tbuckley/cabot-search huggingface dataset:
Relevance of circadian coordination for the outcome of patients with advanced gastro-intestinal (GI) cancer
Authors: F. Lévi, A. Parganiha, P. Innominato, A. Karaboué, A. Poncet, T. Moreau, C. Garufi, C. Focan, B. Coudert, G. A. Bjarnason
Journal: Journal of Clinical Oncology (2008)

15043 Background: Experimental cancer progression is controlled by the circadian timing system whose function can be assessed through non-invasive continuous rest-activity (RA) monitoring. Here, we investigated the relevance of I<O, a critical RA rhythm parameter that compares the relative amounts of activity in bed (I) and out of bed (O), for predicting tumor response, progression-free survival (PFS) and overall survival (OS) in an international cohort of 584 cancer patients (pts). Methods: RA rhythm was monitored for ≥ 48 h using a wrist-worn accelerometer (Ambulatory Monitoring Inc., Ardsley, NY, USA) before chemotherapy delivery (12 centers in 4 countries). A comprehensive database was constructed including pts history and characteristics, treatment received, its tolerability and efficacy. Main items were verified in pt charts and updated for 372 GI pts. This process is ongoing for the remaining pts. Univariate and multivariate analyses (SPSS 15.0) determined the relationship between I<O (range: 50%, no rhythm; 100%, marked rhythm) and pt characteristics, tumor response, PFS and OS. Results: Pts characteristics: 198 men, 174 women; median age, 58.4 y (range: 21–79); WHO performance status 0/1/2, 210/133/29 pts; colon/rectum/other, 260/103/9 pts; 1/2/3 metastatic sites, 164/151/55 pts; % liver involvement, none/≤25%/>25%, 68/158/141 pts; prior chemotherapy, 152 pts. Median I<O at baseline was 97.3 [25th-75th percentile, 93.7 - 99.2]. Chronotherapy was given to 280 pts. A good RA circadian rhythm (I<O above median) predicted for better response (partial + complete: 42.1 vs 30.5%, p = 0.026), median PFS (6.5 vs 4.5 months, p = 0.009) and OS (18 vs 11 months, p < 0.0001). Multivariate analyses confirmed that I<O was an independent prognostic factor (p<0.001) for treatment response jointly with gender (p=0.011) and for PFS and OS jointly with performance status (p = 0.001), number of metastatic sites (p <0.002) and prior chemotherapy (p < 0.015). Conclusions: Pts with metastatic GI cancer achieve better clinical outcome on treatment if their baseline circadian rhythm in rest-activity is maintained. Therapeutics targeted at clock genes or circadian signalling pathways deserve testing for improving the outcome of pts with circadian disruption. No significant financial relationships to disclose.
Randomized phase III clinical trial of two different arms of a combined treatment with carnitine plus celecoxib with or without megestrol acetate for patients with cancer-related anorexia/cachexia syndrome (CACS).
Authors: C. Madeddu, F. Panzone, R. Serpe, G. Antoni, M. C. Cau, F. M. Tanca, M. Dessi', M. Mura, Q. Mela, A. Macciò, G. Mantovani
Journal: Journal of Clinical Oncology (2011)

