tbuckley/cabot-search huggingface dataset:
Real world results of liquid biopsy in stage 3/4 solid tumors and potential ''clinical actionability."
Authors: Rebecca Christian Arend, Angelina Londono, Alba Martínez, Andrew Ford, Charmaine Brown, Chen-Hsiung Yeh, Nader Javadi, Glen J. Weiss
Journal: Journal of Clinical Oncology (2018)

2555 Background: Next-generation sequencing (NGS) of plasma circulating cell-free DNA (cfDNA) and cfRNA, also known as a “liquid biopsy”, is a minimally invasive technique available in the clinic. Here we report initial liquid biopsy results from stage 3 and 4 solid tumors using the Circulogene Theranostics Personalized Gene Profile (CGP, 50-gene panel) on cfDNA and cfRNA. Methods: DNA mutations detected and, where available, PD-L1 expression, ALK, and ROS1 fusions in RNA were retrospectively compiled from CGP ordered at two centers. To be considered clinically actionable and commercially available (CA), the biomarker had to have demonstrated clinical efficacy in human cancer prospective trials using the biomarker and commercially available drug that can target that biomarker. To be considered a clinical trial possibility (CT), one of the biomarkers was required to have a drug in clinical development using the biomarker for the patient’s cancer type and disease stage listing on clinicaltrials.gov during the time period that CGP was ordered. Results: One hundred forty-five patients (median age 66 years, range 25-95; 35 men and 110 women) underwent CGP testing between November 2015 and October 2017. The majority of cancer types were ovarian, breast, pancreatic, uterine, and prostate. Most common DNA mutations recorded were TP53, PTEN, PI3KCA, SMAD4, and BRAF. There was a median of 2 mutations/patient (range 0-11), with a 0.69% sample failure rate. Overall, 36 cases had no detectable mutations (24.8%). There were six samples with PD-L1 results, and one was positive (16.7%), in the range of expected PD-L1 positivity across solid tumors. In addition to the 36 mutation negative cases, 19 cases had no potential match for CA or CT (e.g. APC, GNAS, SMAD4 mutations). Thus, 89 (61.4%) of cases had the potential for CA and/or CT drug identified by liquid biopsy. CGP is priced at approximately $600 per sample comparable to current reimbursement rate. Conclusions: In this real world experience, despite the low plasma sample input, there was a 0.69% sample failure rate, suggesting CGP in situ enrichment is robust. More experience with this assay and linkage with clinical outcomes is warranted.
Medical literature on mobile applications related to cancer.
Authors: Andrea Carolina Anampa-Guzman, Pamela Contreras Chavez, César Gutiérrez, Joanne M. Jeter
Journal: Journal of Clinical Oncology (2017)

e18044 Background: In 2014, there existed 166 mobile applications related to cancer. However, many mobile applications are being developed without published validation by the medical community. The aim of this review was to provide an overview of the studies about mobile applications related to cancer. Methods: Scopus, PubMed, PMC, BVS and Scielo were systematically searched for studies published up to December 2016. A broad search using the terms “neoplasia”, “cancer”, “neoplasm”, “smartphone application” and “mobile app” was conducted. Article abstracts were reviewed for study eligibility, followed by reviews of full papers. We found 195 articles and 48 were included. Articles were included if they reviewed commercial mobile applications or if they described the development and evaluation of a mobile application related to cancer. Articles were excluded if they were about other telehealth technologies, primarily editorials, solely described study protocols, abstracts of congresses or books. Results: The earliest article was published in 2012 and there is an increasing rate of articles published. The majority of articles are original articles (85.42%) and 10 of them are clinical trials. Almost all articles were written in English (95.83%). Nearly 40% of the articles talked about mobile applications for the management of cancer. The intended audience of the mobile applications described in the studies was mostly patients. The cancers most popular among the articles were breast and skin cancers. The countries with the most studies on mobile applications related to cancer are the United States and South Korea. Conclusions: There is a large number of cancer related mobile applications. Further studies would help us understand the current and future use of these health related technologies. [Table: see text]
A phase I dose-escalation study of intraperitoneal (IP) cisplatin, IV/IP paclitaxel, IV bevacizumab, and oral olaparib for newly diagnosed adenxal carcinoma.
Authors: Jason A. Konner, Nicole N Boucicaut, Roisin Eilish O'Cearbhaill, Dmitriy Zamarin, Vicky Makker, Paul Sabbatini, William P. Tew, Karen Anne Cadoo, Rachel N. Grisham, Carol Aghajanian
Journal: Journal of Clinical Oncology (2017)

