tbuckley/cabot-search huggingface dataset:
Comparing diagnosis, management, and outcomes of synchronous versus metacrhonus brain metastases from testicular germ cell tumors (TGCT): Multinstitutional experience from the Spanish Germ Cell Cancer Group (SGCCG).
Authors: Jorge Aparicio, Regina Girones, Pere Roure, Jose R. Germa-Lluch, Sergio Vazquez-Estevez, Alberto Saenz, Javier Sastre, Jose Angel Arranz Arija, Enrique Gallardo, Enrique Gonzalez-Billalabeitia, Alfredo Sanchez-Hernandez, Josefa Terrasa, Ana Hernandez, Carmen Santander, Elena Cillan, Naira Sagastibelza, Daniel Almenar-Cubells, Marta Lopez Brea, José Pablo Maroto
Journal: Journal of Clinical Oncology (2013)

4560 Background: Metastases of testicular germ cell tumors (TGCT) to brain are a rare event. Prognostic is poor and there is little evidence on optimal management of these patients. Methods: A retrospective review of case records of germ cell tumor patients within the Spanish Germ Cell Cancer Group from 1994 to 2012 was conducted. Results: Thirty-tree cases of testicular germ cell tumors from 17 institutions were reported. Nineteen patients (57%) presented with brain metastases at primary diagnosis (group 1: synchronous), thirteen (40%) developed brain metastases at relapse (group 2: metachronous) and only one patient developed brain metastasis during cisplatin based-chemotherapy (3%) (excluded from the analysis). Main demographics and comparison between series are shown on table. Median serum BHCG levels at initial diagnosis were higher in group 1(279.083 versus 175.873), whereas those of AFP were higher in group 2(1320 versus 4181). The most common histology in the primary tumor was choriocarcinoma for group; versus embryonal carcinoma for group 2. Patients had neurological symptoms at diagnosis of brain metastases (63% synchronic/93% metachronus). Performance status was also poor (PS 2-3: 52,6%group 1-62,2% group 2). Four patients (21%) in group 1 had a solitary brain lesion vs seven (54%) on group 2. Median time since last dose of cisplatin to development of brain metastases on group 2 was 6 months (3-22).Median overall survival was 16 months (95% CI 5,3-26,6): group 1: 16 (95% CI 13,9-18);23 group 2 (95% CI 0-165). We have not found significant differences in survival between both groups. Overall 37,5% of patients achieved long-term survival (38,9% in group 1 versus 38,5% in group 2). Patients achieving complete response of brain metastases had a better survival (log rank p:0,003). Conclusions: Long term survival can be achieved in approximately 1/3 of patients with brain metastases. Chemotherapy remains the cornerstone of treatment. Selection bias because of the retrospective nature of review should make us be careful with the conclusions.
Influence of tumor response and treatment schedule on the distribution of tumor recurrence in esophageal cancer patients treated with neoadjuvant chemoradiotherapy.
Authors: Kristien M. Jipping, Jan-Binne Hulshoff, Evita A. van Amerongen, Tim I. Bright, David I. Watson, John Theodorus Plukker
Journal: Journal of Clinical Oncology (2017)

113 Background: Knowledge of pathologic complete tumor response (pCR) and the used neoadjuvant chemoradiotherapy (nCRT) schedule on the distribution of recurrent disease is important in the treatment of esophageal cancer (EC) patients. We assessed the effect of both pCR and different nCRT schedules on the pattern of first tumor recurrences in EC. Methods: The study was performed in two different centers in patients with T1N+/T2-4aN0-3/M0 EC. Patients were treated with nCRT according to the CROSS (carboplatin/paclitaxel/41.4Gy : n=134) and Cis/5FU schedule (Cisplatin/5-fluorouracil/45-50.4Gy : n=88) followed by surgery. First we determined the effect of pCR on tumor recurrence distribution (local, distant or combined) and site-specific recurrences in the CROSS group. After propensity matching on clinical T-stage, clinical N-stage and histology (n=63), we determined the effect of both nCRT schedules on the distribution of tumor recurrence and site specific recurrences. Results: The median follow-up after pCR (n=24) was significant longer ( P=0.001) than in non-complete responders (pNCR); 45.5 (IQR 20.3-69.5) and 20.0 months (12.0-42.3), respectively. The pattern of recurrence also differed significantly ( P=0.001), with 0 (0.0%) and 7 (6.4%) locoregional, 5 (20.8%) and 36 (32.7%) distant, and 0 (0.0%) and 21 (19.1%) local and distant recurrence between the pCR and pNCR group, respectively. Patients with a pCR had significant less local and distant recurrences. With equal median time to recurrence, the distribution of metastases in the matched groups differed only in the numbers of lung metastases ( P=0.029), with 15 (23.8%) and 6 (9.5%), respectively. Conclusions: Patients with a pCR have less local and distant recurrences. With equal time to first recurrence, the nCRT schedule itself had only a minor influence on the distribution of recurrences.
