tbuckley/cabot-search huggingface dataset:
A model for predicting focal ablation candidates in patients with prostate cancer based on MRI and biopsy criteria.
Authors: Brian P. Calio, Abhinav Sidana, Dordaneh Sugano, Sonia Gaur, Amit L Jain, Mahir Maruf, Vladimir Valera, Maria J Merino, Baris Turkbey, Peter L. Choyke, Bradford J. Wood, Peter A. Pinto
Journal: Journal of Clinical Oncology (2017)

31 Background: To determine the accuracy of multiparametric MRI (mpMRI) and fusion biopsy in predicting focal therapy candidates by correlating agreement between patients’ pre-prostatectomy MRI and biopsy findings with whole mount pathology. Methods: Patients who underwent mpMRI and biopsy followed by prostatectomy between 2010-2015 were included in the study. Patients were considered good candidates for focal therapy if they had intermediate risk cancer (max Gleason 3+4 or 4+3 on biopsy) in only one hemisphere of the prostate, and if they had an mpMRI visible lesion(s) on one hemisphere that did not cross midline. Patients were considered poor candidates for focal therapy if they had either low risk cancer (Gleason 6), high risk cancer (Gleason 8, 9 and 10), intermediate risk cancer bilaterally, MRI visible lesions that cross the midline, or contained extracapsular extension or seminal vesicle invasion. Whole mounts of patients considered good candidates were then examined histologically for maximum tumor involvement. Results: 501 patients who underwent prostatectomy between 2010 and 2015 were included in the study, with mean age 60.0 (±10.0) and PSA 6.21 (±6.0). 395 patients were considered poor focal candidates, and 106 were considered good focal candidates. Of these 106, 66 patients had whole mounts available for analysis (14 random biopsy, 52 fusion biopsy). 42/66 (63.6%) patients were confirmed as candidates (6/14 (42.9%) who had random biopsy and 36/52 (68.0%) who had fusion). Candidates failed prediction due to Gleason upgrade in final histopathology in 20/24 (83.3%), and for significant Gleason detection bilaterally in 4/24 (16.7%). Conclusions: Our results suggest that application of mpMRI and biopsy criteria to predict focal therapy candidates may result in undertreatment of a large portion of patients with significant cancer. Results from mpMRI guided targeted biopsy were shown to be a more accurate tool for predicting candidates for focal therapy than results from random biopsy alone. More accurate predictive capability is needed before focal therapy can be widely accepted.
Fertility preservation and decisional regret in young breast cancer survivors: A longitudinal analysis.
Authors: Samantha Rose Dewald, Loki Natarajan, Irene Su
Journal: Journal of Clinical Oncology (2017)

106 Background: Fertility is important to many young breast cancer survivors (YBCS), who face difficult decisions on whether to undergo fertility preservation prior to treatment. Because few longitudinal data assessing decisional regret are available, the objectives of this study were to assess longitudinal changes in decisional regret on fertility preservation following breast cancer diagnosis; determine if fertility preservation treatment decisions are related to decreased decisional regret. Methods: From 3 academic breast cancer programs, 169 YBCS younger than age 45 were recruited at diagnosis between 2009 and 2012 and followed prospectively for ovarian function. Participants completed questionnaires on fertility preservation choices and the Decisional Regret Scale (DRS) during study visits every 6 months for up to 5 years. DRS is scored 0 (no regret) to 100 (highest regret). DRS was dichotomized as none versus any decisional regret. Generalized linear models estimated the change in DRS over time and the association between patient characteristics and DRS. Results: Mean age at diagnosis was 38.7 (SD 4.8). Median total follow-up was 176 days (IQR 84 to 1415 days). Enrollment DRS was available for 89 women; 48% reported decisional regret about fertility preservation (median DRS=20). Participants worried about future fertility were more likely to report decisional regret (p=0.009). 31% underwent fertility preservation, but this was not associated with decisional regret (p=0.65). In repeated measures analysis for the entire cohort, no significant change in DRS occurred over this time period (OR 0.8, 95% CI 0.4-1.7). Worry about future fertility remained significantly associated with DRS over time (OR 55.1, 95% CI 7.7-395.1). Conclusions: In a cohort of YBCS, experiencing decisional regret about fertility preservation persists for years after diagnosis. Those worried about future fertility are more likely to experience decisional regret regarding fertility preservation.
