tbuckley/cabot-search huggingface dataset:
End-of-life chemotherapy and adherence to ASCO’s Top Five List recommendations: A single-center retrospective review.
Authors: Richard Tancredi, Sara Stefani, Lorenzo Gervaso, Vittorio Fregoni, Priti Poojary, Marco Cefalì, Giulia Piacentini, Alberto Riccardi
Journal: Journal of Clinical Oncology (2017)

e21509 Background: End-of-life palliative chemotherapy does not improve quality of life nor does it prolong survival of terminal cancer patients. On the contrary, it is related not only to increased health costs, but also to severe therapy related side effects and to patient and caregiver distress. The first point of the ASCO’s Top Five List, released in 2012, tried to address the issue of chemotherapy overuse near the end of life. We tried to determine the aggressiveness of end of life care at our Institute by evaluating the number of patients who received end-of-life chemotherapy. We also aimed to verify whether the recent ASCO recommendations were followed or not. Methods: Electronic medical records were examined to identify patients who received at least one cycle of palliative chemotherapy and who died either in the Oncology or in the Palliative Care unit of the ICS Maugeri hospital between January 2014 and December 2015. Results: 181 patients were included in the study. 22% (40 patients) of these received chemotherapy in the last 4 weeks, and 6% (10 patients) in the last 2 weeks of life. 45% (18) of patients who were actively treated in the last month of life began a new chemotherapeutic regimen within the same period of time. Recently diagnosed patients were more likely to be treated aggressively in their last weeks of life (chi-square test, p value = 0.007). 12% of patients (7 patients) who started a new chemotherapeutic regimen within 90 days of death had already received 3 or more previous regimens. Futhermore, 16% of them (19 patients) had an ECOG PS of 3 or 4 at the beginning of the last regimen. The median survival since the beginning of the last chemotherapeutic regimen was 63 days for patients with a PS of 1 or 2 and 32 days for patients with a PS of 3 or 4 (Logrank test, p = 0.005). Conclusions: Almost 1 patient out of 4 receives end-of-life chemotherapy at our institute. About 30% of our patients began a new chemotherapeutic regimen even though they were in compromised clinical conditions or did not respond to 3 or more previous regimens. Our data highlight a relevant abuse of active anticancer treatments; efforts should be done to reduce these figures and to focus on supportive care near the end of life.
TCT-651 Novel, preclinical model of aortic banding for evaluation of implantation feasibility and long term durability of transcatheter aortic valves
Authors: Paweł Buszman, Piotr Buszman, Krzysztof Milewski, Carlos Fernandez Ceballos, Magdalena Michalak, Mateusz Kachel, Katarzyna Czerwińska-Jelonkiewicz, Marek Cisowski, Andrzej Bochenek
Journal: Journal of the American College of Cardiology (2018)
Response to apatinib in patients with osteosarcoma: Updated evidence of efficacy and safety.
Authors: Chongqi Tu, Kai Yao, Yong Zhou, Yi Luo, Wenli Zhang, Hong Duan, Li Min
Journal: Journal of Clinical Oncology (2018)

e23500 Background: Osteosarcoma is the most common malignant tumor of bone in teenagers, which displays hyperproliferative characteristics and high vascularity, making vascular endothelial growth factor receptors (VEGFRs) become promising targets. We have reported that Apatinib, an oral tyrosine kinase inhibitor targeting VEGFR-2, showed efficacy in the treatment of osteosarcoma. Here we updated the results of apatinib in osteosarcoma. Methods: This retrospective analysis involved patients with osteosarcoma treated with apatinib for at least one month. Tumor responses were evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Progression free survival (PFS) and overall survival (OS) were assessed by Kaplan–Meier test. And the safety profile was also recorded. Results: From May 2015 to Aug 2017, 57 eligible patients were enrolled, 7 (14.6%), 16 (33.3%) and 22 (45.8%) patients were treated in neoadjuvant/adjuvant, first-line and second-line settings, respectively. Initial dosages of 250, 425, and 500 mg/d were given to 7 (12.3%), 3 (5.3%), and 47 (82.5%) cases, respectively. Median age was 23 (range 9-88), and male to female was 35:22. There are 33 patients with lung metastasis and 2 patients with bone metastasis. Among 46 evaluable patients, 1 patient achieved complete response, 11 patients achieved partial response, 32 patients achieved stable disease and 2 got progressive disease. The objective response rate (ORR) was 26.1%, and the disease control rate (DCR) was 95.7%. At the cut-off date of Dec 5 2017, the median PFS and OS were 13.5 months (95%CI, 6.4–15.3 months) and 18.2 months (95%CI, 15.9–NE months), respectively. The most frequent adverse events (AEs) were hand-foot syndrome (HFS) (37, 64.9%), diarrhea (17, 29.8%), anorexia (10, 17.5%), mucositis (9, 15.8%), and hypertension (9, 15.8%). No death was reported. Conclusions: Longer follow up of this study demonstrated that apatinib is associated with active responses and promising survival in osteosarcoma. Safety profile was consistent with our previous reports. These data support further prospective trials of apatinib in osteosarcoma.
Reply to Zhenjie Wu and Linhui Wang's Letter to the Editor re: Riccardo Bertolo, Riccardo Autorino, Giuseppe Simone, et al. Outcomes of Robot-assisted Partial Nephrectomy for Clinical T2 Renal Tumors: A Multicenter Analysis (ROSULA Collaborative Group). Eur Urol 2018;74:226–32
Authors: Riccardo Bertolo, Riccardo Autorino
Journal: European Urology (2018)
Racial disparities in the diagnosis, surgical management and survival of right sided and left sided colon cancers.
Authors: Sanjay R. Jain, Snigdha Nutalapati
Journal: Journal of Clinical Oncology (2018)

