tbuckley/cabot-search huggingface dataset:
Implementation of an exercise behavior change clinic for men with prostate cancer: Baseline results.
Authors: Sarah Weller, Maria Spillane, Phil Pollock, Monita Sundar, Larry Goldenberg, Lindsay Hedden, Celestia S. Higano
Journal: Journal of Clinical Oncology (2017)

169 Background: Regular physical activity (PA) and resistance training (RT) has been shown to improve the health of prostate cancer survivors (PCS), however participation rates are low. To address survivorship needs and support behaviour change, the Prostate Cancer Supportive Care (PCSC) program implemented an Exercise Physiology (EP) clinic using one-on-one exercise counselling. Our objective was to understand the PA and RT characteristics of PCS and examine the effect of an EP clinic on behaviour change. Methods: After enrolment in the PCSC program, PCS were offered a consultation with an Exercise Physiologist. Subsequent consultations occurred at 3, 6 and 12 months. Clinical data collected at each consultation included physical measures, stage of change (TTM), current exercise (GLTEQ and exercise summary), fatigue (FACIT Fatigue and SIFIR), barriers and facilitators to exercise and a safety screening (PAR-Q+). Information was used during the EP clinic to set PA goals and create an action plan for behaviour change, reviewed each visit. Results: 71 PCS, median age 67 (range 50-86) attended the EP clinic between July 2015 and August 2016. 76% had received primary treatment and 24% were on active surveillance. At first consultation, 63% had an at-risk health profile, with an average BMI of 27kg/m2 (overweight), average waist circumference of 102.6cm (high) and insufficient PA, with only 15% meeting both PA and RT guidelines (150 mins moderate-to-vigorous PA and 2 RT sessions weekly). Average reported fatigue was moderate (4/10 on SIFIR). Stage of change (TTM) showed 44% of PCS at pre-contemplation, contemplation or preparation stages and 54% at action or maintenance stages. Self-reported barriers to exercise included lack of time (24%), laziness (19.7%) and fatigue (18%), while exercising with a spouse/friend/team was the main facilitator to exercise (16.9%). Conclusions: The baseline PA and RT levels of EP clinic PCS is similar to population norms in that the majority of PCS are not meeting current guidelines. Our results demonstrate that the implementation of an EP clinic is feasible. Future follow-up of this cohort will evaluate whether the program creates sustainable PA behaviour change in PCS.
Humoral and cellular immune response after influenza vaccination in patients with postcancer fatigue and patients with chronic fatigue syndrome.
Authors: Hetty Prinsen, Jolanda de Vries, Foekje Stelma, Sasja Mulder, Carla Van Herpen, Jan Willem Leer, Lammy Elving, Gijs Bleijenberg, Hanneke W.M. Van Laarhoven
Journal: Journal of Clinical Oncology (2012)

9070 Background: Postcancer fatigue (PCF) is a frequently occurring problem, impairing quality of life. Patients with chronic fatigue syndrome (CFS) also suffer from severe fatigue symptoms. We hypothesized that in fatigued patients (PCF and CFS) alterations in immune response could explain fatigue symptoms. Therefore, we examined whether the humoral and/or cellular immune response after influenza vaccination differed between fatigued patients and non-fatigued individuals and between PCF and CFS patients. Methods: PCF (n=15) and CFS patients (n=22) were vaccinated against influenza. Age and gender matched non-fatigued cancer survivors (n=12) and healthy controls (n=23) were included for comparison. Antibody responses were measured at baseline and at day 21 by a hemagglutination inhibition test. T cell responses were measured at baseline and at day 7 by a lymphocyte proliferation and activation assay. Results: Both patient groups developed seroprotection rates comparable to the accompanying control groups. Functional T cell reactivity was observed in all groups. Proliferation at baseline was significantly lower in fatigued patients compared to non-fatigued individuals. A significant increase in proliferation from baseline to day 7 was observed in fatigued patients, but not in controls. At day 7, proliferation was not significantly different between fatigued patients and non-fatigued individuals. CD4+CD127-FoxP3+ expression was significantly higher in PCF patients compared to non-fatigued cancer survivors. Conclusions: We observed a lower T cell proliferation at baseline in fatigued patients compared to non-fatigued individuals, suggesting a difference in the baseline state of the immune system between fatigued patients and non-fatigued individuals. Furthermore, the difference in CD4+CD127-FoxP3+ expression between PCF and CFS patients suggests subtle differences in immune state between these two fatigued patient groups. However, since humoral and cellular immune responses after vaccination did not differ significantly between fatigued patients and non-fatigued individuals, vaccination of fatigued patients (PCF and CFS) can be effective.
Chemotherapy-induced changes in the physiologic reserve of elderly patients diagnosed with cancer.
Authors: MJ Molina-Garrido, Carmen Guillen-Ponce, MM Munoz-Sanchez, A. Olaverri Hernandez, Carolina Ortega Ruiperez, JA Santiago Crespo, Alfredo Carrato
Journal: Journal of Clinical Oncology (2012)

