tbuckley/cabot-search huggingface dataset:
A phase Ib study of BGJ398 in combination with imatinib in patients with advanced gastrointestinal stromal tumor (GIST).
Authors: Ciara Marie Kelly, Alexander Noor Shoushtari, Li-Xuan Qin, Sandra P. D'Angelo, Mark Andrew Dickson, Mrinal M. Gounder, Mary Louise Keohan, Ana Sjoberg, Chloe Mcfadyen, Sinchun Hwang, M.H. Heinemann, Jasmine Francis, Samuel Singer, Ronald P. DeMatteo, Cristina R. Antonescu, Ping Chi, William D. Tap
Journal: Journal of Clinical Oncology (2017)

11039 Background: Preclinical studies suggest that imatinib resistance (IR) in GIST can be mediated by MAP-kinase activation via FGF signaling. In FGF stimulated GIST cell lines, BGJ398, a pan-FGFR inhibitor in combination with imatinib, is cytotoxic and superior to imatinib alone, or imatinib in combination with MEK-inhibition. In GIST with FGF signaling, the combination of BGJ398 and imatinib may provide a mechanism to overcome IR. Methods: This phase Ib study of BGJ398 in combination with imatinib was performed in patients (pts) with imatinib resistant advanced GIST. A standard 3+3 dosing schema was utilized to determine the recommended phase II dose. Two treatment schedules were evaluated incorporating imatinib 400mg daily continuously in combination with (A) BGJ daily 3 wks on, 1 wk off or (B) BGJ daily 1 wk on, 3 wks off. Response was evaluated by RECIST and CHOI every 8 wks x4 and then every 12 wks. Results: 16 pts enrolled. Median age 54 (range: 44-77), 81% male, median prior therapy 4 [range: 2-6, 13/16 pts had ≥ 3 prior therapies (81%)]. 12 pts received treatment on schedule A [dose level (DL)1 (BGJ 75mg), n = 6; DL-1 (BGJ 50mg), n = 3; DL-2 (BGJ 25mg), n = 3]: 3 DLTs (myocardial infarction, grade (G)4 CPK elevation, G3 ALT elevation) were observed on schedule A at DL1, hyperphosphatemia (on target effect) was not observed raising concern for therapeutic efficacy at the maximum tolerated dose. Following protocol amendment that allowed an alternative dosing schedule, 4 pts enrolled on schedule B [DL1 (BGJ 75mg), n = 3; DL2 (BGJ 100mg), n = 1]: one DLT occurred (G3 intra-abdominal hemorrhage) at DL2. The most common non-DLT G3/4 toxicity was HTN (2/16pts) and G2 toxicity was prolonged QTc interval (3/16pts). Of the 12 pts with evaluable CT scans, stable disease (SD) was the best response observed in 7 pts by RECIST and 9 pts by CHOI. 3pts achieved SD for &gt; 6 months. 2 pts remain on study at data cut-off (range: 1 – 67 wks). Median progression free survival is 8 weeks. Pharmacokinetic analysis of imatinib and BGJ is forthcoming. Conclusions: In heavily pre-treated pts, durable disease control was observed in 3/16 pts. This signal of efficacy suggests that further evaluation of FGF signaling in the development of IR is warranted. Clinical trial information: NCT02257541.
Neoadjuvant chemotherapy plus concomitant chemoradiation versus concomitant chemoradiation for locoregionally advanced nasopharyngeal carcinoma: A systematic review and meta-analysis of comparative studies.
