tbuckley/cabot-search huggingface dataset:
Pediatric glioblastoma: Results with adjuvant chemoradiation using temozolomide.
Authors: Nikhil Purushottam Joshi, Supriya Mallick, Ajeet Gandhi, Shikha Goyal, Tarun Puri, Pramod Kumar Julka, Dayanand Sharma, Goura Kishor Rath
Journal: Journal of Clinical Oncology (2012)

2072 Background: Paediatric glioblastoma patients are underrepresented in major trials for this disease. The value of concurrent and adjuvant temozolomide is not known in this subset of patients. Methods: We retrospectively analysed our database between 2004 and 2010. All patients were treated with maximally safe surgical resection. This was followed by a uniform treatment schedule of post-operative radiation according to RTOG guidelines with concurrent daily temozolomide at 75 mg per meter square. The radiation dose was 60 Gy in 30 fractions planned by 3 dimensional conformal radiotherapy. 4 weeks later, adjuvant temozolomide was started at 150 mg per meter square, day 1 to 5 every 28 days and escalated to 200 mg per meter square if well tolerated. Log-rank test was used to compare survival distribution. The data was analysed using SPSS 16. Results: 23 patients were analysed. The median age was 11 years (range: 5 to 19 years). 15 males and 8 females were noted. 4 patients had seizures at presentation while 19 did not. 13 patients underwent a gross total resection while 10 underwent a subtotal resection. 5 patients received only concurrent temozolomide while 18 received concurrent and adjuvant temozolomide. The median number of adjuvant temozolomide cycles were 6 (range 2 to 12). The median follow up was 11.9 months (range: 1.6 to 30.1 months). 6 patients were dead and 17 were alive at the time of analysis. The median overall survival was not reached. The median survival for patients receiving only concurrent temozolomide was 13 months while that for patients receiving concurrent and adjuvant temozolomide was not reached and the difference was statistically significant (p=0.0009). The overall survival was not statistically different for age less or more than 10 years, gender, and type of surgery or the number of adjuvant cycles of temozolomide (less or more than 6). Conclusions: Temozolomide may have a role in paediatric Glioblastoma. Both concurrent and adjuvant temozolomide seem to be important for superior overall survival in this group of patients.
Cetuximab/radiotherapy (CET+RT) versus concomitant chemoradiotherapy (cCHT+RT) with or without induction docetaxel/cisplatin/5-fluorouracil (TPF) in locally advanced head and neck squamous cell carcinoma (LASCCHN): Preliminary results on toxicity of a randomized, 2x2 factorial, phase II-III study (NCT01086826).
Authors: Maria Grazia Ghi, Adriano Paccagnella, Daris Ferrari, Paolo Foa, Franco Nole, Franco Morelli, Giuseppe Azzarello, Consuelo D'Ambrosio, Claudia Casanova, Monica Guaraldi, Giovanni Mantovani, Ciro Rossetto, Andrea Bonetti, Salvatore Siena, Lucio Crino, Alberto Buffoli, Haralabos Koussis, Gabriella Pieri, Alessandro Gava, Irene Floriani
Journal: Journal of Clinical Oncology (2012)

