tbuckley/cabot-search huggingface dataset:
P01.111 Using the ASCO and ESMO frameworks to assess the clinical value of tumor treating fields for newly diagnosed Glioblastoma multiforme
Authors: C Proescholdt, J Kelly, A Kinzel, O Bähr
Journal: Neuro-Oncology (2018)

The effectiveness and safety of TTFields in newly diagnosed GBM was recently demonstrated by the final analysis of the large, randomised controlled EF-14 Trial. To account for the need of physicians and policymakers to objectively and comparably capture the clinical value of new cancer treatments, the American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO) have both developed assessment frameworks. We quantified the clinical value of the TTFields treatment in GBM by applying ASCO and ESMO frameworks to the EF-14 trial data. The EF-14 Trial (n=695) proved the effect of adding TTFields to maintenance Temozolomide (TMZ) for newly diagnosed glioblastoma patients. The ESMO Magnitude of Clinical Benefit Scale (MCBS) and the ASCO Net Health Benefit (NHB frameworks provide separate calculations for a) adjuvant therapies and b) treatments for advanced diseases. We applied both classifications to the EF-14 trial data, using either the interim trial results or final 5-year trial results with mature follow up as required by the framework rules. Quality of life data from the EF-14 Trial was also included. Additionally, we performed a literature search to identify reference points for understanding the NHB score and MCBS results for TTFields in GBM. Applying the ASCO framework to the EF-14 data resulted in a NHB score of 56/72 (adjuvant/advanced). The ASCO NHB scores of 56/72 were among the highest reported scores identified in the literature search. Additionally, the ASCO framework valued the reduction in cancer-related symptoms (e.g., pain, weakness of legs) with TTFields. Applying the ESMO framework resulted in MCBS scores of A/5 (adjuvant/advanced). The MCBS scores of A/5 are the highest scores achievable in the ESMO framework. The ESMO framework valued the Health Related Quality of Life (HRQoL) gain during deterioration-free survival time with TTFields. Despite differences in their respective concepts, both the ASCO and ESMO frameworks suggest that adding TTFields to maintenance TMZ for newly diagnosed glioblastoma patients provides patients with significant clinical benefits. The high scores underline the fact, that treatment with TTFields extended progression free and overall survival without additional systemic toxicities.
Oral mucositis in cancer treatment: Cross-national perspective of oncologists in Asia and Saudi Arabia.
Authors: Hanlim Moon, Mohamed Ibrahim A. Wahid, Jin-Ching Lin, Nonette Cupino, Edward Liu, Jin Hyoung Kang, Jeeve Kanagalingam, Shouki Bazarbashi, Nicole Moreira, Harsha Arumugam, Sfefan Mueller
Journal: Journal of Clinical Oncology (2016)

e21613 Background: Oral mucositis (OM) is a common side-effect of cancer therapy. It represents not only a considerable burden on patients’ quality of life but may also limit cancer treatment. This survey aimed at identifying challenges of managing OM from the perspective of doctors in Asia and Saudi Arabia. Methods: Between July and September 2015, a total of 105 medical, haematological, clinical, radiation and surgical oncologists managing OM were recruited from 6 Asian countries as well as Saudi Arabia. Each oncologist completed a 20-minute, face-to-face quantitative interview. Results: With respect to OM communication between doctors and patients, the majority ( > 95%) of oncologists inform their patients about the possibility of OM before initiating cancer treatment. However, only less than 10% of doctors provide drug recommendations or dietary advice to prevent OM before cancer treatment. Less than 2 out of 3 oncologists ask their patients about OM symptoms proactively. For OM management, most doctors (58%) recommend oral mouthwash or gargles. About 40%-50% of doctors also provide advice on oral hygiene and dietary modifications, whereas only 8% supply health care education materials. In case of moderate to severe OM, ~60% of doctors may delay or modify cancer treatment. Mean satisfaction score for current options for OM management was 4.2 out of 7.0 (1.0 = not at all satisfied; 7.0 = extremely satisfied). Important unmet needs cited by doctors include effective and fast-acting agents for OM treatment and symptom relief (61%), as well as effective prophylactics to prevent OM (27%). Conclusions: Although doctors recognize the importance of managing OM, their approach to management of symptoms is largely reactive. OM management ensuring patients’ quality of life may be optimized through raising awareness of the condition and its proactive management. This study was supported by an educational grant from Mundipharma Pte Ltd.
The Affordable Care Act Dependent Coverage Expansion (ACA-DCE): Disparities in impact in young adult oncology patients.
Authors: Elysia Marie Alvarez, Theresa Keegan, Emily E. Johnston, Robert Haile, Lee Sanders, Paul Wise, Olga Saynina, Lisa J Chamberlain
Journal: Journal of Clinical Oncology (2017)

