tbuckley/cabot-search huggingface dataset:
A phase 1b trial of lenvatinib (LEN) plus pembrolizumab (PEM) in patients (pts) with unresectable hepatocellular carcinoma (uHCC).
Authors: Masafumi Ikeda, Max W. Sung, Masatoshi Kudo, Masahiro Kobayashi, Ari David Baron, Richard S. Finn, Shuichi Kaneko, Andrew X. Zhu, Tomoki Kubota, Silvija Kraljevic, Kohei Ishikawa, Abby B. Siegel, Hiromitsu Kumada, Takuji Okusaka
Journal: Journal of Clinical Oncology (2018)

4076 Background: LEN is a multikinase inhibitor of VEGFR 1–3, FGFR 1–4, PDGFRα, RET, and KIT that showed noninferiority with respect to overall survival (OS) compared with sorafenib in the first-line treatment of pts with uHCC in a phase (Ph) 3 trial (REFLECT). PEM is an anti-PD-1 monoclonal antibody that has shown promising activity in HCC. An ongoing Ph 1b study of LEN + PEM has shown promising activity in several solid tumor types. We report preliminary results from a Ph1b trial of LEN + PEM in pts with uHCC. Methods: In this open-label, multicenter study, pts with uHCC, BCLC stage B (not eligible for transarterial chemoembolization) or C, Child-Pugh class A, and ECOG PS ≤ 1 received LEN (body weight ≥ 60 kg: 12 mg/day; < 60 kg: 8 mg/day) daily and 200 mg PEM IV once every 3 wks. Tolerability was evaluated by assessing dose-limiting toxicities (DLTs) during the first cycle in pts who were ineligible for other therapies (3+3 design; Part 1). Once tolerability of the combination was confirmed, additional pts with no prior systemic therapy for uHCC were enrolled (Part 2). The primary endpoint was safety. Secondary and exploratory endpoints included OS, and objective response rate, progression-free survival, and time to progression using modified RECIST (mRECIST). Tumor assessments of complete or partial responses (CR or PR) were confirmed ≥ 4 weeks after initial response. Results: As of December 1, 2017, 18 pts had received LEN + PEM (Part 1: n = 6; Part 2: n = 12). Pts had BCLC stage B (n = 6) or C (n = 12), Child-Pugh scores of 5 (n = 14) or 6 (n = 4), and 4 pts (22%) had received prior sorafenib. No DLTs were reported in Part 1. All 18 pts remained on study. TEAEs occurred in 17 pts (94%); the most common TEAEs were decreased appetite and hypertension (56% each). No new safety signals were identified. Efficacy outcomes are reported in the Table. At data cutoff, tumor reduction from baseline was observed in all evaluable pts except one. Conclusions: LEN + PEM was well tolerated with encouraging anti-tumor activity in pts with uHCC. Clinical trial information: NCT03006926. Part 1 (n = 6) Part 2 (n = 7) Total (n = 13) Best Overall Response, n (%) PR* 4 (67) 2 (29) 6 (46) Stable Disease 2 (33) 4 (57) 6 (46) Progressive Disease 0 (0) 0 (0) 0 (0) Not Evaluable 0 (0) 1 (14) 1 (8) *3 PRs confirmed.
Evaluation of post-procedure hemorrhage in patients with ascites undergoing treatment of hepatic malignancy with thermal ablation utilizing microwave technology.
Authors: Afsheen K. Sherwani, Blake A. Weis, John Guynan, Kirubahara Vaheesan, Ismael P. Moreno, Sameer D. Gadani, Rotimi O. Johnson
Journal: Journal of Clinical Oncology (2016)

