tbuckley/cabot-search huggingface dataset:
The potential clinical and fiscal impacts of blood-based methylated Septin9 testing for colorectal cancer screening.
Authors: Joshua A. Roth, Theo DeVos, Scott David Ramsey
Journal: Journal of Clinical Oncology (2016)

e15072 Background: Colonoscopy and fecal tests are effective at reducing colorectal cancer (CRC) related mortality, yet nearly 35% of those eligible are not screened, in part due to aversion to the test procedures. Accordingly, new blood-based methods may have a role in reducing the unscreened proportion of the population. The objective of this study was to estimate the potential clinical and fiscal impacts of adding blood-based CRC screening with methylated Septin9 DNA (hereafter ‘Septin9’) to reduce the unscreened proportion to 20%, a goal set by the American Cancer Society. Methods: We developed a simulation model to estimate 3 year health outcomes with and without availability of Septin9 in a commercial health plan population (age < 65) with 1m enrollees. The base case compares current U.S. screening distributions (53% colonoscopy, 12% fecal testing, 35% not screened) vs a scenario where Septin9 is covered and used by an additional 15% of the unscreened. Age distributions and CRC incidence were derived from the US census and SEER, respectively. Screening test performance was based on validation studies of Septin9. We included costs of the screening tests, diagnostic colonoscopy, pathologic evaluation of positive colonoscopy findings, and stage-specific treatment of CRC. We calculated the number of expected advanced adenomas (AA), non-advanced adenomas (NAA), and CRC cases in each scenario, as well as total and per-member per-year (PMPY) cost—a measure of health plan expenditure adjusted for plan size and duration of cost impacts. Results: Over a 3-year time horizon, use of Septin9 by 7600 previously unscreened plan members resulted in 4000 more diagnostic colonoscopies, 1900 more pathologic evaluations, 350 more AA findings, 1300 more NAA findings, and 65 more CRC cases. Additional health plan expenditures totaled $18m (PMPY = $6). For reference, a recent study estimated that increasing the colonoscopy screened proportion from 50% to 70% would cost $11 PMPY. Conclusions: Blood-based testing has the potential to improve CRC screening rates and improve cancer and adenoma detection. The fiscal impact of blood-based testing to reach unscreened individuals is similar to other accepted screening tests.
P05.08 Ependymal tumors - Heterogeneity and multidisciplinary behavior in this adult neuroepithelial malignancy
Authors: A L C Vasconcelos, A F P Figueiredo, D Possidónio, L Bujor, M R Dionísio, M L Albuquerque, J Miguéns
Journal: Neuro-Oncology (2018)

Ependymal tumors (ET) are neuroepithelial malignancies of the CNS that occur in both children and in 1.8% of adults. Anatomically arise along the entire neuroaxis comprising the hemispheres, the hindbrain and the spinal cord. More than 20% of primary spinal cord tumors are of ET lineage and all have a variable clinical behavior. In 40% of patients (pts) are incurable because of the scarceness of effective treatment options. The 5-year overall survival (OS) is about 70% to 89% in adult pts. The surgical resection extent has been the only clinical prognostic known associated with survival. The current standard of care includes maximal safe surgical resection, followed by focal radiotherapy (RT). Our goal is to review pts outcome with these rare tumors in adults presented in multidisciplinary board to post-operatory RT. Review of 12 pts with ET diagnosis who underwent RT between 2008–2018. Data collected at Glintt HS ®; Mosaiq ® from our institution database. Local recurrence free survival (LRFS), distance progression-free survival (PFS) and overall survival (OS) were calculated with IBM SPSS Statistics 21.0. Survival curves were generated using Kaplan-Meier method. Surgery resection, histopathological grade WHO classification and RT dose in local recurrence were analyzed. The impact of clinical and therapeutic variables on survival was evaluated by log-rank test. With a median age at diagnosis 44 (23–78) years old. Pts were 2 females and 10 males. Anatomical sites were 1 pt supratentorial; 6 pts infratentorial and 4 pts spinal cord. Staging included in 75% pts lumbar puncture and cranial/neuroaxis MRI. GTR was achieved in 77% of pts. WHO grade was III in 3 pts; grade II in 7 pts and 2 pts grade I. Median RT dose was 54Gy (50.4–59.4) with 2 pts with boost to posterior fossa and one pt 36 Gy for neuroaxis. The 5 and 10-year OS were 78% and 23% respectively, calculated from the surgery data to the last follow-up/death. 5-years free-local recurrence survival (FLRS) 73% calculated from the surgery date to the local recurrence date; with a 5-years distant progression-free survival (PFS) 100%. In this analysis 5-year LRFS was 67% for STR and 80% for GTR (p=0.715); 5-year LRFS was 100% pts WHO I; 0% pts WHO II; 75% pts WHO III (p=0.712) and 5-year LRFS RT doses were 100% > 54 Gy and 75% ≤54Gy (p=0.035). Current analysis includes only 12 pts with different anatomical sites ET, with heterogeneous behaviors, has no power to reveal optimum RT dose nor identify pts WHO grade that deferral post-operatory RT. Our 5 year OS likewise publications for adult. Genetic classification can accrue ET, resulting in more precise diagnostics, sharpen prognostic and improved therapy, beeing now ​surgery and RT therapeutic mainstays.
Predictors of long-term survival in newly diagnosed multiple myeloma (NDMM) patients (pts) enrolled in the Connect MM registry.
Authors: Cristina Gasparetto, Robert M. Rifkin, Howard R. Terebelo, Kathleen Toomey, Brian G. Durie, James W. Hardin, Sundar Jagannath, Lynne I. Wagner, Mohit Narang, Sikander Ailawadhi, E. Dawn Flick, Stanley Kotey, Shankar Srinivasan, Amani Kitali, Amit Agarwal, Rafat Abonour
Journal: Journal of Clinical Oncology (2018)

