tbuckley/cabot-search huggingface dataset:
Feasibility of a pilot study of an intervention to Enhance Communication during Hospice care with Oncology (ECHO).
Authors: Jessica Ruth Bauman, Stephen Schleicher, Ryan David Nipp, Areej El-Jawahri, William F. Pirl, Joseph A. Greer, Jennifer S. Temel
Journal: Journal of Clinical Oncology (2015)

51 Background: When patients with cancer transition to hospice, the role of oncology clinicians can be unclear. During this time, patients and families often feel abandoned by their oncology team. We assessed the feasibility of a novel intervention to enhance continuity of care between the oncology team and patients and their families after they enroll in hospice. Methods: Family caregivers (FCs) of patients with cancer (lung, head and neck, sarcoma, melanoma, and gynecological) who enrolled in home hospice from 3/2014-6/2015 were eligible to participate in the study. The ECHO intervention consisted of check-in phone calls from the oncology team to the FC (weekly x 4 weeks, biweekly x 4 weeks, then monthly), an optional in-person clinic visit, and a bereavement call. FC questionnaires assessing satisfaction, perceived stress, quality of EOL care, and regret were completed at enrollment, weeks 1 and 2, and then every 4 weeks, as well as at a phone interview post- death. The primary outcome was feasibility, which we defined as &gt; 70% of the FCs receiving &gt; 50% of the phone calls and &gt; 70% of the FCs completing &gt; 50% of the questionnaires. Results: Of 37 eligible FCs, 24 (80%) enrolled, 7 were not reached, and 6 declined. At the time of analysis, 19 were evaluable as 2 patients died before the intervention began, 1 FC withdrew, and 2 interventions were ongoing. Median time from hospice referral to study enrollment was 3 days (range 1-7) and from study enrollment to patient death was 34 days (range, 3-135). Clinicians completed 156 of the expected 172 calls (90.7%) to FCs. FCs completed 75 of the expected 91 (82.4%) questionnaires. 100% of the FCs received &gt; 50% of scheduled phone calls and 79% of the FCs completed &gt; 50% of the questionnaires. In qualitative interviews post-death, FCs indicated that the phone calls were appreciated and helpful. Conclusions: This intervention enhancing communication with the oncology team throughout hospice was well received by FCs. Additionally, the intervention proved feasible, as the majority of phone calls and questionnaires were completed. A randomized study is warranted of the impact of ECHO on the quality of EOL care and FC outcomes including satisfaction, bereavement adjustment, and mood. Clinical trial information: NCT02069769.
Everolimus and sunitinib as first- and second-line treatments of patients with metastatic papillary renal cell carcinoma (pRCC): A retrospective study of the GETUG (Groupe Français d’Etude des Tumeurs Uro-Génitales).
Authors: Claude Linassier, Laurence Albiges, Christine Chevreau, Brigitte Laguerre, Stephane Oudard, Marine Gross-Goupil, Gwenaelle Gravis, Francois Goldwasser, Frederic Rolland, Remy Delva, Laura Moise, Jean-Marc Tourani, Cecile Vassal, Sylvie Zanetta, Nicolas Penel, Aude Flechon, Christine Theodore, Philippe Barthelemy, Carolina Saldana, Bernard Escudier
Journal: Journal of Clinical Oncology (2016)

