tbuckley/cabot-search huggingface dataset:
Tumor infiltrating and peritumoral T cells and expression of PD-L1 in BRCA1/2-mutated high grade serous ovarian cancers.
Authors: Kyle Strickland, Brooke E. Howitt, Scott J. Rodig, Lauren Ritterhouse, Alan D. D'Andrea, Ursula Matulonis, Panagiotis Konstantinopoulos
Journal: Journal of Clinical Oncology (2015)

5512 Background: Previous studies have shown that the presence of CD3+ and CD8+ tumor-infiltrating lymphocytes (TILs) and a high CD8+/CD4+ ratio are associated with favorable overall survival in ovarian cancer. Given that BRCA1/2 mutated ovarian cancers are also known to be associated with improved survival, we assessed whether the presence of CD3+, CD8+ and CD4+ TILs is enriched in these tumors compared to non-BRCA1/2 mutated ovarian cancers. Furthermore, we assessed the expression of PD-1 and PD-L1 in these tumors. Methods: In this pilot study, we evaluated 34 high grade serous ovarian cancers with germline BRCA1 (n = 28) and BRCA2 (n = 6) mutations and 18 tumors without germline or somatic mutations in BRCA1, BRCA2 or other homologous recombination (HR) genes. Immunohistochemistry (IHC) was performed for CD3, CD4, CD8, CD20, PD-1 and PD-L1 using standard protocols. For evaluation of TILs, a photomicrograph (40X) of the area of maximum CD3+ intraepithelial lymphocytes was obtained with corresponding photomicrographs for the additional stains. For peritumoral lymphocytes, a semi-quantitative scoring method was utilized. Results: The number ofCD3+ TILs was not significantly different between BRCA1/2-mutated and non-BRCA1/2-mutated ovarian cancers (p = 0.23). However, BRCA1/2-mutated tumors were associated with a strong trend for increased CD8+ TILs (p = 0.06) while demonstrating significantly less CD4+ TILs (p = 0.05) compared to non-BRCA1/2-mutated tumors. Overall, there was a significantly higher CD8+/CD4+ ratio in BRCA1/2-mutated tumors (p = 0.02). Furthermore, peritumoral CD3+ T-cells were significantly increased in BRCA1/2-mutated (p = 0.03) compared to non-BRCA1/2-mutated ovarian cancers. We did not detect statistically significant differences in the intensity or distribution of PD-1 and PD-L1 expression between BRCA1 and non-BRCA1/2-mutated tumors. Conclusions: In this pilot study, BRCA1/2-mutated tumors were associated with significantly higher CD8+/CD4+ ratio of TILs and significantly higher peritumoral T cells. These findings support an additional mechanism for the improved survival of patients with BRCA1/2-mutated ovarian cancers.
Role of ruxolitinib in patients (pts) with myeloproliferative neoplasms (MPNs) treated off clinical trial.
Authors: Kiran Naqvi, Sherry Pierce, Lingsha Zhou, Guillermo Garcia-Manero, Jorge E. Cortes, Hagop M. Kantarjian, Srdan Verstovsek
Journal: Journal of Clinical Oncology (2015)