e19590 Background: Frailty is a biological syndrome of the elderly that is characterized by the loss of the reserve in multiple organ systems. The aims of this study were a) to identify the presence of frailty in the elderly with cancer, by measuring their functional reserve baseline and after chemotherapy treatment, and b) to assess which of the functional reserve parameters checked suffered a change ≥30%, suggestive of frailty. Methods: Prospective cohort study of oncologic patients ≥70 years of age, evaluated in a Spanish Unit of Cancer in the Elderly (from January 2010 to December 2011). Most of patients (88.9%) had a basal status between 0-1 (measured by the ECOG index). We collected information about the individual's physiologic reserve (skeletal muscle mass [SMM], walking speed, peak-flow, grip strength, creatinine clearance [CC] and Pfeiffer test). Parameters of functional reserve were determined at baseline and 4 months after chemotherapy was started. It was used a pre-post design, and a control group of patients not treated with chemoterapy (group B). To identify significant differences between the results of parameters of physiologic reserve it was used a t-student t test for independent groups. It was calculated the change percentage in each of these variables. Results: We analyzed data from 66 patients in group A (treatment with chemotherapy) and 68 in group B (no chemotherapy). Age average: 78.68 years. Gastrointestinal tumors (37.3%) and breast and gynecologic tumors (32.1%), others (30.6%); 28.8% were metastatic tumors. After chemotherapy, there were no significant differences in walking speed (p =0.323), handgrip strength (p =0.162), peak-flow (p =0.954), cognitive status (p =0.078) or CC (p =0.425). However, there was an increase in SMM (0.618 kg, 95% CI: 0.020 to 1.215, p =0.043). Changes after treatment were as follow: SMM and peak-flow increased by 2%, grip strength decreased by 15% and CC was reduced by 0.05%. Conclusions: The elderly physiologic reserve is not modified as a result of chemotherapy treatment, except for SMM. This change could be related to tumor response achievement. None of the physiologic reserve parameters was useful in this setting, as a "marker of frailty".
Extended <i>RAS</i> analysis and subsequent anti-EGFR and anti-VEGF treatment (tx) in PEAK: A first-line phase 2 study of FOLFOX6 + panitumumab (pmab) or bevacizumab (bev) in metastatic colorectal cancer (mCRC).
Authors: Fernando Rivera, Lee Steven Schwartzberg, Meinolf Karthaus, Gianpiero Fasola, Jean-Luc Canon, J. Randolph Hecht, Ying Tian, Hua Yu, Kelly Smith Oliner, William Y. Go
Journal: Journal of Clinical Oncology (2014)

3629 Background: In PEAK, progression-free survival (PFS) was similar and overall survival (OS) was improved with pmab + FOLFOX6 relative to bev + FOLFOX6 in patients (pts) with WT KRAS exon 2 mCRC. In an extended RAS analysis (exons 2, 3, and 4 of KRAS/NRAS), this improvement was enhanced in pts with WT RAS. This analysis evaluates pts who received subsequent biologic therapy in PEAK. Methods: Kaplan-Meier medians for OS were estimated for pts receiving pmab/subsequent anti-VEGF tx and pts receiving bev/subsequent anti-EGFR tx. Analyses were performed on pts with WT KRAS exon 2 and WT RAS from an exploratory, updated analysis (03Jan2013). Results are from the time of randomization. Results: Demographic and baseline characteristics were generally similar with differences of < 20% between arms. Results are shown (Table). Prespecified analyses suggest that individual RAS exons that are WT favor the pmab arm and will be presented. Conclusions: In this exploratory analysis, the time and % of pts to biologic subsequent tx were similar between the arms. Median OS was observed to be longer for pts receiving pmab/subsequent anti-VEGF tx relative to pts receiving bev/subsequent anti-EGFR tx and the improvements were similar to that in the total populations of the WT KRAS exon 2 and WT RAS groups. Clinical trial information: NCT00819780. Pmab + FOLFOX6 Bev + FOLFOX6 Pmab + FOLFOX6 subsequent anti-VEGF Bev + FOLFOX6 subsequent anti-EGFR WT KRAS Exon 2, n 142 143 57 54 OS, events (%) 52 (37) 78 (55) 24 (42) 36 (67) Median (95% CI), mos 34.2 (26.6 - NA) 24.3 (21.0 - 29.2) 34.2 (23.0 - 41.3) 25.3 (22.1 - 29.2) Median (range) time to subsequent tx, mos anti-EGFR 12.0 (3 - 24) anti-VEGF 12.5 (2 - 38) WT RAS, n 88 82 35 30 OS, events (%) 30 (34) 40 (49) 13 (37) 15 (50) Median (95% CI), mos 41.3 (28.8 - 41.3) 28.9 (23.9 - 31.3) 41.3 (26.6 - 41.3) 29.0 (26.0 - 34.4) Median (range) time to subsequent tx, mos anti-EGFR 15.4 (4 - 24) anti-VEGF 13.0 (2 - 38)
Symptom clusters (SCs) in advanced cancer patients (ACPs): A prospective cohort study.
Authors: Pedro Miguel Coecho Barata, Sonia Margarida Duarte De Oliveira, Filipa Santos, Frederico Filipe, Maria Paula Custódio, Alice Cardoso, Marta Alves, Ana Papoila, António Barbosa, Peter G Lawlor
Journal: Journal of Clinical Oncology (2015)

