bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemotherapy and survival benefit in elderly patients with advanced gastric cancer.
Authors: Sugimoto Aya , Nishida Tsutomu , Takahashi Kei , Mukai Kaori , Matsubara Tokuhiro , Hayashi Shiro , Yamamoto Masashi , Nakajima Sachiko , Fukui Koji , Inada Masami
Published: March 2017

45

Background:There is little evidence if chemotherapy (CT) offer survival benefit for elderly patients (EP) with advanced gastric cancer (AGC). Methods: This was a single-centre retrospective study. A total of 118 patients with AGC were hospitalized at our hospital from April 2012 to June 2016. Of them, EP older than 75 years with AGC were eligible for inclusion in the study. Basically, the treatment strategy, chemotherapy (CT) or best supportive care (BSC) were comprehensively decided according to their background. We evaluate the risk factors for survival using the Cox proportional hazard model and explored the optimal indication for CT for EP. Results: Of 118 patients with AGC, 47 patients were enrolled as EP [63% men; mean age, 81 years]. Of EP, 26 patients (55%) received CT and 21 patients received BSC. As first-line CT, 13 patients received S1 monotherapy, the others treated with combination agents. The median overall survival time (MST) was 138 days. There was no significant difference between CT and BSC group (172 vs. 118 days, p = 0. 1087). Univariate analysis revealed the following 5 factors for poor prognosis were significant (defined as p-value < 0.1): Performance status (PS) 3a 2 (HR3.7, 95% CI: 1.5-8.5), C-reactive protein levels 3a 1mg/dL (HR4.0, 95% CI: 1.8-9.4), albumin level < 3g/dL (HR2.1, 95% CI: 1.1-4.3), neutrophil/lymphocyte ratio (NLR) 3a 4 (HR3.7, 95% CI: 1.7-8.5), and diffuse type (HR1.8, 95% CI: 0.9-3.8). As each poor risk factor of 5 and age factor 3a 80 years represents point 1, we calculated total points (0-6) for each patient. Median total points of CT and BSC were 2 and 4, respectively (p = 0.0196). Therefore, we set cut-off point of 3. Then, EP with a total point of 3 and more were classified as high risk group (HR: N = 25) and the others were as low risk group (LR: N = 22). There was significantly longer MST in LR than HR (all EP; 457 vs 105 days, HR: 0.23, p = 0.0002 and EP with CT; 232 vs 113 days, HR:0.26, p = 0.0085). Conclusions: Our findings using the scoring system including 6 factors suggest that EP with a total point 3 and more, were poor prognosis and may not receive benefit from CT for AGC. When judging indication for CT in EP with AGC, this scoring system may be useful, and in case of LR (total point 0-2) may be considered an indication for CT.
Small bowel adenocarcinoma treatment: A single centre experience.
Authors: Bredin Philip , McKendrick Joseph J , Cooray Prasad , Wong Rachel
Published: March 2017

451

Background: Small bowel adenocarcinoma (SBA) has a high mortality. Randomised controlled trials are not feasible due to its rarity, therefore there is no gold standard treatment approach. Surgical resection for early stage disease is the only potentially curative option. Systemic therapeutic options are generally extrapolated from oesophagogastric and colorectal chemotherapy regimens. Methods: This is a retrospective review of treatment and outcomes for SBA patients who attended Eastern Health between 1st January 2010 and 30thJune 2015. Approval was obtained from the Eastern Health Human Research and Ethics Committee. Results: Thirty-six patients with SBA were identified: 16 (44%) duodenal, 12 (33%) ampullary, 6 (17%) jejunal, 2 (6%) terminal ileum, 1 not specified. Median age was 72 and 25 (69%) were male. Stage at diagnosis was as follows: Stage 1 = 4 (11%), Stage 2 = 8 (22%), Stage 3 = 9 (25%) and Stage 4 = 10 (28%). Surgery with curative intent occurred in 19 patients (Whipple’s = 13, wide local excision = 6) of whom 6 received adjuvant (predominantly fluoropyrimidine-based) chemotherapy. One patient died from post-operative complications. At last follow-up, 8 patients remained in complete remission; 11 had relapsed; 3 were lost to follow-up. Three patients had died due to disease. Median relapse-free survival in the curative-intent group was 21.4 months. Median overall survival (OS) has not been reached. Sixteen patients were initially treated with palliative intent. Ten underwent palliative surgery (bypass = 7; resection = 3). Overall, 16 patients commenced palliative chemotherapy, including 8 from the curative-intent group post-relapse. The most commonly used regimen was oxaliplatin plus fluoropyrimidine. Best responses to chemotherapy were partial response = 5 (31%) and stable disease = 4 (25%). Six patients received second-line chemotherapy. Median progression-free survival on first-line chemotherapy was 4.8 months. Median OS was 9.4 months. Conclusions: SBA has a poor prognosis. Although 56% of advanced SBA patients had disease control using chemotherapy extrapolated from other gastrointestinal malignancies, responses were not durable.
The effect of duloxetine on chemotherapy-induced peripheral neuropathy in advanced pancreatic cancer patients receiving gemcitabine plus nab-paclitaxel treatment.
Authors: Suzuki Hidetaka , Shinohara Akira , Ohno Izumi , Mitsunaga Shuichi , Takeno Misaki K , Funazaki Hideki , Kimura Gen , Watanabe Kazuo , Umemoto Kumiko , Sasaki Mitsuhito , Takahashi Hideaki , Imaoka Hiroshi , Hashimoto Yusuke , Ikeda Masafumi , Yamaguchi Masakazu
Published: March 2017