e18076 Background: Ruxolitinib is the only approved therapy for pts with myelofibrosis and polycythemia vera. However, its use in pts not participating in clinical studies has been poorly described. Methods: We reviewed medical records of 45 pts with MPNs (35 post-ET or -PV MF/PMF; 10 CMML/ET/PV/MDS-MPN) that have been treated at our center with ruxolitinib off clinical study. Results: Median duration of therapy was 12.2 months (0.9-28.5) and median follow-up 17.1 months (5.4-36.5). 73% had JAK2V617F mutation; 25 pts had diploid karyotype. Median spleen size by palpation was 11.5 cm (0-28). Fatigue was the most common symptom. 11% started therapy at 20mg twice daily, others started at reduced doses mainly due to anemia or thrombocytopenia. Eighteen of 35 pts with palpable splenomegaly (53%) had a reduction in spleen size by ≥ 50% (complete resolution in 11pts (32%)). Median time to best spleen response was 3 months (0.4-23.6). Improvement in quality of life, including fatigue, weight gain, resolution of fever and night sweats was noted in 19 pts (42%). Seven pts became transfusion dependent after starting ruxolitinib; 1 had an improvement in hemoglobin. At the time of analysis, 18 pts (40%) remained on therapy. 5 pts (20%) discontinued therapy due to anemia/thrombocytopenia. 10 pts transformed to AML with median time to transformation of 9.8 months (3.6-30.1). Nineteen pts (42%) have died; median overall survival was 23.7 months (3.2-36.5). Among pts previously treated with JAK2 inhibitors (n = 19), 37% had a reduction in spleen size. Thirteen pts received concomitant therapy with ruxolitinib including hydroxyurea, danazol and hypomethylating agents. Of the 7 pts treated with hypomethylating agents, 2 had significant improvement in circulating blasts. Danazol was given to 4 pts for anemia, without obvious benefit. Conclusions: Ruxolitinib continues to show benefit in the reduction of spleen size and symptom burden, with limited hematological toxicity, in patients with different MPNs when treated off clinical trial. Its use in combination with other active agents should be explored in clinical studies.
Quantitative contrast peritoneography for intraperitoneal chemotherapy.
Authors: Joshua Leinwand, Xiaotao Guo, Saravanan Krishnamoorthy, Jing Qi, Elethea Hare, Lawrence H. Schwartz, Binsheng Zhao, Robert N. Taub
Journal: Journal of Clinical Oncology (2012)

e13064 Background: Catheter-administered intraperitoneal (IP) chemotherapy is used for peritoneal surface-spreading malignancies to maximize local drug concentrations. Computed tomography (CT) peritoneography can be used to assess for catheter failure and infusate maldistribution, which may contribute to treatment failure and systemic toxicities like cisplatin-induced nephrotoxicity. There is no standard system to assess infusate distribution, and no reported outcomes data from patients assessed with CT peritoneography. We hypothesized that volume and surface area of the compartment available to IP chemotherapy is associated with overall survival and post-treatment estimated glomerular filtration rate (eGFR) in malignant peritoneal mesothelioma (MPM) patients. Methods: Chart review identified 38 MPM patients who underwent CT peritoneograms while receiving IP cisplatin between 2000 and 2011. Volume and surface area of the contrast-filled compartments were calculated by semiautomated computer algorithm supervised by a physician. We retrospectively tested whether surface area and volume were associated with overall survival and post-treatment eGFR, controlling for demographic and disease factors. Results: Larger surface areas were associated with decreased likelihood of mortality, controlling for volume, age, sex and histologic subtype (Hazard Ratio=.999 cm -2 , p=.035). Larger volumes correlated with higher post-treatment eGFR, controlling for pre-treatment eGFR, body surface area (BSA), surface area and the interaction between BSA and volume (β=.154 cc/min/cm 3 , p=.017). Conclusions: The association of larger surface areas with improved overall survival is consistent with more direct drug contact with potential areas of tumor spread. The association of larger volumes with higher post-treatment eGFR is consistent with less cisplatin diffusion into the circulation due to lower intra-abdominal pressures, which vary inversely with volume. CT peritoneography is an appropriate modality to assess distribution of catheter-administered intraperitoneal chemotherapy. Quantitative analysis of contrast-filled compartment surface area and volume may be predictive of treatment efficacy and side effects.
The role of macrophages in docetaxel (DTX) resistance in castrate-resistant prostate cancer (CRPC).
Authors: Lisa Horvath, Mark D. Chatfield, Michelle Lee-Ng, Hui-Ming Lin, Lesley Castillo, Samuel N. Breit, David A. Brown, Mark P. Molloy, Gavin M. Marx, Nick Pavlakis, Michael J. Boyer, Martin R. Stockler, Richard Wykes, Susan M. Henshall, Kate Lynette Mahon
Journal: Journal of Clinical Oncology (2013)