5572 Background: IP cisplatin (Cis) plus IV/IP paclitaxel (Tax) is a standard therapy for optimally debulked adnexal cancer. We previously demonstrated the feasibility of combining bevacizumab (Bev) with this IV/IP regimen. In this study IP Cis, IV/IP Tax, and IV Bev are combined with olaparib (Ola) as front-line therapy. Methods: Patients with newly diagnosed adnexal (ovarian, fallopian tube, or primary peritoneal) carcinoma, acceptable organ function, and KPS ≥ 70% are eligible. Patients receive 6 cycles of chemotherapy plus Bev: Tax 135 mg/m 2 IV over 3 hours on Day 1, Bev 15 mg/kg IV on Day 1 (starting cycle 2), Cis 75 mg/m 2 IP on Day 2, Tax 60 mg/m 2 IP on Day 8. Bev is continued every 3 weeks for 21 treatments after chemotherapy is complete. In addition, Ola is given at escalating doses (50/100/200mg tabs BID) on Days 2-8 during cycles 1-6, and then 300mg BID Daily during cycles 7-22. The primary objective is to evaluate the MTD and safety/tolerability of Ola when combined with IP Cis, IV Bev and IV/IP Tax using a 3+3 dose escalation scheme. Results: Seventeen women have been treated [median age 57 (47-73)]: 8 in cohort 1 (50mg), 3 in cohort 2 (100mg) and 6 in cohort 3 (200mg). Thirteen (76%) completed all 6 cycles of IV/IP cis/tax; 2 (12%) experienced IP port malfunction (both were removed and replaced); 2 (12%) switched from IP Cis to IV carboplatin due to nephrotoxicity (via ATN and/or OCT-2 inhibition). Grade 3/4 toxicities have included: neutropenia (50%), hyperglycemia (12.5%), leukopenia (12.5%), anemia (18.8%), fatigue (12.5%), and lymphopenia (31.3%). There were 2 occurrences of related grade 3 small bowel obstructions (12.5%), during cycles 2 and 7, respectively. There were no perforations or fistulae. Maintenance therapy with Bev + Ola was generally well tolerated. Conclusions: The addition of Ola to this IV/IP regimen appears to be feasible. Ola may increase the risk of creatinine elevation and myelotoxicity. The MTD of intermittent dosing of Ola tabs concurrent with chemotherapy appears to be 200mg BID, while maintenance bev + full-dose ola at 300mg BID continuous appears feasible following IV/IP. Updated results will be presented. Clinical trial information: NCT02121990.
Different degree of response to checkpoint inhibitors in metastatic NSCLC patients according to mutations within KRAS gene.
Authors: Alfredo Addeo, Javier Torralvo, Pierre-Yves Dietrich
Journal: Journal of Clinical Oncology (2018)

e21061 Background: AntiPD1/antiPDL1-based immunotherapy (IO) has changed the prognosis of non small cell lung cancer (NSCLC) with a substantial improvement in overall survival (OS),presenting long lasting responses in subset of patients (pts). Several factors have been associated with the likelihood of better survival i this contest, including smoking exposure and presence of KRAS-mutation. There are no data on IO activity according to specific mutations within KRAS in NSCLC Methods: We have collected cases of stage IV NSCLC pts, KRAS mutated, treated with IO agents within our institution from January 2016 to december 2017. A new generation sequencing test (NGS) was performed in all cases and correlation with the patient clinical outcomes done: disease control rate (DCR) Partial response (PR), progression free survival (PFS) and overall survival (OS) were the endpoint of our study Results: Twenty patients with advanced NSCLC were treated with IO (Nivolumab 65%, Pembrolizumab 25% and Atezolizumab 10%, respectively) from January 2016 to December 2018. The mutations were G12V in 6 pts (30%), G12C in 7 pts (35%), G13C in 3 pts (15%), G12A in 2 pts (10%), G61H in 1 pt (5%) and G12p in 1 (5%). The subgroup included 34% of female, median age of 65 years, and all patients had PS0-1. The immunotherapy (IO) was administered as 1st, 2nd and ≥ 3rd therapy in 10%, 75 % et 15% of the 20 pts, respectively: Within the KRAS mutation group (20 pts) the DCR was 83.5% and the PR was 67%., the PFS was 9.5 months and OS was 35 months. At the time of analysis 7/45 pts were still receiving the immunotherapy treatment. Notably all the patients who carried the G12V achieved a partial response (6 out of 6) to IO regardless the line of treatment with a PFS of 14.2 months and OS 42 months. Conclusions: Our analysis has showed that KRAS-mutation pts represent a subgroup of pts that seem to substantially benefit from IO agents in terms of both response rate, PFS and OS. Notably within the subgroup of NSCLC patients harbouring a KRAS G12V mutation a strong sensibility to IO was seen. Prospective studies and trials are warranted to better define the role of the different KRAS mutations with NSCLC and their different sensitivity to IO.
Efficacy and safety of VCEP-M for induction treatment of mixed phenotypic acute leukemia.
Authors: Ahmad Alhuraiji, Ahmad Shad, Tarek Owaidah, Hazza Alzahrani, Fahed Al Mhareb, Naeem Chaudhri, Fahad Alsharif, Said Mohamed, Ghuzayel Al Dawsari, Mohammad Islam, Amr Hanbali, Syed Osman Ahmed, Mahmoud Deeb Aljurf, Walid Rasheed
Journal: Journal of Clinical Oncology (2016)