8037 Background: There are limited longitudinal data on disease management & outcomes for long-term survivors of MM. The Connect MM Registry is a US, multicenter, prospective observational cohort study designed to examine diagnostic & treatment (tx) patterns, clinical outcomes & QoL in pts with NDMM. Data from Connect MM were used to identify pt- & disease-specific baseline (BL) characteristics associated with ≥ 6 y overall survival (OS) vs death at < 6 y in pts with NDMM. Methods: Adult pts in Cohort 1 (enrolled ≤ 60 days from diagnosis from Sep 2009 - Dec 2011) had sufficient follow-up for evaluation; those censored at < 6 y (study discontinuation, ongoing but survival < 6 y) were excluded. BL characteristics were compared via logistic regression to identify those associated with ≥ 6 y OS (P < 0.05). Results: As of Feb 2017, median follow-up for Cohort 1 (N = 1493) was 65.4 mo. Median age was 67 y (range 24-94), 57% were male, & 59% were standard/low risk per IMWG criteria. Most pts (91%) had ≥ 1 novel agent in their first drug regimen (1L; Table). BL characteristics associated with ≥ 6 y OS by multivariate analyses were: age (≤ 70 vs > 70), ECOG PS (0-1 vs 2-5), lower ISS stage, platelet count (≤ 150 vs > 150 x 109/L), & lack of history of diabetes, del(17p), extramedullary plasmacytoma, or serum-free light chain abnormality. Matrix for predicting OS ≥ 6 y will be included in the presentation. Conclusions: This analysis identified pt- & disease-specific BL characteristics associated with ≥ 6 y OS in pts with NDMM. Higher rates of triplet tx, SCT, maintenance (with/without SCT), & higher response rates were observed in pts with ≥ 6 y OS. Clinical trial information: NCT01081028. ≥ 6 y OS (n = 246) Death < 6 ya (n = 662) First induction regimen in 1L, n (%) Triplet 111 (45) 260 (39) 1 novel tx 160 (65) 452 (68) 2 novel tx 69 (28) 142 (21) SCT in 1L, n (%) 125 (51) 157 (24) + maintenance 89 (36) 89 (13) no maintenance 36 (15) 68 (10) No SCT in 1L, n (%) 121 (49) 505 (76) + maintenance 62 (25) 123 (19) no maintenance 59 (24) 382 (58) Best response to first induction regimen in 1L, n (%) Stringent CR 2 ( < 1) 2 ( < 1) ≥ CR 19 (8) 19 (3) ≥ very good PR 42 (18) 75 (12) Overall response (≥ PR) 72 (31) 147 (24) ≥ minor response 167 (71) 371 (59) a585 pts were censored at < 6 y and excluded. CR, complete response; PR, partial response
Head and neck cancer in octogenarians: A single center experience.
Authors: Parth Anil Desai, Annapurna Saksena, Frank R. Miller, Anand B. Karnad, Sherri Rauenzahn Cervantez
Journal: Journal of Clinical Oncology (2018)

