tbuckley/cabot-search huggingface dataset:
Retrospective cohort study on the safety and efficacy of bevacizumab for metastatic colorectal cancer patients: The HGCSG0801 study—Efficacy of KRAS mutational status.
Authors: Susumu Sogabe, Satoshi Yuki, Hideyuki Hayashi, Hirohito Naruse, Michio Nakamura, Ichiro Iwanaga, Takashi Kato, Tomofumi Takagi, Hiroyuki Okuda, Yoshito Komatsu
Journal: Journal of Clinical Oncology (2012)

680 Background: Mutations of the KRAS gene were identified as a prognostic marker in metastatic colorectal cancer(mCRC). Previously reported data suggests that the longer overall survival (OS) observed with bevacizumab(BV) treatment in mCRC is independent of alterations in the KRAS mutation status. So we analyzed efficacy of bevacizumab combined chemotherapy in mCRC relative to KRAS mutation status. Methods: In the retrospective analysis(n=212) of patients treated with BV(HGCSG0801), additional statistical analyses were done with data from KRAS mutation analyses. The Response Evaluation in Solid Tumors (RECIST) criteria version 1.0 was used to assess tumor response. The Kaplan–Meier method was used to determine Progression-free survival(PFS) and OS. Log-rank test was used to compare with mutant or wild-type KRAS in terms of PFS and OS. All statistical tests were performed using SPSS. Results: KRAS status was assessed in 88 patients (41.5%). Response rate was 58.9% with wild-type and 62.5% with mutant KRAS, that was not significant(p=0.823). The median Progression-free survival was 11.5 months with wild-type and 11.5 months with mutant KRAS, that was not significant(p=0.222). And median OS was 31.8 months with wild-type and 27.5 months with mutant KRAS, that was not significant(p=0.760) as well. Similar results were seen among patients with first-line therapy. Conclusions: Bevacizumab provides clinical benefit in patients with mCRC expressing either mutant or wild-type KRAS.
Gaps in treatment amongst metastatic castration resistant prostate cancer (mCRPC) patients taking abiraterone acetate or enzalutamide.
Authors: Ajay Behl, Lorie Ellis, Dominic Pilon, Yongling Xiao, Patrick Lefebvre, Nancy Ann Dawson
Journal: Journal of Clinical Oncology (2016)

334 Background:Abiraterone acetate (ABI) and enzalutamide (ENZ) are novel oral therapies offering survival benefit to metastatic castration-resistant prostate cancer (mCRPC) patients. The efficacy of cancer treatments rely on patient consistency and adherence to recommended dosage regimens. Factors such as drug-drug interactions and intolerance or toxicities can result in patients or their providers reducing the drug dosage. This study aims to describe treatment discontinuation patterns observed for ABI and ENZ. Methods: The Truven Health MarketScan Research Databases were used to conduct a retrospective analysis of mCRPC patients initiated on ABI or ENZ (index date) between 10/01/2012 to 12/31/2014 with ≥6 months of continuous eligibility prior to index date and a PC diagnosis during the period of continuous eligibility. Patients were observed until loss to follow-up, or end of data availability. Kaplan-Meier (KM) survival curves were used to compare the rates of having a refill gap (i.e., ≥14 days, ≥30 days, or ≥60 days) in patients initiated on ABI or ENZ. Results: The table below summarizes the KM probabilities of having a refill gap among patients initiated on ABI or ENZ. Conclusions: Significantly higher rates of refill gaps ≥30 days and ≥ 60 days were observed for patients initiating ENZ as compared to ABI after 6 months of observation in this initial analysis. Additional research is needed to understand the reasons for gaps in treatment in patients treated with mCRPC therapies. [Table: see text]
Improvement in survival of advanced hepatocellular carcinoma patients: Results of an updated period analysis of SEER database.