Authors: Teng Hwee Tan, Yu Yang Soon, Timothy Cheo, Jeremy Chee Seong Tey, Ivan Weng Keong Tham
Journal: Journal of Clinical Oncology (2017)

e17552 Background: To determine if addition of neoadjuvant chemotherapy (NACT) to concomitant chemoradiation (CCRT) for patients with locoregionally advanced nasopharyngeal carcinoma (NPC) improves overall survival. Methods: We searched MEDLINE for eligible studies comparing NACT plus CCRT versus (vs) CCRT alone for locoregionally advanced NPC. We assessed the methodological quality of the included studies using the MERGE criteria. We performed the meta-analysis with random effects model using Revman 5.3 to estimate the pooled hazard ratios (HR), confidence intervals (CI), P values (P) and I squared statistic (I 2 ). The primary outcome was overall survival (OS); secondary outcomes include progression-free survival (PFS) and adverse events (AE). We used the GRADE approach to appraise the quality of evidence from randomized trials. Results: We found four randomized and five retrospective comparative studies including 2178 patients with low to moderate risk of bias in their methodologic quality. Pooled estimates from both randomized and retrospective studies demonstrated a benefit in PFS (HR 0.78, 95% CI 0.66 to 0.93, P = 0.006, I 2 = 0%) and OS (HR 0.77, 95% CI 0.61 to 0.96, P = 0.02, I 2 = 0%) with NACT. In the randomized trials, there was moderate quality evidence that NACT improved PFS significantly (HR 0.73, 95% CI 0.57 to 0.93, P = 0.01, I 2 = 0%); trend towards OS benefit (HR 0.76, 95% CI 0.56 to 1.03, P = 0.08, I 2 = 0%) and was associated with more frequent AE. There were no significant differences in the results between the randomized and retrospective comparative studies (PFS HR 0.73 vs 0.82, interaction P (IP) = 0.58; OS HR 0.76 vs 0.78, IP = 0.93). Conclusions: Neoadjuvant chemotherapy delays disease progression substantially and may improve survival for locoregionally advanced nasopharyngeal carcinoma. There were no divergent results between randomized and retrospective comparative studies. Future trials should test more effective and/or better tolerated agents during the neoadjuvant therapy phase.
Tumor response dynamics of advanced non-small-cell lung cancer (NSCLC) patients (pts) treated with commercial PD-1 inhibitors in the clinical setting.
Authors: Mizuki Nishino, Suzanne Eleanor Dahlberg, Anika E Adeni, Christine A. Lydon, Hiroto Hatabu, Pasi A. Janne, F. Stephen Hodi, Mark M. Awad
Journal: Journal of Clinical Oncology (2017)

9087 Background: PD-1 inhibitors have shown promising activity in advanced NSCLC, with increasing clinical use. We evaluated tumor burden dynamics in advanced NSCLC pts treated with commercial PD-1 inhibitors to identify imaging markers for clinical benefit. Methods: The study included 160 advanced NSCLC pts (79 males; median age: 65) treated with commercial nivolumab or pembrolizumab monotherapy at DFCI as a part of routine clinical care. Tumor burden dynamics were assessed on serial CT scans during therapy by irRECIST1.1, which uses unidimensional measures and includes new lesions in tumor burden [Clin Cancer Res. 2013;19:3936-43]. Results: Tumor burden change at best overall response (BOR) ranged from -100% to +278% (median: +3.5%). Objective response rate (ORR) was 18% (29/160). Current and former smokers had higher ORR than never smokers (ORR:14% (8/58), 25% (20/79), 4% (1/23); Fisher p = 0.04). Durable disease control with tumor burden &lt; 20% increase from baseline for at least 6 months was noted in 27 pts (17%), which included 11 pts with stable disease as their irBOR. Using an 8-week landmark analysis, pts with &lt; 20% tumor burden increase from baseline at 8 weeks had longer OS than pts with ≥20% increase (median OS:12.4 vs. 4.6 months, p &lt; 0.001). In Cox models using a time varying covariate, pts with &lt; 20% tumor burden increase during therapy had significantly reduced hazards of death (HR = 0.24, p &lt; 0.0001) after adjusting for smoking (HR = 1.77, p = 0.016) and baseline tumor burden (HR = 1.66, p = 0.032). Two pts (1.3%) had atypical response pattern or “pseudoprogression”, where tumor burden showed initial increase and subsequent decrease, which was noted after confirmed irPD on consecutive scans in both pts. Conclusions: An objective response or durable disease control was noted in 25% of advanced NSCLC pts treated with PD-1 inhibitors in the clinical setting. Tumor burden increase of &lt; 20% from the baseline during therapy was associated with longer OS, proposing a practical marker of clinical benefit. Pseudoprogression was uncommon, with tumor decrease noted after confirmed irPD, indicating a limitation of the current strategy for immune-related response evaluation.