6561 Background: Private health insurance is associated with improved outcomes in cancer patients. We know little, however, about the impact of the ACA-DCE, which extended private insurance to young adults (up to age 26) beginning in 2010, on the insurance status of young adults with cancer. This study sought to determine the effect of the ACA-DCE on having private insurance coverage among hospitalized young adult oncology patients. Methods: We performed a retrospective, population-based analysis of hospitalized young adult oncology patients (22-30 years-old) in California during 2006-2014 (n = 11,062) using the Office of Statewide Health Planning and Development database. Multivariable regression analyses examined the social and clinical predictors of having private insurance. Results are presented as adjusted odds ratios (OR) and 95% confidence intervals (CIs). A difference-in-difference analysis examined the influence of the ACA-DCE on insurance coverage by race/ethnicity and zip code federal poverty level. Results: Multivariable regression demonstrated patients of black and Hispanic race/ethnicity were less likely to have private insurance both before and after the ACA-DCE, compared to non-Hispanic white patients. Younger age (22-25 years) was associated with having private insurance after the ACA-DCE implementation (OR 1.18, CI 1.05-1.33; reference, 27-30 years). In the difference-in-difference analysis, private insurance increased among non-Hispanic whites aged 22-25 living in medium- (2006-2009: 64.6% versus (vs) 2011-2014: 69.1%; p = 0.003) and high-income zip codes (80.4% vs 82%; p = 0.043) and among Asian patients aged 22-25 living in high-income zip codes (73.2 vs 85.7%; p = 0.022). Private insurance decreased for all Hispanic patients aged 22-25 between the two time periods. Conclusions: The ACA-DCE provision was an important first step in increasing coverage, but it was not universal and generated disparity in coverage as gains occurred for non-Hispanic white and Asian patients living in higher income zip codes. This policy change was shown to increase coverage for a traditionally underinsured population and attention should now focus on those remaining uninsured.
WINTHER: An international study to select rational therapeutics based on the analysis of matched tumor and normal biopsies in subjects with advanced malignancies.
Authors: Jean-Charles Soria, Jordi Rodon Ahnert, Raanan Berger, Wilson H. Miller, Irene Brana, Yohann Loriot, Tariq I Mughal, Vladimir Lazar, Fanny Wunder, Catherine Bresson, Serge Koscielny, Mohammad Afshar, Pierre Saintigny, Apostolia Maria Tsimberidou, Catherine Richon, Gerald Batist, Amir Onn, Aliza Ackerstein, Eitan Rubin, Razelle Kurzrock
Journal: Journal of Clinical Oncology (2017)

TPS11625 Background: Today, personalized cancer medicine implies matching the patient’s tumor genomic characteristics with molecularly and immune targeted agents. Although there are an increasing number of DNA aberrations that can now be matched to a cognate therapy, some patients do not display such druggable oncogene drivers. Methods: WINTHER is an open non-randomized study involving 6 cancer centers in France, Spain, Israel, Canada and USA applying genomic and also transcriptomic assays to guide treatment decisions. The novelty of the WINTHER approach lies in the use of tumor and matched normal tissue biopsies together and an algorithm for predicting efficacy of therapies. The aim is to provide a rational therapeutic choice for all of the patients enrolled in the study whether or not they harbor actionable DNA alterations. The study endpoint is the comparison of the progression-free-survival (PFS) under the WINTHER selected therapy to the PFS of the last therapeutic line. Patients included have refractory metastatic cancer of any histological type, with at least one prior therapeutic regimen and performance status of 0 to 1. Patients who have received a matched treatment based on a molecular anomaly as their immediate prior therapy were excluded. After consent, patients undergo a tumor and histologically-matched normal tissue biopsy. Extracted DNA and RNA of both tumor and normal from frozen tissues at the local center under common standard operating procedures are sent to centralized laboratories for omics investigations. DNA is investigated at Foundation Medicine Inc. and RNA at Gustave Roussy using Agilent technology. For RNA, the WINTHER algorithm is applied on the differential RNA expression data between tumor and normal tissues and establishes the list of drugs with the presumed higher score of efficacy for each patient. Patients with actionable genomic events enter in ARM A, and patients without any druggable anomaly of the DNA enter in ARM B and are treated using the WINTHER algorithm RNA-based treatment decision tool. To date, the trial has recruited 303 patients. Clinical trial information: NCT01856296.
Initial safety results from a randomized, phase II study of high-risk colorectal cancer patients (stage IIIC) treated with either regorafenib or standard of care (no treatment) after adjuvant FOLFOX.
Authors: Thomas H. Cartwright, Thu-Cuc Nguyen, Allen Lee Cohn, Donald A. Richards
Journal: Journal of Clinical Oncology (2017)

