bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regional and practice setting differences in the management of EGFR rash among mCRC patients treated with panitumumab: Results of a national survey in the United States.
Authors: Hool Kristina , Lowe Kimberly , Garawin Tamer , Bergstresser Rachel , Kafatos George , McNamara Michelle , Collins Seth , Bach Bruce A. 
Published: September 2018

e15170 Background: Skin toxicity can be a limiting factor for the use of anti-EGFR therapies, such as panitumumab, and there are currently no standard practice guidelines for rash management in the United States (U.S.). This study aimed to evaluate if there were regional or practice setting differences in strategies used among oncologists to manage EGFR rash, including utilization of dermatologic and nursing support. Methods: 250 practicing oncologists who had treated at least three mCRC patients with panitumumab in the last year completed an online survey to report their opinions and perceptions regarding skin toxicity management strategies. Participants reported if they were affiliated with an academic/university or a community-based practice. Participants were stratified into years of practice post-fellowship ( < 10 and > 10 years) and geographic region of primary practice (West, Midwest, Northeast, Southern U.S.). Results: Oncologists surveyed did not consistently utilize dermatology support. 40% (n = 99) of practicing oncologists surveyed reported consulting a dermatologist “occasionally.” Less than 5% reported “always” consulting dermatology and 6% reported “never” utilizing dermatology support. Utilization of dermatology support varied significantly by region. In the Southern US more oncologists reported “never” consulting dermatology while in the Midwest more oncologists reported “always” utilizing dermatology support (p = 0.05). While dermatology was inconsistently utilized, oncologists frequently utilized nursing support to minimize and manage anti-EGFR skin toxicity. 73% (n = 182) of oncologists engaged nursing support to “monitor skin toxicity during treatment” and 70% (n = 175) of oncologists had nursing support to “educate on skin toxicity prior to starting treatment.” Conclusions: While nursing support is consistently utilized by oncologists in the management of EGFR rash in mCRC patients treated with panitumumab, use of dermatology support was inconsistent and varied significantly by region. This lack of consistency in toxicity management strategies highlights the need for increased physician education.
HIPEC in treatment of gastric cancer with high risk of carcinomatosis: Russians Regional Centre experience.
Authors: Privalov Alexey , Vazenin Andrey , Antonov Andrey 
Published: September 2018

e15501 Background: Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is a treatment method in patients with gastric cancer having a high risk of development of peritoneal carcinomatosis which can improve treatment results. Methods: HIPEC in a "prophylactic" setting in gastric patients having a high risk of peritoneal carcinomatosis development has been applied in our centre since 2015. This method was used in cases of diffuse type poor-differentiated tumor histology , massive tumor invasion of the stomach serosa and relatively young age of the patient. A “closed” HIPEC technique, with 3 inflow and 3 outflow catheters, RAND HT performer and 7 liters of saline solution with 200 mg cisplatinum was performed. Up to this moment we have treated 8 patients with gastric surgery added by HIPEC. There were 4 men and 4 women. Median age was 48 years. In 2 cases distal subtotal gastric resection was performed, in other 6 cases - total gastrectomy with a D2 lymph nodes dissection. In 2 cases was also performed an edge resection of the pancreas. 2 procedures were performed in cases with ovarian metastases and local diaphragm canceromatosis, with complete cytoreduction. Median surgery time was 4 hours. Results: There was no mortality in early postoperative period, with 25% morbidity. In one case a severe postoperative pancreonecrosis occured which required several re-operations. In one case there has been an acute renal failure, after 3 dialyse sessions the renal function was recovered. Median post-operative hospital stay was 20 days. Two patients are alive without progression on 14 and 23 months respectively. One patient developed a local anastomotic recurrence, no other progression was found, and anastomosis extirpation was performed. Patients having ovarian metastases and local canceromatosis progressed in 6 months, in other cases progression was found in 6 to 12 months. Conclusions: The use of HIPEC doesn't result in elevation of complications or mortality rate. It shows a trend to improve the results of treatment gastric cancer. In cases of already existing canceromatosis the effectiveness of HIPEC is doubtful.
Apatinib for chemotherapy-refractory advanced metastatic gastric cancer: A cost-effective analysis compared with conventional chemotherapy.
Authors: Wu Bin , Li Te , Xu Yuejuan , Zhao Gang 
Published: September 2018

