tbuckley/cabot-search huggingface dataset:
Age, comorbidity, and the risk of death in men with PSA failure following radiation therapy.
Authors: Neil E. Martin, Ming-Hui Chen, Clair Beard, Paul Linh Nguyen, Marian Loffredo, Andrew A. Renshaw, Philip W. Kantoff, Anthony Victor D'Amico
Journal: Journal of Clinical Oncology (2013)

82 Background: Life expectancy data based on age and comorbidity may identify men with favorable post-radiation prostate-specific antigen (PSA) failure kinetics unlikely to experience metastasis despite withholding androgen deprivation therapy (ADT). Methods: Of 206 men with unfavorable-risk prostate cancer (PC) enrolled on a randomized trial of radiation vs. radiation + ADT, 108 had a PSA failure and 53 who did not receive slavage ADT because the PSA had not meet a pre-specified criteria of 10 ng/mL (n=41) or had significant comorbidity (n=12) and were followed with q1 year (yr) bone scan and q6 month (mo) PSA formed the study cohort. Comorbidity, age and established prognostic factors were evaluated with Cox regression to determine factors associated with death after PSA failure. Results: Median age at and interval to PSA failure and PSA doubling time were 76.6 yr (interquartile range [IQR] 71.8-79.3), 49.1 mo (IQR: 37.7 – 87.4), and 25 mo (IQR: 13.1 – 42.8) respectively. After a median follow up of 4.0 yr (IQR: 2.0 – 12.5) post PSA failure, 24 (45%) men died, none from PC and no one developed metastases. The median last follow up PSA was 3.6 ng/mL (IQR: 1.8 - 8.3). Increasing age at PSA failure (adjusted hazard ratio [AHR]: 1.14; 95% CI: 1.03 – 1.25; p=0.008) and the presence of moderate to severe comorbidity (AHR: 12.5; 95% CI: 3.81 – 41.0; p&lt;0.001) were significantly associated with an increased risk of death on multivariate analysis. At 4 yr, 86% above the median age at PSA failure and with moderate or severe comorbidity had died compared to 16% whose age was at the median or less and with no or minimal comorbidity (p&lt; 0.001). Conclusions: Men over age 76 with significant comorbidity and a PSA doubling time &gt; 2 yr following post-radiation PSA failure appear to be good candidates for surveillance. [Table: see text]
Implementing innovative, learner-centered methods to teach oncology fellows how to face difficult conversations.
Authors: Andrew Shaw, Matthew Reilley, Jennifer Leigh McQuade, Walter F. Baile, Daniel E. Epner
Journal: Journal of Clinical Oncology (2016)

27 Background: Oncologists engage in emotionally charged conversations with patients and families about prognosis, goals of care, and end of life transitions. Many oncologists lack key skills for guiding patients through such conversations. Key skills include posing open ended questions to elicit the patient’s perspective, using silence effectively, and responding to emotion with empathy. We previously described a communication skills curriculum for first year medical oncology fellows consisting of a series of one hour monthly seminars (Epner and Baile, Academic Medicine, 2014). We now describe improvements in the curriculum based on extensive feedback from learners and teaching assistants. Methods: Anonymous feedback from first year fellows indicated longer sessions would allow for sufficient warm up and more in depth reflection and opportunity to practice. We therefore consolidated the sessions into quarterly 4 hour workshops. Several fellows also expressed discomfort with participating in role play of clinical scenarios in front of colleagues, so we implemented small group learning in which 3-4 fellows practiced communication skills in facilitated role play scenarios. We also replaced large group role play with narrative medicine techniques, such as reading and discussing medically-themed short stories and reflective writing exercises to allow the greatest amount of participation among learners. Results: Fellows completed anonymous surveys on which they rated items on a 4 point scale, with 1 being best and 4 worst. The average score of the two survey items pertaining to large group role play was 2.6. After changes in the curriculum, items pertaining to narrative medicine averaged 1.3, which was very favorable. Items pertaining to relevance and value of the curriculum also averaged less than 1.5 for all years. Attendance was 100% with the exception of fellows who were on vacation. Conclusions: Learner-centered, interactive innovations to our previous communication skills curriculum were highly rated by fellows and addressed issues of enhanced participation in a learning environment in which fellows felt safe to actively participate, reflect, and interact extensively with their peers.
High recurrence risk in pT1bc HER2-positive, triple-negative, node-negative early breast cancer patients.
Authors: A. Vaccaro, F. Ciancola, L. Pizzuti, I. Sperduti, L. Moscetti, P. Vici, F. Longo, E. Ruggeri, M. Di Seri, M. A. Giampaolo, T. Gamucci
Journal: Journal of Clinical Oncology (2011)

