tbuckley/cabot-search huggingface dataset:
Intensive radiographic and CEA screening and salvage resection in patients with stage II and III colorectal cancer.
Authors: Ahmad Ali Fora, Annie M Patta, Kristopher Attwood, Gregory E. Wilding, Marwan Fakih
Journal: Journal of Clinical Oncology (2012)

405 Background: The objective of this study was to determine the rate of salvage resection in patients with stage II and III colorectal cancer following intensive surveillance. Methods: Patients with stage II and III colorectal cancer with a minimum follow-up of 3 years were included. CEA was obtained every 3 months for 2 years and then every 6 months for years 3 to 5. CT of the chest, abdomen and pelvis was performed every 6 months for 2 years and then yearly for years 3 to 5. Colonoscopy was performed at year 1 and then every 3 years. Results: 177 patients were followed for a median of 59.5 months. 51% were male, and 65 % had colon cancer. Compliance with screening was excellent with 92 % of patients undergoing all scheduled studies within 2 months of the planned date. At the time of this report, the median follow-up of the overall population was 5 years. 44 patients were diagnosed with recurrent disease. 91% of the recurrences were in the first 3 years of follow-up. CT and CEA were the first signs of recurrence in 68% and 14% of patients, respectively. Among the 30 patients diagnosed radiographically, 20 had a normal CEA. 25 patients (57%) with recurrent disease underwent curative intent resection, 12 of whom are still cancer free, with a median follow-up of 6.7 years from salvage surgery. The DFS and OS in the operated recurrent population from the time of salvage resection was 18.8 months (95% CI: 15.5 – 29.4) and not-reached (95% CI: 37.4, NR), respectively. The corresponding OS (from the time of recurrence) of the recurrent population without resection was 20.7 months (95% CI: 21.9, 63.4). The difference in OS between the two groups was highly significant (p = 0.0003). Among the patients undergoing resection, a significant difference was detected in the DFS of resected lung or liver metastases vs. extra-hepatic/pulmonary disease (p = 0.03) and a trend towards improved survival was noted (p = 0.07). Conclusions: Our intensive surveillance strategy resulted in the highest reported salvage rate in stage II and III colorectal cancer and led to a high rate of sustained remissions following salvage surgery. Intensive, 6-monthly, radiographic surveillance and its duration should be investigated further in randomized studies.
A phase Ib/IIa study of NEO-102: A therapeutic antibody to treat pancreatic and colorectal cancers.
Authors: Sandip Pravin Patel, Michael Morse, Muhammad Shaalan Beg, Nilofer Saba Azad, Melony A. Beatson, Sharon Mavroukakis, Philip M. Arlen
Journal: Journal of Clinical Oncology (2014)

243 Background: We have developed a chimeric monoclonal antibody (ab) that targets a variant of MUC5AC that is expressed specifically by human pancreatic (P) and colorectal (C) tumors with minimal reactivity to normal GI mucosa. In the phase (ph) I trial of the initial formulation NEO-101, 5/19 patients (pts) had stable disease (SD) after completing their 1st course of treatment (tx) (4 doses) and overall survival (OS) of &gt;12 months (mos) observed in 3 C and 2 P pts despite disease progression on standard (std) of care tx regimens. The current study utilizes NEO-102, a glycoengineered form of NEO-101 with improved stability and decreased RBC agglutination. Methods: A Ph Ib/IIa open label, multi-center dose-escalation clinical trial with NEO-102 is enrolling pts with advanced P and C cancer refractory to std therapy. Primary objective: measure efficacy by analysis of CT scans pre- and post-therapy using RECIST criteria, OS, clinical laboratory tests, and physical examinations. Secondary objectives: a.determine safety and tolerability of escalating doses of NEO-102; b. assess pharmacokinetics (PK) and select immune responses to the ab at each dose level. Analyses of pt PBMCs for ADCC and immune cytokine profiling utilizing the Milliplex MAP Human Cytokine/Chemokine Panel are planned to assess for immunologic outcome, and for correlation with clinical benefit. Results: Safety analysis has been performed on 3 pts enrolled in the first cohort at the dose level of 1.5 mg/kg IV q2weeks. There were no dose limiting toxicities (DLT) observed. In this cohort, one of the pts is evaluable for SD at 4 mos. The other 2 pts are scheduled for restaging scans. Pts are currently being accrued at the 2 mg/kg dose level. Conclusions: Preliminary results with NEO-102 ab have demonstrated signs of clinical activity based on stabilization of disease in heavily pretreated pts with P and C cancer. Safety has been established at the 1.5 mg/kg dose level and patients are currently being accrued to the 2 mg/kg dose level. If no DLT is observed at the current dose level, we plan to escalate to 3mg/kg and 4mg/kg respectively. Immune biomarker analyses are underway to correlate PBMC ADCC and cytokine profile with tx response. Clinical trial information: NCT01040000.