e18504 Background: Mixed phenotype acute leukemia (MPAL) is a rare subtype of acute leukemia, characterized by an aggressive behavior and a tendency towards resistance to therapy and overall poor outcome. The aim of the study is to evaluate the efficacy and toxicity of VCEP-M protocol. Methods: A retrospective study. We included patients diagnosed with mixed phenotypic acute leukemia at King Faisal Specialist Hospital and research Centre (based on WHO and EGIL criteria) from 2002-2014 treated with upfront VCEP-M Protocol. We excluded patients who are less than 15 years of age and patients treated outside our institution. Data were collected from our electronic tumor registry. Results: We included 19 patients who met the inclusion criteria. Baseline characterisitics are shown below. Ten patients were salvaged at Day 14 Bone marrow with Fludarabine 30mg/m2/d and cytarabine 2gm/m2/d (D1-5) (FA) chemotherapy. Complete remission (CR) rate at day 28 bone marrow was 95% (18 patients). Thirteen patients proceeded to allogenic stem cell transplantation (SCT). All 6 patients who had not had SCT died. Overall survival (OS) and disease free survival (DFS) at 5 years were 54% and 57% respectively. Treatment related toxicity were mainly sepsis (11 patients) and disseminated intravascular coagulation (DIC) (2 patients). There was no reported treatment related deaths. Conclusions: VCEP-M appears effective in the treatment of MPAL with a safe toxicity profile. All patients would likely benefit from SCT. VCEP-mitoxantrone protocol (KFSHRC protocol). Vincristine 1.4 mg/m2 IVP Days 1,8,15&22 Cyclophsphamide 600 mg/m2 IVPB Day 1 Etoposide 100 mg.m2 IVPB daily Days 1-5 Prednisone 60 mg/m2 PO Days 1-28 Mitoxantrone 10 mg/m2 IVPB Days 1-3 Repeat Bone marrow biopsy on day 14 and 28 IT prophylaxis: As per ALL protocol Post remission therapy: In the presence of a sibling donor these patients should be considered for an allogeneic stem cell transplant. Total N=19 Range Median Age (yrs) 24 15-52 Male % 15 (79%) WBC (X109/L) 12.8 2.2-269.4 Hg (g/dL) 9.4 4.9-11.1 Plt (X109/L) 46 7-265 LDH 423 154-3404 CNS involvement 2 (11%) Abn. Cytogenetic 9 (47%) ANC recovery (median, day) 37 16-49 Plt recovery (median, day) 36 14-47 SCT in CR1 13 (68%) Conditioning Cy/TBI (100%) MRD 18 (95%)
Correlation of degree of tumor immune infiltration and insertion-and-deletion (indel) burden with outcome on programmed death 1 (PD1) therapy in advanced renal cell cancer (RCC).
Authors: Martin Henner Voss, Jacqueline Buros Novik, Matthew David Hellmann, Mark Ball, A. Ari Hakimi, Diana Miao, Claire Margolis, Christine Horak, Megan Wind-Rotolo, Guillermo De Velasco, Nizar M. Tannir, Pheroze Tamboli, Leonard Joseph Appleman, Kimryn Rathmell, James J Hsieh, Mohamad Allaf, Toni K. Choueiri, Eliezer VanAllen, Alexandra Snyder, Robert J. Motzer
Journal: Journal of Clinical Oncology (2018)

