bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of marital status on racial disparities in esophageal cancer care.
Authors: Paniagua Cruz Alan , Haug Karlie L. , Zhao Lili , Wadhera Priya , Reddy Rishinda 
Published: September 2018

4056 Background: It is well known that racial disparities exist in cancer treatment and outcomes. The present study examined the impact of marital status as a surrogate for social support on esophageal cancer (EsC) care. Methods: We performed a secondary analysis of data collected from a state cancer registry. We included individuals with an EsC diagnosis between January 1, 2000 and December 31, 2013. A Chi-square test and Fisher’s exact test was used to analyze categorical variables and two-sample t-tests to compare continuous variables. Results: 8754 patients (Caucasian (C) or African American (AA) only) were included, with 88.4% C and 11.6% AA. Staging at diagnosis in C and AA patients revealed that 30.6% vs 28.6% had localized disease, followed by 33.8% vs 32.0% with regional, and 35.6% vs 40.0% with metastatic, respectively (p = .0155). Rates of chemotherapy (53.6% vs 53.5%) and radiation therapy (54.1% vs 56.2%) administration were found to be similar between C and AA patients. In contrast, surgery rates were significantly different between the two groups, with 29.7% of C undergoing surgical resection in comparison to only 12.0% of AA patients (p < .0001). When evaluating marital status, 63.3% of C were married, compared to 33.4% of AA patients (p < .0001). In the AA group, 20.1% of married patients underwent surgery in contrast to only 7.6% of single AAs (p < .0001). Similarly, in the C group, married patients underwent surgery at a rate of 34.5%, while single patients went to surgery at a rate of 22.2% (p < .0001). Surgery contraindication (CI) rates were found to be similar across all groups (5.6% married Cs, 5.2% married AAs, 6.6% single Cs, and 6.5% single AAs) along with surgery refusal rates (1.56% single Cs vs 2.68% married Cs (p = .052), and 1.04% single AAs vs 2.81% married AAs (p = .210)). Conclusions: African American patients receive chemotherapy and radiotherapy at comparable rates to Caucasian patients, but the rates of surgery are significantly lower. Being married was associated with an almost three-fold increase in surgery rates for AA patients, and cause a significant increase in Caucasians too.
Association of the addition of cetuximab to preoperative chemoradiotherapy (CRT) for locally advanced esophageal squamous cell carcinoma (SqCC) with rate of long term survival: Mature results of a prospective phase Ib/II trial.
Authors: Brenner Baruch , Purim Ofer , Gordon Noa , Goshen Lago Tal , Idelevich Efraim , Kashtan Hanoch , Menasherov Nikolai , Fenig Eyal , Sulkes Aaron , Kundel Yulia 
Published: September 2018

4057 Background: Current treatment results in locally advanced esophageal cancer (LAEC) are far from being satisfying. This prospective phase IB/II study evaluated the safety and efficacy of the addition of cetuximab to standard preoperative CRT in this disease. Methods: Patients (pts) with potentially resectable LAEC (T2-4N0-1M0, T1-4N1M0 or T1-4N0-1M1A) received an induction cycle of cisplatin 100 mg/m2, day 1, and 5-FU 1000 mg/m2/day as a continuous infusion (CI), days 1–5, followed 4 weeks later by 50.4 Gy radiotherapy given concurrently with 2 cycles of cisplatin 75 mg/m2 and escalating doses of CI 5-FU, days 1–4 and 29-32. Pts received also 10 weekly infusions of cetuximab, 250 mg/m2, with a loading dose of 400 mg/m2, starting from the induction. The phase II part of the study started when the 5-FU dose during CRT was defined. Surgery was planned 6-8 weeks after CRT. Results: 64 pts were enrolled and 60 completed CRT. Median age was 65 years (range: 38-84 years) and 66% were males. The SqCC/adenocarcinoma ratio was 39%/61% (25/39). Pts had very advanced tumors: 95% T3-T4, 67% N1 and 19% M1A. The most common grade > 3 toxicities were leucopenia (45% of pts) and neutropenia (41%). There were two cases (3%) of fatal toxicities (neutropenic sepsis and sudden death). Among the 55 operated pts, R0 resection was achieved in 51 (93%). There were 8 cases (14.5%) of postoperative mortality, due to infection (3 pts), esophageal leak (2), bleeding (2) and pulmonary insufficiency (1). Pathological down-staging was noted in 72% of pts and pathological complete response (pCR) in 33%. 5y-local control, progression-free survival (PFS) and overall survival (OS) rates for all pts were 94%, 40%, 39%, respectively. Pts with SqCC had a significantly higher pCR rate (52% vs 15%, p = 0.007), 5y-PFS (67% vs. 21%, p = 0.008) and 5y-OS (64% vs. 20%, p = 0.019). Conclusions: This study suggests that the addition of cetuximab to standard preoperative CRT is safe. R0, pCR, local control and long term PFS and OS rates in pts with SqCC tumors are encouraging. Further evaluation of this approach in this population seems warranted.
