tbuckley/cabot-search huggingface dataset:
Diagnostic utility and prognostic performance of a 92-gene cancer classifier to molecularly profile periampullary adenocarcinomas (PAA).
Authors: Michael J. Overman, Huamin Wang, Catherine A. Schnabel, Jeffrey Anderson, Mark G. Erlander, Robert A. Wolff, Gauri R. Varadhachary
Journal: Journal of Clinical Oncology (2013)

4133 Background: Due to the small anatomic size, multiplicity of epitheliums, and suboptimal diagnostics determining the site of origin of PAA is a challenge. We investigated the ability of a 92-gene RT-PCR assay (CancerTYPE ID) to categorize PAA and to prognostically stratify ampullary adenocarcinomas. Methods: 171 PAA patients who underwent pancreaticoduodenectomies were included; samples were histopathologically verified for tumor subtype determination: pancreatic (PAN), extrahepatic biliary (EB), ampullary (AMP), or duodenal (DOUD). Blinded FFPE tumor sections underwent molecular testing. Analytical sets were an initial 45 PAA set evaluating concordance to histopathological tumor types and prognostic performance, and a second set of 126 AMP and DOUD adenocarcinoma for validation of prognostic performance. Results: Of the initial 45 patient cohort, molecular classification of 43 (96%) evaluable samples (13 AMP, 10 PAN, 10 EB, 10 DOUD) showed 91% concordance: AMP [5 intestinal (int), 7 pancreaticobiliary (pb)], PAN [10 pb], DOUD [3 int, 7 gastroesophageal (ge)], EB [7 pb]. The 92-gene assay was prognostic with a median OS of 70 m for ge/int cases vs. 32 m for pb cases, P=0.05. Discordant classifications were ge for 1 AMP and 2 EB samples, and ovary for 1 EB case. Previous unsupervised RNA hierarchical clustering (Overman GI ASCO 2011 a161) of all 13 AMP cases had identified two prognostic groups (a good-prognosis int-like and a poor-prognosis pb-like), which were identical to the 92-gene classification for 12 of the 13 cases. Conclusions: In the initial cohort of 45 patients, the 92-gene assay demonstrated diagnostic utility for molecular site-of-origin classification of PAA; evaluation of the remaining 126 ampullary and duodenal cases will be presented. Results support exploration of this approach for the management of metastatic PAA (in which pathologic review of a primary resection specimen is not an option). Molecular classification of ampullary adenocarcinomas into intestinal and pancreaticobiliary subgroups is prognostically relevant; these and the gastric-like molecular profile of duodenal adenocarcinomas may have therapeutic implications.
Radiation Therapy Oncology Group (RTOG) 9413: Randomized trial comparing whole pelvic radiotherapy (WPRT) to prostate only (PORT) and neoadjuvant hormone therapy (NHT) to adjuvant hormone therapy (AHT).
Authors: Mack Roach, Yan Yan, Colleen Anne Lawton, I-Chow Joe Hsu, Robert A. Lustig, Christopher U. Jones, Marvin Rotman, Kenneth Lee Zeitzer, Maria Werner-Wasik, Harold Kim, Charles R. Thomas, William U. Shipley, Howard Mark Sandler
Journal: Journal of Clinical Oncology (2012)

96 Background: RTOG 9413 demonstrated that NHT+WPRT improved progression-free survival (PFS) compared to NHT+PORT, WPRT+AHT and PORT+AHT. We update primary and secondary endpoints (SE): biochemical failure (BF), time to metastasis (Mets), prostate specific survival (PSS) and overall survival (OS). Methods: RTOG 9413 opened on April 1, 1995, and closed on June 1, 1999, with 1275 eligible pts who were required to have a risk of lymph node (LN) involvement &gt;15% but LN-positive pts were ineligible. They were stratified by T Stage, GS (&lt;7 vs 7-10) and PSA (&gt;30 vs &lt; 30ng/ml) and randomized to PORT +/- WPRT to 70 Gy and NHT or AHT. Hormonal therapy (HT) consisted of flutamide, and leuprolide or goserelin, monthly x 4 mos, beginning 2 mos before RT and continued until RT is completed (NHT) or beginning at the completion of RT (AHT). For this analysis PFS was defined as the first occurrence of local/regional or LN progression, Mets, BF (PSA nadir+2ng/mL), or death from any cause. PSS is defined as a death due to prostate cancer, treatment toxicity or unknown causes with local progression, Mets or BF. Results: For the entire cohort WPRT or NHT did not appear to improve any endpoint compared with PORT or AHT, (although there was a trend for improvement in regional failure for WPRT vs PORT, (p=0.07)). However, there were complex sequence/volume dependent interactions between HT and RT and statistically significant differences between the 4 arms in PFS (p=0.03). There was a trend for NHT+WPRT to improved PFS compared to NHT+PO (p=0.07) and WPRT+AHT (p=0.04). NHT+WPRT was associated with an increased risk of late GI toxicity, 5% compared to 0.6%, 2% and 2% for NHT+PORT, WPRT+AHT and PORT+AHT (p&lt;0.001) but not in GU late toxicity. Conclusions: The failure to improve SE or definitively impact PFS may reflect sample size, pt selection, and inadequate RT doses. RTOG 0924 will test the hypotheses that modern techniques and doses will improve OS without increasing late toxicity.