453

Background: Recently, gemcitabine plus nab-paclitaxel (GN) has come to be used frequently as the first-line chemotherapy for advanced pancreatic cancer. It has been reported that chemotherapy-induced peripheral neuropathy (CIPN) associated with nab-paclitaxel (nab-PTX) may impair the quality of life of the patients, and may, moreover, necessitate dose reduction or early cessation of the chemotherapy, thereby potentially impacting patient survival. However, there are no established treatments against CIPN. Several reports have suggested that duloxetine, which has been proved to be highly effective in managing diabetic peripheral neuropathy, is also effective against CIPN induced by platinum agents and taxanes. The aim of this study was to examine the frequency of nab-PTX related CIPN, its various influences, and the efficacy of duloxetine in the management of CIPN. Methods: Data of 121 pancreatic cancer patients who received GN as first chemotherapy between December 2014 and December 2015 at the National Cancer Center Hospital East, Japan, were analyzed retrospectively. Results: The frequency of CIPN of any grade was 60.3% (73 patients) and that of CIPN of grade ≥ 2 was 21.5% (26 patients). Among the patients who showed CIPN, 34 patients received 20-60 mg of duloxetine once daily, and the remaining patients never received it (no duloxetine group). 18 patients were on duloxetine for more than four weeks (the duloxetine group). 8 patients discontinued duloxetine in less than four weeks because of its side effects, such as, nausea, and somnolence. In the duloxetine group, CIPN was improved in 4 patients, and remained non-progressive in 12 patients. The relative dose intensity (RDI) of nab-PTX since the emergence of CIPN in the duloxetine group was higher than that in the no duloxetine group (63.2 % vs. 48.2 %, p = 0.0046). Conclusions: The frequency of nab-PTX related CIPN at our hospital was almost similar to that of previous reports. The results of this study suggest the possibility that duloxetine not only improves nab-PTX-related CIPN, but delays its progression. Therefore, it might contribute to continuing GN with a high RDI for longer periods of time.
Surrogate endpoint in advanced hepatocellular carcinoma treated with molecular targeted therapy: Meta-analysis of randomized controlled trials.
Authors: Lee Kyung-Hun , Lee Dae-Won , Jang Myoung-Jin , Kim Tae-Yong , Han Sae-Won , Oh Do-Youn , Im Seock-Ah , Kim Tae-You
Published: March 2017

454

Background: Time to progression (TTP) is suggested as a reliable endpoint compared to progression free survival (PFS) in the clinical trials of hepatocellular carcinoma (HCC). However, the correlation between TTP and overall survival (OS) has never been studied. Methods: We searched Pubmed and Embase data to obtain data source. Eligible studies were randomized controlled phase III trials which evaluated the efficacy of systemic chemotherapy or molecular targeted therapy in advanced HCC. The association of treatment effects as shown by the hazard ratio (HR) of TTP and OS in each trial was assessed by Spearman rank correlation coefficient ( rs) and linear regression analysis. The association between median TTP and OS was also investigated. Results: Nine studies with a total of 18 treatment arms and 6318 patients were included. Incremental benefit from the study treatment in TTP from each trial was correlated with incremental benefit in OS. The rs value and R2 value between log (HRTTP) and log (HROS) was 0.73 (95% CI 0.12 – 0.94, p = 0.024) and 0.57. The minimum TTP effect to predict a treatment effect on OS was 0.63. Median TTP was associated with median OS. The rs value between TTP and OS was 0.73 (95% confidence interval (CI) 0.40 – 0.89, p < 0.001) and the corresponding R2 was 0.42. Conclusions: Our study results suggest that TTP could be used as a surrogate marker for OS in the clinical trials of advanced HCC. However, the results suggest modest correlation between treatment effects on TTP and OS. Along with individual-level analysis more evidences are needed to confirm our finding.
Can total psoas area predict toxicity after stereotactic body radiation therapy in borderline resectable and locally advanced pancreatic cancers?
Authors: Jin Will , Mellon Eric , Frakes Jessica M. , Murimwa Gilbert , Hodul Pamela Joy , Pimiento Jose Mario , Soares Heloisa P. , Kim Richard D. , Malafa Mokenge Peter , Hoffe Sarah E.
Published: March 2017

455

Background: Total Psoas Area (TPA), a marker of sarcopenia, found clinical utility as an independent predictor of clinical outcomes in gastrointestinal cancers as a proxy for nutritional status. Our study evaluated the relationship of TPA and other proxies of nutrition like Body Mass Index (BMI) and Body Surface Area (BSA) with outcomes in Borderline Resectable Pancreatic Cancer (BRPC) and Locally Advanced Pancreatic Cancer (LAPC) patients receiving Stereotactic Body Radiation Therapy (SBRT). Methods: In retrospective analysis of an IRB approved database, 183 BRPC and LAPC patients treated with SBRT from 2009-2016 met our selection criteria. Patients underwent gemcitabine based or FOLFIRINOX chemotherapy for 3 months prior to SBRT. Eligible patients were those with pre-SBRT planning CT imaging on Pinnacle, a treatment planning system, and an identifiable L4 vertebra. Bilateral psoas muscles were manually contoured at the L4 vertebral level. This area was normalized by patient height (median = 876.505 mm2/m). ROC curves were created for TPA, BMI and BSA. Toxicities were evaluated by binomial logistic regression; survival functions were evaluated by Kaplan-Meier. Significance was set at p < 0.05. Results: Low TPA (OR = 1.903, p = 0.036) and BSA (OR = 1.836 p = 0.048) were predictive of acute toxicities but only TPA was predictive of Grade 3+ acute toxicities (OR = 10.24, p = 0.040). Both findings were independent of tumor resectability. No association was found between TPA/BMI/BSA and late toxicities, overall survival, local progression or local recurrence. However, BRPC patients survived longer (median = 21.98 months) than their LAPC (median = 16.2 months) counterparts (p = 0.002), independent of nutritional status. Conclusions: Pre-SBRT TPA measurement is readily available and more specific than BMI or BSA as a predictor of serious acute radiotoxic complications following SBRT in BRPC/LAPC patients. However, tumor resectability remains as the only predictor of overall survival in this cohort. Whether initial pre-chemo TPA may predict acute toxicity related to chemotherapy and guide individualization of systemic regimen warrants further investigation.
Clinical outcomes of early-stage ampullary carcinoma: A single institutional experience.
Authors: Manne Ashish , Reddy Sushanth , Li Peng , Contreras Carlo M. , Christein John , Vickers Selwyn M. , Heslin Martin , Jacob Rojymon , Wang Thomas N. , Kasi Anup , Posey James , Paluri Ravi Kumar
Published: March 2017

