tbuckley/cabot-search huggingface dataset:
Perspectives and practices of oncology providers in addressing financial toxicity.
Authors: Meera Vimala Ragavan, Divya Ahuja Parikh, Manali I. Patel
Journal: Journal of Clinical Oncology (2019)

e18342 Background: Few studies have evaluated the perspectives and clinical practices of oncology providers in regards to assisting patients with financial toxicity. Our study sought to assess providers’ attitudes regarding their role in addressing patients’ financial concerns, understand practice patterns in discussing cost of care, and obtain feedback on potential interventions to help address existing barriers. Methods: We developed an 18-question electronic, anonymous survey informed by an extensive literature search and piloted with three physicians with health services research experience. We emailed the survey to 75 attending physicians in Medical Oncology, Hematology, and Radiation Oncology, 117 advance practice practitioners (APPs) and 46 trainees. Responses during the study period 12/12/2018-1/31/2019 were analyzed. Results: A total of 71 (response rate of 30%) participants completed the survey, including 31 attending physicians, 28 APPs, and 12 trainees. Sixty-two percent of participants agreed that oncology providers should openly discuss cost of care with patients. There was wide variation in opinion around whether providers should offer the same treatment recommendations to all patients regardless of cost, with one third stating they agreed, one third stating they disagreed, and one third stating they were neutral. Sixty-one percent of participants did not use any cost-effectiveness tools in decision making. Sixty-three percent of respondents stated that a gap in knowledge of out of pocket costs was the number one barrier to helping patients avoid financial toxicity. The highest ranked intervention of those listed was a guide on available resources for patients with financial needs, voted for by 70% of respondents. Conclusions: Providers identified many barriers at our institution to discussing cost of care, including lack of transparency of out of pocket costs and lack of awareness of available resources. Providers were overwhelmingly interested in incorporating institutional resources and cost-effectiveness tools into their clinical practices. These findings can inform provider-level interventions to better address the financial burden patients face with their cancer care.
Neoadjuvant chemotherapy for muscle-invasive bladder cancer: Dana-Farber Cancer Institute (DFCI) experience.
Authors: Catherine Curran, Archana Agarwal, Amin Nassar, Sarah Abou Alaiwi, Vivek Kumar, Matthew Mossanen, Mark A. Preston, Graeme Steele, Bradley Alexander McGregor, Kerry L. Kilbridge, Guru Sonpavde
Journal: Journal of Clinical Oncology (2019)

e16037 Background: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) extends overall survival in muscle invasive bladder cancer (MIBC) patients (pts) and pathologic complete response (pCR) is associated with improved survival. We conducted a retrospective study at DFCI to examine the impact of different chemotherapy regimens and renal function on pCR and tolerability. Methods: Pts who underwent RC for MIBC were retrospectively studied. Descriptive statistics were calculated, and univariable Cox proportional hazards regression analysis was conducted to examine the prognostic effect of candidate factors (age, gender, chemotherapy regimen, creatinine clearance [Cr Cl] by Cockroft Gault formula) on pCR (ypT0), &lt; ypT2N0 rate and early discontinuation for toxicities. Results: 196 patients treated with NAC were identified from 2002 -2018 (Table). Unconventional regimens (split dose cisplatin or carboplatin combined with gemcitabine) exhibited lower pCR rate (14%), but a moderate &lt; ypT2N0 rate (36%). Among those receiving conventional cisplatin-based regimens, we did not identify an association between renal function (Cr Cl &lt; 60 vs. ≥60 ml/min), age, gender and specific regimen (Cisplatin/Gemcitabine, MVAC, ddMVAC) with pCR or early discontinuation ( &lt; 4 cycles) for toxicities, although the &lt; ypT2N0 rate was numerically higher for MVAC/ddMVAC. The modest size of this cohort limited the analysis. Conclusions: pCR rates were similar with ddMVAC/MVAC and GC for MIBC, with potential superiority of MVAC/ddMVAC to GC for a subset of pts. If Cr Cl ≥50 ml/min, it may be reasonable to consider conventional cisplatin therapies as non-conventional NAC appeared to yield lower depth of benefit emphasizing need for evaluation of new tolerable regimens. [Table: see text]