609 Background: Controversy still exists about adjuvant treatment decision for small node negative (N0) early breast cancer (BC). Retrospective evaluations of clinical and pathological data show different outcomes. The objective of our analysis is to evaluate recurrence risk in patients (pts) with pT1abc, N0 BC accordingly with some prognostic biological factors. Methods: We retrospectively evaluated 600 pts who underwent surgery between 2000 and 2009 in 4 italian oncologic centers. Survival analysis was performed only for pts enrolled until December 2007 (563 pts) in order to obtain a minimum follow up (FU) of 3 years (yr). Results: Median age at diagnosis 59 (range 21-86); premenopausal 28%; invasive ductal carcinoma 89%; Ki 67>15% 51%; histologic grade (G)1 17%, G2 50%, G3 18%, no data in 15% of pts; pT1a 8%; pT1b 37%; pT1c 55%. We defined 3 cohorts: ER positive (ER+) 82%; HER2 overexpressed or amplified (HER2+) 10%; triple negative (TN) 8%. All ER+ pts received adjuvant hormonal treatment. Chemotherapy (CT) was administered in 35% of pts (pT1c 47%, pT1b 23%, pT1a 10%). In HER2+ cohort CT (plus trastuzumab in 50% of pts) was administered in 35/62 pts (57%) and in TN pts 35/50 (70%). Median FU was 60 months. To date 11% of pts recurred. The 5-yr disease free survival (DFS) and overall survival (OS) were91.3.% and 97.7%. DFS according to different cohorts is shown in table. In pT1bc pts there is a trend towards a higher rate of recurrence (HR 1.62, 95% CI 0.80-3.07; p 0.14) in HER2+ and TN cohorts and DFS according to tumor size is b+c vs a with HR 4.43 (95% CI 0.61-31.97; p 0.14). At Cox multivariate analysis Ki67 and histologic G resulted as independent prognostic factors (HR 2.11, 95% CI 1.07-4.15; HR 2.58, 95% CI 1.26–5.25). Conclusions: Grading and Ki67 are confirmed independent prognostic factors. pT1b or c, N0, HER2+ and TN BC have a significant high risk of recurrence. In pT1c HER2+ pts DFS is presumably related to the high percentage (85%) of trastuzumab-treated pts. Effective therapy should be considered for all these unfavourable prognostic subgroups. Data collection is ongoing and update results will be presented. DFS 5-yr % P All pT1 a 100 0.11 b 90.7 c 90.7 ER+ pT1 a 100 0.11 b 94.4 c 90.5 TN pT1 a 100 0.74 b 82.8 c 83.9 HER2 + pT1 a 100 0.35 b 77.4 c 90.6
Plans among American medical oncologists (AMO) for inclusion of trans-arterial chemo-embolization (TACE) as part of first-line therapy in patients with liver only hepatocellular carcinoma (HCC) not amenable to surgical therapy.
Authors: S. Britton, M. Morse, M. R. Green, J. Willey, K. E. Lemke, J. Marshall
Journal: Journal of Clinical Oncology (2010)

e14617 Background: TACE is a widely applied management strategy for patients with HCC. Methods: Using an extensively tested live, case-based, market research vehicle to anonymously acquire prescribing plan data, we assessed plans of > 300 AMOs to include TACE as part of first-line therapy for the setting of extensive intrahepatic HCC, no extrahepatic spread, Childs Pugh status A and PS 1. The consulting interventional radiologist feels the patient is a candidate for TACE. Results: 13% reported no experience with use of TACE. Among the remaining 87%, 30% would plan immediate TACE followed by “systemic therapy consolidation”; 24% TACE followed by observation until progression; 15% TACE and concurrent systemic therapy; 8% systemic therapy followed by TACE; 8% systemic therapy alone; 2% other. In a follow up question concerning the primary driver of these prescribing plans, the largest subgroup (26%) indicated that their plan for TACE followed by systemic therapy was based on the (incorrect) belief that “TACE will only stabilize intrahepatic disease so additional systemic therapy is needed for tumor regression”. Conclusions: TACE is effective therapy in HCC with the potential to improve survival. The majority of AMOs would plan some type of TACE therapy strategy in this setting but our data suggest awareness of evidence based approaches is low. There are no available data to show that adding concurrent or sequential systemic therapy improves the outcome of TACE alone. Phase III testing of this concept is ongoing. There appears to be a major need to clarify among AMOs the optimum use of TACE and systemic therapy in the setting of inoperable HCC without macroscopic extra-hepatic spread. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Xcenda
Prognosis of patients with breast cancer (BC) in southern Brazil based on immunohistochemistry (IHC) and TNM staging.
Authors: A. T. Brunetto, G. Santos Borges, M. C. Araujo, G. Felippe, M. A. Ribeiro
Journal: Journal of Clinical Oncology (2011)