5513 Background: The standard treatment options for LASCCHN are cCHT+RT or CET+RT. Strategies to improve the efficacy with the integration of induction chemotherapy are being investigated. Primary endpoints of this study were to compare: 1) the overall survival (OS) of induction vs. no induction arms; 2) the Grade(G)3-4 in-field toxicity of cCHT+RT vs. CET+RT. Methods: Patients (pts) with unresectable LASCCHN, stage III-IV, ECOG PS 0–1 were randomized to a 2x2 factorial design: Arm A1: cCHT+RT (2 cycles of ciplatin/5fluorouracil); Arm A2: CET+RTX; Arm B1: 3 cycles of TPF followed by the same cCHT+RT; Arm B2: 3 cycles of TPF followed by CET+RT. A total of 204 deaths over 420 pts ( including the 101 randomized in the phase II part of the study comparing cCHT+RT with or w/o induction TPF) were required to detect a HR of death of 0.675 (A1+A2 vs. B1+B2; 2-sided a=0.05; b=0.20) and a 10% difference in G3-4 in-field mucosal toxicity (A1+B1 vs. A2+B2). Results: By February 2012, 387 pts over 413 pts were evaluable for toxicity. 82% of pts were male; median age was 60y; PS: 0=77.8% and 1=22.2%. Disease stage was III (31%) or IV (69%). Sites of disease were oral cavity (21.7%), oropharynx (54.8%), hypopharynx (23.5%). At a median follow-up of 21 months, 126 deaths occurred. Data on G3-4 in-field toxicity (primary endpoint) and compliance to cCHT+RT vs CET+RT are shown in the table. Conclusions: No advantage for CET+RT over cCHT+RT was observed regarding G3-4 in-field toxicities and feasibility. Pts are still being followed-up to assess OS. [Table: see text]
VE-BASKET, a Simon 2-stage adaptive design, phase II, histology-independent study in nonmelanoma solid tumors harboring BRAF V600 mutations (V600m): Activity of vemurafenib (VEM) with or without cetuximab (CTX) in colorectal cancer (CRC).
Authors: Josep Tabernero, Emily Chan, Jose Baselga, Jean-Yves Blay, Ian Chau, David Michael Hyman, Noopur S. Raje, Juergen Wolf, Florin Sirzen, Maria Luisa Veronese, Lada Mitchell, Manuel Hidalgo
Journal: Journal of Clinical Oncology (2014)

3518^ Background: Low prevalence of V600m in non-melanoma cancers requires novel trial designs to assess the activity of BRAF inhibitors. Based on preclinical models that V600m positive (+) CRC upregulates the EGFR pathway and sensitizes to EGFR inhibitors in response to VEM (Prahallad et al Nature 2012), we investigated the activity of VEM in V600m+ CRC with or without CTX. Here we present preliminary efficacy and safety data for the VEM cohort and VEM + CTX dose-finding cohorts. Methods: This multicohort, Simon 2-stage adaptive design, single-proportion study included adult patients (pts) with V600m+ cancers refractory to standard therapy or for whom standard/curative therapy is not available. Pretreated CRC pts received either VEM (960 mg bid) without (cohort 3a) or with CTX (cohort 3b, 3+3 dose escalation) until investigator (INV)-assessed disease progression or unacceptable toxicity. Primary objective was INV-assessed response rate at wk 8 (RECIST v1.1). Maximum tolerated dose (MTD) and recommended dose (RD) were to be determined for the VEM + CTX cohort. Results: Median (range) treatment duration was: cohort 3a, 77 (24-225) d; 3b, 114 (36-279) d. At stage I, no responses were observed in cohort 3a (n=10). In cohort 3b, 14 pts have been enrolled for determination of MTD/RD. No dose-limiting toxicities (DLT) have been observed in dose level (DL) 1 (VEM 720 mg bid/CTX 200 mg/m2/wk) and DL 2 (VEM 720 mg bid/CTX 250 mg/m2/wk); 1 pt experienced a DLT (asymptomatic amylase grade 3 and lipase grade 4 elevation) in DL 3 (VEM 960 mg bid/CTX 250 mg/m2/wk). Preliminary response data are in table. DL 3 was selected as the RD. There were no unexpected safety findings in either cohort. Conclusions: VEM + CTX show early signs of activity in V600m+ CRC; a formal evaluation of efficacy and safety results will be provided at the meeting. VEM monotherapy is not effective in V600m+ CRC. Clinical trial information: NCT01524978. n Week 8 Week 16 Week 24 DL 1 DL2 DL 3 DL 1 DL 2 DL 3 DL 1 DL 2 Pts with tumor assessment 3 2 5 3 1 3 2 1 Complete response 0 0 0 0 0 0 0 0 Partial response 1 1 0 1 0 0 1 0 Stable disease 2 1 3 1 1 2 1 1 Progressive disease 0 0 2 1 0 1 0 0 Clinical benefit 3 2 3 2 1 2 2 1
Comprehensive functional kinase profiling to classify clear cell (cc)-renal cell carcinoma (RCC).
Authors: Amitkumar N. Mehta, Christopher Douglas Willey, Joshua Anderson, Karim Youssry Welaya, Dongquan Chen, Pooja Ghatalia, Ankit Madan, Sunil Sudarshan, Gurudatta Naik, William E. Grizzle, Toni K. Choueiri, Guru Sonpavde
Journal: Journal of Clinical Oncology (2014)

