tbuckley/cabot-search huggingface dataset:
Analysis of relationship between distance to diagnosing provider and Breslow depth at diagnosis
Authors: K. B. Stitzenberg, S. E. Brier, D. W. Ollila, R. C. Millikan, D. M. Mattingly, N. E. Thomas
Journal: Journal of Clinical Oncology (2005)

6018 Background: Mediators of access to medical care, such as geographic isolation, rurality and socioeconomic status, have been associated with stage at diagnosis, treatment, clinical trial involvement and prognosis for various cancers. For melanoma, little is known about the relationship between mediators of access and various outcome measures. We hypothesize that Breslow depth at diagnosis is related to the distance patients travel to reach their diagnosing providers. Methods: An IRB-approved secondary data analysis was performed of all incident cases of invasive cutaneous melanoma in 2000 from a 42 county ascertainment area. Patients and physicians were geocoded to street address; Euclidian distances between patients and providers were calculated. The outcome variable, Breslow depth at diagnosis, was logged for analysis. Simple and multiple linear regression were used to test associations between Breslow depth and distance to provider, age, gender, census tract poverty rate, rurality and availability of local dermatologists. Results: Of 655 eligible cases, 6% were excluded for missing histopathologic data. Median Breslow depth was 0.6mm (mean 1.1±1.6; range 0.1–20.0mm). Median distance to provider was 8 miles (mean 15±31; range 0–386 miles). For every ten mile increase in distance, Breslow depth increased by 6% (p=0.002). For every 10% increase in poverty rate, the Breslow depth increased by 10% (p=0.041). The relationship between Breslow depth and age wasn’t linear: depth was 17% greater for patients 51–80 than for those ≤50 (p=0.016), while depth was 74% greater for patients >80 than for those ≤50 (p<0.001). Gender, rurality, and availability of local dermatologists were not significantly associated with Breslow depth. On multivariate analysis, the associations between Breslow depth at diagnosis and distance to provider (p=0.002) and age (p<0.015) were significant. Conclusions: Distance to provider may be a significant measure of access to melanoma care that captures different information than proxy measures of rurality, poverty, and local availability of providers. Further research is needed to elucidate factors that mediate how far patients travel to reach their diagnosing providers. No significant financial relationships to disclose.
Pharmacodynamic and predictive markers of ipilimumab on melanoma patients’ T-cells.
Authors: J. S. Weber, B. Yu, M. Hall, D. Morelli, D. Yu, Y. Zhang, X. Zhao, A. Sarnaik, W. Wang
Journal: Journal of Clinical Oncology (2011)

2503 Background: The purpose of this retrospective study was to identify peripheral blood biomarkers associated with the therapeutic effect of ipilimumab, a human antibody against cytotoxic T lymphocyte antigen-4 (CTLA-4). Immunophenotypic changes in CD4+ and CD8+ T cells from advanced melanoma patients treated with ipilimumab were identified by gene expression profiling and subsequently validated by flow cytometry Methods: CD4+ and CD8+ T cells were purified by flow cytometry sorting from peripheral blood pre- and post- ipilimumab treatment from stages IIIC/IV melanoma patients rendered free of disease on an adjuvant trial. Microarray analysis of purified CD4+ and CD8+ T cells to identify gene profiling changes induced by ipilimumab were performed in 18 patients. Flow cytometry analysis of a larger, overlapping cohort of 36 patients was performed to confirm effects on T cell phenotypes Results: Ipilimumab augmented total CD4+ T cells and decreased CD4+ and CD8+ naïve T cells. Mean fluorescence intensity (MFI) of proliferation marker Ki67, the Inducible T cell Co-Stimulator (ICOS), and the polarizing regulatory molecule GATA3 were significantly up-regulated on CD4+ and CD8+ T cells (p<0.01 Wilcoxon). Percent expression and MFI of Granzyme B in CD8+ T cells was increased and EOMES (eomesodermin) was decreased on CD8+ T cells (both p<0.04). The MFI of CCR7 and IL-7R on CD4+ T cells was decreased (p<0.001). Increased expression of ICOS and Ki-67 in CD8+ T cells were negatively associated with developing immune related adverse events (p=0.04, Wald), and increased EOMES on CD8+ T cells was associated with shorter relapse free-survival (RFS)(p=0.04). Higher baseline EOMES CD8+ expression was predictive of favorable RFS (p=0.03) Conclusions: Increased expression of proliferation and polarization markers in CD4+ and CD8+ cells, decreased CCR7 and IL-7R on CD4+ T cells and up-regulated Granzyme B in CD8+ T cells may serve as pharmacodynamic indicators of the effects of ipilimumab. Increased activation markers ICOS and EOMES were significantly associated with fewer adverse events and less favorable outcome, respectively, but baseline elevated expression of EOMES appears to predict favorable relapse-free survival in this analysis.