One year follow up results of the FINESSE trial of facilitated PCI
Authors: Stephen G. Ellis, Michael Tendera, Mark A. De Belder, Ad J. van Boven, Petr Widimsky, Luc Janssens, H. R. Andersen, Amadeo Betriu, Stefano Savonitto, Jerzy Adamus, Jan Z. Peruga, Maciej Kosmider, Olivier Katz, Thomas Neunteufl, Julia Jorgova, Maria Dorobantu, Liliana Grinfeld, Paul Armstrong, Bruce Brodie, Howard C. Herrmann, Gilles Montalescot, Franz-Josef Neumann, Mark B. Effron, Elliot S. Barnathan, Eric J. Topol
Journal: Journal of the American College of Cardiology (2008)
Cerebral Cavernous Malformations
Journal: New England Journal of Medicine (1988)

Cerebral cavernous malformations (CCMs) are abnormally large collections of low flow vascular channels without brain parenchyma intervening between the sinusoidal vessels. McCormick (1966) recognized CCMs as one of the four classes of cerebral vascular malformations which include arteriovenous malformations (AVM), developmental venous anomalies (DVA), and capillary telangiectasia. Clinically, CCMs are highly variable in both symptomatic presentation and natural history. Adding to the confusion, CCM has assumed a variety of names in the medical literature including cavernomas, cavernous angiomas, and cavernous hemangiomas, though CCM is the preferred nomenclature. CCMs range in size from punctate to several centimeters in diameter and may occur anywhere in the central nervous system with up to 20% located in the brainstem. CCM may be diagnosed in both young children and adults and may develop de novo or even regress spontaneously during a patient’s lifetime. A thorough understanding of the natural history of this entity is of paramount importance to avoid unnecessary and potentially morbid interventions. Given the heterogeneity of this condition, the ontogenesis, diagnosis, management strategies for CCMs are subjects of ongoing debate among neuroscientists and treatment paradigms continue to evolve.
A phase II study of pembrolizumab and capecitabine for triple-negative (TN) and hormone receptor-positive, HER2-negative endocrine-refractory metastatic breast cancer (MBC).
Authors: Ami N. Shah, Lisa E. Flaum, Alfred Rademaker, Cesar Augusto Santa-Maria, Sarika Jain, Irene B. Helenowski, Kelly Kindy, Tara Dedic, Regina Uthe, Valerie Nelson, Dean Tsarwhas, Massimo Cristofanilli, William John Gradishar
Journal: Journal of Clinical Oncology (2019)

1096 Background: Response rates to single agent immune checkpoint blockade in unselected MBC are low; however, they may be augmented when combined with chemotherapy. Methods: We conducted a single-arm, phase II study of patients with TN or endocrine-refractory MBC who were candidates for capecitabine. Patients were treated with pembrolizumab 200 mg IV day 1 and capecitabine 1000 mg PO BID days 1-14 of a 21-day cycle. The primary endpoint was progression free survival (PFS) and secondary endpoints were overall response rate (ORR), safety and tolerability. The study had 80% power to detect a 2 month (mo) improvement in mPFS with the addition of pembrolizumab over historic controls treated with capecitabine alone. Results: Thirty patients, 16 with TN and 14 endocrine-refractory MBC, were enrolled from 2017-18. Patients had a median age of 51 years and received a median of 1 prior line of therapy for MBC. Of 29 evaluable patients, the mPFS was 4.1 mo (95% CI, 2.3-8.2 mo) and median overall survival was 15.4 mo (95% CI, 8.2-16.6 mo). ORR was 14% (n = 4), stable disease (SD) was 41% (n = 12), and clinical benefit rate (CBR = PR + SD &gt; 6 mo) was 28% (n = 8). The ORR and CBR were similar between disease subtypes (ORR 13% and 14%, CBR 25% and 29% for TN and endocrine refractory, respectively). The 1-year PFS rate was 20.7% and 3 pts have ongoing responses. The most common adverse events were low grade and consistent with those seen in MBC patients receiving capecitabine, including hand-foot syndrome, gastrointestinal symptoms, fatigue, and cytopenias. Toxicities at least possibly from pembrolizumab included grade 3 or 4 liver test abnormalities (7%), rash (7%), and diarrhea (3%), as well as grade 5 hepatic failure in a pt with liver metastases. Conclusions: Compared to historical controls, pembrolizumab with capecitabine did not improve PFS in this biomarker unselected cohort; however, some patients had prolonged disease control. Future studies of chemo-immunotherapy in MBC with liver metastases require close safety monitoring. Clinical trial information: NCT03044730.
