tbuckley/cabot-search huggingface dataset:
Impact of intrathoracic (IT) metastases upon survival in stage IV non small cell lung cancer (NSCLC)
Authors: J. Husain, S. Gopaluni, N. Newman, C. M. Shah, A. Gajra
Journal: Journal of Clinical Oncology (2008)

19051 Background: The current AJCC staging (6th Ed, 2002) for NSCLC defines stage IV by presence of distant metastases (any T, any N, M1). There is no subdivision for IT vs. extrathoracic (ET) metastases. Recent phase III trials in stage IV NSCLC (e.g. ECOG 1594, CALGB 9730, TAX 326 and ECOG 4599) have not stratified for this potential variable. We hypothesize that patients with stage IV NSCLC with IT disease have a longer overall survival. Methods: After IRB approval patient charts were reviewed to obtain data on: age, gender, dates of diagnosis and death, IT vs. ET disease, ECOG performance status (PS). chemotherapy use and smoking. IT disease included metastases to ipsilateral or contralateral lung parenchyma. Patients with metastatic disease outside of the lungs were considered to have ET metastases. Statistical analysis included estimation of overall survival by the Kaplan-Meier method using the log rank test. Cox regression model was used to determine simultaneously the associations between survival and potentially prognostic variables. Results: A total of 193 patients were diagnosed with stage IV NSCLC at VAMC, Syracuse between 1999–2006. The patients were predominantly males (98%) and smokers (98%) with median age of 69 years. A third recieved chemotherapy, 46% had PS of 0–1, and 50% had < 5% weight loss. A total of 159 patients had ET and 34 patients (18%) had IT metastases. On univariate analysis patients with IT metastases had a median survival of 7.3 months vs. 3.4 months for ET disease (p <.01). Other factors favoring survival included good PS (p<.001), weight loss < 5% (p=.02), and use of cytotoxic chemotherapy (p<.001). Among patient who received chemotherapy (n=63), those with IT metastases had a longer median survival (13.5 m vs. 9.5 m, p=.04). On multivariate analysis, site of metastases retained its significance (RR 1.59,C.I. 1.00–2.52) as well as use of systemic chemotherapy (RR for survival without chemotherapy is 0.42, C.I. .28-.64). Conclusions: In addition to use of systemic chemotherapy, the site of metastatic disease is a determinant for survival in our cohort of patients. These data if confirmed in large prospective series make case for modification of current TNM staging system to reflect the impact of IT and ET metastases upon survival. No significant financial relationships to disclose.
Health care utilization by adult Hispanic long term survivors of hematopoietic cell transplantation (HCT): report from the bone marrow transplant survivor study
Authors: P. K. Prasad, C. Sun, K. S. Baker, L. Francisco, S. Forman, S. Bhatia, S. M. Shankar
Journal: Journal of Clinical Oncology (2008)

6608 Background: A third of long-term HCT survivors report severe or life-threatening chronic health conditions, placing significant demands on the healthcare system for a prolonged period of time. However, utilization patterns of healthcare services among minorities differ from those of non-Hispanic whites in the general population. The aim of this study was to evaluate healthcare utilization by adult long-term Hispanic HCT survivors. Methods: A mailed questionnaire was used to assess self-reported health care utilization in three domains: general contact with healthcare system, general physical examination (GPE), and cancer/HCT-related visit. Eligible individuals had undergone HCT between 1974 and 1998, at 21 years of age or older and survived 2 or more years after HCT. Results: The entire cohort consisted of 818 individuals, including 137 Hispanic survivors. The median age at HCT was 38.3 years (range: 21–68 years) and the median length of follow-up was 6.6 years (range: 2–24 years). A larger proportion of Hispanic survivors had family income < $20,000 (45.6% vs. 8.8% in non-Hispanics, p<0.001), high school or lower education (37.5% vs. 6%, p<0.001), and lacked health insurance (22.4% vs. 4.6%, p<0.001). Overall, 97% of non-Hispanic whites and 92% of Hispanics reported medical contact 11+ years after HCT (p=0.15). Compared to 2–5 years after HCT, the prevalence of GPE increased among non-Hispanic whites (67% to 76%, p for trend =0.05) but remained unchanged among Hispanics (66% to 61%, p for trend=0.68) 11+ years after HCT. On the other hand, while the proportion of non-Hispanic white survivors reporting a Cancer/HCT-related visit decreased from 94% at 2–5 years after HCT to 54% 11+ years after HCT (p for trend<0.001), the comparable figures in Hispanics were 96% and 81% (p for trend=0.03). Conclusion: As compared to non-Hispanic whites, Hispanic survivors are less likely to establish contact with a primary care provider years after the HCT and continue to receive care primarily at Cancer/HCT center for many years following HCT. Future studies of this population are needed to establish the factors responsible for this pattern of healthcare utilization. No significant financial relationships to disclose.