e19733 Background: Cancer-related anorexia/cachexia syndrome (CACS) is a multifactorial syndrome characterized by loss of lean body mass (LBM), metabolic alterations, chronic inflammation and fatigue. Methods: In October 2009 we started a phase III randomised study to establish which was the most effective and safest treatment to improve the “key” variables of CACS: increase of LBM, decrease of resting energy expenditure (REE), improvement of fatigue (MFSI-SF) and physical activity (ArmBand). As secondary endpoints we evaluated: grip strength, six minute walk test (6MW), appetite, serum levels of IL-6 and TNF-a, EORTC-QLQ-C30, Glasgow Prognostic Score (GPS), ECOG PS. All patients received as basic oral treatment poliphenols + alpha lipoic acid + carbocysteine + Vitamins A,C,E and were then randomly assigned to: L-carnitine 4 g/d + Celecoxib 300 mg/d (Arm 1) or the same treatment + megestrol acetate (MA) 320 mg/d (Arm 2). Treatment duration: 4 months. The planned sample size was 70 patients for each arm. An interim analysis (intent-to treat) was planned. Results: Sixty cachectic patients (mean age 65.2 ± 8.7 years) with tumors at different sites were enrolled and 57 were evaluable (3 died early due to disease progression). Analysis of changes from baseline showed that LBM assessed by DEXA as well as by L3-CT improved in both arms. Fatigue improved significantly in both arms. REE and physical activity did not show significant changes. As for secondary endpoints, the 6MW test, appetite, GPS and ECOG PS improved significantly. The comparison between the 2 arms by ANOVA test did not show a significant difference. Toxicity was substantially negligible and comparable between arms (1 grade 3 diarrhea in arm 1 and 2, which led to the withdrawal of carnitine for 2 weeks). Conclusions: Both arms showed to be effective as for primary efficacy endpoints (improvement of LBM and fatigue) and some important secondary endpoints. The results of the present trial confirm the efficacy of a combined approach for the treatment of CACS: arm 1, without MA, could be the treatment of choice as it was effective and easier to administer. The trial is ongoing.
The impact of maximum tumor shrinkage of primary site (MTSP) by FOLFIRINOX in the first-line treatment of pancreatic cancer.
Authors: Kei Saito, Masato Ozaka, Ryo Kanata, Ikuhiro Yamada, Takashi Sasaki, Masato Matsuyama, Kouichi Takano, Naoki Sasahira
Journal: Journal of Clinical Oncology (2016)

356 Background: FOLFIRINOX is the first-line chemotherapy for patients with unresectable pancreatic cancer and yielded a longer overall survival, a superior progression-free survival, a higher objective response rate compared with gemcitabine alone. Maximum tumor shrinkage of primary site (MTSP) was associated with the survival outcome in colon cancer. However the data of tumor shrinkage in pancreatic cancer has not been well-documented. Therefore, we re-evaluated FOLFIRINOX focusing on the tumor shrinkage of primary site. We also assessed impact of tumor shrinkage on survival of unresectable pancreatic cancer. Methods: Medical records were retrospectively reviewed for consecutive patients receiving FOLFIRINOX as the first-line chemotherapy between January and December 2014. Response was evaluated by CT scan every 2 or 3 months until the end of treatment. We analyzed patients’ characteristics and rate of MTSP related to overall survival (OS) and progression free survival (PFS). Results: Thirty one patients were analyzed: median age of 62, male gender in 64.5%, performance status of 0 in 90.3%, metastatic cancer in 58.1%, the head of cancer in 41.9%, the UGT1A1 wild type in 48.4%, overall response rate in 25.8%. PFS was 7.7 months (95%CI: 6.57-9.6). Rate of MTSP were 18.8% (locally 18.8%, metastatic 18.1%) and rate of GRs/non-GRs/non-R (GRs (Good responders) were defined as patients whose MTSP were more than 20% and non-GRs (non-Good responders) were less than 20%) were 45.2%/35.5%/19.3%. PFS was 9.0(95%CI, 6.7- ) months in GRs, compared with 6.9(95%CI, 3.6-10.2) months in non-GRs (p = 0.15). Conclusions: MTSP by FOLFIRINOX could not affect PFS of pancreatic cancer.
Radiation oncologist visits and the effect on prostate cancer (PCa) survival among SEER-Medicare patients with stage IV disease.
Authors: E. Onukwugha, C. D. Mullins, M. Grabner, A. Hussain
Journal: Journal of Clinical Oncology (2011)