e15531 Background: Apatinib can improve survival in patients with metastatic gastric cancer (mGC) who do not respond to or who experience progression with second-line chemotherapy. Apatinib Patient Assistance Program (PAP) is implemented for Chinese patients. A cost-effective analysis is needed for apatinib with PAP. Methods: A Markov model was developed to simulate the clinical course of typical patients with chemotherapy-refractory mGC. We estimated 10-year quality-adjusted life-years (QALY), costs, and incremental cost-effectiveness ratios (ICER). The Clinical efficacy and safety were derived from the pivotal phase II and III trials of apatinib. Direct costs were estimated from the perspective of Chinese health care system. One-way and probabilistic sensitivity analyses were conducted. Scenario analysis for Patient Assistance Program (PAP) was checked. Results: Baseline analysis showed that the apatinib increased the cost and QALYs by $7,859 and 0.191, respectively, relative to conventional chemotherapy, resulting in an ICER of $40,997/QALY gained. The ICER was $21,132/QALY when 3+X PAP (paying for 3 months following free donation until disease progressed) was available. Probabilistic sensitivity analyses confirmed that apatinib with 3+X PAP achieved nearly two 2/3 likelihood of cost-effectiveness under the Chinese willingness-to-pay threshold of $ 22,200 per QALY gained. One-way sensitivity analyses found that the utility of progression-free survival was the most influential factor with respect to the robustness of the model. Budget impact analysis estimated that the annual increase in fiscal expenditures would be approximately 0.45 million dollars. Conclusions: Our analysis suggests that apatinib is likely to be cost-effective in patients with chemotherapy-refractory mGC when 3+X PAP is available.
Molecular profiling-selected treatment in metastatic gastric and oesophageal cancer: Real-life clinical experience.
Authors: Purim Ofer , Beny Alexander , Inbar Moshe J. , Brenner Baruch , Dudnik Elizabeth , Bokstein Felix , Temper Mark , Limon Dror , Sarid David , Semenisty Valeriya , Brenner Ronen Mordechay , Peretz Tamar , Idelevich Efraim , Pelles Sharon , Meirovitz Amichay , Russell Kenneth , Voss Andreas , Dvir Addie , Soussan-Gutman Lior , Hubert Ayala 
Published: September 2018

e15537 Background: We evaluated real-life clinical experience with molecular profiling (MP)-guided therapy in metastatic gastric and oesophageal cancer in Israel Methods: This multicenter retrospective cohort study included patients with metastatic gastric or oesophageal cancer who were treated in the participating institutions and underwent MP (Caris Molecular Intelligence). Treatment was considered as having benefit if the ratio between the longest progression-free survival (PFS) post MP and the last PFS pre MP was ≥1.3. The null hypothesis was that ≤15% of patients gain such benefit. Results: The analysis included 46 patients (61% males; median age, 58 years; 57% with poorly-differentiated tumours). At least one actionable (i.e., predictive of response to a specific therapy) biomarker was identified per patient. Immunohistochemistry was performed on all samples and identified 1-8 (median: 3) biomarkers per patient (most commonly: low TS, high TOPO1, high TOP2A). Twenty-eight patients received therapy post MP (1-4 lines). In the 1st-line post MP, 5 patients (18%) achieved partial response and 5 (18%) stable disease; the median (range) PFS was 4.3 (0.4-38.5) months. Twenty-four patients were evaluable for PFS ratio analysis; in 7 (29.2%), the ratio was ≥1.3. In one-sided exact binomial test vs. the null hypothesis, P = 0.019; therefore, the null hypothesis was rejected. Conclusions: Our findings demonstrated that implementing MP is feasible and that MP could provide clinical benefit for a considerable proportion (~30%) of patients with metastatic gastric or oesophageal cancer.
Phase II XELOX + lapatinib treatment in HER2-amplified gastric cancer: Monitoring with serial cell-free DNA genomics.
Authors: Lee Jeeyun , Kim Seung Tae , Banks Kimberly , Lanman Richard B. , Park Joon Oh , Park Young Suk , Lim Ho Yeong , Lee Hyuk , Kim Kyoung-Mee , Kang Won Ki 
Published: September 2018

