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BackgroundBone biomarkers are strongly prognostic for overall survival (OS) in men with castration-resistant prostate cancer but not fully established for hormone-sensitive prostate cancer (HSPC).ObjectiveBone biomarkers in HSPC were prospectively evaluated as part of a phase 3 study of androgen deprivation therapy ± the CYP17 inhibitor orteronel.Design, setting, and participantsPatients were randomly divided into training (n = 316) and validation (n = 633) sets. Recursive partitioning and Cox proportional hazard models were employed.Outcome measurements and statistical analysisBone resorption (C-telopeptide and pyridinoline) and bone formation markers (C-terminal collagen propeptide and bone alkaline phosphatase) were assessed from patient sera.Results and limitationsOf 1279 men, 949 had evaluable baseline bone biomarkers. Optimal cutoffs were identified to define elevated levels of each of the four biomarkers (all p

BACKGROUND: An important issue for patients with cancer treated with novel therapeutics is how they weigh the effects of treatment on survival and quality of life (QOL). We compared QOL in patients enrolled to SWOG S1400I, a substudy of the LungMAP biomarker-driven master protocol. METHODS: SWOG S1400I was a randomized phase III trial comparing nivolumab plus ipilimumab vs nivolumab for treatment of immunotherapy-naïve disease in advanced squamous cell lung cancer. The primary endpoint was the MD Anderson Symptom Inventory-Lung Cancer severity score at week 7 and week 13 with a target difference of 1.0 points, assessed using multivariable linear regression. A composite risk model for progression-free and overall survival was derived using best-subset selection. RESULTS: Among 158 evaluable patients, median age was 67.6 years and most were male (66.5%). The adjusted MD Anderson Symptom Inventory-Lung Cancer severity score was 0.04 points (95% confidence interval [CI] = -0.44 to 0.51 points; P = .89) at week 7 and 0.12 points (95% CI = -0.41 to 0.65; P = .66) at week 13. A composite risk model showed that patients with high levels of appetite loss and shortness of breath had a threefold increased risk of progression or death (hazard ratio [HR] = 3.06, 95% CI = 1.88 to 4.98; P

Diffuse large B cell lymphoma (DLBCL) is an aggressive but potentially curable malignancy; however, cure is highly dependent on the ability to deliver intensive, anthracycline-based chemoimmunotherapy. Nearly one third of cases of DLBCL occur in patients over age 75 years, and advanced age is an important adverse feature in prognostic models. Despite this incidence in older patients, there is no clear accepted standard of care due to under-representation of this group in large randomized clinical trials. Furthermore, insufficient assessments of baseline frailty and prediction of toxicity hamper clinical decision-making. Here, we present an ongoing randomized study of R-miniCHOP chemoimmunotherapy with or without oral azacitidine (CC-486, Onureg) for patients age 75 and older with newly diagnosed DLBCL and associated aggressive lymphomas. The incorporation of an oral hypomethylating agent is based on increased tumor methylation as a biologic feature of older patients with DLBCL and a desire to minimize the injection burden for this population. This is the first randomized study in this population conducted in North America by the National Clinical Trials Network (NCTN) and will enroll up to 422 patients including 40 patients in a safety run-in phase. This study incorporates an objective assessment of baseline frailty (the FIL Tool) and a serial comprehensive geriatric assessment (CGA). Key correlative tests will include circulating tumor DNA (ctDNA) assays at pre-specified timepoints to explore if ctDNA quantity and methylation patterns correlate with response. S1918 has the potential to impact future trial design and to change the standard of care for patients 75 years and older with aggressive lymphoma given its randomized design, prospective incorporation of geriatric assessments, and exploration of ctDNA correlatives. Trial registration: The trial is registered with ClinicalTrial.gov Identifier NCT04799275.