e18044 Background: The incidence of head and neck cancer (HNC) in the elderly is increasing. Although data regarding treatment paradigms for older patients have been published,there is little data for the oldest of the old (≥80 years of age), a cohort that is the fastest growing among the elderly population. We reviewed our experience in managing HNC in this cohort. Methods: This is a retrospective review of consecutive patients with HNC who were ≥80 years of age at their first presentation from January 2012 to January 2016. Demographic, clinical and treatment characteristics were collected and stored using REDCap. Exploratory and descriptive statistical methods were used. Results: 34 patients were identified. The mean age at presentation was 85 years. 52% were men and 49% were active or former smokers. The most common primary site of cancer was oral cavity (45%). The most common stage at presentation was IVA (48%). 32% had previously diagnosed and treated HNC. The treatment & toxicity characteristics are highlighted in table below. Locally advanced stage (III,IVA,IVB) patients receiving multimodality therapy had significantly better mean overall survival (23 months) than single modality therapy (8.5 months) (P < 0.02). Conclusions: Fit elderly patients with HNC including those ≥80 years of age at presentation deserve ideal multidisciplinary care. Multimodality treatment did show improved overall survival compared to a single modality therapy in locally advanced HNC. Palliative care and hospice referral is appropriate for many especially with relapsed/refractory disease. Prospective studies need to be done to define the ideal care of this cohort of the elderly population with HNC. Variable No/ Total evaluable Pathological type 30/34 Squamous cell carcinoma Other 4/34 Initial Treatment Chemotherapy 7 (22%) Radiotherapy 20 (63%) Surgery 17 (53%) Chemotherapy & Radiotherapy 6 (20%) Surgery & Radiotherapy 8(27%) Recurrence/Progression after treatment 12/20 (60%) Toxicity to Chemotherapy/radiotherapy Mucositis 9/21 Rash 5/21 Severe Xerostomia 5/21 Other 2/21 Procedures 11 (34%) Gastrostomy tube Tracheostomy 6 (19%) Hospice for progressed patients 7/12 (58%)
Ex-vivo tumor resection and auto-transplantation: A single-institutional long-term experience.
Authors: Tomoaki Kato, Peter Liou, Gary K. Schwartz, Jean Emond
Journal: Journal of Clinical Oncology (2017)

e15705 Background: Conventionally unresectable tumors involving mesenteric vasculature or critical areas of the liver may be amenable for resection using novel techniques developed from organ transplantation. The concept of ex-vivo resection allows tumor removal and vascular reconstruction in cold perfusion while ensuring visceral preservation, followed by autotransplantation of the remaining organs. Methods: A retrospective chart review of 34 patients at a single-center who underwent ex-vivo tumor resection and auto-transplantation between the years of 2008 and 2016. Results: Indications for ex-vivo resection were tumors involving the hepatic vasculature (hepatic tumors involving vasculature n = 13, pancreatic tumors involving hepatic vasculature n = 7), mesenteric vasculature (n = 9), or both (n = 4) and renal vasculature (n = 1). Tumors included cholangiocarcinoma (n = 6), liposarcoma (n = 6), leiomyosarcoma (n = 4), pancreatic adenocarcinoma (n = 3), and others. 27 out of 34 patients underwent attempted treatments including surgery or chemoradiation prior to ex-vivo resection, with a mean of 2.5 treatments. Types of procedures included: hepatic autotransplantion (n = 11). Whipple procedure with hepatic autotransplantion (n = 8), intestinal autotransplantion (n = 9), and multivisceral autotransplantion (n = 4). The median age was 48 (range 5 to 71). Thirty-day and ninety-day mortality were 8.8% and 11.8%, respectively. Three patients died within 30 days with hepatic artery anastomotic rupture (n = 1) and sepsis (n = 2). Thirty-one patients (91.2%) were discharged alive from the hospital at a median of 20 days. One-year and three-year overall survival rates were estimated at 64.7% and 42.4%, respectively. At the time of submission, 14 patients are alive and 13 are disease free with a median follow-up of 5.8 years. Conclusions: Ex-vivo tumor resection is a highly complex procedure associated with significant morbidity and mortality. Nevertheless, for carefully selected patients with conventionally unresectable tumors, ex-vivo surgery may be a viable option offering reasonable long-term outcomes.
Outcomes of chemoradiotherapy for stage III non-small-cell lung cancer in Brazil.
Authors: Juliano Ce Coelho, Sabrina Richter Bedin, Bruna C Silva, Pedro Emanuel Rubini Liedke, Guilherme Geib, Rafaela Pirolli, Mariane Branco, Carolina Muller, Marco Antonio de Bastiani, Fábio Klamt, Sergio Jobim Azevedo, Gilberto Schwartsmann
Journal: Journal of Clinical Oncology (2016)