e20664 Background: Few studies have longitudinally examined SCs in ACPs. We investigated the presence, stability and prognostic implications of SCs in ACPs. Methods: Consecutive ACPs rated 9 Edmonton Symptom Assessment System symptoms on a 0-10 scale and 10 other symptoms on a 1-5 scale at initial Palliative Care Clinic consultation (T0), two (T2) and four (T4) weeks later. We used the Friedman test to assess temporal change in symptom scores, and a principal component factor analysis to determine SCs at T0, T2 and T4. The prognostic value of SCs was assessed using Kaplan-Meier and Cox multiple regression model estimates. Results: Our sample of 284 ACPs had a median (range) age of 69 (35-94) years and 164 (58%) were male. The most distressing symptoms (at T0, T2 and T4, respectively) were tiredness (86%, 84% and 88%), weight loss (82%, 71% and 58%), dry mouth (82%, 72% and 72%) and lack of well-being (82%, 68% and 68%). No changes over time were observed for most symptoms. Cluster composition analysis at T0 identified 3 factors: tiredness/lack of appetite/lack of well-being (TA), nausea/vomiting/hiccups (NV), and insomnia/sleep disturbance (IS). These SCs accounted for 39% of variance, and maintained 43%, 75% and 66% of their initial composition at T4. Median overall survival was 1.4 (1.0-1.8) months. Patients with TA or NV lived 1.1 (0.8-1.3; 0.6-1.6) months, compared with 6.1 (3.4-8.9) and 2.0 (1.4-2.6) months, respectively, for those in whom they were absent (P < 0.001; P = 0.002). Patients with < 2 SCs lived 1 month longer than those with 2 or more (P < 0.001). Female gender and higher factor scores of TA at T0 were associated with shorter survival (HR = 1.43, p = 0.005; HR = 1.15, p = 0.032). Conclusions: At end-of-life, SCs present with “core” symptoms and have prognostic value. To optimize quality of life in ACPs, further studies are needed to target these SCs and evaluate respective therapeutic interventions.
Pancreatic metastasis from osteosarcoma diagnosed by endoscopic ultrasound fine-needle aspiration biopsy (EUS-FNAB)
Authors: F. Bertucci, J. Araujo, A. Sarran, G. Monges, J. Carvalho Junior, D. Perrot, E. Bories, L. Rossini, M. Giovannini
Journal: Endoscopy (2012)

Corrected by: Pancreatic and lymph node metastases from maxillary osteosarcoma diagnosed by endoscopic ultrasound-guided fine needle aspirationEndoscopy 2012; 44(S 02): E254-E254DOI: 10.1055/s-0032-1310222
Prognostic factors for high-grade soft tissue sarcomas (STS) in the extremities treated by perioperative chemotherapy with ifosfamide (IFO) and doxorubicin hydrochloride (ADM): Using the data from Japan Clinical Oncology Group trial (JCOG0304).
Authors: Kazuhiro Tanaka, Tadashi Hasegawa, Junki Mizusawa, Nobuhito Araki, Hirokazu Chuuman, Mitsuru Takahashi, Toshifumi Ozaki, Toru Hiruma, Hiroyuki Tsuchiya, Hideo Morioka, Hiroshi Hatano, Takuro Wada, Masami Hosaka, Yukihiro Yoshida, Junya Toguchida, Satoshi Abe, Akihiko Matsumine, Koichiro Yokoyama, Haruhiko Fukuda, Yukihide Iwamoto
Journal: Journal of Clinical Oncology (2014)

