tbuckley/cabot-search huggingface dataset:
Final results of hepatic arterial infusion (HAI) plus systemic (SYS) chemotherapy after multiple metastasectomy in patients with colorectal carcinoma metastatic (M-CRC) to the liver: A North Central Cancer Treatment Group (NCCTG) phase II study
Authors: J. S. Bolton, M. J. O'Connell, M. R. Mahoney, D. M. Nagorney, J. A. Mailliard, D. J. Sargent, S. R. Alberts
Journal: Journal of Clinical Oncology (2004)

3527 Background: Patients with multiple liver metastases are at high risk of recurrence after resection. We assessed whether aggressive multimodality treatment improves 5-year survival (S) from 10% to above 30%. This report provides final results for a prior interim report (Bolton, ASCO 2001, #509). Methods: Patients with M-CRC lesions amenable to resection/cryoablation were eligible. All patients had unfavorable characteristics (>1 bilobar mets +/or >4 mets or satellite lesions). Prior adjuvant chemotherapy for a completely resected primary was allowed. Alternating courses of HAI and SYS included floxuridine (FUDR) via HAI at 0.2 mg/kg, d1–14, on wks 0–2, 5–7, 10–12, and 15–17. SYS chemotherapy consisted of bolus leucovorin 20 mg/m2, plus 5-fluorouracil (5FU) 425 mg/m2, d1–5, on wks 3, 8, 13, and 18. Patients: 49 were completely resected; 44% had >4 hepatic metatases; 78% had bilobar disease; 12% had cryoablation; 36 initiated HAI+SYS. Outcome: Patients received a median of 6 cycles (range 1–8) of HAI/SYS. Median follow-up on treated survivors is 6.2 yrs (range 5.2–9.4). 25 of 36 (78%) receiving HAI+SYS have recurred, with initial site(s) of recurrence as liver only (9), extrahepatic only (10), both (9). Survival (S) and freedom from hepatic recurrence (FHR) rates appear below. Conclusions: This trial of adjuvant chemotherapy in completely resected patients with unfavorable characteristics demonstrates promising 5-yr S [31% (95% CI 19–50%)]. This regimen is an effective option for treatment and should be used as a basis for developing improved treatment regimens in this population. Supported by NIH Grant CA25224. Estimated Kaplan-Meier Rates. No significant financial relationships to disclose.
Risk prediction-modeling approach to identify best predictive parameters for urethral strictures after prostate brachytherapy.
Authors: Sandeep Singhal, Matthew Parliament, Muhammad Faisal Jamaluddin, Emma Lee, Ron Sloboda, Nawaid Usmani
Journal: Journal of Clinical Oncology (2017)

87 Background: Urethral strictures (US) are a rare complication of prostate brachytherapy (BXT), with prior studies showing radiation dose to the bulbomembranous urethra is associated with stricture formation. This retrospective case-control study explored clinical and dosimetric parameters associated with the development of BXT-related urethral strictures. Methods: A cohort of 34 patients developed urethral strictures after BXT at our institution for the period of 2008-2014. Each case was matched with two controls (68 controls) that had not developed a US according to similar baseline International Prostate Symptom Score (IPSS), planned prostate volume, post-implant prostate V150, and post-implant prostate D90 dosimetry parameters. US development was compared with clinical (i.e. age, IPSS, etc) and dosimetric (i.e. prostate, urethra, urethra segments) variables. Statistical modeling for risk prediction was applied, which included adjusted R 2 , Mallows’ C Selection (Cp), Schwartz’s information criterion (BIC), forward selection (FS), and backward selection (BS) to identify the parameters with prediction ability of toxicity. CV analysis was performed to select the best subset selection on the full data set in order to obtain the most predictive parameter selection. Results: The results show that the R 2 statistic increases from 6% (only one) to 33 %, (all of the parameters included). The table demonstrates minimum best-fit parameters in the different models. (See table.) CV with minimum standard error (MSE) identified a model with 5 parameters that included age, baseline IPSS, UD30, UD5, and U5mm V200Apex shows best prediction ability for US. Conclusions: This modeling approach, which is novel in BXT, helped to identify a combination of parameters with some predictive ability of radiation toxicity. Further evaluation is required to validation. [Table: see text]
High-throughput exome array for identification of novel polymorphisms associated with clinical outcome in mCRC patients treated with first-line FOLFOXIRI/BEV versus FOLFIRI/BEV (TRIBE trial; NCT00719797).