Pneumocystis jiroveci pneumonia during first and second-line chemotherapy for solid tumours.
Authors: Emma Shaughnessy, Kevin Armstrong, Madeline Rogers-Seeley, Adarsh Das, Domenic Higgs, Andrew Peter Dean
Journal: Journal of Clinical Oncology (2019)

e18330 Background: Pneumocystis jiroveci pneumonia (PJP) is an opportunistic fungal infection, historically associated with individuals with advanced immunodeficiency, sustained temozolamide chemotherapy and in those who have undergone multiple lines of chemotherapy. PJP is now increasingly being recognised in patients undergoing first-line chemotherapy. This is a retrospective study of ten cases of PJP at our institution amongst patients undergoing first or second-line chemotherapy for solid tumours. Methods: An electronic database search was conducted, looking at cases of PJP diagnosed in our institution over a five year period. Ten patients with a history of PJP were identified. These patients’ pharmacy records, pathology, imaging and laboratory results were examined. Results: All identified patients developed PJP whilst undergoing first-line (70%) or second-line (30%) chemotherapy for solid tumours. These included metastatic cancers such as: pancreatic adenocarcinoma (50%), lung cancer (20%), prostate adenocarcinoma (10%), gastric adenocarcinoma (10%); and colon adenocarcinoma (10%). Eight of ten patients were lymphopenic, with lymphocytes counts of 0.1 - 0.5 (reference range 1.0 - 4.0 x 10 9 /L). One patient had a recorded CD4 count of 114 (reference range 500-1500). On the basis of clinical context, ground-glass changes on CT and/or a positive sputum PCR for PJP, each patient was treated with intravenous high-dose trimethoprim/sulfamethoxazole until they were clinically stable. Patients were then switched on to a life-long prophylactic dose. Four patients required intensive care for management of respiratory failure. Nine out of ten patients recovered well without any long-term sequelae and one patient died. Conclusions: PJP is being diagnosed more frequently than previously thought in those receiving first and second-line chemotherapy. Limited research has been conducted into the potential benefit of prescribing trimethoprim/sulfamethoxazole prophylaxis to patients commencing chemotherapy. Monitoring of CD4 count prior to each chemotherapy cycle could provide guidance to oncologists regarding when to commence prophylactic treatment as a means to reducing patients diagnosed with PJP.
A phase I study of the APE1 protein inhibitor APX3330 in patients with advanced solid tumors.
