tbuckley/cabot-search huggingface dataset:
Improving care quality for patients with soft tissue and bone sarcoma by establishing a national virtual tumor board and electronic consultation platform.
Authors: Minggui Pan, Andrew Fang, Maihgan Kavanagh, Brian Kim, Jason D Lee, Craig McCormick, Lee Jae Morse, Subir Nag, Grant Nybbaken, Peter Peng, Corey M. Schwartz, Joseph Song, Denah Renee Taggart, Jeanette Cu Yu
Journal: Journal of Clinical Oncology (2016)

211 Background: Bone and soft tissue sarcomas are relatively uncommon and their management is extremely complex requiring coordinated multidisciplinary expertise for optimal care. Because Kaiser Permanente operates across many geographic regions in the country, in-person tumor board is not practical. Methods: The Kaiser Permanente Northern California medical oncology team has developed a system-based virtual tumor board (VTB) and electronic consultation (EC) platform comprised of experts from several key disciplines including musculoskeletal/surgical oncology, musculoskeletal radiology, pathology, radiation oncology, brachytherapy, medical adult and pediatric oncology. The VTB and EC cases are physician referral-based. The VTB occurs once every two weeks via video conferencing reviewing imaging studies and pathology while EC is available for more urgent cases whenever requested. This platform is available to Kaiser Permanente physicians in Northern and Southern California and other states including Hawaii, Mid-Atlantic, Northwest, Colorado, and Georgia. We conducted a survey targeting referring physicians to assess the value of this service platform in improving sarcoma care. Results: From March 2013 to October 2015, approximately 500 cases have been referred to the VTB and EC. Approximately 2/3 of the cases were referred to the VTB and 1/3 to the EC. The cases include a vast spectrum of bone and soft tissue sarcoma cases that were either newly diagnosed or at the time of relapse or progression. The physician survey on the quality and utilization of this sarcoma platform provided very positive feedback, with 100% responses stating that VTB and EC improved patient care and their confidence in managing patients with sarcoma, 90% stating VTB and EC changed their management to a certain extent. Approximately 90% responders rated VTB and EC very to extremely helpful. Conclusions: We conclude that a system-based VTB and EC can provide an excellent platform for improving quality of care and physician confidence in managing patients with bone and soft tissue sarcoma in an integrated healthcare system.
Melanoma patients treated with dendritic cell vaccination, interleukin-2, and metronomic cyclophosphamide: Results from a phase II trial.
Authors: E. Ellebaek, L. Engell-Noerregaard, T. Z. Iversen, T. M. Frosig, S. R. Hadrup, M. H. Andersen, P. thor Straten, I. M. Svane
Journal: Journal of Clinical Oncology (2011)

e13084 Background: Several clinical trials have evaluated the effect of dendritic cell (DC) vaccination in the treatment of melanoma patients but so far the clinical results have been disappointing. In this trial metronomic cyclophosphamide (Cy) and celecoxib have been added to a treatment regimen with DC vaccination and interleukin (IL-) 2 in the intend to overcome immunosuppressive mechanisms. Methods: 28 patients with progressive metastatic melanoma were included in this phase II trial. Vaccines consisted of autologues DCs pulsed with survivin, hTERT and p53 derived peptides (HLA-A2+) or tumor lysate (HLA-A2-). Vaccine no. 1-4 was given weekly, vaccine 5-10 biweekly and monthly vaccines thereafter until disease progression. Concomitantly the patient was treated with IL-2, 2 MIU for five days following each vaccine, Cy 50 mg twice a day every second week and Celecoxib 200 mg daily. Objectives were safety and tolerability, immunological and clinical responses, time to progression (TTP) and overall survival (OS). Results: The treatment was safe and no grade 3 or 4 adverse events were observed. 16 patients (57%) had SD according to RECIST at 1st evaluation and 8 patients had prolonged SD (7-13.7 months). There were no differences in prognostic factors between the patients with SD and progressive disease (PD) at 1st evaluation. Vaccine induced immune responses have been observed and 5 out of 6 patients with increasing immune responses had SD; the 6th patient had prolonged OS (+ 20 months). Despite the use of metronomic Cy blood level of regulatory T cells (Treg) increased during treatment. The median TTP was 4.5 months and the median OS was 9 months. Patients with SD had a median OS at 13.7 months; patients with PD had an OS at 6.0 months (p = 0.02). Conclusions: It seems that a vaccine induced immune response is more common among patients who achieve SD during treatment. When comparing results from a previous trial without Cy we see that the number of patients obtaining SD more than doubled (57% vs. 24%), PFS was prolonged but unfortunately OS did not improve. Notably, metronomic Cy was unable to reduce Treg level.
Finding the value point in oncology care: Optimizing clinical quality.
Authors: Daniel McCrone, Cecilia Tran, Jessica Flocco, Dudley Gill
Journal: Journal of Clinical Oncology (2013)