Authors: Wu Zhang, Fredrick Schumacher, Fotios Loupakis, David van Den Berg, Chiara Cremolini, Sebastian Stintzing, Yan Ning, Ana Sebio, Stefan Stremitzer, Yu Sunakawa, Satoshi Matsusaka, Shinichi Yamauchi, Rita Elkhoueiry, Alfredo Falcone, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2014)

3632 Background: TRIBE is a phase III randomized trial comparing FOLFOXIRI/ Bev vs FOLFIRI/Bev as first-line treatment for metastatic colorectal cancer. In this post genomic area, whole exome sequence is emerging as an useful tool to identify novel snps to associated with clinical outcome. Here we tested the hypothesis that whole exome sequence may identifies snps to predict clinical outcome in mCRC patients enrolled in TRIBE study. Methods: Genomic DNA was extracted from peripheral blood of 503 pts. Arm A(FOLFIRI/BEV)(n=253); Arm B (FOLFOXIRI/BEV)(n=250), median age 60 years(29-75), Females(n=202) and males(n=301);Median follow up is 32.3 months. The Illumina HumanExome array with custom content was genotyped on 432 pts on Illumina HiSeq plateform. After applying genotyping quality control filters, 385 individuals and 241,812 single nucleotide polymorphisms (SNPs) remained in the analysis. Arm A included 163 pts with a mean age of 59.9 years (SD=9.14) and mean OS of 22.9 months while Arm B included 222 pts with mean age of 59.9 years and mean OS of 23.3 months. A Cox proportional hazard regression analysis was implemented to assess SNP associations with RR,PFS and OS after adjusting for sex, treatment arm, age at trial entry, number of metastases, ECOG, and mutation status for KRAS and BRAF. GenABEL was used for the statistical analysis. Results: Although our main effect analysis did not identify a genome-wide association (P<5x10-8), our preliminary analysis did observe several promising associations between SNPs and OS. Our top association, rs10008360 on chromosome 4(VEGFR-2), with hazard ratio (HR) of 6.49 (P=2.84x10-6). We observed four additional markers associated with OS (P<1.0x10-4). Rare burden testing and pathway analyses are underway to determine additional biological candidates. Updated detailed analysis including response and PFS results will be presented at meeting. Conclusions: This is the first study identifies novel snps may predict which patient could benefit from bevacizumab-based therapy. These preliminary data warrants further validation clinical trials.
S-1 monotherapy or in combination with leucovorin as second-line treatment in gemcitabine-refractory advanced pancreatic cancer: A phase II study.
Authors: Feijiao Ge, Nong Xu, Yuxian Bai, Yi Ba, Yanqiao Zhang, Fei Li, Huayan Xu, Ru Jia, Yan Wang, Li Lin, Jian-Ming Xu
Journal: Journal of Clinical Oncology (2014)

e15222 Background: Previous studies have revealed that the fluorouracil derivative S-1as first-line treatment can bring survival benefit and good tolerability for patients with unresectable pancreatic cancer (PC). S-1 in combination with leucovorin (LV) revealed a better efficacy when treating patients with metastatic colorectal cancer. In this study, we compared the efficacy and safety of S-1 or S-1 in combination with LV (SL) as the second-line treatment for patients with metastatic PC after failing to gemcitabine treatment. Methods: The study was a randomized, open-label, controlled study. Patients with metastatic PC who failed gemcitabine-based chemotherapy randomly received S-1 at a dose of 80mg/m2/day, orally administered twice a day; or orally administered in combination with LV 25mg/time and S-1 alone for 14 days, followed by 7 days rest, for a 21-day cycle. The primary end point was progression-free survival (PFS). Results: A total of 92 patients were enrolled from March 2010 to May 2013. The median overall survival (OS) of 47 cases in the S-1 arm was 5.5 months, and median PFS was 1.9 months. In the SL arm, the median OS of 45 cases was 6.3 months and median PFS was 3.0 months. There was no significant difference in the OS (p=0.829) and PFS (p=0.860) between the two arms. The overall response rate in the S-1 arm was not significantly different from the SL arm (p=0.503). The rate of adverse events of grade 3-4 in the SL arm was significantly higher than those of the S-1 arm (p=0.011). Conclusions: As compared with S-1, SL did not improve the survival of patients with metastatic PC who had failed gemcitabine treatment. Further evaluation of the overall benefit of SL relative to S-1 is warranted, considering the higher adverse event rate of grade 3-4 observed in the SL group. Clinical trial information: NCT01074996.