4572 Background: Comprehensive high throughput functional kinase activity in localized cc-RCC tumors may assist in devising a classification system and help identify therapeutic targets. Methods: Kinomic profiling of fresh frozen cc-RCC tumor lysates was performed using the PamStation12(PamGene Intl). The protein tyrosine kinome (PTK) and serine/threonine kinome (STK) PamChips were used to measure global kinase activity. Advanced network modeling of altered phospho-peptides was performed using MetaCore (Thompson Reuters) while upstream kinase prediction scoring was based off of phosphonet (www.phosphonet.ca). Patients with localized tumors with minimum clinical follow-up of 18 months (mo) were studied to perform a supervised analysis of kinomics guided by objective tumor recurrence. Unsupervised cluster analyses were performed to classify tumors based on kinomics. Results: Tumor was available from 41 pts with localized tumors undergoing surgery and a minimum follow-up of 18 mo. The median age was 61 and baseline pathologic stage was 1, 2, 3 and 4 in 19, 1, 20 and 1 patients, respectively. Unsupervised clustering analyses showed 3 major kinomic groups A, B, C. Potential driver kinases implicated include PFTAIRE (PFTK1), PKG1 and SRC, which were identified in groups A, B, and C, respectively. Network modeling of these kinase groupings identified many Process Mappings including, but not limited to Inflammation pathways (A), translation initiation (B) and immune response and cell adhesion pathways(C).Five of the 9 patients who progressed were classified as Group C, 1 progressor was in Group B, and 3 were in Group A. Supervised analysis showed decreased CDK1, RSK1-4, ERK1-2, PKG2 and AKT2 kinase activity in those who progressed. Twelve tumors exhibited increased PIM1 and MAPKAPK3, and decreased JNK2 and CDK1 compared to normal. Conclusions: Comprehensive kinase profiling of cc-RCC tumors from patients with localized disease was used to classify tumors based on an unsupervised clustering, which appeared to confer differential long-term outcomes while supervised analysis also identified potential pathways related to outcome. Significant heterogeneity of kinases was found with no single dominant kinase.
Comorbidities in the management of patients with lung cancer
Authors: Charlotte Leduc, Delphine Antoni, Anne Charloux, Pierre-Emmanuel Falcoz, Elisabeth Quoix
Journal: European Respiratory Journal (2017)

Lung cancer represents a major public health issue worldwide. Unfortunately, more than half of them are diagnosed at an advanced stage. Moreover, even if diagnosed early, diagnosis procedures and treatment can be difficult due to the frequent comorbidities observed in these patients. Some of these comorbidities have a common major risk factor, i.e. smoking, whereas others are unrelated to smoking but frequently observed in the general population. These comorbidities must be carefully assessed before any diagnostic and/or therapeutic decisions are made regarding the lung cancer. For example, in a patient with severe emphysema or with diffuse lung fibrosis, transthoracic needle biopsy can be contraindicated, meaning that in some instances a precise diagnosis cannot be obtained; in a patient with chronic obstructive pulmonary disease, surgery may be impossible or should be preceded by intensive rehabilitation; patients with interstitial lung disease are at risk of radiation pneumonitis and should not receive drugs which can worsen the respiratory insufficiency. Patients who belong to what are called “special populations”, e.g. elderly or HIV infected, should be treated specifically, especially regarding systemic treatment. Last but not least, psychosocial factors are of great importance and can vary from one country to another according to health insurance coverage.
Phase I study of combination of pasireotide (SOM 230) plus gemcitabine in metastatic pancreatic cancer (MPC).
Authors: Richard D. Kim, Helen Jump, Dung-Tsa Chen, William J. Fulp, David Shibata, Erin Siegel, Gregory M. Springett
Journal: Journal of Clinical Oncology (2013)