Authors: Safi Shahda, Nehal J. Lakhani, Bert O'Neil, Drew W. Rasco, Jun Wan, Amber L Mosley, Hao Liu, Mark R. Kelley, Richard Adam Messmann
Journal: Journal of Clinical Oncology (2019)

3097 Background: APX3330 is an orally administered anti-cancer, anti-CIPN agent targeting the APE1 protein. APE1 maintains NFkB, STAT3, AP-1 and HIF-1a in a reduced form, acting as a regulator of transcription factors. A dual function protein, APE1 also plays a role in protecting against oxidative DNA damage in neurons. APX3330 is a highly selective inhibitor of APE1 redox function in tumors that enhances the neuronal protection function of APE1. Methods: We report on study NCT03375086 evaluating APX3330 in patients with incurable malignancies. Eligibility required adequate organ function, PS 0-2 and tumors not amenable to curative therapy. 1° and 2° objectives included determining the recommended phase 2 dose (RP2D), the safety and PK/PD profiles of APX3330 and reporting any RECIST anti-tumor activity. Patients received APX3330 b.i.d, in 21-day cycles. AE evaluation included 1 pt/cohort until the occurrence of ≥ G2 toxicity at which time the study proceeded in a 3+3 design. Additional patient were also recruited in cohorts in order to attain PK/PD and biopsy samples. Results: Between 2/18 and 8/18, 19 subjects (13M, 6F) with median age of 69 y started therapy. Dose (mg/d) escalation and number of patients treated (n) per each cohort proceeded as follows: 240 mg (1), 360 (4), 480 (2), 600 (6) and 720 (6). APX3330 was well tolerated at dose levels from 240-600 mg/d. The most frequent treatment-related adverse event (all grades) was G1 fatigue. A G3 rash occurred in two subjects at the 720 mg level defining 600 mg/d as the RP2D for further development. Six subjects had disease stabilization for ≥ 4 cycles, and of these, four subjects with the following diagnosis, RECIST response and days on study included: (CRC, PR, 356), (Endometrial, SD, 316), (Melanoma, SD, 245), (Prostate, SD, 246). Final PK and PD data, including proteomic, transcriptome, APE1 serum levels and CTC analyses are pending and will be reported at the conference. Conclusions: APX3330 is an orally administered inhibitor of APE1. This phase I study identified 600 mg PO daily as the RP2D for further development. RECIST evaluation identified signs of clinical activity in this un-selected population of patients with advanced cancer. PD analyses indicate APX3330 mediated targeting of the APE1 protein. Clinical trial information: NCT03375086.
The promise of Immuno-oncology: implications for defining the value of cancer treatment
Authors: Howard L. Kaufman, Michael B. Atkins, Prasun Subedi, James Wu, James Chambers, T. Joseph Mattingly, Jonathan D. Campbell, Jeff Allen, Andrea E. Ferris, Richard L. Schilsky, Daniel Danielson, J. Leonard Lichtenfeld, Linda House, Wendy K. D. Selig
Journal: Journal for ImmunoTherapy of Cancer (2019)

The rapid development of immuno-oncology (I-O) therapies for multiple types of cancer has transformed the cancer treatment landscape and brightened the long-term outlook for many patients with advanced cancer. Responding to ongoing efforts to generate value assessments for novel therapies, multiple stakeholders have been considering the question of “What makes I-O transformative?” Evaluating the distinct features and attributes of these therapies, and better characterizing how patients experience them, will inform such assessments. This paper defines ways in which treatment with I-O is different from other therapies. It also proposes key aspects and attributes of I-O therapies that should be considered in any assessment of their value and seeks to address evidence gaps in existing value frameworks given the unique properties of patient outcomes with I-O therapy. The paper concludes with a “data needs catalogue” (DNC) predicated on the belief that multiple key, unique elements that are necessary to fully characterize the value of I-O therapies are not routinely or robustly measured in current clinical practice or reimbursement databases and are infrequently captured in existing research studies. A better characterization of the benefit of I-O treatment will allow a more thorough assessment of its benefits and provide a template for the design and prioritization of future clinical trials and a roadmap for healthcare insurers to optimize coverage for patients with cancers eligible for I-O therapy.
Adrenal metastases in malignant melanoma, is it a privileged site?
