tbuckley/cabot-search huggingface dataset:
Insufficient involvement of the family physician (FP) in the care of chemotherapy-treated cancer patients: A barrier to comprehensive medical care.
Authors: Eytan Ben-Ami, Hadar Merom, Fabienne Sikron, Jessica Livneh, Siegal Sadetzki, Ido Wolf
Journal: Journal of Clinical Oncology (2013)

e17536 Background: Following advancement in the oncology field, increasing numbers of patients are receiving ambulatory active treatment for prolonged periods of time. Many of these patients suffer from additional comorbidities and require comprehensive medical care. We aimed to assess the perception of cancer patients regarding the role of the FP and the oncologist in their care during times of active cancer treatment. Methods: A survey was conducted among 265 consecutive chemotherapy-treated patients at the day care clinic of the Oncology Institute at Sheba Medical Center in Israel. Results: Median age was 60 years (range 22-86), 184 (69%) were woman and 147 (55%) were Israeli born. All patients belonged to one of four Israeli HMOs, 96% had a regular FP and 70% met with him during the prior month. While 78% of the patients evaluated that their FP had sufficient time to devote to them, only 32% and 27% thought their FP was trained to or wished to treat medical problems occurring while receiving chemotherapy. Yet, a majority of patients (76%) stated that involvement of the FP is important to them. Surprisingly, 85% perceived the oncologist as having enough time to devote to their care and 60% perceived him as being capable of dealing with non-oncological problems. However, only 30% stated that the oncologist communicates with the FP. Accordingly, 72% of the patients stated that in the case of an urgent problem they will turn first to the oncology institute and only 9% will turn to their FP. Indeed, 46% had unscheduled visits to the day care facilities during the prior month. Conclusions: Our data indicate lack communication between team members and inadequate medical training as major barriers for comprehensive medical care for chemotherapy-treated cancer patients. This may adversely affect medical care, decrease satisfaction among physicians and increase unnecessary workload. A change of the current situation requires collaboration between FPs and oncologists at the local and national levels and should include standardization of communication measures as well as implementation of required aspects in educational programs of both specialties.
A single-arm, open-label, multicenter phase II trial (CheckMate 172) of nivolumab (NIVO) safety in European patients (pts) with advanced melanoma (MEL) who have progressed after ipilimumab therapy (IPI).
Authors: Dirk Schadendorf, Paolo Antonio Ascierto, Enrique Espinosa, John B. A. G. Haanen, Frank Hermann, Paul D. Nathan
Journal: Journal of Clinical Oncology (2015)

TPS9083 Background: In recent years, the treatment landscape for advanced MEL has evolved with approval of an anti-CTLA-4 antibody (IPI), BRAF/MEK inhibitors and anti-programmed death-1 (PD-1) antibodies (NIVO and pembrolizumab). In a phase III study with pts previously treated with IPI, NIVO had an objective response rate of 32% (vs 11% with chemotherapy) and a manageable safety profile. Anti-PD-1 antibodies have been associated with select adverse events (AEs; i.e., those with a potential immunologic etiology), most of which resolve using established safety management guidelines. However, further safety information would be desirable in pts who progressed after prior IPI, particularly in pt subgroups that were under-represented in previous studies. Consequently, this phase II trial will assess the safety of NIVO in a large population of European pts with stage III or IV MEL progressing after prior IPI treatment, including a separate prospective cohort of pts with ECOG performance status (PS) 2. Methods: Eligible pts are ≥ 18 years of age, have histologically confirmed malignant stage III (unresectable) or stage IV MEL, have ECOG PS 0–1 (Cohort 1) or 2 (Cohort 2), were previously treated regardless of BRAF mutation status and have evaluable RECIST v1.1-defined disease progression. Pts will be treated with NIVO 3 mg/kg every 2 weeks (Q2W) until progression or unacceptable toxicities for a maximum of 24 months. Safety assessments will be performed Q2W in Cohort 1 and Q1W in Cohort 2. Tumor assessments will begin at week 12. The primary objectives are to determine the rate and frequency of high-grade (CTCAE v4.0 grade 3 or higher), treatment-related, select AEs. Secondary objectives are to characterize the outcome (grade of resolution; duration of AE-specific treatment) of high-grade, select AEs and to estimate overall survival and investigator-assessed best overall response. Approximately 1,800 pts will be enrolled across Europe, including a maximum of 300 pts with ECOG PS 2. Clinical trial registration number: NCT02156804. Clinical trial information: NCT02156804.
Phase II prospective study on trabectedin (T) in BRCA-mutated and BRCAness phenotype advanced ovarian cancer (AOC) patients (pts): The MITO 15 trial.
Authors: Domenica Lorusso, Gabriella Ferrandina, Sandro Pignata, Roberto Sorio, Antonella Pietragalla, Anna Maria Mosconi, Carmela Pisano, Giorgia Mangili, Fabio Martinelli, Cristina Masini, Grazia Artioli, Filomena Narducci, Marilena DI Napoli, Francesco Raspagliesi, Giovanni Scambia
Journal: Journal of Clinical Oncology (2014)

