tbuckley/cabot-search huggingface dataset:
The association of T cells with survival in mesothelioma.
Authors: Serena J Chee, Maria Lopez, Toby Mellows, Aiman Alzetani, Gareth Thomas, Christian H.H Ottensmeier
Journal: Journal of Clinical Oncology (2015)

7560 Background: Mesothelioma is a rare, aggressive cancer associated with asbestos inhalation. Treatment results are poor regardless of the modality used, with median survival of 4-18 months. Immunotherapy is now established as an important therapeutic option in many solid tumours including mesothelioma, but predictive markers for benefit are absent. Previous studies suggest that CD8 infiltration in mesothelioma may confer survival benefit. TIL density may therefore identify patients with ongoing immune attack, accessible for boosting by immune activation. Methods: Tissue Microarrays (TMA) were constructed with triplicate 1mm cores from a consecutive series of 213 formalin-fixed paraffin-embedded samples from mesothelioma patients. TMA slides were stained for T-cell populations - CD3, CD4, CD8 and CD45RO. Positive cells in 3 high-powered fields (X40) per core were manually scored. The mean score was used to account for tumour heterogeneity. Medians were used as cut point between high and low counts and correlated with clinical data. Results: In contrast to previous smaller studies (Yamada et al, 2010; Ankuru et al, 2008), density of tumour infiltrating CD3, CD4 and CD8 cells was not associated with survival outcomes (p = 0.224, p = 0.205, p = 0.243 respectively). However, a high CD4:CD8 ratio ( > 0.61) was associated with better survival (p = 0.007) with significant ROC curve analysis (AUC = 0.764, p = 0.001). Furthermore, a low CD45RO level was also associated with better survival (p = 0.002) in this cohort. Conclusions: In this unselected mesothelioma cohort, better survival is associated with a high CD4:CD8 ratio and low density of CD45RO memory T cells. Comparison with data from other cancer types suggest that, disease specific immune regulation controls outcome, which is reflected in the particulars of the immune infiltrate in each cancer. For example, a high CD4:CD8 ratio is similarly associated with better survival in cervical cancer (Shah et al., 2011) but not in colorectal cancer (Diederischsen et al., 2003). A better understanding of these immunological drivers and comparative immunometry with other solid tumours types is needed to tailor disease-specific choices for immunotherapy in mesothelioma.
Outcome predictors in patients receiving high-dose interleukin-2 therapy for the treatment of metastatic melanoma and renal cell carcinoma.
Authors: Jeremy D. Whyman, Whitney Hitchcock, Spencer L. James, Joseph J. Shatzel, Marc S. Ernstoff
Journal: Journal of Clinical Oncology (2014)

e20055 Background: Although multiple therapies for metastatic renal cell carcinoma (RCC) and metastatic melanoma (MM) exist, high dose interleukin-2 (IL-2) remains a viable treatment option for a certain subset of patients. A small percentage of patients treated with high dose IL-2 will achieve partial or complete responses to therapy as well as prolonged overall survival, although the subset of patients who will benefit most remains unclear. We aimed to look at several pretreatment and treatment parameters to determine which correlate with improved outcomes. Methods: We conducted a retrospective review of all patients undergoing IL-2 therapy for RCC and MM at our institution from January 1, 2007 through December 31, 2012. We examined multiple patient variables including baseline disease state, pre-treatment laboratory values and treatment-associated side effects. We used multivariate analysis to determine which of the former affected outcomes. Our primary outcome of interest was overall survival. Secondary outcomes included progression free survival and response to treatment. Results: 74 patients were included in the analysis, of which 53 had MM (72%) and 23 had RCC (28%). Factors associated with worse overall survival included higher baseline platelet count (HR: 1.02 p=0.022), longer time to peak granulocyte count peak (HR: 1.24 p=0.026) and higher peak creatinine (HR: 1.004 p=0.023). Factors associated with improved overall survival included the development of exfoliative dermatitis during treatment, (HR: 0.04 p=0.001) and prior chemotherapy (HR: 13.3, p=0.001). The appearance of a rash during treatment (HR: 0.26 p=0.024) correlated with improved PFS, and higher peak lymphocyte count correlated with both improved PFS (HR: 0.99 p=0.009) and decreased odds of progressive disease (OR: 0.99 p=0.034). Conclusions: IL-2 remains a therapeutic option for certain patients with metastatic RCC and MM, and offers a curative response in a small subset of patients. We have shown that multiple pre-treatment and treatment parameters correlate with outcome in patients receiving IL-2 and should be considered as potential biomarkers in prospective designed databases.
Long-term complete remission with ipilimumab in metastatic castrate-resistant prostate cancer: case report of two patients
Authors: Luc Cabel, Elika Loir, Gwenaelle Gravis, Pernelle Lavaud, Christophe Massard, Laurence Albiges, Giulia Baciarello, Yohann Loriot, Karim Fizazi
Journal: Journal for ImmunoTherapy of Cancer (2017)