Post-treatment alterations in 18F-dihydrotestosterone (FDHT) and FDG PET/CT in metastatic castration-resistant prostate cancer (mCRPC) treated with cabozantinib.
Authors: Josef J. Fox, Eric C. Haupt, John Humm, Karen A. Autio, Dana E. Rathkopf, Hebert Alberto Vargas, Heiko Schöder, Hedvig Hricak, Steven M. Larson, Howard I. Scher, Michael J. Morris
Journal: Journal of Clinical Oncology (2013)

5073 Background: Cabo is a multitargeted kinase inhibitor that has demonstrated complete and partial responses in mCRPC as assessed byTc-99 MDP bone scintigraphy. FDG and FDHT PET/CT demonstrate glucose metabolism and androgen receptor binding, respectively. We are exploring these tracers as response biomarkers in mCRPC treated with cabo. Methods: Patients (pts) treated with cabo were scanned with FDHT and FDG PET at baseline and after 6, 12, and 24 weeks (wks) of treatment. 5 index lesions were selected at baseline for each PET modality. The hottest slices from each were averaged (SUVmaxavg) and measured on post-treatment scans. The concordance of the post-treatment alterations of the two tracers (rise vs. decline) was examined, as were PSA alterations. Results: All 16 pts had FDG avid and 15 had FDHT avid disease. Baseline median FDHTmaxavg was 10.84 (3.52 – 18.52) and FDGmaxavg was 6.26 (2.74 – 14.7). Post-treatment alterations are described (Table). Conclusions: Most pts with mCRPC demonstrate diminution of FDHT uptake after 6 and 12 wks of treatment with cabo. These declines are matched by FDG 50-60% of the time, and correlate with PSA declines even less frequently. The etiology of the extent and degree of FDHT declines, and lack of concordance with post-treatment PSA changes, warrant further investigation, and correlation with other imaging modalities and clinical outcomes. Clinical trial information: NCT00588185. [Table: see text]
The IFN-λ-IFN-λR1-IL-10Rβ Complex Reveals Structural Features Underlying Type III IFN Functional Plasticity
Authors: Juan L. Mendoza, William M. Schneider, Hans-Heinrich Hoffmann, Koen Vercauteren, Kevin M. Jude, Anming Xiong, Ignacio Moraga, Tim M. Horton, Jeffrey S. Glenn, Ype P. de Jong, Charles M. Rice, K. Christopher Garcia
Journal: Immunity (2017)
Impact of primary tumor stage on survival following resection of metachronous liver and/or lung metastases in colorectal cancer.