Pediatric cancer registry Turkey: 2009-2016 (TPOG &amp; TPHD).
Authors: M. Tezer Kutluk, Akif Yesilipek
Journal: Journal of Clinical Oncology (2017)

e22015 Background: Each year 300.000 new cancer cases are expected in children &amp; adolescents aged 0-19 years at global level. Although the long term survival rates have been improved to 85% in high income countries it is lower than this LMICs. Pediatric registries are essential for planning, evaluation, comparison for pediatric cancer care. This study focuses to pediatric cancer registry in Turkey. Methods: Turkish Pediatric Oncology Group and Turkish Pediatric Hematology Association established a WEB based cancer registry in Turkey in 2002. The registry information for 2002-2008 was presented earlier. This study, now, is including the distribution of pediatric cancer registry for the years of 2009-2016. International Childhood Classification System was used in classification. Basic demographic findings, ICD-O-3 morphology &amp; topography codes were recorded for each cases. Results: During the 8 years from 2009 to 2016, 13123 pediatric cancer cases were recorded. For all cases, median age was 6.5 year (0–17; M/F 7356/5759, 3 hermaphrodite). Age distribution was 0–4 yrs, 41.3%; 5–9 yrs, 24.3%; 10–14 yrs , 23.2%; 15–19 yrs, 11.0%. 7 cases older than were registered (%0.1). The distribution of tumor types were [number of cases, percentage of total, median age years, M/F]: Leukemia (3751, 28.6%, 5.5, 2148/1603); Lymphoma and other RES tumors (2381, 18.1%, 9.5, 1613/763); CNS [brain &amp; spinal] (1672, 12.7% , 7.13, 908/764); Symphatetic system (1053, 8.0% , 2.42, 550/503); Retinoblastoma (339, 2.6%, 1.33, 188/151); Renal (675, 5.1%, 3.33, 314/361); Liver (217, 1.7% , 1.75, 116/101); Malignant bone (892, 6.8 %, 12.55, 486/406); Soft tissue sarcomas (868, 6.6% , 7.21, 518/350); Germ cell (818, 6.2%, 7.58, 292/523); Carcinoma and other malignant epithelial (391, 3.0% , 13.60, 191/200); Other/non-specific malignant (66, 0.5%, 6.54, 32/34) tumors. Five year survival rate was found as 69.5 %. Conclusions: This registry since 2002 became a critical source for health care professionals in Turkey. Survival rates for children increased from 65% to 70% based on the latest information from this study. This is compatible with Turkey’s development level as an upper middle income country. This data also allows us to use the registry information at national and international studies.
A Randomized Clinical Trial of n-of-1 Trials—Tribulations of a Trial
Authors: Reza D. Mirza, Gordon H. Guyatt
Journal: JAMA Internal Medicine (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
IFCT-1001 CHIVA trial: A phase II study of carboplatin (Ca) plus pemetrexed (P) followed by P maintenance, as first-line therapy for human immunodeficiency virus (HIV)–associated advanced non-squamous non-small cell lung cancer (NS-NSCLC).
