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      Pancreatic cancer—A disease in need: Optimizing and integrating supportive care

      1 , 1 , 2 , 1 , 2 , 3
      Cancer
      Wiley

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          Abstract

          Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy that continues to be challenging to treat. PDAC has the lowest five-year relative survival rate compared to all other solid tumor malignancies and is expected to become the second-leading cause of cancer-related death in the United States by 2030. Given the high mortality, there is an increasing role for concurrent anti-cancer and supportive care in the management of patients with PDAC with the aims of maximizing length of life, quality of life (QoL), and symptom control. Emerging trends in supportive care that can be integrated into the clinical management of patients with PDAC include standardized supportive care screening, early integration of supportive care into routine cancer care, early implementation of outpatient-based advance care planning, and utilization of electronic patient reported outcomes for improved symptom management and QoL. The most common symptoms experienced are nausea, constipation, weight loss, diarrhea, anorexia, and abdominal and back pain. This review article includes current supportive management strategies for these and others. Common disease-related complications include biliary and duodenal obstruction requiring endoscopic procedures and venous thromboembolic events. Patients with PDAC continue to have a poor prognosis. Systemic therapy options are able to palliate the high symptom burden but have a modest impact on overall survival. Early integration of supportive care can lead to improved outcomes. Pancreatic cancer is an aggressive malignancy with a poor prognosis. Early involvement of supportive care with honest prognostication, outpatient advance care planning, and utilization of electronic patient reported outcomes is recommended for improvement in quality of life, symptom management, and overall survival.

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          Most cited references76

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          Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer.

          Patients with cancer have a substantial risk of recurrent thrombosis despite the use of oral anticoagulant therapy. We compared the efficacy of a low-molecular-weight heparin with that of an oral anticoagulant agent in preventing recurrent thrombosis in patients with cancer. Patients with cancer who had acute, symptomatic proximal deep-vein thrombosis, pulmonary embolism, or both were randomly assigned to receive low-molecular-weight heparin (dalteparin) at a dose of 200 IU per kilogram of body weight subcutaneously once daily for five to seven days and a coumarin derivative for six months (target international normalized ratio, 2.5) or dalteparin alone for six months (200 IU per kilogram once daily for one month, followed by a daily dose of approximately 150 IU per kilogram for five months). During the six-month study period, 27 of 336 patients in the dalteparin group had recurrent venous thromboembolism, as compared with 53 of 336 patients in the oral-anticoagulant group (hazard ratio, 0.48; P=0.002). The probability of recurrent thromboembolism at six months was 17 percent in the oral-anticoagulant group and 9 percent in the dalteparin group. No significant difference between the dalteparin group and the oral-anticoagulant group was detected in the rate of major bleeding (6 percent and 4 percent, respectively) or any bleeding (14 percent and 19 percent, respectively). The mortality rate at six months was 39 percent in the dalteparin group and 41 percent in the oral-anticoagulant group. In patients with cancer and acute venous thromboembolism, dalteparin was more effective than an oral anticoagulant in reducing the risk of recurrent thromboembolism without increasing the risk of bleeding. Copyright 2003 Massachusetts Medical Society
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            Early Versus Delayed Initiation of Concurrent Palliative Oncology Care: Patient Outcomes in the ENABLE III Randomized Controlled Trial.

            Randomized controlled trials have supported integrated oncology and palliative care (PC); however, optimal timing has not been evaluated. We investigated the effect of early versus delayed PC on quality of life (QOL), symptom impact, mood, 1-year survival, and resource use.
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              Induction of T-cell Immunity Overcomes Complete Resistance to PD-1 and CTLA-4 Blockade and Improves Survival in Pancreatic Carcinoma.

              Disabling the function of immune checkpoint molecules can unlock T-cell immunity against cancer, yet despite remarkable clinical success with monoclonal antibodies (mAb) that block PD-1 or CTLA-4, resistance remains common and essentially unexplained. To date, pancreatic carcinoma is fully refractory to these antibodies. Here, using a genetically engineered mouse model of pancreatic ductal adenocarcinoma in which spontaneous immunity is minimal, we found that PD-L1 is prominent in the tumor microenvironment, a phenotype confirmed in patients; however, tumor PD-L1 was found to be independent of IFNγ in this model. Tumor T cells expressed PD-1 as prominently as T cells from chronically infected mice, but treatment with αPD-1 mAbs, with or without αCTLA-4 mAbs, failed in well-established tumors, recapitulating clinical results. Agonist αCD40 mAbs with chemotherapy induced T-cell immunity and reversed the complete resistance of pancreatic tumors to αPD-1 and αCTLA-4. The combination of αCD40/chemotherapy plus αPD-1 and/or αCTLA-4 induced regression of subcutaneous tumors, improved overall survival, and conferred curative protection from multiple tumor rechallenges, consistent with immune memory not otherwise achievable. Combinatorial treatment nearly doubled survival of mice with spontaneous pancreatic cancers, although no cures were observed. Our findings suggest that in pancreatic carcinoma, a nonimmunogenic tumor, baseline refractoriness to checkpoint inhibitors can be rescued by the priming of a T-cell response with αCD40/chemotherapy.
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                Author and article information

                Journal
                Cancer
                Cancer
                Wiley
                0008-543X
                1097-0142
                August 02 2019
                November 15 2019
                August 05 2019
                November 15 2019
                : 125
                : 22
                : 3927-3935
                Affiliations
                [1 ]Gastrointestinal Oncology Service Memorial Sloan Kettering Cancer Center New York New York
                [2 ]Division of Solid Tumor Oncology Weill Cornell Medical College New York New York
                [3 ]Department of Medicine, David M. Rubenstein Center for Pancreatic Cancer Research Memorial Sloan Kettering Cancer Center New York New York
                Article
                10.1002/cncr.32423
                6819216
                31381149
                e8f72f75-86b7-4046-b74e-2826598ba610
                © 2019

                http://onlinelibrary.wiley.com/termsAndConditions#vor

                http://doi.wiley.com/10.1002/tdm_license_1.1

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