tbuckley/cabot-search huggingface dataset:
Pharmaceutical involvement in phase II breast cancer clinical trials.
Authors: A. Schneider, T. Zhang, A. Kamal, K. Patel, E. P. Hamilton, J. M. Peppercorn
Journal: Journal of Clinical Oncology (2011)

6104 Background: Pharmaceutical industry (PHI) involvement in breast cancer clinical trials is increasing and may correlate with positive outcomes. We sought to further investigate the prevalence and potential impact of PHI involvement in breast cancer research through evaluation of recently published breast cancer phase II trials (BP2T). Methods: Phase II clinical trials from June 2005 – June 2010 were identified in MEDLINE by search terms “breast cancer” and “phase II” and limits of English language, human subjects, and “clinical trials”. Trials were abstracted by 2 independent reviewers for industry involvement, report of possible conflicts of interest (COI), trial design, setting, interventions, accrual, and outcomes. PHI trials were defined by any report of industry involvement. “Positive” outcomes was defined by assessment of authors conclusions. Descriptive statistics and Fisher’s exact test are reported. Results: 298 eligible trials were abstracted. 181 (61%) reported PHI including 44 (15%) with industry authorship. For 114 (38%) trials a COI was identified. COI was reported more frequently among PHI trials vs. non-PHI trials (58% vs. 7%, p < 0.001 ). Among PHI trials, 132 (73%) involved metastatic disease, 44 (24%) neoadjuvant, and 9 (5%) other settings. 125 (69%) PHI trials were single arm, 29 (16%) randomized, 15 (9%) Phase I/II, 13 (7%) nonrandomized with multiple cohorts. PHI trials were more likely to have US sites (78% vs. 52%, p < 0.001), to include > 50 patients (54% vs. 38%, p = 0.006), to evaluate biologic therapy (38% vs. 25%, p = 0.04) and to include correlative science (34% vs. 17%, p = 0.002) compared to non-PHI trials. Average time to accrual was 27 months for PHI vs. 30 months for non-PHI trials. 140 (77%) PHI trials and 93 (79%) non-PHI trials were positive (p = 0.8). Conclusions: The majority of BP2T involve pharmaceutical industry support, and many include an author with COI. The prevalence of PHI support and frequency of COI highlights the importance of managing COI while supporting academia/industry collaboration. PHI support correlates with some aspects of study design and study characteristics, but correlation with positive outcomes as noted in some prior studies is not seen among this more homogenous dataset.
Fractionation of palliative radiotherapy in metastatic breast cancer: Selection and survival.
Authors: Yushen Qian, Sara Dudley, Ben Y Durkee, Kiran Kumar, Aadel Chaudhuri, Erqi L. Pollom, Sonya Aggarwal, Kathleen C. Horst, Daniel Tandel Chang
Journal: Journal of Clinical Oncology (2015)

201 Background: Various schedules of palliative radiotherapy (pRT) are prescribed for metastatic breast cancer (MBC) patients. Length of treatment can vary from a single day to three weeks. Single fraction pRT provides similar pain relief vs. multi-fraction pRT for bone metastases, but retreatment rates are higher. In the era of targeted and hormonal therapy, patients with MBC can survive many years after their initial diagnosis. We investigated whether patients with MBC who were prescribed single fraction pRT had poorer prognoses and experienced shorter survival than patients who were prescribed multi-fraction pRT. Methods: Patients at a single institution with MBC underwent pRT, with fractionation schedules including 8 Gy in 1 fraction (fx), 20 Gy in 5 fx, 30 Gy in 10 fx, 37.5 Gy in 15 fx between 2001-2015. 392 treatments were prescribed (109/241/29/13 in each regimen as above). Date of death was obtained from medical records, Social Security Death Index, or published obituaries. Patients who were alive or whose date of death could not be determined were censored at the date of their last encounter. Survival was calculated from the start of treatment to the date of death or censorship. Results: Patients treated with 37.5 Gy in 15 fx (MS 20 months, p = 0.002) or 30 Gy in 10 fx (MS 22 months, p = 0.03) experienced longer survival than patients treated with 8 Gy in 1 fx (MS 8 months). There was no significant survival difference between patients treated with 20 Gy in 5 fx (MS 18 months, p = 0.49) and patients treated with 8 Gy in 1 fx. There was no significant survival difference between patients treated by the three multi-fractionation schedules. Conclusions: MBC patients who were prescribed 37.5 Gy and 30 Gy lived longer than patients who were prescribed 8 Gy of pRT. No statistically significant difference was found between patients who were prescribed 20 Gy compared to 8 Gy, possibly due to the lower number of patients who received these regimens. Single fraction pRT was more likely to be prescribed to patients who would ultimately have shorter survival. More research is needed, ideally across multiple institutions, to explore the correlation between physician estimation of patient survival and selection of pRT regimen for patients with MBC.
Design of RESILIENCE: A phase (Ph) III trial comparing capecitabine (CAP) in combination with sorafenib (SOR) or placebo (PL) for treatment (tx) of locally advanced (adv) or metastatic HER2-negative breast cancer (BC).
Authors: J. Baselga, L. S. Schwartzberg, O. Petrenciuc, M. Shan, W. J. Gradishar
Journal: Journal of Clinical Oncology (2011)