456

Background: Ampullary carcinoma [AC] is a rare malignancy associated with favorable prognosis among pancreatobiliary tumors. Pancreaticoduodenectomy [PDY] is considered to be curative for early stage cancers. The role of adjuvant chemotherapy [CT] or combination chemoradiation [CRT] remains uncertain for stage I/II. In this analysis we reviewed our institution’s experience with AC. Methods: From 2005 to 2015, 62 patients with stage 1 and 2 AC with at least one year follow up after PDY were reviewed. Clinical and pathologic factors and disease status were obtained from chart review. The patients’ demographical and oncological characteristics are summarized. The univariate Cox proportional hazard model was conducted for evaluating the parameters associated with overall survival. Kaplan-Meier method and log-rank was used to compare the time-to-events. Results: Adjuvant treatment was administered in 61%: CT (32%), CRT (29%) 39% surgical alone. The median overall survival [OS] for the study cohort is 60 months with 3 yr OS at 58% and 5 yr OS at 50%. Recurrence noted in 21% of patients. About half of patients surviving five years were alive at 10 years. Lymph node [LN] metastases (57%) predicted worse PFS (HR 2.29, 95% CI (1.13-4.61), p = 0.021) but did not significantly affect OS (HR 1.2, 95% CI (0.84-3.61);p = 0.13). There were no postoperative deaths following surgery.Peri- pancreatic extension [PPE] (20%) and peri-neural invasion [PNI] (16%) was also found to be determinants for poor OS. Current data did not suggest lympho-vascular invasion (24%) predict OS (HR 1.20, 95% CI (0.49, 2.96);p = 0.63 or PFS(HR 1.45 (0.65, 3.20),p = 0.36). When compared to surgery alone adjuvant CT or CRT had no statistically significant difference in terms of PFS (p = 0.53) or OS (p = 0.96). Conclusions: The use of adjuvant treatment may be most useful at improving long-term disease control in patients with high-risk features; however, no significant difference between CT and CRT was demonstrated in our series. This could be due to small sample size and needs further validation in larger cohort. PDY with regional lymphadenectomy is appropriate for early-stage AC, but worst outcomes seen in patients with PPE, PNI and LN involvement.
Analysis of outcomes in metastatic pancreatic cancer: Real-world experience in academic cancer centers.
Authors: Popa Elizabeta C. , Rabinovich Emma , Sohal Davendra , Arbour Kathryn Cecilia , Kim Timothy Suyong , Lu Yao , Christos Paul J. , Khorana Alok A. , Shah Manish A.
Published: March 2017

458

Background: FOLFIRINOX is an active regimen for metastatic pancreatic cancer demonstrating a median overall survival of 11.1 months at the expense of significant treatment-related toxicity. Dose modifications are routinely used in clinical practice however there is little data regarding impact on outcomes and use of second line therapy. In this study we report on the treatment course and outcomes of 92 patients treated at two academic centers. Methods: We conducted an IRB-approved retrospective cohort study of patients with metastatic pancreatic adenocarcinoma treated with first line FOLFIRINOX between 2011 and 2015. Hazard ratios were calculated by Cox proportional hazard models and median survival was estimated using Kaplan-Meier method. Results: 92 patients were identified with a median follow-up of 13.2 months (range 1.2-47.3 mo); 57 males (62%), ECOG 0/1 = 75 (82%). Fifty-four percent required dose reductions of >25% in at least one of three component drugs within the first 6 cycles [95% CI 0.44, 0.65]. Irinotecan was dose reduced in 43% of patients (n=39) while 64% required modification or discontinuation of 5FU. Ten patients (11%) received the full dose of FOLFIRINOX as originally published and 17 patients (25%) discontinued FOLFIRINOX due to toxicity. 60% of patients demonstrated disease control at first imaging assessment after 4-6 cycles of treatment. Median PFS was 7.11 months (95% CI: 5.06-8.51) and OS 13.01 months (95% CI: 9.17-16.95). There was a decrease in PFS and OS associated with a dose reduction of two or more drugs with a HR of 1.68 (95% CI 1.01-2.82, p=0.048) and 1.98 (95% CI 1.08-3.65, p=0.027) respectively. Sixty-seven patients [73%] went on to receive 2nd line therapy [n=67] with 55% receiving gemcitabine-based regimens, the majority with nab-paclitaxel [82%]. Forty-two patients demonstrated progressive disease [63%]. Conclusions: Modest FOLFIRINOX dose modifications are prevalent in clinical practice and are not associated with a reduction in efficacy. A median survival of 13 months with dose modified FOLFIRINOX is compelling. Dose reduction of 2 or more agents was associated with diminished survival. Second line therapy following FOLFIRINOX was associated with modest activity.
FDG PET/CT in pancreatic cancer staging and management: A retrospective study.
Authors: Kinupe Abrahao Ana Beatriz , Ung Yee , Ko Yoo-Joung , Berry Scott R.
Published: March 2017