Prostate cancer is one of the most common cancers in men and the fourth leading cause of cancer mortality worldwide. Although major progress has been achieved in the last years for patients with metastatic castrate-resistant prostate cancer (mCRPC), thanks to next-generation androgen receptor axis targeted drugs, taxanes, and bone-targeted agents, immunotherapy has not been widely approved and used for the treatment of prostate cancer. Two large studies with ipilimumab, an anti-CTLA-4 (cytotoxic T-lymphocyte antigen 4) antibody reported improved progression-free survival, but not statistically improved overall survival at the primary analysis (CA184 043 and CA184 095).Here, we report on two patients who received ipilimumab in these trials and are still in long-term complete remission with a follow-up of 64 and 52 months respectively after the initiation of ipilimumab. Immunohistochemical staining for hMLH1, hMSH2, hMSH6 and PMS2 was performed on archival prostate biopsy samples from one of the two patients; they exhibited normal protein expression. Interestingly for this patient, a high CD3+ and CD8+ T cell infiltration was observed on archival prostate biopsies as well as Treg FoxP3+ T cells.Ipilimumab produces clinical activity in patients with CRPC, including very long responders with no detectable residual disease.
Incidence of secondary malignancies (SM) in patients (pts) with germ cell tumors (GCT) who received high-dose chemotherapy (HDCT): A retrospective study from the European Society for Blood and Marrow Transplantation (EBMT) database.
Authors: Andrea Necchi, Giovanni Rosti, Manuela Badoglio, Patrizia Giannatempo, Simona Secondino, Francesco Lanza, Paolo Pedrazzoli
Journal: Journal of Clinical Oncology (2017)

409 Background: Little is still known about the incidence of SM in young adult pts with GCT after HDCT, owing to the rarity of the disease, and the need for long term follow-up (FUP) data registries. In Europe, the EBMT systematically collect relevant data and may provide a suitable platform for retrospective analyses. Methods: Criteria for patient selection included diagnosis of GCT, adult male gender, ≥ 2yr of FUP after the administration of HDCT. Summary statistics were used to describe pt characteristics and outcomes. χ 2 tests were used to compare groups according to the length of FUP. Kaplan-Meier estimates were used to estimate overall survival (OS) since the diagnosis of SM. Log-rank test was used to compare OS in pt subgroups. Univariable Cox regression analyses examined clinical factors potentially associated with OS following SM diagnosis. Results: From 1981 to 2014, 9,153 autografts, accounting for 5,100 pts, have been registered. Of them, 1,855 had ≥ 2yr of FUP. Among the latter, a total of 56 cases of SM were identified (3.0%). 28 (50%) had solid SM, 22 (39.3%) hematologic SM (5 had uncoded SM). Median age at first HDCT was 34 years (IQR: 30-42), median age at development of SM was 42 (37-51). 26 pts (46.4%) received single HDCT cycle, 22 (39.3%) multiple HDCT cycles (8 unknown). 31 pts had ≥ 5 yr FUP, 25 pts 2-5 yr FUP. Solid SM were developed more frequently in those with longer FUP ( ≥ 5 yrs) compared to hematologic SM (p = 0.008). Median follow-up (FUP) was 76.9 months. Univariably, the type of SM (solid vs. hematologic) was significantly associated with OS. Hematologic vs solid SM: HR: 3.49 (95%CI: 2.09-10.47, p &lt; 0.001). Median OS of pts who developed solid SM was 32.8 months compared to 7 months of those with hematologic SM. The retrospective nature of the data is the major limitation. Conclusions: The incidence of SM in GCT pts who have received HDCT is a concern. During the FUP, there seems to be a non-overlapping risk of developing solid or hematologic SM, with a significantly different prognostic impact. These data may be important to improve patient counselling and the planning of post-HDCT FUP.
Utilization and impact of adjuvant chemotherapy (AC) in surgically resected stages I-III non-small cell lung cancer (NSCLC).
Authors: Christina D. Williams, Ajeet Gajra, Apar Kishor Ganti, Michael J. Kelley
Journal: Journal of Clinical Oncology (2013)