TPS124 Background: SOR is an oral multikinase inhibitor with antiangiogenic/antiproliferative activity. A randomized Ph 2b screening trial (SOLTI 0701) that compared SOR+CAP vs PL+CAP in patients (pts) with adv BC demonstrated significant improvement in progression-free survival (PFS) for the SOR arm (median 6.4 vs 4.1 mo; hazard ratio=0.58; 1-sided P=0.0006). Most drug-related adverse events were grade 1/2 in severity with the exception of grade 3 hand-foot skin reaction/syndrome (HFSR/HFS) (44% in SOR+CAP vs 14% in PL+CAP). The SOLTI 0701 results suggest a role for SOR+CAP in the tx of BC and warrant confirmation in a Ph 3 trial. Methods: RESILIENCE is an ongoing double-blind, randomized Ph 3 trial designed to compare SOR+CAP vs PL+CAP in adv HER2-negative BC. Eligibility criteria include: ≥18y of age; ≤1 prior chemotherapy regimen for adv BC; and resistant to/failed taxane and anthracycline or no indication for further anthracycline. Prior hormonal or radiation tx is allowed, but prior VEGF tx is not. Pts with significant cardiovascular disease or active brain metastases are not eligible. Pts are stratified by hormone receptor status, geographic region, and prior chemotherapy for adv BC (Y/N) and randomized (1:1) to CAP (1000 mg/m2 po twice daily [BID], days 1–14 of 21) in combination with SOR (po BID, days 1–21, total dose 600 mg/day) or matching PL. CAP and SOR/PL doses can be escalated to 2500 mg/m2 per day and 800 mg/day, respectively, as tolerated, or reduced to resolve toxicity but dose re-escalation is not allowed. Guidelines are provided for prophylactic and symptomatic tx of HFSR/HFS. Radiographic assessment is every 6 wk for the first 36 wk, and every 9 wk thereafter. The primary endpoint is PFS. Secondary endpoints include overall survival, time to progression, overall response rate, duration of response (RECIST 1.1 criteria), and safety. Enrollment began in Nov 2010 with a target of ~519 pts. The trial is registered at ClinicalTrials.gov (NCT01234337). Conclusions: RESILIENCE will provide definitive PFS data for SOR+CAP in adv HER2-negative BC and better characterize the benefit-to-risk profile.
Clinical Trials in the Genomic Era
Authors: Erel Joffe, Alexia Iasonos, Anas Younes
Journal: Journal of Clinical Oncology (2017)

Personalization of therapy to target specific molecular pathways has been placed in the forefront of cancer research. Initial reports from clinical trials designed to select patients for appropriate treatment on the basis of tumor characteristics not only have generated considerable excitement but also have identified several challenges. These challenges include the overcoming of regulatory and logistic difficulties, identification of the best selection biomarkers and diagnostic platforms that can be applied in the clinical setting, definition of relevant outcomes in small preselected patient populations, and the design of methods that facilitate rapid enrollment and interpretation of clinical trials by aggregating data across histologically diverse malignancies with common genetic alterations. Furthermore, because our knowledge of the functional consequences of many genetic alterations lags, investigators and sponsors struggle with choosing between ideal clinical trial designs and more practical ones. These challenges are amplified when more than one biomarker is used to select patients for a combination of targeted agents. This review summarizes the current status and challenges of clinical trials in the genomic era and proposes ways to address these challenges.
Transition care clinic: Evidence-based survivorship care.
Authors: Raman Deol, Matthew C. Cheung, Elisabeth M. Del Giudice, Angela Boudreau, Debbie Miller, Simron Singh
Journal: Journal of Clinical Oncology (2013)