Definitive radiotherapy in the management of node-positive bladder cancer: A National Cancer Data Base (NCDB) analysis.
Authors: William Allen Stokes, Chad G Rusthoven, Norman Yeh, Brian D. Kavanagh
Journal: Journal of Clinical Oncology (2016)

394 Background: The survival impact of definitive radiotherapy (RT) in lymph node positive (N+) non-metastatic (M0) bladder cancer is unclear, as reflected in the National Comprehensive Cancer Network (NCCN) guideline recommendation for chemotherapy (CT) with or without RT in this population. We conducted the present analysis of the NCDB to determine whether RT at a definitive dose would be associated with improved overall survival (OS) in patients with N+ bladder cancer. Methods: NCDB was queried for subjects diagnosed from 1998-2012 with cN1-3 M0 cancer of the urinary bladder who did not undergo cystectomy. Definitive RT included external beam radiotherapy to the pelvis or bladder regions to a cumulative dose of ≥ 54Gy (per NCCN guideline for gross nodal disease). Cox regression was used to assess the association of definitive RT with overall survival while controlling for patient-related, tumor-related, and treatment-related factors. Results: 3,298 N+ subjects not undergoing cystectomy were identified, of whom 840 (25.5%) received any RT and 392 (11.9%) received ≥ 54Gy. In the entire cohort, multivariate analysis adjusting for age, year, sex, race, location, income, comorbidity, histology, grade, T-stage, N-stage, and receipt of chemotherapy demonstrated an OS benefit (HR for death 0.69; 95%CI 0.59-0.82; p &lt; 0.01) with cumulative RT dose ≥ 54Gy. On subgroup analysis, this OS benefit persisted both among the 1905 patients (331 receiving ≥ 54Gy) undergoing CT (HR 0.66; 95%CI 0.46-0.95; p = 0.02) and among the 1393 patients (61 receiving ≥ 54Gy) not undergoing CT (HR 0.67; 95%CI 0.55-0.82; p &lt; 0.01). Conclusions: In the largest analysis to date of definitive radiotherapy for N+ bladder cancer, receipt of a definitive RT dose was associated with improved OS, irrespective of receipt of CT. Intermediate oncologic endpoints including locoregional control and disease-free survival were unavailable for analysis. With a minority of N+ subjects receiving any radiotherapy, this intervention appears to be underutilized among these patients.
Bevacizumab (BV) continuation following BV progression: Meta-analysis of five consecutive recurrent glioblastoma (GBM) trials.
