Risk factors for contralateral breast cancer in postmenopausal breast cancer survivors in the NIH-AARP Diet and Health Study.

PURPOSE: The role of established breast cancer risk factors and clinical characteristics of the first breast cancer in the development of contralateral breast cancer (CBC) among postmenopausal women is unclear. METHODS: We identified 10,934 postmenopausal women diagnosed with a first primary breast cancer between 1995 and 2011 in the NIH-AARP Diet and Health Study. CBC was defined as a second primary breast cancer diagnosed in the contralateral breast ≥ 3 months after the first breast cancer. Exposures included pre-diagnosis risk factors (lifestyle, reproductive, family history) and clinical characteristics of the first breast cancer. We used multivariable Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Over a median follow-up of 6.8 years, 436 women developed CBC. We observed an increasing trend in CBC risk by age (p-trend = 0.002) and decreasing trend by year of diagnosis (p-trend = 0.001) of the first breast cancer. Additional risk factor associations were most pronounced for endocrine therapy (HR 0.68, 95% CI 0.53-0.87) and family history of breast cancer (HR 1.38, 95% CI 1.06-1.80, restricted to invasive first breast cancer). No associations were found for lifestyle (body mass index, physical activity, smoking, alcohol) or reproductive factors (age at menarche, parity, age at first birth, age at menopause). CONCLUSIONS: This study suggests that clinical characteristics of the first breast cancer and family history of breast cancer, but not pre-diagnosis lifestyle and reproductive factors, are strongly associated with CBC risk among postmenopausal women. Future studies are needed to understand how these factors contribute to CBC etiology and to identify further opportunities for prevention.

Financial Burdens of Cancer Treatment: A Systematic Review of Risk Factors and Outcomes.

BACKGROUND: Patients with cancer experience financial toxicity from the costs of treatment, as well as material and psychologic stress related to this burden. A synthesized understanding of predictors and outcomes of the financial burdens associated with cancer care is needed to underpin strategic responses in oncology care. This study systematically reviewed risk factors and outcomes associated with financial burdens related to cancer treatment. METHODS: MEDLINE, Embase, PubMed, PsychINFO, and the Cochrane Library were searched from study inception through June 2018, and reference lists were scanned from studies of patient-level predictors and outcomes of financial burdens in US patients with cancer (aged ≥18 years). Two reviewers conducted screening, abstraction, and quality assessment. Variables associated with financial burdens were synthesized. When possible, pooled estimates of associations were calculated using random-effects models. RESULTS: A total of 74 observational studies of financial burdens in 598,751 patients with cancer were identified, among which 49% of patients reported material or psychologic financial burdens (95% CI, 41%-56%). Socioeconomic predictors of worse financial burdens with treatment were lack of health insurance, lower income, unemployment, and younger age at cancer diagnosis. Compared with patients with health insurance, those who were uninsured demonstrated twice the odds of financial burdens (pooled odds ratio [OR], 2.09; 95% CI, 1.33-3.30). Financial burdens were most severe early in cancer treatment, did not differ by disease site, and were associated with worse health-related quality of life (HRQoL) and nearly twice the odds of cancer medication nonadherence (pooled OR, 1.70; 95% CI, 1.13-2.56). Only a single study demonstrated an association with increased mortality. Studies assessing the comparative effectiveness of interventions to mitigate financial burdens in patients with cancer were lacking. CONCLUSIONS: Evidence showed that financial burdens are common, disproportionately impacting younger and socioeconomically disadvantaged patients with cancer, across disease sites, and are associated with worse treatment adherence and HRQoL. Available evidence helped identify vulnerable patients needing oncology provider engagement and response, but evidence is critically needed on the effectiveness of interventions designed to mitigate financial burden and impact.

Pharmacological management of cachexia in adult cancer patients: a systematic review of clinical trials.

BACKGROUND: Cachexia is a multisystem syndrome characterized by weight loss, anorexia, loss of muscle mass, systemic inflammation, insulin resistance, and functional decline. Management of cachexia involves addressing multiple underlying biological mechanisms. Previous review on pharmacological management of cancer cachexia identified progestins and corticosteroids as effective agents for treatment of cachexia. However, to date no consensus exists on a single effective or standard treatment for management of cachexia. The aim of this systematic review is to determine the effectiveness of pharmacological treatments used to manage cachexia among adult cancer patients. METHODS: We performed literature searches of PubMed (NLM), Embase (Ovid), and Medline(Ovid) to identify clinical trials focused on pharmacological management of cancer cachexia among adult cancer patients from 2004 to 2018. Three reviewers screened a random selection of abstracts to measure for interrater reliability. After this step, each screener screened two-thirds of all abstracts and 177 studies were identified for full text review. The primary outcome was impact of pharmacological management on change in either weight or lean body mass in cancer patients. RESULTS: We identified 19 articles (representing 20 RCTs) that focused on pharmacological management of cancer cachexia. Agents showing promising results included Anamorelin and Enobosarm. Anamorelin at 50 or 100 mg per day for 12 weeks showed a consistent benefit across all studies and resulted in significant improvement in weight as compared to baseline among cancer patients. Enobosarm at 1 and 3 mg per day was also effective in improving lean body mass and QOL symptoms among advancer stage cancer patients. Finally, use of combination agents provide evidence for targeting multiple pathways underlying cachexia mechanism to achieve maximum benefit. No agents showed functional improvement in cancer patients. CONCLUSION: Anamorelin as a single agent shows promising results in improving cachexia related weight loss among cancer patients. Further research on combination therapies may be helpful to address critical gaps in cachexia management.

