tbuckley/cabot-search huggingface dataset:
Phase II study of trabectedin in pretreated patients with recurrent epithelial ovarian cancer (REOC).
Authors: Marco Marinaccio, Emilia Mele, Vito Lorusso, Valeria Vincenza Fumarulo, Fausta Sozzi, Ettore Cicinelli
Journal: Journal of Clinical Oncology (2013)

5559 Background: The prognosis of patients with REOC is extremely poor after several lines of chemotherapy. The choice and timing of therapies must be individualized to optimize survival and quality of life. This open-label, nonrandomized, phase II study was aimed at evaluating efficacy and toxicity of Trabectedin as a single-agent therapy in patients with preteated Recurrent Epithelial Ovarian Cancer (REOC). Methods: Sixteen patients (median age 51 yrs, range 44 – 71) with REOC who progressed after 2 (18.7%), 3 (56.3%) or 4 (25.0%) previous lines of chemotherapy were treated with Trabectedin at the dose of 1.1 mg/m2 via a 3-hour i.v. infusion with dexamethasone pretreatment every 3 weeks until disease progression, unacceptable toxicity or when a stability of disease was reached. Clinical objective response was the primary efficacy endpoint; the secondary one was safety. Response to treatment was assessed according to Response Evaluation Criteria in Solid Tumours (RECIST, version 1.1), and toxicities were graded according to NCI Common Toxicity Criteria, version 2.0. Results: The median number of treatment cycles per patients was 5 (range, 2-9 cycles). A total of 81 cycles were administered. A dose reduction was never required. Main toxicities included anemia (20.9%), leucopenia (15.0%), thrombocytopenia (4.5%) and asthenia (22.2%). No deaths were attributable to therapy. No one showed complete response, while 9/16 partial response (56.2%) and 4/16 stable disease (25.0%) were observed. 3/19 pts (18.8%) progressed on therapy. The median progression-free interval was 18 weeks in patients with partial response; stable disease was maintained for a median time of 12 weeks. Conclusions: Trabectedin 1.1mg/m2 given as a 3-hour i.v. infusion every 3 weeks was well tolerated and has confirmed a very interesting antitumor activity in this heavily pretreated population and it seems also to be a very tolerable regimen. The co-treatment with dexamethasone improves the safety of Trabectedin by reducing drug-induced myelosuppression and hepatotoxicity. Trabectedin has a manageable toxicity profile, and can be safely administered thanks to its secure action profile also in patients with no other viable therapeutic options.
Objective response by mRECIST to predict survival in hepatocellular carcinoma: A multivariate, time-dependent analysis from the phase III BRISK-PS study.
Authors: Josep M. Llovet, Joong-Won Park, Ferran Torres, Thomas Decaens, Eveline Boucher, Jean-Luc Raoul, Masatoshi Kudo, Charissa Chang, Valerie Boige, Eric Assenat, Yoon-Koo Kang, Ho-Yeong Lim, Ian Walters, Riccardo Lencioni
Journal: Journal of Clinical Oncology (2015)

4084 Background: mRECIST (modified Response Evaluation Criteria In Solid Tumors) was developed to overcome the limitations of standard RECIST in hepatocellular carcinoma (HCC) response assessment. Retrospective studies have correlated objective response (OR) by mRECIST with overall survival (OS) in patients treated by loco-regional therapies. We investigated whether OR by mRECIST predicted OS using data from a double-blind, placebo-controlled, randomized phase III trial. Methods: In the BRISK-PS study, 395 patients with advanced HCC who progressed on/after or were intolerant to sorafenib were randomly assigned (2:1) to receive brivanib plus best supportive care (BSC) or placebo plus BSC. Tumor assessments were performed every 6 weeks by contrast-enhanced computed tomography or magnetic resonance imaging. Assessment of response was done by central radiological review using mRECIST. Multivariate models using time-dependent covariate analysis defined variables with independent prognostic value (SPSS 18 and SAS 9.2). Results: 210/226 (93%) patients in the brivanib arm and 101/108 (94%) in the placebo arm, who had baseline and on-study scans available for central blinded review, were evaluable according to mRECIST. 26/210 patients on brivanib and 2/101 on placebo achieved partial response (p < 0.01). At the end of follow up, 284 patients had died, the median OS for the brivanib arm being 9.4 months. As per mRECIST response assessment, median OS was 16.4 months (n = 26; 95% CI, 15.7 – NA) for brivanib responders and 8.3 months (n = 237; 95% CI, 7.2 – 9.7) for brivanib non-responders (hazard ratio, 0.28; 95% CI, 0.14 – 0.55, p < 0.01). Independent predictors of OS at multivariate time-dependent analysis were ORR by mRECIST, vascular invasion/extrahepatic spread, AFP > 200 ng/mL and bilirubin > 1.5 mg/dl. Conclusions: ORR by mRECIST is an independent predictor of OS in HCC patients receiving a systemic multikinase inhibitor, brivanib. mRECIST response is a marker of antitumor activity and warrants further evaluation in prospective clinical trials exploring novel agents in HCC patients. Clinical trial information: NCT0901901.
Unilaterally Decreased Striatal Dopamine Transporter Caused by Venous Anomaly
Authors: Lode Goethals, Sophie Bourgeois, Yannick De Brucker, Hendrik Everaert, Frank W. De Geeter
Journal: Clinical Nuclear Medicine (2017)