5530^ Background: T is a minor groove DNA binding agent with suggested activity in homologous recombinant defective (HRD) pts. This prospective phase II study was designed to evaluate activity of T in BRCA mutated and BRCAness phenotype AOC pts. The trial was partially supported by Pharma-Mar. Methods: AOC pts with documented BRCA mutation or BRCAness phenotype defined as at least 2 previous response to platinum (P), were treated with T (1.3 mg/m2q 21 i.v.) until disease progression. According to the number (N) of previous P responses, pts were stratified in moderately P sensitive (MPS, <3 P responses) and highly P sensitive (HPS, > 3 previous P responses). Results: 100 pts were enrolled and 88 were evaluable for response (52MPS, 46 HPS) after a median FU of 6 months (range: 1.5-20). Patient characteristics: median age 59 (range 49-73); 86% of tumours were serous and 60% were grade 3; median N of previous chemotherapy lines was 4 (range 2-14); median N of administered T cycles/pt was 6 (1-15), median cumulative T dose 11.0 mg/m2(range 1.9-30). In the whole population ORR was 41%, media PFS 18 weeks and median OS was not reached (NR). Oncologic outcome according to P sensitivity is shown in the Table. Among 518 administered cycles the most frequent Grade 3-4 haematological toxicities (per cycle) were: neutropenia 17.3%, leukopenia 7.7%, anemia 2.7%, thrombocytopenia 2.3%; the most frequent non-haematological Grade 3 toxicity was transaminitis 5.2%. Evaluation of responses according to BRCA mutational status, expression profiling and DNA polymorphisms of genes involved in DNA repair is ongoing. Conclusions: T represents a valuable treatment option in the specific setting of AOC pts showing multiple platinum responses. Clinical trial information: 2011-001298-17. MPS 46 pts (%) HPS 42 pts (%) Complete responses 0 4 (9.5) Partial responses (PR) 15 (32.6) 17 (40.5) Overall response rate (ORR) 15 (32.6) 21 (50) Stabilizations of disease (SD) 12 (26.1) 10 (23.8) Progression of disease 19 (41.3) 11 (26.2) Progression-free survival (PFS, weeks) 11 24 Overall survival (OS, weeks) 40 NR
Impact of preoperative sarcopenia and accelerated muscle loss on survival after resection of pancreatic cancer.
Authors: Kyungjin Lee, Moon Hyung Choi, Seung Bae Yoon, In Seok Lee, Chul-Hyun Lim, Jin Soo Kim, Yu Kyung Cho, Jae Myung Park, Bo-In Lee, Young-Seok Cho, Myung-Gyu Choi
Journal: Journal of Clinical Oncology (2017)