Authors: D. A. Reardon, J. J. Vredenburgh, A. Desjardins, K. Peters, A. D. Coan, J. E. Herndon, H. S. Friedman
Journal: Journal of Clinical Oncology (2011)

2030 Background: Although BV benefits most recurrent GBM patients, the duration of benefit is limited and subsequent survival after BV progression is poor due to lack of effective therapeutic options. Methods: We performed a meta-analysis of five consecutive phase II BV salvage trials conducted at our institution to evaluate potential prognostic factors and to assess outcome following BV trial progression for recurrent GBM patients. Results: The five BV salvage trials included similar eligibility, treatment and assessment criteria and enrolled 172 recurrent GBM patients. Outcome across the trials was comparable and traditional prognostic factors including age, KPS and degree of prior treatment did not predict outcome. Following progression on BV trial therapy, 95 patients (68%) received additional therapy including 42 patients who were initially treated with a non-BV regimen and 53 who received a BV regimen. Patients who received non-BV therapy did not differ from those who received BV therapy with regard to age, number of prior episodes of progression, time from original diagnosis or duration on BV trial therapy. The median overall survival (OS) and OS at 6 months (OS-6) for patients who received a BV regimen after progression on a BV trial was 6.1 months (95% CI: 5.2, 7.6) and 51.1% (95% CI: 36.7, 63.8), while the median OS and OS-6 for patients treated with a non-BV regimen were 4.5 months (95% CI: 2.5, 5.4) and 31.0% (95% CI: 17.8, 45.0), respectively (p=0.0135). After adjusting for known risk factors, BV therapy was the only factor associated with OS for patients undergoing further therapy after BV trial progression (hazard ratio 0.564; p-value 0.0287). Conclusions: Among recurrent GBM patients, clinical factors may poorly predict outcome for BV therapy. Outcome following BV failure is poor, but continuation of BV improves OS compared to available non-BV therapy.
A phase I and biological correlates study of capecitabine (CAP) + oxaliplatin (OX) + radiation therapy (RT) in locally advanced rectal cancer (LARC)
Authors: M. G. Fakih, A. Rajput, G. Y. Yang, L. Pendyala, K. Toth, D. D. Lawrence, J. L. Smith, N. A. Soehnlein, L. Flaherty, Y. M. Rustum
Journal: Journal of Clinical Oncology (2005)

3633 Background: Weekly CAPOX (825/50) + RT schedule has been used in phase II studies in LARC with an increased rate of toxicity. Given the lack of adequate support for the selected (825/50) dose, we conducted a phase I study with biological correlates. The objectives of the study were to determine the optimal dose of CAPOX and identify predictors of pathological response. Methods: A standard 3+3 escalation/de-escalation schema was followed. Patients (pts) with untreated LARC (T3–4 or N1–2) were eligible. OX was given weekly x 5 [50mg/m2: dose level 1 (DL1)]. CAP was given BID M-F on RT days (825mg/m2 BID). RT was given daily M-F (1.8 Gy/fraction x 28). CAPOX and RT started on day 1. Endorectal tumor biopsies (ERTB) were done prior to and on day 3 of treatment. ERTB were assayed for TS, TP, and ERCC1 by RT-PCR and for TS, TP, DPD, and apoptosis by IHC. Baseline and changes in expression were correlated with pathological response. Results: 12 pts were enrolled (median age 61; M/F 7/5; ECOG 0/1 7/5; T3/4 11/1; N0/N+ 6/6). 6 pts were treated on DL1 (825/50): 2 had a DLT of G3 diarrhea. 6 patients were then treated on DL (-1) (CAPOX 725/50): 1 pt had a DLT of G3 diarrhea/ileus. 8 pts underwent surgery: 2 pts had a complete pathological response (pCR) and 3 a near-pCR (foci of microscopic disease); 5/8 pts had T down-staging; 2/3 pts had nodal down-staging. A complete endoscopic response was seen in 9 pts but did not correlate with pathological response. No upregulation in day 3 TP levels was seen by RT-PCR or IHC. RT-PCT TP expression correlated poorly with expression by IHC. TS (RT-PCR), TP (IHC or RT-PCR), ERCC-1 baseline expression or up/down-regulation with CAPOX/RT did not predict for pathological response. The medians for apoptosis at baseline differed: 5 apoptosis/HPF for “T-down-staged group” (n=4) versus 2 for “no T-down-staging group” (n=3) (p=0.09, exact 2-sided Wilcoxon test). Conclusion: Weekly CAPOX is a convenient schedule that is associated with considerable efficacy. Elevated baseline apoptosis may be related to pathological down staging. CAPOX (725/50) is the maximum tolerated dose (MTD) and has been selected for an ongoing phase II study. No significant financial relationships to disclose.