e15582 Background: The presence of ascites has been considered a relative contraindication for performing percutaneous thermal ablation of hepatic tumors due to concerns for hemorrhage. The purpose of our study was to evaluate the incidence of post-procedure hemorrhage in patients with ascites who underwent percutaneous thermal ablation of hepatic malignancy at our institution. We believe that the presence of ascites should not be a contraindication, especially given the efficacy of ablation in treating hepatic tumors. Methods: We performed a retrospective review of 78 patients who underwent thermal ablation of the liver between 1/1/2014 and 9/29/2015. Of these, 19 patients had imaging evidence of ascites at the time of their procedure (excluding those with trace ascites). 4 of the 19 patients underwent microwave ablation twice during this time period. Thus, 23 total sessions of ablation were evaluated. In order to assess for post-procedure hemorrhage, post-procedural vital signs, pre/post ablation hemoglobin levels, hospital readmission statistics, and imaging were reviewed, if available. Results: Patients ranged in age from 55-86 years. All but two had a diagnosis of hepatocellular carcinoma. Mean preprocedure INR was 1.3 and mean platelet count was 82,000/microliter. Most patients had Child-Pugh class B cirrhosis (one had class A and three had class C cirrhosis). All procedures were performed with Covedien Emprint or NeuWave Certus microwave probes. 1-2 probes were used in each case. The tract was cauterized during probe removal in all cases. There was no evidence of post-procedure hemorrhage in any of the 23 sessions of microwave ablation. Conclusions: Percutaneous microwave ablation of hepatic malignancy in patients with ascites has been a safe treatment at our institution with no post-procedure hemorrhage reported to date.
A novel method of intra-arterial chemotherapy for oral cancer.
Authors: Masatoshi Ohmae, Itsuro Kato, Yusei Fujita, Noritoshi Meshii, Ayako Motoki, Mitsuhiro Nakazawa, Narikazu Uzawa
Journal: Journal of Clinical Oncology (2018)

e18086 Background: In most intra-arterial chemotherapy (iaCT) cases, high-dose anticancer agents are administered weekly or biweekly via an intra-arterial catheter. This approach remarkably improves curative efficacy, but can cause adverse events that decrease the patients' quality of life or result in discontinuation of chemotherapy. Here, we describe a superselective iaCT approach for oral cancer, wherein the intra-arterial catheter is retrogradely inserted via the superficial temporal artery (STA) and/or occipital artery (OA). Methods: We applied this new iaCT method in 25 patients with stage II or III oral cancer. In this approach, the catheter was superselectively placed in the tumor-feeding arteries via STA/OA cut-down. The extra-arterial portion of the catheter was connected to an infusion reservoir implanted subcutaneously around the mastoid process through the subcutaneous tunnel. The catheter and reservoir were placed completely under the skin to reduce the possibility of catheter-related issues such as infection and displacement of the catheter from its intended position. Anticancer agents (30 mg/m2 of cisplatin with/without 10 mg/m2 of docetaxel) were intra-arterially administered through the reservoir twice a week for 3 weeks for a total doses of 180 mg/m2 of cisplaninwith 30 mg/m2 of docetaxel. Computed tomography, positron emission tomography, and biopsy were performed to evaluate the treatment effects. Results: All patients developed CTCAE4.0 Grade 2 oral mucositis in the flow area of the intended artery, with most cases resolving within 6 months. No systemic adverse effects such as hematologic toxicity or renal/hepatic injury were observed. Conclusions: The novel method described herein decreased the occurrence of iaCT-related adverse events while retaining the superselectivity advantage of iaCT.
The impact of type and timing of radiation therapy (RT) relative to ipilimumab on survival in metastatic melanoma patients.
Authors: Ridhi Gupta, C Bryce Johnson, Eva Marie Suarez, Keisuke Shirai
Journal: Journal of Clinical Oncology (2016)

e21013 Background: Stage IV melanoma patients treated with ipilimumab (Ipi) have a median survival of 40 to 44 weeks (wks). Recent studies have demonstrated the combination of RT and Ipi can improve outcomes in these patients. However, the type and timing of RT needed to optimize clinical outcomes for this treatment combination remain unknown. Methods: A retrospective chart review was performed for Stage IV melanoma patients treated with Ipi at the Medical University of South Carolina from October 2009 to December 2014. For data collection and analysis, patients were divided into 5 groups based on the treatment: Ipi only and other 4 groups also receiving RT. These 4 were divided based on timing of RT relative to Ipi (concurrent v/s non-concurrent) and the type of RT received (Stereotactic Radiosurgery v/s non-SRS). Concurrent RT was defined as RT given between 4 wks before and 10 wks after any Ipi cycle. The median RT dose for SRS was 18 Gy/fraction and for non-SRS was 6 Gy/fraction. The primary outcome measured was overall survival, analyzed by Kaplan-Meier method. Results: Of the 73 patients that received Ipi, 59 also received RT. The median follow-up was 143 wks. A significant difference in median survival was noted with the addition of RT to Ipi compared to Ipi alone (143 v/s 70 weeks; p=0.03).There was no significant survival difference between the concurrent RT (118 wks) versus non-concurrent RT groups (139 wks) (p = 0.4). However, a significant benefit in survival was noted on comparing the SRS (concurrent + Non-concurrent ) group with the Ipi only group (118 v/s 70 wks; p=0.04). A considerably improved survival difference was noted between the group receiving concurrent SRS (163 wks) compared to the groups receiving non-concurrent SRS (100 wks) , concurrent non-SRS (82 wks) and Ipi only (p < 0.05; Table 1 for all comparisons). Conclusions: Based on our data, both the type and timing of RT relative to Ipi are important to further improve survival in Stage IV melanoma patients treated with Ipi. Outcomes by analysis group. All patients Ipi only SRS concurrent SRS Non- Concurrent Non-SRS concurrent N 73 14 21 13 14 Median survival (wks) 139 70 163 100 82
Treatment decisions and employment of breast cancer patients: Results of a population-based survey.
Authors: Reshma Jagsi, Paul Abrahamse, Kamaria Lee, Lauren P. Wallner, Nancy K. Janz, Ann S. Hamilton, Kevin C. Ward, Monica Morrow, Allison W. Kurian, Christopher Ryan Friese, Sarah T. Hawley, Steven J. Katz
Journal: Journal of Clinical Oncology (2017)

