tbuckley/cabot-search huggingface dataset:
Study KBP-2010-CPHG: Characteristics and management of 7,051 new cases of lung cancer managed in French general hospitals in 2010.
Authors: Chrystele Locher, Dominique Herman, Geoffroy De Faverge, Hubert Barbieux, Christine Lemonnier, Khaldoun Hakim, Didier Debieuvre, Jean-Pierre Gury, Jean-Michel Marcos, Michel D Arlhac, Pablo Ferrer Lopez, Pierre-Alexandre Hauss, Olivier Raffy, Fabrice Paganin, Eric Huchot, Jean-Bernard Auliac, Francis Martin, Mahmoud Zureik, Francois Blanchon, Michel Grivaux
Journal: Journal of Clinical Oncology (2012)

1574 Background: An initial epidemiologic study was performed in 2000 by the French College of General Hospital Respiratory Physicians (Study KBP-2000-CPHG). Over the last 10 years, lung cancer management changed: new drugs such as targeted therapies appeared; new diagnostic techniques such as exploration for genetic mutations in the tumour have been developed; a new TNM classification has been drawn up. The aims of this study were to describe patient characteristics, first-line management, 1, 4 and 5-year survival rates and to compare the results with those of Study KBP-2000-CPHG. Methods: A prospective multi-centre study included all patients ≥18 years presenting with a new case of primary lung cancer, histologically or cytologically diagnosed between 1 January and 31 December 2010 and managed by one of the participating centers. A standardised form was completed for each patient. A steering committee checked the exhaustivity of data’s collection. Results: 7,610 patients from 119 general hospitals were included between 1 January and 31 December 2010. The main patient characteristics were: mean age 65.5 years (+/-11.3); 24.3% female; 10.9% non-smokers, 39.9% ex-smokers, 49.2% current smokers; 68.9% performance status 0 and 1; 9.1% of patients had lost &gt;10 kg within the previous 3 months. The main tumour characteristics were: 13.7% small-cell lung cancer; 46.2% adenocarcinoma, 26.8% squamous-cell carcinoma; EGFR mutation, explored in 30.5% of cases, were found in 10.5% of cases; 16.4% stage IA to IIB, 13.4% stage IIIA, 10.2% stage IIIB and 60.0% stage IV. First-line treatments were: curative surgery, 16.6%; chemotherapy, 63.4%; radiotherapy alone, 17.8%; combined radio-chemotherapy, 8.8%; and supportive care, 11.1%. Targeted therapy was used in 6.6% of patients treated by chemotherapy. Conclusions: In 10 years, characteristics of lung cancer patients changed with an significantly increase of women, non-smokers, adenocarcinoma histology and stage IV at diagnosis.
Impact of rural/urban residence on relative survival (RS) in patients with kidney cancer: An analysis of 14576 patients from the Austrian National Cancer Registry (ANCR).
Authors: Martin Marszalek, Henrike E Karim-Kos, Stephan Madersbacher, Monika Hackl, Michael Rauchenwald
Journal: Journal of Clinical Oncology (2017)

491 Background: Access to medical diagnostics and treatment might be limited for patients living in rural areas compared to urban residents. To evaluate the potential impact of urban/rural residence, we analyzed trends in RS for patients diagnosed with kidney cancer between 1998 and 2009 in Austria. Methods: All patients with kidney cancer aged ≥18 years, diagnosed from 1998-2009 were derived from the ANCR (n=14,576). Patients were categorized into two groups: rural (n=7,537) and urban (n=7,039) based on a complex algorithm considering infrastructure, commuter interrelations, accessibility of centers, and tourism at the time of diagnosis. Relative survival was calculated based on complete follow-up until December 31 st , 2014. Poisson regression modeling was used to evaluate survival differences between the two groups and to calculate the relative excess risk of dying (RER). Analyses were performed for the total patient population and primary metastatic patients (M+). Results: Distribution of sex, age, stage of disease, year of diagnosis, and surgical treatment did not differ between rural and urban patients. Five-year RS was 74% for rural compared to 73% for urban patients (RER for rural: 0.88, 95% CI 0.81-0.95). In M+ patients, 5-year RS was 14% for both residence groups. On multivariate analysis, residence remained as an independent predictor for survival in the overall kidney cancer population (RER of rural patients 0.87, 95% CI 0.81-0.94). For M+ patients the RER was 0.90 ( 95% CI 0.81-1.00). For patients without surgery, rural patients were even stronger benefited in their survival than urban patients (overall population: RER 0.81, 95% CI 0.74-0.89; M+ patients: RER 0.84, 95% CI 0.73-0.97) wherereas in surgical patients RS did not differ between rural and urban patients. Conclusions: An advantage in RS was observed for kidney cancer patients living in rural areas. This advantage was evident in metastatic and non-metastatic patients, especially in patients who did not undergo surgery for (metastatic) kidney cancer. These results suggest that access to medical health care for kidney cancer patients in Austria is not limited by rural residence.
Impact of palliative care on end-of-life management of cancer patients dying in the hospital.
Authors: Syed Mustafa Karim, Jamal M Zekri, Ehab Mosaad Abdelghany, Azhar Rizvi, Aboelkhair Al-Gahmi, Husna Munsoor, Imran Ahmad, Reyad Dada, Mohammed Iqbal Ansari, Ian G. Kerr
Journal: Journal of Clinical Oncology (2013)