141 Background: The Odette Cancer Centre (OCC) is the sixth largest comprehensive cancer centre in North America. In 2012/2013 fiscal year it is projected there will be 19,633 new cases and 82,293 follow-up visits, of which 16% of new and 24% of follow-ups will be for gastrointestinal (GI) and hematology disease sites. Current specialty cancer clinics are not well equipped to provide evidence-based survivorship care. Methods: The Transition Care Clinic (TCC) was developed for colorectal cancer and lymphoma patients transitioning from acute care at OCC back to their primary care provider (PCP) for follow-up, assessment, and surveillance after completion of active treatment. Patients are seen by a family medicine physician and advanced practice nurse and receive comprehensive survivorship care, individualized treatment summaries, and post-treatment care plans. An accompanying web resource continues to connect patients to OCC after discharge and provides survivorship specific information. Results: An eight month pilot resulted in 66 visits and 28 discharges, of which 53% of visits and 93% of discharges were for GI patients and 47% and 7% respectively for hematology. The 28 discharges resulted in resource utilization savings of 122 OCC clinic visits and 118 hospital CT scans. Symptom screening results across the domains of anxiety, depression, pain, and tiredness were on par with other cancer patients, dispelling concern that these patients experience different/more symptoms after treatment and during transition. Finally, patient feedback indicated that those that found it difficult to attend OCC appointments appreciated knowing guidelines were available and were comfortable with PCP follow-up, while others whose PCP missed initial presenting symptoms preferred cancer centre “specialists” and were not comfortable. Conclusions: There is need for inter-disciplinary development of survivorship and transition programs with buy-in from disease sites, multimodality consensus, revision of eligibility criteria for lymphoma, and efficiencies to complete comprehensive treatment summaries. Short and long-term outcomes to be measured include recurrences and secondary cancers, adherence to guidelines, patient quality of life, and satisfaction.
Prognostic factors and the impact of different classification systems in the gynecologic sarcomas (GS) outcome
Authors: X. Gonzàlez Farré, A. López Pousa, M. Quintana, J. Fernández Plana, D. Páez López-Bravo, À. Roselló, O. Gallego, S. Bagué, A. Tibau, J. Pérez, A. Barnadas Molins
Journal: Journal of Clinical Oncology (2008)

21505 Background: Prognostic factors for GS used in available studies are the presence of metastasis, performance status and factors included in FIGO staging. The objective of this retrospective study was to analyze clinical and pathological prognostic factors, trying to improve the usual (FIGO) classification. Methods: We analyzed 75 patients with ovarian (11) or uterine sarcoma (64) diagnosed from 6/1983 to 12/2007. Pathology: 26 leiomyosarcoma, 35 carcinosarcoma, 10 endometrial stromal, 4 high-grade undifferentiated sarcoma. Results: Medium age was 57 (26–82) years. With a median follow-up of 30.4 months (6–305), 5-year and 10-year survival was 71% and 69%. Survival significant prognostic factors in the univariate analysis: histologic subtype (stromal 100%, leiomyo 69%, carcinosarcoma 64%, undifferentiated 50%, p=0.01); tumor grade (I=100%, II=80%, III=58%, p=0.0003); AJCC sarcoma staging (I=100%, II=71%, III=68%, IV=55%, p=0.005); FIGO staging (I=89%, II=67%, III=58%, IV=50%, p=0.004). Disease relapse occurred in 36 (48%) patients: local only 54%, distant 31%, both 15%. Median time to relapse 13 months, 5-year and 10-year survival was 38% and 32%. Median survival in local vs distant recurrence was 21 and 13 months (non-significant). 5-year survival in radical intention treatment of relapse was 65% vs 13% in palliative setting patients (p<0.001). Conclusions: Histologic type and tumor grade should be considered prognostic factors in GS. FIGO and AJCC staging methods have a good correlation with prognosis. Radical treatment (surgery ± radiotherapy) of relapsed disease should be always considered. No significant financial relationships to disclose.
Clinical research in surgical oncology: An analysis of clinicaltrials.gov.
Authors: Amber S Menezes, Alison Barnes, Adena S Scheer, Husein Moloo, Robin P Boushey, Rebecca Ann C Auer
Journal: Journal of Clinical Oncology (2012)