e22175 Background: DTX improves symptoms and survival in advanced CRPC, however ~ 50% of patients have chemoresistant disease. Given the toxicity of cytotoxic treatment in this population, there is an urgent need for early chemoresistance markers, a greater understanding of chemoresistance mechanisms and the development of new therapies. This study examined whether early changes in cytokine levels predict chemoresistance and explored the role of macrophages in cytokine generation and chemoresistance in vitro. Methods: 28 cytokines were measured pre/post cycle 1 of chemotherapy from 59 men with metastatic CRPC. Cytokine levels were correlated with PSA response and OS. DTX sensitive PC3 and DTX resistant PC3Rx cells were cultured alone and in coculture with U937 monocytes +/- DTX treatment. Conditioned media (CM) was analysed by a 36 cytokine array panel and by ELISA for MIC1. CM from U937 cells exposed to DTX was used to treat PC3 cells combined with escalating DTX doses. Results: Change in the levels of 10 cytokines over 1 cycle of chemotherapy (MIC-1 p=0.003; IL1ra p=0.004; IL1b p=0.01; IL4 p&lt;0.001; IL5 p=0.041; IL6 p=0.003; IL7 p=0.009; IL8 p=0.017; IL12 p=0.004; IFNg p=0.001) was associated with clinical benefit (PR + SD vs PD). The combination of changes in MIC1, IL4 and IL6 best predicted PSA response (ROC AUC 0.88, 95% CI 0.79-0.97). PC3Rx/U937 coculture expressed more cytokines, chiefly markers of alternative macrophage differentiation, compared to PC3/U937 co-culture (IL10 17-fold; IL27 15-fold). DTX treatment enhanced cytokine production by PC3Rx/U937 coculture while reducing cytokine levels in PC3/U937 CM. The IC70 for DTX in PC3 cells incubated with CM from DTX exposed U937 cells was 10 fold greater than with U937 CM without DTX exposure. Conclusions: Early changes in circulating cytokine levels, especially those involved in macrophage activity, were associated with chemoresistance in men with CRPC. In vitro studies revealed a cytokine-mediated interaction between the macrophages and the DTX resistant cells when treated with DTX that was not apparent in the DTX sensitive cell model. When considered together, these data suggest a significant role for host macrophages in the development of DTX resistance in CRPC.
Premorbid body mass and mortality in patients with hepatocellular cancer: A systematic review and meta-analysis.
Authors: Arjun Gupta, Avash Das, Nivedita Arora, Kaustav Majumder, Preet Paul Singh, Muhammad S. Beg, Siddharth Singh
Journal: Journal of Clinical Oncology (2017)

477 Background: Excess body weight is associated with increased risk of developing hepatocellular cancer (HCC), but its effect on HCC mortality remains unclear. We performed a systematic review and meta-analysis to assess the association between premorbid body mass index (BMI) and HCC mortality. Methods: Through a systematic search of major databases and conference proceedings, up to March 2016, we identified observational studies reporting the association between premorbid BMI, and HCC-related mortality. We estimated summary adjusted hazard ratio (aHR) with 95% confidence intervals (CI), comparing obese (BMI &gt; 30 kg/m 2 ) and overweight (BMI 25-29.9 kg/m 2 ) categories with reference category using random effects model; heterogeneity was measured using the inconsistency index (I 2 ). Results: 9 studies were included in which 6,052 HCC deaths occurred in 1,599,453 cancer-free individuals at cohort inception. 5 studies reported data as obese vs. overweight vs. normal BMI, and 4 reported data as obese + overweight combined (BMI &gt; 25 kg/m 2 ). On meta-analysis, pre-morbid obesity was associated with higher HCC-related mortality, as compared to individuals with normal BMI (obese: aHR, 1.96; 95% CI, 1.46-2.46, I 2 = 37%; overweight: aHR, 1.08; 95% CI, 0.97-1.21, I 2 = 0%), in dose-dependent manner. This effect was stronger in males [3 studies, aHR, 2.50; 95% CI, 2.02-3.09] vs. females [2 studies, aHR, 1.45; 95% CI, 1.08-1.97]. This effect was seen primarily in Western populations [4 studies, aHR, 2.10; 95% CI, 1.77-2.48], but not in Asian population [1 study, aHR, 1.10; 95% CI, 0.63-1.92]. Conclusions: In this meta-analysis, there was a dose-dependent increase in HCC-related mortality with pre-morbid obesity, particularly in men, and in Western populations. Strategies targeting obesity-induced metabolic abnormalities may provide novel pathways for HCC therapy.
Expression of serpin B5 in colorectal cancer: Its relationship with CEA expression.
Authors: Ji Yeon Baek, Sun Young Kim, Hee Jin Chang, Ji Won Park, Hyo Seong Choi, Dae Yong Kim, Jae Hwan Oh, Hyun Yang Yeo, Kyunghee Kim
Journal: Journal of Clinical Oncology (2013)