Incidence rate and clinical-pathological features of hereditary diffuse gastric cancer patients in China.
Authors: Qiu Miaozhen , Xu Rui-hua , Zhou Yi-xin , Jin Ying , Wang Zi-Xian 
Published: September 2018

4065 Background: Familial clustering is seen in 10 % of gastric cancer cases and approximately 1-3 % of gastric cancer arises in the setting of hereditary diffuse gastric cancer (HDGC). Little is known about the incidence rate and clinical-pathologic features of HDGC in Chinese patients. Methods: We retrospectively collected gastric adenocarcinoma patients who were diagnosed in Sun Yat-sen University Cancer Center between January 2002 and December 2014. All the patients had detailed record of family history and Lauren classification. All of statistical analyses were performed using the Intercooled Stata 13.0 (Stata Corporation, College Station, TX). Results: 7431 patients were enrolled for analysis. The incidence rate of HDGC was 3.97% (295/7431). There were 124 (42.03%) male and 171 (57.97%) female patients. The median age was 35 (Mean ±SD: 35.23±7.50). The most common sites were gastric body (49.47%) and fundus (35.09%) . The distribution of AJCC 7thTNM stage was 47 (16.32%) stage I, 59 (20.49%) stage II, 88 (30.55%) stage III and 94 (32.64%) stage IV. Only 92 patients received the HER2 immunohistochemistry test. 4 (4.35%) patients were HER2 IHC +++ and 8 (8.70%) patients were ++. The median survival was 80 months for the whole population and 15 months for stage IV patients. Conclusions: The incidence rate of HDGC was 3.97% in China. About one third of the patients were diagnosed at stage IV. Early detection of HDGC was warranted in China.
Phase I/II study of durvalumab and tremelimumab in patients with unresectable hepatocellular carcinoma (HCC): Phase I safety and efficacy analyses.
Authors: Kelley Robin Kate , Abou-Alfa Ghassan K. , Bendell Johanna C. , Kim Tae-You , Borad Mitesh J. , Yong Wei-Peng , Morse Michael , Kang Yoon-Koo , Rebelatto Marlon , Makowsky Mallory , Xiao Feng , Morris Shannon R. , Sangro Bruno 
Published: September 2018

4073 Background: Durvalumab and tremelimumab, investigational monoclonal antibodies against PD-L1 and CTLA-4 immune checkpoints, respectively, have shown efficacy in monotherapy and offer promise in combination for patients (pts) with HCC. This is a phase I/II, open-label, randomized study of durvalumab combined with tremelimumab in unresectable HCC. Methods: Phase I part of this study is a safety run-in cohort treated at the recommended phase II doses of the durvalumab/tremelimumab combination (20 and 1 mg/kg IV Q4W respectively for 4 doses followed by 20 mg/kg Q4W durvalumab alone) in pts with unresectable HCC with or without concomitant HBV or HCV infection who progress on, are intolerant to, or have refused sorafenib therapy. Secondary objectives include evaluation of antitumor activity. Here we present results of a preplanned analysis from the completed phase I part of the study. Results: As of 10 January 2017, 40 pts have been enrolled (11 HBV+, 9 HCV+, 20 uninfected). 30% had no prior systemic therapy; 93% were Child Pugh Class A. 24 (60%) had ≥1 treatment-related AE; 20% had ≥1 grade ≥3 related AE. Most common (≥15%) treatment-related AEs: fatigue (20%), increased ALT (18%), pruritus (18%), and increased AST (15%). Most common grade ≥3 related AE was asymptomatic increased AST (10%). 24 pts have discontinued treatment: 3 due to treatment-related AEs (grade 3 pneumonitis, grade 3 colitis/diarrhea, asymptomatic grade 4 elevated AST and ALT), 16 due to progressive disease, 4 due to death unrelated to treatment (cardiac arrest, variceal bleed, progressive disease, probable HCC rupture), and 1 other (pt entered hospice care). 40 pts were evaluable for response at ≥16 weeks follow-up. Conclusions: No unexpected safety signals with durvalumab and tremelimumab were seen in this unresectable HCC population. Clinical activity observed predominantly in uninfected pts though interpretation limited by small subsets. Enrollment to the phase II portion of the study is ongoing. Clinical trial information: NCT02519348. [Table: see text]
A phase II study of sorafenib and yttrium-90 glass microspheres for advanced hepatocellular carcinoma, BCLC stage C.
