tbuckley/cabot-search huggingface dataset:
Association of gamma-H2AX expression with clinopathologic characteristics and clinical outcomes in breast cancer.
Authors: Sherry X. Yang, Eric Polley, Dat Nguyen
Journal: Journal of Clinical Oncology (2016)

11577 Background: Histone H2AX phosphorylation at Ser139 (gamma-H2AX) represents an event of cellular response to DNA double-strand breaks and constitutive expression of gamma-H2AX may reflect intrinsic DNA repair defects or genomic instability in cancer. This study evaluates association of gamma-H2AX expression with clinicopathologic variables and clinical outcome in breast cancer. Methods: Gamma-H2AX expression was examined by immunohistochemistry in 956 primary tumor specimens in patients with stage I, II or III breast cancer. Associations between gamma-H2AX and clinicopathologic variables were evaluated by chi-squared test. Overall survival (OS) between gamma-H2AX-positive and -negative tumors in specific treatment groups was estimated by Kaplan-Meier method and differences were compared by log-rank test. Results: Tumor gamma-H2AX expression data was available for 826 patients and median follow-up in OS was176 months, ranging from 13 to 282 months. Gamma-H2AX-positive tumors, compared to negative, were more poorly differentiated and frequently associated with hormone receptor-negative status as well as positive p53 staining (All P< 0.0001). For patients who received chemotherapy alone (n = 118), median OS was 63 months (95% CI, 29 – 83) in gamma-H2AX-positive tumors as compared with 170 months (95% CI 94 to 235) in gamma-H2AX-negative tumors (P = 0.002). In those treated with radiation therapy alone (n = 78), median OS was 162 months (95% CI, 78 to 243) in gamma-H2AX-positive tumors versus 198 months (95% CI, 143 to not reached) in gamma-H2AX-negative tumors (P = 0.15). Conclusions: Gamma-H2AX expression is significantly associated with poor clinicopathologic features. Patients with gamma-H2AX-positive tumors had poor clinical outcomes in the chemotherapy treatment group. In contrast, patients with gamma-H2AX-positive tumors treated with radiation had comparable outcomes to those with gamma-H2AX-negative tumors. The impact of radiation therapy for patients with gamma-H2AX-positive tumors warrants further investigation in a randomized approach.
Oncological supportive-care unit (OSU): An effective toxicity management model.
Authors: Aurora Mirabile, Emanuela Foglia, Fiorenza Frigo, Elisabetta Del Grosso, Lucia Barbarini, Antonella Bovio, Chiara Butti, Fabrizio Ciambelli, Sergio Pauli, Isabella Ricci, Elisabetta Gargiola, Enrica Aloisio, Giovanna Oliva, Salvatore Agatino Artale
Journal: Journal of Clinical Oncology (2017)

e18301 Background: Oncological patients (pts) frequently experience treatment-related toxicities worsening outcome. According to literature data, 23% - 50% emergency department (ED) and/or hospital admissions in this setting could be avoidable and hesitate in higher management costs and worse quality of life (QoL). Cancer treatment adherence rate is 27% - 87%, mostly related to chemotherapy and post-surgical side effects. Since May 2014 we established an OSU to improve clinical outcome and treatment adherence, to reduce ED access/hospital admissions and toxicities management costs. Methods: All OSU data have been recorded in a database which includes daily management costs into an Italian regional regimen called MAC (Complex Ambulatory Macro-activities). ED accesses were recorded by our “First aid ED operative system”. Hospitalizations costs were evaluated according to regional DRG (Diagnosis Related Group) value and Hospital Discharge Register (HDR). All pts admitted to OSU should answer to two validated questionnaires regarding QoL and anxiety: FACT-G (General FunctionalAssessment Cancer Therapy) and HADS (Hospital Anxiety and depression Scale). We compared toxicities management costs 20 months before