e15660 Background: Higher Colorectal cancer (CRC) incidence and mortality in African American (AA) is largely attributed to molecular characteristics, advanced stage of diagnosis, and inadequate access to health care. We aimed at determining etiological role of surgical status in the noted disparities, stratified by site of origin, stage at diagnosis, race and gender for both left (Lt) and right (Rt) sided CRC. Methods: Surveillance, Epidemiology and End Results (SEER) database was analyzed for the study period 2004 to 2014. Microscopically confirmed Rt CRC were identified using primary site codes 18.0, 18.2, 18.3 and 18.4 and Lt CRC using 18.5, 18.6, 18.7 and 19.9. Proportions obtained were analyzed using chi square test and p-Value < 0.05 was considered statistically significant. Results: Total of 212,913 CRC cases were identified, 49.7% were female. AA were relatively younger compared to whites (64 years ±13 vs 68 years ±14). AA when compared to whites were significantly more likely to be diagnosed at Stage IV (Rt.23.6% vs. 17.4%; Lt.23.1% vs. 18.9%) and whites were more likely at Stage I (Rt.20.8% vs. 19.4%; Lt.24.3% vs.20.5%) & II (Rt.29.5% vs. 24.3%; Lt. 22.9% vs. 21.1%). No difference was noted for Stage III CRC. AA have worse 5 year survival rates for all stages compared for both Lt and Rt CRC (Stage I – Lt.88.8% vs 93.9%, Rt. 88.1 % vs 92.8% ; Stage II – Lt. 75.3 % vs 81.8%, Rt. 81.8% vs 86.6%; Stage III – Lt. 64.5% vs 72.7% Rt. 60.1%vs 64.0% ; Stage IV – Lt. 10.6% vs 14.9% Rt. 7.9% vs 11.0%). Significantly more AA were not recommended surgery for Stages I, II and IV in both Rt and Lt sided CRC. AA were also significantly more likely to refuse recommended surgery only for Lt Stage IV CRC. Significantly higher proportion of whites received surgery only for Stages II and IV for Rt CRC and Stage I, II and IV for Lt CRC. Conclusions: Given worse relative 5 year survival rates in AA and no significant racial differences with respect to surgical status and other tumor characteristics especially for stage III CRC, whether the observed survival disparities were largely driven by molecular characteristics for AA stage III CRC should be further analyzed.
Genomic characterization of acral lentiginous melanoma: Identification of altered metabolism as a potential therapeutic target.
Authors: Sarah Ann Weiss, Carlos N Martinez, Eleazar Vega-Saenz de Miera, Igor Dolgalev, Richard L. Shapiro, Adriana Heguy, Eva Hernando, Tomas Kirchhoff, Iman Osman
Journal: Journal of Clinical Oncology (2016)