e20613 Background: A substantial number of cancer patients receive inpatient care at the end-of-life (EoL). Involvement of palliative care teams during the course of cancer treatment has been shown to improve quality of life (QoL) in cancer patients. In this study, we compare the EoL care of cancer patients dying in the hospital under medical oncology (MO) and palliative care (PC) services. Methods: A retrospective review of medical records of adult cancer patients who received chemotherapy during their illness and died in our hospital between January 2010 and January 2012 was conducted. The quality metrics measured as endpoints were: chemotherapy given within 21 days of death, death in the ICU, CPR at time of death, and time from last chemotherapy to death (TLCD). These endpoints were compared between patients who died under the MO service (cohort A) and those dying under PC service (cohort B). Chi-square test and T-test were used to compare the endpoints between the two cohorts. Results: Of the 106 cancer patients who died in the hospital, 40 and 66 were in cohorts A and B respectively. 30% of all patients were 65 years of age or older, and were equally distributed between the two cohorts. Patients in cohort A were more likely to receive chemotherapy within last 3 weeks of life (27.5% versus 7.5%, p=0.012, 95% CI 4.16-37.15), to have CPR at time of death (15% versus 0%, p=0.005, 95% CI 4.2-29.8) and to die in the ICU (52.5% versus 1.5%, p=&lt;0.001, 95% CI 33.3-67.1) as compared to patients in cohort B. The average time from last chemotherapy to death was significantly longer (221 days) for cohort B patients as compared to cohort A patients (96 days), p=0.01. Patients in cohort A who had PC consultation during their hospitalization had no differences in the measured endpoints when compared to patients in cohort B. Conclusions: Cancer patients who die in the hospital while under MO service without PC involvement tend to have more aggressive EoL care. This may impact negatively on some QoL features. Early referral to palliative care services may facilitate better understanding and fulfillment of the needs of cancer patients and their caregivers by the healthcare-providers.
Quality of life in patients with malignant ascites during catumaxomab treatment: Results from the CASIMAS trial.
Authors: Florian Lordick, Jalid Sehouli, Ignace B. Vergote, Per Rosenberg, Andreas Schneeweiss, Andreas Block, Christoph Salat, Giovanni Scambia, Dominique Berton-Rigaud, Salvatore Siena, Armando Santoro, Andres Cervantes-Ruiperez, Jean Paul Guastalla, Christophe Tournigand, Nicoletta Colombo, Alexander Serg Dudnitchenko, Vladimir Bondar, A.M. Westermann, Ann-Katrin Gonschior, Pauline Wimberger
Journal: Journal of Clinical Oncology (2012)