ImportanceThe combined 28 years of data of medical aid in dying (MAID) between Oregon (OR) and Washington (WA) are the most comprehensive in North America. No reports to date have compared MAID use in different US states.ObjectiveTo evaluate and compare patterns of MAID use between the states with the longest-running US death with dignity programs.Design, setting, and participantsA retrospective observational cohort study of OR and WA patients with terminal illness who received prescriptions as part of their states' legislation allowing MAID. All published annual reports, from 1998 to 2017 in OR and from 2009 to 2017 in WA, were reviewed. A total of 3368 prescriptions were included.Main outcomes and measuresNumber of deaths from self-administration of lethal medication vs number of prescriptions written.ResultsA combined 3368 prescriptions were written in OR and WA, with 2558 patient deaths from lethal ingestion (76.0%). Of the 2558 patients, most were male (1311 [51.3%]), older than 65 years (1851 [72.4%]), and non-Hispanic white (2426 [94.8%]). The most common underlying illnesses were cancer (1955 [76.4%]), neurologic illness (261 [10.2%]), lung disease (144 [5.6%]), and heart disease (117 [4.6%]). Loss of autonomy (2235 [87.4%]), impaired quality of life (2203 [86.1%]), and loss of dignity (1755 [68.6%]) were the most common reasons for pursuing MAID. Time between drug intake to coma ranged from 1 to 660 minutes and time from drug intake to death ranged from 1 to 6240 minutes. In the 1557 patients for whom rates of complications were reported, 1494 (96.0%) did not experience a complication (592 of 626 [94.6%] in OR and 902 of 931 [96.8%] in WA). Eight patients (

ImportanceThe combined 28 years of data of medical aid in dying (MAID) between Oregon (OR) and Washington (WA) are the most comprehensive in North America. No reports to date have compared MAID use in different US states.ObjectiveTo evaluate and compare patterns of MAID use between the states with the longest-running US death with dignity programs.Design, setting, and participantsA retrospective observational cohort study of OR and WA patients with terminal illness who received prescriptions as part of their states' legislation allowing MAID. All published annual reports, from 1998 to 2017 in OR and from 2009 to 2017 in WA, were reviewed. A total of 3368 prescriptions were included.Main outcomes and measuresNumber of deaths from self-administration of lethal medication vs number of prescriptions written.ResultsA combined 3368 prescriptions were written in OR and WA, with 2558 patient deaths from lethal ingestion (76.0%). Of the 2558 patients, most were male (1311 [51.3%]), older than 65 years (1851 [72.4%]), and non-Hispanic white (2426 [94.8%]). The most common underlying illnesses were cancer (1955 [76.4%]), neurologic illness (261 [10.2%]), lung disease (144 [5.6%]), and heart disease (117 [4.6%]). Loss of autonomy (2235 [87.4%]), impaired quality of life (2203 [86.1%]), and loss of dignity (1755 [68.6%]) were the most common reasons for pursuing MAID. Time between drug intake to coma ranged from 1 to 660 minutes and time from drug intake to death ranged from 1 to 6240 minutes. In the 1557 patients for whom rates of complications were reported, 1494 (96.0%) did not experience a complication (592 of 626 [94.6%] in OR and 902 of 931 [96.8%] in WA). Eight patients (

INTRODUCTION: The American Joint Committee on Cancer (AJCC) staging system undergoes periodic revisions to maintain contemporary survival outcomes related to stage. Recently, the AJCC has developed a novel, systematic approach incorporating survival data to refine stage groupings. The objective of this study was to demonstrate data‐driven optimization of the version 9 AJCC staging system for anal cancer assessed through a defined validation approach. METHODS: The National Cancer Database was queried for patients diagnosed with anal cancer in 2012 through 2017. Kaplan–Meier methods analyzed 5‐year survival by individual clinical T category, N category, M category, and overall stage. Cox proportional hazards models validated overall survival of the revised TNM stage groupings. RESULTS: Overall, 24,328 cases of anal cancer were included. Evaluation of the 8th edition AJCC stage groups demonstrated a lack of hierarchical prognostic order. Survival at 5 years for stage I was 84.4%, 77.4% for stage IIA, and 63.7% for stage IIB; however, stage IIIA disease demonstrated a 73.0% survival, followed by 58.4% for stage IIIB, 59.9% for stage IIIC, and 22.5% for stage IV (p <.001). Thus, stage IIB was redefined as T1‐2N1M0, whereas Stage IIIA was redefined as T3N0‐1M0. Reevaluation of 5‐year survival based on data‐informed stage groupings now demonstrates hierarchical prognostic order and validated via Cox proportional hazards models. CONCLUSION: The 8th edition AJCC survival data demonstrated a lack of hierarchical prognostic order and informed revised stage groupings in the version 9 AJCC staging system for anal cancer. Thus, a validated data‐driven optimization approach can be implemented for staging revisions across all disease sites moving forward. Evaluation of the 8th edition American Joint Committee on Cancer staging system demonstrated a lack of hierarchical prognostic order for anal cancer. Thus, the version 9 American Joint Committee on Cancer staging system for anal cancer was revised through a validated and data‐driven approach and should similarly be applied across all disease sites moving forward. [ABSTRACT FROM AUTHOR]