505 Background: pRCC accounts for 15% of all renal cancers. Two French prospective phase II trials demonstrated efficacy of both Sun and Eve in first-line treatment of metastatic disease (RAPTOR (NCT00688753) and SUPAP (NCT00541008)). Most patients (pts) usually receive the alternate drug at progression. We report the first series of drug sequencing in pRCCs. Methods: We updated clinical data of metastatic pts with pathologically documented pRCC, who were treated in firs line or more with Sun or Eve, from 2/06 to 6/15, in 24 GETUG centers. Results: 196 pts (166 men, 30 women), median aged of 61 years, with histological subtypes (HST) I (28 pts), II (122 pts) or unclassified (46 pts), were treated for metastatic pRCC in 1st-line: group 1 Su 50 mg daily 4/6 weeks (n=158 pts) ; group 2 Eve 10 mg daily (n=38 pts). 76 pts were included in the RAPTOR or SUPAP studies. The median follow-up was 59.5 months. We found no difference between the 2 groups in terms of patients’ characteristics, clinical benefit in first-line (CR+PR+SD) (71% vs 72%; p=0.95) or progression-free survival (PFS) (PFS-1: 5.7 vs 4.6 months; p=0.152). Reasons for treatment discontinuation were tumor progression (74% vs 70%) or toxicity (26 vs 30%) (p=0.58). 134 pts received the alternative drug in second-line (group 1: Eve; group 2: Sun) with similar clinical benefit (64% vs 58%; p=0.69) and median PFS (PFS-2: 3.5 vs 3.0 months p=0.98). Overall survival (OS) did not differ between the two groups (16.4 vs 17.6 months; p=0.58). Age, Karnofsky performance status &lt; 80 (KPS-80), HST, platelet (Plts) and absolute neutrophil counts (ANC), hemoglobin and calcium levels, time from diagnosis to metastases (TTM) were studied as prognostic variables. In multivariable analysis, only Plts and KPS-80 had prognostic impact on EFS-1, whereas ANC, KPS-80 and TTM were prognostic for OS. We found a trend in favor of HST I vs non I, with no statistical difference in terms of PFS or OS. Conclusions: In this large retrospective series of metastatic pRCC pts, Sun and Eve had good compliance and similar efficacy in terms of first-, second-line PFS and overall survival.
Correlation of myocardial perfusion, as assessed by positron emission tomography, and left ventricular ejection fraction and exercise tolerance in patients with idiopathic dilated cardiomyopathy
Authors: A vandenHeuvel, DJ vanVeldhuisen, PK Blanksma, RL Anthonio, Hmj Siebelink, JM Staudt, W Vaalburg
Journal: Circulation (1997)
Relationship of EGFR-independent activation of PI3K in KRAS wild-type colorectal cancers and cetuximab resistance.
Authors: Ryan Bruce Corcoran, Hiromichi Ebi, David P. Ryan, Jeffrey A. Meyerhardt, Jeffrey A. Engelman
Journal: Journal of Clinical Oncology (2013)

385 Background: Therapies targeting receptor tyrosine kinases (RTKs) are typically effective only when they lead to simultaneous inhibition of PI3K-AKT and MEK-ERK signaling. Cetuximab is a monoclonal antibody against EGFR that has been approved for treatment of metastatic colorectal cancer (CRC). Studies have suggested that its benefit is restricted to patients with KRAS wildtype (WT) CRC. However, even in KRAS WT CRC, the response rate to single-agent cetuximab is low, and the mechanistic basis for this is not well-understood. Methods: The ability of cetuximab to inhibit PI3K-AKT and MEK-ERK signaling in a panel of KRAS WT CRC cell lines was assessed by immunoblotting. Paired biopsies from CRC patients obtained pre-treatment and after 3 weeks of cetuximab were evaluated by immunohistochemistry and proteomic techniques to assess inhibition of PI3K activity. We preformed immunoprecipitations (IPs) of the regulatory subunit of PI3K from cell lines and primary CRCs to identify RTKs involved in PI3K activation. Cetuximab-based therapeutic combinations were evaluated in KRAS WT CRC cell lines and xenograft models. Results: Cetuximab led to effective inhibition of MEK-ERK signaling (&gt;75% reduction in phospho-ERK), but led to incomplete inhibition of PI3K-AKT signaling (0-50% reduction in phospho-AKT) in all KRAS WT CRC cell lines tested. Analysis of paired biopsies from patients with KRAS WT CRC obtained pre-treatment and after 3 weeks of cetuximab demonstrated that the PI3K pathway remained active in many patients, despite cetuximab therapy. PI3K regulatory subunit IPs from cell lines and primary CRCs revealed multiple RTK inputs to PI3K, most notably from IGFIR. Combined treatment with cetuximab and an IGFIR inhibitor or a PI3K inhibitor led to improved efficacy in vitro and to tumor regressions in KRAS WT CRC xenograft models. Conclusions: Cetuximab fails to inhibit PI3K signaling in some KRAS WT CRCs. Additional RTKs other than EGFR play a role in PI3K activation in these cancers, which may contribute to cetuximab resistance. Combining cetuximab with targeted therapies directed against the PI3K pathway may lead to improved efficacy in KRAS WT CRC, and should be evaluated in future clinical trials.
The prognostic significance of LDH levels in patients with relapsed/refractory seminoma and their predictive value of the new international prognostic score.
Authors: T. Powles, C. Mollevi, A. Kramar, A. Lorch, J. Beyer
Journal: Journal of Clinical Oncology (2011)