e15610 Background: It is important to identify biomarkers that predict which patients may benefit from the dual EGFR/HER2 inhibitor, lapatinib in HER2 amplified GC. Methods: We evaluated the efficacy of combining lapatinib with capecitabine and oxaliplatin (CapeOx) treatment in patients with previously untreated, HER2-overexpressing gastric cancer GC with limited metastases. A parallel biomarker study was conducted by IHC, and cfDNA NGS. Results: Thirty-two HER2-overexpressing AGC patients were enrolled between May 2013 – Nov 2015. Complete response (CR) was confirmed in 7 patients. Of 32 patients, we were able to obtain 10 primary-metastasis paired samples. Of 10 paired samples, 6 patients had concordant HER2 results and 4 patients had discordant HER2 positivity between primary and metastasis. Of discordant patients, patient #22 had gastric HER2 2+ but synchronous SCN LN HER2 0 and had progressive disease after one cycle. All of the patients with H index > 200 had tumor reductions. Beyond HER2 overexpression, other genomic alterations (e.g., CRKL amplification) associated with differences in lapatinib sensitivity and/or PFS. One patient with de novo resistance to lapatinib had HER2 and CRKL co-amplifications. We confirmed CRKL overexpression in both tumor tissues and established matched patient-derived cell (PDC) lines via IHC. CRKL knockdown reversed HER2-overexpressed PDC sensitivity to lapatinib. Lastly, serial cfDNA genomics from 11 enrolled patients change during lapatinib treatment demonstrates emergence of MET amplification and myc amplification at progression. Conclusions: This is the first report to show 1) CRKL amplification as a culprit molecule for lapatinib resistance; 2) cfDNA genomics demonstrating tumor evolution during lapatinib treatment which can potentially guide to subsequent treatment. Clinical trial information: 02015169.
Identification of patient population with longer survival when treated with S-1 plus cisplatin via predictive enrichment strategy analysis of the FLAGS phase III trial.
Authors: Ajani Jaffer A. , Takeuchi Madoka , Takeuchi Masahiro 
Published: September 2018

e15612 Background: FLAGS, a randomized phase III trial, compared S-1, an oral fluoropyrimidine, plus cisplatin (SP) with 5-fluorouracil plus cisplatin (FP) in the first-line treatment for advanced gastric cancer (AGC). The purpose of this analysis was to discover a clinically significant covariate model using the Predictive Enrichment Strategy Analysis (PESA) to identify a patient population most likely to benefit from the treatment. Methods: PESA is a newly introduced concept proposed by the United States Food and Drug Administration and provides robust results. Consensus-based 15 clinical covariates were selected for enrichment analysis and a large cohort with no missing data (889 patients) was analyzed for model development. The models generated were cross-validated 200 times and ROC-AUC for the Cox PH model with the selected variables by the enrichment analysis were computed. Results: ECOGPerformance status (PS = 1) was the strongest covariate and most significant in identifying the enrichment group for SP. In the population with PS = 1, the OS in the SP group was significantly longer than the FP group (Hazard Ratio [HR] = 0.798, 95%CI = (0.66-0.96) p = 0.0166) Other covariates with high potential to be associated with benefit included: diffuse-type histology, presence of peritoneal metastases, and the lack of liver metastases. Various models using different combinations of the covariates were compared using ROC-AUC analysis and found that the model including all four covariates had the best ROC-AUC (0.566, 95%CI = (0.546-0.587)). Conclusions: PESA identified a cross-validated, robust model (PS, diffuse histology, peritoneal mets, and no liver mets). This patient population is associated with improved OS in Advanced Gastric Cancer patients who receive SP. An independent validation of this model will be carried out with data derived from the DIGEST trial. NCT00400179
Efficacy and safety of FOLFIRINOX in advanced cholangiocarcinoma.
Authors: Kim Byung Moon , Armenio Vincent Anthony 
Published: September 2018