e15152 Background: Standard adjuvant therapy for colorectal cancer (CRC) is fluoropyrimidine or FOLFOX. The stage IIIC relapse rate is high with a median 5 year survival of only 28%. The multi-kinase inhibitor regorafenib has shown significantly improved overall survival (OS) versus placebo in 3 rd -line+ metastatic CRC patients (pts) in 2 phase III trials. We explore whether adding regorafenib to standard adjuvant therapy is able to reduce the high relapse rates in stage IIIC CRC pts. Methods: This study compares efficacy and safety of adjuvant FOLFOX +/- 6 cycles of regorafenib in IIIC CRC pts. Study endpoints include: finding the starting dose of regorafenib that allows ≥75% pts to complete therapy after adjuvant FOLFOX. The first 50 pts are being randomly assigned to either 120 or 160 mg of regorafenib daily for 3 weeks followed by 1 week of rest for a total of 6 cycles. We report the initial safety results on the first 24 pts treated. 6 pts discontinued treatment; 2 received 120 mg and 4 received 160 mg Results: Of the pts completing 6 cycles of regorafenib 120 mg vs 160 mg, the most common grade 3 toxicities were hypertension (0 vs. 30%), rash (10 vs.30%), and lipase elevation (0 vs 10%). No grade 4 or 5 toxicities were observed. Conclusions: The interim analysis reveals no increased toxicities from the addition of regorafenib at either 120 mg or the approved dose (160 mg), to adjuvant FOLFOX. Toxicities observed were mostly grade 1 or 2 and medically manageable. No safety signals have been identified. This study continues to enroll pts. Clinical trial information: NCT02425683.
Individual funding request process is bad for everyone
Authors: Mitzi A J Blennerhassett
Journal: BMJ (2018)

The individual funding request process is not only unfair and unreasonable, it is detrimental to doctors as well as patients.1

In 2005 I had difficulty accessing a course of manual lymphatic drainage for midline lymphoedema that was caused by NHS cancer treatment. Eventually the primary care trust commissioned an intensive course at a hospital that usually treated only arm lymphoedema. This was monitored and …
Horizon: An ambispective study of 663 patients who initiated pembrolizumab for advanced melanoma within the French early access program.
Authors: Nicolas Meyer, Laurent Mortier, Caroline Dutriaux, Marie Thérèse Leccia, Brigitte Dreno, Evelyne Boos, Catherine Hunault, Lynda Benmahammed, Philippe Saiag
Journal: Journal of Clinical Oncology (2018)