464

Background: FDG PET/CT scan (PET) has been approved by Cancer Care Ontario since 2011 for pancreatic cancer patients who have potentially resectable disease. A recent prospective study supported the use of PET in patients with a pancreatic mass and showed improved staging accuracy. Herein, we reviewed the outcomes of PET in the disease staging and management of patients with pancreatic mass at a single academic center. Methods: We collected demographics, CA 19-9 level, CT, MRI and PET results of patients with suspicious pancreas mass followed at Sunnybrook Health Sciences Centre from April to August 2011. We reviewed disease staging after CT/MRI and clinical management decision after PET result. We excluded patients with proven non-primary adenocarcinoma of the pancreas from the analysis. Results: In this cohort, 58 patients had PET scans. 14 patients with non-primary adenocarcinoma of the pancreas were excluded. From 44 patients analyzed, 61% of them were females, median age 70, 19 patients had biliary obstruction with biliary drain, CA 19.9 was elevated preoperatively in 27 patients (level above 1400 was seen in 37% of 44 patients), pancreatic mass median SUV = 4.8 and 7 patients had SUV < 2.5 with no FDG avid at the pancreas mass (both biopsy proven). Ten patients were discovered to have metastatic disease on PET. PET results were discordant with the CT/MRI disease staging in 34% of cases. PET revealed metastatic disease in 7 patients with prior CT or MRI considered to be negative for metastasis. PET showed localized disease in 8 patients with suspicious metastasis on CT or MRI. However, none of the patients underwent pancreatic resection. Clinical management was changed after PET results in 80% of patients with discordant PET and CT/MRI results. Conclusions: In this single-centre retrospective analysis, PET results changed the metastatic disease status depicted by CT or MRI in 34% of patients and clinical management was guided by PET results for the majority of those patients. This supports the use of PET as a tool to guide staging and treatment of pancreas cancer.
The surgical Apgar score is an independent prognostic factor in patients with pancreatic cancer undergoing pancreaticoduodenectomy followed by adjuvant chemotherapy.
Authors: Atsumi Yosuke , Aoyama Toru , Kazama Keisuke , Murakawa Masaaki , Shiozawa Manabu , Kobayashi Satoshi , Ueno Makoto , Morimoto Manabu , Yukawa Norio , Oshima Takashi , Yoshikawa Takaki , Rino Yasushi , Masuda Munetaka , Morinaga Soichiro
Published: March 2017

472

Background: We investigated the impact of the surgical Apgar score (SAS) on survival in patients with pancreatic cancer and recurrence after curative surgery followed by adjuvant chemotherapy. Methods: This study included 103 patients who underwent curative surgery for pancreatic cancer between 2005 and 2014. Patients with a SAS of 0-4 were classified into the low SAS group, while those with a SAS of 5-10 were classified into the high SAS group. The risk factors for overall survival (OS) and recurrence-free survival (RFS) were identified. Results: The OS rates at 3 and 5 years after surgery were 23.0% and 14.4%, respectively, in the low SAS group and 32.3% and 21.4%, respectively, in the high SAS group, which was a statistically significant difference (p = 0.039). The RFS rates at 3 and 5 years after surgery were 13.1% and 13.1 %, respectively, in the low SAS group and 21.4% and 19.2%, respectively, in the high SAS group, which was a marginally significant difference (p = 0.100). Multivariate analysis demonstrated that the SAS was a significant independent risk factor for OS and a marginally significant risk factor for RFS. Conclusions: The SAS was a risk factor for OS in patients who underwent curative surgery followed by adjuvant chemotherapy for pancreatic cancer. The surgical procedure, perioperative care and surgical strategy should be carefully planned to improve survival.
Neoadjuvant FOLFIRINOX and/or gemcitabine/nab-paclitaxel for advanced pancreatic adenocarcinoma.
Authors: Turner Keli , Narayanan Sumana , Attwood Kristopher , Hochwald Steven N. , Iyer Renuka V. , Kukar Moshim
Published: March 2017

473

Background: Neoadjuvant chemotherapy is increasingly being utilized for locally advanced (LAPC)/borderline resectable pancreatic cancer (BRPC); however, long term follow up data is sparse. At our institution, we use FOLFIRINOX as the regimen of choice. Gemcitabine (Gem) and nab-Paclitaxel (Abraxane) is utilized in patients not suited for FOLFIRINOX or if they have poor radiographic response and/or develop significant toxicities to FOLFIRINOX. The aim of this study was to report our institutional experience with neoadjuvant therapy for patients with advanced pancreatic cancer. Methods: A retrospective review was performed of all patients with BRPC or LAPC who received FOLFIRINOX (or a modified regimen), Gem/nab-Paclitaxel, or both prior to surgical resection. FOLFIRINOX was typically given for 4 – 6 cycles while gem/nab-Paclitaxel was given for 2 cycles. Results: From January 2011 to December 2015, 39 patients were identified who met the study criteria. Eight patients received FOLFIRINOX alone (median age 62), 20 patients received FOLFIRINOX + Gem/nab-Paclitaxel, and 11 received only Gem/nab-Paclitaxel (median age 72). Eighteen patients (46%) completed the intended cycles of chemotherapy. Twenty two patients had a radiologic and/or biomarker response. Exploration was performed in 25 of 39 (64%) patients of whom 20 (51%) underwent curative resection. Of the 20 resected patients, there were no post-operative deaths. The median tumor size, median lymph node ratio, and R0 resection rates were 2.4 cm, 0, and 85% for the entire cohort. Median follow up was 20.7 months. The median overall survival for the resected cohort was not reached vs 13.5 months in the no resection group; two year overall survival for the resection vs. no resection groups was 87% vs 16% (p < .001). Conclusions: FOLFIRINOX and/or Gemcitabine/nab-Paclitaxel as neoadjuvant therapy for LAPC/BRPC is fairly well tolerated, leads to appreciable rates of margin negative surgical resection, and a significant overall survival advantage.
The utilization of palliative radiation therapy to the liver for hepatocellular carcinoma.
Authors: Onyeama Sara-Jane N. , Hammad Abdulrahman Y , Johnston Fabian McCartney , Gamblin T. Clark , Robbins Jared Rex
Published: March 2017