e14606 Background: Serpin B5 is a candidate tumor suppressor but its oncogenic activity has been also reported. Its function may be affected by interacting proteins. The aim of this study was to assess the relationship between serpin B5 and carcinoembryonic antigen (CEA) expressions in CRC. We also analyzed the clinicopathological significance of serpin B5 expression in colorectal cancer (CRC) patients. Methods: Two-dimensional gel electrophoresis (2-DE) analysis and matrix-associated laser desorption ionization mass spectrometry (MALDI-MS) were used to identify differentially expressing proteins according to CEA suppression. Serpin B5 and CEA expressions were evaluated by western blot and ELISA assays. Immunohistochemical expression of serpin B5 was assessed retrospectively in tissues from 377 CRC patients, and correlations between serpin B5 and clinicopathological parameters were analyzed. Results: Downregulation of serpin B5 was identified in CEA-suppressed LoVo cell line using 2-DE and MALDI-MS analyses, and further significant positive correlations between serpin B5 and CEA levels were also found in human CRC cell lines and in blood of CRC patients. Tissue expression of serpin B5 in CRC was significantly associated with serum CEA, histologic grade, stage, lymph node metastasis, liver metastasis, lymphatic and perineural invasion, and infiltrative border. High expression of serpin B5 was also associated with a reduced DFS (P = 0.001) and OS (P = 0.017). Conclusions: This is the first study describing relationship between serpin B5 and CEA expression in CRC. High expression of serpin B5 was also associated with worse prognosis in patients with CRC, and its expression may correlate with CEA levels in CRC.
The patterns of care of follicular lymphoma: First-line treatment in academic and community practice setting.
Authors: Philip Schulman, Elaine Whyler, Vlad Kozlovsky, Evan W. Alley, Paul Gilman, Arlene A. Forastiere
Journal: Journal of Clinical Oncology (2014)

e19515 Background: Follicular Lymphoma remains an incurable B-cell lymphoproliferative disorder with many treatment options, rituximab being the single most common therapy. Methods: In order to establish current patterns of care for this disease, to ascertain differences in age, treatment setting(academic vs community) and time frame, data was collected over a 2 year period from the eviti web based decision support platform database of first line treatment plans submitted for commercial insurance pre-authorization. Results: This review consists of 152 consecutive patients with 79 males. Ages ranged from 30-86 with a median of 60. The most common plan submitted was single agent (SA) rituximab accounting for 79 (59%) of the total. Rituximab/bendamustine totaled 31 (21%) and R/CHOP like regimens 36 (23%) (R/CVP 11 and R/CHO P 25). There was no difference in age for the various regimens with the median age for SA rituximab of 60, R-bendamustine, 62, R/CVP 57 and R/CHOP 58. Academic submissions for SA rituximab totaled 56% with R/CVP, R/CHOP 20 % and R/bendamustine 24%. Private practice submissions were SA rituximab, 53% while R/bendamustine, 24% and R/CHOP/CVP, 23%. The difference in prescribing frequency for SA Rituximab versus the other regimens remained constant throughout the 2 year period. Of note, bendamustine was FDA approved in the 4thquarter of 2008. Conclusions: The treatment of Follicular Lymphoma remains static with SA rituximab the preferred treatment option in spite of recent approval of bendamustine with an excellent safety and efficacy profile. R/bendamustine has superseded the use of R/CHOP only modestly, in the community and slightly more commonly in the academic setting, in spite of recent data suggesting benefit for bendamustine. There is no difference in prescribing patterns and no difference with respect to age. In the academic vs. community setting. The treatment of follicular lymphoma remains a mild, gentle paradigm with SA rituximab still the most common intervention. Further prospective, randomized studies are needed to evaluate whether more aggressive intervention will lead to survival benefit.
Survival comparison between malignant lymphoma HIV+ versus HIV- in the post HAART era: INEN 2005-2011.
Authors: Luis Ernesto Cuéllar Ponce de león, Luis Miguel Miranda Rosales, César Samanez Figari, Carlos Vallejos Sologuren
Journal: Journal of Clinical Oncology (2012)