9524 Background: Acral lentiginous melanoma (ALM) is a histologic subtype of melanoma with distinct clinical and biological features compared to common cutaneous melanoma. KIT alterations have been implicated as oncogenic drivers, yet phase II trials of KIT inhibitors in advanced ALM demonstrate limited clinical efficacy. Identification of effective targeted treatment strategies remains a challenge given the limited existing data on the molecular underpinnings of ALM. Methods: We examined a cohort of ALM patients enrolled in NYU’s melanoma biorepository to identify genetic alterations underlying ALM. Whole exome sequencing (WES) was performed in a discovery cohort on genomic DNA extracted from fresh-frozen ALM tumors and matched whole blood. RNA sequencing (RNAseq) data were then incorporated with WES to increase confidence in identifying recurrent nonsynonymous somatic mutations. Genes with recurrent mutations were examined in an independent validation cohort using target capture probes. Results: In the discovery cohort (n = 8), we identified recurrent somatic mutations in known cancer-related genes, in addition to KIT and NF1, involving: metabolism (GPAT2), epigenetic regulation (EZH2), and growth factor receptors (FGFR2). We also identified 10 genes with recurrent somatic mutations not previously catalogued in COSMIC and validated by RNAseq, some of which involve: cytokinesis (CNTROB), metabolism (SLC13A3), NF-kappaB signaling and cell death (CARD14), tumorigenesis (KIAA1109) and neuronal regulation (TENM3). Targeted sequencing of these genes in the validation cohort (n = 26) confirmed the incidence of somatic mutations in CNTROB (15%), SLC13A3 (8%), CARD14 (11%), KIAA1109 (23%) and TENM3 (23%). Conclusions: We identified genes involved in metabolism that have recurrent mutations in ALM tumor samples. These findings may support a role for targeting metabolic pathways in ALM. The highest confidence mutations have been prioritized for in vitro functional assays to test their candidacy as impactful drivers with potential for future targeted therapeutic approaches.
What do patients really want to know?
Authors: Anesa Waheda Ahamad, Paul E. Wallner, Sharon Salenius, Rudi Ross, Eduardo Fernandez
Journal: Journal of Clinical Oncology (2017)

e18261 Background: We describe and analyze the quantity, nature and spectrum of questions asked by patients at consultation for radiotherapy to clarify the volume of questions that patients have and to inform the extent to which pre-composed non-personalized educational material is sufficient. Methods: With IRB approval, we retrospectively reviewed records of consultations that were performed by a single radiation oncologist from 2012 to 2016. Patients had been asked to list all of their questions exhaustively, which were then documented. To define topics for data abstraction, questions were extracted from records of a pilot group from the initial six-month period. One hundred and seventy five questions were obtained and were condensed into 57 information topics that were further grouped in to 34 themes, nine subjects and 2 broad areas. Results: A total of 2,386 questions were posed by 396 patients. The median number of questions asked per patients was 6, range 0 to 16 and interquartile range 4. There were 878 disease-related questions (36.8% of all questions) and 1,358 radiation modality-related questions (56.9% of all questions). The frequency of questions on each of nine subjects is listed in the Table. Conclusions: It is important to elicit all patients’ questions and concerns during consultation. Since almost 40% of all questions were disease-related regarding the details of the individual’s tumor, pre-composed non-personalized educational material is not sufficient. The 3 most frequently asked subjects also cannot be adequately given as a set on non-personalized information: they require details of their individualized radiotherapy logistics, side effects and radiation technical details. Further study is needed to measure the amount of time and effort required to evaluate and manage the information needed and whether the practice of personalization of information merits additional reimbursement or coverage. [Table: see text]
Where have we gone wrong? Phase II trials (Ph2t) do not inform the results of phase III trials (Ph3t) in platinum resistant ovarian cancer (PROC).
Authors: Tami Grunewald, Monica Tang, Julia Chen, Sally Lord, Michael Friedlander, Chee Khoon Lee
Journal: Journal of Clinical Oncology (2016)