474

Background: Despite retrospective and prospective clinical trials conveying the efficacy of palliative radiation therapy (RT) to the liver, this modality is not commonly used. The purpose of this project is to evaluate trends, dose schemas, and techniques of palliative RT to the liver in current practice. We aim to identify factors associated with overall survival using patient data from the National Cancer Database (NCDB). Methods: Using the NCDB, we analyzed patients with hepatocellular carcinoma (HCC) diagnosed from 2004-2012 treated with palliative RT. Various patient factors were reviewed and survival analyses were performed. Doses were converted to biological effective dose (BED) to compare the different fractionation schemas. Univariate and multivariate analyses were performed with Kaplan Meier and Cox regression tests. Results: A total of 3,267 HCC patients were identified who were treated with palliative intent. Of these 877 (27%) received radiation therapy and only 138 (4% of total, 16% of RT) received radiation therapy to the liver. For those treated with palliative radiation to the liver, the median age was 61 years. Patients with stages I, II, III and IV disease comprised 15%, 15%, 45%, and 25% respectively. Various dose schema and techniques were used. 38% were treated with advanced radiation techniques (24% stereotactic body radiation therapy (SBRT), 14% Intensity-modulated radiation therapy (IMRT). A total of 79 (57%) patients received 10 or fewer fractions, but 32 (40%) of those were SBRT. The median survival was 4.7 months with 16% mortality at 1 month. On multivariate analysis, stage 3 (HR 2.625, p = 0,013) and stage 4 tumors (HR 2.701, p = 0.018), no chemotherapy (HR 1.743, p = 0.025), and lower radiation dose (HR 0.982, p = 0.003) was associated with worse overall survival. Conclusions: Palliative radiation to the liver is not frequently used in patients with HCC. As a result, there is minimal standardization of dose, modality, or treatment schedule. Better understanding of prognostic factors may help better determine the most appropriate plan for each patient to coordinate treatment length with projected survival.
Incidence of venous thromboembolic events following major pelvic and abdominal surgery for cancer.
Authors: Serrano Aybar Pablo Emilio , Dhamanaskar Kavita , Elit Laurie , Parpia Sameer , Linkins Lori-Ann , Simunovic Marko , Ruo Leyo , Bhandari Mohit , Levine Mark Norman
Published: March 2017

478

Background: The recommendation to administer extended-duration (28 days) venous thromboembolic events (VTE) prophylaxis with low molecular weight heparin in patients undergoing abdominal and pelvic surgery for cancer has not been widely implemented mainly because most studies focus on asymptomatic events with unknown clinical significance. The objective of this study was to determine the post-hospital discharge VTE incidence in these patients who do not receive post-hospital discharge prophylaxis. Methods: Prospective cohort study of patients undergoing abdominal and pelvic operations for cancer within the gastrointestinal tract, hepatobiliary (HPB) system or gynecological organs, with surgery lasting > 1 hour, post-operative stay < 28 days, and not undergoing anticoagulant therapy. Patients were evaluated at 1, 3 and 6 months from index operation for the presence of VTE by means of a screening ultrasound at 28 days and a questionnaire at each follow-up. The proportion with 95% confidence interval (CI) of VTE was calculated. Multivariable logistical regression was performed. Results: Of 284 patients, there were 79 (28%) colorectal, 97 (35%) HPB and 100 (35%) gynecology. All patients received pre- and post-operative in-patient prophylaxis. The proportion of VTE at 6 months was 7%, 95% CI 4.4-10.7 (20 events). Most events occurred between 3-6 months, 4.6%, 95% CI 2.46 – 7.7. Only one event occurred at one month after surgery (0.35%, 95% CI 0.06-1.97). 50% of the cohort had screening ultrasound, all of which were negative. Events were evenly distributed according to the type of surgery. The proportion of patients who died was 6.6%, 95% CI 3.5 – 9.4 (17 patients, 2 of which had a VTE-related death). In the multivariable analysis, post-operative chemotherapy was significantly associated with VTE, odds ratio (OR) 2.74, 95% CI 1.07-6.99. Caprini score was also associated with VTE but was not significant when included in the multivariable analysis, OR 1.19, 95% CI 0.99-1.42. Conclusions: Incidence of VTE following abdominal cancer surgery is low. Most events occur between 3-6 months from surgery. Post-operative chemotherapy is significantly associated with post-hospital discharge VTE.
Sorafenib treatment in recurrent hepatocellular carcinoma post liver transplantation.
Authors: Fallah-Rad Nazanin , Cao Yanshuo , Knox Jennifer J. , Jang Raymond Woo-Jun , Dhani Neesha C. , Sapisochin Gonzalo , Grant David , Greig Paul D , Lilly Leslie , Chen Eric
Published: March 2017