Use of preoperative ultrasound (US)-guided fine needle aspiration cytology (FNAC) to identify positive sentinel nodes (SN) in melanoma.
Authors: Alexander Christopher Jonathan Van Akkooi, Petra Siegel, Saskia Gooskens, Alfred Schoengen, Wolfram Sterry, Alexander M. Eggermont, Christiane A. Voit
Journal: Journal of Clinical Oncology (2013)

e20035 Background: The surgical Sentinel Node (SN) is standard of care worldwide for the staging of AJCC stage I/II melanoma patients. It remains unclear if SN followed by early lymph node dissection in case of metastasis can lead to a survival benefit. Unlike other cancers, US-guided-FNAC has not been proven effective in melanoma. Aim was to analyze sensitivity (sens), specificity (spec), positive (PPV) and Negative (NPV) predictive values with use of the Berlin Morphology criteria, a low threshold for performing repeated FNAC and overnight cytology reports. Methods: Between 2001 and 2010 over 1,000 stage I / II consecutive melanoma pts have undergone US-FNAC prior to SN. All patients underwent lymphoscintigraphy prior to US-FNAC. Peripheral Perfusion (PP), Loss of Central Echoes (LCE), Balloon Shaped (BS) are the Berlin Morphology Criteria, which were registered. FNAC was performed (3-4x) in case any of these factors were seen. SN tumor burden was measured according to the Rotterdam Criteria. All patients underwent SN or LND in case of positive FNAC. Results: Mean/med Breslow thickness 2.59/1.57 mm (0.2 – 44 mm). Mean/med follow-up 39 / 32 months (0 – 115). Ulceration (ulc) present in 24 %. SN pos rate was 20.8 % (208 / 1000). 34.2% underwent FNAC. 8.9% was FNAC positive; this was 26% of all FNAC. Sens was 51%. Spec, PPV and NPV were 99%, 95% and 89%. Sensitivity was highest for T4 (76%) and in ulc (63%) tumors. PP, LCE, BS had sens of 51%, 37%, 24%. Sens of US-FNAC increased with increasing SN tumor burden (12% in &lt; 0.1 mm to 61% in &gt; 1 mm). PP was an early sign of metastasis (58% in &lt; 0.1 mm mets). Threshold for pos FNAC was 0.4 mm in maximum diameter. 5-yr survival correlated to US-FNAC status (93% in neg, 51% in pos). 5-yr survival of pts with PP was 82% vs. 46% in BS vs. 92% in neg pts (P=0.001). Conclusions: US-FNAC according to the Berlin Morphology criteria can correctly identify half of the positive SNs, prior to the surgical SN procedure. PP is an early sign of metastasis, BS is a late sign. US-FNAC can significantly reduce the amount of unnecessary surgical SN procedures. US-FNAC sensitivity correlated with increasing T-stage, increasing SN tumor burden and ulc. US-FNAC can accurately predict survival.