DNA methylation signature for the assessment of metastatic risk in primary renal cell cancer.
Authors: Inga Peters, Christel Reese, Natalia Dubrowinskaja, Wiebke Inga Antonopoulos, Martin Krause, Tu Nghi Dang, Alexander Grote, Albert Becker, Jörg Hennenlotter, Arnulf Stenzl, Hossein Tezval, Markus A Kuczyk, Juergen Serth
Journal: Journal of Clinical Oncology (2017)

516 Background: Transition from localized renal cell cancer (RCC) to metastatic disease is associated with an immense mortality. Beside clinicopathological risk estimation, a molecular prediction of metastatic risk from primary cancers with a sufficient diagnostic accuracy is not available. We biometrically identified a candidate metastasis associated methylation signature (MAMS) in a genome-wide in silico DNA methylation analysis of TCGA data and carried out a double evaluation study using tissues from localized RCC, primary metastatic RCC, and distant metastases. Methods: Candidate MAMS was identified by genome-wide random forest analyses of TCGA methylation level 3 data aiming for classification of 230 primary RCC without distant metastases and 52 metastasized tumors. Forty-nine pyrosequencing and/or quantitative methylation specific PCR analyses were established for a total of 20 candidate methylated loci. For evaluation of MAMS, DNA was isolated and bisulfite converted from the primary RCC tissue cohort (n=187) as well as 99 distant metastases. Localized RCCs consisted of 92 pT1a/b tumors (clear cell, 73; papillary, 16; chromophobe, 2; not classified, 1) without lymph node or distant metastases. RCC samples of primary metastatic disease were obtained from 31 patients. Results: Single candidate loci showed specific hypermethylation when metastatic tissues were compared to primary RCC samples. Random forest analysis showed that MAMS including nine methylation loci achieved a sensitivity of 93% and a specificity of 89% (AUC 0.95) for differentiation of localized RCC and metastases (chi square, p = 3.4*10 -29 ). Positive, negative likelihood, and diagnostic odds ratios were 8.6, 0.08, and 108. Using this random forest model for prediction of primary RCCs associated with distant or lymph node metastases revealed a sensitivity of 58% and specificity of 94% (AUC 0.84, p = 1.0*10 -9 ). Positive, negative likelihood, and diagnostic odds ratios were 9.2, 0.45, and 20.5. Conclusions: A negative MAMS test result retrospectively reduced the probability of metastasis 15-fold in the localized disease cohort, suggesting a prospective evaluation for a possible clinical translation of MAMS in handling RCC patients.
High-grade extrapulmonary neuroendocrine carcinomas and small cell lung cancer: Different entities, same treatment.