272 Background: New Century Health is an Oncology Care Management company. Evidence-based medicine is not a new trend, however, we believe that New Century Health has developed a way to quantify quality and cost outcomes based on our innovative approach to utilizing Clinical Pathways and Compendia. Methods: A retrospective clinical review was performed on 1,938 chemotherapy treatment requests (CTRs) withdrawn or recommended adverse determination (RAD), in calendar year 2012, for two national health insurance carriers. Financial impact associated with the clinical intervention was calculated at ASP +6%, net of confirmed resubmissions. Resubmissions are defined as those approved treatment requests received within one month of the original withdrawal/RAD for an alternative treatment resulting from the original withdrawal/RAD. Financial impact of gross administrative errors was mitigated through manual adjustments to the projected costs. Results: The average combined membership was 795,679; 5,731 unique patients had requests for chemotherapy treatment during 2012, generating 15,446 CTRs. Twelve point five (12.5) percent (1,938) of those were withdrawn/RAD resulting in a net impact of $15.1 million. Of the 1,938 withdrawn/RAD, 12.4% (241) resulted in increased quality with an associated increase in cost ($1.8M). Conclusions: New Century Health believes that cost effective treatment is a function of quality and not the ultimate goal at the expense of patient outcomes. Detailed retrospective case studies were performed on all of the requests that resulted in additional costs. New Century Health believes that in each case the quality of care or patient safety was significantly improved by our peer-to-peer clinical interventions. This is a patient-centric innovative approach to evidence-based medicine that embraces necessary cost increases in favor of clinical quality and patient safety.
Geographic and racial disparities in the utilization of low-volume cystectomy hospitals for bladder cancer.
Authors: Martin Francis Casey, Tal Gross, Kristian D. Stensland, William K. Oh, Matt D. Galsky
Journal: Journal of Clinical Oncology (2014)

302 Background: Extensive research has demonstrated volume-outcome benefits for select cancer surgeries, such as cystectomy. However, barriers to the use of high volume cystectomy hospitals have not been comprehensively explored. Methods: The New York Statewide Planning and Research Cooperative System was utilized to obtain data on all inpatients who underwent cystectomy for bladder cancer from 1997-2011. Volume status was defined by dividing patients into quintiles based on the number of cystectomies performed by each hospital in 1997-2001. Multiple logistic regression was used to assess the impact of distance and race on use of low volume hospitals. Driving distances were calculated using a geographic information system. Race was stratified by the racial profile of a subject’s community to explore the underlying causes of racial disparities. Results: A cohort of 8,712 cystectomy patients was identified. The number of available high volume hospitals increased over time, consistent with regionalization of surgeries. Minimum travel distance to high volume hospitals decreased over time for the general population, but living &gt;21 miles still increased risk for low volume hospital utilization (see Table). Racial disparities were most prominent among blacks living in black communities, despite generally living closer to high volume hospitals (median travel distance of 5.3 miles versus 16.6 miles for whites living in white communities). Conclusions: Regionalization of cystectomies has occurred in New York State, as has been observed in multiple other regions of the United States. However, geographic and racial disparities exist in the use of high volume cystectomy hospitals. [Table: see text]
A comprehensive analysis of clinical and tumor characteristics with BRAF and KRAS mutations status in adjuvant colon cancer trial N0147.
Authors: Robert R. McWilliams, Michelle R. Mahoney, Daniel J. Sargent, Garth D. Nelson, Frank Sinicrope, Paul J Limburg, Stephen N. Thibodeau, Axel Grothey, Joleen Marie Hubbard, Steven R. Alberts
Journal: Journal of Clinical Oncology (2012)