Authors: Armelle Lavole, Pascale Tomasini, Isabelle Monnet, Lize Kiakouama-Maleka, Xavier Quantin, Laurent Taillade, Hervé Lena, Philippe Fraisse, Henri Janicot, Clarisse Audigier-Valette, Alain Makinson, Alexandra Langlais, Marie Paule Lebitasy, Franck Morin, Jacques Cadranel
Journal: Journal of Clinical Oncology (2016)

9076 Background: Lung cancer and especially NS-NSCLC, is the first cause of mortality by cancer in the HIV population. However, recommendations for treatment of advanced NSCLC are lacking in this population, as HIV seropositivity is an exclusion criteria from most trials. We conducted a multicenter phase II trial to evaluate the efficacy and safety of CaP induction followed by P maintenance, in HIV associated advanced NS-NSCLC. Methods: Four cycles of CaP were administered, followed by P until progression in controlled patients with PS ≤ 2 after induction. The primary endpoint was a ≥ 30% disease control rate (DCR) after 12 weeks. Secondary endpoints were objective response rate, progression-free (PFS) and overall survival (OS), as well as the incidences of adverse events (AE) and opportunistic infections. Results: 61 patients (pts) were enrolled between 05/2011 and 07/2015. Baseline characteristics were a median age of 52 years, 75.4% males, 82% PS < 2 and 93.4% current/former smokers. Median CD4 count at diagnosis and at nadir were 418 cells/µL (range 18-1230) and 163 cells/µl (1-822), respectively. Median HIV viral load was 39 copies/µL (0-95499) and 96% pts received antiretroviral treatment. 80.3% of pts did not receive cotrimoxazole, prophylaxis agains pneumocystis jiroveci and toxoplasmosis. DCR after 4 cycles was 50.8 % (95%CI: 38.3-63.4): 38.7% were partial responses and 61.3 % stable diseases. After a median follow-up of 26 months, median PFS was 3.6 (2.7-4.4) and median OS 7.6 (5.7-13.2) months. Grade ≥ 3 hematological AE during cycles 1 to 4 included: leucopenia (3.3%), neutropenia/febrile neutropenia (53.3%/6.7%), anemia (30.0%), and thrombocytopenia (35%). Grade ≥ 3 non-hematological AE were nausea (5%), vomiting (5%), renal failure (0%), paresthesia (0%) and infection (6.6%). Two death-related sepsis was observed, but no opportunistic infections. Conclusions: Four cycles of CaP induction, followed by P maintenance, were effective and reasonably well-tolerated in first-line therapy of HIV-infected patients with NE-NSCLC. Clinical trial information: NCT01296113.
Copy number variants signature in two patients with relapsed acute promyelocytic leukemia.
Authors: Jacopo Nanni, Giovanni Marconi, Maria Chiara Fontana, Cristina Papayannidis, Silvia Lo Monaco, Carmen Baldazzi, Antonella Padella, Giorgia Simonetti, Andrea Ghelli Luserna di Rorà, Valentina Robustelli, Nicoletta Testoni, Maria Chiara Abbenante, Stefania Paolini, Eugenia Franchini, Emanuela Ottaviani, Giovanni Martinelli, Luca Bertamini
Journal: Journal of Clinical Oncology (2017)

e23207 Background: Nowadays, Acute Promyelocytic Leukemia (APL) is a disease entity with a very high rate of cure and an estimated 2-year overall survival of 97%. Early death, rather than resistant disease so common in all other subtypes of AML, has emerged as the major cause of treatment failure, and relapse is a very rare occurrence. Methods : We collected data of all the APL referred to our institution from 2014. Within 23 patients, we encountered 20 new diagnosis and 2 relapse of APL. We analyzed blasts in samples obtained from Bone Marrow with Single Nucleotide Polymorphisms Array Cytoscan HD. Results: We compared copy number alterations in both relapsed patients with alterations detected in the pool of 20 newly diagnosed APL and we found specific signatures of CNVs for each patient. There were several copy number alterations related to each patient: the first patient presented gain of ROBO2, GRIP1, CTNNB1, SOX6, PBX1, GRIK2, CDKAL1 and loss FAF1, CREBBP, SBF1; the second patient presented gain of ROBO1, MAPK10, CADPS2, APBA1 and loss of GRIP1 and MYB. Subsequently we focused our attention on ROBO and GRIP1genes because they were alterated in both relapsed patients: ROBO proteins are associated to K channels while GRIP1 is involved in various critical functions, for example in androgen receptor binding, beta-catenin binding, glucocorticoid receptor binding, and it is also a regulator of glutamate metabolism, a well-known pathway in Leukemic Stem Cells. Conclusions: APL relapse is a very rare entity, and it is announced to become rarer with the advances in first line therapy. Molecular characteristics are hard to analyze without an effort to collect and bank samples together from multiple institutions. Since relapses, especially relapses out of follow-up period, represent a sudden life-treating condition for patients, to predict patients at higher risk of relapse we selected two candidate genes that could be involved in pathways favoring relapse. By the analysis of ROBO 1-2 and GRIP1 at the diagnosis of APL we could establish a different and strict follow-up program for patients with these alterations. Acknowledgement: ELN,AIL,AIRC,prog. Regione-Università 2010-12 (L. Bolondi), FP7 NGS-PTL project,HARMONY.