e18524 Background: The incidence of non-Hodgkin lymphoma in HIV patients (ARLs) is higher than in general population. In the HAART era AIDS-related lymphoma (ARL) are more frequent in patients with advanced age, delayed diagnosis, non adherent HAART, multiresistant strains of HIV. The aim of this study is to compare the clinical characteristic, prognosis factors and survival of malignant lymphomas HIV( +) vs HIV(-) at the Instituto Nacional de Enfermedades Neoplásicas. Methods: Study retrospective, individually matched, case-controlled study according to HIV serologic status (positive vs negative) for patiens newly diagnosed of non-Hodgkin lymphoma between 2005 and 2011. Results: We included 51 cases HIV (+) and 102 controls HIV (-) (Table). On diagnosis, anemia (Hemoglobin &lt; 110 g/L) and opportunistic infections (OI) were statiscal more frequent (p&lt;0.05) in ARL. The overall response to chemotherapy (ORC) was 76.4% (cases) and 89.2% (controls) (p&lt;0.05). In multivariate analysis ECOG ≥ 2, OI and no response to chemotherapy increase mortality risk in ARL (p&lt;0.05). ARL had lower 6-year Disease Free Survival (DFS) (16.0 vs 25 months) (p&gt;0.05) and lower 6- year Overall survival (OS) (37.9 vs 49.7 months (controls) (p&lt;0.001) than HIV (-) patients. Conclusions: In multivariate analysis ECOG ≥ 2, OI and no response to chemotherapy were adverse prognostic factors for OS in ARL. ORC is lower in ARL, though similar DFS of patients with malignant lymphoma HIV(+) vs HIV(-). [Table: see text]
Safety and efficacy of regorafenib post-marketing surveillance (PMS) in Japanese patients with metastatic colorectal cancer (mCRC).
Authors: Yoshito Komatsu, Kei Muro, Kensei Yamaguchi, Taroh Satoh, Hiroyuki Uetake, Takayuki Yoshino, Toshirou Nishida, Hajime Takikawa, Takeyuki Kato, Masayuki Chosa, Toshiyuki Sunaya, Yuka Yamamoto, Yoko Hamada, Toshiaki Watanabe, Kenichi Sugihara
Journal: Journal of Clinical Oncology (2017)