e15075 Background: For the past decade, gemcitabine (GEM) has been considered the standard chemotherapeutic agent in the treatment of MPC. SOM-230 is a multi-targeted somatostatin (SST) receptor (sst1,2,3 and 5) analog with five times the affinity of other SST receptor analogs and a potent inhibitor of insulin growth factor -1(IGF-1). SST receptors and IGF receptors are highly expressed in pancreatic cancer therefore potentially making it a valuable target. Methods: Patients with previously untreated MPC and ECOG PS 0-1 were eligible for the trial. A 3+3 dose escalation design was used. Patients with MPC received GEM 1000 mg/m 2 (30-min, once-weekly IV infusion for 3 out of 4 weeks) and SOM 230 according to dose escalation. 2 dose levels (DL) were planned. (40mg and 60 mg IM once a month). Following MTD determination the plan was to expand the cohort to 10 more patients to assess efficacy. In the expanded cohort plasma levels of IGF-I, IGFBP (insulin growth factor binding protein)-1, and IGFBP-3 were measured at baseline and with each restaging CT scan. Results: 20 patients were enrolled with 16 patients evaluable for safety and efficacy. 3 patients were each enrolled in DL1 and DL2. No dose limiting toxicities related to SOM 230 were observed at any dose level. MTD was not reached. Therefore cohort at 60mg was expanded to 10 patients to assess efficacy. Median age was 65.5 years; 6 males and 10 females. Most common grade 3 or 4 toxicities were hyperglycemia (n=5), increased bilirubin (n=2), neutropenia (n=1), thrombocytopenia (n=1) and fatigue (n=1). Two of 16 evaluable pts (12%) had confirmed partial responses (PR), and 9 had stable disease (56%) as best response. Median PFS for all pts was 4.1 months and overall survival was 8.0 months. As of Feb 2 nd 2013 there are 3 patients who are still actively receiving treatment on the trial. One patient still has stable disease after 11 months. Plasma levels of IGF-I, IGFBP-1, and IGFBP-3 were measured and will be presented. Conclusions: SOM 230 (60 mg IM monthly) plus gemcitabine was well tolerated in pts with MPC. Preliminary efficacy in a cohort of 16 pts with MPC looks promising and warrants further evaluation Clinical trial information: NCT01385956.
Let Us Not Forget the Long-term Safety Concerns of Sacubitril/Valsartan
Authors: Cian P. McCarthy, John W. McEvoy
Journal: JAMA Cardiology (2017)

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Risks and benefits of phase 1 oncology trials, 2001 through 2012.
Authors: Yoko Korenaga Fukuda, Erich Huang, Shanda Finnigan, S. Percy Ivy, Larry Rubinstein, Naoko Takebe
Journal: Journal of Clinical Oncology (2014)

2552 Background: The primary objective of phase I clinical trials is to evaluate the tolerability and pharmacokinetics of a new agent. Phase I trials in oncology remain ethically controversial. Our previous analysis from year 1991 through 2002 reported a response rate of 10.6 percent and a toxicity-related death rate of 0.49 percent. An increasing number of molecular targeted agents are under investigation and these results may not reflect current phase I oncology trials. Methods: We reviewed all non-pediatric phase 1 oncology trials sponsored by the Cancer Therapy Evaluation Program at the National Cancer Institute between January 1, 2001 and December 31, 2012. We report the rates of response to treatment, of stable disease, of grade 4 toxic events, and of treatment-related deaths. Results: We analyzed 286 trials, comprising 8314 participants. All 8314 participants were evaluated for toxic events, whereas 6604 participants were evaluated for response. The overall response rate (complete and partial response) and disease control rate (complete and partial response and stable disease) were higher than in the previous analysis. (13.2 percent vs 10.6 percent, p-value < 0.0001, 52.6 percent vs 34.1 percent, p-value < 0.0001, respectively.) 1651 participants (19.86 percent) experienced at least one grade 4 toxic event that was at least possibly related to the treatment. The overall rate of death at least possibly related to the treatment was 0.99 percent. The overall rates of death due to toxic events and grade 4 toxic events were both higher than in the previous analysis. (1.02 percent vs 0.49 percent, p –value < 0.0001, 19.86 percent vs 14.3 percent, p-value < 0.0001, respectively.) All p-values reported are 2-sided. Conclusions: The rates of response and toxicity in non-pediatric phase 1 oncology trials were higher than in the previous analysis and more than 50 percent of patients achieved at least stable disease. The higher disease control rate may be due to greater use of cytostatic molecularly targeted agents. More toxic-related deaths were reported, but this may be because of the change in serious adverse events reporting requirements by the FDA. Rate of death that was probably or definitely related to the treatment remained stable at about 0.2 percent.
Implementation of lung cancer nurse coordinator significantly enhances patient care and delivery of appropriate chemotherapy.
Authors: Kelly Zibrik, Janessa J. Laskin, Cheryl Ho
Journal: Journal of Clinical Oncology (2015)