446 Background: MutKRAS and mutBRAF are important predictive and prognostic markers, respectively, in colorectal cancer (CRC). However, little is known about why some tumors harbor these mutations. N0147 is a phase III adjuvant trial for stage III CRC patients (N=3397) in which patients completed questionnaires and tumor variables and KRAS/BRAF mutation status was assessed. Methods: 2,323/3,397 patients who were enrolled prior to a 2008 amendment requiring KRAS testing completed a Patient Questionnaire. Primary tumors were assessed for mutKRAS and mutBRAF using standard methods; MMR status was determined using IHC. Multivariate analysis was performed to identify predictors of mutation status. Results: 60% and 86% of mutKRAS and mutBRAF tumors were right-sided, respectively. MutKRAS was less likely if there was a family history of CRC and in ever-smokers, and was nearly mutually exclusive with mutBRAF. MutBRAF was associated with deficient MMR (dMMR), high grade histology, and 4+ positive lymph nodes at surgery. MutBRAF was more likely in patients age &gt; 70, retired persons, ever-smokers, but was less likely in non-whites and men. Conclusions: Smoking, family history of CRC, and dMMR status are associated with lower frequency of mutKRAS , but higher mutBRAF. Both mutations tend to be right sided, and mutBRAF is more common in the elderly, females, and non-Hispanic whites. [Table: see text]
Impact of the Provisional Revised-IPSS (R-IPSS) in 265 MDS Patients Treated with Azacitidine (AZA): The Groupe Francophone Des Myelodysplasies (GFM) Experience
Authors: Mathilde Lamarque, Sophie Raynaud, Raphael Itzykson, Sylvain Thepot, Bruno Quesnel, Francois Dreyfus, Odile Beyne Rauzy, Pascal Turlure, Norbert Vey, Christian Recher, Caroline Dartigeas, Laurence Legros, Jacques Delaunay, Sorin Visanica, Aspasia Stamatoullas, Pierre Fenaux, Lionel Ades
Journal: Blood (2011)
Changes in biomarkers and DNA methylation in breast cancer survivors enrolled in the ENERGY weight loss trial: A pilot study.
Authors: Wendy Demark-Wahnefried, Cheryl L Rock, Rebecca L. Sedjo, Adetunji Toriola, Jingxia Liu, Tim Byers, Patricia A. Ganz, Xiangqin Cui, Hemant Tiwari, Devin Absher, Graham A. Colditz
Journal: Journal of Clinical Oncology (2016)

181 Background: In 2014, an ASPO position statement was released calling for action regarding cancer survivors’ needs for weight management. Reduction of body weight is hypothesized to affect several cancer-related biological pathways. Methods: The Exercise and Nutrition to Enhance Recovery and Good health for You (ENERGY) trial is the largest weight loss trial completed to date among breast cancer survivors. In it, 692 stage Ic-IIIc breast cancer survivors were randomized to an intensive, group-based weight loss intervention with 26 contacts over one year or to a non-intensive intervention with two contacts over the same time period. Results recently reported in JCO showed significantly greater weight loss in the intensive intervention arm compared to the non-intensive arm. A pilot study exploring baseline to 6-month changes in gene methylation and expressed biomarkers was undertaken in 30 chemo-naïve, post-menopausal, non-Hispanic white women who participated in this study. Results: Several significant differences in mean change scores (standard error) between the intensive vs. non-intensive groups were noted, i.e., insulin: -4.19(0.80) vs. 0.42 (1.01)/p = 0.0016; c-peptide: -0.49(0.14) vs. 0.40(0.19)/p = 0.0009; leptin: -15.73(1.79) vs. 2.53(1.78)/p &lt; 0.0001; adiponectin:leptin ratio: 0.67(0.15) vs. 0.010(0.064)/p = 0.0007; homeostasis model of insulin resistance (HOMA-IR): 20.00(4.65) vs. 9.57(5.00)/p = 0.0003; sex hormone binding globulin 20.45(4.61) vs. 8.65(8.00)/p = 0.023; and Follistatin-Related Protein-3 (FSTL3): 0.48(0.19) vs. -0.88(0.55)/p = 0.0497. While effects were in the direction hypothesized for c-reactive protein, interleukin-6, vascular endothelial growth factor, and tumor necrosis factor no significant differences were noted. Significant differences in DNA methylation also were noted for genes encoding for Follistatin Related Protein (corresponds to FSTL3), and those on hormonal/growth pathways (e.g., AMOTL1, ESR, EGR3), inflammatory pathways (e.g., TNFRS10A/TRAIL-R1, C14orf106), and metabolic pathways (e.g., ZBED3, GABRA). Conclusions: While results are based on a small sample and not corrected for multiple testing, they provide evidence that weight loss affects several biomarkers and pathways that impact cancer and which warrant further investigation. Clinical trial information: NCT01112839.
The feasibility and safety conversion surgery in stage IV gastric cancer.
Authors: Tsutomu Sato, Ken Nishimura, Norisuke Nakayama, Osamu Motohashi, Kenki Segami, Shigeya Hayashi, Taiichi Kawabe, Toru Aoyama, Tsutomu Hayashi, Takanobu Yamada, Takashi Oshima, Yasushi Rino, Takashi Ogata, Haruhiko Cho, Takaki Yoshikawa
Journal: Journal of Clinical Oncology (2015)