Chemokine receptors seem to impact on patient survival in head and neck squamous cell carcinoma
Authors: M. H. Federico, C. M. Campofiorito, F. R. Mangone, S. Maistro, F. S. Pasini, K. C. Brunialti, C. N. Lehn, F. Walder, M. B. Carvalho, M. M. Brentani, I. Snitcovsky
Journal: Journal of Clinical Oncology (2006)

15527 Background and Methods: Chemokine receptors seem to be involved in tumor spread to lymph nodes and influence outcome in cancer patients (pts). Here, we have determined the mRNA expression of CCR7, CX 3 CR1 and CXCR1 chemokines, by means of Ribonuclease Protection Assay, in 60 fragments of primary tumor and matched adjacent mucosa of pts with head and neck squamous cells carcinoma (HNSCC) submitted to curative surgery. For Kaplan Meier survival curves, pts were categorized for each chemokine as positive or negative if above or equal/below median densitometric value of the entire tumor group. Results: In the whole study population, CCR7 status did not impact on overall survival (OS) (P=0.118, Log Rank) and on disease free survival (DFS) (P = 0.102), neither. When the subgroup of oral SCC was considered (n = 19), the CCR7 negative pts (n = 10) presented a longer DFS and OS (median DFS and OS not reached) as compared to CCR7 positive pts (n = 9) (mDFS: 4.9 months, P = 0.001 and mOS 10.47 months P = 0.003). In the HNSCC group as a whole, the CX 3 CR1 negative pts presented a trend toward longer OS (mOS 26.60 months in negative group, n = 25 vs 15.43 months in the positive group, n = 35, P = 0.073) and a longer DFS (mDFS not reached in CX 3 CR1 negative vs 9.20 months in positive pts, P = 0.041). In the oral SCC subgroup, CX 3 CR1 negative pts (n = 8) presented significantly better DFS (mDFS not reached) as compared to CX 3 CR1 positive pts (n = 11, mDFS 4.9 months, P = 0.004). OS was also superior for oral SCC CX 3 CR1 negative (mOS not reached) as compared to positive pts (mOS 10.47 months, P = 0.008). Taking into account larynx SCC, mDFS and mOS were not reached for CX 3 CR1 negative pts (n = 5) as compared to positive pts (n = 11, mDFS 8.57 months, P = 0.016; mOS 12.37 months, P = 0.041). In larynx subgroup, the other receptor associated to an advantage in terms of both DFS and OS was the negativity for CXCR1 (mDFS not reached for negative vs 8.47 months for positive pts, P = 0.006; mOS not reached for negative vs 8.47 months for positive pts, P = 0.025). Conclusions: Even if the mechanisms are not clear, our data suggest that low expression of CCR7, CX 3 CR1 and CXCR1 mRNA may be markers of better outcome in Head and Neck Squamous Cell Carcinoma. Further studies are warranted to confirm these results. No significant financial relationships to disclose.
Results of the ASCO survey of cancer survivorship research: Summary and implications.
Authors: Paul B. Jacobsen, Julia Howe Rowland, Electra D. Paskett, Flora Van Leeuwen, Chaya S. Moskowitz, Sweatha Katta, Dana Wollins, Leslie L. Robison
Journal: Journal of Clinical Oncology (2015)

9567 Background: The ASCO Survivorship Committee identified the need to better understand the current scope of cancer survivorship research in order to identify future research priorities. A committee workgroup recently completed a survey addressing this issue. Methods: A survey was conducted previously to assess engagement of ASCO members in survivorship care and research. Of 14,098 members contacted, 2,899 (20.6%) responded. Of this group, 679 self-identified as (co-)principal investigator of a survivorship-related study. A follow-up survey was subsequently sent to these members and to 838 individuals at NCI-designated Cancer Centers identified through other means as being engaged in cancer survivorship research. The survey asked respondents to describe study characteristics (e.g., design, participants, outcomes) for each IRB-approved cancer survivorship-related study for which they served as (co-)principal investigator. Results: 609 of 1517 recipients (46%) responded and reported on 714 studies. 65% of studies were observational (OBS) and 35% were interventional (INT). OBS studies mostly focused on lymphoid/hematopoietic (26%), breast (19%), and more than one (13%) cancer, while INT studies mostly focused on breast (34%), more than one (15%) and lymphoid/hematopoietic cancers (10%). Age at time of diagnosis/treatment was most commonly 40-64 years for OBS (26%) and INT (32%) studies and least commonly > 65 years for OBS studies (24%) and < 21 years for INT studies (11%). Time since diagnosis was most commonly < 2 and least commonly > 5 years for OBS (39%, 29%) and INT (48%, 15%) studies. The most common primary/secondary objectives were physical (32%), quality of life (27%) and health behavior (22%) outcomes for OBS studies and quality of life (34%), physical (31%) and health behavior (25%) outcomes for INT studies; the least common objective was patterns and quality of care for OBS (2%) and INT ( < 1%) studies. Conclusions: Findings identify key gaps in current research that should be prioritized for future study. These include the relative lack of research on several common cancers (e.g., colorectal, prostate, and lung), on long-term and older ( > 65) and younger ( < 21) survivors, and on survivorship care delivery and quality.