e21519 Background: Pembrolizumab (PBZ), a monoclonal anti-PD1 antibody, has been approved in France as a first-line treatment of patients with advanced melanoma in Oct. 2015. Although this treatment has been shown to significantly improve OS and PFS of patients with advanced melanoma, few data are available on its use in a real-life setting. Horizon is an ambispective analysis of patients who initiated PBZ between Jun. 2014 and Sept. 2015, within the French early access program (ATU-temporary authorization for use). We present the results of the 2nd interim analysis (data cutoff 01/07/2017) Methods: Horizon is a national multicenter ambispective cohort study of patients who initiated PBZ (2mg/Kg/3weeks) for advanced melanoma through the ATU in France between Jun. 2014 and Sept. 2015. Primary objective was to evaluate the 5-years OS (from the 1st infusion of PBZ to death). Secondary objectives were to 1-characterize response duration (DoR) to 1st tumor progression or death, whichever came first), ORR (proportion of patients with CR or PR based on radiological criteria) and DCR (% of patients with confirmed CR, PR or SD for at least 24 weeks based on radiological criteria); 2-evaluate the 5-years PFS (from the 1st infusion of PBZ to progression); 3- describe the use of PBZ in clinical practice. OS, PFS and DoR were analyzed using Kaplan Meier survival analysis. Results: A total of 663 patients, (sex ratio M/F = 1.15) were included with a median follow-up of 12.95 months (95%CI: [11.15-16.16]). Around 26% of patients were melanoma treatment-naïve at PBZ initiation. The median OS was 14.89 months (95%CI: [12.26-18.03]); the 2- and 3-years OS rates were 38.9% and 30.7% respectively. The median PFS was 3.25 months (95%CI [2.98-3.7]). ORR was 36.4%, DCR was 41.3%. Patients with BRAF mutation, increased LDH, ECOG > 1, brain metastases or < 70 years-old, had poorer therapeutic outcomes. No significant toxicity was observed as compared to previous reports on PBZ. Conclusions: This analysis of real-life use of PBZ provides therapeutic outcomes similar to phase III studies results, and confirms the acknowledged predictors of response in melanoma (i.e. LDH, BRAF mutation).
Preliminary results of a first-in-human, first-in-class phase I study of MTL-CEBPA, a small activating RNA (saRNA) targeting the transcription factor C/EBP-α in patients with advanced liver cancer.
Authors: Debashis Sarker, Elizabeth Ruth Plummer, Bristi Basu, Tim Meyer, Kai-Wen Huang, T.R. Jeffry Evans, Duncan Spalding, Yuk Ting Ma, Daniel H. Palmer, Cheng Ean Chee, Nagy A Habib
Journal: Journal of Clinical Oncology (2018)

2509 Background: MTL-CEBPA is a liposomal formulation of saRNA targeting the transcription factor C/EBP-α, which acts as a master regulator of liver homeostasis and multiple oncogenic processes including cell cycle control, proliferation and angiogenesis and inhibits hepatocellular cancer (HCC) tumor growth in preclinical models. MTL-CEBPA is the first saRNA and the first drug targeting C/EBP-α entering clinical trials. Methods: Patients (pts) with advanced HCC (Child-Pugh A/B) or secondary liver cancer, were enrolled in a 3+3 dose escalation study. MTL-CEBPA is administered as a 1-hr IV infusion on Day 1, 8 and 15 of a 28 day cycle. The primary endpoint was safety and the secondary endpoints included PK, liver function improvement and anti-tumor activity. Correlative studies include C/EBP-α mRNA levels in PBMCs and tumor tissue, evaluation of C/EBP-α downstream target genes (e.g.TGFβ) and distal target engagement in WBCs (e.g.IL-6, NF-κB). Results: 19 participants have been treated across 5 dose levels (28-130 mg/m2): 13M/6F, median age 67 yrs (range 27 - 80), ECOG PS 0/1: 9/10. Tumour types include HCC (13), colorectal (4) and fibrolamellar (2). The most common treatment-related AEs (all grades/grade 3) include fatigue (9/1), diarrhoea (5/0), AST increase (5/1), low platelets (2/1) hyperbilirubinaemia (5/1) and hypophosphataemia (4/1). Maximum tolerated dose has not yet been reached. Serum PK analysis shows a terminal half life of > 24 hrs, with dose proportional Cmax and AUC. Analysis of WBCs showed a significant increase of C/EBP-α expression during treatment providing evidence of target engagement. Of 10 evaluable pts with HCC, 4 pts have had SD≥ 4months, with one patient having an ongoing PR for 18 months associated with 73% decrease in tumour volume and reduction in IL-6, NF-κB and IFN-γ. Conclusions: Once weekly MTL-CEBPA therapy was well tolerated, shows promising PD and initial clinical response in patients with advanced HCC. Updated results for the dose escalation will be presented. Clinical trial information: NCT02716012.
A comprehensive genomic analysis of squamous cell carcinomas of the lung, esophagus, and head and neck.
Authors: Lara Ann Kujtan, Paul Case, Robin Imperial, Omer M Toor, Ateeq Khaliq, Varsha Muthukumar, Kevin F Kennedy, Ramzi M Mohammad, Arif Hussain, Timothy J. Pluard, James Case, Janakiraman Subramanian, Ashiq Masood
Journal: Journal of Clinical Oncology (2018)