10577 Background: STS are rare malignant tumors and relatively resistant against chemotherapy. We have previously reported the efficacy of perioperative chemotherapy with ADM and IFO for STS in the extremities (JCOG0304) in ASCO 2011(abstract ID:#10078). In the present study, we carried out analysis of the factors influencing on survival of the patients in JCOG0304. Methods: Patients with operable, high-grade non-round cell STS (T2bN0M0) in the extremities were treated with preoperative ADM 60mg/m2 plus IFO 10g/m2 for 3 courses with 3-week interval, followed by operation and postoperative 2 courses of the same regimen. The histological grade of the tumor was assessed using both FNCLCC system (FNCLCC grade) and positivity of Ki67 in the tumor cells (MIB-1 grade). Promising prognostic factors identified by log-rank test were included in multivariate Cox regression model. Results: A total of 72 patients were enrolled in JCOG0304 and 70 all eligible patients were analyzed for this study. The clinical factors regarding age, sex, performance status, histologic subtype, tumor differentiation score, mitosis, and necrosis of biopsy specimen did not significantly influence on overall survival (OS). Although FNCLCC grade was also not associated with OS, histologic grade assessed using MIB-1 (grade 2 vs 3) was only the factor significantly associated with OS (HR 4.12 (95%CI:0.89-19.09), p=0.049). MIB-1 was also associated with OS on multivariate analysis (HR:4.05 (95%CI:0.86-19.15), p=0.077). Conclusions: Among factors tested in the present study, only MIB-1 grade was associated with survival of the patients treated in JCOG0304. This is the first clinical trial demonstrating that MIB-1 expression is prognostic factor of the patients with operable STS in the extremities. The results indicate that MIB-1 system might be useful for the better evaluation of histological grade of STS. Clinical trial information: C000000096.
Phase 1b dose-escalation and cohort-expansion study of the safety, tolerability, and efficacy of a novel transforming growth factor-β receptor I kinase inhibitor (galunisertib [G]) administered in combination with the anti-PD-L1 antibody (durvalumab [D]) in recurrent or refractory metastatic pancreatic cancer.
Authors: Davide Melisi, Susan C. Guba, Maria Karasarides, Valerie Andre
Journal: Journal of Clinical Oncology (2017)

TPS501 Background: Transforming growth factor-β (TGF-β) can suppress adaptive and innate anti-tumor immune responses. G (LY2157299) is an oral small molecule inhibitor of TGF-β receptor I kinase that down-regulates phosphorylation of SMAD2, abrogating activation of the canonical pathway. Programmed cell death-ligand 1 (PD-L1) is upregulated in a broad range of cancers including pancreatic; expression of PD-L1 helps tumors evade immune system detection through binding to PD-1 on cytotoxic T lymphocytes. D (MEDI4736) is an anti-PD-L1 monoclonal antibody that blocks PD-L1/PD-1 interactions. Blockade of both TGF-β and PD-L1 pathways could reverse immunosuppression associated with these molecules by activating adaptive and innate anti-tumor immune responses. Methods: This two part phase 1b open-label study will enroll patients (pts) with recurrent or refractory metastatic pancreatic cancer. Part 1 is a 3+3 dose-escalation assessment of the safety and tolerability of G (4 escalating doses) and D (constant dose). After dose-limiting toxicity evaluation, cohort expansion with approximately 25 pts at the dose determined in the dose escalation portion will occur. Eligible pts have recurrent or refractory metastatic pancreatic cancer ( ≤ 2 prior systemic regimens) regardless of PD-L1 status; ECOG PS 0-1. Pts who have received prior therapy targeting T-cell costimulation or checkpoint pathways, or have received a TGF-β R1 kinase inhibitor are not eligible. Pretreatment and on-treatment biopsies will be obtained. The primary objective is to assess safety and tolerability of G in combination with D by identifying dose-limiting toxicities and to assess safety of the combination at the dose-escalation-established dose. Secondary objectives are pharmacokinetics; immunogenicity; preliminary anti-tumor activity; overall survival. Exploratory objectives are to examine biomarkers relevant to G, D, and the disease state. Enrollment began on 15-June-2016; as of 13-Sep-2016, 1 pt entered treatment. Clinical trial information: NCT02734160.
Left versus right sided colorectal cancer: Teasing out drivers of disparity in outcomes in metastatic disease.
Authors: Belinda Lee, Shehara Mendis, Margaret Lee, Rachel Wong, Suzanne Kosmider, Jeremy David Shapiro, Desmond Yip, Simone Anne Steel, Louise M. Nott, Ross Jennens, Lara Rachel Lipton, Matthew E. Burge, Sumitra Ananda, Peter Gibbs
Journal: Journal of Clinical Oncology (2017)