e15117 Background: Management of advanced-stage PCa frequently requires multimodal therapy and there is a hypothesized benefit of consulting with multiple specialists prior to commencing active treatment. We tested whether pre-treatment multi-specialist care (PTMSC) is associated with PCa-specific survival. Methods: We examined patients older than 65 within SEER-Medicare diagnosed with stage IV PCa between 1994 and 2002, who were receiving hormone-, radiation-, or chemotherapy and who saw a urologist plus a radiation oncologist (RO) during follow-up through 2004. We defined PTMSC as post-diagnosis visits to a urologist and a RO before treatment initiation. The effect of PTMSC on PCa mortality was analyzed using a Cox model among stage IV patients and in subgroups with (M1) and without (M0) metastatic disease. Separate models were estimated in a propensity-score matched sample to control for observable selection bias and using non-PCa mortality as an outcome to assess for unobservable selection bias. Results: Among the treated men, 2,045 saw a urologist and a RO (11% saw both before starting treatment). The median time to the initial post-diagnosis urologist visit was 1 month and the median time to the initial post-diagnosis RO visit was 6 months. Fifty-nine percent of Stage IV PCa patients had incident M1 disease. Overall mortality was 61% and median follow-up was 37 months. PCa mortality was significantly lower in the PTMSC vs. no PTMSC group (17% vs. 50%, p<0.001). In covariate-adjusted models, PTMSC was associated with PCa-specific survival in the original sample (full sample: HR 0.47; M0: HR 0.38; M1: HR 0.52; all p<0.01) and in the propensity-score matched sample of 440 men (HR: 0.45, 95% CI: 0.30-0.68, p<0.001). PTMSC did not impact non-PCa mortality in a covariate-adjusted model (HR: 1.09, 95% CI: 0.77-1.53, p=0.63). Conclusions: Stage IV PCa patients with visits to urologists and ROs have longer survival when those visits occur prior to treatment initiation. The effect is observed in both M0 and M1 patients and is maintained in a propensity-matched sample. Future research should explore whether the hypothesized benefit of multi-specialist care occurs in routine clinical practice.
Neoadjuvant chemoradiotherapy with S-1 in patients with borderline resectable pancreatic cancer.
Authors: Masashi Hattori, Tsutomu Fujii, Masaya Suenaga, Suguru Yamada, Mitsuro Kanda, Naoki Iwata, Daisuke Kobayashi, Chie Tanaka, Goro Nakayama, Hiroyuki Sugimoto, Masahiko Koike, Shuji Nomoto, Michitaka Fujiwara, Yasuhiro Kodera
Journal: Journal of Clinical Oncology (2014)

302 Background: The aim of this study was to investigate the efficacy and safety of neoadjuvant chemoradiotherapy (NACRT) with S-1 (oral fluoropyrimidine) followed by surgery for the treatment of borderline resectable pancreatic cancer that involved the major visceral artery or the portal venous system. Methods: Twenty-eight patients with pancreatic cancers that abutted the SMA in 10, the CHA in 7, the both SMA and CHA in 1, and occluded the SMV/PV in 10 were treated with NACRT at a single institution. Radiation therapy was delivered at a total dose of 50.4 Gy in 28 fractions. S-1 was administered orally at a dose of 80 mg/m(2)/day for 14 consecutive days followed by a 7-day rest period during radiation therapy. After radiotherapy and 2 courses of S-1, restaging was done to evaluate secondary resectability. Results: Of the all patients, 25 underwent a full course of NACRT, and NACRT terminated in 3 patients because of grade 3 leukopenia in 2 and tumor bleeding in 1. Partial response was achieved in 3 patients and stable disease in 22. Twenty-four patients (86%) underwent surgical resection, and all had margin-negative (R0) resections. Only two patients (8%) had major morbidity as Clavien-Dindo’s classification III or more, and there was no operative or in-hospital mortality. Pathological examination revealed that more than 50% of tumor cells had disappeared in 14 cases and all cases achieved Evans’ score IIa and more. Conclusions: Neoadjuvant chemoradiation with S-1 was feasible and promising therapy for borderline resectable pancreatic cancer that involves the major artery or the portal venous system.
Expression of HMGA2 in PB Leukocytes and Purified CD34+ Cells from Normal Individuals and Patients with Myelofibrosis and Myeloid Metaplasia.
Authors: Joris R. Andrieux, Chrystèle Bilhou-Nabera, Jean Loup Demory, Olivier Pierre-Louis, Brigitte Dupriez, Nathalie Grardel, Agnès Charpentier, Vincent Praloran, Francis Bauters, Jean Luc Laï, Marie-Caroline Le Bousse-Kerdilès
Journal: Blood (2004)
Adoption of neuroendocrine tumor (NET) research into treatment guidelines: Are rare cancers neglected?
Authors: J. R. Strosberg, L. K. Kvols
Journal: Journal of Clinical Oncology (2010)