Authors: Binay Kumar Shah, Amit Bhandari, Krishna Bilas Ghimire, Sajani Manandhar
Journal: Journal of Clinical Oncology (2015)

383 Background: Sorafenib was approved by FDA for treatment of advanced unresectable hepatocellular carcinoma (HCC) patients in November 2007. In this study, we update survival trends in advanced HCC using Surveillance, Epidemiology, and End Results (SEER) data. Methods: We selected patients with advanced HCC diagnosed from January 2001 to December 2010 from SEER 18 registries. We excluded diagnosed at autopsy, from death certificate only, or those without survival date. We calculated 1- and 2- year relative survival rates in pre-sorafenib (2001-2007) and post-sorafenib (2008-2010) era by age, sex and ethnicity among using SEER*stat software. Results: The total number of advanced HCC patients during 2001-2010, 2001-2007 and 2008-2010 were 5,092, 2,747 and 2,345 respectively. The 1- and 2- year survival rates of patients improved significantly from pre-sorafenib era to post-sorafenib era (1 year RS: 17.20±0.7% to 19.90±0.80%, Z=2.63; 2 year RS: 8.00±0.5% to 8.7±0.60%, Z=2.31). Survival rates of male patients improved significantly in post-sorafenib era (1 year RS: 16.4±0.80 to 19.4±0.90%, Z=2.18; 1 year RS: 7.4±0.60% to 8.6±0.70%, Z=2.18). There was no improvement in survival rates of female patients. Similarly, younger patients had improvement in survival rates in post-sorafenib era compared to pre-sorafenib era (1 year Z value 2.46; 2 year Z value 2.23). There was no improvement in survival rates of older patients. Conclusions: Since FDA approval of sorafenib, survival rates of patients with advanced hepatocellular carcinoma have improved. The improvement in survival rates is limited to males and younger patients
Sustained Immune Competency and Long Term Molecular Remissions in FL Patients with FLIPI Risk Factors &gt;1, Treated Front Line with R-CHOP Followed by Consolidative 90 Y-Radioimmunotherapy and Maintenance Rituximab
Authors: Neil L Berinstein, Nancy M Pennell, Mary-Anne Cussen, Kevin R Imrie, Eugenia Piliotis, Rena Buckstein, Zeina Ghorab, Ellen Anne Miles, Alden E. Chesney, Matthew Cheung
Journal: Blood (2012)
Dose-finding study of 153Sm-EDTMP in patients with poor prognosis osteosarcoma
Authors: D. Loeb
Journal: Journal of Clinical Oncology (2008)

10539 Background: Osteosarcoma is a radioresistant tumor, requiring ≥70 Gy for disease control. 153Samarium ethylenediaminetetramethlenephosphonate (153Sm-EDTMP) is a bone-seeking radiopharmaceutical that targets osteoblastic skeletal metastases. Our primary goal was to identify a dose of 153Sm-EDTMP that would allow hematopoietic recovery within 6 weeks. Secondary goals included evaluation of efficacy and quantification of the radiation delivered to target lesions. Methods: Patients aged ≤ 40 years with high-risk osteosarcoma detectable on 99mTc bone scan were treated with intravenous 153Sm- EDTMP. Beginning with the FDA-approved dose of 1.0 mCi/kg, the first increase was by 40%. Thereafter dosing was determined by the continuous reassessment method (CRM), using a target frequency of dose limiting toxicity (DLT) of 30%. The CRM algorithm was applied after evaluation of every 2 patients. DLT was defined as failure of hematopoietic recovery (ANC < 750/mm3 or platelet count < 75,000/mm3) after 6 weeks. 153Sm-EDTMP scans were performed 4 hours and 24–48 hours after. Medical internal radiation dosimetry (MIRD) formalism was employed to calculate the actual doses of radiation adsorbed by the target lesions and normal bone. Radiographic response assessment was performed. Results: The MTD in the 13 enrolled patients was 1.21 mCi/kg, 20% higher than the FDA-approved dose. The 90% confidence interval for the DLT rate at the dose of 1.21 mCi/kg is 15% - 54%. The only DLT was hematologic, particularly delayed platelet recovery. Two subjects with significant pulmonary involvement experienced Grade 2–3 pulmonary toxicities at 1.2 and 1.4 mCi/kg that were likely tumor-mediated, not related to study drug. No other significant non-hematologic toxicities were observed. MIRD formalism determined that 3.4 - 39.3 Gy were delivered to target lesions. Tumor adsorbed dose showed no interpatient correlation with administered dose. Tumor avidity for 153Sm-EDTMP appeared variable and unrelated to tumor volume. Stable disease was achieved in 6/13 patients. Conclusions: 153Sm-EDTMP can be safely administered to patients with osteosarcoma. The development of chemoradiotherapy regimens for osteosarcoma patients with bone metastases is feasible. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Cytogen
Clinical outcomes of intermediate risk metastatic germ cell tumors (IRGCT): Results from a single-institution series.