Bevacizumab in combination with cisplatin and docetaxel as first line treatment of patients (pts) with advanced or metastatic, non squamous, non-small-cell lung cancer (NSCLC)
Authors: N. Ferrer, A. Paredes, J. M. Muñoz-Langa, M. Mendez, M. Cobo, T. de-Portugal, V. Giner, S. Garcia, R. Gallego, J. Torrego
Journal: Journal of Clinical Oncology (2008)

19109 Background: Bevacizumab (B) has been shown to improve response rates and survival in pts with advanced non-squamous NSCLC when combined with carboplatin and paclitaxel (FDA & EMEA-approved indication) or with cisplatin and gemcitabine (EMEA-approved). However, there are limited data on the safety and efficacy of B in combination with other widely used chemotherapy doublets for NSCLC. This is a preliminary safety report of a single-arm, open-labeled, phase II trial of B, docetaxel and cisplatin for pts with NSCLC. Methods: In this single-stage phase II trial, patients received docetaxel(75 mg/m2), cisplatin (75 mg/m2), and B (15 mg/kg IV) on day 1 every 3 weeks for up to 6 cycles followed by B 15 mg/kg alone every 3 weeks until disease progression. Eligibility criteria included chemotherapy-naïve stage IIIB or IV incurable NSCLC of non-squamous histology, PS 0–1, no brain metastases, no history of gross hemoptysis, no evidence of tumour invading major blood vessels, stable cardiac condition and no full dose anticoagulation.The primary endpoint was progression-free survival, with secondary endpoints of TTP, RR, OS and safety. Results: 12 pts have been enrolled with a planned sample size of 47 pts. Baseline characteristics were: 2 females, median age 67 years old (62–72), PS 0 (5 pts) or 1 (7 pts), stage IIIB (2 pt) or IV (10 pts). Median number of cycles was 2 (range 0–4). 11 pts are evaluable for toxicity. Hematological toxicities: 2 pts with grade 4 neutropenia (1 febrile neutropenia), 1 pt with grade 4 leucopenia, 1 pt with grade 3 neutropenia. The most common grade 3/4 non-hematological toxicities included fatigue ( N=1, gr 3), diarrhea (N=1, gr 4), xerostomia (N=1, gr 3), dyspnea (N=1, gr 4), skeletal pain (N=1, gr 3), hemoptysis (N=1, gr 5) and flebitis (N=1, gr 3). 4/11 pts are off treatment (1 progression, 1 SAEs, 1 protocol violation, 1 docetaxel allergic reaction). 4 patients were evaluable for tumor response, 2 PR, 1 SD, and 1 PD. Conclusions: preliminary analysis shows that the combination of Bevacizumab, docetaxel and cisplatin is safe, well tolerated and shows a trend of promising activity. Enrollment continues and updated results will be presented. No significant financial relationships to disclose.
Relationship of time to testosterone (T) and PSA rises during the first “off treatment” interval (1OFF) of intermittent androgen deprivation (IAD) with time to castration resistance (CRPC) and prostate cancer mortality (PCM) in men with biochemical relapse (BR).