FOLFIRINOX in locally advanced and metastatic pancreatic cancer.
Authors: Jason Edward Faris, Theodore S. Hong, Shaunagh McDermott, Darrell R. Borger, Alexander R Guimaraes, Jennifer Yon-Li Wo, Dushyant Sahani, Lauren Elizabeth Dias, Jill N. Allen, Andrew X. Zhu, Janet E. Murphy, Eunice Lee Kwak, David P. Ryan, Jeffrey W. Clark, Lawrence Scott Blaszkowsky
Journal: Journal of Clinical Oncology (2012)

e14615 Background: The phase III trial of 5-FU, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) demonstrated improved survival compared to gemcitabine in good performance status (PS) patients (pts) with metastatic pancreatic cancer (Conroy et al, NEJM 2011). Less is known about the efficacy and tolerability of FOLFIRINOX in the non-clinical trial setting. In this retrospective analysis, we report our institutional experience with FOLFIRINOX. Methods: 38 pts with locally advanced (LAPC) or metastatic pancreatic cancer (MPC) who began treatment with FOLFIRINOX between 7/2010 and 6/2011 were identified. Clinical characteristics, gradable toxicities, and molecular genotyping results were tabulated. Formal radiographic review was performed to determine best overall response rates (ORR). All pts receiving FOLFIRINOX were assessed for toxicities, while pts receiving ≥2 cycles were assessed for response. Results: 26 pts received FOLFIRINOX for MPC and 12 pts for LAPC. The median age was 60 (range 39-76). 29/38 pts were men, 26/38 had received no prior chemotherapy, and 11/38 had biliary stents. Overall, 12 partial responses (PR) were observed in 33 evaluable pts (ORR 36%); 11/12 partial responses were in chemo-naïve pts. In evaluable pts with MPC, there were 7 PR (ORR 33%), and 11 pts with stable disease (SD). In LAPC, there were 5 PR (ORR 42%), and 7 pts with SD. Following FOLFIRINOX, two pts with LAPC have subsequently undergone R0 resection. 18/38 pts required an ED visit or hospitalization during treatment. Grade 3/4 neutropenia was observed in 12 pts; 8/12 had not received prophylactic growth factor from the start of FOLFIRINOX. There were 6 pts with febrile neutropenia, 6 pts with grade 3/4 thrombocytopenia, and 5 pts with grade 3/4 anemia. 1 pt died with bacteremia in the setting of febrile neutropenia. 22 pts had molecular genotyping at multiple loci performed: 17/22 were KRAS mutation positive, and 3 pts with KRAS mutations also had TP53 mutations. 4 pts were wild-type at all loci tested, and 3 of these pts had a PR on FOLFIRINOX. Conclusions: In a non-clinical trial setting, FOLFIRINOX demonstrated activity in both LAPC and MPC, but is associated with significant toxicities, with nearly half of pts requiring an ED visit or hospitalization.