4584 Background: The IPFSG recently published a prognostic score for patients with relapsed germ cell tumours (J Clin Oncol 2010,28:4906). It did not specifically address seminomas, however, which have distinct characteristics and considered to have excellent outcomes after salvage chemotherapy. Methods: A subgroup of 204 seminomas from the International Prognostic Factor Database was analyzed. All patients experienced unequivocal relapse/progression after at least three cisplatin-based chemotherapy cycles and received conventional-dose or high-dose salvage chemotherapy. In addition to the variables of the score published by the IPFSG, we analyzed age and LDH at salvage for their prognostic significance by univariate and multivariate Cox regression analysis. Results: The impact of the IPFSG score remained highly significant in multivariate analysis. In addition, LDH ≥ 1.5 the upper limit of normal (ULN) was significant in univariate [HR 1.96; CI: 1.06-3.61] and multivariate analysis [HR 1.90; CI: 1.00-3.62]. Age, however, was not significant. Therefore LDH was incorporated into the score: values ≥ 1.5 x ULN added an additional prognostic point to the score and moved very low and low risk patients to the next unfavourable group. Three prognostic groups were thus generated, which better subdivided seminoma patients than the original IPFSG score. Progression-free survival at 2 years: “very low risk” (n=23) 85.7% (95% CI: 62-95), “low risk” (n=44) 62.7% (95% CI: 46-75), “intermediate risk” (n=35) 36.2% (95% CI: 20-52). Overall survival at 3 years: “very low risk” 88.8% (95% CI: 62-97), “low risk” 71.3% (95% CI: 55-83), “intermediate risk” 52.9% (95% CI: 34-68). Overall, 102 patients could not be reliably classified due to missing values. Conclusions: In relapsed seminoma, the inclusion of LDH improves the prognostic score previously published by the IPFSG and helps to identify less favorable subgroups with outcomes not dissimilar to non-seminoma patients.
Bilateral multifocal papillary type I renal cell carcinoma: Clinical characteristics and association with chronic renal insufficiency.
Authors: Daniel Su, Chinonyerem Okoro, Arvin George, W. Marston Linehan, Adam R. Metwalli
Journal: Journal of Clinical Oncology (2014)

482 Background: Patients with bilateral multifocal (BMF) RCC are at risk for multiple surgeries, progressive loss of renal tissue and chronic renal insufficiency. Although BMF papillary type I RCC is commonly associated with Hereditary Papillary Renal Cell Carcinoma (HPRC), with mutation of the MET proto-oncogene, sporadic (non-familial) BMF Pap1 RCC is far more common. Here we describe the histologic and clinical phenotype as well as clinical management of a population of patients with BMF RCC that has papillary type I histology that is distinct from the HPRC population. Methods: From 2000 to 2013, patients who were evaluated at the National Cancer Institute and were diagnosed with BMF on cross sectional imaging were included. Patients who tested negative for MET proto-oncogene mutation, who have a pathologic diagnosis of papillary type I were included. Phenotypic manifestations and clinical management were analyzed. Results: 61 patients with an average age of 54.3 years were identified. A disproportionate number (22, 36%) of these patients were of African American descent. Fifty seven (93%) were male. Two patients were found to have had metastatic disease on presentation (3%); 17 patients underwent unilateral radical nephrectomy for renal mass (28%) even though the average largest tumor diameter was only 2.9 cm. 12 patients (19%) underwent partial nephrectomy. The average preoperative serum creatinine was 1.48 mg/dl and average eGFR 62.2 ml/min, there was no difference between in eGFR in African American patients and Caucasian patients (62.09 ml/min and 63 ml/min). This population had an average of 2 tumors per side, many patients also had numerous cysts on both kidneys. Conclusions: BMF papillary type I RCC represents a novel entity which disproportionally affects African Americans. These patients often present with renal insufficiency and are at significant risk for further renal deterioration. As a small percentage of these patients with BMF papillary type I will present with metastatic disease, active surveillance until the largest renal tumor reaches 3 cm is recommended.
Association of age 40 and older with adverse outcome in metastatic testicular cancer (TC).
Authors: Rowan Miller, Sarah C Markt, Elizabeth O'Donnell, Brandon David Bernard, Laurence Albiges, Carlos Lago-Hernandez, Stephanie A. Curreri, Clair Beard, Alexi A. Wright, Christopher Sweeney
Journal: Journal of Clinical Oncology (2015)