Authors: Hui-Li Wong, Vishal Boolell, Suzanne Kosmider, Kathryn Maree Field, Rachel Wong, Jeremy David Shapiro, Prasad Cooray, Ian Hayes, Ian Faragher, Malcolm Steel, Peter Gibbs
Journal: Journal of Clinical Oncology (2015)

3557 Background: Resection of isolated liver and/or lung metastases in patients (pts) with metastatic colorectal cancer (mCRC) offers a chance at long-term survival. Multiple prognostic models have been developed to predict outcomes following resection, but the role of primary tumor stage remains controversial, contributing to a recent debate regarding the impact of stage on the value of routine pt follow-up. Methods: Consecutive pts with resected liver and/or lung metastases following prior therapy for an early stage CRC entered into a comprehensive, prospective database between 2000 and 2014 were identified. Cox regression analysis was performed to examine the impact of initial tumor stage on overall survival. Results: 867 pts with metachronous mCRC were identified; median follow-up was 40.1 months. 215 (25%) had undergone liver and/or lung resection, including 21 with initial stage I CRC, 53 with stage II colon cancer (CC), 70 with stage III CC and 71 with locally advanced rectal cancer (LARC). 5-year overall survival (OS) declined with increasing stage: 100% in stage I, 75% in stage II, 35% in stage III and 52% in LARC (P < 0.001). On multivariate analysis, initial stage was predictive of OS, where best outcomes were seen in pts with stage I or II disease (Table). Conclusions: Pts with a previous stage I primary cancer contribute only a small proportion of those undergoing resection of metachronous disease but have excellent outcomes, suggesting routine follow-up of stage I pts is worthwhile. With increasing primary tumor stage, survival outcomes deteriorate. However, the majority of 5-year survivors are pts with high-risk primaries, justifying follow-up in this pt group. Better markers of recurrence risk and of benefit from metastasectomy would be beneficial. Hazard ratio 95% CI P Primary stage Stage III (Ref) LARC Stage II Stage I - 0.69 0.29 N/A* 0.38-1.25 0.13-0.66 0.218 0.003 Age (years) < 65 (Ref) ≥ 65 - 0.98 0.56-1.70 0.930 Disease-free interval (months) < 12 (Ref) ≥ 12 - 0.57 0.32-1.04 0.069 Metastatic sites Liver (Ref) Lung Liver and lung - 0.97 2.03 0.55-1.73 0.45-9.19 0.924 0.360 No. of lesions 1 (Ref) ≥ 2 - 1.28 0.71-2.29 0.407 Resection margin R0 (Ref) R1/2 - 1.25 0.43-3.60 0.683 *No events
Smoking habits of relatives of patients (pts) with cancer.
Authors: Mutlu Hayran, Saadettin Kilickap, Tamer Elkiran, Hakan Akbulut, Huseyin Abali, Deniz Yuce, Diclehan Kilic, Serdar Turhal
Journal: Journal of Clinical Oncology (2012)

9050 Background: We aimed to determine the rate and habitual patterns of smoking, intentions of cessation, dependence levels and sociodemographic characteristics of relatives of cancer patients. Methods: The smoking habits of relatives of cancer pts were evaluated with a questionnaire and Fagerstrom test (FT) of nicotine dependence. FT and a questionnaire form were filled in by the volunteers. The quit rate of the relatives of the cancer pts was compared with the rates declared in the literature. Results: A total of 560 subjects who have relatives of pts with cancer. The median age of those with lower and higher Fagerstrom scores (FS) were 40 years and 42 years, respectively (p&lt;0.001). We found no association between FS and sociodemographic variables, such as the subject's medical status, gender, living in the same house, educational status, family income, closeness and time spent with the cancer pts. Only 2% of the subjects started smoking after cancer was diagnosed in their relative and almost 20% of subjects had quit smoking within the year. Spontaneous quit rates of these subgroup of smokers (20%) was significantly higher than reported self-quit rates (max. ~10%) in the literature (p&lt;0.001). Conclusions: The FS is known to be helpful in determining who would benefit from a cigarette smoking cessation program. We also show here that the cancer diagnosis in a smoker's family motivates this individual to quit smoking and may create a time window for any involved health staff to intervene for help. This study was designed by the Turkish Oncology Group, Epidemiology and Prevention Subgroup. [Table: see text]