7538 Background: Clinical trials demonstrating improved survival with AC for stages I-III NSCLC are limited in their applicability to broader populations. We sought to describe the pattern of AC use and its correlation with survival in the population-based VA system. Methods: We conducted a retrospective analysis of pts with stages I-III NSCLC in the VA Central Cancer Registry. Descriptive statistics were used to examine patterns of AC use over an 8 yr period and to obtain survival rates associated with use of AC. Chi-square was used to compare distributions. Results: Among 28,173 pts with stages I-III NSCLC in 2001-2008, 10,043 had surgical resection. The proportion receiving AC was 9% (stage I), 34% (II), and 40% (III). Receipt of AC increased for each stage, with the greatest increase observed in stage II (2001-03: 12%; 2004-05: 41%; 2006-08: 50%). About 90% received a platinum agent; among these carboplatin was most common (77%) but by 2008 43% received cisplatin. For stages II and III in 2001-2003, the 3-year survival rate was similar irrespective of AC use. In latter time periods, survival rates were significantly higher for stage II AC pts (2004-2005: 53 vs 43%, p=0.03; 2006-2008: 58 vs 46%, p=0.001). Stage III AC pt diagnosed in 2006-2008 had a higher 3-yr survival (52 vs 36%, p&lt;0.001). For all stages and years combined, use of cisplatin yielded a better 3-yr survival rate compared to carboplatin (62% vs 55%; p=0.01). 3-yr survival for stage I, II, and III, regardless of AC, increased over time (stage I: 60, 64, and 69%; stage II: 44, 47, 52%; stage III: 33, 40, and 44%). The fraction of lung cancer pts diagnosed at each stage during the 3 time periods was not significantly different. Conclusions: This retrospective study suggests a significant increase in use of AC for NSCLC in the VA, though half of surgically treated pts with stage II and III did not receive AC in 2006-2008. By univariate analysis, AC use is associated with a significantly better 3-yr survival for resected stage II and III NSCLC and the stage-specific 3-year survival for all pts improved over time in association with increasing use of AC. Cisplatin is associated with better survival compared to carboplatin. Multivariate analysis is planned.
Population based PSA screening in Mexico City.
Authors: Jaime Omar Herrera-Caceres, Eduardo Gonzalez-Cuenca, Andrea G. Manzanera, Laura K. Aguilar, Estuardo Aguilar-Cordova, Ricardo Alonso Castillejos-Molina, Guillermo Feria Bernal
Journal: Journal of Clinical Oncology (2017)

92 Background: Since the U.S. Preventive Task Force recommended against PSA screening in 2012, the polemic between the benefit of early detection and the risk of early overtreatment, has been heightened. Furthermore, in countries where diagnosis is delayed even in symptomatic men and resources are limited for treating advanced disease, the impact of limiting PSA screening may be greater resulting in a shorter incidence/mortality ratio. In Mexico PSA screening is not widely used and many men are never diagnosed with PCa. Thus, the true incidence of PCa is unknown and yet it is the number one cause of cancer morbidity and mortality in men. The current study was designed to evaluate the incidence of PCa in a random population of men from Mexico City using PSA screening. Methods: Prospective enrollment of 3,837 men &gt; 50 years old without previous history of PCa underwent PSA testing. Men with a PSA &gt; 4ng/ml were selected for a second analysis and for completion of a questionnaire on prostate health history. Men with confirmed elevated PSA are being invited to further evaluation and possible biopsy by a urologist. Results: Median age was 59 years (interquartile range 56 to 63 years). In this cohort, 412 (10.8%) men had a total PSA &gt; 4ng/ml (5% of those &lt; 55 years vs. 26% of those &gt; 70 years). From these men, 284 had a repeat PSA approximately 3 months after the first evaluation (median 98 days). A total of 229 men had a 2 nd PSA above 4mg/ml, 25 had PSA &gt; 20ng/ml. During evaluations, 309 men completed the questionnaire showing that 29% had previous PSA testing, 11% had a previous DRE, 4% had history of a previous biopsy and 2% identified having a family history of PCa. Conclusions: Greater than 10% (n = 412/3837) of men from a random screen in Mexico City were found to have elevated PSA ( &gt; 4ng/ml). Of these, 12% (n = 48) and 6% (n = 25) had levels consistent with intermediate- and high-risk disease, respectively. Most of these ”high-PSA” patients did not have a previous PSA evaluation despite symptoms, representing a considerable number of patients in whom screening could be life-saving intervention. A low awareness of family history of PCa could be representative of both the lack of diagnosis of PCa and general ignorance regarding this disease. We continue evaluating and doing biopsies to patients with indication.
Relationship of age, smoking, alcohol use, and exercise among adults with cancer.
Authors: Shani Malia Alston, Allison Mary Deal, Brittaney-Belle Elizabeth Gordon, Trevor Augustus Jolly, Grant Richard Williams, Samara Ann Dixon, Hyman Bernard Muss
Journal: Journal of Clinical Oncology (2013)

