and 12 weeks until progression) and predictive biomarkers. Pre-specified PRO domains were global quality of life, dysphagia, eating and odynophagia. Analysis by ANCOVA of change in PRO at 4 weeks adjusted for baseline. Results: 450 patients were recruited from 51 UK centres and no difference in OS was detected. There was evidence that PFS was better in the intervention arm (P 35 days, G 49 days; HR=0.795, 95%CI 0.66, 0.96, p=0.017). Questionnaire compliance rates were excellent at baseline (94%) and at 4 weeks (77%). Patients in the gefitinib arm reported significantly better social function (9.26; 95%CI 1.94 to 16.58; p=0.013) and significantly fewer problems with odynophagia (-8.61; 95%CI -14.49 to -2.73; p=0.004), constipation (-15.24; 95%CI -22.83 to -7.65; p=0.0001) and speech (-10.40; 95%CI -16.13 to -4.67; p=0.0004) than patients receiving placebo but more problems with diarrhoea (19.23; 95%CI 11.79 to 26.27; p<0.0001). All other PRO domains were similar between the two groups. Conclusions: Gefitinib did not improve overall survival in esophageal cancer patients after chemotherapy however there was significant PFS improvement and improvement in quality of life and palliation of symptoms albeit with an excess of diarrhoea. Clinical trial information: 29580179.
Phase II trial of miniDOX (reduced-dose docetaxel/oxaliplatin/capecitabine) in “suboptimal” patients with advanced gastric cancer (AGC): TTD 08-02.
Authors: Rivera Fernando , Massuti Bartomeu , Salcedo Matilde , Sastre Javier , Martínez-Galán Joaquina , Valladares-Ayerbes Manuel , Serrano Raquel , Garcia De Paredes Marisa , Tabernero Josep , Galan M. Carmen , Mozo Jose Luis Manzano , Diaz Rubio Eduardo , Conde Veronica , Reboredo Margarita , Vazquez Silvia , Layos Romero Laura , Pascual Francisco Javier Ramos , Aranda Enrique
Published: February 2017

87

Background: Chemotherapy has improved overall survival (OS) in patients (p) with AGC and docetaxel (D), oxaliplatin (O) and capecitabine (X), have shown consistent activity in this setting. We defined "Suboptimal" p as those with PS ECOG-2 and/or weight loss 10-25% and/or age ≥70 years. This population is usually underrepresented in AGC clinical trials. Methods: We explored in 43 previously untreated "suboptimal" AGC p the "miniDOX" regimen (D: 40 mg/m2 iv, d1; O: 80 mg/m2 iv d1; C: 625 mg/m2 po bid, d1 to 21, every 21d; after 6 courses only C was maintained). D and O dose were allowed to be increased to 45 and 90 mg/m2 respectively (dose level +1) and to 50 and 100 mg/m2 (level +2) if less than grade 2 toxicity after the first 2 courses. One p that did not received any dose of chemotherapy, was included in the ITT efficacy analysis but not in the safety analysis. Primary endpoint was Response Rate (RR), Toxicity, Progression Free Survival (PFS) and OS were secondary objectives. Results: p characteristics: PS ECOG-2:12 p, Weigh loss 10-25%:23 p; median age 73.3 years (40-87); 32 males; locally advanced:8 p/metastatic:35 p; Primary site:Gastric 32 p/ EGJ 11; In 19 p the dose of D and O were increased to level +1 and in 8 of them to level +2. Worst toxicity per p (Grade 3-4): neutropenia: 5 p (3 of them with febrile neutropenia); pulmonary embolism (PE):4 p (3 of them suffered sudden death and the PE was suspected but not confirmed); diarrhea:9 p; paronychia:2 p; CVA:1 p; renal failure:1 p (this p suffered infection/bacteriemia without neutropenia and died); hand-foot syndrome:4 p and asthenia:5 p. Response: CR:1 p, PR:23 p (RR: 56%), SD:12 p, Progression:3 p, No determined:4 p; With a median follow-up of 27 months, 36 p have died (toxicity:4 p, progressive disease:32 p). Median and 1 year actuarial PFS and OS are 5.5 months/19% and 13.3 months/54% respectively. Conclusions: Although relevant the toxicity of miniDOX has been found, its activity is encouraging in "suboptimal" pts with AGC and this combination should be further investigated in this setting. Clinical trial information: NCT00733616.