Emergency department presentation with colorectal cancer.
Authors: Yasmin A. Zerhouni, Nelya Melnitchouk, Eric Schneider, Aparajita Singh
Journal: Journal of Clinical Oncology (2017)

e15094 Background: Despite screening protocols shown to reduce mortality, colorectal cancer (CRC) remains the 2nd leading cause of cancer death in the US. CRC patients who have emergent surgery have worse outcomes than those treated electively. We examined presentation and index hospital outcomes for emergency department (ED) patients with a primary diagnosis of CRC. Methods: The 2013 Healthcare Cost and Utilization Project Nationwide Emergency Department Sample was queried and all patients with a primary ICD-9-CM diagnosis of CRC were identified. Descriptive analyses were weighted to the level of the US population. Results: Among 134,869,015 ED visits, approximately 44,717 patients received a primary diagnosis of CRC. Patients with CRC were older (68 vs. 40 years, p &lt; 0.001) and more likely to be male (50.4% vs. 44.3%, p &lt; 0.001) than those presenting for other reasons. Among CRC patients, 88.6% were older than 50 years with males younger than females (66 vs. 70y, p &lt; 0.001) and 90.4% were insured. 88.6% were admitted of whom 44% underwent oncologic resection. Females were more likely to undergo resection (47% vs.42%, p = &lt; 0.001) and to be older at time of surgery (71 vs. 68, p = &lt; 0.001). Average length of stay was 12.5 days for surgical vs. 6.6 days for non-surgical patients (p &lt; 0.001). After admission, 68.0% of those admitted vs. 64.7% of patients who had surgery were discharged home. 6.9% of admitted CRC patients and 4.7% of surgical patients died in-hospital. Average total charges were $124,846 for patients undergoing resection vs. $53,542 for inpatients who did not undergo surgery (p &lt; 0.001). Conclusions: Most patients presenting to the ED for CRC are admitted and many require surgical intervention. Because nearly 90% were 50 or older and insured, further research is warranted to determine if increased screening among eligible patients might reduce the numbers of ED presentations and emergent surgical procedures for CRC.
Clinicopathogenomic analysis of mismatch repair proficient colorectal adenocarcinoma to uncover novel prognostic subgroups with differing patterns of genetic evolution.
