Association of Early Palliative Care With Chemotherapy Intensity in Patients With Advanced Stage Lung Cancer: A National Cohort Study.

INTRODUCTION: Patients with advanced lung cancer have a poor prognosis, but both chemotherapy and early palliative care (EPC) have been shown to improve survival and quality of life (QOL). The relationship between palliative care and receipt of chemotherapy receipt is understudied. We sought to determine if EPC is associated with chemotherapy receipt and intensity among patients with advanced stage lung cancer. METHODS: Retrospective cohort study of patients in the national Veterans Health Administration (VA) with stage IIIB or IV lung cancer diagnosed between January 2007- December 2013. EPC was defined as a specialist-delivered palliative care received within 90 days of cancer diagnosis. Outcomes included any chemotherapy receipt and high-intensity chemotherapy receipt defined as: i) more than 4 cycles of a platinum-based doublet, ii) ≥3 lines of chemotherapy, iii) Bevacizumab/Cetuximab triplet therapy, iv) Erlotinib use prior to 2011, and v) chemotherapy in the last days of life. Logistic regression was used to determine the association between EPC and chemotherapy receipt after adjustment for patient and tumor characteristics. RESULTS: Among the entire cohort (N=23,566), 37% received EPC and 45% received any chemotherapy. Among those with EPC, 34% received chemotherapy compared to 51% among those without EPC (Adjusted Odds Ratio (AOR=0.55, 95% CI: 0.51-0.58). Patients who received EPC had reduced receipt of high-intensity chemotherapy including >4 cycles of platinum-based doublet (AOR=0.68, 95% CI: 0.60-0.77), ≥ 3 lines of chemotherapy (AOR=0.61, 95% CI: 0.53-0.71), triplet therapy (AOR=0.68, 95% CI: 0.56-0.82) and use of erlotinib prior to 2011 (AOR=0.66, 95% CI: 0.55-0.79). Patients with EPC were more likely to receive chemotherapy in the last 14 (AOR=1.65, 95% CI: 1.44-1.87) and 30 days (AOR=1.67, 95% CI: 1.51-1.85) of life compared to those without EPC. CONCLUSIONS: EPC was associated with reduced receipt of both any chemotherapy and high-intensity chemotherapy. However, receipt of chemotherapy at the very end-of-life was increased among patients with EPC compared to those without EPC. Among patients with advanced lung cancer, EPC may optimize patient selection for chemotherapy receipt leading to reduced use of high-intensity therapy by focusing on quality of life in accordance with patients' performance, preferences and goals of care.

The Oncology Specialist's Role in POLST Form Completion.

INTRODUCTION: Patients with cancer and oncology professional societies believe that advance care planning is important, but we know little of who actually has this conversation. Physician Orders for Life-Sustaining Treatment (POLST) forms can help to document these important conversations to ensure patients receive the level of treatment they want. We therefore sought to determine the specialty of those signing POLST forms for patients who died of cancer to better understand who is having this discussion with patients. METHODS: Retrospective cohort study including all deaths due to cancer in Oregon between January 1, 2010, and December 31, 2011. Death certificates were matched to POLST forms in the Oregon POLST Registry, and the signing physician's specialty was determined using the Oregon Medical Board's database. RESULTS: A total of 14 979 people died of cancer in Oregon in 2010 to 2011. Of which, 6145 (41.0%) had at least 1 POLST form in the Registry. Oncology specialists signed 14.9% of POLST forms, compared to 53.7% by primary care, 15.3% by hospice/palliative care, 12.8% by advanced practice providers, and 2.7% by other specialists; 51.8% of oncology specialists did not sign a POLST form, whereas 12.5% completed 10 or more. CONCLUSION: Oncology specialists play a central role in caring for patients with cancer through the end of their lives, but not in POLST completion. Whether or not they actually sign their patients' POLST forms, oncology specialists in the growing number of POLST states should integrate POLST into their goals of care conversations with patients nearing the end of life.

Frequency and level of evidence used in recommendations by the National Comprehensive Cancer Network guidelines beyond approvals of the US Food and Drug Administration: retrospective observational study.