e20582 Background: Smoking, alcohol use, and exercise among cancer patients (pts) are important health concerns due to their effects on treatment outcomes. Few studies have focused on health behaviors (HB) in this group. The goal of this study was to assess HB in cancer pts seen at an academic medical center. Methods: The Health Behavior Questionnaire (HBQ) is a nine-item survey that assesses smoking, alcohol and exercise behaviors based on the 2006/7 National Health Interview Survey (http://www.cdc.gov/nchs/nhis.htm). Pts completed the HBQ from 2010 to present as part of two breast cancer (BC) trials and a geriatric assessment trial. The Jonckheere-Terpstra test compared differences among groups as age increased (Jonckheere, Biometrika 41:1/2, 1954). Results: Of 371 pts, 66% were age ≥60 (median 66), 81% white, 16% black and 95% were female. BC was most common (92%). 5% were current and 40% former smokers. 43% reported having ≥1 drinks per week (dpw). Alcohol users averaged 5 dpw (range of 1-18). 40% never exercised vigorously (≥10 minutes that causes heavy sweating or large increases in heart rate/breathing). Older pts were less likely to exercise (p &lt;0.001). Pts who exercised vigorously were more likely to drink (p&lt;0.02). Former smokers were more likely to use alcohol (p&lt;0.0004). The frequency of HB by age is tabulated below. Conclusions: The % of current smokers in this sample of cancer pts was lower than the national average (5% vs 19%) as was the % of current drinkers when compared nationally (43% vs 51.5%). There was no association of age with alcohol use or smoking status. Older pts in this cohort were significantly less likely to report vigorous exercise. As exercise is important for older pts, future studies in exercise intervention would be beneficial. Support: Breast Cancer Research Foundation, New York, NY and Lineberger Comprehensive Cancer Center, Chapel Hill, NC. [Table: see text]
Asthma Is Associated With Subsequent Development of Inflammatory Bowel Disease: A Population-based Case–Control Study
Authors: M. Ellen Kuenzig, Cheryl Barnabe, Cynthia H. Seow, Bertus Eksteen, Maria E. Negron, Ali Rezaie, Remo Panaccione, Eric I. Benchimol, Mohsen Sadatsafavi, J. Antonio Aviña-Zubieta, Gilaad G. Kaplan
Journal: Clinical Gastroenterology and Hepatology (2017)

Asthma and the inflammatory bowel diseases (IBD) each arise through complex interactions between genetic and environmental factors, and share many environmental risk factors. We examined the association between asthma and Crohn's disease or ulcerative colitis.We performed a population-based case-control study using health administrative data from the province of Alberta, Canada. The odds of a diagnosis of asthma preceding the diagnosis of either Crohn's disease (N = 3087) or ulcerative colitis (N = 2377) were compared with the odds of diagnosis of asthma among persons without IBD (N = 402,800) using logistic regression. Effect measure modification by age at diagnosis of IBD (16 years or less, 17-40 years, or older than 40 years) was tested using a likelihood ratio test.A diagnosis of asthma was associated with increased odds of incident Crohn's disease (adjusted odds ratio [OR], 1.45; 95% confidence interval [CI], 1.31-1.60). No effect measure modification was observed for age at diagnosis for Crohn's disease (P = .42). However, we observed effect measure modification by age at diagnosis for ulcerative colitis (P = .0103), with an adjusted OR of 1.49 (95% CI, 1.08-2.07) among individuals diagnosed at an age of 16 years or less (OR) and an adjusted OR of 1.57 (95% CI, 1.31-1.89) among individuals diagnosed at an age older than 40 years. However, there was no association between asthma and ulcerative colitis among individuals diagnosed between ages 17 and 40 (adjusted OR, 1.05; 95% CI, 0.86-1.26).In a population-based case-control study, we associated asthma with Crohn's disease, and with early and late-onset ulcerative colitis.
Predictors for locoregional recurrence for clinical stage III-N2 non-small cell lung cancer with nodal downstaging after induction chemotherapy and surgery.
Authors: Feiran Lou, Arya Amini, Arlene M Correa, Randall L Baldassarre, Andreas Rimner, Jack A. Roth, Stephen Swisher, James Huang, Ara A. Vaporciyan, Steven H. Lin
Journal: Journal of Clinical Oncology (2012)