and 20 months during OSU. Results: From May 2014 to December 2015, 302/719 pts were admitted to OSU for a supportive care therapy. We obtained the reduction of the costs of the ED access/hospital admission to 52%, while the gain in management was 59% (see table). PS ECOG improved in 9 (18%) pts while it was unchanged in 41 (82%) pts. Adherence to oncologic treatment was satisfactory (95%) and the average values of total FACT and HADS in the follow-up phase improved compared to baseline in 63% and 43% of pts respectively. Conclusions: The interim analysis suggests that OSU improves clinical outcome in terms of QoL and treatment adherence. Moreover, our OSU model demonstrated the possibility to reduce toxicity-related ED accesses/hospital admissions and management costs. [Table: see text]
TCT-833 Does an Occluded RCA Affect Prognosis in Patients Undergoing PCI or CABG for Left Main Coronary Artery Disease? Analysis From the EXCEL Trial
Authors: Shmuel Chen, Dimitri Karmpaliotis, Bjorn Redfors, Evan Shlofmitz, Ori Ben-Yehuda, Aaron Crowley, Ghazaleh Mehdipoor, David Kandzari, Adrian Banning, Marie-Claude Morice, David Taggart, Joseph Sabik, Patrick Serruys, A. Pieter Kappetein, Gregg Stone
Journal: Journal of the American College of Cardiology (2018)
The impact of comprehensive genomic profiling in the management of patients with metastatic solid tumors in a developing country.
Authors: Pablo M. Barrios, Marcio Debiasi, Carolina Cauduro, Fábio Herrmann, Gabriela Marchese, Gustavo Guthmann Pesenatto, Franciele A. Menegat, Gabriel Prolla, Carlos H. Barrios, Andre Poisl Fay
Journal: Journal of Clinical Oncology (2016)

e18038 Background: Comprehensive genomic profiling (CGP) in patients with advanced solid tumors can suggest alternative targeted therapies (TT) or inform clinical trial criteria that may improve clinical outcomes. However, access to both cancer drugs and clinical trials are limited in developing countries. The impact of clinically relevant genomic alterations (CRGA) in changing clinical decisions and outcome in cancer patients is unknown in this scenario. Methods: Forty-nine patients with advanced solid tumors from a single institution in Brazil assayed with CGP were analyzed. CGP was performed using the Foundation Medicine platform in all cases. Clinico-pathological characteristics, genomic data and survival outcomes were retrospectively collected using uniform template. Results: Twentyout of 50 patients (40%) were female andthe median age was 55.0 years (range 18 - 85 years). The most frequent tumor type was lung cancer in 14 patients (28%) and breast cancer in 7 patients (14%). Three patients had no genomic alterations (GA). In 47 patients, 182 GA were found (median 3.0 GA/patient). Out of these, 118 were CRGA (median 2.0 CRGA/patient). Nine patients (18%) received TT based on CGP results (Table 1). Four out of 14 lung cancer patients (28.5%) were treated with TT informed by CGP. A total of 356 clinical trials were identified (median 7 clinical trials/patient), but were not available locally. Conclusions: CGP changed clinical practice in 18% of patients in a country with limited access to cancer drugs. Clinical trials were identified for 94% of patients. None of those had access to the trials, emphasizing the highly unmet need for early phase clinical studies in developing countries. Clinical outcome of patients treated based on CGP results will be presented. Tumor type GA TT Lung Adenocarcinoma EGFR Afatinib/AZD9291 Lung Adenocarcinoma EGFR Erlotinib Lung Adenocarcinoma ALK Crizotinib Lung Mucoepidermoid Carcinoma ALK Ceritinib Cholangiocarcinoma ERBB2 amplification Traztuzumab Cholangiocarcinoma BRAF Vemurafenib Medistinal Germ Cell Tumor PTEN Everolimus Upper Tract Urothelial Carcinoma ERBB2 Neratinib Ovary Serous Carcinoma PIK3CA Everolimus
PTEN loss as a predictive biomarker in head and neck squamous cell cancer (HNSCC) patients treated with cetuximab (C).