4518 Background: Mutation load and neoantigen burden predict benefit from anti-PD1 therapy across several cancers but are generally low in RCC. Pan-cancer comparisons highlight RCC for its enriched tumor immune infiltrate and a high proportion of indels, which may be immunogenic. We investigated these phenomena in anti-PD1 treated patients (pts) with comparison to pts receiving tyrosine kinase inhibitors (TKI). Methods: Whole exome sequencing (WES) was done for 77 tumors from 2 anti-PD1 treated pt cohorts; 25 pts provided RNAseq data. Overall mutation burden, indels, and predicted neoantigens were quantified. ESTIMATE and CIBERSORT algorithms were used to infer abundances of immune infiltrate and detailed immunophenotypes from RNAseq. We investigated correlation of molecular features with overall survival (OS) and durable clinical benefit (DCB = progression free survival > 6mo). A cohort of TKI-treated pts with no prior anti-PD1, previously analyzed as part of the TCGA, was used for comparison (35 with WES, 33 with RNAseq). Results: Higher overall immune infiltration correlated favorably with DCB in the PD1 cohort (stratified Mann Whitney test; p = 0.05) but not in TKI treated pts (p = 0.84). As the two most abundant infiltrating cell types, M2 macrophages (p < 0.001) but not CD8+ T cells (p = 0.22) associated with DCB from anti-PD1 therapy; neither associated with outcomes in TKI pts (p = 0.15, p = 0.76). Expectedly, mutation counts were low (median 68; inter-quartile range 45-93). While neither mutation nor neoantigen burden impacted on OS with anti-PD1 therapy (stratified Cox Proportional HR 1.02; p = 0.6; HR 1.01; p = 0.69, respectively), association with OS was significant for frameshift indel count (HR 0.85; p = 0.006). Correlation was similar but did not reach significance in TKI pts (HR 0.87; p = 0.07). Conclusions: In anti-PD1 treated RCC pts, baseline tumor immune infiltration, particularly by M2 macrophages, associated favorably with outcome. In contrast to other cancers, mutation and neoantigen load did not affect treatment outcomes; yet higher indel counts appeared to confer superior OS. Such associations were not seen for TKI treated pts.
A pilot pre-surgical study evaluating anti-PD-L1 durvalumab (durva) plus anti-CTLA-4 tremelimumab (treme) in patients with muscle-Invasive, high-risk urothelial bladder carcinoma who are ineligible for cisplatin-based neoadjuvant chemotherapy.
Authors: Jianjun Gao, Arlene O. Siefker-Radtke, Neema Navai, Matthew T. Campbell, Rebecca Slack, Charles Guo, Ashish M. Kamat, Surena F. Matin, John N. Papadopoulos, John C. Araujo, Amishi Yogesh Shah, Jorge M Blando, Luis M Vence, Fei Duan, Sreyashi Basu, Shalini Singh, Hao Zhao, Colin P.N. Dinney, Padmanee Sharma
Journal: Journal of Clinical Oncology (2018)

e16524 Background: In patients with muscle-invasive bladder cancer (MIBC), especially those with high risk features including lymphovascular invasion, hydronephrosis, T3b disease, or variant histology, cisplatin-based neoadjuvant chemotherapy followed by cystectomy improves overall survival as compared to cystectomy alone. However, it is estimated that over 50% of patients with MIBC are ineligible for cisplatin-containing therapy. Therefore, we propose to use durva plus treme as neoadjuvant therapy for this population of patients. Methods: We carried out a single-arm, pre-surgical clinical trial with durva + treme in patients with localized, high-risk MIBC who are ineligible for cisplatin-containing chemotherapy due to decreased renal function, neuropathy, hearing loss, or heart failure (NCT02812420). Each patient will receive durva (1500 mg) plus treme (75 mg) on weeks 1 and 5. Patients will then undergo surgery at week 9-11. Pre- and post-treatment blood and tumor samples will be collected for immunological and genomic analyses for clinical correlation. Results: Twelve patients have been enrolled on this trial. Six patients have completed cystectomy as of January 30, 2018. Of these 6 patients, 3 (50%) had pathologically complete response (pCR); one (17%) did not respond; two (33%) had upstaging of disease. Of the two upstaged patients, one was found to have tumor progression in a pre-existing pelvic lymph node and was taken off trial, treated with chemotherapy, then had cystectomy with pCR. Only 1 of 12 patients developed grade 3 immune related toxicity. Immunologic and molecular analyses are ongoing on all collected samples. Conclusions: To date, out data indicate that durva plus treme may be an effective and well tolerated neoadjuvant therapy for patients with MIBC ineligible for cisplatin-based therapy. Based upon these data, we have expand this pilot trial from 15 to 35 patients. We will also report correlative biomarker data. Clinical trial information: NCT02812420.
Association of minority-serving hospitals with lower resources for cancer care.
Authors: Kim Felder Rhoads
Journal: Journal of Clinical Oncology (2016)