Phase I study of everolimus (RAD001) with irinotecan (Iri) and cetuximab (C) in second-line metastatic colorectal cancer: Hoosier Oncology Group GI05-102.
Authors: B. Myre, M. Yu, J. Picus, J. A. Bufill, W. A. Harb, M. Burns, A. J. Spittler, Y. Zeng, C. R. Currie, E. G. Chiorean
Journal: Journal of Clinical Oncology (2011)

523 Background: Preclinically, mTOR and EGFR inhibitors are synergistic. We hypothesize that the mTOR inhibitor RAD001 would enhance efficacy and prevent resistance when added to an anti-EGFR agent. The purpose of the phase I portion of this study was to determine the safety and maximum tolerated dose (MTD) of daily RAD001 combined with weekly Iri and C in mCRC. Methods: Pts who failed first-line therapy, including an Iri-regimen, were treated with Iri 125 mg/m 2 weekly x 2 every 3 weeks, C 400 mg/m 2 loading dose, then 250 mg/m 2 weekly, and escalating doses of RAD001 orally: 5 mg qod, 5 mg qd and 10 mg qd during 21-day cycles, with a “3+3” design. The study was amended after the first 9 pts enrolled, to include stopping rules for excessive toxicity beyond what was expected for diarrhea, nausea/vomiting and febrile neutropenia due to Iri, and skin rash due to C. Enrollment excluded pts with UGT1A1*28, but allowed KRAS mutated mCRC. RAD001 PK was done on C2D1, and archival tumors were analyzed for pharmacodynamic markers. Results: 28 pts were enrolled, median age 61 y (25-77), 15 male, ECOG PS 0/1 (19/9). Reasons for treatment discontinuation were: PD (7), adverse events (AEs) (6), pt withdrawal, symptomatic deterioration and non-compliance (1 each). Prior to study's amendment* (n=9), 3 pts were not evaluable for DLT due to: Iri intolerance after one dose (1), non-compliance (1) and gr 3 C infusion reaction (1). DLTs and number of cycles are listed in Table. Following protocol amendment, 2 pts had DLT in cohort 3 (gr 3 mucositis), thus the MTD was 5 mg RAD001. The most common grade 3/4 AEs were: diarrhea (10), neutropenia (5), fatigue (4), acne-rash (4), mucositis (2), nausea (2), vomiting (1). Among 19 pts evaluable for response, there were 1 CR, 2 PR, (RR 16%), 9 SD (47%), 7 PD (37%). PK and pharmacodynamic data is ongoing. Conclusions: The MTD of RAD001 of 5 mg QD with Iri/C weekly is safe and clinically active. A randomized phase II study is near starting accrual. [Table: see text] [Table: see text]
ICU deaths in advanced cancer patients: Reasonableness of ICU admissions.