e12013 Background: It is estimated that 50,000 new cases of BC will be diagnosed in Brazil in 2011. Currently, TNM staging is the most widely used prognostic factor. The classification of different histological subtypes of BC may further improve the survival estimation and help guiding on the selection of the best therapeutic approach. Due to the lack of epidemiological data in Brazil, we have carried out this study. Methods: The main objective of this study was to evaluate the 3 year disease-free survival (DFS) and overall survival (OS) rates women with BC treated with curative intent. Subgroups according to IHC findings were defined as follow: hormone+/erbB2-, hormone+/erbB2+, hormone-/erbB2+, and hormone-/erbB2-. Prognostic correlation with TNM staging using standard univariate analysis was performed. Review of 253 medical records of patients treated during the period from 01/01/2001 to 31/05/2006 at the Department of Mastology (in USFC, UNIVALI, Clinica de Neoplasias Litoral and UNACON) was undertaken. Adjuvant treatment was administered as per ASCO guidelines. Results: The 3-year DFS rates for hormone+/erbB2- (136pts), hormone+/erbB2+ (48pts), hormone-/erbB2+(17pts), and hormone-/erbB2- (52pts) were: 86.03%, 72.92%, 76.47% and 65.38%, respectively (p=0,01). Similarly, the 3-year OS rates were 93.40%, 95.84%, 88.24% and 84.62%, respectively (p=0,01). By comparing the DFS according to IHC subtypes with the DFS according to TNM staging, our data demonstrates that 136 patients with hormone+/erbB2- tumors have a better prognosis regardless of their clinical stage (stage I 29pts ; stage II 78 pts; stage III 28 pts). Out of these, 71 pts (52%) received adjuvant radiotherapy, 72 patients (53%) chemotherapy and 121 pts (90%) hormonal therapy. There was no significant association with DFS for histological grade or clinical stage in this larger subgroup. Conclusions: This study containing limited epidemiological data of BC patients from Southern Brazil suggests that IHC is a prognostic factor at least as important as the TNM staging regarding DFS. The short follow-up time made inappropriate any conclusions for OS.
Predicting the risk of gastrointestinal (GI) toxicity in early colon cancer (CC) patients (pts) treated with adjuvant chemotherapy: Developing a GI toxicity scoring system.
Authors: Gillian Gresham, Jasleen Sidhu, Navraj Malhi, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2014)