OBJECTIVE: To determine the differences between recommendations by the National Comprehensive Cancer Network (NCNN) guidelines and Food and Drug Administration approvals of anticancer drugs, and the evidence cited by the NCCN to justify recommendations where differences exist. DESIGN: Retrospective observational study. SETTING: National Comprehensive Cancer Network and FDA. PARTICIPANTS: 47 new molecular entities approved by the FDA between 2011 and 2015. MAIN OUTCOME MEASURES: Comparison of all FDA approved indications (new and supplemental) with all NCCN recommendations as of 25 March 2016. When the NCCN made recommendations beyond the FDA's approvals, the recommendation was classified and the cited evidence noted. RESULTS: 47 drugs initially approved by the FDA between 2011 and 2015 for adult hematologic or solid cancers were examined. These 47 drugs were authorized for 69 FDA approved indications, whereas the NCCN recommended these drugs for 113 indications, of which 69 (62%) overlapped with the 69 FDA approved indications and 44 (39%) were additional recommendations. The average number of recommendations beyond the FDA approved indications was 0.92. 23% (n=10) of the additional recommendations were based on evidence from randomized controlled trials, and 16% (n=7) were based on evidence from phase III studies. During 21 months of follow-up, the FDA granted approval to 14% (n=6) of the additional recommendations. CONCLUSION: The NCCN frequently recommends beyond the FDA approved indications even for newer, branded drugs. The strength of the evidence cited by the NCCN supporting such recommendations is weak. Our findings raise concern that the NCCN justifies the coverage of costly, toxic cancer drugs based on weak evidence.

Lung cancer specialists' opinions on treatment for stage I non-small cell lung cancer: A multidisciplinary survey.

PURPOSE: The current standard of care for surgically eligible stage I non-small cell lung cancer (NSCLC) is surgical resection, but emerging data suggest that stereotactic body radiation therapy (SBRT) is potentially as effective as surgery. However, specialist views of the current evidence about SBRT and how they would incorporate a randomized controlled trial (RCT) into practice is unclear. We sought to understand specialist opinions about evidence regarding treatment of stage I NSCLC and how this translates into practice and clinical trial implementation. METHODS AND MATERIALS: We used a 28-item, web-based survey that invited all participating providers from the American Society for Radiation Oncology, American Thoracic Society Thoracic Oncology Assembly, and the International Association for the Study of Lung Cancer to share opinions regarding practice beliefs, treatment of stage I NSCLC, and a clinical trial scenario. RESULTS: A total of 959 surveys were completed; 64% were from radiation oncologists (ROs) and 49% were from outside the United States. The majority of ROs (80%) reported that current evidence indicates that SBRT has the same or a better benefit compared with surgery for surgically eligible patients with stage I NSCLC; 28% of non-radiation oncologists (NROs) indicated the same (P < .01). Almost all ROs (94%), compared with 62% of NROs, would permit surgically eligible patients to enroll in an RCT of SBRT versus surgery (P < .01). Most ROs (82%) and NROs (87%) believed that changing practice in thoracic surgery would be somewhat difficult, very difficult, or impossible (P = .066) even if an RCT showed better survival with SBRT. CONCLUSIONS: NROs believe that SBRT is much less effective than surgery, contrary to ROs, who believe that they are similar. Most would support an RCT, but NROs would do so less. Changes in surgical practice may be challenging even if an RCT shows better mortality and quality of life with SBRT. These results are helpful in the creation and dissemination of RCTs that are designed to understand this question.

Heparin-induced thrombocytopenia: a tremendous opportunity for randomization.

: Heparin-induced thrombocytopenia and thrombosis (HITT) is both life-threatening with a complex immune-mediated process and clinically challenging to diagnose and treat. What further complicates matters is that thrombocytopenia is a frequently encountered laboratory value but rarely results in clinical signs of HITT. Decades into its initial description, we have anticoagulants with a small therapeutic index and associated high cost. The diagnosis is sometimes equivocal given our current laboratory diagnostics, and can take days to confirm. Furthermore, prior studies that resulted in the approval of anticoagulants for the treatment of heparin-induced thrombocytopenia have been imperfectly designed. Further evaluations of patients with HITT could more adequately define these difficult issues.