e20073 Background: Patients with stage III non-small-cell lung cancer are commonly treated with chemoradiotherapy (CR), witch improves local control, progression free survival (PFS) and overall survival (OS), but also increases toxicity. Patients from Brazil are usually underrepresented in clinical trials and data on real life outcomes are lacking. Methods: From January 2005 to December 2013, all patients with locally advanced non-small cell lung cancer (NSCLC) treated with etoposide/cisplatin (EP) with concurrent radiotherapy at a University Hospital in South of Brazil were identified by electronic database. Medical records were reviewed and demographic data, tumor and treatment characteristics were collected. OS and PFS were estimated by Kaplan-Meier curves. Multivariate analysis was performed to identify factors associated with survival. Statistical analysis was performed with SPSS 22.0. Results: Eighty-eight patients were colected for this analysis. Patient characteristics revealed a mean age of 59.73 ± 10.32 years, 66% male, 91% caucasian, a positive smoking history in 90%, ECOG performance status of 0-1 in 92%, loss of more than 10% of body weight in 34% and stage IIIA and IIIB in 46% and 54%, respectively. Forty-four patients (50%) had adenocarcinoma, 32 (37%) squamous cell and 12 (13%) other histologies. Sixty-five patients (74%) completed the whole treatment and 44 (50%) achieved complete or partial response. The median follow-up is 14.17 months. The PFS was 8,45 months (95% IC, 6.56 to 10.34). In 21 patients (24%) the first relapse was in the original tumor, in 41 (46%) it was systemic and in 16 (18%) unknown. Seventy-eight patients (83%) have died with an OS of 14.17 months (95% IC, 10.37 to 17.97). In multivariable analysis, clinical stage (IIIA vs IIIB) was independently associated with worst prognostic in OS, HR of 2.19 (95% IC, 1.24 to 3.88). Conclusions: To our knowledge, this is the largest report of patients from Brazil with concurrent chemoradiation treatment for stage III NSCLC. Our outcomes are slightly worst that those reported in clinical trials. Factors affecting outcomes should be further studied.
Neutrophil extracellular trap production contributes to pathogenesis in SIV-infected nonhuman primates
Authors: Ranjit Sivanandham, Egidio Brocca-Cofano, Noah Krampe, Elizabeth Falwell, Sindhuja Murali Kilapandal Venkatraman, Ruy M. Ribeiro, Cristian Apetrei, Ivona Pandrea
Journal: Journal of Clinical Investigation (2018)

Neutrophil extracellular traps (NETs) are involved in the pathogenesis of many infectious diseases, yet their dynamics and impact on HIV/SIV infection have not yet been assessed. We hypothesized that SIV infection and the related microbial translocation trigger NET activation and release (NETosis), and we investigated the interactions between NETs and immune cell populations and platelets. We compared and contrasted the levels of NETs between SIV-uninfected, SIV-infected, and SIV-infected antiretroviral-treated nonhuman primates. We also cocultured neutrophils from these animals with either peripheral blood mononuclear cells or platelets. Increased NET production was observed throughout SIV infection. In chronically infected animals, NETs were found in the gut, lung, and liver, and in the blood vessels of kidney and heart. Antiretroviral therapy (ART) decreased NETosis, albeit above preinfection levels. NETs captured CD4+ and CD8+ T cells, B cells, and monocytes, irrespective of their infection status, potentially contributing to the indiscriminate generalized immune cell loss characteristic to HIV/SIV infection, and limiting the CD4+ T cell recovery under ART. By capturing and facilitating aggregation of platelets, and through expression of increased tissue factor levels, NETs may also enhance HIV/SIV-related coagulopathy and promote cardiovascular comorbidities.
Phase I study of carboplatin (C), pegylated liposomal doxorubicin (PLD) and everolimus (E) in platinum-sensitive epithelial ovarian, Fallopian tube or primary peritoneal cancer in first relapse (NCT01281514).
Authors: Lainie P. Martin, Angela Jain, Christina Chu, Gina Mantia-Smaldone, Stephen C. Rubin, Eric A. Ross, Russell J. Schilder
Journal: Journal of Clinical Oncology (2018)