ARID2 modulates DNA damage response in human hepatocellular carcinoma cells
Authors: Atsushi Oba, Shu Shimada, Yoshimitsu Akiyama, Taketo Nishikawaji, Kaoru Mogushi, Hiromitsu Ito, Satoshi Matsumura, Arihiro Aihara, Yusuke Mitsunori, Daisuke Ban, Takanori Ochiai, Atsushi Kudo, Hiroshi Asahara, Atsushi Kaida, Masahiko Miura, Minoru Tanabe, Shinji Tanaka
Journal: Journal of Hepatology (2017)
Evaluation of patients, safety, and financial implications of sipuleucel-T (SipT) for treatment of metastatic castrate-resistant prostate cancer (mCRPC): Early real-world experience at USC.
Authors: S. Pak, M. Reed, M. Luther, M. Averia, S. Desai, J. K. Pinski, T. B. Dorff, D. I. Quinn, B. Chan
Journal: Journal of Clinical Oncology (2011)

e15124 Background: Sipuleucel-T is an immunotherapy approved for the treatment of asymptomatic or minimally symptomatic mCRPC based on the IMPACT trial. There are limited data in the use of SipT in pts outside clinical trials and those with history of chemo, opioid use or visceral metastases. Our study is an evaluation of initial SipT usage at USC. Methods: We assessed 34 pts who received at least one SipT infusion between Jun 2010 -Jan 2011. A prospective log was used to track pts with EMR to correlate clinical variables for all pts. Financial data were obtained from USC authorization department. Results: Of 76 pts screened in a tumor board setting with criteria based on IMPACT trial eligibility; 44 pts met treatment indication, 34 pts received treatment. Cohort medians: time from enrollment to treatment: 7.5 wks; Age: 71yrs (R: 54-85); Gleason: 8; PSA: 25ng/ml (R:0.03-4530); CTCs: 2 (0-43); Follow-up: 4 mths. Prior chemo: 13/34 (38%); history of opioid use: 6/34 (18%). Sites of disease - bone: 27/34 (79%), LN: 18/34 (53%), visceral: 2/34 (6%). Central line: 5/34 (15%). Insurance: Medicare (MC) only 10/34 (29%), MC + Suppl 4/34 (12%), Private (HMO 8, PPO 12): 20/34 (59%). 27/34 (79%) pts completed all 3 infusions, 5/34 (15%) pts received < 3 infusions due to intercurrent comorbidity or progressive cancer. Analysis of these 5 pts revealed median age: 78, median PSA: 233 ng/ml. 3 pts had prior chemo and opioid use. All pts had bone metastases, 1 patient has bone + visceral. 3 pts died due to disease progression. Toxicity was minimal. 3 pts developed chills, one with rigors. 1 patient had an infusion extravasation. Reimbursement was forthcoming on all pts, with private insurance paying at or above Medicare rates. Conclusions: SipT infusion is relatively safe and well tolerated. Time of follow-up is too short to assess for efficacy data. Financial reimbursement was better with Private insurance compared to Medicare. 15% pts failed to complete therapy. These pts were characterized by: older age, higher baseline PSA values and opioid use that would have precluded their involvement in IMPACT trial. Tumor board criteria have been tightened to exclude such pts.
Phase I trial of ALT-801, a first-in-class T-cell receptor (TCR)-interleukin (IL)-2 fusion molecule, plus gemcitabine (G) for Bacillus Calmette Guerin (BCG)-resistant non-muscle-invasive bladder cancer (NMIBC).