Patterns of relapse and second malignancy after adjuvant external beam radiation therapy for stage I-II seminoma.
Authors: Erik Steven Anderson, Michael Ryan Folkert, Michael J. Zelefsky, Kaled M. Alektiar, Sean Matthew McBride, Darren R. Feldman, Joel Sheinfeld, Marisa Kollmeier
Journal: Journal of Clinical Oncology (2017)

428 Background: To determine relapse rate, patterns of relapse and risk of second malignancy (SM) from a large single institution experience of adjuvant external beam radiation therapy (RT) for stage I-II seminoma. Methods: 463 patients with clinical stage I (n = 339) and II (n = 124) seminoma underwent adjuvant RT (median 25.5Gy) between 2/1990 and 11/2015. Data was gathered by retrospective chart review. Patients with &gt; 5 years of follow-up (n = 312) were included in analysis of SM risk. Of stage II patients, 72% (89/124) received a boost to gross disease (median 4.5Gy). Field design was para-aortic nodal region only (n = 96), para-aortic and ipsilateral pelvic nodal region (n = 351) or para-aortic and bilateral pelvic nodal region (n = 8). Field design was not available for 8 patients. Patients were followed with clinical exam, serial imaging, and tumor markers. Relapse and SM were confirmed pathologically. Results: At median follow-up of 7.9 years, there were 20 relapses (median 13.2 months; range 2.5-55.3 months). There were 9 and 11 relapses in stage I and II patients, respectively, with 7/20 (35%) occurring &gt; 2 years after RT. Relapses were identified by clinical symptoms (n = 7), imaging (n = 9), or elevated serum markers (n = 4). Sites of relapses included the lung/mediastinum (n = 10), retroperitoneum/pelvis (n = 5), bone (n = 3) and inguinal nodes (n = 2). 15 (3 pelvic) occurred after para-aortic and ipsilateral pelvic lymph node RT, while 5 (2 pelvic) occurred after para-aortic RT alone. 19/20 patients received cisplatin-based chemotherapy for relapse and were without evidence of disease at last follow-up (median 123 months). Of 35 total non-testicular SM (33 patients), 17 (48.6%) were in the RT field, 4 (11.4%) were marginal and 14 (40%) were out of field. Common SM were prostate (10), lymphoma (4), bladder (3) and kidney (3). The 5 and 10 year overall survival for the cohort is 99.2% and 97.9%, respectively. Conclusions: Stage I-II seminoma patients have a low risk of relapse and SM following adjuvant RT. Relapse is less common in patients treated with para-aortic and pelvic fields. More than 1/3 of relapses occur more than 2 years after adjuvant RT, necessitating long term clinical, radiographic and biochemical follow-up.
Germline testing in hereditary cancer genes subsequent to the identification of mutations in tumor specimens.