Authors: Kaseb Ahmed Omar , Abdel-Wahab Reham , Murthy Ravi , Hassan Manal , Raghav Kanwal Pratap Singh , Xiao Lianchun , Morris Jeffrey , Avritscher Rony , Odisio Bruno C. , Ohaji Chimela , Wolff Robert A. , Yao James C. , Mahvash Armeen 
Published: September 2018

4083 Background: Combined use of sorafenib and local therapy for treating unresectable hepatocellular carcinoma (HCC) is not well established. Notably, most common cause of death in HCC is liver failure, therefore we tested the promise of controlling the local tumors even in the setting of advanced/metastatic disease to improve survival. Our study aimed to assess the efficacy and safety of combined use of sorafenib and yttrium-90 resin microspheres (Y90 RMS) in unresectable HCC defined as Barcelona Clinic Liver Cancer class C. Methods: Between October 2013 and August 2016 we enrolled 40 advanced stage HCC patients, 38 patients were treated with sorafenib followed (after 4 weeks) with Y90 RMS at MD Anderson Cancer Center. Survival analysis was done to evaluate median overall survival (OS) and progression-free survival (PFS). We used modified Response Evaluation Criteria in Solid Tumors (RECIST) to assess response to treatment and the Common Terminology Criteria for Adverse Events (CTCAE) v4.0 to evaluate the grading of treatment related toxicity. Results: The majority of our patients were males (74%), white (47%), 66% of patients had underlying liver cirrhosis, 26% had vascular invasion, and 26% had extrahepatic disease. The estimated median OS and 95% confidence interval (CI) in months was 18.46 (12.29 – NA) and the estimated PFS was 12.29 months (5.72 – 18.79). Stable disease (SD) was observed in 44.74% of patients, while 28.95% achieved partial response (PR). Grade III-IV adverse events included fatigue (n = 3), hyperbilirubinemia (n = 2), thrombocytopenia (n = 1), proteinuria (n = 1), hyponatremia (n = 1), elevated liver enzymes (n = 4), hypertension (n = 4), diarrhea (n = 1), nausea (n = 1) and vomiting (n = 2). Conclusions: This is the first prospective study to evaluate sorafenib followed by Y90 in HCC. Our study included patients with metastatic HCC and showed that combined use of sorafenib and Y90 was tolerable and was associated with longer OS and PFS compared to previous studies which evaluated sorafenib alone. However, future randomized phase III studies are warranted to assess sorafenib+/-Y90 in metastatc disease setting. Clinical trial information: NCT01900002.
Neoadjuvant FOLFIRINOX for patients with borderline resectable or locally advanced pancreatic cancer: Results of a decision analysis.