386 Background: We sought to determine factors associated with poorer outcome in older patients (≥ 40) with TC in a large institutional dataset. Methods: A retrospective review of a 1095 patient, IRB approved database, of men treated for TC between 1997 and 2012 at the Dana-Farber Cancer Institute was performed. Information regarding histology, stage, treatment and patient characteristics was obtained from electronic medical records. Using logistic regression analysis and Cox proportional hazard regression we investigated the association between age and outcome for (a) men with clinical stage 1 (CS1) TC and (b) men with metastatic TC, either at diagnosis or following CS1 relapse. Results: 26% of the TC patients were ≥ 40 at diagnosis. Amongst the 616 men with CS1 disease 150 (24%) were age ≥ 40, there was an association with increased likelihood of seminoma (OR 2.46, 95%CI 1.68-3.60) and larger tumour size (&gt; 4cm, OR 1.81, 95%CI 1.23-2.66). Age ≥ 40 was not associated with an increased risk of relapse (HR 0.931, 95%CI 0.575-1.505, p=0.77). 605 men (159, 26% ≥ 40) with metastatic disease were identified. Men ≥ 40 were more likely to have seminoma (OR 3.07 95%CI 2.07-4.54). Distribution of IGCCC prognostic stage was similar in men &lt; 40 and ≥ 40. After adjusting for stage and histology, men ≥ 40 were more likely to receive chemotherapy other than BEP as their primary treatment (OR 1.87 95%CI 1.17-3.00, p=0.009) and men ≥ 40 were also more likely to receive non-optimal chemotherapy than men &lt; 40 (OR 2.91 95%CI 1.12-7.60, p=0.03). When adjusted for confounding variables, age ≥ 40 was associated with a non-significant increased risk of relapse (HR 1.467 95%CI 0.94-2.29, p=0.09) post primary treatment and a significant increased risk of death from TC (HR 2.41 95%CI 1.41-4.11, p=0.0013), which was greater for those with non-seminoma (HR 2.54 95%CI 1.45-4.44, p=0.0011) than seminoma (HR 1.53, 95%CI 0.33-7.2, p=0.56). Conclusions: Men ≥ 40 years diagnosed with metastatic TC were less likely to be cured with therapy for metastatic disease compared to men &lt; 40.
Physical activity in patients with unresectable pancreatic adenocarcinoma: A multicentric randomized controlled study (APACaP study).
Authors: Cindy Neuzillet, Mathieu Vergnault, Aude-Marie Foucaut, Marina Touillaud, Franck Bonnetain, Pascal Hammel
Journal: Journal of Clinical Oncology (2015)

TPS506 Background: Exercise during chemotherapy (CT) is a promising strategy to reduce fatigue and improve health-related quality of life (QoL). It has been shown feasible and efficient in various cancers, including at advanced stage. Effects of physical activity in advanced pancreatic ductal adenocarcinoma (PDAC) have never been explored to date. We aim to evaluate the effects of a physical activity intervention in this setting. Methods: Randomized national multicentric interventional study to test the efficacy of an unsupervised home-based 16-week physical exercise program. Specificities of PDAC for physical activity program implementation will be taken into account (physical activity partner instead of patients groups, nutritional management). Main inclusion criteria: histologically confirmed, unresectable PDAC; scheduled for CT; WHO PS 0-2; age ≥ 18; physical activity partner. Two study arms: intervention group invited for the exercise program (aerobic and resistance exercises) in addition to usual care; control group receiving usual care alone. Primary objective: effects on fatigue (MFI-20) and health-related QoL (EORTC-QLQ-C30) at week 16, unified as co-primary endpoint. Secondary objectives: effects on pain, anxiety and depression, nutritional status, insulin resistance, CT tolerance, survival; adherence to the program. Number of patients: 200. PDAC patients are strongly affected by fatigue, thus they are expected to benefit from a physical activity intervention. Moreover, exercise may have a beneficial effect on tumor outcomes, by reducing insulin resistance and insulin/IGF-1 secretions. Such intervention may appear challenging because of multiple cancer-related symptoms (fatigue, depression, pain, denutrition) that can appear as barriers to physical activity. Conversely, we hypothesize that a physical exercise program, by taking into account PDAC specificities, may improve symptoms and health-related QoL. If this intervention is proven to be feasible and effective, such standardized physical exercise programs might be proposed in complement to CT in patients with advanced PDAC as a logical next step. Clinical trial information: NCT02184663.
Adjuvant pelvic radiotherapy in patients with stage IVA rectal adenocarcinoma.
Authors: Croix C. Fossum, Lindsay B. Romak, Ryan K. Funk, William S. Harmsen, Michael G. Haddock, Michelle A. Neben-Wittich, James A. Martenson, David W. Larson, Kellie L. Mathis, Rory L. Smoot, Joleen Marie Hubbard, Christopher Leigh Hallemeier
Journal: Journal of Clinical Oncology (2016)