479

Background: Liver transplantation (LT) is a potentially curative treatment for patients (pts) with selective hepatocellular carcinoma (HCC). HCC recurrence post LT is estimated to be 15-20%. Data on systemic therapy post-recurrence is scarce and limited case series suggest that sorafenib (SOR) may have benefit in this population. We reviewed a single center experience with SOR in recurrent HCC post LT. Methods: A retrospective review was conducted on patients with recurrent HCC post LT at University Health Network (UHN) who were treated with SOR. Pt characteristics were collected including age, gender, comorbidities, background liver disease, type of LT, and time to recurrence after LT. Treatment information collected included: initial SOR dose and subsequent adjustments, adverse events (AEs), duration of treatment and survival. Results: Between 2006 and 2016, 24 patients were identified. The average age was 60 years (range: 18-72), most patients were male (20/4), living/cadaveric transplant: 11/13. HCC etiology included hepatitis B (10), alcohol (4), NASH (3), hepatitis C (2), hemochromatosis (2), Budd-Chiari (2) and unknown (1). The average time to recurrence of HCC was 16.08 (range: 1.5-60) months post LT. There was a bimodal time to recurrence with a median of 6 months. SOR starting doses were 200 mg BID in 18 pts, 300 mg BID in 1 and 400 mg BID in 4. 14 pts required dose adjustment due to AEs, mainly relating to fatigue and palmar-plantar syndrome. The median time on treatment was 2.5 (range: 0.25-37) months, 4/24 patients were on treatment > 6 months. The average time to progression on SOR and/or discontinuation due to AEs was 4.30 (+/- 7.2) months. Conclusions: SOR is reasonably tolerated in patients with recurrent HCC post LT, with expected AE profiles. In this small case series, the median time on sorafenib was short and estimated time to progression was shorter than that in non-transplant HCC population. Overall, sorafenib has limited activity in this population, but selected patients may derive extended benefit. Better understanding of responders and investigations of other therapies are needed for this population.
Microarray-based tumor molecular profiling to direct choice of cisplatin plus S-1 or oxaliplatin plus S-1 for advanced gastric cancer: A multicentre, prospective, proof-of-concept phase 2 trial.
Authors: Yong Wei-Peng , Rha Sun Young , Tan Iain B. , Choo Su-Pin , Syn Nicholas , Koh Vivien , Tan Shi Hui , So Jimmy , Shabbir Asim , Tan Chee Seng , Ng Matthew Chau-Hsien , Tai David Wai-Meng , Lee Ming Hui , Wu Jeanie , Yeoh Khay Guan , Tan Patrick Boon Ooi , Kim Hyo Song
Published: March 2017

48

Background: Theoxaliplatin/S-1 (SOX) and cisplatin/S-1 (SP) regimens are interchangeably used in the management of advanced gastric cancer (AGC). We previously developed a classification tool using gene expression signatures which successfully stratified gastric cancer cell lines and primary tumour samples according to their sensitivity to SOX or SP ( Tan et al, Gastroenterology 2011). We now report the first prospective study to evaluate the feasibility and efficacy of using a genomic classifier to tailor treatment in this setting. Methods: Pts with histologically-confirmed locally-advanced, metastatic and recurrent GC were recruited from 3 centres in Singapore and South Korea. Tumours were analysed using the Affymetrix HG-U133 Plus 2.0 array and results were used to classify pts as G1 (oxaliplatin-sensitive), G2 (cisplatin-sensitive) and G3 (status unclear or gene expression not available). G1 and G2 pts were matched to SOX and SP regimens respectively, while G3 pts were assigned SOX. The primary endpoint was best overall response; secondary endpoints were turnaround time and biomarker analyses. Results: Between July 2, 2010, and Apr 2, 2015, we screened 85 AGC pts. 74 pts received at least 1 cycle of treatment and were evaluable for analysis. Median turnaround time was 7 working days (IQR, 5–9). The misclassification rate was 6%. After an initial 30 pts in the G1 subgroup were treated with SOX, subsequent pts ( N = 13) classified as G1 received the SP regimen. The ORR were 44.8%, 8.3%, 26.7% and 55.6% for G1 SOX, G1 SP, G2 SP ( N = 19), G3 SOX ( N = 12) respectively; and was higher in G1 pts treated with SOX compared with SP ( P = 0.033). Post hoc genomic reclassification based on Lei et al (Gastroenterology 2013) confirmed the utility of the metabolic subtype as a predictive marker of benefit from chemotherapy (log rank P value for PFS = 0.004). Conclusions: This bench-to-bedside effort establishes that molecular profiling to direct choice of conventional chemotherapy for AGC is possible within a reasonable timeframe. The clinical utility of our genomic classifiers in question are promising but warrant further investigation. Clinical trial information: NCT01100801.
Modified FOLFIRINOX regimen in advanced biliary tract adenocarcinoma.
Authors: Rauthan Amit , Patil Poonam
Published: March 2017

484

Background: The treatment of advanced biliary tract adenocarcinoma is based on chemotherapy with Gemcitabine with Cisplatin or Oxaliplatin in various combinations. After seeing the high efficacy of FOLFIRINOX regimen in advanced pancreatic cancers, we studied the efficacy and safety of a modified FOLFIRINOX regimen in advanced biliary tract adenocarcinoma. Methods: We retrospectively reviewed patient with advanced biliary tract adenocarcinoma who were treated with modified FOLFIRINOX regimen from April 2013 to March 2016 in a tertiary hospital. The schedule of modified FOLFIRINOX was - Oxaliplatin 85 mg/m2, Irinotecan 150 mg/ m2, Leucovorin 400 mg/m2, and 5 fluorouracil 2400 mg/m2given as a 46-hour continuous infusion, every 2 weeks. All patients received primary prophylactic growth factors. The objective was to evaluate the efficacy and safety of FOLFIRINOX regimen. Results: 20 patients with untreated advanced biliary tract adenocarcinoma were enrolled. The median age was 55 (range 31 to 66 years). All patients had good performance status. 2 patients had a complete response (10%), 8 patients had a partial response (40%), 5 patients had stable disease (25%) and 5 patients had progression (25%). The median progression free survival was 6 months and the median overall survival was 10 months. The major toxicities were grade 3/4 neutropenia (30%), oral mucositis (20%), fatigue (20%) and neuropathy (10%). Dose reduction was required in 30% patients. Conclusions: A modified FOLFIRINOX regimen is an effective regimen in good performance status patients with advanced biliary tract adenocarcinoma. Dose modifications are required to reduce toxicity of the regimen. It needs to be further studied in a phase 3 study in comparison to Gemcitabine based regimens.
Surgical management of pancreatic cancer at a regional health system.
Authors: Chevinsky Aaron , Sanchez Federico Augusto , Weese James Leighton , Papenfuss Wesley , Sahajpal Ajay , Deshur William
Published: March 2017