10052 Background: Many patients with breast cancer work for pay at time of diagnosis, and the treatment plan may threaten their livelihood. Given rapidly evolving policies, evidence, and treatment options, we evaluated work experiences in a contemporary population-based sample of breast cancer patients to inform initiatives to reduce the burden of cancer care. Methods: We surveyed women aged 20-79 years diagnosed with stages 0-II breast cancer as reported to the SEER registries of Georgia and Los Angeles in 2014-15. Of 3672 eligible women, 2502 responded (68%); we analyzed 1006 who reported working prior to diagnosis. Multivariable models evaluated correlates of missing &gt; 1 month and stopping work altogether vs missing ≤1 month. Results: In this diverse sample (48% white, 19% black, 20% Latina, 11% Asian), most pts (62%) received lumpectomy; 16% had unilateral mastectomy (8% with reconstruction); 23% had bilateral mastectomy (19% with reconstruction). One third (33%) received chemotherapy. The vast majority (84%) worked full time at diagnosis, but only 50% had paid sick leave, 39% disability benefits, and 38% flexible work schedules. Surgical treatment was strongly associated with missing &gt; 1 month of work (OR 7.8 for bilateral mastectomy with reconstruction vs lumpectomy) and with stopping altogether (OR 3.1 for bilateral mastectomy with reconstruction vs lumpectomy). Chemotherapy receipt (OR 1.3 for missing &gt; 1 month; OR 3.9 for stopping altogether) and race (OR 2.0 for missing &gt; 1 month and OR 1.7 for stopping altogether, blacks vs whites) also correlated. Those with paid sick leave were less likely to stop working (OR 0.5), as were those with flexible schedules (OR 0.3). Those with disability benefits were more likely to stop working (OR 1.6) or miss &gt; 1 month of work (OR 2.7). Conclusions: Working patients who received more aggressive treatments, particularly surgery, were much more likely to experience substantial employment disruptions. Given the growing choice of bilateral mastectomy by patients seeking peace of mind, particularly among young women with years of potential employment ahead, these findings suggest the importance of discussing impact of treatment decisions on employment. Funded by NCI P01CA163233.
Phase II study of efficacy of bevacizumab plus chemotherapy in management of malignant pleural effusion (MPE) in non-squamous non-small cell lung cancer (NSCLC) patients with MPE unsuccessfully controlled by tube drainage or pleurodesis (North East Japan Study Group Trial NEJ-013B-2).
Authors: Rintaro Noro, Kunihiko Kobayashi, Jiro Usuki, Yukio Hosomi, Masaru Nishitsuji, Hiroaki Okamoto, Mitsunori Hino, Koichi Hagiwara, Akihiko Miyanaga, Masahiro Seike, Kaoru Kubota, Akihiko Gemma
Journal: Journal of Clinical Oncology (2017)