Authors: Virginia Speare, Jill S Dolinsky, Holly Laduca, Carrie Horton, Laura Panos, Carla Mason, Emily Dalton, Elizabeth Chao
Journal: Journal of Clinical Oncology (2015)

1527 Background: Molecular profiling of tumors is crucial in identifying targeted therapies. Secondarily, tumor DNA sequencing has the potential to reveal germline mutations leading to the diagnosis of a hereditary cancer predisposition. We sought to determine the frequency and clinical significance of germline testing performed at one laboratory subsequent to tumor profiling. Methods: Retrospective review of a laboratory database revealed 74 germline test orders following identification of mutations in tumor specimens from 54 patients. Age at cancer diagnosis, family history and a description of the patient’s tumor including associated somatic mutations were obtained from test requisitions. Germline targeted sequencing was performed with DNA isolated from blood or saliva. Pathogenic mutations identified in hereditary cancer predisposition genes were included for analysis. Results: Ten of 74 (13%) tumor mutations were confirmed in the germline. The remaining mutations are presumed to be somatic. Mutations were identified in 5 of 17 genes with the majority of germline findings in BRCA1 (3) and BRCA2 (4). Although TP53 alterations were most frequently submitted for germline analysis, none were confirmed in the germline, despite 3/18 patients meeting National Comprehensive Cancer Network (NCCN) criteria for TP53 germline testing. Based on available clinical history, 3 patients who did not meet NCCN testing criteria carried a BRCA2 germline mutation. Conclusions: Patients with germline mutations who did not meet criteria for testing represent a portion of high-risk individuals who may not otherwise be identified in the absence of tumor profiling results. In addition, germline mutation detection varied between genes. These insights may prove useful in identification of patients appropriate for cancer predisposition evaluation. Gene # Mutations from Tumors # Confirmed in Germline (% met testing criteria) APC 3 0 ATM 2 0 BRCA1 4 3 (100%) BRCA2 12 4 (25%) CDH1 4 0 CDKN2A 3 0 CHEK2 1 1 (NC) MEN1 6 0 MLH1 1 0 MSH2 2 0 MSH6 2 0 NF1 6 1 (100%) PTEN 6 1 (100%) RB1 2 0 STK11 1 0 TP53 18 0 VHL 1 0 NC = no criteria available
Association of DOCK6 with cancer stem cell development and as an independent prognostic factor of gastric cancer.
Authors: Chia-Siu Wang, Chung-Ying Tsai, Kam-Fai Lee, Liang-Mou Kuo, Kwang-Huei Lin
Journal: Journal of Clinical Oncology (2017)

68 Background: The prognosis of advanced gastric cancer (GC) remains poor, and the key players in molecular pathogenesis are predominantly unknown at present. Methods: In order to identify novel prognostic factor of GC, we compared the data of iTRAQ proteomics from 6 GC samples with that of Oncomine database from 86 GC samples to intersect 122 high-expression proteins in gastric cancer tissue. The candidate biomarkers were further characterized in fresh GC tumor tissues compared with adjacent non-tumor tissue by using Q-RT-PCR, immunohistochemical staining and western blot. GC cells with depletion of DOCK6 were examined to identify downstream molecules and establish their effects on cell motility, invasion and gastric cancer stem cell (CSC) markers. The possible signaling pathway of DOCK6 were also investigated. Results: DOCK6 is identified as one of the potential GC biomarkers in iTRAQ proteomics. Our data confirm the overexpression of DOCK6 in GC tumor tissue compared with adjacent non-tumor tissue. In addition, the clinical data shows higher DOCK6 expression was positive correlated to depth of invasion, lymph node metastasis, vascular invasion and pathological stage. Furthermore, higher DOCK6 expression represented significantly shorter cumulative survival both in univariate and multivariate analysis for survival outcome. Depletion of DOCK6 repressed the cell migration, proliferation, sphere formation, anchorage-independent growth and tumorigenicity as well as gastric cancer stem cell (CSC) markers. In order to explore the downstream effector of DOCK6, we correlated thousands of gene with DOCK6 in three GC dataset published in the literature. The DOCK6 positive-correlated genes were subsequently analyzed by Metacore. They were significantly involved in WNT/β-catenin signaling pathway. Our result demonstrates nuclear b-catenin, as well as CD44, was decreased accompanied by depleting DOCK6. Moreover, the interaction between DOCK6 and β-catenin was observed in GC cells. Conclusions: Our studies unveil the role of DOCK6 in the self-renewal of CSC and propose DOCK6 as an independent marker of tumor progression.