Partitioning of excess mortality in population-based cancer patient survival studies using flexible parametric survival models.

Background: Relative survival is commonly used for studying survival of cancer patients as it captures both the direct and indirect contribution of a cancer diagnosis on mortality by comparing the observed survival of the patients to the expected survival in a comparable cancer-free population. However, existing methods do not allow estimation of the impact of isolated conditions (e.g., excess cardiovascular mortality) on the total excess mortality. For this purpose we extend flexible parametric survival models for relative survival, which use restricted cubic splines for the baseline cumulative excess hazard and for any time-dependent effects. Methods: In the extended model we partition the excess mortality associated with a diagnosis of cancer through estimating a separate baseline excess hazard function for the outcomes under investigation. This is done by incorporating mutually exclusive background mortality rates, stratified by the underlying causes of death reported in the Swedish population, and by introducing cause of death as a time-dependent effect in the extended model. This approach thereby enables modeling of temporal trends in e.g., excess cardiovascular mortality and remaining cancer excess mortality simultaneously. Furthermore, we illustrate how the results from the proposed model can be used to derive crude probabilities of death due to the component parts, i.e., probabilities estimated in the presence of competing causes of death. Results: The method is illustrated with examples where the total excess mortality experienced by patients diagnosed with breast cancer is partitioned into excess cardiovascular mortality and remaining cancer excess mortality. Conclusions: The proposed method can be used to simultaneously study disease patterns and temporal trends for various causes of cancer-consequent deaths. Such information should be of interest for patients and clinicians as one way of improving prognosis after cancer is through adapting treatment strategies and follow-up of patients towards reducing the excess mortality caused by side effects of the treatment

Relapse Risk and Loss of Lifetime After Modern Combined Modality Treatment of Young Patients With Hodgkin Lymphoma : A Nordic Lymphoma Epidemiology Group Study

PURPOSE: Estimates of short- and long-term survival for young patients with classic Hodgkin lymphoma (cHL) are of considerable interest. We investigated cHL prognosis in the era of contemporary treatment at different milestones during the follow-up. PATIENTS AND METHODS: On the basis of a Nordic cohort of 2,582 patients diagnosed at ages 18 to 49 years between 2000 and 2013, 5-year relapse risks and 5-year restricted losses in expectation of lifetime were estimated for all patients and for patients who achieved event-free survival (EFS) for 12 (EFS12), 24 (EFS24), 36 (EFS36) or 60 (EFS60) months. The median follow-up time was 9 years (range, 2.9 to 16.8 years). RESULTS: The 5-year overall survival was 95% (95% CI, 94% to 96%). The 5-year risk of relapse was 13.4% (95% CI, 12.1% to 14.8%) overall but decreased to 4.2% (95% CI, 3.8% to 4.6%) given that patients reached EFS24. Relapse risk for patients treated with six to eight courses of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) was comparable to that of patients treated with six to eight courses of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) despite more adverse risk criteria among patients treated with BEACOPP. Both from diagnosis and if EFS24 was reached, the losses in expectation of lifetime during the following 5 years were small (from diagnosis, 45 days [95% CI, 35 to 54 days] and for patients who reached EFS24, 13 days [95% CI, 7 to 20 days]). In stage-stratified analyses of 5-year restricted loss in expectation of lifetime, patients with stages I to IIA disease had no noteworthy excess risk of death after they reached EFS24, whereas risk remained measurable for patients with stages IIB to IV cHL. CONCLUSION: Real-world data on young patients with cHL from the Nordic countries show excellent outcomes. The outlook is particularly favorable for patients who reach EFS24, which supports limited relapse-oriented clinical follow-up

Solving the Phosphorus Pollution Puzzle: Synthesis and Directions for Future Research

Despite the success of efforts to reduce phosphorus (P) pollution from point sources, P from non-point agricultural sources remains a vexing problem with many U.S. water bodies having impairments. Key to solving the P pollution puzzle is to take stock of progress to date, the puzzle pieces available, and the gaps to be filled. In this paper, we synthesize the state of knowledge on P pollution, discuss the state of existing public programs, and review economists’ contributions to informing P pollution policies. We review the water quality valuation literature, identifying limitations in the linkages to policy-relevant environmental quality metrics. We examine how and why P is used agriculturally, along with recent advances in market-based policy design and field testing. We survey new knowledge in biology and engineering, including improved understanding of the fate and transport of P. In light of recent learning and persistent knowledge gaps, we recommend directions for economic research to add needed pieces to the puzzle of how to protect our water bodies. Puzzle gaps meriting attention include mechanisms to target public funds more effectively in voluntary abatement programs, policy design for emerging mitigation technologies, new ways to implement performance-based policies, means to leverage social norms and behavioral cues, changes in the “pay-the-polluter” paradigm, and application of state-of-the-art evaluation methods to conservation programs. Beyond the realm of public policy lies that of private supply chains, where establishment of environmental standards holds additional promise. Rich research opportunities exist for economists in tandem with biologists, engineers, and other