e21660 Background: Prospective and retrospective studies on intrapleural therapy of malignant pleural effusion (MPE) have reported that the success rate for controlling pleural effusion was 50–70% at 2.5 months, and that the median post-pleurodesis survival time was 6-9 months. When pleurodesis is unsuccessful, and the lung is not fully expanded after drainage, the patients cannot receive effective chemotherapy. Vascular endothelial growth factor (VEGF) plays a pivotal role in the pathogenesis of MPE. Here, a multicenter phase II trial was conducted to evaluate bevacizumab therapy in non-squamous non-small cell lung carcinoma patients with unsuccessful management of MPE. Methods: Non-squamous NSCLC patients with MPE who had received unsuccessful tube drainage or pleurodesis received chemotherapy with bevacizumab (15 mg/kg) every 3 weeks. The primary endpoint was Pleural effusion control rate (PECR), defined as the percentage of patients without reaccumulation of MPE for 8 weeks. The secondary endpoint was pleural Progression-free survival (PPFS), defined as PFS without reaccumulation of MPE. Results: Fifteen of 20 patients entered received a median of 4 cycles of carboplatin plus paclitaxel or pemetrexed including maintenance therapy with bevacizumab. The PECR was 80% of treated patients (95% CI: 78-82%). PPFS was 16.6 months (95% CI: 11.46-21.80 months). The response rate (RR) and disease control rate (DCR) were 45% (95% CI: 39.6-50.4%), and 80% (95% CI: 78.0-82.0 %), respectively, and the median PFS and overall survival (OS) were 9.8 months (95% CI: 4.38-15.28 months) and 19.6 months (95% CI: 4.38-15.28 months), respectively. Toxicities of grade ≥3 included neutropenia (50.0%), thrombocytopenia (10.0%), proteinuria (10.0%), hypertension (2.0%), pulmonary embolism (5%). Conclusions: The combination of bevacizumab with chemotherapy demonstrated efficacy with acceptable toxicities in controlling MPE in patients with non-squamous NSCLC whose MPE was unsuccessfully controlled by tube drainage or pleurodesis.
Choice of radioactive iodine treatment for thyroid cancer: Results from a population-based survey.
Authors: Lauren P. Wallner, David Reyes-Gastelum, Ann S Hamilton, Kevin C. Ward, Sarah T. Hawley, Megan Rist Haymart
Journal: Journal of Clinical Oncology (2018)

159 Background: For many patients with differentiated thyroid cancer, use of radioactive iodine (RAI) does not improve survival or reduce recurrence risks. Yet, most patients continue to receive RAI suggesting the need for a better understanding of patient perspectives regarding RAI decision making. Methods: All eligible sequentially diagnosed patients with thyroid cancer in 2014-15 from the Georgia and Los Angeles SEER registries were surveyed (N = 2097, current response rate: 63%). Patients with intermediate risk thyroid cancer where selective RAI use is recommended were included in this analysis (N = 1357). Patients were asked whether or not they felt they had a choice to receive RAI (yes/no), how strongly their physician recommended initial RAI treatment (5 point Likert responses: Strongly against RAI--Strongly recommended RAI), whether they received RAI (yes/no), how satisfied they were with their RAI decision (5-pt Likert-type scale), categorized as more (score ≥4) vs. less satisfied. Multivariable logistic regression was used to assess 1) association between patient characteristics and perception of no RAI choice, 2) perception of no RAI choice with receipt of RAI and 3) perception of no RAI choice with decision satisfaction. Results: In this sample,over half (57%) of the respondents perceived they did not have a RAI choice, and the majority of them (76%) received RAI. The odds of perceiving no RAI choice was greater among Hispanic and Asian patients (Hispanic OR: 1.4, 95%CI: 1.0, 1.9, Asian OR: 1.9, 95%CI: 1.2, 2.9), and those whose physician strongly recommended RAI (OR: 1.9, 95%CI: 1.4, 2.6). Patients who perceived they did not have a RAI choice were more likely to receive RAI (Adjusted OR: 3.2, 95%CI: 2.1, 4.9) and report lower decision satisfaction (Adjusted OR: 2.7, 95%CI: 1.9, 3.7). Conclusions: Many patients in whom selective RAI use is recommended, particularly those of more vulnerable groups, did not feel they had a choice about whether or not to receive RAI. Patients who perceived they did not have a RAI choice were more likely to receive RAI and report lower decision satisfaction, suggesting a need for more shared treatment decision making to reduce overtreatment.
Rh-endostatin combined with pemetrexed/cisplatin followed by rh-endostatin plus pemetrexed maintenance in NSCLC: A retrospective comparison with standard chemotherapy.
Authors: Shengyu Zhou, Yuankai Shi, Lijie Zuo, Xiaohui He, Jinping Pi, Jun Jin
Journal: Journal of Clinical Oncology (2018)