Authors: Choi Jin , Nipp Ryan David , Tramontano Angela , Ali Ayman , Zhan Tiannan , Kong Chung Yin , Pandharipande Pari , Dowling Emily , Ferrone Cristina , Hong Theodore S. , Schrag Deborah , Fernandez-del Castillo Carlos , Ryan David P. , Hur Chin 
Published: September 2018

4117 Background: With the advent of more effective therapies for metastatic pancreatic ductal adenocarcinoma (PDAC), efforts to incorporate these agents, such as FOLFIRINOX, into the neoadjuvant setting are increasing. However, the efficacy and cost-effectiveness of using neoadjuvant FOLFIRINOX for patients with borderline resectable or locally advanced PDAC are unknown. We performed a decision analysis to assess the value of neoadjuvant FOLFIRINOX versus upfront surgery and adjuvant therapy. Methods: We developed a mathematical simulation model to evaluate the efficacy and cost-effectiveness of neoadjuvant FOLFIRINOX compared to upfront surgery and adjuvant therapy. We used published and institutional data as inputs to inform model development. Model outcomes included overall and disease-free survival, net benefits expressed as discounted quality-adjusted life-years (QALYs), costs in US dollars, and cost-effectiveness expressed as an incremental cost-effectiveness ratio. We used deterministic and probabilistic sensitivity analyses to explore the uncertainty of model assumptions. Results: Model estimated median overall survival (29 vs 23 months) and disease-free survival (14 vs 13 months) were better for neoadjuvant strategy compared with upfront surgery. Neoadjuvant strategy resulted in an additional 0.68 life-years gained, or 0.57 QALYs, at a cost of $59,000/QALY gained. Sensitivity analysis found that cancer recurrence rates affected model results the most. Our findings were otherwise robust with respect to changes in other model parameters, including chemotherapy toxicity, surgical complications and cancer mortality. Probabilistic sensitivity analyses showed that neoadjuvant strategy was cost-effective 80% of the time with a willingness-to-pay threshold of $100,000/QALY. Conclusions: Our model results demonstrate that neoadjuvant strategy is preferable to upfront surgery for patients with borderline resectable or locally advanced PDAC from both an efficacy and cost-effectiveness standpoint. Additional clinical data are needed to further define the long-term effectiveness of neoadjuvant FOLFIRINOX to confirm our results.
Molecular profiling of advanced pancreatic cancer (PC) patients from a phase I/II study using circulating tumor DNA.
Authors: Catenacci Daniel V.T. , Green Emma , Epstein Michael , Jones Greg , Morris Clive D. , O'Day Emily , Lomnicki S , Maranto Melissa , Karrison Theodore G. , Kindler Hedy L. 
Published: September 2018

4124 Background: PC has a poor prognosis with a 5-year survival of 9%. Targeted therapies have yet to demonstrate improved outcomes in this disease. Circulating tumour DNA (ctDNA) may be used as a non-invasive method for the detection and quantification of genomic abnormalities. We performed a retrospective-prospective study to assess molecular alterations in the ctDNA of advanced PC patients. Methods: Plasma samples were banked from patients enrolled in the previously reported Phase Ib/II trial of gemcitabine with placebo or vismodegib (NCT01064622; Catenacci et al JCO 2015). Eligible patients had unresectable PC and no prior therapy for metastatic disease. Patient samples ( < 3ml) collected pre-treatment and at regular intervals and stored for ~6-8 years were analyzed using InVision (enhanced tagged-amplicon sequencing) for “hotspot” regions of 34 genes, including KRAS (exons 2 and 3), and select full gene coverage. Results: Of 113 patients enrolled in the trial, a cohort of 72 patients were included in this study. Baseline plasma ctDNA profiling detected any genomic event in 88% of patients (SNV/indels found at range of 0.07%-23% allele fraction (AF) with 20% detected at < 0.5% AF). Patients had between 1-5 mutations (median, 2): KRAS mutations were detected in 80% of patients tested, of which 86% had concurrent KRAS/TP53 mutation(s) and 16% with concurrent KRAS/TP53/CDK2NA. Of note, 2 cases presented with IDH1 point mutations (R132C, R132H). An ERBB2 amplification and a FGFR2 amplification were detected in 2 individuals. An update on the analyses will include serial ctDNA testing during treatment and correlation with outcomes. Conclusions: ctDNA analysis of this cohort of banked PC plasma samples described the landscape of genomic aberrations at baseline and over time, including rare but potentially important actionable events including ERBB2 and FGFR2 amplifications and IDH1 mutation. We demonstrate a sensitive method for re-analysing trial outcomes, despite limiting plasma volume and time lapse since samples were collected.