e13095^ Background: Malignant Ascites (MA) is associated with a poor prognosis and limited palliative treatment options. To demonstrate the value of a new treatment the assessment of quality of life (QoL) is of particular importance. Following the demonstration of catumaxomab’s potential to stabilize QoL and prolong the time to first deterioration of QoL, results from CASIMAS give evidence that the QoL of patients remains unaffected during catumaxomab treatment Methods: In a two-arm, open-label, multicentre phase II/III study 219 patients were randomized to catumaxomab plus premedication of 25 mg prednisolone (111 pts) or to catumaxomab alone (108 pts) QoL was measured using the EQ-5D visual analogue scale (EQ-VAS). The EQ-VAS reports the respondent’s self-rated health on a vertical scale where the endpoints are labelled “Best imaginable health state” (100) and “Worst imaginable health state” (0). This information is used as a quantitative measure of health outcome. Patients were asked to complete EQ-VAS during the treatment period (d 0, 3 and 10) and follow-up (d8, 28). Descriptive analyses were performed according to EQ-5D User Guide (Version 4.0). Additionally ascites related symptoms were measured with a disease specific FACIT patient questionnaire. Results: For the pooled population (catumaxomab plus prednisolone and catumaxomab alone) longitudinal analysis of the EQ-VAS showed no relevant changes in mean score during the treatment period of catumaxomab (d0: 51.5; d3: 50.9; d10: 51.0) and compared to screening (52.7). An increase in mean values was observed in the follow-up period (d8: 53.9, d28: 57.1). Descriptive comparison of both treatment groups revealed no major differences in QoL and ascites related symptoms during the treatment and follow-up period, indicating that prednisolone has no impact on patient`s self-rated health. Conclusions: This analysis shows that QoL as measured by EQ-VAS remains unaltered during the treatment with catumaxomab and improves after the treatment period. The improvement is plausible due to the prolonged-puncture-free survival and is consistent with previous observations of QoL changes during and after intraperitoneal treatment with catumaxomab.
Interim analysis of a phase I/II study of panobinostat in combination with bevacizumab for recurrent glioblastoma.
Authors: Eudocia Quant Lee, David A. Reardon, David Schiff, Jan Drappatz, Alona Muzikansky, Samantha Hammond, Sean Aaron Grimm, Andrew David Norden, Rameen Beroukhim, Christine Sceppa McCluskey, Andrew S. Chi, Tracy Batchelor, Katrina H. Smith, Sarah C. Gaffey, Mary Gerard, Susan M. Snodgrass, Jeffrey J. Raizer, Patrick Y. Wen
Journal: Journal of Clinical Oncology (2013)

2013 Background: Bevacizumab is frequently used to treat recurrent GBM, but responses are generally not durable. Panobinostat is a histone deacetylase inhibitor with anti-neoplastic and anti-angiogenic effects in GBM and may work synergistically with bevacizumab. We conducted a multicenter phase I/II trial of panobinostat in combination with bevacizumab in patients with recurrent GBM. Methods: In the phase II trial, patients with recurrent GBM were treated with oral panobinostat 30 mg three times per week, every other week, in combination with bevacizumab 10 mg/kg every other week. The primary endpoint was 6-month progression-free survival (PFS6) and the study was powered to discriminate between a 35% and 55% PFS6 rate (85% power at an alpha level of 0.07). A planned interim analysis specified suspension of accrual and careful data review if 12 or more of the first 21 patients accrued to the study progress within 6 months of initiating treatment. Patients with recurrent GBM enrolled in the phase I study at the maximum tolerated dose (which is the phase II dose) were eligible for inclusion in the interim analysis. Results: Thirteen of the first 21 patients accrued to the GBM arm of the study had progressed within 6 months of initiating study treatment. The study was closed to further accrual and a planned interim analysis was performed. Median age was 53 (range 22-66) and median KPS was 80% (60%-100%). PFS6 rate was 33.9% [95% CI 12.8, 56.5), median was PFS 5 months [95% CI 3 months, NR], and median OS was 342 days [95% CI 203 days, NR]. Five patients (23.8%) achieved partial responses. Conclusions: Although reasonably well-tolerated, this phase I/II study of panobinostat and bevacizumab in recurrent GBM did not meet criteria for continued accrual and the study was closed. Updated outcome and safety data will be presented at the meeting. Study Supported by: Novartis and Genentech Clinical trial information: NCT00859222.
Pleuropulmonary blastoma: The causative role of germ-line <i>DICER1</i> mutations.
Authors: Leslie Ann Doros, Jiandong Yang, Amanda Field, Christopher Rossi, Gretchen M Williams, Kris Ann Pinekenstein Schultz, Louis P Dehner, Yoav H. Messinger, D Ashley Hill
Journal: Journal of Clinical Oncology (2013)