e14672 Background: Adoption of research findings into treatment guidelines may vary. Integration of new research data into guidelines in rare diseases such as NETs, may differ from that seen with common, well-characterized cancers like breast carcinoma. Methods: Guidelines from national and international societies with a focus on breast cancer or NETs were reviewed to determine when and how clinical research findings influence recommended treatment practice. Results: In breast cancer, pivotal trials of taxanes were reported in May 1998 and Nov 2000, and first integrated into guidelines in 2003 (National Comprehensive Cancer Network [NCCN] breast cancer guidelines). Pivotal data regarding aromatase inhibitors were released in Dec 2001 and Dec 2008, with key guideline adoption first in 2002 (NCCN) and 2009 (St Gallen International Expert Consensus), respectively. By contrast, there have been few randomized, placebo-controlled studies in patients with NETs. Studies evaluating interferon-α ± somatostatin analogues, and studies of radiolabeled somatostatin analogues have been limited to phase II trials. Consequently, guidelines have typically remained inconclusive and important NETs guidelines from NCCN and the European NET Society (ENETS) remain noncommittal on the use of these agents. However, after presentation of the antiproliferative effect of octreotide LAR in a randomized, double-blind, placebo-controlled phase III study (PROMID) at ASCO-GI Jan 2009, NCCN NETs guidelines were updated in May 2009 to reflect octreotide LAR as an antitumor therapy. The first guidelines issued by the North American NETs Society (NANETS; publication in Pancreas April 2010) will also include the PROMID findings. Conclusions: Integration of research into guidelines can be affected by study quality, strength of findings and guideline review schedules. First guideline adoption occurred within < 1 to 4 years after presentation of pivotal breast cancer studies. With PROMID, 4 and 16 months elapsed between data release and publication of updated NCCN and new NANETS guidelines, respectively, demonstrating rapid uptake with the availability of key data. Other guidelines are under review. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis Novartis
Tolerance of neoadjuvant chemoradiation for rectal cancer in patients age 70 or older.
Authors: D. N. Cagney, C. Cagney, C. Gillham
Journal: Journal of Clinical Oncology (2011)

e19565 Background: Neoadjuvant chemoradiotherapy is the standard of care for locally advanced rectal cancer. However there is a lack of data available on the tolerance of elderly patients to this treatment. Aim: To evaluate tolerance and toxicity of neoadjuvant chemoradiotherapy in rectal cancer patients older than 70 years. Methods: We performed a retrospective review of all patients treated with long course neoadjuvant chemoradiotherapy {50.4Gy in 28 fractions with continuous infusion i.v. 5-FU alone (225 mg/m2/day)}.From November 2001 to June 2010, 92 patients were treated for histologically proven locally advanced rectal adenocarcinoma (< 12 cm from the anal verge) classified as either T3 or T4, N0 or N1-2 M0 disease. Correlation between proportions was tested using a Fisher f test. Results: Twenty were aged >70 years (median 73yrs) and 72 under 70 (median 58yrs). Planned radiation therapy was completely delivered in 17 (85 percent) of the older age group and in 67 (93 percent) of the younger age group (p>0.05). The full protocol dose of chemotherapy was delivered in 14 (70%) and 64 (89%) patients of older and younger age group respectively (p>0.05). The main causes of chemotherapeutic schedule violation in the older age group were CTC grade 3/4 diarrhoea (3 patients) and grade 3 neutropenia (3 patients) All older patients underwent surgical treatment six to eight weeks after CRT as follow: low anterior resection (12 patients) and abdominoperineal resection (8 patients). Conclusions: Our results emphasize that age should not be the only deciding factor in the treatment of locally advanced rectal cancer. We would be keen for patients receive the most intensive and appropriate treatment thought to be safe and effective according to their biological age and comorbidities according to the recommendations of the International Society of Geriatric Oncology.
Activity of pazopanib in chemo-resistant patients with germ cell tumors (GCT): First results of the open-label, single-group, phase II PAZOTEST-01 trial.
Authors: Patrizia Giannatempo, Nicola Nicolai, Elena Farè, Daniele Raggi, Luigi Piva, Davide Biasoni, Mario Catanzaro, Tullio Torelli, Silvia Stagni, Massimo Maffezzini, Alessandro Crestani, Elena Togliardi, Roberto Salvioni, Alessandro M. Gianni, Andrea Necchi
Journal: Journal of Clinical Oncology (2014)