Authors: Evan Y. Yu, Kevin F Kuo, Rachel Hunter-Merrill, Roman Gulati, Suzanne P Hall, Teresa E Gambol, Ruth D Etzioni, Celestia S. Higano
Journal: Journal of Clinical Oncology (2012)

99 Background: A recent phase III trial of intermittent vs. continuous AD supports IAD as standard of care for men treated with AD for BR. To identify potential factors during 1OFF prognostic for time to CRPC or PCM, relationships with times to T and PSA rises from our prospective trial of IAD in men with BR were analyzed. Methods: 72 patients were treated with IAD, each cycle consisting of 9 months of leuprolide and flutamide followed by a variable “off treatment” interval. T and PSA were followed monthly; AD was resumed when PSA reached a pre-specified value. Cycles repeated until CRPC, defined as ≥2 PSA rises with T&lt;50 ng/dL. We evaluated patients who completed 1OFF and reached T&gt;50 with a Cox proportional hazards model, controlling for age at study entry, to quantify association of time to first T&gt;50 with time from this point to CRPC or PCM. Similarly we quantified association of PSA rise during 1OFF and after first T&gt;50 with these endpoints. Results: A longer time to PSA rise during 1OFF or after T&gt;50 was associated with longer time to CRPC, while longer time to first T&gt;50 was marginally associated with shorter time to PCM. Specifically, a 30-day increase in time to PSA rise during 1OFF or after T&gt;50 was associated with a 21% or 27% reduction in the risk of CRPC, while a 30-day increase in time to first T&gt;50 was associated with a 39% increase in the risk of PCM. Conclusions: That longer time to PSA rise during 1OFF was associated with longer time to CRPC is not surprising, but the association between longer time to first T&gt;50 and time to PCM has not been reported. To validate these findings, an extended analysis is underway and will be presented. [Table: see text]
Phase II clinical trial of axitinib in metastatic pheochromocytomas and paraganlgiomas (P/PG): Preliminary results.
Authors: Mauricio Emmanuel Burotto Pichun, Maureen Edgerly, Margarita Velarde, Susan Elaine Bates, Roland Daerr, Karen Adams, Karel Pacak, Tito Fojo
Journal: Journal of Clinical Oncology (2015)

457 Background: Malignant pheochromocytoma/paraganglioma (P/PG) is a rare malignancy. Management of metastatic disease includes surgery, external radiation, 131 I-MIBG and systemic chemotherapy. CVD (cyclophosphamide, vincristine and dacarbazine) is the only chemotherapy commonly used to treat metastatic disease. Putative anti-angiogenic agents such as the tyrosine kinase inhibitor (TKI) axitinib target a well-recognized pathway thought to be active in many tumors. Methods: Patients with histologically confirmed P/PG previously treated or naive to treatment received axitinib at initial dose of 5 mg BID. Primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival, response rate and safety. Results: Between January and September 2014 nine patients have been enrolled. The median age was 54.7 years, (range 42.5 – 70.5); median number of previous systemic treatments was one (range 0 – 3). Three of the nine patients achieved a partial response. An additional 5 patients have had tumor shrinkage insufficient to qualify as a partial response with only one patient response scored as progression. Tumor shrinkage has been observed in lymph node, soft tissue and lung metastases; and has been associated with reductions in circulating cathecholamines. Median time to progression has not been reached. A total of 50 cycles have been administered. Toxicity has led to a reduction of the dose of axitinib from a starting dose of 5 mg BID to 3 mg BID in six and 2 mg BID in two patients. The axitinib dose could be increased to 7 mg BID in only one patient Principal grade 3-4 toxicities included hypertension (6 patients), fatigue (4 patients), diarrhea (1 patient) and mucositis (1 patient). Conclusions: Preliminary data shows axitinib can result in tumor shrinkage in patients with a diagnosis of malignant P/PG. The high rate of dose reduction related to toxicity may reflect a different pharmacokinetic profile of the drug in these patients a possibility now under investigation. Clinical trial information: NCT01967576.