486

Background: 53,070 new PC in the US (2016) are expected with 41,780 deaths. PC care is evolving, multidisciplinary care, neoadjuvant chemotherapy (NCT) and Radiation (RT) and new adjuvant chemotherapy (ACT) regimens (GTX, GAX, FOLFIRINOX) now improve survival. Methods: Reviewed all surgeries for presumed PC to determine how many pts had NCT, ACT and/or RT, determine how many had RO (margin negative) resection, and proportion of >10 lymph nodes (LNs) removed and subsequent pt outcome. Results: PC was dx in 371 pts in 2014-15 (2014-192, 2015-179). During this period 82 pts were explored for proven or suspected PC. 50 (61%) had PC, and 35(70%) had resection with curative intent (30% unresectable or metastatic). Other DX included cancers of the ampulla (5), bile duct (4), or other cancers (7) and benign disease (16). The majority were performed at 1 hospital (84%). 82% of resections were RO, and 74% had >10 LNs removed. 86% of pts referred for surgery received CT, of which 51% received NAC and 52% received RT (37% pre-operatively). 42% of resected PC pts are alive and 24% are without evidence of disease (NED) up to 31 months post-operatively. 50% of pts with an R0 resection are alive (32% NED) as are 46% of those who had >10 LNs removed (31% NED). 45% of those with both an R0 resection and >10 LNs removed are alive (25% NED) 50% of pts with negative LNs (38% NED) compared to 47% of pts who had positive LNs (27% NED). Conclusions: NAC+/- RT is becoming the standard for most pts with operable or borderline resectable PC, allowing early metastatic disease to be recognized, and a higher probability of RO resection. Predictability of resection can be difficult even with sophisticated preoperative imaging. Interdisciplinary cooperation and treatment planning between medical, surgical and radiation oncology is key to improving survival and allowing for a seamless transition between treatment modalities. Negative surgical margins and negative lns provide the best survival. Only through the integration of pre and post-op therapies can we hope to see continued survival improvements.
Is gemcitabine effective for pancreatic cancer after progression to FOLFIRINOX?
Authors: Fernandes Bruno Melo , Bitton Rafael Caparica , Sabbaga Jorge , Hoff Paulo Marcelo
Published: March 2017

489

Background: Cytotoxic chemotherapy with FOLFIRINOX (5-Fluoracil + Irinotecan + Oxaliplatin) is considered the standard treatment for fit patients (pts) with pancreatic adenocarcinoma. Disease progression after FOLFIRINOX invariably occurs, and there is no definition on the optimal strategy for the second-line treatment of these pts. Gemcitabine is effective for advanced pancreatic cancer as first-line treatment, but its role after FOLFIRINROX progression is unknown. The present study aims to assess the efficacy of gemcitabine for treatment of advanced pancreatic cancer after progression to FOLFIRINOX. Methods: Single-institution, retrospective analysis of all pts consecutively diagnosed with advanced pancreatic cancer between January/2010, and October/2015, who received Gemcitabine as second line chemotherapy after progression to first line chemotherapy with FOLFIRINOX. Tumor responses were assessed through RECIST 1.1. PFS and OS were calculated using Kaplan Meier method. Results: 28 pts were included in our analysis. Median age was 55 years (38-75), and 19 pts (67%) were male. The median ECOG was 1 (0-2). Pts received a median of 9 cycles of FOLFIRINOX as first line treatment (1-27), with an objective (ORR) response rate of 39%. The median number of second-line Gemcitabine cycles was 3 (1-8), with an ORR of 3%, and a 17% rate of disease control (stable disease + partial response). Five patients (18%) discontinued second line Gemcitabine due to toxicities and the remaining 23 (82%) due to disease progression. Median overall survival was 5.6 months (0,36-11,5) and median progression-free survival was 2 months (0.2-7.7). Grade ≥ 3 toxicities with Gemcitabine were experienced by 18% of the patients. No treatment-related deaths were reported. Conclusions: Gemcitabine after progression to FOLFIRINOX presented a modest activity on the present study, with prospective trials being necessary to further assess this issue. Due to the palliative goal of the treatment, with the objective of improving patient´s quality of life, the significant risk of treatment-related adverse events and the low efficacy of Gemcitabine should be considered before prescribing Gemcitabine routinely as a second-line treatment for pancreatic cancer.
Combined analysis of three randomized phase III trials comparing S-1 monotherapy and S-1 combination therapy for first-line treatment of advanced gastric cancer.
Authors: Takeuchi Madoka , Ichikawa Wataru , Shitara Kohei , Sunakawa Yu , Oba Koji , Michimae Hirofumi , Saad Everardo D. , Koizumi Wasaburo , Sakata Yuh , Furukawa Hiroshi , Buyse Marc E. , Takeuchi Masahiro , Fujii Masashi , Nakajima Toshifusa
Published: March 2017

