IMPORTANCE Although consensus statements support the preoperative treatment of borderline resectable pancreatic cancer, no prospective, quality-controlled, multicenter studies of this strategy have been conducted. Existing studies are retrospective and confounded by heterogeneity in patients studied, therapeutic algorithms used, and outcomes reported. OBJECTIVE To determine the feasibility of conducting studies of multimodality therapy for borderline resectable pancreatic cancer in the cooperative group setting. DESIGN, SETTING, AND PARTICIPANTS A prospective, multicenter, single-arm trial of a multimodality treatment regimen administered within a study framework using centralized quality control with the cooperation of 14 member institutions of the National Clinical Trials Network. Twenty-nine patients with biopsy-confirmed pancreatic cancer preregistered, and 23 patients with tumors who met centrally reviewed radiographic criteria registered. Twenty-two patients initiated therapy (median age, 64 years [range, 50–76 years]; 55% female). Patients registered between May 29, 2013, and February 7,2014. INTERVENTIONS Patients received modified FOLFIRINOX treatment (85 mg/m2 of oxaliplatin, 180 mg/m2 of irinotecan hydrochloride, 400 mg/m2 of leucovorin calcium, and then 2400 mg/m2 of 5-fluorouracil for 4 cycles) followed by 5.5 weeks of external-beam radiation (50.4 Gy delivered in 28 daily fractions) with capecitabine (825 mg/m2 orally twice daily) prior to pancreatectomy. MAIN OUTCOMES AND MEASURES Feasibility, defined by the accrual rate, the safety of the preoperative regimen, and the pancreatectomy rate. RESULTS The accrual rate of 2.6 patients per month was superior to the anticipated rate. Although 14 of the 22 patients (64% [95% CI, 41%–83%]) had grade 3 or higher adverse events, 15 of the 22 patients (68% [95% CI, 49%–88%]) underwent pancreatectomy. Of these 15 patients, 12 (80%) required vascular resection, 14 (93%) had microscopically negative margins, 5 (33%) had specimens that had less than 5% residual cancer cells, and 2 (13%) had specimens that had pathologic complete responses. The median overall survival of all patients was 21.7 months (95% CI, 15.7 to not reached) from registration. CONCLUSIONS AND RELEVANCE The successful completion of this collaborative study demonstrates the feasibility of conducting quality-controlled trials for this disease stage in the multi-institutional setting. The data generated by this study and the logistical elements that facilitated the trial's completion are currently being used to develop cooperative group trials with the goal of improving outcomes for this subset of patients. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01821612
Barring holocausts, demographic forecasts suggest a "demographic winter" lasting 500-1,OOO years and eliminating most habitat for wildlife in the tropics. About 2,000 species of large, terrestrial animals may have to be captively bred if they are to be saved from extinction by the mushrooming human population. Improvements in biotechnology may facilitate the task of protecting these species, but it probably will be decades at least before cryotechnology per se is a viable alternative to captive breeding for most species of endangered wildlife. We suggest that a principle goal of captive breeding be the maintenance of 90% of the genetic variation in the source (wild) population over a period of 200 years. Tables are provided that permit the estimation of the ultimate minimum size of the captive group, given knowledge of the exponential growth rate of the group, and the number of founders. In most cases, founder groups will have to be above 20 (effective) individuals.
Zoos and aquariums exhibit many rare species, but sustain few for long periods. Demanding genetic, demographic, and behavioral requirements are a part of the sustainability challenge, and historical zoo goals and limiting animal management objectives are another, but they have been overtaken by worldwide wildlife population contraction and endangerment. New policies are essential for zoo continuance and, if vanishing species are to be helped by zoo propagation, they must be given priority. However, zoos have little animal carrying capacity and propagation must be much more sharply focused. In addition, it is becoming urgent that zoos help to support parks and reserves and, where possible, manage some especially endangered species mutually with parks.
Collection-based institutions-zoos, aquariums, museums, and botanical gardens-exhibit wildlifeand thus have a special connection with nature. Many of these institutions emphasize a mission of conservation, and, undeniably, they do contribute directly to conservation education and conservation science. They present an exceptional opportunity for many urban residents to see the wonders of life, and they can contribute to education and habitat preservation. Because many collection-based institutions now hold a stated mission of conservation, we suggest eight potential questions to evaluate actions toward that mission: (1) Does conservation thought define policy decisions? (2) Is there sufficient organizational funding for conservation activities?(3) Is there a functional conservation department? (4) Does the institution advocate for conservation? (5) Do conservation education programs effectively target children and adults? (6) Does the institution contribute directly to habitat protection locally and internationally? (7) Do exhibits explain and promote conservation efforts? and (8) Do internal policies and activities protect the environment? These questions are offered as a place to begin discussion. We hope they will help employees and administrators of a collection-based institution (and citizens of the surrounding community) think about and support their institution's conservation activities. Public support and praise for institutions that are striving toward solutions for conservation problems and pressure on organizations that are moving more slowly toward a conservation orientation can help shift more resources toward saving nature. Evaluación de la Misión de Conservación de Zoológicos, Acuarios, Jardines Botánicos o Museos de Historia NaturalResumen: Las instituciones basadas en colecciones (zoológicos, acuarios, museos y jardines botánicos) exhiben vida silvestre. Por lo tanto, tienen una conexión especial con la naturaleza. Muchas de estas instituciones destacan una misión de conservación y, sin duda contribuyen directamente a la educación y la ciencia de la conservación. Brindan una oportunidad excepcional para que muchos residentes urbanos vean las maravillas de la vida, y pueden contribuir a la educación y a la preservación del hábitat. Debido a que en la actualidad muchas de las instituciones basadas en colecciones tienen una misión de conservación manifiesta, sugerimos ocho preguntas potenciales para evaluar las acciones hacia el cumplimiento de esa misión: (1) ¿Las consideraciones sobre la conservación definen las decisiones sobre políticas? (2) ¿Hay suficiente financiamiento organizacional para las actividades de conservación? (3) ¿Hay un departamento de conservación que funcione? (4) ¿La institución aboga por la conservación? (5) ¿Los programas de educación en conservación se ‡ Miller et al. Conservation and Collection-Based Institutions 87enfocan eficientemente sobre niños y adultos? (6) ¿La institución contribuye directamente a la conservación del hábitat a nivel local e internacional? (7) ¿Las e...
Pancreatic ductal adenocarcinoma (PDAC) harbors the worst prognosis of any common solid tumor, and multiple failed clinical trials indicate therapeutic recalcitrance. Here we use exome sequencing of patient tumors and find multiple conserved genetic alterations. However, the majority of tumors exhibit no clearly defined therapeutic target. High-throughput drug screens using patient-derived cell lines found rare examples of sensitivity to monotherapy, with most requiring combination therapy. Using PDX models, we confirmed the effectiveness and selectivity of the identified treatment responses. Out of greater than 500 single and combination drug regimens tested, no single treatment was effective for the majority of PDAC tumors, and each case had unique sensitivity profiles that could not be predicted using genetic analyses. These data indicate a shortcoming of reliance on genetic analysis to predict efficacy of currently available agents against PDAC, and that sensitivity profiling of patient-derived models could inform personalized therapy design for PDAC.
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