12123 Background: Squamous cell carcinomas (SCC) of the lung, esophagus and head and neck (H&N) are indistinguishable by histology. Data from large-scale genomic studies have identified significant similarities in the mutational profiles of these tumors. Combined genomic analysis will lead to the discovery of unique molecular similarities and dissimilarities of these tumors. Methods: We analyzed whole exome, RNA, miRNA and methylation data of 1221 patients with lung (39.6%), esophagus (26.3%), and HPV-negative H&N SCC (34.1%) from the Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC). WTSI Mutational Signature Framework was used to develop mutational signatures (MS). Results: Nine novel significantly mutated genes were identified in the combined analysis, including PYHIN1, a key mediator in the inflammasome pathway. Mutations in the inflammasome pathway (PYHIN1, MNDA, CIITA, AIM2, IFIT, IFNG), which is key for tumor antigen processing and presentation to T cells, were identified in 136 SCC samples (11.1%). All mutations were mutually exclusive of one another. We also discovered a novel tumor suppressor gene mutation in Asian patients with esophageal SCC, NEFH (7%), which was mutually exclusive of the TP53 mutation. Seven novel gene amplifications and two deletions were detected in the combined population. Two novel MS with high stability (0.83 and 0.85) were recognized in H&N (7% and 13% of all mutations) with maximum cosine similarities of 0.37 and 0.34 respectively. All TCGA samples displayed COSMIC MS 1(age-related), 2 (APOBEC), and 4 (tobacco-related), while the esophageal ICGC sample showed COSMIC MS 13(APOBEC) and 17(unknown). Conclusions: Our analysis identified a novel tumor suppressor mutation in Asians with esophageal SCC. We report possible dysregulation of the tumor antigen-processing pathway in a small but significant proportion of patients. Two novel MS in H&N SCC were identified, and the remaining MS were similar across all three tumor types in the TCGA. Esophageal ICGC tumors had different mutational profiles suggesting a unique mutational process in Asians.
Thymoma and thymic carcinoma case series: The Christie Hospital.
Authors: Alicia Conway, Kimberly Fletcher, Raees Mohammed, Zena Salih, Ourania Romanidou, George Papaxoinis, Margaret Harris, Yvonne J. Summers
Journal: Journal of Clinical Oncology (2016)

e20110 Background: Thymic epithelial tumours (TETs) are rare epithelial mediastinal tumours with an incidence of 1.7/1,000,000 people in Europe. At diagnosis most pts are asymptomatic, however TETs are associated with autoimmune (AI) syndromes, most notably myasthenia gravis (MG). Prognosis is good with 5-year survival rates of 96%, 86%, 69%, and 50% for stages I-IV respectively. Treatment is dependant on histology, stage and resectability. As relatively uncommon malignancies, various staging classifications and international guidelines on management are currently in use for TETs. The aim of this retrospective single centre study of sequential patients diagnosed with TET was to compare our data against pre-existing international guidelines, with a view to producing standardised local management guidelines. Methods: All cases of TET in the Greater Manchester region (population 3.4 million) between January 2009 and December 2014 were identified from pathology records. Retrospective data collection of demographics, histology, stage, management and patient outcomes were collated from health records, radiology and pathology databases. Results: Pre-op chemotherapy (CT) occurred in 4 pts (1 R0, 1 R1, 2 R2). 1 pt with R2 resection had post op CT. 22 pts had post-op radiotherapy (RT) (5 R0, 13 R1, 2 R2). There were 8 deaths in this cohort with OS at 1, 2 and 4 years 93%, 91% and 71% respectively. Median follow-up was 30 months. For stages I-II: OS 1-y=97%, 2-y=97%, 4-y=80%, compared to stages III-IV: OS 1-y=78%, 2-y=67%, 4-y=33%, median=47 months (p=0.006). Conclusions: Incidence of TET’s in Greater Manchester is higher than expected (2.6:1,000,000), however demographics are consistent with published data. Management and survival of pts was in keeping with international guidelines, however follow up was not standardised. As a result of this study local guidelines for management and follow up have now been established. Type Thymoma:thymic 44:4 Sex Male:female 21 (44%): 27 (56%) Age Mean Age (range) 58.5 (25-83) Autoimmune conditions MG 9 (20%) Other 7 (15%) Stage Masaoka-Koga I:II:III:IV 15 (31%):24 (50%):8 (17%):1 (2%) Initial treatment Radical RT 1 (2%) BSC 1 (2%) Surgery 46 (96%) Resection outcomes n=46 R0:R1:R2 27 (59%):14 (30%):5 (11%)