Frequent discussion of insomnia and weight gain with glucocorticoid therapy: an analysis of Twitter posts
Authors: Rikesh Patel, Maksim Belousov, Meghna Jani, Nabarun Dasgupta, Carly Winokur, Goran Nenadic, William G. Dixon
Journal: npj Digital Medicine (2017)

In recent years, social media websites have been suggested as a novel, vast source of data which may be useful for deriving drug safety information. Despite this, there are few published reports of drug safety profiles derived in this way. The aims of this study were to detect and quantify glucocorticoid-related adverse events using a computerised system for automated detection of suspected adverse drug reactions (ADR) from narrative text in Twitter, and to compare the frequency of specific ADR mentions within Twitter to the frequency and patterns of spontaneous ADR reporting to a national drug regulatory body. Of 159,297 tweets mentioning either prednisolone or prednisone between 1st October 2012 and 30th June 2015, 20,206 tweets were deemed to contain information resembling an ADR. The top AE MedDRA® Preferred Terms were 'insomnia' and 'weight increased', both recognised non-serious but common side effects. These were proportionally over-reported in Twitter when compared to spontaneous reports in the UK regulator's ADR reporting scheme. Serious glucocorticoid related AEs were reported less frequently. Pharmacovigilance using Twitter data has the potential to be a valuable, supplementary source of drug safety information. In particular, it can illustrate which drug side effects patients discuss most commonly, potentially because of important impacts on quality of life. This information could help clinicians to inform patients about frequent and relevant non-serious side effects as well as more serious side effects.
Temsirolimus and intensive re-induction chemotherapy for 2nd or greater relapse of acute lymphoblastic leukemia (ALL): A Children’s Oncology Group study.
Authors: Susan R. Rheingold, James Whitlock, Sarah K. Tasian, David T. Teachey, Michael J. Borowitz, Xiaowei Liu, Charlotte H. Ahern, Charles Minard, Elizabeth Fox, Brenda Weigel, Susan Blaney
Journal: Journal of Clinical Oncology (2015)

10029 Background: PI3K/mTOR signaling, a critical pathway in cell proliferation, metabolism, and apoptosis, is commonly dysregulated in ALL. A phase 1 trial of the mTOR inhibitor temsirolimus in combination with re-induction chemotherapy was performed in children with second or greater relapse of ALL. Methods: Temsirolimus was administered with 4-drug chemotherapy (UK R3 ALL re-induction; Parker, Lancet 2010). The starting dose level (DL1) of intravenous temsirolimus was 10mg/m2 weekly x3 ; subsequent cohorts received temsirolimus 7.5mg/m2 weekly x3 (DL0); or 7.5mg/m2weekly x2 (DL-1). PI3K pathway inhibition was measured by phosphoflow analysis (PFA) of peripheral blood. Results: Sixteen patients, age 1-21, [15 pre B-ALL (3 MLL infants, 2 Ph+); 1 T-ALL] were enrolled, 15 were evaluable. Dose-limiting toxicity (DLT) occurred in 2/5 patients at DL1; 3/6 at DL0 and 3/5 at DL-1. DLTs were hypertriglyceridemia, mucositis, gastric ulcer, hypertension with reversible posterior leukoencephalopathy, elevated GGT and alk phos, and severe infections including 1 death due to sepsis. Seven patients had a complete response, 3/7 had MRD < 0.01% at end therapy. Responses occurred at all dose levels of temsirolimus. Phospho(p)S6 and/or p4EBP1 were inhibited in a subset of patients with compensatory upregulation of pPI3K, pmTOR, and pAkt. High basal PI3K pathway signaling was observed in patients with poorer response to therapy. Conclusions: Temsirolimus in combination with UK R3 chemotherapy can induce responses in children with ALL; however, this intensive regimen is associated with unacceptable toxicity. A trial evaluating temsirolimus in combination with etoposide/cyclophosphamide in children with relapsed ALL is ongoing. Clinical trial information: NCT01403415. Dose Level ID Response DLT 10mg/m2 x 3 1 MLL PD 7.5mg/m2 x 3 2 N/A 3 MLL PD HTN, Mucositis, GGT 4 CRp 5 PD HyperTG 6 CR 7.5mg/m2 x 2 7 PD 8 died Sepsis, Mucositis, RPLE 9 PD Ulcer 10 CRp 11 T-ALL PD GGT 12 Ph+ CR 13 MLL PD 14 Ph+ CRp GGT, Anorexia, Alk phos 15 CR Hyper TG 16 CR HyperTG
Establishing a neoadjuvant platform for developing targeted agents: Degarelix prior to prostatectomy for patients with intermediate- and high-risk prostate cancer.