Authors: Rao Rashid Mushtaq, Dexiang Gao, Christopher Raeburn, Richard P. Tobin, William Robinson
Journal: Journal of Clinical Oncology (2019)

e21016 Background: Currently there is a very limited data reporting response of adrenal metastases to immunotherapy in patients with metastatic malignant melanoma. Certain sites in the body may serve as sanctuary sites due to tumor microenvironment. Lower response rates and shorter PFS are reported in malignant melanoma with liver metastases while higher objective response rates are seen with lung metastases. We hypothesized that adrenal glands are sanctuary sites for melanoma metastases and thus would have poor response to immunotherapy due to steroid production in the adrenals making microenvironment less optimum for the anti-tumor effects of immunotherapy. Methods: A retrospective single-institution chart review of all malignant melanoma with metastasis to adrenal gland treated at University Colorado Hospital from 2008 till 2018, with age ≥ 18 yrs of age who received at least one dose of immunotherapy. Immune-related response criteria (irRC) was used to assess the response to immunotherapy on the imaging. Kaplan Meier estimate, and Chi square test were used for statistical analysis. Results: Sixty-five patients met the inclusion criteria. Mean age of 61 yrs. with range from 25 to 90 yrs. 71% were males and 95% were Caucasians. Median duration of follow up was 51.3 months with range of 1.5-212 months. Forty-three percent were cutaneous, 35% unknown primary, 11% each with mucosal and ocular melanoma. Based on the category of malignant melanoma, 60% were metastatic, 12% nodular, 8% choroidal, 8% superficial spreading, 6% acral lentiginous and 6% other. BRAF mutations were present in 38%, wild type in 54% and unknown in 8%. NRAS was mutated in 18% and wild type in 17% and unknown in 65% of the patients. Comparison of response between adrenal metastasis and non-adrenal metastasis, showed that 71% adrenal metastases had progressive disease compared to 54% of non-adrenal metastases. The overall response rate (ORR) to immunotherapy was 15% in adrenal metastases compared to 20% of non-adrenal metastases. Disease control rate (DCR) was 29% in adrenal metastases compared to 46% non-adrenal metastases with p value = 0.015. Conclusions: The adrenal glands appear to be a sanctuary site for metastases in patients with malignant melanoma receiving immunotherapy. The reasons behind this are unclear but may be related to the microenvironment and local corticosteroid production suppressing the immune response. Preliminary data examining cellular responses in nine surgically removed adrenal metastases support this hypothesis and will be presented.
The efficacy of immune checkpoint inhibitors and PD-L1 status in patients with advanced non-small cell lung cancer harboring oncogenic driver alterations: Immuno-oncology biomarker study in LC-SCRUM-Japan.
Authors: Kiyotaka Yoh, Shingo Matsumoto, Kei Kunimasa, Masahiro Kodani, Koichi Nishi, Taku Nakagawa, Shunichi Sugawara, Tomohiro Kato, Jun Sakakibara-Konishi, Yuichiro Hayashi, Koji Tsuta, Noriko Motoi, Genichiro Ishii, Koichi Goto
Journal: Journal of Clinical Oncology (2019)

9046 Background: The efficacy of immune checkpoint inhibitors (ICI) and PD-L1 status in patients with advanced non-small cell lung cancer (NSCLC) harboring oncogenic alterations has not been fully investigated. We initiated this immuno-oncology biomarker study as part of nationwide genomic screening by LC-SCRUM-Japan (LC-SCRUM-IBIS). Methods: Lung cancer patients enrolled in LC-SCRUM-IBIS underwent targeted next-generation sequencing (NGS) with Oncomine Comprehensive Assay, PD-L1 immunohistochemistry (IHC) assays and further whole-exome sequencing (WES) to determine tumor mutation burden. According to subtype of oncogenic alterations, the efficacy of ICI and PD-L1 status were analyzed. Results: Between Feb 