49

Background: S-1 is the gold standard for first line therapy of advanced gastric cancer in Asia. There have been multiple meta-analyses published researching and comparing the efficacy and safety of S-1 monotherapy versus combination1,2. However there has been no analysis using actual trial data. Methods: Actual data from three randomized Phase III trials were combined to compare the efficacy of S-1 Monotherapy and S-1 combination therapy. The START trial, comparing S-1 and combination S-1 with docetaxel, SPIRITS, comparing S-1 and combination S-1 with cisplatin and TOP-002, comparing S-1 and S-1 combination with irinotecan, were merged and combined. For this analysis, the three S-1 arms were combined (n = 642) and the different S-1 combination therapy were combined (n = 617) creating two new treatment arms. The primary efficacy outcome of overall survival, progression free survival and subset analysis of overall survival stratified by baseline characteristics were performed. Results: A total of 1248 patients, including 210 Korean patients from the START were used in the analysis. The median overall survival days for S-1 combination and monotherapy was 382 [209, 648] and 321 [177, 597] and median progression free survival days for S-1 combination and monotherapy was 153 [81, 267] and 122 [61, 204]. Both overall survival (p = 0.0088 HR = 0.85 (0.76,0.96)) and progression free survival ( p = < 0.001 HR = 0.75 (0.67,0.85)) was significantly longer in the combination therapy arm compared to the monotherapy arm. Conclusions:Although there are limitations, the analysis re-confirms that S-1 combination therapy shows to be more efficacious compared to S-1 monotherapy for advanced gastric cancer patients. It must be noted that heterogeneity of the S-1 arm was not carefully considered when combining the S-1 data for the trials. In addition, the results are limited to the Asian (Japanese and Korean) population.
Gemcitabine and S-1 as first-line chemotherapy in patients with metastatic or advanced pancreatic cancer.
Authors: Fang Weijia , Zhao Peng , Zheng Yi , Jiang Weiqin
Published: March 2017

492

Background: Gemcitabine and S-1 are both effective antitumor chemotherapeutic agents for pancreatic cancer. We evaluate the efficacy and safety of the combination of gemcitabine (GEM) and S-1 (GS) as first-line chemotherapy in Chinese patients with metastatic or advanced pancreatic cancer. Methods: Patients with previously untreated metastatic or advanced pancreatic cancer who had measurable lesion(s) were enrolled. Gemcitabine was administered intravenously at a dose of 1,000 mg/m (2) during 30 min on days 1 and 8 and oral S-1 was given twice daily (BSA < 1.25 m(2), 80 mg/day; 1.25 ≤ BSA < 1.50 m(2), 100 mg/day; 1.50 m(2) ≤ BSA, 120 mg/day) on days 1-14 followed by a drug-free interval of 1 week every 21-day cycle. Results: Twenty-five patients were enrolled between 2012 and 2014. The assessed overall response rate was 24 % partial response in 6 patients, 56 % stable disease in 14 patients, and 20 % progressive disease in 5 patients. Sixteen patients (64 %) received second-line chemotherapy. The estimated median progression-free survival and median overall survival times were, respectively, 5.6 months (95 % CI 4.1-6.7 months) and 10.2 months (95 % CI 6.5-14.2 months). The major hematological toxicities were included grade 3/4 leucocytopenia in 8 patients (32 %), grade 3/4 neutropenia in 13 patients (52 %), and one patients (4 %) suffered grade 1 febrile neutropenia. The common grade 3/4 non-hematological toxicity was Anorexia, rash and fatigue, held the proportion of 12%, 16% and 12%, respectively. Conclusions: Gemcitabine and S-1 (GS) combination therapy showed promising activity with acceptable toxicities as first-line chemotherapy in Chinese patients with metastatic or advanced pancreatic cancer.
The Charlson age comorbidity index to predict prognosis in patients with resected pancreatic cancer.
Authors: Asano Tomonari , Fujii Tsutomu , Yamada Suguru , Yabusaki Norimitsu , Ninomiya Go , Nakayama Goro , Sugimoto Hiroyuki , Koike Masahiko , Fujiwara Michitaka , Kodera Yasuhiro
Published: March 2017

495

Background: The Charlson age comorbidity index (CACI) is a useful measure of comorbidity to standardize the evaluation of surgical patients and has been reported to predict postoperative mortality in various cancers. Methods: A total of 379 patients who underwent R0/R1 resection for pancreatic cancer between 2003 and 2014 were enrolled in this study. According to the CACI, the age-adjusted comorbidity index was calculated by weighting individual comorbidities; CACI < 4 was considered the low-CACI group, whereas CACI ≥ 4 was considered the high-CACI group. The correlations between the CACI and clinicopathologic features and survival outcomes were statistically analyzed. Results: The patients with a high CACI were more likely to be old and had higher CA19-9 levels and lower incidences of portal vein resection and blood transfusion. The rate of patients who received chemotherapy was significantly higher in the low-CACI group than in the high-CACI group (87% vs. 69%, P< 0.0001). There was no difference in relapse-free survival (RFS) between the low- and high-CACI groups; however, the overall survival (OS) rate was significantly higher in the low-CACI group than in the high-CACI group ( P= 0.047). Multivariable analysis showed that a high CACI was a predictor of poor survival. In the high-CACI group, patients with high relative dose intensity (RDI) for postoperative adjuvant chemotherapy had significantly better RFS and OS than those with low RDI (both P< 0.0001). Conclusions: The CACI was a significant independent predictor of prognosis and compliance for postoperative adjuvant chemotherapy and could be clinically useful for decision-making in the treatment strategy for pancreatic cancer.