420 Background: Baseline demographics and clinical factors may contribute to a pt’s overall risk for developing chemotherapy-related GI toxicity, such as nausea, vomiting, and diarrhea. We aimed to develop a GI toxicity scoring system to better stratify early CC pts who may be at higher risk of developing GI toxicity from adjuvant FOLFOX chemotherapy. Methods: Pts diagnosed with early CC from 2005 to 2008 and treated with FOLFOX at the British Columbia Cancer Agency were reviewed. GI toxicities of interest included (1) nausea/vomiting, (2) diarrhea, and (3) any GI side effects. Baseline variables that were analyzed consisted of age, sex, ECOG, time to adjuvant chemotherapy (TTAC), and laboratory parameters. Stepwise regression was used to develop a multivariate model for each toxicity and a weighted risk scoring system was subsequently devised based on the magnitude of the parameter estimates in the multivariate model. Results: In total, 475 pts were included: median age was 62 years (range 26-89), 16.2% were aged &gt;70 years, and 54.5% were men. The majority (90.1%) was ECOG 0/1. Independent predictors for nausea/vomiting included age &gt;70 years (OR 2.46, 95%CI 1.3-4.8, p=0.011), GFR &lt;50 (OR 1.68, 95% CI 1.1-2.7, p=0.025), and TTAC &gt;8 weeks (OR 1.33, 95% CI 0.9-2.1, p=0.14) whereas independent predictors for diarrhea included age &gt;70 years (OR 1.44, 95% CI 0.79-2.62, p=0.12) and GFR &lt;50 (OR 1.67, 95% CI 1.1-2.6, p=0.018). The multivariate model for the risk of any GI toxicity included age &gt;70 years (OR: 2.61, 95% CI 1.1-6.1, p=0.049), GFR &lt;50 (OR 1.69, 95% CI 1.1-2.6, p=0.0038), and TTAC &gt;8 weeks (OR 1.79, 95% CI 1.2-2.7, p=0.0059). Points were assigned: 2 points for long TTAC and poor GFR and 1 point for advanced age. The study cohort was classified into their risk groups based on their score (Table). Conclusions: We developed a simple 5-point scoring system to stratify early CC pts receiving adjuvant FOLFOX into low and high risk groups for GI toxicity based on baseline clinical factors. Further validation of this scoring system is required. [Table: see text]
A Four Protein Plasma Fingerprint of Acute Graft Versus Host Disease (GVHD) Predicts Long Term Survival.
Authors: Sophie Paczesny, Sung Choi, Thomas Braun, Carrie Kitko, Krijanovski Oleg, Shawn G. Clouthier, Angela Weyand, Dan Bickley, Dawn Jones, Joel Whitfield, John E. Levine, James L. Ferrara
Journal: Blood (2007)
Short-term clinical outcomes from a randomized controlled trial to evaluate laparoscopic and open surgery for stage II-III colorectal cancer: Japan Clinical Oncology Group study JCOG 0404 (NCT00147134).
Authors: Seiichiro Yamamoto, Masafumi Inomata, Seigo Kitano, Hiroshi Katayama, Junki Mizusawa, Fumio Konishi, Kenichi Sugihara, Masahiko Watanabe, Yasuhiro Shimada, Yoshihiro Moriya
Journal: Journal of Clinical Oncology (2012)

538 Background: The benefits of laparoscopic surgery (LAP) in comparison with open surgery (OP) have been suggested; however, the long-term survival after LAP for advanced colorectal cancer (CRC) requiring complete mesocolic excision is still unclear. We conducted a study to confirm the non-inferiority of LAP to OP in terms of overall survival with less frequent post-operative morbidity. The primary analysis is planned in 2014, and short-term outcomes including post-operative complications are presented here. Methods: Only accredited surgeons from 30 Japanese institutions participated. Eligibility criteria included histologically proven CRC; tumor located in the cecum, ascending, sigmoid or rectosigmoid colon; T3 or deeper lesion without involvement of other organs; N0–2 and M0; tumor size =&lt;8 cm; patient age 20-75 years. Patients were randomized preoperatively by the minimization method. Patients with pathological stage III received adjuvant chemotherapy with fluorouracil plus leucovorin. The primary endpoint is overall survival, and the planned sample size was 1050. Results: A total of 1057 patients were randomized (OP: 528, LAP: 529) between October 2004 and March 2009. Patients assigned to LAP had less blood loss than those assigned to OP (median 30 ml vs 85 ml, p&lt;0.001), although LAP lasted 52 minutes longer than OP (p&lt;0.001). Radicality of resection, as assessed by the number of resected lymph nodes, did not differ between the two groups. LAP was associated with earlier recovery of bowel function (p&lt;0.001), and with a shorter hospital stay (p&lt;0.0001) than OP. Morbidity and mortality until discharge did not differ between the two groups, except for fewer wound-related complications in LAP (p=0.007). Conclusions: Short-term clinical benefits of LAP were demonstrated, and laparoscopic surgery for advanced CRC can be performed safely by experienced surgeons. If the non-inferiority of LAP in overall survival is demonstrated in the primary analysis planned in 2014, LAP will be the new standard surgical procedure for CRC.
Can we accurately identify chemotherapy-related acute care visits in administrative data?
Authors: Monika K. Krzyzanowska, Katherine Enright, Rahim Moineddin, Lingsong Yun, Mohammed Ghannam, Eva Grunfeld
Journal: Journal of Clinical Oncology (2014)