Authors: Daniele Raggi, Salvatore Lo Vullo, Patrizia Giannatempo, Daniele Giardiello, Nicola Nicolai, Luigi Piva, Davide Biasoni, Mario Catanzaro, Tullio Torelli, Silvia Stagni, Massimo Maffezzini, Luigi Mariani, Roberto Salvioni, Andrea Necchi
Journal: Journal of Clinical Oncology (2015)

380 Background: IRGCT comprises a consistent category of metastatic patients (pts), and information on the recommended management of these pts should be updated. Usually they enter clinical trials for poor prognosis GCT. We aimed to address the heterogeneity of this category and to identify clinical prognostic factors for sub-stratification of pts. Methods: Data on consecutive pts with IRGCT and who received treatment at Fondazione INT Milano in the time-frame 02/1980-03/2014 were collected. Cox regression analyses were done evaluating potential prognostic factors for overall survival (OS, primary endpoint) to first-line therapy. Each factor was evaluated in a multivariable model. An exploratory OS comparison between outlier groups was undertaken with Kaplan Meier curves and logrank test. Results: Data on 181 pts were collected. Median age was 27 yrs (IQR 22-32), 10 pts had a retroperitoneal (RP) primary, 6 had pure seminoma. 72 (39.8%) had lung metastases and 54 (32.3%) bulky (i.e. ≥10cm) RP lymph-nodes (LN). Pts received cisplatin, bleomycin and etoposide (PEB, n=156) or vinblastine (PVB, n=23), 2 other treatments. Median follow up was 173 months (IQR: 87-237). Globally, 5-y PFS and OS were 66.8% (95%CI: 60.1-74.2) and 83.3% (77.8-89.2). However, 5-y OS for pts with AFP 5,000-10,000 IU/ml (N=19) was 61.8% (95%CI: 43.0-88.7) while it was 89.1% (95%CI: 81.2-97.7) for nonseminomas with elevated LDH only (N=57) and similar for elevated HCG only (N=22); overall p&lt;0.001. Multivariable analysis for OS is shown in the table (c-index= 0.63). Distribution of variables over time: bulky RP LN and elevated LDH were more frequent in earlier series (p=0.003 and 0.011). Conclusions: The prognostic heterogeneity of IRGCT category is a matter of fact and should be addressed by clinical trials. Pts with highly elevated AFP have an OS similar to poor prognostic category, while those categorized by elevated HCG or LDH only are close to good risk ones. [Table: see text]
C-MET gene copy number variation (CNV) analysis by quantitative PCR (qPCR) assay in Caucasian patients with gastric cancer (GC).