Authors: Nnamdi Eze, Christine H. Chung, Veronique Neumeister, Teresa Sandoval-Schaefer, Ju-Whei Lee, Barbara Burtness
Journal: Journal of Clinical Oncology (2017)

e17520 Background: No biomarker of C resistance has been identified in HNSCC. PTEN loss is present in approximately 30% of HNSCC. Biomarker analysis of the E5397 study suggested that addition of C to cisplatin in R/M HNSCC improves PFS in PTEN high/PIK3CA wild type patients but not those with PTEN loss or PIK3CA mutation. We hypothesized that PTEN testing may aid patient (pt.) selection for C therapy in HNSCC. Methods: MCC15780 was a phase II randomized trial of C plus sorafenib or C plus placebo in R/M HNSCC. 52/56 pts. in this study received C. PTEN analysis using AQUA as previously described was performed on tumor from 38 pts. Automated image capture was performed with HistoRx PM-2000 using the AQUAsition software. AQUA PTEN cut off determined as 1177 based on the first tertile.Fisher’s exact test used to compare low and high expression group. Event-time distributions estimated by Kaplan-Meier and compared using log-rank. Stratified Cox proportional hazards models used to estimate hazard ratios (HR) and test for significance for OS and PFS. All p-values are two-sided. A level of p &lt; 0.05 is considered statistically significant. Results: 12/37 (32%) tumors were PTEN low. There was statistically significant improvement in PFS in PTEN high tumors compared to PTEN low tumors (HR (high/low) =0.33, 95% CI= (0.14, 0.75), p=0.008); and this remains significant after adjusting for age, sex, race, and ethnicity (HR (high/low) =0.27, 95% CI= (0.11, 0.67), p=0.004). Conclusions: PFS is significantly longer in PTEN high tumors compared to PTEN low tumors (HR=0.33, 95% CI= (0.14-0.75), p=0.008) in patients with R/M HNSCC treated with C. This finding remains significant after adjusting for age, sex, race, and ethnicity (HR=0.27, 95% CI= (0.11-0.67), p=0.004).This warrants PTEN analysis of specimens from larger cetuximab-based RCT. [Table: see text]
Association of high CD8+ tumor infiltrating lymphocytes at prostatectomy with improved survival of prostate cancer patients.
Authors: Yuanquan Yang, Kristopher Attwood, Cassandra Versaggi, Angela Omilian, Wiam Bshara, Bo Xu, Eric Kauffman, James Mohler, Khurshid Guru, Qiang Li, Saby George, Per Basse, Carl Morrison, Antonios Papanicolau-Sengos, Pawel Kalinski, Gurkamal S. Chatta
Journal: Journal of Clinical Oncology (2018)

5068 Background: High CD8+ tumor infiltrating lymphocytes (TILs) are associated with improved survival in many solid tumors. However, its prognostic value in prostate cancer (PCa) is unclear. Methods: Tumor microarrays of 290 patients with localized PCa who underwent radical prostatectomy (RP) at Roswell Park Comprehensive Cancer Center were retrospectively analyzed using immunohistochemistry. High risk patients were preferentially included to ensure adequate post-RP events for correlation. Six malignant and three benign cores from each patient were stained with anti-CD8 antibody (Dako, M7103). CD8+ cells were scored using Aperio (Leica Biosystems). Patients with < 5-year follow-up were excluded. The CD8+ cell density was dichotomized at 25th percentile. Clinical outcomes collected from a prospective quality assurance database were compared in high vs low TIL group. PSA persistence and recurrence were defined using NCCN prostate cancer guidelines. Results: 230 patients with median age 61 years met follow-up requirement. There were no significant differences in age, Gleason sum (GS), diagnostic PSA, margin status and pTNM stage between high vs low TIL group. High TILs were associated with improved 5-year overall survival (OS) (98% vs 91%, p = 0.008) and PCa-specific survival (99% vs 95%, p = 0.041) when compared to low TILs. High intratumoral/benign CD8 ratio ( > 1) was associated with improved metastasis-free survival (p = 0.031). The median biochemical recurrence (BCR)-free survival was longer in high TIL group (62 vs 42 m). However, statistical significance was not reached (p = 0.18). The prognostic import of high TILs was independent of surgical pathology. In subgroup analysis, it was also associated with improved 5-year OS (97% vs 88%, p = 0.042) in GS > 7 or pT3/4 patients (n = 149, 65%) and prolonged BCR-free survival (NR vs 58 months, p = 0.036) in GS < = 7 and < = pT2 patients. In contrast, the CD8 density of benign cores was not associated with clinical outcomes. Conclusions: High CD8+ TILs are independently associated with improved survival after RP in this majority of high-risk PCa population. This observation suggests that immunomodulation aimed at promoting CD8+ TILs may be beneficial.