185 Background: Administrative data is increasingly being used to study treatment related complications that lead to acute care visits such as emergency department visits or hospitalizations (ED+H). We evaluated the accuracy of diagnosis codes for identifying chemotherapy related acute care visits (CRVs) among women with breast cancer. Methods: We prospectively developed algorithms to identify CRVs from administrative data in women receiving adjuvant chemotherapy for breast cancer in Ontario, Canada. Sensitivity (SN) and specificity (SP) were calculated for 3 scenarios: chemotherapy related ED visit, chemotherapy related H, and febrile neutropenia (FN) related visit using the chart as the gold standard. Since there is no specific diagnosis code for FN, three definitions of FN were considered: general (defined as fever or infection or neutropenia as main reason for visit), moderate (neutropenia as main reason for visit) or strict (fever or infection plus neutropenia). The population based cohort was generated by linking several health databases to identify women who had at least one ED+H during adjuvant chemotherapy for breast cancer between 2007-2009. The validation cohort consisted of 490 randomly selected cases from this cohort. Results: The population-based cohort consisted of 8,359 patients of whom 43.4% had at least one ED+H including 1,496 women who had multiple visits resulting in 6,293 unique ED+H. Of these, 73.1% were considered CRVs based on our algorithm. The algorithm performed well in identifying CRVs that included an H either from ED (SN 90%, SP 100%) or directly from home (SN 91%, SP 93%) but less well for ED visits that did not result in H (SN 65%, SP 80%). Depending on which FN algorithm was used, 1.4-24% of visits were considered FN related. The general FN algorithm had excellent SN regardless of whether the visit involved H (94-98%) but SP was moderate (66-80%). The strict FN algorithm had good SP (78-99%) but SN was highly variable (13-89%). The moderate FN algorithm provided the best tradeoff between SN (69-97%) and SP (76-98%). Conclusions: CRVs can be identified from administrative data with reasonable confidence, obviating the need for chart abstraction to evaluate chemotherapy related serious events.
Analysis of DNA Methylation at the Human Alpha Globin Cluster during Hematopoiesis.
Authors: Supachai Ekwattanakit, Helena Ayyub, Kevin Clark, Fatima Marques-Kranc, Sue Butler, Jackie Sloane-Stanley, Jacqueline A Sharpe, Stefano Colella, Jiannis Ragoussis, Vip Viprakasit, Richard J Gibbons, Douglas R Higgs
Journal: Blood (2008)
Genetic sequence variants (GSV) in relation to acute and late toxicities in head and neck cancer (HNC) patients treated with radiation therapy (RT).
Authors: F. Meyer, I. Bairati, W. Xu, A. K. Azad, G. Liu
Journal: Journal of Clinical Oncology (2011)

5507 Background: Genetic variation may partly explain differences in normal tissue toxicities after RT; yet no clear picture has emerged from RT toxicity studies of common GSV in candidate genes. In a large cohort of HNC patients treated with RT, we assessed whether 8 GSV, systematically selected from published sources, predicted acute or late RT toxicity,: TP53 rs1042522; ERCC4 rs1799801; ERCC2 rs1799793; ERCC2 rs13181; XRCC1 rs25487; XRCC3 rs861539; GSTM1 deletion; GSTT1 deletion. Methods: In a secondary analysis of a randomized trial of vitamin E supplementation in 540 stage I-II HNC patients treated with RT, RT toxicities were assessed using RTOG Acute Radiation Morbidity Criteria (during RT, 1 month after RT) and RTOG/EORTC Late Radiation Morbidity Scoring Scheme (at 6, 12 months after RT). The most severe time and tissue-specific RT toxicity, graded 0-4, was taken as an overall measure of acute/late toxicity. All 8 GSV were genotyped from blood leucocyte derived DNA. Ordinal logistic regression estimated odds ratios (OR) and 95% confidence intervals (CI) for toxicity, adjusted for known toxicity predictors in multivariate models. The false discovery rate (FDR) due to multiple testing was taken into account. Results: As crude and adjusted ORs associated with GSV were similar, we controlled for FDR by adjusting the p-values associated with the crude ORs. For late toxicity, no statistically significant association was observed with any of the 8 GSV. For acute toxicity, one statistically significant association was observed: The OR of acute toxicity was 1.43 (CI: 1.11-1.85) for the XRCC3 rs861539 (Thr241Met). XRCC3 (X-Ray repair, complementing defective, in Chinese Hamster 3) is part of a BRCA2-FANCD2-FANCG complex that promotes homologous recombination and interacts with rad51. Conclusions: In our study, the rare allele of XRCC3 rs861539 was associated with increased acute RT toxicity, but not late toxicity. Previous studies of this SNP only assessed late toxicity, fibrosis or telangiectasia, with no clear results. Though results are promising, our study also underlines the limitations of the candidate gene approach to identify GSV that could predict RT toxicities.