In Vivo Response to Sequential Tyrosine Kinase Inhibitors (TKI) in Chronic Myeloid Leukemia (CML) Modeled Based on In Vitro Properties of Particular BCR-ABL Kinase Domain (KD) Mutations.
Authors: Elias Jabbour, Hagop Kantarjian, Dan Jones, Susan O’Brien, Stefan Faderl, Zeev Estrov, Farhad Ravandi, Jorge Cortes
Journal: Blood (2007)
Prospective evaluation of the response to prednisone-dexamethasone switch in castration-resistant prostate cancer patients treated with abiraterone pre- and post-docetaxel.
Authors: Nuria Romero-Laorden, Elena Castro, Rebeca Lozano, M Isabel Sáez, Jeannette Valero, Floortje Van de Poll, M Paz Nombela, Juan Francisco Rodriguez-Moreno, A. Montesa, Gala Grau, Leticia Rivera, David Olmos
Journal: Journal of Clinical Oncology (2016)

327 Background: Abiraterone acetate (AA) administered with prednisone (P) to reduce mineralocorticoid-related adverse events improves survival in CRPC with a favourable tolerance profile. However, in the phase I/II of AA without steroids, dexamethasone 0,5mg/day was added after biochemical progression reaching a 25% of PSA decline. Lorente et al (BJC, 2014) showed durable biochemical responses in 40% of cases treated with AA and steroid switch in the post-docetaxel setting. We hypothesize that P to D switch in patients with biochemical progression to AA+P would lead to secondary responses also in the pre-docetaxel setting. Methods: Change of P 5mg/12h to D 0.5mg/24h was prospectively tested in clinically stable CRPC with biochemical progression ( &gt; 25% PSA rise over nadir, confirmed in a second determination) and/or limited radiological progression ( &lt; 3 new bone/lymphatic metastasis, non-bulky), after ³12 weeks of AA+P. PSA was monitored q4wks. CT- &amp; bone-scans were performed every 12-16 weeks. Biochemical and radiological responses were evaluated by PSAWG2 and RECIST criteria. Survival outcomes were calculated using Kaplan-Meier method. Results: 18 patients were included (11 pre- &amp; 7 post-docetaxel). Median age 72 (60-85); visceral, bone and/or lymph metastasis were present in 17%, 83% and 50% of patients. Median PSA at AA+P and AA+D commencement was 81 ng/ml and 100ng/ml, respectively. Biochemical response was observed in 83% of patients: 56% with a PSA decrease ≥ 30%, and 28% with PSA decrease ≥ 50%. Median biochemical progression-free survival (bPFS) with AA+P was 5.7 months (CI95% 2.9-9.1) and 3.8m (CI95% 1.4-6.5) in the pre- and post-docetaxel setting, respectively. Median bPFS with AA+D was 5.4m (1.2-8.8) and 2.5 (CI95% 1.1-2.9) in the pre- and post-docetaxel settings. Two radiological partial responses were observed with AA+D. Conclusions: Clinically stable patients with limited disease progression after AA+P may benefit from steroid switch in both the pre- and post-docetaxel settings.