258 Background: Sarcopenia and accelerated muscle loss leading to cachexia is commonly observed in patients with pancreatic cancer. This study aimed to assess the influence of sarcopenia and accelerated skeletal muscle on survival in pancreatic cancer patients who underwent surgery. Methods: We analyzed the data of patients who were diagnosed with pancreatic adenocarcinoma who underwent surgery from 2008 to 2015. Skeletal muscle areas and changes were analyzed from two sets of computed tomography images at L3 vertebral levels obtained before and after resection of cancer. Sarcopenia was determined by the sex-specific cut-offs by an international consensus on the definition of cancer cachexia. Results: Among 175 patients, 83(47.4%) had preoperative sarcopenia and median survival were significantly shorter than patients without sarcopenia (423 vs. 694 days, p = 0.001). In addition, 50 (28.6%) patients with accelerated muscle loss after surgery ( &gt; 15%/90 days) showed poorer survival compared with the patients without accelerated muscle loss (423 vs. 637 days, p = 0.017). Sarcopenia (hazard ratio [HR], 1.96: 95% confidence interval [CI], 1.24-3.10) and accelerated muscle loss (HR, 1.73: 95% CI, 1.10-2.72) were identified as independent predictors of survival on multivariate analyses. Combining these two factors, patients who had both preoperative sarcopenia and accelerated muscle loss showed the poorest survival after surgery compared with the other groups (p &lt; 0.001). Conclusions: Preoperative sarcopenia and accelerated muscle loss identified by CT scans have negative impact on survival after resection of pancreatic cancer. Early detection and intensive nutritional support were essential for cachexic patients with pancreatic cancer.
Pilot SCAT trial: Spanish customized adjuvant chemotherapy (CT) based on BRCA1 mRNA expression levels (l) in resected stage II-IIIA non-small cell lung cancer (NSCLC) patients (p).
Authors: Jose Miguel Sanchez, Manuel Cobo, Rafael Arrabal, Bartomeu Massuti, Jose Manuel Rodriguez Paniagua, Teresa Moran, Julio Astudillo, Ulpiano Jimenez, Yat Wa Pun, David Aguiar Bujanda, Jorge Freixenet, Jose-Luis Gonzalez-Larriba, Florentino Hernando-Trancho, Jose Gómez-Codina, Juan-Carlos Penalver, Natividad Martinez Banaclocha, Guillermo Lopez-Vivanco, Joaquin Pac, Miquel Taron, Rafael Rosell
Journal: Journal of Clinical Oncology (2012)

7011 Background: Surgical resection is the standard treatment in early stages of NSCLC. Nonetheless, long-term survival rate even after surgical resection is disappointing. Several randomized trials and meta-analyses confirmed the survival benefit of adjuvant cisplatin-based CT for stage II and IIIA. BRCA1 is a component of multiple DNA repair pathways, functions as a molecular determinant of response to cytotoxic chemotherapeutics agents, and is an independent prognostic variable in resected p. Since BRCA1 mRNA expression has been linked to differential sensitivity to cisplatin and antimicrotubule drugs, BRCA1 expression may provide additional information for customizing adjuvant CT. Methods: Completely resected p with pathological lymph node involvement (N1, N2) received 4 cycles of customized adjuvant CT according BRCA1 l. Low l: gemcitabine-cisplatin, intermediate l: docetaxel-cisplatin, high l: docetaxel. Overall survival (OS) was the primary endpoint. Multivariate analysis for time to relapse (TTR) and survival was performed. Results: Eighty-three p were elegible. Most of the patients were male (83%). Type of surgery: 23% pneumonectomy, and 77% lobectomy or bilobectomy. Fifty-three per cent had low BRCA1 l, 33,7% intermediate l, and 13,3% expressed high l. Most of the tumors with adenocarcinoma histology had low l (71%). With a median follow-up of 41.6 months (m), median TTP for the whole group was 22.9 m (13.4-32.5): 20.3 m for low l, 56.5 m for intermediate l, and 51.9 m for high l (P=0.31). Median OS for the whole group was 63.6 m (33.3-93.9): 55 m for low l, and not reached for intermediate and high l (P=0.58). Forty-three p (51.8%) are still alive. Conclusions: Selection of customized CT based on BRCA1 expression l is feasible and could increase time to relapse and survival in resected N1-N2 p. No statistical differences for survival: 55 months for gemcitabine-cisplatin, and not reached for docetaxel-cisplatin and for docetaxel as single agent. Randomized phase III SCAT trial with the addition of a non-pharmacogenomic control arm is ongoing (372 patients included).
Utility of Schwartz Center Rounds in fostering compassion, communication, teamwork, and caregiver support
Authors: P. Mann, L. Schapira, T. Lynch, R. Penson
Journal: Journal of Clinical Oncology (2009)