Authors: Juliana Florinda De Mendonga Rego, Raphael Salles S. Medeiros, Maria Ignez Freitas Melro Braghiroli, Breno Galvao, Joao Evangelista Bezerra Neto, Rodrigo Ramella Munhoz, Juliana Mariotti Guerra, Lidia Kimura, Suely Nonogaki, Tulio Eduardo Flesch Pfiffer, Gilberto Castro, Paulo Marcelo Hoff, Duilio Rocha Filho, Frederico Costa, Rachel Pimenta Riechelmann
Journal: Journal of Clinical Oncology (2015)

e15176 Background: Small cell lung cancer (SCLC) and high-grade extrapulmonary neuroendocrine carcinomas (EPNEC) share similar histopathological features and treatment, but outcomes may differ. We evaluated the expression of biomarkers associated with platin-resistance and their impact on response rate (RR) to chemotherapy (Cx) and overall survival (OS) in these entities. Methods: We retrospectively analyzed patients (pts) with advanced EPNEC and SCLC treated with platinum-based Cx. All samples were revised by a single pathologist (R.S.S.M.). Paraffin-embedded tumor samples were tested for Ki-67, ERCC1, Bcl-2 and Lin28a expression by immunohistochemistry. H-score was obtained multiplying intensity of staining (0-3) by the percentage of positive cells (0-100), ranging 0-300 ( > = 200 considered positive). Biomarkers were analyzed as both categorical and continuous variables. RR was determined by RECIST 1.1. Association between each biomarkers expression and RR was assessed using Chi-square or Fisher’s exact test for categorical variables and simple logistic regression for continuous variables. OS was estimated by the Kaplan-Meier method and curves were compared by log-rank. Results: From Jul/2006 to Jul/2014, 142 pts were included in the study: 82 (57.7%) were SCLC with median Ki67 of 60%, 60 (42.3%) were EPNEC with median Ki67 of 50%. Baseline clinical characteristics were similar in both groups. With a median of 5 cycles per pt (N = 123 evaluable pts), the RR was significantly higher in the SCLC group (86.7% vs 44.6%; p < 0.001). Median OS was higher among EPNEC pts (12.3 vs 11.1 months; HR: 0.67, 95%CI: 0.46-0.99; p = 0.046). Bcl2 was expressed in 38 (46.3%) SCLC pts and in 17 (28.3%) EPNEC pts (p = 0.03). Neither ERCC1 (p = 0.555) nor Lin28a (p = 0.074) positivities were different between the groups. RR to Cx was not different and no prognostic impact of any of studied markers was seen. Conclusions: The outcome of SCLC and EPNEC is significantly different despite treatment similarities. SCLC had a higher RR with shorter OS. On the other hand, EPNEC had lower RR with longer OS. In both groups, ERCC1, Lin28a, BCL-2 and Ki67 did not have any predictive or prognostic value in pts treated with Cx.
Prognostic significance of the recurrence pattern and risk factors for recurrence in patients with proximal gastric cancer.
Authors: Ahmet Bilici, Fatih Selcukbiricik, Bala Basak Oven Ustaalioglu, Deniz Tural, Mesut Seker, Mahmut Gumus, Suheyla Serdengecti
Journal: Journal of Clinical Oncology (2013)

e15117 Background: The proximal gastric cancer (GC) is usually diagnosed at advanced stage and it had relatively high recurrence rate after curative resection due to high incidence of lymph node metastasis. This study aimed to investigate the pattern and time of recurrence and to evaluate the risk factors for relapse of proximal GC. Methods: Between 2000 and 2012,110 patients with recurrent proximal GC undergoing radical gastrectomy were retrospectively analyzed.The prognostic significance of the recurrence time and pattern at the diagnosis of relapse and the relationship between the pattern of recurrence and the other clinicopathological factors were evaluated. Results: The median time to recurrence was 34 months, 52.7% of patients had relapse within 2 years. The most recurrence patterns were hematogenous and peritoneal metastasis, respectively (47.3 and 39.1%). Hematogenous and loco-regional recurrence were significantly associated with younger age (p=0.04) and proximal resection was related with higher incidence of all recurrence patterns (p&lt;0.001). Moreover, advanced pT stage was significantly correlated with increased hematogenous and peritoneal recurrence (p=0.002). The median disease-free survival (DFS) and overall survival (OS) times for patients with distant-lymph nodes and hematogenous recurrences were significantly worse than those of patients with loco-regional and peritoneal recurrences (DFS, 9.7 vs. 23.4 vs. 35.4 vs. 43.9 months, p=0.014; OS, 19 vs. 46.4 vs. 70.2 vs. 66.8 months, p=0.04, respectively). Multivariate analysis showed that the time of recurrence [p&lt;0.001, HR: 0.37), pN stage, clinical stage and surgery type were independent prognostic factors for OS. The presence of lymph node metastasis was an independent risk factor for both overall and early recurrence (p=0.004, OR: 0.51). Conclusions: Our results indicate that the time of recurrence, surgery type, lymph node metastasis and clinical stage were independent prognostic indicators for OS, while only the presence of lymph node metastasis was an independent risk factor for early recurrence. Total gastrectomy and adequate lymph nodes dissection were rational curative treatment option for proximal GC.