591 Background: The conduction of randomized clinical trials has expanded in medical specialties, but to a far lesser degree in surgery. This is due to design challenges with standardization of treatment, blinding and lack of surgeon equipoise. The objective of this study was to assess the current landscape of clinical trials in surgical oncology registered at clinicaltrials.gov. Methods: Data was extracted from clinicaltrials.gov using the following search engine criteria: ‘Cancer’ as Condition, ‘Surgery OR Operation OR Resection’ as Intervention, and Non-Industry sponsored. The search was limited to Canada and the United States and included trials registered from January 1, 2001 to January 1, 2011. The search was performed on March 23, 2011 by three investigators in parallel. The total number of oncology trials was also obtained. Results: Of 9990 oncology trials, 1049 (10.5%) included any type of surgical intervention. Of these trials, 125 (11.9%; 1.3% of all oncology trials) manipulated a surgical variable, 773 (73.7%) assessed adjuvant/neoadjuvant therapies, and 151 (14.4%) were observational studies. Trials assessing adjuvant therapies focused on systemic treatment (362 trials, 46.8%) and multimodal therapy (129 trials, 16.7%). Of the 125 trials where surgery was the manipulated variable, 59 trials (47.2%) focused on surgical techniques (including minimally invasive) or devices, 45 trials (36.0%) studied invasive diagnostic methods, and 21 trials (16.8%) evaluated surgery vs. no surgery. The majority of the 125 trials were non- randomized (72, 57.6%), and Phase III trials accounted for less than one-quarter (29, 23.2%). Conclusions: The number of registered surgical oncology trials is small in comparison to oncology trials as a whole. Clinical trials specifically designed to assess surgical interventions are vastly outnumbered by trials focusing on adjuvant therapies, and are frequently non-randomized. Randomized surgical oncology trials account for &lt;1% of all registered cancer trials. Barriers to the design and implementation of randomized trials in surgical oncology need to be clarified to facilitate higher-level evidence in surgical decision making.
Phase III trial of doxorubicin (A)/cyclophosphamide (C) (AC), docetaxel (D), and alternating AC and D (AC-D) as front-line chemotherapy for metastatic breast cancer (MBC): Japan Clinical Oncology Group trial (JCOG9802)
Authors: N. Katsumata, H. Minami, K. Aogi, T. Tabei, M. Sano, N. Masuda, J. Andoh, T. Ikeda, N. Ishizuka, S. Takashima
Journal: Journal of Clinical Oncology (2005)

521
Clinical trial availability compared to incidence rates for adolescent and young adult cancer.
Authors: D. J. Indelicato, A. Bleyer
Journal: Journal of Clinical Oncology (2011)

6119 Background: Evidence suggests that adolescent and young adult cancer patients (AYAs) enrolled in clinical trials have improved outcomes; however, AYAs are far less likely to enroll in clinical trials than children or older adults. A cited barrier to enrollment includes the lack of available clinical trials. The goal of this analysis is to use EmergingMed’s comprehensive trial listing and SEER age-incidence data to identify potential gaps in clinical trials for AYA cancers. Methods: The EmergingMed database contains all publicly available cancer treatment trials in the U.S. and Canada. To obtain the number of enrolling trials for AYAs, EmergingMed analyzed the age criteria for all open trials in the database. The number of trials available was evaluated per year of age for ages 15-19 and by 5-year intervals for ages 20-39. SEER cancer incidence and U.S. census data were used to estimate the number of patients in the U.S. newly diagnosed with specific cancer types. Results: Among both 15-19 and 20-39 year-olds with cancer, there were >5 clinical trials available for each 100 patients diagnosed in 2010 with carcinoma of the lung, pancreas, and bladder and <2 per 100 patients each with Hodgkin or non-Hodgkin lymphoma, melanoma, Ewing sarcoma, osteosarcoma, chondrosarcoma, thyroid carcinoma, medulloblastoma/PNET and ependymoma. Among 15-19 year-olds with cancer, there were also <2 per 100 patients each with acute lymphoblastic leukemia, acute myeloid leukemia and rhabdomyosarcoma. Conclusions: In 2010, there was a deficit of clinical trials in North America for most of the common cancers in AYAs: lymphoma, melanoma, thyroid cancer, primitive brain tumors, and, for adolescents, acute leukemia. In contrast, from purely a numerical standpoint, there may be an adequate number of clinical trials available for AYAs with select carcinomas. Further investigation is needed to understand other AYA barriers such as geographic trial distribution and eligibility criteria other than age. These data may help inform strategic prioritization of trial development for AYA cancer patients.
The characteristics of pancreatic neck cancer.
Authors: Hiroki Yamaue, Seiko Hirono, Manabu Kawai, Ken-Ichi Okada, Motoki Miyazawa, Atsushi Shimizu, Yuji Kitahata, Masaki Ueno, Shinya Hayami, Yoshinobu Shigekawa, Atsushi Miyamoto
Journal: Journal of Clinical Oncology (2016)