Sinoatrial Node Dose Is Associated With Worse Survival in Patients Undergoing Definitive Stereotactic Body Radiation Therapy for Central Lung Cancers.

PURPOSE: Our purpose was to evaluate the clinical consequences of sinoatrial node (SAN) and atrioventricular node (AVN) irradiation in patients undergoing stereotactic body radiation therapy (SBRT) for central non-small cell lung cancer (NSCLC) tumors. METHODS AND MATERIALS: A single-institutional retrospective review of patients with primary NSCLC undergoing definitive SBRT for centrally located thoracic tumors from February 2007 to December 2021 was performed. The SAN and AVN were contoured in accordance with a published contouring atlas, and the maximum dose (Dmax) and mean dose (Dmean) for each structure were calculated. Sequential log rank testing between the 50th and 90th percentiles was used to identify potential cutoff values for the corresponding dosimetric parameters and overall survival. RESULTS: Among 93 eligible patients, the median age was 72.5 years (IQR, 66.6-78.3), and median follow-up was 32.4 months (IQR, 13.0-49.6). The median SAN Dmax and Dmean were 95 cGy (range, 9-5394) and 58 cGy (range, 7-3168), respectively. The median AVN Dmax and Dmean were 45 cGy (range, 4-2121) and 34 cGy (range, 3-1667), respectively. Candidate cutoff values for SAN Dmax and Dmean were 1309 and 836 cGy, respectively. No associations between AVN parameters and survival outcomes were identified. Upon multivariate Cox regression, the SAN Dmax cutoff (hazard ratio [HR], 2.03 [1.09-3.79]; P = .026) and SAN Dmean cutoff (HR, 2.22 [1.20-4.12]; P = .011) were significantly associated with overall survival. For noncancer-associated survival, the SAN Dmax cutoff trended toward significance (HR, 2.02 [0.89-4.57]; P = .092), and the SAN Dmean cutoff remained significantly associated (HR, 2.34 [1.05-5.18]; P = .037). CONCLUSIONS: For patients undergoing SBRT for NSCLC, SAN Dmax and Dmean were significantly associated with worse overall survival using cut-off values of 1309 and 836 cGy, respectively. Further studies examining the effect of SAN irradiation during SBRT are warranted.

Trends in risk for therapy-related myelodysplastic syndrome/acute myeloid leukemia after initial chemo/immunotherapy for common and rare lymphoid neoplasms, 2000-2018.

Background: Historically, survivors of common lymphoid neoplasms (LNs) had increased risks for therapy-related myelodysplastic syndrome/acute myeloid leukemia (tMDS/AML). Despite major treatment advances in the treatment of LNs over the last two decades, a comprehensive evaluation of tMDS/AML trends following both common and rare LNs treated in this contemporary period is lacking. Methods: In US cancer registries during 2000-2018, we identified 1496 tMDS/AML cases among 186,503 adults who were treated with initial chemo/immunotherapy for first primary LN and survived ≥1 year. We quantified tMDS/AML standardized incidence ratios (SIRs), excess absolute risks (EARs, per 10,000 person-years), and cumulative incidence. Findings: The highest tMDS/AML risks occurred after precursor leukemia/lymphoma (SIR = 39, EAR = 30), Burkitt leukemia/lymphoma (SIR = 20, EAR = 24), peripheral T-cell lymphoma (SIR = 12, EAR = 23), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL; SIR = 9.0, EAR = 27), and mantle cell lymphoma (SIR = 8.5, EAR = 25). Elevated risks (SIRs = 4.2-6.9, EARs = 4.9-15) also were observed after all other LN subtypes except hairy cell leukemia and mycosis fungoides/Sézary syndrome. Among patients treated more recently, tMDS/AML risks were significantly higher after CLL/SLL (SIR2000-2005 = 4.8, SIR2012-2017 = 10, Ptrend = 0.0043), significantly lower after Hodgkin (SIR2000-2005 = 15, SIR2012-2017 = 6.3, Ptrend = 0.024) and marginal zone (SIR2000-2005 = 7.5, SIR2012-2017 = 2.3, Ptrend = 0.015) lymphomas, and non-significantly lower after mantle cell lymphoma (SIR2000-2005 = 10, SIR2012-2017 = 3.2, Ptrend = 0.054), lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (SIR2000-2005 = 6.9, SIR2012-2017 = 1.0, Ptrend = 0.067), and plasma cell neoplasms (SIR2000-2005 = 5.4, SIR2012-2017 = 3.1, Ptrend = 0.051). EAR and cumulative incidence trends generally were similar to SIR trends. Median survival after tMDS/AML was 8.0 months (interquartile range, 3.0-22.0). Interpretation: Although tMDS/AML risks are significantly elevated after initial chemo/immunotherapy for most LNs, patients treated more recently have lower tMDS/AML risks, except after CLL/SLL. Though rare, the poor prognosis following tMDS/AML emphasizes the importance of continued efforts to reduce treatment-associated toxicity. Funding: This research was supported in part by the Intramural Research Program of the National Cancer Institute, National Institutes of Health. LMM, GMD, REC, and CBS verified the data, and all authors had access to the data and made the decision to submit for publication.