376 Background: Patients (pts) with germ cell tumors (GCT) who fail to be cured following multiple chemotherapy (CT) courses (± high-dose CT) have an extremely poor prognosis and long-term remissions are anecdotal. Pazopanib (PZP) is a potent and selective, orally available, TKI of VEGFR1, 2, and 3, PDGFRα, PDGFRβ, and cKit. Here we report the initial results of the ongoing open-label, single-group, phase II study which is sponsored by INT Milano (ClinicalTrials.gov NCT01743482). Methods: Pts with refractory GCT received pazopanib 800 mg/day orally until disease progression or evidence of unacceptable toxicity/side effects. Eligibility requirements included failure of at least two platinum-based CT, including high-dose CT. All pts underwent measurement of serum tumor markers (STM), a computed tomography and a FDG-PET after one month of treatment and q2 months thereafter. Results: From May 2013 to July 2013, five pts were enrolled, three in fourth, and two in fifth-line. Median age was 39 (IQR: 33 to 48). Three out of five had failed high-dose chemotherapy (HDCT), two had an extragonadal primary, all pts had at least one elevated STM at baseline, the sole parameter in one patient, two had liver metastases, four pts had a retroperitoneal relapse. Four had elevation of alfafetoprotein (AFP), one of human choriogonadotropin (HCG). Four were nonseminomas, one a pure seminoma. After the first month of treatment, four out of five pts had a decrease in marker levels, one patient had disease progression (PD). Two of the responding pts had a necrotic evolution of disease at computed tomography corresponding to a RECIST and metabolic (PET/CT) progression, two had a stable disease. Two-month follow up is available for three out of four responders: one interrupted PZP for toxicity and had a marker PD, another an increase to baseline levels and the last one a further reduction (pure seminoma, one out of five confirmed response at two months). There were two cases of hepatic toxicities (one G2 and one G3-4 with dose interruption). Conclusions: PZP is endowed with preliminary activity in extensively pretreated patients with GCT. The unique availability of STM in interpreting densitometric and metabolic response might provide insights into response assessment of solid tumors under antiangiogenic therapy. Clinical trial information: NCT01743482.
First report of a randomized phase II trial of multi-epitope vaccination with melanoma peptides for cytotoxic T cells and helper T cells in patients with metastatic melanoma: An Eastern Cooperative Oncology Group Study (E1602).
Authors: C. L. Slingluff, S. J. Lee, K. A. Chianese-Bullock, W. C. Olson, L. H. Butterfield, P. D. Leming, J. M. Kirkwood
Journal: Journal of Clinical Oncology (2010)

8508 Background: This multicenter randomized trial was designed to evaluate, in advanced previously treated melanoma, whether melanoma helper peptides augment CD8+ T-cell responses to a melanoma vaccine and improve clinical outcome. Methods: ECOG enrolled 174 patients with measurable stage IV melanoma into 4 treatment groups, each vaccinated with 12 MHC class I-restricted melanoma peptides (12MP) to stimulate CD8+ T cells alone (group A), plus either a tetanus peptide (group B) or a mixture of 6 melanoma helper peptides (6MHP) to stimulate CD4+ T cells (group C), or with 6MHP alone (group D), in incomplete Freund's adjuvant (IFA) plus GM-CSF. Clinical outcomes were recorded. CD8+ T-cell responses were assessed by in vitro stimulated IFN-gamma ELIspot assay, and CD4+ T-cell responses were assessed by proliferation assay. 167 were evaluable for toxicity, and 126 (of 142) analyzable for immunologic and clinical outcomes. Results: Vaccines were generally well-tolerated, but nine grade 4 toxicities were reported in 6 patients (4%): hematologic (5), tumor pain (1), infection (1), cardiac (1), and CNS (1). Best clinical response was PR in 6/126 evaluable patients (5%). Median survival was 11.4 months (95% CI 9.9,14.9) without differences among groups. CD8+ and CD4+ T-cell responses were induced by 12MP, 6MHP, and tetanus peptides (Table, marked with an asterisk). CD8+ responses were highest in groups A (39%) and B (46%). Conclusions: These multipeptide vaccine preparations stimulate CD4+ and CD8+ T-cell responses in patients with advanced melanoma, and are associated with objective clinical regressions in 5% of patients. Combination of the 12MP and 6MHP melanoma peptides to stimulate both CD4+ and CD8+ T cells adds no clinical or immunologic benefit over use of either peptide mixture alone, but each was associated with immunologic and clinical responses. CD8+ response CD4+ response Clinical response rate Group Vaccine N 12MP Tetanus peptide 6MHP A 12MP alone 36 39%* 11% 0% 3% B 12MP + tetanus 28 46%* 57%* 4% 4% C 12MP + 6MHP 28 29%* 4% 36%* 7% D 6MHP alone 34 3% 0% 35%* 6% Total 126 29% 17% 18% 5% Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Immatics Immatics Berlex/Genzyme, GlaxoSmithKline University of Virginia Patent Foundation