7043 Background: Pathologic downstaging following induction chemotherapy in patients with stage III-N2 NSCLC is a well-known positive prognostic indicator. However, the predictive factors for locoregional recurrence (LRR) in these patients are largely unknown. Methods: Between 1998-2008, 153 patients with clinically or pathologically-staged III-N2 NSCLC from two cancer centers in the United States were treated with induction chemotherapy and surgery. All patients had pathologic N0-1 disease, and no one received postoperative radiotherapy. LRR were defined as disease recurrence at the surgical site, lymph nodes (levels 1-14 including supraclavicular) or both. Overall survival (OS) was calculated using the Kaplan and Meier method and comparisons were made using the log-rank test. Univariate and multivariate Cox proportional hazards model were used to assess the association of LRR and risk factors. Results: The median follow up time for survivors was 39.3 months. Baseline pretreatment N2 nodal involvement was staged by either pathologic confirmation (18.2%) or PET/CT (81.8%). Overall, the 5 year LRR rate was 30.8% (n=38), with LRR being the first site of failure in 51% (22 of 43). The 5 year OS for patients with LRR compared to those without was 21% versus 60.1%, respectively (p&lt;0.001). Using multivariate analysis, significant predictor for LRR was pN1 versus pN0 disease at time of surgery (p&lt;0.001, HR 3.43, 95% CI 1.80-6.56) and trended for squamous histology (p=0.072, HR 1.93, 95% CI 0.94-3.98). The 5-year LRR rate for N1 versus N0 disease was 62% versus 20%, respectively. Neither single versus multistation N2 disease (p=0.291) nor initial staging by mediastinoscopy versus PET/CT (p=0.306) were predictors for LRR. We found that N1 status was also predictive for higher distant recurrence rate (p=0.021, HR 1.91, 95% CI 1.10-3.30) but only trended for poorer OS (p=0.123, HR 1.48, 95% CI 0.90-2.44). Conclusions: LRR remains high in resected stage III-N2 NSCLC patients after induction chemotherapy and nodal downstaging, particularly in patients with persistent N1 disease. Postoperative radiotherapy may be needed for these high-risk patients.
A comprehensive analysis of molecular profiles across over 10,000 tumor and germ-line exomes across more than 20 tumor types: Novel mechanisms and targets for clinical treatment.
Authors: Shahrooz Rabizadeh, Stephen Charles Benz, John Z Sanborn, Charles Joseph Vaske, Patrick Soon-Shiong
Journal: Journal of Clinical Oncology (2014)

11031 Background: Whereas the clinical world is familiar with genomic assays targeted to a limited number of mutations as a means to derive molecular insight to therapies, the power to deliver more comprehensive, non-assumptive, and stochastic molecular analysis is now available to guide treatment decision that is unbiased to traditional tissue-by-tissue assignment of therapeutics or a priori assumptions that a few hundred DNA mutations are drivers of the cancer. Methods: Over 10,000 tumor and germ line exomes and RNA-seq data representing over 5,000 patients across more than 20 tumor types were processed using Contrastor, a cancer genome differentiation algorithm designed to detect variants (germline and somatic), copy-number alterations (overall and allele-specific), and genomic rearrangements. RNA-seq data was used to confirm the presence of alterations in the transcript when available. Paradigm, an algorithm that integrates genomic and transcriptomics data and designed to identify key altered cell signaling pathways, was used to reveal shared pathways amongst independent tumor types. Results: Aggregating the top altered genes across tissues reveals very few genes are dominated with alterations present in single diseases. DNA repair and kinase signaling proteins appear to be the predominantly altered classes, with transcriptional proteins also highly altered (TP53, MLL, CREBBP). A surprising number of new targets for pharmaceutical discovery were uncovered, and particularly in patients with no clear therapeutic options based on the analysis of “actionable” genes. Despite patients having unique molecular profiles, Paradigm revealed shared pathways across tissue types driving tumor progression that are likely targets for therapeutic intervention. Conclusions: The vast landscape and ample number of mutations identified in this comprehensive analysis illustrates the complexity of cancer genomics and the need for transcriptomics driven pathway analysis to identify the focal points of therapeutic intervention.