E-WE Thrombin (ProCase) Inhibits Thrombin Mediated TAFI Activation and Accelerates TPA-Induced Thrombolysis
Authors: Erik I Tucker, Brandon Markway, Michael Wallisch, Norah Green Verbout, Christina Lorentz, Marschelle Carris, Owen J.T. McCarty, Andras Gruber
Journal: Blood (2016)
Sex differences in non-small cell lung cancer (NSCLC) patients (p) participating in Spanish Lung Cancer Group (SLCG) trials
Authors: D. Isla, E. Felip, P. Garrido, N. Viñolas, R. García-Campelo, P. Lianes, I. Bover, J. Terrasa, J. J. Sánchez, R. Rosell
Journal: Journal of Clinical Oncology (2007)

7679 Background: Previous findings about differences by sex in lung cancer have prompted us to undertake a retrospective analysis of clinicopathologic and genetic features in women (W) with advanced NSCLC participating in first-line chemotherapy (CT) SLCG trials. Methods: Data on age, histology, PS, CT schedule, XRCC3 (DNA repair capacity gene) single nucleotide polymorphisms (SNPs) assessment in DNA from peripheral blood lymphocytes and CT outcomes were obtained. Smoking history was not available. Results: 1,191 p included in 4 SLCG trials from 2001 to 2005 treated with CT based on CDDP/GEM, CDDP/DOC or DOC/GEM were analysed. 163 p (14.9%) were W. W were significantly younger than men (M) (median, 57 yrs vs 61 yrs, P&lt;0.0001). Adenocarcinoma was the most frequent histology subtype for W but not for M (77.3% vs 46.8%, P&lt;0.0001). There were not significant differences by sex considering PS (0/1) (P&lt;0.85), stage (IIIB/IV)(P&lt;0.18) or overall response rate (P&lt;0.45). Median time to progression (TTP) was 6.8 months (m) vs 5.3 m (P&lt;0.009) in favour of W. Median overall survival (OS) was 12.9 m for W vs 9.3 m for M (P&lt;0.001). XRCC3 SNPs were distributed similarly between sexes. Both SNPs genotyping of XRCC3 241Met/Met and Thr/Met conditioned better survival in W vs M (P&lt;0.05 and P&lt;0.008). In a multivariate analysis, sex was an independent predictive marker for both OS (HR 1.5, 95% CI 1.2–1.9, P&lt;0.0001) and TTP (HR 1.4, 95% CI 1.1- 1.7, P&lt;0.001), others independent variables found were PS, age, type of CT (only for OS), but not XRCC3 241 genotype. Conclusions: Significant differences have been detected in advanced NSCLC by sex in this retrospective first-line SLCG trials analysis according to age, histology and survival favouring W that are in agreement with previous data. Undertaking prospective sex-specific research is crucial in order to determine the best treatment choice and it could be considered gender as a stratification factor in future phase III trials. No significant financial relationships to disclose.
Assessing Performance of Internal Medicine Residents—Reply
Authors: Karen E. Hauer, Eric S. Holmboe, Furman S. McDonald
Journal: JAMA (2017)

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Associations among socioeconomic status (SES), patterns of care and outcomes in breast cancer (BC) patients (pts) in a universal health care system: Ontario’s experience.