Final results of a pharmacokinetic (PK) study of capecitabine (X) in combination with oxaliplatin (O) for patients (pts) with metastatic colorectal cancer (MCRC)
Authors: M. Gil-Delgado, G. Bastian, B. Paule, J.-P. Spano, O. Rixe, G. Des Guetz, S. Urien, J. Amaury-Soares, J.-L. Breau, D. Castaing, D. Khayat
Journal: Journal of Clinical Oncology (2005)

3685 Background: This trial was conducted to establish potential PK interactions between X and O when administrated in combination (XELOX regimen) and to evaluate neurotoxicity when O is administered by 6-hour infusion. Methods: Pts received O 130mg/m2 6-hours infusion d1 + X 1000mg/m2 bid d2–15. Treatment was repeated q3w if there was no G3/4 non-hematological adverse events and neutrophils were >1000 and platelets were >100,000. PK analysis was performed on d1 for O and on d2&15 for X. Blood sampling: d1 (30’ before end of O infusion and 1h30 after end of infusion); d2&15 (30’, 1h, 2h and 4h after X). X, dFdU, 5-FU and FBAL were monitored by HPLC or GC-MS. O (total and ultrafilterable) was monitored by Atomic Absorption Spectrometry. PK of X and its metabolites were compared when X was given with or without O to establish drug interaction. Urine samples were collected, when possible, before and 4hs after X. Results: Between Apr03 and Dec04, 23 MCRC pts (9 men, 14 women) were enrolled. Baseline characteristics: 16 colon, 3 junction and 4 rectum; median age 57 [45–78]; ECOG PS 0 (61%), 1 (26%), 2 (13%). Most common metastatic sites were the liver (56%) and lung (30%). 78%, 17% and 4% of pts received XELOX as first-, second- or third-line treatment, respectively. Median no. of cycles: 4 [1–9]. All 23 pts are evaluable for safety and 16 for efficacy. The ORR was 69% (4 CR and 7 PR). Most common G 3/4 adverse events were diarrhea (G3 35%) and neutropenia (G3/4 9%). 1 pt had septic shock, 1 had chest pain (d2 of 1st cycle), and 1 pt died due to unexplained cause. There was no hand-foot syndrome and only mild paresthesia (26%). 15 pts were evaluated for PK on d1, 2&15. No statistically significant differences were observed in PK parameters between d2&15 for X, 5-FU and FBAL, indicating a lack of pharmacological interaction with O. Conclusion: XELOX is highly active, well tolerated and is easy to administer. The neurological toxicity normally associated with O is manageable when O is infused over 6 hours on d1, q3w. No significant financial relationships to disclose.
Survival of pancreaticoduodenectomies with venous reconstruction using a population-based database.
Authors: Bryan S. Goldner, Federrico Tozzi, Laleh Melstrom, Susanne Warner, Gagandeep Singh
Journal: Journal of Clinical Oncology (2016)

340 Background: Locally advanced disease requiring pancreaticoduodenectomy (PD) with venous reconstruction is a controversial topic that is often determined by careful patient selection. There are numerous published single institution, but sparse multicenter studies, demonstrating the safety and efficacy of PD with venous reconstruction. The goal of this study is to evaluate survival outcomes in patients who underwent a PD with our without venous reconstruction utilizing a large statewide database. Methods: The California Cancer Registry (CCR) was used to obtain data on all PD performed from 2000-2011. This data was merged with Office of Statewide Planning and Development data to obtain inpatient hospitalization data. ICD-09 codes were used to identify all PD with or without venous reconstruction. Data was obtained on demographics, disease process, surgery, hospitalization statistics, and survival. Venous reconstruction was divided into venous segmental resection with reconstruction (VSR) and primary repair of the vein with a patch (PR). Survival was analyzed using Kaplan-Meier Survival analysis (KM). Results: Data were obtained on 5,228 patients who underwent PD, 3.7% (161) underwent venous reconstruction (148; 2.8% VSR and 43; 0.8% PR). A significant overall survival difference between PD and all vascular reconstruction was observed (23 months vs 17 months respectively, p &lt; 0.001). Further analysis revealed no significant difference in survival between standard PD and PD with PR (median 21 months; p = 0.2). However, there was a significant survival advantage of PD compared to PD with VSR (21 vs 16 months respectively, p &lt; 0.001). Evaluation of length of stay and complications revealed no statistical difference (p = 0.07 and p = 0.8). Conclusions: Venous reconstruction in PD is associated with worse survival compared to PD alone. Interestingly, patients who had a PR had a better survival than VSR alone. Overall survival for all comers of vascular reconstruction remains inferior which reinforces the biology of disease as an important predictor of outcomes as well as shorter segment portal vein involvement conferring improved survival.