e17708 Background: Involvement of nurse coordinators (NC) in oncology care is becoming increasingly common to facilitate more timely access to treatment for patients. The NC role in lung cancer at the BC Cancer Agency (BCCA) involves developing algorithms for staging investigations, molecular tests and referrals. BC has a publicly funded health care system and reflex molecular testing is not available. The purpose was to evaluate referral practice, timelines and molecular testing for advanced NSCLC patients, pre and post implementation of a nurse triage coordinator. Methods: The study included patients referred to the BCCA – Vancouver Centre with advanced NSCLC in 2011 baseline and 2014 after the implementation of a NC. EGFR and ALK testing is available for stage IIIB/IV non squamous NSCLC. Referral patterns, systemic therapy/radiotherapy (XRT), timelines, molecular testing parameters were collected. Results: 408 patients were included: 212 in 2011, 196 in 2014. Medical oncology (MO) endpoints comparing 2011 to 2014: referral rates remained the same, the proportion who received systemic treatment increased 57% vs 69% (p = 0.05). Time from referral to MO consult 18 d vs 15.5 d (p = 0.11), referral to systemic therapy delivery was reduced 48 d vs 38 d (p = 0.016). Molecular testing: time from referral to EGFR result was reduced 34 d vs 20 d (p < 0.001), EGFR result available at MO consult increased 6% vs 37% (p < 0.001), rate of molecular testing increased 62% vs 91% (p < 0.001), EGFR mutation positive (19% vs 26% p = 0.26). For radiation oncology (RO) endpoints: RO consults 87% vs 80% (p = 0.05), the same proportion of patients received XRT (91% vs 87%). Time from referral to RO consult 10 d vs 8 d (p = 0.005), referral to XRT 18 d vs 11.5 d (P < 0.001). Conclusions: Implementation of a NC reduced wait times from referral to treatment for MO and RO. The proportion of patients who underwent molecular testing increased and the EGFR positivity rate remained the same, therefore more patients received appropriate first line targeted therapy. Participation of a nurse coordinator during triage activities suggests that physician, diagnostic and clinical resources are more correctly allocated.
Fifteen years experience of the Brazilian Osteosarcoma Treatment Group (BOTG)
Authors: A. S. Petrilli, B. de Camargo, V. Odone Filho, D. Lustosa, M. L. Borsato, L. M. Calheiros, A. L. Brunetto, J. H. Barreto, A. A. Ferraro
Journal: Journal of Clinical Oncology (2009)

10039 Background: This is a 15-year analysis of disease characteristics and treatment outcome from three consecutive studies of BOTG. Results from protocols III and IV were previously published (J Clin Oncol. 24:1161–8, 2006). Methods: 604 histologically confirmed high-grade osteosarcoma patients were enrolled into these multicentric studies (with 4, 5, and 20 institutions in studies III, IV, and 2000, respectively). Results: Of the 604 patients, 578 were evaluable with osteosarcoma of extremities, mean age at enrollment of 14, mean time to diagnosis of 4.4 months, advanced disease (tumors diameter &gt; 12cm) in 45% and metastatic disease in 30% of the patients. Statistically significant prognostic factors were: tumor size, histological response (Huvos grade), presence of metastasis at diagnosis and type of surgery. Time to diagnosis was not predictable of survival. Advanced disease was associated to presence of metastasis and to a poorer histological response. During the first 5 years, 53% of the patients had conservative surgery with 19.6% of local recurrence and these numbers were 65.5% and 14% in the next 5 years and 62.3% and 11% during the last 5 years. The overall survival (OS) at 5 years was 44%, 45% and 46% respectively. In the whole cohort of patients, overall survival (OS) was 45.7% at 5 years and 43% at 10 years and event free survival (EFS) was 43% and 34%. For non-metastatic patients, OS was 56.5% and 54% and EFS was 53% and 44%, respectively. Conclusions: Over these 15 years, we were able to increase limb salvage procedures with a significant drop in local recurrence, reaching survival rates similar to some international studies. This cumulative experience enabled the expansion of the collaborative group, the identification of prognostic factors, dissemination of knowledge, and the development of the current protocol for osteosarcoma treatment, which is a multicentric, randomized study with good quality data collection over 26 sites in Latin America. No significant financial relationships to disclose.