Bosutinib vs imatinib for newly diagnosed chronic myeloid leukemia in the BFORE trial: 24-month follow-up.
Authors: Jorge E. Cortes, Michael J. Mauro, Michael W.N. Deininger, Charles Chuah, Dong-Wook Kim, Vamsi Kota, Jeffrey Howard Lipton, Philippe H. Rousselot, Dragana Milojkovic, Phillipp D. Le Coutre, Valentin García Gutierrez, Rocco J. Crescenzo, Eric Leip, Fiona An, Nathalie Bouxin, Andreas Hochhaus, Tim H. Brümmendorf, Carlo Gambacorti-Passerini
Journal: Journal of Clinical Oncology (2018)

7002 Background: Bosutinib is a dual Src/Abl tyrosine kinase inhibitor approved for the treatment of newly diagnosed chronic phase (CP) chronic myeloid leukemia (CML) and CML resistant/intolerant to prior therapy. Here we compare efficacy of first-line bosutinib and imatinib after ≥24 mo (median: 27 mo) of follow-up. Methods: In the ongoing, open-label, phase 3 BFORE trial (NCT02130557), 536 patients were randomized 1:1 to bosutinib (n = 268) or imatinib (n = 268 [3 untreated]). Results: Higher molecular and complete cytogenetic response (MR and CCyR) rates were observed for bosutinib vs imatinib at 12 mo; these differences continued after ≥24 mo (Table). The between-arm difference in major MR (MMR) rate was retained at 24 mo; however, differences in rates of deeper MRs (MR4 and MR4.5) were smaller. Times to MR and CCyR were shorter for bosutinib vs imatinib, consistent with 12-mo data. There were 6 transformations to accelerated/blast phase with bosutinib and 7 with imatinib. 71% vs 66% remained on bosutinib vs imatinib treatment. Conclusions: At 24 mo, a higher MMR rate was maintained with bosutinib vs imatinib. The results support the use of bosutinib as first-line therapy for CP CML. Clinical trial information: NCT02130557. Intent-to-treat (ITT) Population Bosutinib Imatinib n = 268 n = 268 P* Cumulative, any time on-treatment, % MMR 68.7 59.3 .024 MR4 39.9 31.3 .040 MR4.5 25.7 19.0 .063 CCyR† 82.5 76.8 .113 MMR by 24 mo, % 67.2 57.5 .020 MMR, % At 12 mo 46.6 36.2 .013 At 24 mo 61.2 50.7 .015 MR4, % At 12 mo 20.5 11.6 .005 At 24 mo 32.8 25.7 .073 MR4.5, % At 12 mo 7.5 3.0 .020 At 24 mo 13.1 10.8 .428 Time to response (based on cumulative incidence), hazard ratio (HR)‡ MMR 1.37 .004 CCyR† 1.34 .005 MR4 1.39 .025 MR4.5 1.42 .054 Overall survival (OS),§ % – At 12 mo 99.6 98.1 At 24 mo 99.2 97.0 * 2-sided P values not adjusted for multiple comparisons; P value for OS not provided until 5-y analysis† Modified ITT population (bosutinib n = 246; imatinib n = 241); Philadelphia chromosome-positive patients with e13a2/e14a2 transcripts‡ Bosutinib vs imatinib; HR > 1 indicates shorter time to response for bosutinib§ 3 and 9 deaths in the bosutinib and imatinib arm, respectively, due to adverse event related (0 vs 1) or unrelated (2 vs 2) to study drug, disease progression (1 vs 3), and other causes (0 vs 3)
Efficacy and safety of examethasone, high dose cytarabine, and carboplatin (DHAC) with and without rituximab (R) as a salvage regimen for relapsed/refractory (R/R) lymphoma.