721 Background: The oral multikinase inhibitor regorafenib (REG) was approved for unresectable mCRC in Japan in 2013 based on the results of the global CORRECT phase 3 trial, which included 100 Japanese patients (pts). A PMS (NCT01843400) was conducted to assess the safety and efficacy of REG for the treatment of Japanese mCRC in clinical practice. Methods: Pre-registration was applied in the PMS. Adverse events (AEs), laboratory tests, drug exposure and anti-tumor effects were prospectively monitored for 6 months after initiating REG. One-year survival data was also collected. Target enrollment was 1,250 pts. Results: 1,303 pts were enrolled from March 2013 to May 2015. At the interim analysis as of August 2015, 787 pts were evaluable for safety and efficacy: male 57%; age ≥ 65 yrs 52%; ECOG Performance Status (PS) 0/1/2 40%/51%/10%; KRAS status wild-type/mutant 50%/47%; treatment line of REG 3 rd /4 th / ≥ 5 th line 40%/36%/24%; starting dose of REG 160 mg/120mg 66%/22%. Drug related adverse events (AE) were reported in 702 pts (89%). Most common AEs were hand foot skin reaction [(HFSR) 56%], liver dysfunction (32%, including 17% hepatic laboratory abnormalities), hypertension (27%), platelet count decreased (17%) and fatigue (14%). Rates of any grade of the major AEs typically peaked the first 2 months after starting REG and were relatively stable afterwards. Median time to treatment failure (TTF) was 2.1 months [range 1.9– 2.2]; median overall survival (OS) was 7.0 months [range 6.3– 7.8]. In exploratory analyses, rates of any grade and ≥ grade 3 HFSR and liver dysfunction were higher at the starting dose of 160mg (the dose of the first day of the first cycle) than in that of 120mg or less. Pts who had HFSR had a significantly longer OS than pts who did not (hazard ratio 0.573; 95% confidential interval0.470–0.698; p &lt; 0.0001). TTF of pts with PS 0 tended to be longer than that of pts with PS ≥ 1. Conclusions: The safety and efficacy profiles of REG in Japanese pts in clinical practice are consistent with those of Japanese pts in the CORRECT trial. The results from &gt; 1200 pts enrolled in the PMS will be presented at the meeting. Clinical trial information: NCT01843400.
Twitter mentions and academic citations in the urologic oncology literature.
Authors: Solomon Hayon, Ian Stormont, Meagan M Dunne, Mohummad Minhaj Siddiqui
Journal: Journal of Clinical Oncology (2017)

70 Background: Social media use has dramatically increased in academic medicine with over 70% of journals now using twitter accounts. This calls into question if there is a measurable association between academic impact and Twitter use. We sought to quantify the relationship between the number of Twitter mentions and the number of academic citations a urologic oncology publication receives. Methods: 210 papers from 7 prominent urology journals were examined 18 months after publication from December 2014-January 2015. Articles were evaluated with 2 citation based “bibliometrics” (Scopus, Google Scholar) and 1 social media based metric (Altmetric). Altmetric software allowed for individual tweets regarding an article to be examined. Scores and Twitter mentions for oncology and non-oncology publications were compared using ANOVA and contingency analysis. Results: 79 articles were oncology related while 131 pertained to other topics. The mean number of Twitter mentions for oncology articles was 4.1, compared to 2.4 for non-oncology articles (p=0.004). Articles with at least one twitter mention had 2.0 fold more Scopus citations (p&lt;0.01), 2.1 fold more Google Scholar citations (p&lt;0.01), and 27.8 fold higher Altmetric scores (p&lt;0.001). Oncology authors tended to be more active on Twitter, with 13.9% of oncology authors self-tweeting their own articles versus 5.3% of non-oncology authors (p=0.04). Authors self-tweeting oncology articles was associated with an increased number of citations, with a 10.3 and 7.9 mean citation increase in Google Scholar and Scopus scores (p=0.04 and p=0.01) compared to non-self-tweeted oncology articles. (See table.) Conclusions: Social media appears to be more prominent in the urologic oncology community. The number of citations a urologic oncology publication receives is associated with the number of mentions it has on Twitter. Authors self-tweeting articles may be a factor that increases paper visibility and academic impact. [Table: see text]
Stalking the Diagnosis
Authors: Anand Vaidya, Charles A. Morris, John J. Ross
Journal: New England Journal of Medicine (2010)

A 58-year-old woman presented to her primary care physician after several days of dizziness, weakness, urinary frequency, fever, and dry mouth. A urinary dipstick test was positive for leukocyte esterase and nitrites, and a urine culture grew more than 105 colony-forming units Escherichia coli per milliliter. She returned for scheduled follow-up . . .