Creating an online resource providing hospital cancer surgery volumes in California.
Authors: Christina A Clarke, Laurence C Baker, Jennifer Malin, Joseph Parker, Merry Holliday-Hanson, Niya Fong, Stephanie Teleki, Lance Lang, Maryann O'Sullivan
Journal: Journal of Clinical Oncology (2016)

172 Background: Little evidence is available to help patients and providers, payers and policymakers find the highest-quality hospitals for cancer surgery. We initiated a groundbreaking effort in California ( www.calqualitycare.org ) to publicly report hospital cancer surgery volume data online. Methods: With financial support from the nonprofit California HealthCare Foundation, we assembled a multidisciplinary team to oversee the project and ensure sound methodology. We obtained existing hospital discharge summary data from the California Office of Statewide Health Planning and Development (OSHPD). We selected cancer surgeries eligible for display through comprehensive review of the literature addressing the association of hospital volume and mortality. We found eleven cancer sites with sufficient evidence of association including bladder, brain, breast, colon, esophagus, liver, lung, pancreas, prostate, rectum, and stomach. Experts advised volume calculation and display of results. Leaders of low volume hospitals were interviewed to understand the reasons for low volume. Results: In 2014, about 60% of cancer surgeries in California were performed at hospitals in the top 20% of volume, but many hospitals performed low numbers of complex procedures, with the per hospital median number of surgeries for esophageal, pancreatic, stomach, liver, or bladder cancer surgeries at 4 or less. Low-volume hospitals included rural and urban hospitals, with small and large bed sizes, and teaching and non-teaching status. At least 670 Californians received cancer surgery at hospitals that performed only one or two surgeries for a particular cancer site; 72% of those patients lived within 50 miles of a top-20% volume hospital. Conclusions: This project demonstrates the potential for public information about hospital volumes to point patients towards high-volume and away from low-volume hospitals. Data regarding 2014 volumes are now available online.
Epoetin Alfa vs Standard of Care Decreases Number of Packed Red Blood Cell Transfusions in Patients Receiving Hyper-CVAD for Acute Lymphocytic Leukemia, Lymphoblastic Lymphoma, and Burkitt’s Lymphoma.
Authors: Maria E. Cabanillas, Deborah A. Thomas, Hagop Kantarjian, Gloria N. Mattiuzzi, Benjamin N. Bekele, Maria C. Foudray, Jennifer L. Cassat, Jorge E. Cortes
Journal: Blood (2006)
Evaluation of circulating tumor cells (CTCs) enumeration and 18F-Choline positron emission tomography/computed tomography (FCH PET/CT) as early efficacy response biomarkers in metastatic castration-resistant prostate cancer (CRPC) patients (pts) treated with abiraterone acetate.
Authors: Sylvestre Le Moulec, Christophe Massard, Eric Gontier, Françoise Farace, Cyrus Chargari, Philippe Vielh, Olivier Aupee, Lionel Vedrine, Herve Foehrenbach, Karim Fizazi
Journal: Journal of Clinical Oncology (2012)

63 Background: Circulating tumor cells (CTCs) and FCH PET/CT are both promising tools for treatment monitoring in CRPC pts. In this study, we assessed prostate specific antigen (PSA), CTC and FCH PET/CT for monitoring treatment response in metastatic CRPC pts receiving recently approved abiraterone acetate therapy after chemotherapy. Methods: Twenty nine metastatic CRPC pts progressing after docetaxel chemotherapy received abiraterone acetate 1,000 mg daily with prednisone 5 mg twice daily in continuous 28-day cycles. Pts were evaluated monthly for efficacy and safety. CTCs counts (using the CellSearch assay) and FCH PET/CT were performed at baseline and at 4 weeks (PERCIST criteria and SUV Peak). Results: After one month of treatment, 12 pts (41%) had a PSA rise and 17 pts (59%) had a PSA decline. At baseline, 18 pts had detectable CTCs (at least 5 CTCs), and 6 of them (33%) had a decline from at least 5 to less than 5 CTCs after 4 weeks of treatment. 10 of 29 pts (34%) had a &gt; or = 30% decline in CTCs. Amongst 22 pts who were evaluable by FCH PET/CT, response assessment was as follows: response (n=8), stable disease (n=12), progression (n=1). PSA decline and CTCs levels correlated in 16 of 29 pts (55%), and were discordant in 13 of 29 pts (45%). In all 12/29 pts (41%) with a 50% or more decline in PSA both a CTCs response and a FCH PET/CT response was observed. In patients with a PSA rise while on abiraterone acetate, 8 pts did not have a CTCs increase or a CTC conversion from unfavourable to favorable, and 7 of 8 pts had a PSA decline at 3 months or a FCH PET/CT response. No flare phenomenon on FCH PET/CT was observed. Conclusions: Monitoring pts with CRPC who receive abiraterone using both CTCs and metabolic imaging indicate discrepancy in 45% with response assessment using PSA. Association between CTC drop, early FCH PET/CT response and clinical benefit is currently under study.