44 Background: In 1997, OR enacted a voter initiative allowing terminally ill residents to self-administer physician-prescribed medication to end their lives. Statute requires prescriptions written for lethal medications be reported; the state also collects demographic and intended use data. We wished to to evaluate and report participation trends.OR's Public Health Division gathers compliance forms from prescribing/consulting physicians, pharmacists, and psychiatrists, prescribing physician follow-up forms, and death certificates. Data from 1998-early 2016 were reviewed, collated, and interpreted.1,545 prescriptions were written; 991 pts died from legally-prescribed lethal medication. The % of prescription recipients dying from drug use per yr ranged from 48-82, with no significant trend (logistic regression 2-sided p = .90) The prescribing rate increased 12%/yr on average through 2013, with a 28% increase in 2014 and 40% in 2015, not explainable by growth in population. Characteristics of 991 pts dying from drug: Most recipients had cancer (77%); 8% had ALS, 4.5% lung disease, 2.6% heart disease, and 0.9% HIV. 5.3% were sent for psychiatric evaluation. M/F (%) 51.4/48.6; median age (years) 71 (range 25-102); race white/black/asian/hispanic (%) 97/0.1/1.3/1; hospice Y/N (%) 90.5/9/5. 94% died at home. Estimated median time between intake and coma (min): 5 (range 1-38); to death (min): 25 (range 1-6240). 3.3% had known complications. Reasons for DWD (%): ADL not enjoyable 90; loss of autonomy 92, dignity 79, or bodily functions 48; inadequate pain control 25; financial 3.The number of prescriptions written for ORDWDA medications increased annually since enactment. The % of recipients self-administering drugs has varied. Very few pts are referred for psychiatric consultation prior to DWD. Most pts dying from lethal medications have cancer, and the overwhelming majority expire at home. Medications used are effective and rapidly acting. Little evidence exists disadvantaged pts are disproportionally using DWD. Pts use DWD for reasons related to QOL, autonomy, and dignity, and relatively rarely because of inadequate pain palliation. Future studies should evaluate why many pts prescribed lethal drugs choose not to take them.

44 Background: In 1997, OR enacted a voter initiative allowing terminally ill residents to self-administer physician-prescribed medication to end their lives. Statute requires prescriptions written for lethal medications be reported; the state also collects demographic and intended use data. We wished to to evaluate and report participation trends.OR's Public Health Division gathers compliance forms from prescribing/consulting physicians, pharmacists, and psychiatrists, prescribing physician follow-up forms, and death certificates. Data from 1998-early 2016 were reviewed, collated, and interpreted.1,545 prescriptions were written; 991 pts died from legally-prescribed lethal medication. The % of prescription recipients dying from drug use per yr ranged from 48-82, with no significant trend (logistic regression 2-sided p = .90) The prescribing rate increased 12%/yr on average through 2013, with a 28% increase in 2014 and 40% in 2015, not explainable by growth in population. Characteristics of 991 pts dying from drug: Most recipients had cancer (77%); 8% had ALS, 4.5% lung disease, 2.6% heart disease, and 0.9% HIV. 5.3% were sent for psychiatric evaluation. M/F (%) 51.4/48.6; median age (years) 71 (range 25-102); race white/black/asian/hispanic (%) 97/0.1/1.3/1; hospice Y/N (%) 90.5/9/5. 94% died at home. Estimated median time between intake and coma (min): 5 (range 1-38); to death (min): 25 (range 1-6240). 3.3% had known complications. Reasons for DWD (%): ADL not enjoyable 90; loss of autonomy 92, dignity 79, or bodily functions 48; inadequate pain control 25; financial 3.The number of prescriptions written for ORDWDA medications increased annually since enactment. The % of recipients self-administering drugs has varied. Very few pts are referred for psychiatric consultation prior to DWD. Most pts dying from lethal medications have cancer, and the overwhelming majority expire at home. Medications used are effective and rapidly acting. Little evidence exists disadvantaged pts are disproportionally using DWD. Pts use DWD for reasons related to QOL, autonomy, and dignity, and relatively rarely because of inadequate pain palliation. Future studies should evaluate why many pts prescribed lethal drugs choose not to take them.