We describe a finding of unilaterally decreased binding of 123I-ioflupane in the basal ganglia in a 78-year-old woman that could be attributed to an underlying developmental venous anomaly.
Effect of decipher test on adjuvant treatment decision-making among men with high-risk pathology at radical prostatectomy: Results from a multicenter prospective PRO-IMPACT study.
Authors: John L. Gore, Marguerite du Plessis, Maria Santiago-Jimenez, Kasra Yousefi, Darby Thompson, David Chen, William Clark, Michael Franks, Lawrence Ivan Karsh, Adam S. Kibel, Hyung Lae Kim, Brian R. Lane, Yair Lotan, William Thomas Lowrance, Paul Maroni, Scott David Perrapato, Edouard John Trabulsi, Robert J. Waterhouse, Elai Davicioni, Daniel W. Lin
Journal: Journal of Clinical Oncology (2017)

24 Background: The decision to provide adjuvant therapy to men with high risk pathology after radical prostatectomy (RP) is confounded by tremendous uncertainty. We prospectively evaluated the impact of the Decipher test, which predicts metastases after RP, on men and providers decision quality. Methods: 150 adjuvant pts were enrolled by 43 urologists from 19 practices. Pts with pathologic T3 stage or positive surgical margins (SM+) after RP were included. Participating physicians provided a treatment (Tx) recommendation before and after exposure to Decipher test results. Pts completed validated surveys on health-related quality of life, decisional conflict, and PCa-related anxiety. Results: Median patient age at RP was 64 years; 67% and 50% had pT3 and SM+ pathology, respectively. Decipher classified 46%, 22% and 32% of men as low-, intermediate- and high-risk, respectively. Pre-Decipher, observation was recommended for 89%. Post-Decipher, 18% (95% CI 12-25%) of Tx recommendations changed. Men’s Decisional Conflict Scale (DCS) scores decreased (indicating higher decision quality) after exposure to Decipher results (median DCS pre-Decipher 25 [IQR 8-44], median DCS post-Decipher 19 [IQR 2-30], p&lt;0.001), with greatest decreases in the subdomains of decision uncertainty and decision support. Low-risk Decipher results experienced a trend toward decreased PCa-specific anxiety (p=0.13) and a significant reduction in fear of PCa recurrence (p=0.02). Physicians’ median DCS scores decreased from 32 [IQR 28-36] to 28 [IQR 12-42] (p&lt;0.001). Decipher results were associated with the decision to pursue ART in an MVA analysis (OR 1.48; 95% CI 1.19-1.85, p&lt;0.001). Conclusions: Observation is the predominantly prescribed management strategy for men with high risk features at RP. Knowledge of Decipher results was associated with Tx decision-making: men at low risk for metastasis had higher rates of observation recommendations and men at high risk had higher rates of ART recommendations. Decision quality was improved and PCa-specific anxiety was decreased for men exposed to Decipher results. Clinical trial information: NCT02080689.
Is a stable disease according to RECIST criteria a real stable disease in GIST patients treated with imatinib mesylate (IM) included in the intergroup EORTC/ISG/AGITG trial?
Authors: A. Le Cesne, M. Van Glabbeke, J. Verweij, P. Casali, J. Zalcberg, P. Reichardt, R. D. Issels, I. R. Judson, J. Y. Blay
Journal: Journal of Clinical Oncology (2006)