Predicting the risk of cardiovascular comorbidity in cancer survivors.
Authors: A. Y. Tashakkor, A. Moghaddamjou, W. Y. Cheung
Journal: Journal of Clinical Oncology (2011)

9071 Background: Preventable conditions, such as heart disease and diabetes mellitus, represent a major threat to the life of many cancer survivors (CS). However, there are limited data on how to identify CS at the greatest risk who may benefit most from prevention. Our goals were to: 1) characterize the clinical factors associated with ischemic heart disease (IHD) and congestive heart failure (CHF) among CS; and 2) develop a stratification schema for predicting the risk of cardiovascular comorbidity in CS. Methods: CS and noncancer controls (NCC) were identified from the U.S. National Health and Nutrition Examination Survey. Multivariate logistic regression models were constructed to determine independent clinical factors associated with an increased relative risk (RR) for cardiovascular comorbid conditions. Based on a composite scoring system that assigned 1 point for each risk factor identified, a cardiovascular risk stratification schema was devised that correlated the risk score with the prevalence of cardiovascular comorbidity in CS. Results: A total of 2,734 CS and 23,832 NCC were included: mean age was 45.0 years (SD 17.4), 48.1 % were male, and 88.6% were White in the entire cohort. Baseline characteristics were similar between CS and NCC. When compared to NCC, CS were significantly more likely to report IHD (8.5 vs. 2.9%, p<0.01), CHF (7.1 vs. 2.0%, p<0.01), or both (3.2% vs. 0.67%, p<0.01). Based on multivariate analyses, risk factors for cardiovascular problems included: age ≥ 60 (RR 6.4, 95% CI 5.3-7.7); male gender (RR 1.8, 95% CI 1.6-2.1); racial minorities (RR 1.7, 95% CI 1.4-2.1); those who were separated or widowed (RR 2.4, 95% CI 1.8-3.4); less than high school education (RR 1.5, 95% CI 1.3-1.8); and an annual income less than $20,000 (RR 1.9, 95% CI 1.6-2.3). A cardiovascular risk stratification schema for IHD and CHF in CS was developed (Table). Conclusions: Independent risk factors for IHD and CHF in CS were identified. A risk stratification schema may be helpful in developing a risk-based approach to cardiovascular preventive strategies for CS. Prevalence of cardiovascular conditions based on risk score. Comorbidity Risk score ≤ 2 3 4 5+ IHD 0.8% 6.4% 13.6% 19.5% CHF 0.4% 6.2% 10.6% 16.7% IHD and CHF 0.2% 2.2% 3.2% 9.1%
Association of germ-line variation with platinum-based chemotherapy response in patients (pts) with urothelial carcinoma (UC).