164 Background: Conversion surgery could be an option for stage IV gastric cancer when distant metastasis (M1) is disappeared by palliative chemotherapy, however, feasibility, safety and efficacy of surgery after long-term chemotherapy remains unclear. Methods: This retrospective study examined 21 gastric cancer patients who underwent curative conversion surgery between 2001 and 2013. Postoperative complications were evaluated according to the Clavien-Dindo classification. Overall survival (OS) was estimated by Kaplan-Meier method. Results: Median follow-up period (range) was 43.9 months (7.2-72.1 months). The number of M1 factors was one in 17 patients and two in 4, including metastases to non-regional lymph node in 11, peritoneum in 11, and liver in 3. The regimen of chemotherapy was S-1/CDDP in 11 patients, S-1/docetaxel/CDDP in 5, S-1/docetaxel in 2, 5FU/leucovorin/paclitaxel in 1, CPT/CDDP in 1, and S-1 monotherapy in 1. The median duration from initiation of chemotherapy to disappearance of M1 factor was 3.5 months and the median duration from initiation of chemotherapy to the operation was 7.5 months. A total of 19 patients (90.4%) underwent over D2 lymphadenectomy including modified D2 in 2 patients, D2 in 16, and D2 plus para-aortic nodal dissection in 3. M1 tumor was not resected except para-aortic nodal dissection in 3 patients. The median operation time and bleeding were 205 minutes and 228 ml, respectively. Grade 2/3/4 morbidities were observed in 5 patients (23.8%); 2 pancreatic fistula (grade 2), 2 abdominal abscess (grade 2 and 3), and 1 anastomotic leakage (grade 3). No mortality was observed. Pathological response of the primary tumor, defined as disappearance of more than two third of the tumor cells, was 66.7% including 19.0% of complete response. The overall survival (OS) after initiation of chemotherapy was 90.5% at 1-year, 85.7% at 2-year, and 75.9% at 3-year with median survival time (MST) of 52.9 months, while OS after surgery was 90.5% at 1 year, 76.2% at 2-year, and 64.5% at 3-year with MST of 40.9 months. Conclusions: Curative conversion gastrectomy for stage IV gastric cancer was feasible and safe. Considering excellent survival, conversion surgery has a value to be evaluated in prospective studies.
Four in 10 European doctors may leave UK after Brexit vote, BMA survey finds
Authors: Ingrid Torjesen
Journal: BMJ (2017)

More than four in 10 doctors from the European Economic Area who work in the UK are considering leaving since the referendum result on the UK’s membership of the EU, a survey has found.1

The BMA’s survey of 1193 EEA doctors working in the UK found that 42% were considering leaving since the public’s decision that the UK should quit the EU, and a further 23% were unsure whether to stay.

European doctors said that they felt significantly less committed to working in the UK in light of the referendum result: on a scale of one to 10, their commitment has fallen from an average of nine before the referendum to six after the result.

They also …
Emerging concepts in combination chemotherapy for metastatic pancreatic cancer: A systematic review of randomized controlled trials.
Authors: Basile M. Njei, Ivo C. Ditah, Alexei Shimanovsky, Priscilla Owusu, John W Birk
Journal: Journal of Clinical Oncology (2013)