9510 Background: From 2/2001 to 2/2002, 946 patients (pts) with advanced GIST were randomized to IM at two dose levels within a controlled EORTC/ISG/AGITG trial. This analysis investigates whether achievement of an objective response, according to the RECIST criteria, has any predictive value for time to progression (TTP) and overall survival (OS). Methods: According to the protocol, the 3 first disease measurements were foreseen at 2, 4, and 6 months (m). Results of those measurements were classified in 6 categories: PR (&gt;30% reduction of the tumor load), MR (10–30% reduction), NC- (0–10% reduction), NC+ (0–20% increase), PD (&gt; 20% increase or new lesions), and subjective PD (clinical PD, no measurements). Pts included the analyses were those still followed at the measurement point, who had not previously progressed. Results: A total of 906 pts had measurable disease at entry; from those, 852 were evaluable at 2 m, 681 at 4 m and 642 at 6 m. At all measurement time points, PR and MR resulted in similar TTP and OS; this was also true for NC- and NC+, and for PD and subjective PD. As an example, for the evaluation at 4 m, the median TTP was respectively 2.50, 2.55, 1.86, 1.65, 0.31 and 0.30 years in the 6 groups of pts, while the 3 years OS estimate were 71%, 72%, 57%, 56%, 32% and 0%. Pts were subsequently classified as responders (more than 10% reduction of the tumor load), no change (less than 10% reduction and less than 20% increase) and PD (&gt; 20% increase, new lesions or clinical PD). This new response category is highly predictive of further progression or survival, for the 2 first measurements points, and in both therapeutic arms, but pts stable at 6 m had the same survival as responders at 6 m. In addition, RECIST response documented at 2, 4 and 6 m resulted in similar TTP and OS. Conclusions: The RECIST criteria are only optimal for identifying IM-resistant GISTs (PD &gt; 20%) and not adequate for the evaluation of IM efficacy. All pts exhibiting at least a 10% reduction (until complete response) of the tumor load have to be considered as responders to IM (IM-sensitive GISTs). A real stabilisation of the disease consisting in a less than 10% tumor reduction and a less than 20% tumor increase identifies pts who have an intermediate sensitivity to IM. [Table: see text]
Adverse effects on health and wellbeing of working as a doctor: views of the UK medical graduates of 1974 and 1977 surveyed in 2014
Authors: Fay Smith, Michael J Goldacre, Trevor W Lambert
Journal: Journal of the Royal Society of Medicine (2017)

Summary Objective To report on any adverse effects on health and wellbeing of working as a doctor, as described by senior doctors. Design Questionnaires sent in 2014 to all medical graduates of 1974 and 1977. Participants 3695 UK medical graduates. Setting United Kingdom. Main outcome measures Statements about adverse effects upon health, wellbeing and career. Results The aggregated response rate from contactable doctors was 84.6% (3695/4369). In response to the question ‘Do you feel that working as a doctor has had any adverse effects on your own health or wellbeing?’, 44% of doctors answered ‘yes’. More GPs (47%) than hospital doctors (42%) specified that this was the case. Three-quarters of doctors who answered ‘yes’ cited ‘stress/work–life balance/workload’ as an adverse effect, and 45% mentioned illness. In response to the statement ‘The NHS of today is a good employer when doctors become ill themselves’, 28% of doctors agreed, 29% neither agreed nor disagreed and 43% disagreed. More women doctors (49%) than men doctors (40%) disagreed with this statement. More general practitioners (49%) disagreed than hospital doctors (37%). Conclusions Chronic stress and illness, which these doctors attributed to their work, were widely reported. Although recent changes may have alleviated some of these issues, there are lessons for the present and future if the NHS is to ensure that its medical workforce receives the support which enables current doctors to enjoy a full and satisfying career and to contribute fully to health service provision in the UK. Older doctors, in particular, need support to be able to continue successfully in their careers.
The impact of a novel reimbursement (reimb) model on physician (phys) revenue.
Authors: Bruce A. Feinberg, Tim Olson, Winston Wong, Joseph Cooper, Jeffrey A. Scott
Journal: Journal of Clinical Oncology (2012)