Authors: D. J. Gallagher, V. Joseph, R. J. Hamilton, I. Ostrovnaya, I. R. Garcia-Grossman, J. C. Riches, A. M. Regazzi, J. A. Przybylo, M. Gaudet, M. I. Milowsky, K. Offit, D. F. Bajorin
Journal: Journal of Clinical Oncology (2011)

4511 Background: Platinum-based therapy improves outcome in advanced UC, both in the neoadjuvant and metastatic disease setting. Since cell line and human studies in other cancers show associations between germ-line variants and platinum response, we hypothesized similar associations in UC. Methods: Saliva or blood was collected from pts with UC diagnosed between 1984 and 2010. SNPs (n=80) were selected based on reported associations with UC and/or platinum response and genotyped using the Sequenom MassARRAY iPLEX system. Analyses were based on advanced UC pts who achieved either a complete or partial response to cisplatin or carboplatin therapy. A multivariate predictive model was created using logistic regression incorporating germline variants (treated both as a categorical and continuous variable) and clinical prognostic factors. Results: This analysis focused on 205 pts of whom 72 received neoadjuvant therapy and 133 received therapy for unresectable or metastatic disease. After adjusting for the MSKCC clinical risk score (0-2) using Karnofsky Performance Status and visceral metastases (JCO, 1999: 17:3173), 4 SNPs retained independent associations with response. A SNP Score was created by summing the number of “at-risk” alleles (0-2) from each of the 4 SNPs (maximum score=8). We observed that the greater the SNP Score, the lower the response rate (Table). Conclusions: We identified germ-line genetic variants that appear to alter response of UC to platinum-based therapy. Furthermore, a model using these genetic variants may predict response to therapy better than clinical factors alone. Independent validation and analysis of survival are ongoing. SNP score 0-1 2-3 4-5 6-8 % response, all (n) 84% (19) 59% (92) 32% (78) 19% (16) Neoadjuvant (n) 85% (7) 67% (31) 33% (27) 22% (7)
SUNCAP, a phase II study with sunitinib and capecitabine in patients with metastatic colorectal cancer (MCRC) refractory to previous treatment with 5FU/irinotecan/oxaliplatin.
Authors: B. Samson, J. Latreille, N. T. Nguyen, C. Sperlich, D. Berbiche, C. Tournigand
Journal: Journal of Clinical Oncology (2011)

545 Background: Patients (pts) with MCRC refractory/resistant to Irinotecan and Oxaliplatin have a poor prognosis. Sunitinib is an oral TKI that selectively inhibits the VEGFR 1, 2, 3, PDGFR and FLT3, CSF-1R, RET. Phase II studies with single agent sunitinib in patients with MCRC did not demonstrate a meaningful ORR but showed acceptable safety profile and warranted further study. Methods: We conducted a phase II escalating dose of sunitinib (S) and capecitabine (C) to assess the efficacy of this oral treatment given on a 2 wks every 3 wks schedule, (level 0, S: 37,5 mg, C: 2,000mg/m 2 , level +1, S: 50 mg, C: 2,000 mg/m 2 , level +2, S: 50 mg, C: 2,500 mg/m 2 and level -1:S: 25 mg, C: 1,500 mg/m 2 . Treatment was initiated at level 0 and increased at level +1 and +2 at cycle 3 and 5 if no grade 2/3 toxicity was observed. Between 02.2009 and 06.2010, 15 pts previously exposed to oxaliplatin/irinotecan/bevazizumab were enrolled, all of them had progressive disease at the time of study entry. Primary objective was ORR. Treatment was given until PD or unacceptable toxicity. Results: Pts characteristics were: sex: 12M/3F, median age: 65 years [41-75], primary tumors: colon: 13, rectum: 2, ECOG PS 0/1: 8/7, median nb of metastatic sites: 3, KRAS status: WT/MT/Unknown: 1/9/5. Escalating to level +1:53%, level +2: 7%. Median nb of cycles received/pt: 5. All pts were evaluable for toxicity (tox): SAEs: 40%, any tox. grade 1/2/3(%): 93/60/ 40. Neutropenia gr. 1/2/3(%): 13/13/7, thrombocytopenia gr.1/2/3(%): 13/20/7. Fatigue gr.1/2/3(%): 27/20/7. Nausea gr.1: 27%. Diarrhea gr.1: 13%. Hand foot syndrome gr. 1/2/3 (%): 13/13/27. Mucositis gr. 1/2/3(%): 7/20/7. Hypertension gr.2: 13%. Thyroïd gr.1: 27%. ORR (CR+PR): 0%, confirmed SD: 7/15: 47%, PD: 8/15: 53%. Median PFS: 137 days [95%CI: 112-162], median OS: 291 days [95%CI: 99-482]. Conclusions: In this heavily pretreated patients, sunitinib in combination with capecitabine appears feasible, with acceptable toxicity. 47% of patients had a confirmed stable disease. Although no objective response was observed, the high level of stable disease may suggest a role of this combination for maintenance therapy. [Table: see text]
Routine multiplexed mutational analysis of colorectal cancers (CRCs): A single-institution experience.