e15620 Background: Cholangiocarcinomas are invasive carcinomas of uncommon diagnosis and often diagnosed at an advanced and metastatic stage. To this date, there is limited clinical data to support a standard chemotherapy regimen. Single agent systemic chemotherapy such as 5FU or gemcitabine achieves ORR of about 25% while combination regimens including 5-FU, adriamycin, mitomycin or 5-FU and cisplatin has OS of less than a year. Methods: We conducted a single institution retrospective analysis of survival, response and toxicity in patients with advanced or metastatic hepatobiliary carcinoma who had been treated with fluoropyrimidine, irinotecan, and oxaliplatin combination therapy from October 2008 to May 2015. Primary endpoint was PFS measured as the date of first treatment until evidence of clinical progression and/or death. Secondary endpoint was toxicity based on National Cancer Institute Common Terminology Criteria for Adverse Events(NCI CTCAE) for non hematologic and hematologic toxicity. Patients were age greater or equal to 18, histologically confirmed, locally advanced unresectable or metastatic adenocarcinoma of the biliary tract (intrahepatic or extrahepatic cholangiocarcinoma), treatment naive or one prior chemotherapy, ECOG performance status of 0-2. Results: Twenty-five patients were eligible for analysis. A total of six patients (24%) received FOLFIRINOX either as first line therapy or as a second line therapy after progression on gemcitabine based regimen. The median PFS was 5 months (151 days). The median OS was about 14.5 months (436 days). Frequency of hematologic toxicity was more common than non-hematologic toxicity. Thrombocytopenia (67%) and nausea (67%) were the most common adverse event. No treatment related death was recorded. All patients discontinued therapy due to disease progression. Conclusions: In this single institution retrospective outcome analysis, FOLFIRINOX was shown to have activity in maintaining disease control as either a first or second line therapy in advanced cholangiocarcinoma. Hematologic and non-hematologic side effects were frequent but manageable without significant treatment delay or discontinuation. There was no treatment related deaths.
Biopsy practices for the diagnosis of hepatocellular carcinoma (HCC).
Authors: Raybould Alison L , Chang YunKyung , Barritt Alfred S , Hayashi Paul H , Sanoff Hanna Kelly 
Published: September 2018

e15646 Background: American Association for the Study of Liver Disease (AASLD) guidelines endorse radiographic diagnosis of HCC if key features are present on dynamic contrast-enhanced imaging (arterial hyperenhancement and venous washout) with biopsy for those without these features. As many HCC patients (pts) are diagnosed outside liver transplant centers, we sought to describe the methods of diagnosis of HCC and factors associated with biopsy in routine care in the US. Methods: HCC cases were identified from 2 data sources: SEER-Medicare (M) 2004-2011 and North Carolina Central Cancer Registry (NCCCR) linked to Medicare, Medicaid and private claims 2004-2013. Diagnostic confirmation was identified from registries as pathologic (path) or clinical. Key covariates included age, cancer stage, cause and severity of cirrhosis, and comorbid disease. Specialty consultation, prediagnosis imaging, AFP testing were determined from claims -3 to 0 months from diagnosis. Multivariable logistic regression was used to identify factors associated with path. Results: Path was obtained in a majority of HCC pts: 68% of 10,989 in SEER-M, 72% of 1,809 in NCCCR. In SEER-M, claims for contrasted abdominal CT were more common in those with path than those without (34 vs 30%) but not for MRI (14 vs 14%). Odds of path was higher in pts with contrasted CT (adjusted odds ratio [OR] 1.48, 95% confidence interval [CI] 1.30-1.69) or MRI (OR 1.53, CI 1.31-1.80) vs pts without imaging. In NCCCR, CT (51 vs 41%) and MRI (35 vs 34%) were performed more. Both were associated with increased odds of biopsy vs pts without imaging: contrasted CT scan (OR 1.74, CI 1.22-2.47) or MRI (OR 1.48, CI 1.02-2.13). In neither cohort did ultrasound increase odds of path over no imaging. Pts seen by an oncologist (OR SEER-M 1.66, CI 1.46-1.89) were more likely to have path than pts not seen by oncology. In SEER-M, pts seen at abdominal transplant centers were less likely to have path (OR 0.87, CI 0.77-0.98). Conclusions: Most pts diagnosed with HCC had path confirmation of cancer despite internationally accepted guidelines supporting radiographic diagnosis. The use of biopsy was greater among those with cross-sectional imaging, suggesting this high biopsy rate cannot solely be explained by nondiagnostic imaging.
Using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to predict efficacy of axitinib for treatment of advanced hepatocellular carcinoma (HCC).
Authors: Huang Po-Hsiang , Chen Bang-Bin , Lin Zhong-Zhe , Shen Ying-Chun , Chao Yee , Shao Yu Yun , Cheng Ann-Lii , Hsu Chiun 
Published: September 2018