Authors: David R. Braxton, Ray Zhang, Jennifer J. Morrissette, Arturo Loaiza-Bonilla, Emma E. Furth
Journal: Journal of Clinical Oncology (2016)

e15043 Background: Cancer somatic genetic evolution is a direct contributor to heterogeneity at the clonal and molecular level in colorectal adenocarcinoma (COAD). We sought to examine genetic evolution in COAD and establish clinical significance with regard to clinicopathologic and outcome data. Methods: A retrospective specimen based study design was employed. 123 cases of routinely collected mismatch repair proficient COAD were sequenced on the illumina truseq amplicon assay (47 gene panel). Measures of intratumoral heterogeneity (subclonal populations, allelic imbalances) were assessed and the preferential timing of mutational events was estimated and correlated to clinicopathologic data (Chi-squared analysis). Hierarchical clustering was performed with variables reaching statistical significance. A progression free survival (PFS) subanalysis was performed on 55 patient status post colectomy using the Kaplan-Meier survival analysis, logrank test, and cox-multivariate models. PFS was defined by radiological methods. Results: Patient age (p = 0.013) and specimen percent tumor (p = 0.033) were associated with subclonal populations, and biopsy (p = 0.044) and metastasis (p = 0.044) returned fewer mutations per case. APC and TP53 mutations preferentially occurred early while alterations in FBXW7, FLT3, SMAD4, GNAS, and PTEN preferentially occurred as late events. Temporal heterogeneity was evident in KRAS and PIK3CA mutations. Hierarchical clustering revealed a TP53 mutant subtype and a MAPK-PIK3CA subtype with differing patterns of late mutational events. Survival subanalysis showed a decreased median progression free survival for the MAPK-PIK3CA subtype (8 months vs. 13 months; univariate logrank p = 0.0380, cox model p = 0.018). Neoadjuvant therapy associated mutations were found for ERBB2 (p = 0.0481) and FBXW7 (p = 0.015). Conclusions: Our data indicate novel molecular subtypes of mismatch repair proficient COAD display differing patterns of genetic evolution which correlate with clinical outcomes. Furthermore, we report treatment acquired and/or selected mutations in ERRB2 and FBXW7.
Estrogen receptor (ER), progesterone receptor (PR) and Her2neu receptor expresssion: Change from baseline to first metastasis in breast cancer—Single center experience from developing country.
Authors: Manish Sharma, Ajay Gogia, S V Suryanarayana Deo, Nootan Kumar Shukla, Dayanand Sharma, Sanjay Thulkar, Rakesh Kumar, Prabhat Singh Malik, Sushma Bhatnagar, Sandeep Mathur
Journal: Journal of Clinical Oncology (2018)

e13095 Background: Biomarker status change have been documented in various studies. However, data from developing countries are sparse. This study is performed to document biomarker discordance, site of metastasis and progression free survival of metastatic breast cancer patients. Methods: We performed an ambispective review of paired hormone receptor [estrogen receptor(ER)/progesterone receptor (PR)] and human epidermal growth factor receptor (HER/2neu) status. We included total 97 patients. Biomarker status documented at baseline and at first metastasis, which is confirmed by two pathologists. Clinical and radiological parameter documented at baseline and at subsequent follow up. Results: In the cohort of 97 patients, we observed that discrepancy was present in 23 (23.7%) in ER, 28 (28.9%) in PR and 13 (14.7 %) in HER2/neu receptor status. 11 (11.3%) had positive to negative and 12 (12.4%) had negative to positive ER. 19 (19.6%) had positive to negative and 9 (9.2%) had negative to positive PR. 7 (7.2) had positive to negative and 6 (6.2%) had negative to positive HER2/neu receptor status. In our cohort, 36 (37.2%) had single site metastasis [14 (14.4%) bone, 11 (11.3%) lung, 6 (6.2%) liver and 5 (5.2%)non-regional lymph node metastasis] and 61 (62.8%) patients had more than one site of metastasis. Most common site of metastasis was bone, followed by lung,non-regional lymphnode, liver, skin and brain. Median progression free survival of whole cohort was 26 (IQR 16-47) months. It was 47 (IQR 27-82) months in ER/PR positive, 28 (IQR 25-48) months in ER/PR/HER2/neu positive, 19 (IQR 13-30) months in only HER2/neu receptor positive and 14 (IQR 11-19) months in triple negative breast cancer patients. Conclusions: This study demonstrated that continued metastatic disease evolution in breast cancer may be associated with different tumor biology which leads to change in hormone receptor status. Repeat biomarker studies of metastatic lesions appear warranted, for prognosis and especially if patient planned for targeted therapy.