e16540 Background: CareFirst BlueCross BlueShield (CFBCBS) partnered with Cardinal Health Specialty Solutions (CHSS) to launch the first cancer care clinical pathway in the US in Aug 2008. CFBCBS, CHSS, and members of the provider network sought to create a unique mechanism of reimb for network phys as part of the pathways 2nd-generation program. Fee schedules for IV medications (meds) were reduced, and fee schedules for evaluation and management (EM) codes were increased, so that on an aggregate, weighted basis there was no expected change in overall phys reimb. This would allow phys focus on optimal treatment course without the financial incentive to prescribe chemotherapy (CT). We analyzed the impact of this novel reimb model on phys revenue after 1 year (yr). Methods: Thirty-one CFBCBS network medical oncologists comprising 14 practices volunteered to participate in the pilot program. Using the 2009 benchmark yr, all IV CT J codes, administration (admin) codes, and EM codes were analyzed. Phys were then being paid above Medicare allowable for IV meds. The design of the pilot program was to shift payment for IV meds to Medicare allowable and move the extra dollars to enhance EM codes. This process was prorated more heavily weighted towards the new pt codes. Phys were also offered the option of having meds white bagged through a specialty pharmacy. The same codes from 6 mo of 2011, the yr the plan was instituted, were collected and extrapolated to reflect 12 mo of program experience and compared to pre-program data from 2009. Results: In 2009, phys generated 25,282 J codes, 24,950 EM codes, and 19,340 admin codes. In 2011, they generated 22,288 J codes, 23,040 EM codes, and 15,634 admin codes. The net impact on phys revenue in 2011 was -1.5% (range +2% to -4%) compared to 2009. None of the practices selected the white bag specialty option. Conclusions: This data demonstrates that a reimb model that shifts the focus of reimb from drug sales to cognitive services is possible and can be created by a collaborative effort between payers and providers with minimal impact to overall phys revenue. Despite the parity that can be achieved, phys continue to prefer the “buy and bill” model. Evaluation of changes in phys patterns of care due to this reimb methodology is ongoing.
Prognostic value of CD8<sup>+</sup>CD45RO<sup>+</sup> tumor-infiltrating lymphocytes (TIL) and PD-L1 in cholangiocarcinoma.
Authors: Dae Won Kim, Domenico Coppola, Young Chang, Richard D. Kim
Journal: Journal of Clinical Oncology (2017)

286 Background: Cholangiocarcinoma is a malignancy arising from the epithelial cells of the biliary tract with poor prognosis. TILs and PD-L1 have a prognostic impact in various solid tumors. We aimed to investigate TILs and PD-L1 expression and their clinical relevance in cholangiocarcinoma. Methods: Formalin-fixed paraffin-embedded tumor samples from 41 patients with resected and histologically verified cholangiocarcinoma between 1990 and 2015 were identified and immunohistochemically (IHC) stained with anti-CD8, anti-CD45RO and the anti-PDL1 mouse IgG1 (clone 5H1; Thompson) antibodies. Stained tumor samples were reviewed and enumerated by a GI pathologist. PD-L1 positivity was defined ≥ 5% of tumor cells with a minimum of 100 evaluable tumor cells. The association between expression of PDL1, CD8 or CD45RO and survival was investigated using Kaplan-Meier survival and COX proportional hazard regression analyses. Results: The median age of patients was 64 (41-85) with 53% male. 22%, 41% and 37% were stage I, II and III, respectively. CD8 was positive in 16 (39%), CD8CD45RO (memory CD8 cells) was positive in 5 (12%), and PD-L1 was positive in 19 (46%). With a median follow-up of 21.4 months, tumors with CD8+CD45RO+ TIL has better cancer specific survival (median: unreached vs 41.2mo, HR = 0.27, 95% CI: 0.09-0.83, P = 0.023) and overall survival (median: unreached vs 21.4mo, HR = 0.34, 95%CI: 0.14-0.82, P = 0.016) than CD45RO-. The expression of CD8 alone or PD-L1 in tumor was not associated with prognosis. Multivariate analysis showed that CD8+CD45RO+ TIL (HR = 0.13, 95% CI: 0.02-0.99, P = 0.049) as well as stage, adjuvant treatment and R0 resection (microscopically margin-negative) were independent predictors of OS. Conclusions: Presence of CD8 memory T cells (CD8+CD45RO+) in tumor microenvironment was associated with significant better clinical outcome, and the expression of PD-L1 on cholangiocarcinoma cells may suggest a potential therapeutic target of antiPD-L1 antibody therapy in cholangiocarcinoma.
CK14, FOXA1, and androgen receptor (AR) expression in patients (pts) with triple-negative breast cancer (TNBC).
Authors: Ayca Gucalp, Margaret D. Krasne, Kiran A. Jakate, Esther N. Drill, Yong Hannah Wen, Muzaffar Akram, Alice Y. Ho, Gaorav P. Gupta, Edi Brogi, Clifford A. Hudis, Tiffany A. Traina
Journal: Journal of Clinical Oncology (2014)