Authors: Jeffrey Baron, Megan Menon, Ryan B Hare, Ian Lund, Alice Mohr, Cherie Rondeau, Margaret Syta, Kimberly Celotto, Swaminathan Padmanabhan Iyer, Seema Bhat, Francisco J. Hernandez-Ilizaliturri
Journal: Journal of Clinical Oncology (2016)

e19023 Background: Adequate cytoreduction with cisplatin-based chemotherapy is commonly used prior to high dose chemotherapy and autologous stem cell support (HDC-ASCS) among R/R aggressive lymphoma patients. However, it is associated with significant cisplatin-related toxicities. Swapping cisplatin with another platinum agent could decrease treatment related toxicities. Methods: To this end, we developed the DHAC regimen and retrospectively studied the clinical outcome of patients receiving this regimen between 06/00 and 07/12 (N = 40). Outcomes included overall response rate (ORR), overall survival (OS) and treatment related toxicities. DHAC consisted of: Dexamethasone at 15mg/m2/dose po q6 hrs x 10 doses, High-dose Cytarabine at 3gr/m2 (1.5gr/m2 if > 50 yrs old) intravenously (IV) q12 hrs for 4 doses and Carboplatin at 200mg/m2 IV q24hrs for 2 doses. When utilized, patients received rituximab at 375mg/m2, 24-48 hrs prior to each DHAC cycle. Growth factor support and anti-microbial prophylaxis was implemented 24 hrs post chemotherapy. The regimen was repeated every 21 days. Responses were assessed after 2 cycles with patients proceeding to HDC-ASCS once optimal cytoreduction was obtained. Results: Median age 61yrs; 58% male; 28% had diffuse large B-cell lymphoma (DLBCL), 27% transformed DLBCL, 7.5% follicular lymphoma (FL); 7.5% Hodgkin lymphoma (HL), 12.5% chronic lymphocytic leukemia (CLL), and 10% mantle cell lymphoma (MCL). Median number of prior therapies was 2 (0-6). Median number of DHAC ± R cycles was 2. The ORR was 52% with a complete response (CR) rate of 38%. HDC-ASCS was performed in 38%. Refractory disease to prior therapy was associated with lower CR rates (P = 0.003) and shorter OS (210 days vs. not reached) (P = 0.049). DHAC ± R was well tolerated with manageable grade 3/4 hematologic toxicities. Conclusions: DHAC ± R is a safe and effective salvage regimen for relapsed/refractory aggressive lymphoma. Refractory disease to prior therapy was associated with poor clinical response to this regimen and shorter OS, stressing the need to develop alternative therapeutic strategies for this subgroup of aggressive lymphoma patients.
Patient knowledge, attitudes, and expectations of cancer immunotherapies.