2017 and May 2018, 1017 lung cancer patients were enrolled. Of these, 832 NSCLC patients had adequate tumor samples and were included in this analysis. Targeted NGS showed that major oncogenic alterations included 157 EGFR, 83 KRAS, 33 MET, 30 HER2, 25 FGFR, 22 PIK3CA, 19 ALK, 15 ROS1, 10 RET, 5 BRAF and 13 others. High expression of PD-L1 ( &gt; 50% of tumor cells by 22C3) were observed in RET (70%), MET (67%), ROS1 (53%), KRAS (41%) and BRAF (40%) positive tumors. One-hundred five patients were evaluable for the efficacy of ICI, including 80 non-squamous and 25 squamous histology. Among them, 104 were treated with PD-1/PD-L1 monotherapy and only 1 in combination therapy of ICI. Median treatment line was 2 (range, 1-9). The response rate was 19% (20/105) and median progression-free survival (PFS) and overall survival (OS) were 3.3 and 18.3 months. In 50 patients harboring at least one oncogenic alterations, the response rate, PFS and OS were 18% (9/50), 3.3 and 24.8 months. Among 9 responders to ICI, 3 had KRAS, 2 had MET and 1 each had ALK/EGFR/HER2/RET. Six (26%) of 23 patients with both high PD-L1 expression and at least one oncogenic alterations responded to ICI. Conclusions: PD-L1 status seemed to vary among patients with advanced NSCLC harboring oncogenic alterations. New biomarker for ICI therapy in this population should be moreover explored. Updated results on WES analysis will be presented at the meeting.
Camrelizumab combined with capecitabine and oxaliplatin followed by camrelizumab and apatinib as first-line therapy for advanced or metastatic gastric or gastroesophageal junction cancer: Updated results from a multicenter, open label phase II trial.
Authors: Lin Shen, Zhi Peng, Yan-Qiao Zhang, Jia Wei, Feng Wang, Jieer Ying, Yanhong Deng, Kangsheng Gu, Ying Cheng, Xianglin Yuan, Juxiang Xiao, Linna Wang, Jianjun Zou
Journal: Journal of Clinical Oncology (2019)

4031 Background: Capecitabine plus oxaliplatin (CAPOX) is one of the standard first-line treatments for advanced or metastatic gastric cancer. Camrelizumab (SHR-1210, an anti–PD-1 antibody) shows promising anti-tumor activity in patients (pts) with advanced or metastatic gastric or gastroesophageal junction (G/GEJ) cancer. Camrelizumab combined with CAPOX for untreated G/GEJ cancer was assessed as a part of an ongoing multicenter, open-label phase 2 trial (cohort 1), and encouraging preliminary results were reported. Here, we present the updated safety and efficacy data. Methods: In this cohort, systemic treatment naïve pts with HER2 – advanced or metastatic G/GEJ adenocarcinoma were given camrelizumab 200 mg on Day 1, capecitabine 1000 mg/m 2 bid on Days 1–14 and oxaliplatin 130 mg/m 2 on Day 1 of each 21-day-cycle for 4 to 6 cycles followed by camrelizumab 200 mg every 3 weeks plus apatinib 375 mg qd until disease progression or intolerable toxicity. The primary endpoint was objective response rate. Results: At data cutoff (Jan 20, 2019), 43 of the 48 enrolled pts were evaluable. Partial response was observed in 28 pts (65%), and 19 (44%) were confirmed. Stable disease in 14 pts and progressive disease in 10 pts were reported. Median estimates for duration of response and progression-free survival were not reached. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 9 pts (21%), included neutropenia, diarrhea, rash and elevated ALT, whereas none of the TRAEs was fatal. Ten pts without progression after 4–6 cycles of camrelizumab and CAPOX combination therapy all received camrelizumab plus apatinib as sequential therapy, and no new safety signals were observed. Conclusions: The updated results confirmed that camrelizumab plus CAPOX followed by camrelizumab plus apatinib was well tolerated with noteworthy responses as first-line therapy in advanced or metastatic G/GEJ cancer pts. Expansion of this cohort in a phase 3 study are under way. Clinical trial information: NCT03472365.