e21198 Background: Recombinant human endostatin (rh-endostatin) is an inhibitor of tumor angiogenesis that acts on neovascular endothelial cells. Previous studies showed improved clinical outcome for rh-endostatin plus standard chemotherapy in advanced non-small cell lung cancer (NSCLC) patients. However, it is unclear whether rh-endostatin is effective and safe when added to pemetrexed/ciplatin and used as maintenance therapy. Methods: We retrospectively evaluated the data from untreated NSCLC patients who had received rh-endostatin plus pemetrexed/cisplatin or pemetrexed/cisplatin from November 2013 to January 2017. The inclusion criteria were pathologically or cytologically confirmed stage III or IV non-squamous lung cancer, and no previous systemic treatment. The primary endpoint was progression-free survival (PFS). Results: A total of 56 and 39 patients received rh-endostatin plus pemetrexed/cisplatin and pemetrexed/cisplatin, respectively, in which 34 and 29 underwent maintenance treatment. The baseline characteristics were similar between the two groups. The median PFS was 10 months (95% CI, 5.85-14.15) in the rh-endostatin group and 8.2 months (4.04-12.36) in the chemotherapy group without significant difference (p = 0.13). For patients underwent maintenance treatment, rh-endostatin plus pemetrexed was associated with a prolonged PFS than single-agent pemetrexed when PFS was calculated from first dosing [13.7 (9.41-17.99) vs 8.2 months (4.16-12.24), p = 0.032]. Patients who received rh-endostatin plus pemetrexed maintenance had extended PFS than those who only receive induction treatment (13.7 [9.41-17.99] vs 5 months [3.21-6.79], p = 0.003). There were no significant differences in the incidence of drug-related adverse events or grade 3-4 adverse events between the two groups. Conclusions: First-line rh-endostatin plus pemetrexed/cisplatin followed by rh-endostatin plus pemetrexed maintenance improves PFS for patients with advanced non-squamous NSCLC with favorable safety profile, supporting its application as first-line and maintenance treatment.
Outcomes for young children with molecularly defined ependymoma treated on the multi-institutional SJYC07 clinical trial.
Authors: Santhosh Upadhyaya, Giles W. Robinson, Brent Orr, Arzu Onar-Thomas, Catherine A Billups, Gregory T. Armstrong, Zsila Sousan Sadighi, Tim Hassall, Daniel C. Bowers, Anne Elizabeth Bendel, John R Crawford, Sonia Partap, Paul Klimo, Julie H Harreld, Christopher L Tinkle, Daniel J. Indelicato, Frederick A Boop, Thomas E. Merchant, David W. Ellison, Amar J. Gajjar
Journal: Journal of Clinical Oncology (2018)

10548 Background: Retrospective reports of poor outcomes of ependymoma (EPN) subgroups, posterior fossa A (PF-EPN-A) and supratentorial C11orf95–RELA (ST-EPN-RELA), need confirmation in prospective trials. Methods: Fifty-four children (median age 1.6 y, range 0.4–3.1) with newly diagnosed EPN (WHO grade II/ III) were treated (2008–2016) with maximal safe surgical resection + chemotherapy (high-dose methotrexate, vincristine, cisplatin and cyclophosphamide), consolidation using focal conformal radiation therapy (RT) to 54Gy (M0) or additional cyclophosphamide/topotecan with no RT (M+) and 6 months of oral maintenance chemotherapy. DNA methylation was performed using Infinium MethylationEPIC BeadChip and profiled on the DKFZ MN2.0 classifier. Fluorescent in-situ hybridization was used to determine tumor 1q status. Results: No participant had imaging evidence of metastatic disease at diagnosis (M0 = 40, M1 = 1, CSF not obtained = 13). At a median follow-up of 3.6 y (range, 1.0-9.3), 49 patients (91%) were alive with a 4-y PFS = 77.0%±7.5% and OS = 91.3%±5.2%. There was no significant difference in outcomes by subgroup [4-y PFS: PF-EPN-A (n = 42), 74.3%±8.2%; ST-EPN-RELA (n = 8), 80%±20.7%; ST-EPN-YAP (n = 4), 100%, p = 0.42]. Five patients with PF-EPN-A had 1q gain but no difference in outcome (p = 0.59 for OS and p = 0.15 for PFS). For 6 patients with subtotal resection (STR) prior to RT, outcome was inferior to those of the 48 with gross-total or near-total resection (4-y PFS = 27.8%±16.7% vs 81.7%±7.3%, p = 0.047). Fourteen patients experienced progression at a median time of 28 mos (range, 1.7m–7.3 y). Recurrence was distant (n = 7), local (n = 6), or combined (n = 1), 3/14 recurred at 6 (n = 2) and 7 years post diagnosis. Conclusions: In a uniformly treated, prospective EPN cohort, we found no significant difference in PFS or OS by molecular subgroup; however, the number of ST-EPN-RELA was small. In our data, 1q was not associated with outcome in PF-EPN-A, though only 5 subjects had 1q gain. Patients with STR prior to RT had inferior outcomes. Close surveillance and follow-up beyond 5 years is warranted due to risk of metastasis and late progression. Clinical trial information: NCT00602667.