337 Background: Pancreatic neck cancer occurs in the small region surrounded by the common hepatic artery (CHA), gastroduodenal artery (GDA), and portal vein (PV). The specific clinicopathological characteristics of pancreatic neck cancer remain unclear. This study aimed to identify specific biological behaviors of pancreatic neck cancer for the improvement of treatment outcomes. Methods: This study was a retrospective cohort study and comparative outcomes design. In 63 (19.4%) of 325 consecutive pancreatic cancer patients who underwent surgery, the tumor was located in the pancreatic neck. Clinicopathological characteristics and prognostic factors specific to pancreatic neck cancer were analyzed by comparison to those of pancreatic head or body/tail cancers. Results: The rates of radiographic and pathological PV and/or superior mesenteric vein (PV/SMV) invasion were higher in patients with pancreatic neck cancer (radiographic: 84.1%, pathological: 36.5%) than those with pancreatic head and body/tail cancers (radiographic, head: 67.3%, body/tail: 25.0%, pathological, head: 26.0%, body/tail: 6.3%). The most frequent lymph node metastasis was found in the region along the CHA in pancreatic neck cancer, and the spots most likely to show a positive surgical margin were the dissected surface of the PV and the root of the GDA and/or CHA. For pancreatic neck cancer patients, five independent poor prognostic factors were found: pathological PV/SMV invasion (P= 0.005), moderately or poorly differentiation (P= 0.001), positive lymph node ratio ≥ 0.1 (P&lt; 0.001), surgical margin length ≤ 1 mm (P= 0.018), and no completion of planned postoperative adjuvant therapy (P&lt; 0.001). Conclusions: Pancreatic neck cancer showed specific clinicopathological characteristics and prognostic factors after resection. Patients with these risk factors might need multimodality treatment strategies, including neoadjuvant therapy, in order to prolong the survival, although further studies will be necessary to confirm our findings.
Baseline evaluation of the patient-centered oncology care model.
Authors: Manasi A. Tirodkar, Sarah Hudson Scholle
Journal: Journal of Clinical Oncology (2014)

50 Background: The patient-centered medical home (PCMH) model of care is being widely adopted as a way to provide accessible, proactive, coordinated care and self-care through primary care practices. During active treatment for cancer, the oncology practice is often the primary setting supporting the patient and coordinating cancer treatment. For this project, we are implementing a Patient-centered Oncology Care model in five oncology practices and evaluating the impact on cost, quality, and patient experiences. Methods: To determine the structures and processes present in the practices at baseline, we conducted a self-assessment on the standards, followed with an on-site “audit” for compliance with the standards. To get a sense for organizational culture and motivation to change, we conducted site visits which included interviews with providers, staff and patients and observation of clinical encounters and workflow. Results: Among the highest priority structures and processes, the most common were telephone triage, symptom management, advance care planning, and the use of evidence-based guidelines. The least common were patient/family orientation, availability of same day appointments, discussion and documentation of goals of therapy, symptom assessment, and tracking of appointments. All of the practices had made patient-centered care a priority and staff were motivated to change. There was variation in the way providers and the care team used health information technology during clinical workflow. There was also variation in which staff coordinated care for patients and whether or not financial counseling was offered. All of the practices stated that they needed to work on implementing survivorship care planning, shared decision-making, and patient engagement in quality improvement and practice transformation Conclusions: The pilot oncology practices have many structures and processes in common. However, there is little standardization within practices in the way these processes are established and documented. Practices vary in how they are implementing patient-centered care processes. However, with motivation to change, staff and providers are actively engaged in the transformation process.
Inhibiting Binding of Sickle Red Cell ICAM-4 to Endothelial Cell αVβ3 Integrin Decreases Red Cell Adhesion and Vaso-Occlusion.
Authors: Dhananjay Kaul, Xiao-du Liu, Xiaoqin Zhang, Tosti Mankelow, Stephen Parsons, Frances Spring, Xiuli An, Narla Mohandas, David Anstee, Joel Anne Chasis
Journal: Blood (2004)