228 Background: Even though gemcitabine monotherapy is commonly used as first-line treatment for metastatic pancreatic cancer, many novel treatment approaches have focused on combination chemotherapy. FOLFIRINOX, a combination of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin, has recently been shown to improve survival compared to gemcitabine. However, it is unclear whether survival benefits are counterbalanced by a poor quality of life due to the adverse effects. The aim of this study was to review emerging strategies that enhance treatment of patients with metastatic pancreatic cancer. Methods: Two authors independently conducted a comprehensive search of the Cochrane library PUBMED, and published proceedings from major oncologic and gastrointestinal cancer meetings from January 1980 to July 2012. Only published randomized controlled trials were eligible for inclusion. Our primary outcome measures were: progression-free survival (PFS), overall survival (OS) and serious adverse events (grade 3 or 4). Results: Thirty-one studies involving 7,957 patients were included in the analysis. There was an overall statistically significant increase in OS (RR 1.10, 95% CI 1.03-1.30) and PFS (RR 1.27, 95% CI 1.14-1.46) for the gemcitabine-based combination therapy group versus the gemcitabine monotherapy group. Subgroup analysis showed that only patients with fluoropyrimidine and platinum containing regimens showed prolonged survival: RR 1.33, 95% CI 1.04-1.76 and RR 1.38, 95% CI 1.08-1.76, respectively. The most common severe adverse event (neutropenia) was found in 45% of patients treated with FOLFIRINOX. Conclusions: Overall, gemcitabine in combination with fluoropyrimidine or platinum containing regimens can improve overall survival in patients with metastatic pancreatic cancer compared to gemcitabine alone. Even though, FOLFIRINOX therapy is associated with better survival outcomes than gemcitabine, the prolonged survival comes at the cost of poorer quality of life due to a higher incidence of adverse events. More data is needed from studies involving novel combination therapy such as hedgehog pathway inhibitors and radio-immunotherapy.
Preliminary results of preoperative FOLFOX chemotherapy for locally advanced colon cancer patients with therapeutic drug monitoring of 5-FU.
Authors: Javier Rodriguez, Patricia Martin Romano, Azucena Aldaz, Ana Chopitea, Jorge Baixauli, Jose Carlos Subtil, Laura Zufia, Carlos Garzon, Iosu Sola, Eduardo Castanon, Jose Luis Hernandez-Lizoain
Journal: Journal of Clinical Oncology (2014)

579 Background: Preoperative chemotherapy is an alternative approach undergoing active clinical research in patients (pts) with locally advanced colon cancer (LACC). The aim of this study was to assess the feasibility and preliminary evidence of activity of a direct monitoring of 5-FU levels based on pharmacokinetically (PK) guided dose adjustments. Methods: LACC pts (T4 or T3 with extramural depth &gt;5mm) diagnosed after a colonoscopy and spiral CT were scheduled to receive 4 cycles of Oxalipatin (85mg/m²), Leucovorin (400 mg/m²), bolus 5-FU (400 mg/m2) and infusional 5-FU (initial dose of 2400mg/m² in 46h and then tailored according to PK monitoring to reach an area under the curve (AUC) between 25-30 mg·h·L-1). Surgery was planned 4 to 6 weeks after the completion of chemotherapy treatment. All pts were staged at baseline and before surgery. Pathological tumor regression was graded according to the MSKCC classification. Toxicity was reported according to the NCI-CTCAE 4.0. Results: From March 2011 to April 2013, 16 pts (M/F: 10/6; median age 56) with LACC were evaluated. Median dose of 5-FU was 4750 mg. 70.6% pts required a 5-FU dose increase to reach the target AUC. Median 5-Fu plasma clearance was 199,58 L/h. Side effect profile included G3 neutropenia (6 pts), G2 diarrhea (5 pts), G2 nausea (3 pts) and G2 asthenia (4 pts). Neoadjuvant treatment was discontinued in 2 pts due to small bowell obstruction requiring surgery. No progressive disease was observed during preoperative chemotherapy. A radiological dowstaging was achieved in 9 pts (56.25%). All pts underwent surgery (laparoscopy-assisted 50%) with an R0 resection rate of 93.75%. There were no treatment-related deaths. Pathological responses (MSKCC score) included grades 4, 3+ and 3 in 12.5%, 12.5% and 25% of pts, respectively. Median number of harvested nodes was 23.5 (7-51) with a ypN0 rate of 75%. Median time to hospital discharge was 7 days. After a median follow-up of 7 months (3-27), the 2-year actuarial median PFS and OS were 67.5% and 100%. Conclusions: Preoperative PK-adjusted FOLFOX in LACC pts achieves major pathological responses in almost 50% the pts and a remarkable R0 resection rate. Further research seems warranted.