5559 Background: There has been little change in the outcome of patients with PROC over the last 20 years despite large numbers of patients entered on clinical trials. We examined the design and results of Ph2t and Ph3t to understand the potential reasons for this in an effort to improve clinical trial design in PROC. Methods: We conducted a systematic review of Ph2t and Ph3t in PROC published between January 2000 and March 2015. We extracted data on objective response rate (ORR) and 6-month progression-free survival rate (PFS6) in Ph2t and Ph3t. Inter-study heterogeneity was assessed using the Q statistic. Where possible, we compared outcomes for the experimental agents tested in Ph3t with the corresponding Ph2t. Results: We identified 65 Ph2t with 74 treatment arms comprising 3,270 participants. The median Ph2t sample size was 40 (range 8-215). The median ORR and PFS6 were 20% and 30% respectively. Across Ph2t, we observed substantial heterogeneity in ORR (range 0-64%; P heterogeneity < .001) and PFS6 (range 4-74%; P heterogeneity < .001). 43 Ph2t (66%) concluded that the investigational agents should be considered for Ph3t. However only 7 Ph3t with 14 treatment arms comprising 2,366 participants could be identified. The median Ph3t sample size was 254 (range 125-828). For both experimental and control agents, the median ORR and PFS6 were 10% and 30% respectively. Across Ph3t, heterogeneity was less for ORR (range 0-27%; P heterogeneity < .001) and PFS6 (range 13-52%; P heterogeneity < .001). Only 1 Ph3t (14%) met its primary endpoint. ORR of agents tested in Ph3t correlated poorly with ORR of corresponding Ph2t (r = 0.03). Conclusions: Despite multiple investigational agents tested in Ph2t in 1000’s of women, only a minority progressed to Ph3t and only 1 Ph3t in PROC reported improved outcomes in the experimental arm. The results of Ph2t do not inform or correlate with the results of Ph3t. Potential reasons for this include significant patient heterogeneity, problems with the definition of platinum resistance and selection of appropriate trial endpoints in these patients. All these should be addressed in clinical trials in PROC to improve patient outcomes rather than continue as before.
Development of the joint Children’s Cancer Hospital Egypt (CCHE-57357) Dana-Farber Boston Children’s Hospital Pediatric Oncology Fellowship Program.
Authors: Manal Zamzam, Hanafy Hafez, Reham Khedr, Sherif Abouelnaga, Mohamed Abdelbaki, Leslie Lehmann, Liliana C. Goumnerova, Kathleen Houlahan, Mark W. Kieran, Patricia Pruden
Journal: Journal of Clinical Oncology (2017)

e18226 Background: Children diagnosed with cancer in low- and middle-income countries (LMIC) have markedly inferior outcomes compared to those in high income countries. While some of these issues can be resource availability, a major problem is the quality of training and traditional methods of clinical practice where decision making is centered on the most senior person on the team. To ensure real change, highly-trained locally based specialists with a strong emphasis on problem-solving and critical thinking using evidence-based approaches are needed. Methods: The Children’s Cancer Hospital Egypt (CCHE-57357) and Dana-Farber Boston Children’s Hospital (DFBCH) at Harvard Medical School developed a 30 month pediatric oncology fellowship training program following the American Academy of Pediatrics fellowship guidelines. The primary objective of the program was to implement a shared education model to develop highly educated physicians who are able to follow evidence-based approaches and who are committed to sustained practice in LMIC. Results: DFBCH staff provide ongoing education to the fellows through visits to CCHE-57357 every 2-3 months, weekly video sessions with the fellows for case presentation and journal clubs, and weekly conference calls with the fellowship program staff to ensure that the goals and objectives for each fellow and the program are met. Each of the current 15 fellows spend 6 weeks/year in Boston participating in evidence-based multi-disciplinary based rounds; the remainder of the curriculum takes place at CCHE-57357 and incorporates an array of individual, small group and e-learning modules specifically created for the program. Three classes of fellows have been enrolled and the senior class will graduate in the spring of 2017. Conclusions: Training of fellows following the same standards and methods as those applied to North American candidates is feasible and has the potential to advance the quality of education and expertise in LMIC. By focusing on the education of the next generation of clinicians, the opportunity to implement many of the important principles of clinical care can be realized.
Radiation therapy in primary testicular lymphoma (PTL): Does practice match the standard of care?
Authors: Thomas Ollila, Adam J. Olszewski
Journal: Journal of Clinical Oncology (2018)