Authors: Alexander Kumachev, Maureen E. Trudeau, Kelvin K. Chan
Journal: Journal of Clinical Oncology (2014)

6625 Background: The Canadian health care system was designed to provide equitable access to equivalent standards of care. We aim to examine if BC pts with different SES received different care and had different overall survival (OS) in Ontario, Canada’s largest province. Methods: Female pts diagnosed with BC between 2003-2009 were identified from the Ontario Cancer Registry and linked to databases related to physician claims, hospital and emergency visits and provincial funding programs to ascertain demographics, cancer stage (CS), comorbidities, mammography use, surgery type, adjuvant chemotherapy (chemo), radiation (RT), and vital statistics. SES was defined as neighbourhood income by postal code attained from Statistics Canada and divided into income quintiles (Q1-Q5; Q5=highest). Univariate and multivariable analyses were used to examine the association between i) SES and mammogram screening and BC treatments, and ii) SES and OS. Results: 34,446 BC pts with CS available were identified. 76.0% were > 50 years old. The proportion of CS I, II, III and IV were, 41.4, 38.8, 14.9, & 4.9%, respectively. Screening mammograms (1-5 years prior to diagnosis) rates were significantly higher with higher SES (Q5 = 50.1% and Q1=41.7% (OR = 1.43, 95% CI: 1.32-1.56, p<0.0001)) for pts age >55. Pts with higher SES were more likely to be diagnosed at an earlier CS (p<0.0001, Q5=44.3% & Q1=37.7% were diagnosed with CS (OR = 1.31, 1.23-1.41)). Pts with higher SES were more likely to receive adjuvant chemo (p<0.0001, Q5 vs. Q1 OR = 1.18, 1.10-1.26) and RT (p<0.0001, Q5 vs. Q1 OR = 1.24, 1.15-1.33). There were no obvious differences in adjuvant trastuzumab (T-mab) use (p=0.62), breast conserving surgery (p=0.057) and time between surgery and adjuvant chemo (p=0.15) based on SES. The 5 year OS rates for Q1-Q5 were 80.0, 81.0, 82.2, 83.9 & 85.7%, respectively (p<0.0001). After adjusting for age, CS, comorbidities, rural residence, use of adjuvant chemo, T-mab, RT and surgery type, higher SES remained associated with better OS (p=0.0017). Conclusions: Higher SES is associated with more use of screening and treatments, and better OS in BC pts in a universal health care system.
Preliminary results of a randomized study of the safety and tolerability of three oxaliplatin-based regimens as first-line treatment for advanced colorectal cancer (CRC) (“Tree” study)
Authors: L. Welles, H. Hochster, R. Ramanathan, L. Wong, L. Hart, A. Shpilsky, G. Jirau-Lucca, D. Emanuel
Journal: Journal of Clinical Oncology (2004)

3537 Background: Oxaliplatin (Eloxatin)/fluoropyrimidine (O/F) combinations are highly effective in the treatment of CRC, but there is debate about the merits of different fluoropyrimidine (F) administration schedules & formulations. This randomized, multicenter study assessed the safety & tolerability of three O/F regimens (bolus, infusional and oral). Methods: Eligibility: Age ≥ 18, measurable metastatic CRC (mCRC), no prior chemotherapy for mCRC, ECOG performance status ≤1. The primary study endpoint is the incidence of Grade (gr.) 3/4 toxicities (tox) on each arm; secondary endpoints include standard efficacy measures. Regimens: FOLFOX: O 85mg/m2, leucovorin (LV)350mg, 5-FU bolus 400mg/m2 and infusional 2400mg/m2over 46 hours, every (q) 2 weeks (wks); bFOL: O 85mg/m2 days 1&15, LV 20 mg/m2 and bolus 5-FU 500mg/m2 days (d) 1,8,15, q 4 wks; CapeOx: O 130 mg/m2 d 1, Capecitabine 1000 mg/m2 orally twice daily for 14 d q 3 weeks. Treatment is continued until disease progression or unacceptable tox. Results: Safety data are available for 106 of 150 patients (pts). Overall incidence of gr.3/4 tox was similar on FOLFOX and bFOL, with more gr. 3 neutropenia (n) on FOLFOX (but only 1 episode febrile n), & more withdrawals on bFOL (p=ns). CapeOx had a higher incidence of gr. 3/4 non-hematologic tox, & more pts required study discontinuation due to tox (p=0.004, Fisher's exact test). A protocol Amendment with bevacizumab added to each regimen, reduced Cape dose, & planned accrual of 210 pts has begun enrollment. Data are not yet available. Conclusions: Preliminary data indicate that the 3 O/F regimens are well tolerated. More patients on CapeOx arm were withdrawn for tox, & cape dose has been reduced by 15%. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sanofi-Synthelabo, Inc. Sanofi-Synthelabo Sanofi-Synthelabo Sanofi-Synthelabo.