Authors: Simranjot Shokar, Elena Buldo, Lillian L. Siu, Aaron Richard Hansen, Anna Spreafico, Jeffrey Doi, Lindsay Carlsson, Philippe L. Bedard
Journal: Journal of Clinical Oncology (2018)

e18551 Background: Cancer immunotherapy drugs are now approved to treat many types of cancer. Little is known about patient knowledge, attitudes, and expectations of cancer immunotherapies. Methods: A 28-item self-administered questionnaire was developed by a multidisciplinary panel and pre-tested on 7 cancer patients. The questionnaire included a 12-item knowledge test on general knowledge of the immune system and cancer immunotherapies. Participants were asked about their attitudes, expectations, and sources of information consulted to learn about immunotherapies. Patients were eligible if ≥ 18 years of age, any stage of cancer, and fluent in English. Participants were recruited from ambulatory clinics at the Princess Margaret Cancer Centre. Results: Of 108 cancer patients recruited from May to August 2017, 63% were female and the median age was 60 years (range 24-79). Participants were well educated, with 75% reporting post-secondary education. Tumor types included 39% breast, 19% genitourinary, 17% gastrointestinal, 10% lung, and 15% other. Of the total sample, 75% had no prior immunotherapy and 33% had previously participated in a clinical trial. The mean knowledge score was 6.4 (54%) ± 2.8, and 76% of participants expressed an overall favorable attitude towards immunotherapies (≥5 rating out of 7-point Likert scale). In multivariate analysis, participants who scored higher on the knowledge test had favorable attitudes (p= 0.01), prior immunotherapy treatment (p= 0.04), and previously discussed immunotherapy with a healthcare provider (HCP) (p= 0.04). If given the choice, 12% of participants would stop current standard treatment to start experimental immunotherapy. The Internet (44%) and HCP (40%) were the most common sources of information consulted to learn about immunotherapies. Conclusions: Patient knowledge of cancer immunotherapies is limited, although their attitudes are generally favourable and their expectations are high. Patient education should be prioritized along with the development of novel cancer immunotherapy treatments.
Haemodynamics and serial risk assessment in systemic sclerosis associated pulmonary arterial hypertension
Authors: Jason Weatherald, Athénaïs Boucly, David Launay, Vincent Cottin, Grégoire Prévot, Delphine Bourlier, Claire Dauphin, Ari Chaouat, Laurent Savale, Xavier Jaïs, Mitja Jevnikar, Julie Traclet, Pascal De Groote, Gérald Simonneau, Eric Hachulla, Luc Mouthon, David Montani, Marc Humbert, Olivier Sitbon
Journal: European Respiratory Journal (2018)

The prognostic importance of follow-up haemodynamics and the validity of multidimensional risk assessment are not well established for systemic sclerosis (SSc)-associated pulmonary arterial hypertension (PAH). We assessed incident SSc-PAH patients to determine the association between clinical and haemodynamic variables at baseline and first follow-up right heart catheterisation (RHC) with transplant-free survival. RHC variables included cardiac index, stroke volume index (SVI), pulmonary arterial compliance and pulmonary vascular resistance. Risk assessment was performed according to the number of low-risk criteria: functional class I or II, 6-min walking distance (6MWD) &gt;440 m, right atrial pressure &lt;8 mmHg and cardiac index ≥2.5 L·min −1 ·m −2 . Transplant-free survival from diagnosis (n=513) was 87%, 55% and 35% at 1, 3 and 5 years, respectively. At baseline, 6MWD was the only independent predictor. A follow-up RHC was available for 353 patients (median interval 4.6 months, interquartile range 3.9–6.4 months). The 6MWD, functional class, cardiac index, SVI, pulmonary arterial compliance and pulmonary vascular resistance were independently associated with transplant-free survival at follow-up, with SVI performing better than other haemodynamic variables. 1-year outcomes were better with increasing number of low-risk criteria at baseline (area under the curve (AUC) 0.63, 95% CI 0.56–0.69) and at first follow-up (AUC 0.71, 95% CI 0.64–0.78). Follow-up haemodynamics and multidimensional risk assessment had greater prognostic significance than at baseline in SSc-PAH.