Authors: N. Galluccio, A. Ruzzo, E. Canestrari, P. Lorenzini, S. d'Emidio, V. Sisti, V. Catalano, F. Andreoni, C. Zingaretti, M. De Nictolis, C. Ligorio, F. Cappuzzo, M. Magnani, F. Graziano
Journal: Journal of Clinical Oncology (2011)

4038 Background: Activation of the c-MET oncogene promotes tumor growth, invasion and metastasis. It has been shown that c-MET mutations are almost lacking in GC, while there is limited information on c-MET activation by CNV in caucasians. We investigated c-MET CNV in GC patients in Italy. Methods: A single-institution surgical database was used for this retrospective analysis. High risk stage II-III consecutive patients who underwent gastrectomy (R0 with D2 lymphadenectomy) between 1998 and 2007 were selected. For each case, formalin-fixed paraffin-embedded tumor specimens were used for DNA extraction and c-METCNV detection by the TaqMan Gene Copy Number Assay (Applied Biosystem). The relative number of copies of three c-MET regions (Hs01602615 in exon 3, Hs05027935 in exon 12, Hs02884964 in exon 21) was determined. A sample was defined as c-METCNV>2 when this status was found in at least two of the three studied c-METregions. Results were analyzed for association with clinico-pathologic features and survival outcomes. Results: In 214 gastric carcinomas 98 cases (45%) showed c-MET CNV>2. No significant association with clinico-pathologic features was detected except for tumor histotype according to Lauren’s classification (p=0.01). c-MET CNV>2 occurred in 63/98 (64%) and 35/98 (36%) cases of intestinal and non-intestinal subtypes, respectively, while c-MET CNV<2 occurred in 64/116 (55%) and 52/116 (45%) cases of intestinal and non-intestinal subtypes, respectively. After a minimun follow-up time of three years, there were 87 relapses (40%). Log-rank tests showed significantly worse relapse-free survival (p=0.0008) and overall survival (p=0.0001) in patients with c-MET CNV>2. In multivariate models, these associations remained significant together with tumor stage. Conclusions: qPCR showed c-MET CNV in GC caucasian patients with impact on clinical outcomes. This finding is relevant to the current development of anti-MET therapeutics in this lethal disease. Ongoing analyses are refining the prognostic role of c-MET CNV considering CNV subgroups within the >2 copies group.
Management and outcomes of clinical stage II a/b seminoma: Results from the National Cancer Database.
Authors: Jonathan J. Paly, Phillip John Gray, Chun Chieh Lin, Helmneh Sineshaw, Ahmedin Jemal, Jason Alexander Efstathiou
Journal: Journal of Clinical Oncology (2015)

378 Background: Testicular seminoma is the most common solid tumor seen in patients aged 15-35 and disease specific survival approaches 100% in controlled studies, even for those with node-positive disease. We sought to describe modern practice patterns as well as survival outcomes and factors associated with receipt of adjuvant therapy for patients presenting with initial clinical stage (CS) IIA/B disease. Methods: Data on patients diagnosed with CS IIA/B testicular seminoma from 1998-2011 were extracted from the National Cancer Data Base. Demographic, clinical, treatment, payer characteristics were evaluated using multivariate logistic regression to identify factors associated with receipt of chemotherapy or adjuvant radiation therapy (ART) within 6 months of orchiectomy. Five-year Kaplan-Meier overall survival (OS) by CS and treatment was calculated. Results: In total, 2,185 patients with CS II A/B were included. Management included orchiectomy alone (11.35%), adjuvant chemotherapy (27.46%), or ART (52.72%). In multivariate analysis, receipt of orchiectomy plus ART rather than adjuvant chemotherapy was more likely with CS IIA status (OR 2.4, p &lt; 0.01), treatment outside of teaching or NCI network institution (OR 1.9-2.8, p &lt; 0.02), or tumor size ≥4cm (OR 1.6, p &lt; 0.01). Receipt of ART was less likely in Hispanic patients (OR 0.6, p=0.03) or in those diagnosed from 2006-2011 (OR 0.5, p &lt; 0.01). Five-year OS for all patients was 97.2% for orchiectomy + ART, and 93.9% for orchiectomy + chemotherapy (log-rank p = 0.01). For CS IIA patients, 5-year OS was 98.3% for orchiectomy + ART versus 93.6% for orchiectomy + chemotherapy (log-rank p &lt; 0.01). Differences in OS for CS IIB treated with chemotherapy or ART were not statistically significant. Conclusions: Consistent with national guideline recommendations, our analysis suggest that compared to chemotherapy, ART is associated with a survival advantage for CS IIA patients. Chemotherapy or ART showed no significant difference in effectiveness in patients with CS IIB. Disease bulk, race, treatment center type, and time period are associated with choice of adjuvant therapy. Longer follow-up and validation of these results is needed to account for late effects of treatment.