Oral nicotinamide to reduce actinic cancer: A phase 3 double-blind randomized controlled trial.
Authors: Andrew James Martin, Andrew Chen, Bonita Choy, Pablo Fernandez Penas, Gary Halliday, Robyn Dalziell, Catriona McKenzie, Richard A Scolyer, Haryana M. Dhillon, Janette L. Vardy, Gaya St George, Nira Chinniah, Diona Damian
Journal: Journal of Clinical Oncology (2015)

9000 Background: Nicotinamide (vitamin B3) enhances DNA repair and prevents cutaneous immune suppression after ultraviolet (UV) radiation exposure. It reduces photocarcinogenesis in mice, and human non-melanoma skin cancers (NMSC) in Phase 2 clinical trials. We report the outcomes of the Phase 3 Oral Nicotinamide to Reduce Actinic Cancer (ONTRAC) Study. Methods: ONTRAC was a double-blind RCT conducted in two tertiary treatment centers in Sydney, Australia from 2012-2014. 386 immune competent participants with ≥ 2 histologically-confirmed NMSC in the past 5 years were randomized (1:1) to oral nicotinamide 500mg bd (NIC) or matched placebo (PBO) for 12 months. The primary endpoint was the number of new NMSCs to 12 months. Secondary endpoints included number of squamous cell carcinomas (SCCs), basal cell carcinomas (BCCs), and actinic keratoses (AKs) to 12 months. Skin reviews by dermatologists were performed 3 monthly. The sample size provided 90% power to detect a 33% difference in NMSC rates. Analysis was by intention-to-treat. Results: The mean age of study population was 66 years, the mean number of NMSC in the past 5 years was 8, and 63% were men. Treatment discontinuation rates were 9% for PBO versus 10% for NIC. 99% of patients underwent at least one post-baseline skin assessment. The average NMSC rate was significantly lower for NIC (1.77) than PBO (2.42). The estimated relative rate reduction (RRR) was 0.23 (95% CI: 0.04 to 0.38, p = 0.02) adjusting for center and NMSC history, and 0.27 (95% CI: 0.05 to 0.44; p = 0.02) with no adjustment. Treatment effects of comparable magnitude were found for both BCCs (RRR = 0.20, 95% CI: -0.06 to 0.39, p = 0.1) and SCCs (RRR = 0.30, 95% CI: 0 to 0.51, p = 0.05). AK counts were reduced for NIC compared to PBO by 11% at 3 months (p = 0.01), 14% at 6 months (p < 0.001), 20% at 9 months (p < 0.0001) and 13% at 12 months (p < 0.005). There were no clinically relevant differences in adverse event rates between the two arms. Conclusions: Nicotinamide reduces NMSC formation in high risk patients and is well tolerated. Furthermore, it is widely accessible as an inexpensive over-the-counter vitamin supplement and presents a new chemopreventive opportunity against NMSCs that is readily translatable into clinical practice. Clinical trial information: ACTRN12612000625875.