e20640 Background: Schwartz Center Rounds are a multidisciplinary forum where clinicians discuss difficult emotional and social issues that arise in caring for patients with the goal of improving the patient-caregiver relationship. Rounds were initiated at the MGH Cancer Center in 1997 and have since grown to include 165 sites including 24 cancer centers nationwide. We report on a recent evaluation of the impact of Rounds. Methods: The Schwartz Center Rounds evaluation focused on three major research questions: 1) Do professional caregivers have increased insight into the non-clinical aspects of care after attendance at Rounds? 2) Is there increased teamwork among caregivers after attendance? 3) Do caregivers perceive increased support after attendance at Rounds? The evaluation included a retrospective survey of 256 caregivers at six sites where Rounds had existed for ≥ 3 years; 44 semi-structured interviews with participants at these sites; and pre/post surveys of 222 caregivers from ten hospitals newly implementing Rounds. Results: The highest percentage of attendees were nurses (35%), followed by physicians (23%), social workers (15%), psychologists (4%), physical therapists (6%) and clergy (5%). After attending Rounds, participants reported increased insight into psychosocial aspects of care; enhanced compassion; increased ability to respond to patients’ social and emotional issues; enhanced communication amongst caregivers; greater appreciation of colleagues’ roles and contributions. Attendees reported decreased feelings of stress and isolation and a greater sense of teamwork. Participants reported that Rounds discussions led to changes in institutional practices or policies. Conclusions: Schwartz Center Rounds provide a forum for discussion of challenging psychosocial and emotional issues arising during clinical care. Evaluation data suggests this educational strategy may enhance compassion, professional support, communication, teamwork, and instigate institutional changes that enhance patient care. We are currently exploring other outcomes, including but not limited to the impact of rounds on quality of patient care and patient safety. [Table: see text]
ARDS in the setting of FOLFOX/cetuximab based chemoradiotherapy for locally advanced esophageal adenocarcinoma (E2205).
Authors: Ramla NAMISANGO Kasozi, Anita Choudhary, Michael K. Gibson, Paul J. Catalano, Lawrence Kleinberg, Charles A. Staley, Lori J. Sokoll, Wei Song, Mary Frances Mulcahy, Lawrence P. Leichman, Al Bowen Benson
Journal: Journal of Clinical Oncology (2017)

121 Background: E2205 was a single-arm, phase II trial that added an epidermal growth factor receptor (EGF-R) inhibitor, cetuximab (C), to CRT. The trial was closed early due to pulmonary toxicity. We investigated the potential role of cetuximab and type of radiation (IMRT vs conventional). Methods: Patients were treated with CRT: Oxaliplatin (OX) 85mg/m 2 days 1,15,29; infusional 5-fluorouracil (5-FU) 180mg/m 2 /24hours x 35 days; C 400mg/m 2 day 1 then 250mg/m 2 days 8,15,22,29 and radiation (IMRT allowed) 180cGy/day x 25 fractions (Monday-Friday), followed by esophagectomy. Results: Of 21 eligible patients enrolled, 17 had surgery (died pulmonary embolism 4 days after CRT, died G3 diarrhea/PD during CRT, died sepsis/hypoxia during CRT). pCR = 7/17. Four post-op deaths from acute respiratory distress syndrome (ARDS) resulted in 7 total study-related deaths. None of the patients who received IMRT died (0/3). 1/6 had ARDS if more than 4 fields with conventional or 3D planning was used. 3 of 15 treated with RT that met the criteria of E1201 guidelines (no more than 3-4 RT fields, normal lung more than 2 cm outside the target volume &lt; 40 Gy, no IMRT). Overall, there was no demonstrable association of ARDS to radiation technique: 4/22 overall, 0/3 if IMRT was used. Conclusions: This regimen is not recommended. There is no clear association between use of IMRT and ARDS. The cause of ARDS remains undetermined. Cetuximab may have played a role. Clinical trial information: NCT00551759.
Addressing tobacco use and cessation in cancer patients: Practices, perceptions, and barriers reported by oncology providers.
Authors: Graham Walter Warren, James Roger Marshall, K. Michael Cummings, Benjamin A Toll, Ellen R. Gritz, Alan Hutson, Shiva Dibaj, Roy S. Herbst, James L. Mulshine, Nasser H. Hanna, Carolyn Dresler
Journal: Journal of Clinical Oncology (2013)