10024 Background: Pleuropulmonary blastoma (PPB) is a rare, aggressive childhood lung cancer that is often the first manifestation of the PPB-DICER1 familial tumor predisposition which includes other benign and malignant conditions. The initial genetic mutation is inherited by a germ-line loss of function of DICER1 gene which was discovered by Hill et al. It is proposed that loss of DICER1 expression alters miRNA regulation of key regulatory cellular mechanisms which promote tumor growth. PPB can progress from the purely cystic, curable Type I to a high-grade Type III having a dismal prognosis. We sought to determine the frequency of DICER1mutation in the largest cohort of PPB patients to date. Methods: We obtained germ-line DNA from saliva or blood samples from 113 PPB patients collected from 2005-2012. DNA was extracted using the Maxwell 16 Research System (Promega Corporation, Madison WI). Sample quality and quantity was checked using the Nanodrop 2000 (Thermo Scientific, Wilmington, DE). Sequencing was performed using the Sanger sequencer. For a subset of cases we used targeted sequencing services or full gene sequence analysis (Ambry Genetics, Aliso Viejo, CA). Results: Seventy-four (65.5%) PPB patients were found to have deleterious DICER1germ-line mutations. The most common mutation type found was small insertion/deletions. These 74 samples were composed of 7 (9.5%)Type Ir PPBs, 22 (29.7%)Type I PPBs, 24 (32.4%) Type II PPBs, and 21 (28.4%)Type III PPBs. The following Table shows a summary of mutation types identified. Conclusions: Our results confirm that DICER1 germline mutations are the most common genetic alterations in PPB making it critical for genetic testing to be performed at diagnosis. Additionally, this underscores the need for important correlative studies to describe the genotype-phenotype relationship in order for appropriate screening guidelines to be developed and implemented to allow for early detection. While a majority of cases are explained by germline DICER1 mutations using current sequencing methods, further investigation is warranted to elucidate other possible mechanisms in the development of PPB. [Table: see text]
A U.S.-based prospective, multi-center, non-interventional study of the role of comprehensive genomic profiling in the clinic.
Authors: Norma Alonzo Palma, Zachary Chalmers, Yali Li, Mark Bailey, Jeffrey S. Ross, Sohail Balasubramanian, Deborah Morosini, Siraj Mahamed Ali, Alex Parker, Phil Stephens, Vincent A. Miller, Filip Janku
Journal: Journal of Clinical Oncology (2015)

e22183 Background: Comprehensive genomic profiling is increasingly incorporated in cancer treatment decision-making in an effort to identify druggable genomic events. FoundationOne (F1) is next-generation sequencing-based comprehensive genomic profile introduced clinically in 2012. Prior work has highlighted the ability of this approach to identify clinically relevant genomic alterations (CRGA), i.e.-changes associated with an approved agent or a mechanism-based clinical trial, in more than 80% of pts (Johnson et al. Oncologist, 2014). To describe clinician’s use of F1 in practice, we undertook an observational registry study. Methods: This is an ongoing study to characterize use of F1 in routine clinical practice. Planned duration is > 2 years with ~18 months for patient (pt) enrollment and > 1 year follow-up/pt. Pts for whom F1 was ordered, informed consent was obtained and a F1 report was issued were considered eligible for participation. Results: 496 pts from 26 sites (community 81% ) comprise the predefined baseline analysis population. Median age was 59 and 54% were female. Most common tumor types were lung (16.7%), breast (12.3%) and CRC (11.1%) with pts having received an average of 3 lines of therapy prior to F1 testing (range 1-17). Most common reasons for ordering F1 was progression of disease (33.7%) and diagnosis of metastatic disease (30.6%). F1 found at least one clinically relevant genomic alteration (CRGA) in 86.6% of pts. Physicians were asked to report on prior molecular testing. In the subset of pts in whom molecular testing (EGFR, HER2, KRAS, etc.) was ordered prior to F1 (28.4%, 141/496), at least one CRGA was uncovered by F1 in 92.9% (n = 131) of pts. In 19.8% of pts (n = 28) an FDA-approved therapy option in that tumor type was detected. Conclusions: Use of F1, in a primarily community setting, is feasible and uncovers CRGA in almost 87% of pts. Analysis of use of “matched” targeted therapies, enrollment on clinical trials and outcomes is ongoing. Clinical trial information: NCT01851213.
Multi-institutional multiplexed genetic analysis in lung adenocarcinoma (AC): The Lung Cancer Mutation Consortium (LCMC I) experience.
Authors: Dara Aisner, Lynette M. Sholl, Marileila Varella-Garcia, Lynne D Berry, Dora Dias-Santagata, Ignacio Ivan Wistuba, Heidi Chen, Junya Fujimoto, Kelly Kugler, Wilbur A. Franklin, Bruce E. Johnson, John D. Minna, Mark G. Kris, Paul A. Bunn, David J. Kwiatkowski
Journal: Journal of Clinical Oncology (2014)