Authors: Alva B Weir, Katheryn M Ryder, Harvey B. Niell, Muthia Muthia, Karen Clark
Journal: Journal of Clinical Oncology (2014)

199 Background: Previous evaluations of care and outcomes for cancer patients who die in intensive care (ICU) settings have been limited to large databases. Little detailed information exists regarding the decision making in these eventually futile efforts. Reasonableness of admission has not been evaluated in detail. Methods: Previous evaluations of care and outcomes for cancer patients who die in intensive care (ICU) settings have been limited to large databases. Little detailed information exists regarding the decision making in these eventually futile efforts. Reasonableness of admission has not been evaluated in detail. Results: In our patients the mean duration of cancer awareness was 7.3 months. The majority (38) had expected duration of life prior to ICU of 6 months or less. Only 16 patients had documented discussions regarding treatment preferences or advanced directives prior to hospital admission. In establishing reasonableness of admission: 8 were post procedure complications; 21 had an ECOG performance status of 0-1 prior to admission; 14 had been notified of their incurable cancer for one month or less; an additional 3 patients had a life expectancy &gt; 6 months. Of the 52 ICU deaths of patients with advanced cancers, 31 (60%) met our criteria for reasonableness of admission in spite of advanced cancer. Of the remaining 21 patients, 9 had advanced directives in place prior to hospitalization, but without specific decisions regarding ICU care. Only 23% of futile ICU admissions in advanced cancer patients lacked both advanced directives prior to hospital admission and reasonableness of ICU admission by the above criteria. Conclusions: The majority of patients with advanced cancer who die in the ICU in our medical center are reasonable admissions, as defined by recent diagnoses, good performance status, &gt; 6 month life expectancy and admission for post procedure complications.
Distinct contributions of complement factors to platelet activation and fibrin formation in venous thrombus development
Authors: Saravanan Subramaniam, Kerstin Jurk, Lukas Hobohm, Sven Jäckel, Mona Saffarzadeh, Kathrin Schwierczek, Philip Wenzel, Florian Langer, Christoph Reinhardt, Wolfram Ruf
Journal: Blood (2017)
Metabolic response by choline positron emission tomography (cPET) to enzalutamide (ENZ) in castration-resistant prostate cancer (CRPC) patients (pts): Preliminary results of a monoinstitutional prospective study.
Authors: Francesca Maines, Orazio Caffo, Davide Donner, Antonello Veccia, Franca Chierichetti, Enzo Galligioni
Journal: Journal of Clinical Oncology (2014)

76 Background: ENZ is a new generation hormone therapy, able to produce a survival improvement in CRPC pts pre-treated with docetaxel. In Italy, ENZ is not approved yet for the daily clinical practice but until few months ago it was available through a named patient programme (NPP). Since in our Hospital CRPC pts are regularly assessed by cPET to evaluate the treatment response, so pts treated with ENZ were monitored in the same way. Methods: Eligible pts received ENZ at the standard dose of 160 mg po daily until progression. The cPET was performed at baseline, at the 3 rd treatment month and thereafter every 4 mos. For each cPET we recorded the median of the maximum standard uptake values (SUVmax) of the 5 most choline-avid region of interest (ROI) and the overall number of ROIs with SUVmax &gt; 2.5. A progressive disease (PD) was defined as the increase ≥ 30% of median SUVmax or the appearance of at least two new ROIs; a partial response (PR) as the reduction ≤ 30% of median SUVmax compared to the baseline; otherwise we considered the disease as stable (SD). Results: Out of the 31 CRPC pts treated with ENZ in our hospital from 09/12 to 03/13, 28 had complete cPET data for evaluation. The baseline median SUVmax of all evaluable pts was 10.82. At 3 mos the median SUVmax decreased to 9.30 (7 PR, 12 SD, 9 PD). Among the 19 pts evauable at 7 mos, the median SUVmax was 7.15 (8 PR, 9 SD, 2 PD). The correlation between the best metabolic response and the prostate specific antigen (PSA) response is showed in the Table. Conclusions: Our preliminary data showed a good concordance between the cPET response and biochemical response in either responding or progressing pts, while most of the pts with stable metabolic parameters showed a good PSA reduction. This is to our knowledge the first report concerning the metabolic response to ENZ and its correlation to PSA response. Further studies are required to define the role and use of cPET in monitoring the treatment efficacy in pts receiving ENZ. [Table: see text]
A phase I study of investigational agent SGI-110 combined with irinotecan in previously treated metastatic colorectal cancer patients.