Subgroup analysis by prior lines of metastatic therapy (mtx) in NAPOLI-1: A global, randomized phase 3 study of liposomal irinotecan (nal-IRI) ± 5-fluorouracil and leucovorin (5-FU/LV), vs. 5-FU/LV in patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDAC) who have progressed following gemcitabine-based therapy.
Authors: Macarulla Teresa Mercade , Siveke Jens T. , Wang-Gillam Andrea , Li Chung-Pin , Bodoky Gyorgy , Dean Andrew Peter , Yanshen Shan , Jameson Gayle S. , Lee Kyung-Hun , Blanc Jean-Frédéric , Chiu Chang-Fang , Schwartsmann Gilberto , Braiteh Fadi S. , Cunningham David , Chen Li-Tzong , Von Hoff Daniel D. , Mamlouk Khalid Kevin , Bhargava Parul , de Jong Floris A. , Hubner Richard 
Published: September 2018

4127 Background: In the NAPOLI-1 study, nal-IRI+5-FU/LV significantly increased median OS vs. 5-FU/LV control (6.1 vs. 4.2 mo; unstratified HR = 0.67 [0.49–0.92]; p = .012). This is a subgroup analysis by prior lines of mtx. Methods: Study methodology has been published (Wang-Gillam; Lancet 2016). This exploratory subgroup analysis compares outcomes in pts with 0–1 vs. ≥2 prior mtx lines, based on primary survival analysis data (cut-off February 2014) of the ITT population. Results: OS, PFS and CA19-9 response rates in pts with 0–1 (65.8% of pts) or ≥2 (34.2%) prior mtx lines are shown (see Table). Median OS for nal-IRI+5-FU/LV improved vs. 5-FU/LV by 2.1 mo to 6.2 mo (HR = 0.66; p = .03) in pts with 0–1 prior mtx lines and by 1.1 mo to 5.4 mo (HR = 0.68; p = .18) in pts with ≥2 prior mtx lines. The safety profile was similar between subgroups with nal-IRI+5-FU/LV (≥grade 3 drug-related AEs: 43 [55%] with 0–1 and 20 [51%] with ≥2 prior mtx lines). Conclusions: This post-hoc subgroup analysis shows significant increases for nal-IRI+5-FU/LV over 5-FU/LV in OS, PFS and CA19-9 response in pts with 0–1 prior mtx lines. Median OS benefit was less prominent in later lines, but conclusions are restricted by limited pt numbers. Clinical trial information: NCT01494506. [Table: see text]
Planned survival analysis from KEYNOTE-045: Phase 3, open-label study of pembrolizumab (pembro) versus paclitaxel, docetaxel, or vinflunine in recurrent, advanced urothelial cancer (UC).
Authors: Bajorin Dean F. , De Wit Ronald , Vaughn David J. , Fradet Yves , Lee Jae-Lyun , Fong Lawrence , Vogelzang Nicholas J. , Climent Miguel Ángel , Petrylak Daniel Peter , Choueiri Toni K. , Necchi Andrea , Gerritsen Winald , Gurney Howard , Quinn David I , Culine Stephane , Sternberg Cora N. , Mai Yabing , Puhlmann Markus , Perini Rodolfo F. , Bellmunt Joaquim 
Published: September 2018

4501 Background: Second-line chemotherapies (chemo) for advanced UC have limited clinical benefit (OS, 7-9 mo). Data from the open-label, phase 3 KEYNOTE-045 study (NCT02256436) showed significantly longer OS with pembro v chemo (median, 10.3 v 7.4 mo; hazard ratio [HR], 0.73; P = 0.002) in recurrent, advanced UC. Data from a planned survival analysis are presented. Methods: Pts had histologically or cytologically confirmed UC, progression after platinum, ECOG PS 0-2, measurable disease (RECIST v1.1), and ≤2 lines of systemic therapy. Pts were randomly assigned 1:1 to pembro 200 mg Q3W or investigator’s choice of paclitaxel 175 mg/m2 Q3W, docetaxel 75 mg/m2 Q3W, or vinflunine 320 mg/m2 Q3W. Primary efficacy end points were OS and PFS (RECIST v1.1, blinded central review). ORR (RECIST v1.1, blinded central review) was a secondary end point. Results: 542 pts were enrolled (pembro, 270; chemo, 272). Baseline characteristics were generally similar between arms. As of Jan 18, 2017, median follow-up was 18.5 mo (range, 14.2-26.5). Median OS was significantly longer with pembro v chemo (10.3 v 7.4 mo; HR, 