1561 Background: Tobacco use is associated with adverse outcomes in cancer patients, but there are limited data on tobacco cessation support by oncology providers. Methods: Duplicate surveys were sent to the membership of the International Association for the Study of Lung Cancer (IASLC) and the American Society of Clinical Oncology (ASCO) asking about tobacco assessment and cessation practices, perceptions of tobacco use by cancer patients, and barriers to implementing tobacco cessation. The results of 1,507 responses from IASLC and 1,197 responses from ASCO are reported. Results: At initial consult, most respondents asked about tobacco use (90% in both surveys), asked if smokers would quit tobacco use (79-80%), advised patients to stop smoking (81-82%). Most respondents felt that tobacco affects cancer outcomes (87-92%) and that tobacco cessation should be a standard part of clinical care (86-90%). However, few discussed medication options (40-44%) or actively provided smoking cessation assistance (39% in both surveys). Fewer respondents asked about tobacco use at follow-up and few reported adequate tobacco cessation training (29-33%). Dominant barriers to providing cessation interventions included patient resistance to cessation treatment (67-74%) and inability to get patients to quit tobacco use (58-72%), but very few believed tobacco cessation was a waste of time (8-12%). Lack of time, reimbursement, lack of training, and lack of resources were reported as barriers in less than 50% of respondents. Conclusions: Oncology providers feel tobacco affects cancer outcomes and cessation should be a standard part of clinical care. Most assess tobacco use, but few discuss medication options or provide active cessation support. Efforts are needed to improve cessation methods in cancer patients and to improve access to tobacco cessation support for cancer patients.
Rare germline <i>TP53</i> variants in lung adenocarcinoma.
Authors: Erin Michelle Parry, Dustin L Gable, Susan E Stanley, Mary Y. Armanios
Journal: Journal of Clinical Oncology (2015)

1548 Background: TP53 is one of the most commonly altered genes in lung adenocarcinoma, with as many as 50% of all cases possessing somatic inactivating mutations. Germline mutations in TP53 predispose to a wide variety of cancers in Li-Fraumeni syndrome. While lung cancer is generally not considered a classic Li-Fraumeni malignancy, several studies have indicated it may appear at an earlier age in this cancer-prone syndrome. Methods: We tested the frequency of germline TP53 mutations in an unselected cohort of lung adenocarcinoma cases sequenced as part of The Cancer Genome Atlas (TCGA) project. At the time of data access (October 1, 2014), germline exome and genome data were available for download from 531 subjects, and clinical information was available on 94% of these cases (n = 497). After Data Access Committee approval, we extracted raw bam files that included the TP53 sequence, called and annotated the variants. We considered variants with high (greater than 20x) coverage, and then excluded those with a minor allele frequency of 0.005 or greater in control populations. Suspected pathogenic variants were then confirmed by examining the matched tumor sequence data or a replicate normal tissue sample using the same methods. Results: Four cases carried germline missense variants in TP53 (0.8%), and all of them fell in the DNA binding domain. Three of the mutations were previously described in Li-Fraumeni syndrome and all of mutations have been reported as somatically mutated in various cancers. The mean age at lung cancer diagnosis was 58 years (range 41-73) and one individual was male. One of the cases was a never smoker (female), and another subject had a prior history of thymic carcinoma, a diagnosis that has been documented in Li-Fraumeni syndrome. Conclusions: Our data suggest that a subset of lung adenocarcinoma patients carry germline mutations in TP53, pointing to a role for inherited factors in lung cancer susceptibility. This diagnosis may be overlooked in cases where genomic data is filtered for background germline variants, and is relevant for genetic counseling and screening decisions.
The Comparison of Efficacy Between Generic and Branded Imatinib in Achievement of Overall Survival and Cytogenetic Responses in CML Patients in Bosnia and Herzegovina
Authors: Amina Kurtovic Kozaric, Erna Islamagic, Jerald P. Radich, Emina Suljovic Hadzimesic, Azra Hasic, Sabira Kurtovic
Journal: Blood (2016)
Systemic Inflammation Recruits Ccr7+ Dendritric-Biased Granulocyte-Macrophage Progenitors to Lymphatic Circulation in a Non-Canonical Traf6-Dependent Manner
Authors: Juana Serrano-Lopez, Josefina Serrano, Cuiping Zhang, Ashley Wellendorf, Jing Fang, Joaquin Sanchez-Garcia, H. Leighton Grimes, Daniel T Starczynowski, Jose A Cancelas
Journal: Blood (2015)
Resetting the Circadian Clock Might Boost Metabolic Health
Authors: Bridget M. Kuehn
Journal: JAMA (2017)

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