Open-ended concept elicitation with breast cancer (BC) patient advocates to inform patient-reported outcome (PRO) endpoints in neoadjuvant and adjuvant trials of trastuzumab emtansine (T-DM1).
Authors: Alicyn K. Campbell, Ellie Guardino, Elyse S. Caplan, Jenna Glazer, Kimberly Sabelko, Mary Lou Smith, Joan Venticinque, Hope Wohl
Journal: Journal of Clinical Oncology (2013)

172 Background: There is no standard for measuring health-related quality of life (HRQoL) using PROs in (neo)adjuvant BC clinical trials. Further, in (neo)adjuvant treatment (tx), pre-surgical cytotoxic therapy may initially worsen HRQoL. The development of tools to measure PRO endpoints in (neo)adjuvant clinical trials could be improved with a better understanding of the issues that impact HRQoL in this population. Patient (Pt) advocates, many of whom are BC survivors, may provide valuable insight to inform PRO strategy and optimal selection of PRO endpoints in clinical trials. Methods: A workshop with BC pt advocates was conducted to inform T-DM1 BC PRO strategy. It consisted of open-ended concept elicitation to identify symptomatology, tx-related side effects, and common reasons for tx discontinuation during (neo)adjuvant therapy for BC. Results: For younger pts, hot flashes and issues with sexuality and fertility were described as the most concerning issues. For older pts, peripheral neuropathy was described as the most concerning issue. Regardless of age, most pts reportedly struggle with cognitive dysfunction, anxiety, and depression. Chemotherapy-associated side effects considered most distressing to pts of all ages were alopecia, fatigue, diarrhea, neutropenia, peripheral neuropathy, and hand-foot syndrome (HFS). Neutropenia was considered most likely to cause a physician-instigated tx break, and HFS was most likely to precipitate a pt-instigated tx break. Assessing post-operative pain and satisfaction with post-surgical tx outcome (whether breast conserving or mastectomy) were emphasized. Conclusions: Open-ended concept elicitation with pt advocates is a collaborative and informative way to identify the most relevant concepts for further study. Increased collaboration with advocates to support qualitative research may improve the ability of trial results to assist pts in making informed tx decisions. Earlier engagement of pts and advocates can support the development of new PROs that offer more precision and inform PRO instrument selection to adequately quantify tx impact.
Examination of the influence that lymphatic and venous involvement gives consequence of stage I non small-cell lung cancer in new TNM classification.
Authors: K. Kojima, N. Fujiwara, H. Arai
Journal: Journal of Clinical Oncology (2010)

7074 Background: Some reports that lymphatic and venous involvement is a prognostic factor have appeared in stage I non small-cell lung cancer in previous TNM classification. The new classification (UICC-TNM 7th) has been already used, but in this classification, the lymphatic and venous involvement is not yet considered in the stage. Methods: We investigated the influence that lymphatic and venous involvement gives recurrence rate of stage I non small-cell lung cancer in new TNM classification. We analyzed 216 stage IA-IB cases that consequence is clear among 488 cases of non small-cell lung cancer to whom radical operation was performed in our hospital in Nov.1993 - Dec.2004. We used Kaplan Meyer analysis for survival rate, the chi-square test for comparison of recurrence rate and Logistic regression analysis for multivariate analysis. Results: In 216 cases, p-T1a, p-T1b and p-T2a cases were 68, 53 and 95. And five year survival rate was 94%, 88% and 72% in each stage. Analysis of all cases showed that recurrence rate is significantly high in lymphatic and venous involvement positive cases (p<0.001), and subclass analysis in p-T1a and p-T2a groups showed the same results (p-T1a:p=0.006, p-T2a:p=0.04). In multivariate analysis of the p-T2a group, p factor was an only significant recurrence factor (p=0.04), but lymphatic and venous involvement was the only significant recurrence factor (p=0.005) when the p2 cases were excluded from this group. Conclusions: It is supposed that lymphatic and venous involvement may be an important recurrence factor of stage I non small-cell lung cancer (except p2 cases) in a new classification same as a previous classification. No significant financial relationships to disclose.