Authors: Judy Sing-Zan Wang, Elske C. Gootjes, Jennifer N. Uram, Marianna Zahurak, Anthony B. El-Khoueiry, Henk M.W. Verheul, Nita Ahuja, Nilofer Saba Azad
Journal: Journal of Clinical Oncology (2015)

TPS797 Background: Studies have suggested that epigenetic modifications may play a role in oncogenesis and acquired chemoresistance in certain cancers including colorectal cancer (CRC). Our preclinical data has shown that DNA hypermethylation may confer acquired chemoresistance, and that combining a hypomethylating agent can re-induce tumor sensitivity to irinotecan in CRC cell lines. We propose a phase I study to assess the safety and tolerability of SGI-110 with irinotecan therapy in metastatic colon cancer previously treated with irinotecan. This will be followed by a randomized phase II study to evaluate efficacy of the combination. Methods: We will enroll 12-22 patients at two institutions with metastatic colon adenocarcinoma previously treated with irinotecan to our phase I study. Dose escalation will be performed in a traditional 3+3 design, where patients receive SGI-110 30-45mg/m2 SQ days 1-5 in combination with irinotecan 125mg/m2 days 1, 8, and 15 (depending on the dose level) every 28 days, with or without G-CSF. Patients will be monitored for safety and tolerance with laboratory studies, clinical exam, and periodic CT scans to assess response to therapy. In addition, pharmacokinetic studies on peripheral blood and paired tumor biopsies will be obtained to assess for global demethylation and evaluation of biomarkers. Major eligibility criteria include measureable disease with accessibility for paired tumor biopsies, and prior treatment with irinotecan without limit on number of total therapies. Current Enrollment: Dose level 1 enrolled 6 patients and encountered 1 DLT following expansion for safety assessment. Dose level -1 enrolled 3 patients and encountered 2 DLTs, which has since prompted amendments for additional dose levels with modifications to scheduled growth factor support. Dose level -1G enrollment began in September 2014. Clinical trial information: NCT01896856.
Survival impact of esophagectomy after chemoradiation for adenocarcinoma of the esophagus.
Authors: Ravi Shridhar, Jessica Freilich, Sarah E. Hoffe, Khaldoun Almhanna, William J. Fulp, Binglin Yue, Kenneth L. Meredith
Journal: Journal of Clinical Oncology (2014)

132 Background: To determine the impact of esophagectomy on survival in patients with adenocarcinoma (AC) of the esophagus cancer after chemoradiation (CRT). Methods: A database of esophageal cancer was queried for nonmetastatic patients with AC treated between 2000 and 2011 with CRT. Overall survival (OS) and recurrence-free survival (RFS) curves were calculated according to the Kaplan-Meier method and log-rank analysis. Multivariate analysis (MVA) was performed by the Cox proportional hazard model. Results: We identified 154 patients (60 without surgery; 94 with surgery) who were included in the analysis. The only differences between the 2 groups were more advanced stage and younger age in the surgery group. Patients undergoing surgery had significantly higher survival. Median and 5 year OS for surgical patients was 4.1 years and 43.6% versus 1.9 years and 35.6% for non surgical patients (p=0.007). MVA for OS and DFS revealed that factors associated with increased survival were surgical resection, tumor length &lt;5 cm, male gender, and lower stage. Age, tumor location, radiation dose/technique, and induction chemotherapy were not prognostic. There was a trend towards improved survival on univariate analysis (p=0.10) and MVA (p=0.063) for surgery patients compared to non-surgical patients who were healthy enough for surgery pre-CRT (n=38), and no difference in OS in nonsurgical patients healthy enough for surgery post-CRT (n=22). Conclusions: Esophagectomy after CRT dramatically improves survival in patients with AC after CRT. Trimodality therapy should continue to remain the standard of care for esophageal AC. However, surgery should be performed at high volume centers.