Correlation of tumor infiltrating lymphocytes and outcome in primary central nervous system lymphomas
Authors: T. Y. Kang, A. Thomas, L. Tsao, D. M. Peereboom, E. Hsi
Journal: Journal of Clinical Oncology (2008)

2064 Background: Primary central nervous system lymphomas (PCNSL) are aggressive non-Hodgkin’s lymphomas (NHL) confined to the CNS. While PCNSL are large B-cell lymphomas (LBCL) morphologically indistinguishable from systemic LBCL, PCNSL generally have a worse prognosis. Tumor infiltrating lymphocytes (TIL) have been suggested to play a role in tumor growth in many malignant diseases including NHL. Although TIL are also commonly seen in PCNSL, their roles here have not been formerly studied. Herein we evaluated the prognostic implications of TIL in PCNSL. Methods: We retrospectively reviewed PCNSL cases available at our institution. The TIL subsets were evaluated using CD3, FOX-P3, and TIA-1 immunohistochemical stains. Enumeration of TIL subsets was performed by AT and LT independently and blinded from survival data. Cells were counted at high power (400x) and averaged over 2–4 fields depending on the specimen size. Statistical analysis of survival was performed via Wilcoxon rank-sum and log-rank tests. Results: Between 2002 and 2007, a total of 29 cases of PCNSL with tumor blocks available for analysis were reviewed (17 males, 12 females, median age: 66 years). The median survival was 5.8 months (range 0.8–61 months). There was an average of 164 T-cells per high-powered field (hpf) ranging from 25–621 cells/hpf. FOX-P3+ cells averaged 19 cells/hpf (range 1–108 cells/hpf). TIA-1+ cells averaged 74 cells/hpf (range 0–293 cells/hpf). Although no significant association between the number of regulatory cells (FOX-P3+) or cytotoxic cells (TIA-1+) and survival was identified (p=0.5 and 0.1, respectively), log-rank test showed that the subset of patients with high CD3 counts had improved outcome (p=0.03). This is especially the case for patients with low TIA-1/FOX-P3 ratio. Conclusions: Our study demonstrated that TIL of PCNSL contain cytotoxic and regulatory subsets which may, along with the total CD3 counts, correlate with outcome. The results suggest that immune function in the CNS may affect outcome but that further studies are needed to confirm and expand on our findings. No significant financial relationships to disclose.