1126 Background: TNBC is recognized to be heterogeneous based on gene expression profiling. An AR+, androgen-dependent subset of TNBC benefits from antiAR drugs. FOXA1, a nuclear mediator of steroid receptor signaling is involved in the regulation of ER and AR. FOXA1 expression in ER+ BC correlates with better prognosis; the significance of FOXA1 in TNBC is not established. We report the rates of FOXA1 expression in relationship to AR, basal markers and outcome in a retrospective cohort of pts with TNBC. Methods: We identified 1,032 pts with resectable, TNBC (ER/PR<1%; HER2 0-2+/FISH <2) who had surgery at MSK (1998-2006). Exclusion criteria: neoadjuvant chemotherapy, radiation, inflammatory/metastatic BC. We constructed tissue microarrays from 311 primary tumors (>1cm, post 2002) with three 0.6mm cores per tumor. Standard IHC methods were used. Scored positive: FOXA1 >3 per Badve CCR 2007; AR and EGFR paralleled the ASCO/CAP criteria for ER and HER2 respectively; CK5/6 and CK14 any cytoplasmic stain. Associations were analyzed with Fischer Exact/Spearman correlation tests. Log Rank test was used for survival analysis. Results: 303 pts met eligibility criteria. # of positive/evaluable cases: AR 16/283 (6%), FOXA1 79/273 (29%), CK5/6 185/290 (64%), CK14 128/278 (46%) and EGFR 234/289 (81%). There was a significant correlation between FOXA1 and AR (p=1.19E-10). There were inverse correlations between FOXA1 and CK14 (p=0.003), AR and CK14 (p=0.004) and AR and EGFR (p=0.018). 264/291 (91%) pts met Nielsen criteria (NC) for basal-like BC (BLBC). 94% (15/16) of AR+ tumors and 98% (121/124) of CK14+ tumors co-expressed NC. 46% of BLBC by NC expressed CK14. CK14 expression was associated with worse DFS (p=0.003, 5-year DFS 69% vs. 83%) and OS (p=0.01, 5-year OS 71% vs. 85%). FOXA1 expression was not associated with a significant difference in DFS (HR 0.98, p=0.26) or OS (HR 0.99, p=0.52). Conclusions: CK14 expression was the only prognostic marker for survival in our cohort. A high proportion of the AR+ tumors are BL according to NC, which is contradictory to gene expression data. There may be differences between these subsets or discordance between protein expression of AR and molecular subtype of TNBC (luminal AR vs. BL).
The era of geriatric oncology: Phase II/III trials over the decades.
Authors: Jane Sze Yin Sui, MinYuen Teo, Jacklyn Sze Tin Sui, Sarah Louise Picardo, Lynda M. O'Riordan, Michael Thomas McCarthy, Deirdre Kelly, John McCaffrey
Journal: Journal of Clinical Oncology (2015)

e20519 Background: The incidence of cancer is expected to rise significantly with aging population. Historically, clinical trials were less likely to enrol older patients (pts) out of concerns for factors such as co-morbidities and altered physiological reserve, leading to older pts being under-treated due to deficit in the evidence base. There has been a call for increasing geriatric-specific cancer clinical trials (GCCT). This study sought to examine trends in GCCT, and investigate their characteristics. Methods: We performed a PubMed search for all phases II and III studies published between 1990 and 2014 with a combination of the following search terms: “elderly”, “geriatric”, “cancer” and “carcinoma”. The following data were extracted from identified studies: year of publication, cancer subtypes, sample size per trial, eligibility criteria (e.g. age and ECOG performance status) and treatment regimen details. Results: 106 GCCT with a total of 8604 pts were identified, of which 89 (84%) were Phase II. Median age was 75 years (range: 69 to 83 years). Rise in number of GCCT were observed, with 5 studies before 2000 and 12 studies in 2014, with a substantial rise seen after 2010 - 47 trials (43%) were conducted after 2010. Median number of pts per trial in 2000 and in 2014 was 43 and 49. However, larger trials were seen after 2010 as 11 (31%) of Phase III trials were from this time period. Most common disease types were: lung (57%), colo-rectal (13%) followed by lymphoma (11%), while breast and prostate GCCT constitute 9% and 1% respectively. Adopted eligible age criteria of these studies were: ≥ 70 years (63.1%), ≥ 65 years (18.8%) and ≥ 75 (12.0%). Only 5 trials (4.7%) used geriatric assessment tools as enrolment criteria. Most commonly required ECOG statuses were: ECOG PS 0-2 (69.5%), 0-1 (18.1%) and 0-3 (4.7%). 61 (44.5%) trials investigated modified treatment regimens, of which 34 (55.7%) tested alternative dosage and n = 27 (44.3%) alternative scheduling. Conclusions: We observed rising trend of GCCT. However, traditional entry criteria were still used and adoption of geriatric assessment tools remains low. Efficacy of geriatric-specific trials and their ability to redefine treatment paradigms for older patients should be further investigated.