711 Background: For patients with stage IVA rectal cancer with liver metastases treated with curative-intent chemotherapy and surgery, the role of adjuvant pelvic radiotherapy (RT) is unclear. The purpose of this study was to evaluate the impact of pelvic RT on oncologic outcomes in this patient population. Methods: We retrospectively reviewed medical records of all patients with stage IVA rectal adenocarcinoma with liver metastases treated with curative-intent resection of the primary tumor and all liver metastases at our institution between 1991 and 2010. Patient and treatment characteristics were compared between patients who did or did not receive pelvic RT using chi-square and unpaired ttests. Survival and recurrence estimates were calculated from date of initial diagnosis using the Kaplan-Meier method. Local recurrence (LR) was defined as recurrence in the pelvis occurring at or before distant recurrence (DR). Cox regression was used to compare rates of freedom from LR (FFLR), freedom from DR (FFDR), and overall survival (OS) between patients who did or did not receive pelvic RT. Results: The analysis included 65 patients. Median patient age at diagnosis was 59 years (range, 27-87). Tumor stage was T2 (n = 4), T3 (n = 53), or T4 (n = 8). The median number of liver metastases was 2 (range, 1-14). Surgery was low anterior resection (n = 54) or abdominoperineal resection (n = 11). All patients received perioperative fluoropyrimidine based chemotherapy. Pelvic RT was administered to 35 patients (54%), either preoperatively (n = 22) or postoperatively (n = 13). Median RT dose was 50.4 Gy (range 25-58). Patient characteristics were similar for those who did or did not receive pelvic RT. Median follow-up was 3.7 years. The 3-year estimates of FFLR, FFDR and OS were 81% vs 58% (p =.056), 35% vs 29% (p =.75), and 66% vs 71% (p =.81) for RT vs no RT, respectively. Conclusions: In this analysis of patients with stage IVA rectal cancer with liver metastases undergoing curative intent therapy, pelvic RT (vs. no pelvic RT) was associated with a trend to lower rates of LR and similar rates of DR and OS.
Human Granulocyte-Macrophage Colony-Stimulating Factor (hGM-CSF) Induces Inhibition of Intrathymic T-Cell Development in hGM-CSF Receptor Transgenic Mice
Authors: Yuko Yasuda, Ichiko Nishijima, Sumiko Watanabe, Ken-ichi Arai, Albert Zlotnik, Thomas A. Moore
Journal: Blood (1997)
Oncology quality improvement as a cornerstone of the transition to accountable care.
Authors: John C. Ruckdeschel, William T. Sause, Tom Belnap, Cory Jones, Braden D. Rowley
Journal: Journal of Clinical Oncology (2012)

141 Background: Accountable care is defined as moving the incentives for health care from a system that rewards volume and procedures to one that rewards improvements in the quality of care for a defined population. To prevent this process from deteriorating into solely a cost reduction exercise, physicians, and hospitals need to develop a valid, reproducible, and effective means of measuring quality and impacting behavior to reduce variation and improve quality of care. The Intermountain Healthcare Oncology Clinical Program’s (OCP) experience with Oncology Quality Improvement (OQI) offers several key lessons for enabling this process. Methods: OQI initiatives are developed by a multidisciplinary physician-based team tasked with directing standardization and ensuring optimal care delivery. The team uses clinical knowledge, peer-reviewed literature, and data from an enterprise data warehouse to develop goals. Performance is measured against a goal which focuses on variation between physicians and facilities. Individual physician data is compared to de-identified data of peers, facilities, and the system. A physician champion performs academic detailing for physician groups across the system and is critical to the success of the program. Results: Over the past decade, the OCP initiated over 30 projects designed to measure and improve quality of oncology care delivery. Breast cancer projects included breast conservation in surgical management, reducing axillary dissection for ductal carcinoma in situ and sentinel node biopsy rather than axillary dissection. The OCP also explored standardizing lymph node resection during colorectal cancer surgery and subsequently the utilization of adjuvant chemotherapy. Imaging based goals included improving mammography callback rates and using PET/CT during preoperative assessment of lung cancer. In most instances the process resulted in significant, sustainable OQI. Conclusions: The investment in program and clinician staff is significant, and the requirements and costs for a sophisticated data system are real. However, an OQI program can provide meaningful improvements in the quality of cancer care and is an important step to facilitate the transition to accountable care.