Authors: Guru Sonpavde, Charles Joel Rosser, Chong-xian Pan, Rahul Atul Parikh, Jeffrey Nix, Jeffrey R. Gingrich, Liza Hernandez, Bee-Yau Huang, Hing C. Wong
Journal: Journal of Clinical Oncology (2016)

451 Background: Novel agents are necessary to treat BCG-resistant NMIBC to avoid radical cystectomy (RC). This phase I clinical trial evaluated the safety and activity of ALT-801, a recombinant humanized TCR-IL-2 fusion protein in BCG-resistant NMIBC. Methods: This is a Phase I trial using the 3+3 design to evaluate intravenous (IV) ALT-801 plus IV G 1000 mg/m 2 in BCG-resistant high-risk NMIBC patients (pts) defined as high grade Ta, T1 or carcinoma in situ, size &gt; 4 cm or multi-focal tumors. BCG-intolerant pts, those who refused or were unfit to undergo RC were also eligible. Initially, patients received ALT-801 monotherapy; an amendment added G. Pts received induction of 2 cycles, with a 13-day rest between cycles. Each cycle consisted of 4 doses of ALT-801 on Day 3, Day 5, Day 8, and Day 15 and 2 doses of G, one each on Day 1 and Day 8. Pts who have a biopsy-proven complete response (CR) after induction received one maintenance cycle and underwent response assessment. The initial dose of ALT-801 was 0.08 mg/kg with 2 step-down doses allowed if dose limiting toxicities (DLTs)- 0.06 mg/kg and 0.04 mg/kg. Results: 2 pts in cohort one received ALT-801 alone at 0.08 mg/kg per dose, a 3 rd pt received G and ALT-801 at 0.08 mg/kg per dose. Grade ≥ 3 hepatotoxicity in the 3 rd patient led to a step-down to 0.06 mg/kg dose. One pt in the 0.06 mg/kg dose experienced a DLT (Grade ≥ 3 hepatotoxicity) and the cohort was expanded to 6 pts with no further DLTs. Other attributed adverse events were: anorexia, pruritus, rash, edema, fatigue, chills. For the 0.06 mg/kg ALT-801 + G regimen, 6 pts received up to 2 cycles of induction and 4 pts received the maintenance cycle. All pts have completed therapy without further DLTs. CR was observed in 3 pts, which was durable in 2 pts lasting ≥ 18 months. Preliminarily immune studies have shown transient IFN-γ and IL-6 but not TNF-α and IL-10 induction after ALT-801 dosing. Conclusions: ALT-801 plus gemcitabine was feasible in BCG-resistant NMIBC and demonstrated immune responses and potential durable clinical activity. Further evaluation in expansion cohorts in a phase Ib/II trial is planned. Clinical trial information: NCT01625260.
A phase Ib clinical trial of the multitargeted kinase inhibitor lenvatinib (E7080) in combination with everolimus for treatment of metastatic renal cell carcinoma (RCC).
Authors: Ana M. Molina, Thomas E. Hutson, James M. G. Larkin, Anne Gold, Corina Andresen, Karen Wood, Robert John Motzer, M. Dror Michaelson
Journal: Journal of Clinical Oncology (2013)

358 Background: Lenvatinib (L) is an oral tyrosine kinase inhibitor targeting VEGFR1-3, FGFR 1-4, RET, KIT, and PDGFβ. Everolimus (E) is an oral mTOR inhibitor approved for RCC. This Phase (Ph) 1b/2 study investigates the combination of L plus E in RCC patients (pts) (NCT01136733). The Ph 1b component reported here assessed safety, tolerability, and maximum tolerated dose (MTD). Methods: Pts with advanced unresectable or metastatic RCC, ECOG PS 0-1, age ≥18 y, were eligible for Ph 1b. Pts received L plus E, daily, in 28-day cycles. A standard 3+3 dose-escalation design with expansion cohort was used to identify the MTD. Results: 20 pts (M/F: 14/6; median age: 59 y [range 46-72]; median of 2 prior therapeutic regimens [range 0-5]; 17/20 pts [85%] had received prior anti-VEGF treatment (tx); 7/20 pts [35%] had also received prior mTOR-targeted tx) were treated at 3 dose levels of L (12 mg [n=7]; 18 mg [n=11]; 24 mg [n=2]) in combination with E 5 mg. DLTs were observed in 4 pts: G3 nausea and vomiting (1 pt) and G2 mucositis (1 pt) with 24 mg; G3 elevated creatinine phosphokinase, G2 fatigue, and G1 reflux with 18 mg; G3 abdominal pain with 12 mg. The MTD was L 18 mg plus E 5 mg. Median duration of tx was 19 wk (range 1-68, 6/20 (30%) pts ongoing). The most common tx-related adverse events (AEs), all grades, were fatigue 50% (G3, 5%); diarrhea 40% (G3, 10%); mucosal inflammation 40%; proteinuria 40% (G3, 10%); decreased appetite 35%; nausea, vomiting each 35% (each G3 5%); hypertension 35%; rash 30%; dry skin, epistaxis, weight decreased, constipation, edema peripheral (G3 5%), each 20%. There was 1 G4 tx-related AE of hypercholesterolemia. In the MTD and lower-dose cohorts, partial response (PR) was observed in 6/18 (33%) pts; durable stable disease (SD) (≥23 wk) or PR were achieved in 11/18 (61%) pts. Median PFS was 442 days (approx. 15 mos) in MTD and lower-dose cohorts. Conclusions: Lenvatinib 18 mg in combination with everolimus 5 mg appeared to be well tolerated when administered to multiply pretreated patients with advanced RCC in this Ph1b study. The PRs observed and SD durability warrant further evaluation in this refractory population during the ongoing Ph 2 part of the study. Clinical trial information: NCT01136733.