Authors: Karim A. Touijer, Yingbei Chen, Brett Stewart Carver, Jonathan A. Coleman, Vincent Paul Laudone, Melanie Hullings, Samantha Spenser Ehrlich, Mia DeNunzio, Victor E. Reuter, James Andrew Eastham, Daniel Costin Danila, Susan F. Slovin, Michael J. Morris, Yu Chen, Peter T. Scardino, Howard I. Scher, Dana E. Rathkopf
Journal: Journal of Clinical Oncology (2014)

TPS5105 Background: We hypothesize that the unmet drug development needs in prostate cancer can be addressed using a standardized short exposure neoadjuvant clinical trial framework that ensures tumor tissue is available for profiling, the biomarker assays used are validated, and that trials are designed to address specific questions. This ongoing pilot study explores the response to short exposure androgen deprivation therapy (ADT) with degarelix prior to prostatectomy. The aims of the trial are to assess: (1) two time intervals to determine the maximal change in PC proliferation (Ki-67) and apoptosis rates (caspase-3) following ADT; (2) the association between PTEN status and maximal changes in proliferation and apoptosis rates in patients treated with ADT; and (3) the association between PI3K pathway (pAKT and pS6) and proliferation and apoptosis rates after treatment with ADT in relation to other markers of PC (ERG, AR and NCOA2). Methods: Thirty intermediate and high risk patients planning to undergo prostatectomy will be accrued. Two or more cores of the diagnostic biopsy must involve at least 3 mm of tissue with adenocarcinoma. Patients are randomized to receive degarelix (240 mg SC) either 4 or 7 days prior to radical prostatectomy based on the proliferation and apoptotic indexes in malignant human prostate biopsies taken 1-10 days after surgical castration which have demonstrated that maximal changes occur by day 7. (Ohlson, N., et al. Prostate 2005) Patients undergo open, laparoscopic, or robotic radical prostatectomy and are followed 6 weeks post-operatively. The first 20 patients have been successfully treated. Supported by funds from NCI P50-CA92629 SPORE in Prostate Cancer and PCF. Drug supplied by Ferring Pharmaceuticals. Clinical trial information: NCT01542021.
Potentially actionable kinase fusions in inflammatory myofibroblastic tumors.