e15656 Background: Axitinib, a potent inhibitor of vascular endothelial growth factor receptor, has moderate antitumor efficacy for advanced HCC. Vascular response (VR) measured by DCE-MRI has been demonstrated to correlate with efficacy of systemic therapy for advanced HCC. Methods: Patients enrolled into a phase 2 trial of axitinib as second-line therapy for advanced HCC (NCT01273662) with liver tumors evaluable by DCE-MRI were included. Patients must have documented progression on or intolerance to sorafenib and Child-Pugh class A liver function. The primary endpoint was disease stabilization, defined as complete or partial response per RECIST1.1 or stable disease lasting for 8 weeks without progression of tumor-related symptoms. The quantitative parameter Ktrans and semi-quantitative parameter peak, measured by DCE-MRI at baseline and after 2 weeks of axitinib treatment, were used to evaluate VR, defined by a greater than 40% decrease of Ktrans or peak. Results: From April 2011 to March 2016, 40 patients were enrolled at National Taiwan University Hospital and 5 at Taipei Veterans General Hospital, all had documented progression after sorafenib treatment. Disease stabilization rate was 62.2% (95% CI 48.0-76.4). Median progression-free survival (PFS) and overall survival (OS) were 2.2 months (95% CI 0.3-4.1) and 10.1 months (95% CI 3.6-16.5) respectively. 33 patients were evaluable for VR. VR evaluated by peak was significantly associated with better PFS (5.5 vs. 1.8 months, HR 0.41, 95% CI 0.16-1.02, p = 0.04) and OS (13.0 vs. 5.8 months, HR 0.28, 95% CI 0.09-0.85, p = 0.02). Treatment-related adverse events were compatible with previous reports of axitinib. Conclusions: VR measured by DCE-MRI may help identify HCC patients most likely to benefit from axitinib treatment. Clinical trial information: NCT01273662. [Table: see text]
Final phase Ib data for the oral c-Met inhibitor tepotinib in patients with previously treated advanced hepatocellular carcinoma.
Authors: Faivre Sandrine J. , Blanc Jean-Frédéric , Merle Philippe , Fasolo Angelica , Iacobellis Angelo , Decaens Thomas , Villa Erica , Trojan Jorg , Grando Véronique , Ellers-Lenz Barbara , Zhao Charles , Raymond Eric 
Published: September 2018

e15676 Background: The prognosis for patients (pts) with advanced hepatocellular carcinoma (HCC) after failure of sorafenib is poor, with few systemic therapy options. c-Met is a receptor tyrosine kinase implicated in the progression of HCC. Tepotinib, a highly selective c-Met inhibitor, has shown activity first-line in patients with c-Met+ HCC. We report final results of a phase Ib study of tepotinib in pts with advanced HCC after failure of first-line sorafenib. Methods: Eligible pts were ≥18 years with advanced HCC, Child-Pugh Class A, ECOG PS 0-1, and progression after ≥4 weeks of sorafenib. Tepotinib doses of 300 and 500 mg/day on a 21-day cycle were explored to establish the recommended phase II dose (RP2D) of tepotinib. Secondary objectives included antitumor activity by RECIST v1.1, biochemical response, and safety. Results: Seventeen pts were enrolled: 4 pts received tepotinib 300 mg/day and 13 pts 500 mg/day, confirmed as the RP2D. Fourteen pts experienced treatment-related adverse events (TRAEs), the most frequent being peripheral edema (n = 5, 2 grade 3), lipase increase (2, 1 grade 3), acute kidney injury (2, 1 grade 3), renal impairment (2, 1 grade 3), fatigue (2), nausea (2), asthenia (2). One pt with peripheral edema permanently discontinued treatment. No grade ≥4 TRAEs and no dose-limiting toxicities (DLTs) were reported. The best overall response was partial response (PR) in 2 pts and stable disease (SD) in 4 pts. The duration of the PRs was 57 and 91 weeks. In the first of these pts, tumor size decreased by 55% and serum alfa-fetoprotein (AFP) levels had decreased from 15,923 μg/L at baseline to < 3,000 μg/L by day 15 of cycle 2 and remained at this level until progression. In the second pt, tumor size decreased by > 60% from baseline. No consistent change in AFP was seen in pts with SD. Median overall survival was 7.2 months (range 0.7–22.9 months). Conclusions: The RP2D of tepotinib as second-line therapy for pts with advanced HCC who progress after sorafenib treatment is 500 mg/day. Tepotinib was well tolerated at this dose and showed signs of activity. The ongoing phase II part of this trial is investigating the efficacy and safety of tepotinib 500 mg/day in pts with c-Met+ HCC. Clinical trial information: NCT02115373.