Outcome of infants and young children with newly diagnosed medulloblastoma treated on Head Start III protocol.
Authors: G. Dhall, L. Ji, K. Haley, J. P. Grimm, F. H. Gilles, S. L. Gardner, J. C. Allen, A. Cornelius, K. R. Pradhan, J. H. Garvin, R. S. Olshefski, J. Hukin, M. Comito, S. Goldman, S. J. Thompson, A. Hirt, M. P. Atlas, A. W. Walter, R. Sposto, J. L. Finlay
Journal: Journal of Clinical Oncology (2011)

2011 Background: The use of high dose chemotherapy with autologous hematopoietic cell rescue (AuHCR) is a potentially curative approach to the management of young children with medulloblastoma (MB), with the additional benefit of avoiding the late effects of irradiation. We report the outcome of young children with MB treated on “Head Start” III, a prospective, multi-national clinical trial. Methods: Between April 2003 and December 2009, 92 children with newly-diagnosed MB were enrolled amongst 29 participating institutions. All children were to receive 5 induction cycles (vincristine, cisplatin, cyclophosphamide, etoposide, high dose methotrexate - cycles 1, 3, 5), and vincristine, cyclophosphamide, oral VP-16 and temozolomide (cycles 2, 4), followed by 1 consolidation cycle of myeloablative chemotherapy (thiotepa, carboplatin, etoposide) and AuHCR. Only children between 6 -10 years old or with residual tumor pre-consolidation, were to receive irradiation after consolidation. Results: The 3-year event-free (EFS) and overall survival (OS) rates (+/−SE) for all patients, patients with localized (M0) disease (n=39), and patients with disseminated (M1+) disease (n=51) were 47 +/− 6% and 65 +/− 6%, 63 +/− 8% and 80 +/− 7%, and 33 +/− 8% and 54 +/− 8%, respectively. The 3-year EFS and OS (+/−SE) for all patients with desmoplastic, classical and anaplastic MB were 89 +/− 6% and 86 +/− 8%, 26 +/− 7% and 58 +/− 8%, 36 +/− 17% and 31 +/− 22%, respectively and for M0 patients were 93 +/− 6% and 93 +/− 6%, 41 +/− 12% and 71 +/− 13%, 50 +/−20% and 67 +/−19%, respectively. 3-year irradiation free EFS was 49 +/−6% for all patients. In multivariate Cox regression analyses, histology was the only significant independent predictor of EFS after adjusting for metastatic status, initial extent of resection of the primary tumor, regimen, age and sex (p<0.001). Desmoplastic MB patients had significantly better EFS than patients with classic tumors (HR=0.11, 95%CI=0.033, 0.35). No significant difference was found between anaplastic and classic tumors. Conclusions: We report the best survival data published so far on young children with desmoplastic and anaplastic MB, while avoiding craniospinal irradiation in half of the patients.
Effect of dementia diagnosis on receipt of postoperative colon cancer chemotherapy.