Authors: Emily Chan, Laura Williams Goff, Dana Backlund Cardin, Jordan Berlin, Mia Alyce Levy, Cindy L Vnencak-Jones, William Pao
Journal: Journal of Clinical Oncology (2015)

599 Background: Colorectal tumors harbor mutations in genes that play key roles in CRC carcinogenesis and that may enable prioritization of appropriate anti-cancer therapy. KRAS testing is part of standard of care testing prior to initiation of anti-epidermal growth factor receptor antibodies. Other mutations are emerging as significant drivers, but they are not yet part of routine screening. Methods: As part of Vanderbilt-Ingram Cancer Center’s Personalized Cancer Medicine Initiative, we developed a clinical algorithm to genotype patient’s colorectal tumors using a SNaPshot-based assay (multiplexed PCR, primer extension, and capillary electrophoresis) designed to detect 65 somatic mutations in 7 genes (KRAS, BRAF, AKT1, PIK3CA, SMAD4, PTEN, and NRAS) important in CRC carcinogenesis. Adult patients with metastatic CRC were consented for genotyping of tumor tissue. Mutational profiling was performed in Vanderbilt’s CLIA-certified Molecular Diagnostics Laboratory. Results were reported in the electronic medical record for clinical use. Results: Study enrolled from May 2012 to February 2014. SNaPshot results were available from 126 patients. 49 tumors (38.9%) were wildtype for all mutations tested. 58 (46.0%) tumors had a KRAS mutation, including one with two KRAS mutations; the most common was G12D (n=23), but two had a Q61H mutation and two had a K117N mutation, which are not included in some commercial KRAS tests. Ten (8.9%) tumors carried the V600E BRAF mutation. Nine (7.1%) tumors harbored a PIK3CA mutation. Three (2.4%) tumors had mutations in SMAD4. Four (3.2%) tumors had a NRAS mutation. One (0.8%) tumor had a PTEN mutation. Nine (7.1%) tumors harbored double mutations, the most common being KRAS and PIK3CA double mutations (N=6). 24 (19%) subjects subsequently were treated on clinical trial therapy, including 6 subjects on therapy based on the SNaPshot results. Not surprisingly, RAS results impacted use of anti-EGFR therapy. Conclusions: 61% of the tumors carried at least one mutation in the seven genes tested, suggesting that trials of tumor genotyping-based treatment assignment are feasible. Study was supported by Vanderbilt University Medical Center.
Real-Life Experience of Nivolumab in Heavily Pretreated Relapsed and Refractory Classical Hodgkin Lymphoma
Authors: Ohad Benjamini, David Lavie, Eldad J Dann, Chava Perry, Ory Rouvio, Olga Shvetz, Anatoly Nemets, Ruth Perets, Revital Saban, Avichai Shimoni, Dina Ben-Yehuda, Arnon Nagler, Abraham Avigdor
Journal: Blood (2016)