Clinical and biological significance of growth factor receptor bound protein 7 on progression in hepatocellular carcinoma
Authors: S. Itoh, A. Taketomi, S. Tanaka, T. Gion, T. Yoshizumi, Y. Soejima, K. Shirabe, M. Shimada, Y. Maehara
Journal: Journal of Clinical Oncology (2005)

9527 Background: Although hepatocellular carcinoma (HCC) is one of the most common cancers, the mechanisms that regulate its development and progression remain unclear. We reported that focal adhesion kinase (FAK) played an important role in HCC progression, especially vascular invasion (Clinical Cancer Research 2004). The objective of this study was to investigate whether growth factor receptor bound protein 7 (Grb7), which is one of downstream molecules of FAK, is involved in the progression of human HCC. Methods: Grb7 expressions in HCC cell lines were analyzed using Western blot analysis. Immunohistochemistry (IHC) analysis for Grb7 was performed on paraffin embedded tissues in 64 HCC samples, respectively. We also investigated the correlation between the Grb7 expression and the clinical outcome. Moreover, we established the Grb7 knock down HCC cell lines using RNA interference (RNAi) method. Using these cells, we evaluated its biological features in vitro and in vivo. Results: Western blot analysis showed Grb7 expression in HCC cell lines. Grb7 positive HCC was observed in 18 of 64 patients (28.1%), and also correlated with portal venous invasion (p<0.01), intra-hepatic matastasis (p<0.01), and hepatic venous invasion (p<0.05), and tendency for a poor prognosis. Grb7 positive expression correlated significantly with FAK positive expression (p<0.01). Grb7 knock down cells showed significantly lower level of invasion potential than the control cells using invasion assay (p<0.01) and wound healing assay (p<0.01). Grb7 knock down cells also showed lower level of tumor growth than the control cells in nude mice (p<0.01). Conclusions: The present study showed that Grb7 are strongly expressed in HCC cells and involved in the invasion potential of HCC. Grb7 could be a novel molecular target for HCC therapeutics. No significant financial relationships to disclose.
Changes in expression levels of excision repair cross-complementing group 1 (ERCC1) and dihydropyrimidine dehydrogenase (DPD) after first-line oxaliplatin-based chemotherapy for metastatic colorectal cancer: Results of a multicenter study.
Authors: Hideo Baba, Yoshifumi Baba, Shinji Uemoto, Eiji Oki, Yasuharu Ikeda, Masakazu Yamamoto, Hiroyuki Matsuda, Mitsuo Shimada, Norihiro Kokudo
Journal: Journal of Clinical Oncology (2014)

463 Background: Our previous single-center study showed that expression levels of ERCC1 (a nucleotide excision repair pathway gene) and DPD (a pyrimidine catabolic pathway gene) in liver metastases from colorectal cancers (CRCs) were significantly higher in patients given oxaliplatin as first-line chemotherapy than those not given oxaliplatin. We conducted this multicenter study to validate our findings and better define a basic rationale for second-line therapy for metastatic CRC resistant to first-line therapy. Methods: Irinotecan-naive patients with mCRC (n = 190) were enrolled at 17 sites in Japan. Resected liver metastases were available for 91 patients who had received FOLFOX (or FOLFOX plus bevacizumab; FOLFOX group) and 99 who had not received oxaliplatin-based chemotherapy (non-oxaliplatin group). We measured mRNA expression levels of ERCC1 and DPD by real-time RT-PCR. Protein expression levels of ERCC1 and DPD were evaluated immunohistochemically. The methylation level of the long interspersed nucleotide element-1 (LINE-1; a surrogate m arker of global DNA methylation) was determined by pyrosequencing. Results: The median age at liver resection was 64 years (range, 32–89). Baseline features (e.g., sex, histology) were similar in the groups. Expression levels of DPD at the mRNA and protein levels were significantly higher in the FOLFOX group than in the non-oxaliplatin group (p &lt; 0.05). The mRNA expression level of ERCC1 was slightly, but not significantly higher in the FOLFOX group than in the non-oxaliplatin group (p = 0.053). Interestingly, ERCC1 expression levels correlated with DPD expression levels (r = 0.38, p&lt; 0.0001). LINE-1 methylation levels were similar in the groups. Conclusions: This multicenter study confirmed increased expression levels of DPD after first-line oxaliplatin-based chemotherapy, which may affect chemosensitivity to subsequent therapy. ERCC1 expression and epigenetic control by mechanisms such as aberrant promoter methylation of specific genes warrant further investigation.