7544 Background: National guidelines recommend contralateral testicular radiation as part of therapy for primary testicular lymphoma (PTL) regardless of stage, yet adherence to this in clinical practice is uncertain. We examined factors associated with receipt of radiation and overall survival (OS) of patients with PTL treated with or without radiation. Methods: Using data from the National Cancer Data Base (2004-2014), which contains > 80% of lymphomas diagnosed in the United States (US), we evaluated patients with diffuse large B-cell PTL who were treated with multiagent chemotherapy. We examined factors associated with receipt of radiation using log-binomial regression for relative risk (RR) with 95% confidence intervals (CI). OS was analyzed in a multivariable extended Cox model, accounting for immortal time bias. Results: Out of 1,821 patients, only 49.7% received radiation therapy. In a multivariable model, significant factors associated with lower use of radiation included black race (RR 0.66, 95%CI, 0.44-0.99), age 71-80 (RR 0.83, 95%CI, 0.75-0.93) or > 80 (RR 0.52, 95%CI 0.42-0.65) relative to age 60-70, Ann Arbor stage 2 (RR 0.78, 95%CI, 0.68-0.89) or 3/4 (RR 0.74, 95%CI, 0.66-0.84) relative to stage 1, and presence of comorbidities (RR 0.84, 95%CI, 0.75-0.95). There were no significant differences by income, insurance status, distance to hospital, or type of hospital (community or academic). Among patients who received radiation therapy, OS was 86% (95%CI, 83-88%) at 3 years (y) and 79% (95%CI, 75-82%) at 5 y, whereas for those who did not it was 66% (95%CI, 63-70%) at 3 y and 57% (95%CI, 53-60%) at 5 y. Receipt of radiation was associated with lower mortality adjusting for other factors (hazard ratio 0.68, 95%CI, 0.56-0.82). Conclusions: Nearly half of PTL patients in this “real-world” analysis do not receive radiation therapy despite a benefit supported by prospective trials. Association with socio-demographic factors and with survival suggest that delivery of radiation therapy may be an indicator of expertise or overall quality of care in PTL. Further research should examine if other components of PTL therapy like central nervous system prophylaxis are also suboptimally delivered in the US.
TCT-292 Superimposed Stents for Suboptimal Immediate Angiographic Result in Left Main Coronary Artery Lesions After Implantation of a First Stent. Angiographic and Clinical Outcomes.
Authors: Karl Isaaz, Benjamain Haber, Gael Bouchou, Jérémy Terreaux, Antoine Gerbay, None alexis cerisier, Sarah Balichard, Antoine Da Costa
Journal: Journal of the American College of Cardiology (2018)
A circulating miRNA signature to implement diagnostic imaging analysis in young early-stage breast cancer patients.
Authors: Laura Paladini, Giulia Bottai, Carlotta Raschioni, Andrea Sagona, Valentina Errico, Rosalba Torrisi, Giuseppe Canavese, Wolfgang Gatzmeier, Erika Barbieri, Arianna Rubino, Carlo Rossetti, Marco Eboli, Paolo Malerba, Marta Scorsetti, Lidija Antunovic, Marco Alloisio, Armando Santoro, Alberto Testori, Corrado Tinterri, Libero Santarpia
Journal: Journal of Clinical Oncology (2016)

11562 Background: Mammography is the standard for breast cancer (BC) screening and diagnosis. However, its limited accuracy and false-positive results necessitate the identification of novel complementary biomarkers. Circulating microRNAs (c-miRNAs) represent a class of biomarkers with the potential of improving the diagnostic performance of current imaging analysis. Methods: C-miRNA profiles of paired pre- and post-operative serum samples from 402 patients with early-stage BC were analyzed by quantitative reverse transcriptase polymerase chain reaction. Wilcoxon and Mann-Whitney tests were used to identify significantly dysregulated c-miRNAs. Validation was performed on an independent cohort of BC samples (n = 160), in benign breast lesions (n = 60), and in healthy individuals (n= 50). A logistic regression model was used to identify diverse miRNA signatures with the highest diagnostic efficacy. Diagnostic performance of c-miRNA signatures and mammography was evaluated using Receiver Operating Characteristic (ROC) curves. Results: The expression of 15 miRNAs was able to cluster breast cancer patients from healthy donors, pre- and post-operative patients. Eleven miRNAs showed diagnostic potential (area under the curve (AUC) of 0.61 to 0.72). A combination of five miRNAs (miR-10b, miR-21, miR-133a, miR-148b, and miR-155) demonstrated a substantial higher diagnostic value compared with mammography (AUC = 0.89 vs AUC = 0.81, respectively). Importantly, the diagnostic performance of the miRNA signature was consistently better than mammography alone among women under the age of 50 (AUC = 0.91 vs AUC = 0.74, respectively). Of note, a single miRNA (miR-155) was significantly associated (P< 0.001) with lymph node involvement, potentially substantiating histologic evaluation in breast cancer (without biopsy). Conclusions: These results suggest the assessment of circulating miRNAs as useful non-invasive diagnostic markers that increase the diagnostic performance of mammography, particularly in young early-stage BC patients. All together these data motivate the development of a next-generation system that combines the use of molecular biomarkers with breast imaging techniques.