Authors: Christine Marie Lovly, Doron Lipson, Geoff Otto, Tina Brennan, Sabita Sankar, Philip J. Stephens, Vincent A. Miller, Cheryl M. Coffin
Journal: Journal of Clinical Oncology (2013)

10513 Background: Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal neoplasm that harbors anaplastic lymphoma kinase (ALK) gene rearrangements in approximately 50% of cases. ALK inhibitors have been validated as an effective therapeutic approach in this subset of IMTs. The goal of this study was to characterize a series of IMTs using both immunohistochemistry (IHC) and next generation sequencing (NGS). Methods: 30 formalin-fixed, paraffin-embedded IMT specimens from 28 patients were evaluated by IHC for ALK expression using standard techniques. DNA was extracted and sequenced using a targeted capture-based NGS assay for 3769 exons of 236 cancer-related genes and 47 introns of 19 commonly rearranged genes, including 8 tyrosine kinases in a CLIA laboratory (Foundation Medicine). Selected specimens were also evaluated for ALK fusions by fluorescence in-situ hybridization (FISH). Results: 20 samples were ALK positive and 10 samples were ALK negative by IHC. Targeted NGS was successfully performed in 16/20 ALK positive and 10/10 ALK negative cases. Among the 16 ALK positive cases analyzed by NGS, 12 harbored ALK fusions with various 5’ gene fusion partners, including LMNA, TPM3, TPM4, SEC31A, TFG, RANBP2, and CLTC. The remaining 4 were also negative by FISH suggesting a different mechanism of ALK overexpression. Among the 10 ALK negative cases, 2 harbored ALK fusions (EML4-ALK, TPM3-ALK). In the other 8 ALK negative samples, 2 contained distinct ROS1 fusions (YWHAE-ROS1, TFG-ROS1) and 1 contained a PDGFRβ fusion (NAB2-PDGFRβ), none of which have been described in IMT samples to date. Overall, kinase gene fusions were identified in 18/26 (69%) evaluable samples. Conclusions: This study represents the most comprehensive NGS analysis of IMTs. 12/12(100%) ALK IHC and FISH positive cases contained ALK fusions, while 5/8 (63%) of distinct ALK IHC negative cases harbored kinase fusions, involving ALK, ROS1, or PDGFRβ. Since these fusions are all targetable with existing kinase inhibitors (i.e. crizotinib, dasatinib), this study suggests that IMTs should be routinely profiled for kinase fusions and not just by ALK IHC. Efforts are ongoing to identify “driver mutations” in the fusion-negative specimens.
Does <i>EGFR</i> mutation define the histological predominant subtype of lung adenocarcinoma?
Authors: Eri Sugiyama, Koichi Goto, Genichiro Ishii, Tomohiro Haruki, Shingo Matsumoto, Shigeki Umemura, Kiyotaka Yoh, Seiji Niho, Hironobu Ohmatsu, Kanji Nagai, Yuichiro Ohe
Journal: Journal of Clinical Oncology (2013)

7557 Background: In 2011, invasive adenocarcinomas were newly classified into the five predominant subtypes by IASLC/ATS/ERS: lepidic, papillary, acinar, micropapillary, and solid. The purpose of this study is to investigate the correlation between EGFRmutation and the histological predominant subtype of lung adenocarcinoma. Methods: Among a total of 1,736 patients with lung adenocarcinoma who underwent surgical resection from 2002 to 2011 in National Cancer Center Hospital East, 1,507 were classified into invasive adenocarcinoma. 526 of whom were examined EGFR mutation status. Histological predominant subtypes were evaluated at the maximum cut surface of tumors. The EGFR mutation analysis was performed by PCR-invader method. Treatment efficacy of EGFR-tyrosine kinase inhibitors (TKIs) in 73 relapsed patients with EGFRmajor mutations were also examined. Results: 526 adenocarcinomas were consisted of 95 lepidic (18%), 221 papillary (42%), 80 acinar (15%), 9 micropapillary (2%), and 121 solid predominant subtype (23%). EGFR mutations were detected in 227 adenocarcinomas (43%), and its frequency in the solid subtype (22%) was significantly less than that of other histological subtypes (lepidic 47%, papillary 53%, and acinar 44%; P &lt; 0.01). The proportion of minor mutations, other than exon 21 L858R and exon 19 deletions, were significantly higher in the solid subtype (22%) than that of the others (lepidic 4%, and papillary 12%; P &lt; 0.01). In 73 patients with EGFR major mutations treated by EGFR-TKIs, the response rate was not different between histological subtypes (lepidic 86%, papillary 76%, acinar 89%, and solid 60%). Conclusions: The correlation between histological predominant subtypes of lung adenocarcinoma and the presence of EGFR mutations or the efficacy of EGFR-TKI were not identified in this study. Little is known about the reason why EGFR minor mutations were highly detected in the solid subtype of adenocarcinoma, however it is possibly due to the high frequency of heavy smokers in solid subtype (heavy smoker: solid 67% vs. others 27-44%).