5580 Background: The PI3K/AKT/ mTOR pathway may play an important role in chemotherapy resistance in ovarian cancer. (E) is an orally administered mTOR inhibitor approved for multiple indications. This Phase I trial evaluated the feasibility of combining E with C and PLD in women with recurrent, platinum sensitive ovarian cancer. Methods: Patients were administered C AUC 5 with PLD 30 mg/m2 on 28 day cycles, and escalating doses of E, starting at 2.5 mg/day. Planned Phase I doses of E were 2.5 mg/d, 5 mg/d, 7.5 mg/d and 10 mg/d. The study used a modified TITE-CRM design with a requirement that cohort 1 complete 6 cycles of chemotherapy with E at 2.5 mg/d prior to dose escalation. The primary endpoint was safety and tolerability. Results: 21 patients were treated on study. There was a DLT of rash at dose level(DL) 1, 2.5 mg/d; patient discontinued treatment on trial after cycle 1. 5 additional patients completed 6 cycles at DL1 without DLT. 3 patients completed 6 cycles of treatment at DL3, 7.5 mg/d, but 2 experienced DLT and required dose reduction. 12 patients were enrolled at DL2; no DLTs were seen at DL2. 7 patients completed 6 cycles without dose modification. 1 patient required dose modification of E for thrombocytopenia. 2 patients stopped treatment early due to disease progression. 2 patients experienced hypersensitivity reactions to Doxil, and failed desensitization. They were permitted to remain on study with C and E, but were considered inevaluable. DLTs included rash,(n = 1 at DL1), headache (n = 1 at DL3) and thrombocytopenia (n = 1 at DL3). The most common AEs included neutropenia, anemia, stomatitis, rash, nausea, vomiting, diarrhea and constipation (42-90%). Grade 3 AEs included neutropenia (n = 3), thrombocytopenia (n = 2), stomatitis (n = 1), rash (n = 1) and PE/DVT (n = 2). The MTD of E in combination with C and PLD was determined to be 5 mg/d. 3 patients experienced a CR and 11 patients experienced a PR, for a RR of 67%. 3 patients experienced stable disease and 3 experienced disease progression. Conclusions: C with PLD and E at 5 mg/day is tolerable with intriguing activity in women with platinum sensitive relapsed ovarian cancer. Clinical trial information: NCT01281514.
Equity in access to tyrosine kinase inhibitors among veterans diagnosed with renal cell carcinoma.
Authors: Julie Ann Lynch, Kristine E. Lynch, Kelly Kristin Filipski, Brygida Berse, Donna Rivera, Ji Won Chang, Daniel Jacob Becker, Olga Efimova, Scott DuVall
Journal: Journal of Clinical Oncology (2017)

e18051 Background: Tyrosine kinase inhibitors (TKIs) have dramatically improved outcomes of advanced renal cell carcinoma (RCC) patients, although complete remission is uncommon. Disease-specific survival in RCC varies by race/ethnicity, but race is not an independent predictor of survival within single-payer healthcare systems, pointing to the importance of access to treatment. We analyzed patient-level utilization of three TKIs (sunitinib, sorafenib, and pazopanib) among veterans with RCC. Methods: In this retrospective cohort study, we used data from Department of Veterans Affairs (VA) Corporate Data Warehouse to identify veterans diagnosed with RCC from 2006 to 2015 and exposed to TKIs, and to obtain their demographic and clinical information. The distribution of patients’ characteristics across treatments was evaluated using chi square and t-tests. Results: Of 2,410 patients exposed to TKIs, 956 (40%) received more than one TKI. Sunitinib was prescribed to 1,761 (73%) patients, pazopanib to 766 (32%), and sorafenib to 600 (25%) patients. The use of sorafenib declined steadily over time, from 37% of patients diagnosed in 2006 to 2% of those diagnosed in 2015, while the use of pazopanib grew from 8% to 38%, respectively. The comparison group were unexposed patients in Stage IV RCC (N = 1,144). Patients exposed to targeted treatments were significantly younger at diagnosis than those with no exposure (mean [M] age 65 years, SD 9 vs. m = 70 years, SD 10; p &lt; 001). There were no statistically significant racial/ethnic or gender differences between patients exposed and unexposed to TKIs. Exposed patients had significantly higher body mass index (BMI) than unexposed (M = 29.6, SD 6 vs m = 27.9, SD 6, respectively; p &lt; 0.01). Receipt of TKI was positively correlated with both surgery and chemotherapy, and negatively correlated with Charlson comorbidity index (p &lt; 0.01). Conclusions: We documented equal access to TKIs treatment within the VA among RCC patients of different ethnic backgrounds and gender. Treatment with TKIs was correlated with younger age and fewer comorbidities, but higher BMI. We observed trends in use of individual TKIs, with more recently approved pazopanib gradually replacing sorafenib and sunitinib.