Cyclooxygenase-2 expression and localization in basal cell carcinoma
Authors: T. E. Olencki, J. Pham, T. Oberyszyn, S. Peters
Journal: Journal of Clinical Oncology (2008)

20015 Background: Although changes in cyclooxygenase (COX-2) expression during carcinogenesis have been documented for neoplasms arising from various sites, studies of COX-2 expression in basal cell carcinoma (BCC) are limited. Significant COX-2 expression has been reported in many studies of cutaneous squamous cell carcinoma (SCC). In contrast, limited studies in BCC using various techniques are heterogeneous, with 3–80% of cases reported as positive. We focused our study on possible COX-2 expression in BCCs with squamous differentiation (BCCSQ). Patient specimens were de-identified prior to evaluation. This retrospective review is IRB exempt. Methods: We examined 28 BCCSQs, 10 conventional BCCs and 10 SCCs by immunohistochemistry with an antibody directed against COX-2 (1:50 dilution; clone SP21, LabVision, Fremont, CA). Tumor cells with and without COX-2 expression were counted and expression was localized either within or at the periphery of tumor lobules. Expression was graded (0) when fewer than 1% of tumor cells were positive; (1+) 1–25% positivity; (2+) 26–50% positivity; (3+) 51–75% positivity; and (4+) 76–100% positivity. Results: BCCSQs were graded as: 0 (2 cases); 1+ (16); 2+ (6); and 3+ (4). Conventional BCCs were graded as: 0 (2 cases); 1+ (5); 2+ (1); 3+ (1); and 4+ (1). Squamous areas in BCCSQs demonstrated only focal variable COX-2 staining. In 26/28 BCCSQs and 8/10 BCCs COX-2 localized to the periphery of superficial and nodular tumor lobules or was present diffusely in any infiltrative component. All SCCs demonstrated patchy 1+ to 2+ COX-2 staining. BCCSQs and conventional BCCs with an infiltrative component displayed the highest staining for COX-2 compared to superficial and nodular types. Conclusions: Increased COX-2 expression in any infiltrative component or at the periphery of tumor lobules in BCCSQs and conventional BCCs suggests that COX-2 expression may be related to dermal invasion. Possible tumor promoting mechanisms for COX-2 include stimulation of angiogenesis and anti-apoptotic functions. Increased COX-2 expression in BCCs suggests a therapeutic target for clinical trials. No significant financial relationships to disclose.
Reduced-Intensity Conditioning (RIC) Regimen Followed by Allogeneic Stem Cell Transplantation (alloSCT) for Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLCL). A Retrospective Study from the Societe Francaise de Greffe de Moelle et de Therapie Cellulaire (SFGM-TC) Registry.
Authors: Anne Sirvent, Michael Hummelsberger, Zina Chir, Nathalie Dhedin, Catherine Faucher, Jean-Pierre Jouet, Michel Attal, Patrice Chevalier, Marie Robin, Reza Tabrizi, Pierre Bordigoni, Jean-Henri Bourhis, Agnes Buzyn, Nathalie Contentin, Jerome Cornillon, Frederic Garban, Mauricette Michallet
Journal: Blood (2006)