11030 Background: Molecular analysis of lung AC has become standard of care for therapy selection. LCMC I collectively enrolled 1102 patients from 14 institutions with the goal of performing molecular analysis to identify therapy options. Technical aspects of the genomic testing, specimen and clinical correlations are presented. Methods: Testing for mutations in 8 genes (EGFR, KRAS, ERBB2, AKT1, BRAF, MEK1, NRAS, PIK3CA), and analysis of ALK and MET by FISH, was performed at 6 labs. Proficiency testing was carried out with blinded samples. Statistical analyses were performed for analysis completion, specimen types, testing methodology, mutation findings and clinical variables. Results: Five methodologies (SNaPshot®, mass spectrometry, Sanger +/- PNA, sizing) were variably employed for detection of mutations, with analytic sensitivities of ~5% allele frequency. All sites passed proficiency testing. 1006 specimens had at least one mutation analysis completed, 733 specimens had full genotyping results. Mutation detection rates did not vary according to method of analysis. Higher rates of specimen inadequacy were seen in biopsy (36/136; 23%) and cytology (23/65; 36%) compared to surgical (13/268; 5%) specimens at the site that analyzed the most cases. Biopsy and cytology samples, when acceptable showed no difference in mutation or FISH assay completion or positivity rate. Multiple analyses are summarized in the table. Double mutations were seen in 3.8% of samples. Conclusions: Molecular analysis is possible in a multi-institutional setting with consistent results. Cytology and small biopsy specimens were commonly sufficient for multiplex testing, although sample insufficiency was a common reason for exclusion (53% of excluded cases), and contributed to lack of assay completion. Multiple associations were identified between specific mutations and clinicopathologic features. Gene marker (% +) Associations found (All p<0.01) EGFR (22%) Female, never smoker, Asian, bone metastases KRAS (25%) Tobacco exposure, lack of bone metastases, non-Asian, older age at dx ALK (9%) Never smoker, younger age at dx, liver metastases MET amp (3%) Male ERBB2 (2%) Never smoker BRAF (2%) None
Correlation between in vitro chemotherapy sensitivity and PARP-1 expression in patients with breast cancer.
Authors: Cornelia Liedtke, Jens Packeisen, Carsten Denkert, Ludwig Kiesel, Ulf Vogt, Berit Mueller, Kenneth R. Hess, Horst Buerger
Journal: Journal of Clinical Oncology (2012)

10627 Background: Based on its potential use as a therapeutic target through PARP inhibitors expression of Poly-A-Ribose-Polymerase-1 (PARP-1) has come into scientific focus. Furthermore, it could be demonstrated that cytoplasmic PARP-1 expression varies depending on molecular breast cancer subtypes and that it correlates with an increased response to neoadjuvant taxane-anthrazykline containing chemotherapy (von Minckwitz et al., J Clin Oncol 2011). In-vitro-chemotherapy sensitivity and resistance assays (CSRAs) are a means to directly measure chemotherapy sensitivity in a given tumor uninfluenced by host factors. Methods: We conducted a systematic immunohistochemical tissue-microarray (TMA)-based analysis of 550 samples of invasive breast cancers to evaluate the expression of a set of molecular markers including estrogen receptor (ER), progesterone receptor (PR) and HER2 as well as PARP-1. Triple negative breast cancers (TNBC) were identified through lack of (over-)expression of ER, PR and HER2. All carcinomas were analyzed in an in vitro CSRA protocol for epirubicin/docetaxel (ED) and epirubicin/cyclophosphamide (EC). In-vitro-chemotherapy sensitivity was analyzed using an adenosine triphosphate (ATP) bioluminescence assay. Results: Moderate/high expression of PARP-1 was found in 48 and 33% of cases with TNBC and non-TNBC, respectively (p=0.015). No correlation between TNBC phenotype and cytoplasmic expression was observed. However, increased expression of both cytoplasmic and nuclear PARP-1 was correlated with an increased in-vitro sensitivity against ED (p=0.012 and 0.025, respectively) but not EC (p=0.27 and 0.62, respectively). Conclusions: Our results support previous observations demonstrating a significant correlation between expression of PARP-1 and an increased sensitivity against taxane-anthracycline chemotherapy independent of tumor phenotype.