682 Background: Patients (pts) with metastatic colorectal cancer (mCRC) arising from a right sided colon cancer (RCC) have an inferior survival versus pts with a left sided primary (LCC). Previous analyses have suggested that multiple factors contribute. Methods: The Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) Registry has prospectively collected data on consecutive mCRC pts at 32 sites (Australia and Hong Kong) from July 2009. LLC were defined as those distal to the splenic flexure. We analysed patient, tumour, treatment and outcome data. Results: Of 1763 patients, median age 67 years (range 18 – 100), 1201 patients (68.1%) had a LCC. RCC were more common in pts ≥ 70 years old (53.9% vs 38.5%, p &lt; 0.01) and females (50.7%, p &lt; 0.01). Where tested, KRAS (50.9% vs 41.5%, p &lt; 0.01) and BRAF (19.1% vs 6.4%, p &lt; 0.01) mutations were more common in RCC. Where tested, dMMR was more common in RCC (11.0% vs 3.2%, p &lt; 0.01). Pts with a RCC more often had peritoneal metastases (25.9% vs 12.5%%, p &lt; 0.01) and were less likely to have liver metastases (69.8% vs 77.9%, p &lt; 0.01) or resection of metachronous metastases (31.8% vs 43.6%, p &lt; 0.01). LCC more commonly received chemotherapy in the 1 st (86.1% vs 80.3%, p = 0.02) and 2 nd (49.7% vs 43.0%, p = 0.04) line setting. There was no difference in ECOG performance status or co-morbidity for LCC vs RCC. Overall survival for pts with a RCC was 20.6 months vs 27.9 months for LCC L-sided tumours (HR 1.395, p &lt; 0. 0001). Conclusions: Our data confirms that pts with mCRC arising from a RCC have an inferior survival. This appears multifactorial due to associations with adverse clinical and molecular features, metastatic pattern, and less therapy, some of which are related. A multivariate analysis is being performed.
The somatic mutational landscape in soft tissue sarcoma: Early results from TCGA data.
Authors: Andrew Scott Brohl, Hardik R Shah, Ying-Chih Wang, Andrew Kasarskis, Robert G. Maki
Journal: Journal of Clinical Oncology (2015)

10508 Background: The widespread use of next-generation sequencing has uncovered the genomic landscape in many tumor types. Given the disease rarity and histologic diversity, much less is known about the somatic mutational landscape in soft tissue sarcoma. Methods: Publicly available whole exome sequencing data from the Cancer Genome Atlas (TCGA) sarcoma project was downloaded and processed using well-established bioinformatics pipelines. Recurrent mutations were analyzed for statistical significance and potential oncologic relevance. Pan-sarcoma and histology-specific mutational frequencies were calculated. Results: Matched tumor-normal whole exome sequencing was available for 242 patients at the time of analysis. The disease histologies include 92 leiomyosarcoma, 51 dedifferentiated liposarcoma, 44 undifferentiated pleomorphic sarcoma, 24 myxofibrosarcoma, 9 malignant peripheral nerve sheath tumor, 8 synovial sarcoma, 1 desmoid tumor, and 13 lacking clinical annotation at the time of analysis. There were a median 475 high-confidence somatic variants detected [range 127-7153]. Statistically significant recurrent mutations include recurrent inactivating mutations in 3 well-established tumor suppressors, TP53, ATRX, and RB1, found in 27.3%, 8.7% and 6.2% of the total cohort respectively. Differential mutational frequency of these genes was noted between histological subtypes. Additional statistically significant recurrent mutations in genes of less clear oncologic significance are noted, as are additional recurrent mutations in other known cancer genes, but found in frequencies not meeting statistical significance. Conclusions: To our knowledge this is the first attempt to analyze the somatic mutational landscape in soft tissue sarcoma from TCGA whole exome sequencing data. We report statistically significant recurrent mutation in three tumor suppressor genes with clear oncogenic implication. Additional recurrent mutations of interest due to either mutational frequency or mutational impact in other cancer types are noted. A comprehensive analysis of genomic data is underway by the TCGA sarcoma analysis group.
A New BACOPP Schedule Is Feasible and Effective in Elderly Hodgkin’s Lymphoma Patients - Interim Results of a Multicenter Phase-II Trial of the German Hodgkin Study Group (GHSG).
Authors: Lucia Nogova, Michal Sieniawski, Hildrud Nisters-Backes, Veronika Jennissen, Volker Diehl, Andreas Engert, Andreas Josting
Journal: Blood (2005)