6547 Background: Disparities in colorectal cancer (CRC) are longstanding. Previous studies show links between minority use of low quality hospitals, suggesting a role for location of care in disparities. No studies have linked the impact of hospital structure with processes of care in minority serving hospitals (MSH). The purpose of this study is to compare structural factors; financial characteristics and processes of care in MSH versus other settings. Hypothesis: MSH have fewer structural and financial resources for cancer care and lower adherence to evidence-based care. Methods: California Cancer Registry linked with patient discharge data and hospital characteristics identified all cases of CRC in California (2001-2006). MSH was defined by top quartile of minority discharges in the state. Structural characteristics included teaching hospital, CRC volume, rural location, NCI and Commission on Cancer (CoC) accreditation. Financial characteristics included disproportionate share; Medicaid utilization and ownership. Evidence based care was defined by the National Comprehensive Cancer Network (NCCN). Chi-square analysis tested for significant differences between hospital groups. Results: Of 354 hospitals, 96 (27%) were MSH. Compared to non-MSH, there was no difference in the proportion of academic MSH. A quarter of MSH were high volume versus non-MSH settings (39%, p = 0.04). Only 3% of MSH were rural versus non-MSH (16.3%, p < 0.001). There were no NCI accredited MSH (versus 9 non-MSH, p = 0.03); and only 20% were CoC accredited (versus 33.3% non-MSH; p = 0.03). The majority of MSH (68%) were disproportionate share hospitals (versus 16% of non-MSH; p = 0.001). More MSH were high Medicaid service settings (52% vs. 2.4%; p < 0.0001). There was no difference in hospital ownership. More MSH settings had low level compliance with delivery of appropriate surgery (50% versus 25.6%; p < 0.0001); delivery of indicated radiation (38.7% versus 31.2; p < 0.001). There was no difference in chemotherapy. Conclusions: Minority serving hospitals in California have limited infrastructure to deliver high quality cancer care which may explain low guideline adherence. MSH use may explain disparities in CRC and may provide targets for interventions to address them.
The different strategy of managing anastomosed fistula following radical resection for colon and rectal cancer.
Authors: Haitao Jiang, Xiaojie Tan, Xiaodong Liu, Maoshen Zhang, Yun Lu
Journal: Journal of Clinical Oncology (2018)

e15708 Background: To compare the application value and opportunity of enterostomy bypass and active drainage foranastomotic fistula after radical resection for colorectal cancer. Methods: Retrospective analysis of 62 cases of anastomotic fistula after radical resection of colorectal cancer were treated in our department from June 2013 to December 2017, including 26cases of anastomotic fistula after surgical resection of colon cancer and 36 cases of anastomotic fistula after surgical resection of rectal cancer. After anastomotic fistula were conformed, the patients were given to replace the dual-lumen-tube drainageto drain the intestinal content and nutrition support for conservative management until the fistula healed or given transverse colon stoma or ileum stoma to bypass the intestinal content for surgicalintervention for the fistula. Results: All the anastomotic fistula after radical colectomy for colon cancer were healed after conservative treatment (0/26 vs 12/36, P < 0.01), the average fistula healing time was 20.5 days, but only 12 cases of anastomotic fistula after surgical resection of rectal cancer healed by active drainage, other cases were healed after given transverse colon stoma to bypass the intestinal content, the average time of stoma was 20 days after fistula occurred, and the average fistula healing time was 24.5 days (20.5 d vs 24.5 d, p = 0.004), which was longer than that of anastomotic fistula after colectomy of colon cancer.The percentage of transverse colon stoma needed for the anastomotic fistula after radical resection of rectal cancer was significantly higher than that of anastomotic fistula after radical colectomy of colon cancer (24/36 vs 0/26, P < 0.01). The cost of anastomotic fistula after surgical resection of rectal cancer was higher than that of anastomotic fistula after surgical resection of colon cancer (2,500 USD vs 1,800 USD,P < 0.01) Conclusions: Most of anastomotic fistula after radicalcolectomy of colon cancer can be healed by conservative treatment, but most of anastomotic fistulasfollowingradical resection of rectal cancer were healed by transverse colon stoma to bypass the intestinal content, the stoma opportunity was 3 weeks postoperatively.