Authors: Yingjia Chen, Thomas John Semrad, Rosemary Donaldson Cress, Laurel A. Beckett
Journal: Journal of Clinical Oncology (2015)

769 Background: Colon cancer and dementia have a high risk of co-occurrence. Prior studies found that patients with dementia have higher mortality than non-demented counterparts, mostly from non-cancer causes. We hypothesized that a dementia diagnosis using an improved algorithm would be associated with reduced use of postoperative therapy. Methods: In addition to the claims-based algorithm for dementia published by Centers for Medicare and Medicaid Services that uses SEER-Medicare Medicare Provider Analysis and Review, Carrier Claims, Home Health Agencies, and Outpatient files, we developed a medication-based algorithm using the part D file based on prescription for any of the five FDA-approved dementia drugs (donepezil, galantamine, memantine, rivastigmine, tacrine). We measured agreement between the two diagnostic algorithms with k-statistics. Using each algorithm and a final combined algorithm, we used multivariable logistic regression adjusting for demographics and disease characteristics to examine the effect of dementia on the use of post-operative colon cancer chemotherapy. Parallel analyses restricted the population to later-stage cancer patients (stage III/IV). Results: 46,126 patients diagnosed between 2007 and 2009 were identified. 20% had dementia by either of the algorithms. 9% of the dementia cases were identified through Part D data. The two algorithms showed moderate agreement (k&gt;0.49, p=0.007). After surgery, those patients with dementia by the combined algorithm were less likely to receive chemotherapy (OR = 0.641, 95% CI: 0.597-0.688). Those with dementia identified by part D data were even less likely to receive chemotherapy than those identified by the claims algorithm (OR=0.617, 95% CI: 0.466-0.816 for medication; OR=0.767, 95% CI: 0.684-0.860 for claims). A similar pattern was detected when restricting to stage III/IV patients (OR=0.667, 95% CI: 0.457-0.973). Conclusions: Part D data increases the sensitivity for identifying dementia cases in SEER-Medicare. Patients with dementia are significantly less likely to receive post-operative chemotherapy. Thus, reduced postoperative colon cancer therapy among patients with dementia may contribute to higher cancer-related mortality.
Bidirectional intraperitoneal chemotherapy with oxaliplatin in the context of CRS and HIPEC in patients with peritoneal carcinomatosis.
Authors: G. Glockzin, H. J. Schlitt, P. Piso
Journal: Journal of Clinical Oncology (2011)

568 Background: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) provide a promising therapeutic option for selected patients with peritoneal carcinomatosis. The use of oxaliplatin as an intraperitoneal cytostatic agent seems to further improve the efficacy of the combined treatment concept. Nevertheless, additional toxicity in comparison to mitomycin C and/or doxorubicin might be exspected. Methods: Between 02/2008 and 08/2010 40 patients underwent CRS and HIPEC with oxaliplatin at a concentration of 300 mg/sqm at the University Medical Center Regensburg. Thirty-five of these patients received bidirectional chemotherapy with additional intravenous application of 5FU/LV and 5 patients intraperitoneal oxaliplatin only. Perfusion time was 30 and 60 minutes, respectively. A matched-pair analysis was performed to compare IP oxaliplatin to our former standard HIPEC with mitomycin C and doxorubicin. Matching criteria were operating time, age and sex. Results: The mean operating time in the OX and the MMC group was 315 and 313 minutes, respectively. The mean age was 52 and 51 years, and 15 versus 16 patients were female, respectively. Median hospital stay was 15.5 days in the OX group and 17 days in the MMC group. The median stay on ICU was one day in both groups. The grade 3/4 morbidity rate was 42.5 % versus 37.5 % (p = 0.648). Five versus six patients had to be reoperated. Perioperative morbidity was 2.5 % versus 0 %. Main complications in the OX group were pleural effusion (5), thrombosis (2), cardiac arrhythmia (2), and abscess (2). In the MMC group postoperative morbidity was mainly caused by ileus (4), anastomotic leakage (3), pulmonary embolism (2), and wound infection (2). Conclusions: Our data suggest that the use of IP oxaliplatin in the context of CRS and HIPEC does not increase perioperative morbidity and/or mortality rate. Nevertheless, randomized controlled trials are required to determine the best intraperitoneal chemotherapeutic regimen regarding toxicity and oncological outcome. No significant financial relationships to disclose.