0.70; P < 0.001), and significance was maintained regardless of PD-L1 expression as measured by combined positive score (HR: CPS < 1%, 0.84; CPS ≥1%, 0.59; CPS < 10%, 0.76; CPS ≥10%, 0.57). OS benefit with pembro v chemo was seen regardless of age, ECOG PS, prior therapy, liver metastases, histology, and choice of chemo. The 18-mo OS rate (95% CI) was 36.1% (30.1%-42.0%) with pembro v 20.5% (15.2%-25.8%) with chemo (KM estimate). PFS was not different between arms. ORR was higher with pembro v chemo (21.1% v 11.0%), and median (range) duration of response was longer (not reached [1.6+-20.7+ mo] v 4.4 mo [1.4+-20.3]). 69% (pembro) v 36% (chemo) of responses lasted ≥12 mo. Fewer pts experienced a treatment-related AE with pembro v chemo (any grade, 61.3% v 90.2%; grade ≥3, 16.5% v 49.8%). Conclusions: The OS benefit and superior safety profile of pembro over chemo are maintained with longer follow-up. Combined, these results support the potential of pembro as a new standard of care for patients with UC who previously received platinum. Clinical trial information: NCT02256436.
Phase II study of alternate sunitinib schedule in patients with metastatic renal cell carinoma.
Authors: Jonasch Eric , Slack Rebecca , Geynisman Daniel M. , Milowsky Matthew I. , Rathmell Kimryn , Stovall Summer , Juarez Donna , Plimack Elizabeth R. , Tannir Nizar M. , Rini Brian I. 
Published: September 2018

4513 Background: Sunitinib is an antiangiogenic agent indicated for the treatment of metastatic renal cell carcinoma (mRCC). Sunitinib is given in a 4 week on, 2 week off (4/2) schedule. Significant toxicities are observed in patients in the 3rd and 4th weeks of therapy. We hypothesized that a 2 week on, 1 week off (2/1) schedule would provide improved toxicity without compromising efficacy. Methods: A multicenter, single arm study was performed, with patients initiating sunitinib 50mg on a 2/1 schedule. Schedule and dose alterations were performed if grade > 3 toxicities were observed. The primary objective was to determine the percentage of patients who experienced grade > 3 fatigue, diarrhea, or HFS. The sample size of 60 patients was selected to ensure the upper bound of a 95% confidence would fall below standard schedule rate of 25%-30% if sample rate was 10%-15%, respectively. Secondary outcomes included response rate (RR), progression free survival (PFS) and dose reductions. Results: Between August 2014 and April 2016, 60 patients were enrolled, and 59 treated. Patients had a median age of 65.5 years (ranging from 45-92). 24% of patients (14/59) had grade 3 or higher fatigue, diarrhea, or HFS (95% CI: 13.6%, 36.6%). This is similar to the average of the 4 week on, 2 week off schedule of 25%-30%, and the lower bound of the confidence interval is in the center of our target rate of 10%-15%. Among events at least possibly related to study drug, patients were most likely to experience the expected events of diarrhea (75% with 5 grade 3 events), fatigue (71% with 6 grade 3 events), and HFS (54% with 3 grade 3 events). 22 (37%) patients responded (25.0%, 50.9%). Among patients with secondary endpoint data available, median PFS was 19.3 months (95% CI: 8.2, NR) and 33/56 (59%) of patients underwent dose reduction. Conclusions: Sunitinib administered in a 2/1 schedule in this study did not result in a lower rate of grade 3 or higher fatigue, diarrhea or HFS when compared to historical data from trials employing a 4/2 schedule. However, efficacy data showed robust response rate and a prolonged PFS, suggestive of long-term tolerability in patients receiving sunitinib on a 2/1 schedule. Evaluation of toxicity kinetics and patient quality of life is ongoing. Clinical trial information: NCT02060370.