Comparing Risk for Second Primary Cancers After Intensity-Modulated vs 3-Dimensional Conformal Radiation Therapy for Prostate Cancer, 2002-2015.

Importance: Compared with 3-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT) can spare nearby tissue but may result in increased scatter radiation to distant normal tissue, including red bone marrow. It is unclear whether second primary cancer risk varies by radiotherapy type. Objective: To evaluate whether radiotherapy type (IMRT vs 3DCRT) is associated with second primary cancer risk among older men treated for prostate cancer. Design, Setting, and Participants: In this retrospective cohort study of a linked database of Medicare claims and Surveillance, Epidemiology, and End Results (SEER) Program population-based cancer registries (2002-2015), male patients aged 66 to 84 diagnosed with a first primary nonmetastatic prostate cancer from 2002 to 2013, as reported to SEER, and who received radiotherapy (IMRT and/or 3DCRT without proton therapy) within the first year following prostate cancer were identified. The data were analyzed from January 2022 through June 2022. Exposure: Receipt of IMRT and 3DCRT, based on Medicare claims. Main Outcomes and Measures: The association between radiotherapy type and development of a subsequent hematologic cancer at least 2 years after prostate cancer diagnosis or a subsequent solid cancer at least 5 years after prostate cancer diagnosis. Hazard ratios (HRs) and 95% CIs were estimated using multivariable Cox proportional regression. Results: The study included 65 235 2-year first primary prostate cancer survivors (median [range] age, 72 [66-82] years; 82.2% White patients) and 45 811 5-year survivors with similar demographic characteristics (median [range] age, 72 [66-79] years; 82.4% White patients). Among 2-year prostate cancer survivors (median [range] follow-up, 4.6 [0.003-12.0] years), 1107 second hematologic cancers were diagnosed (IMRT, 603; 3DCRT, 504). Radiotherapy type was not associated with second hematologic cancers overall or any specific types evaluated. Among 5-year survivors (median [range] follow-up, 3.1 [0.003-9.0] years), 2688 men were diagnosed with a second primary solid cancer (IMRT, 1306; 3DCRT, 1382). The overall HR for IMRT vs 3DCRT was 0.91 (95% CI, 0.83-0.99). This inverse association was restricted to the earlier calendar year period of prostate cancer diagnosis (HR2002-2005 = 0.85; 95% CI, 0.76-0.94; HR2006-2010 = 1.14; 95% CI, 0.96-1.36), with a similar pattern observed for colon cancer (HR2002-2005 = 0.66; 95% CI, 0.46-0.94; HR2006-2010 = 1.06; 95% CI, 0.59-1.88). Conclusions and Relevance: The results of this large, population-based cohort study suggest that IMRT for prostate cancer is not associated with an increased risk of second primary cancers, either solid or hematologic, and any inverse associations may be associated with calendar year of treatment.

Assessment of surveillance versus etiologic factors in the reciprocal association between papillary thyroid cancer and breast cancer.

BACKGROUND: Mutually increased risks for thyroid and breast cancer have been reported, but the contribution of etiologic factors versus increased medical surveillance to these associations is unknown. METHODS: Leveraging large-scale US population-based cancer registry data, we used standardized incidence ratios (SIRs) to investigate the reciprocal risks of thyroid and breast cancers among adult females diagnosed with a first primary invasive, non-metastatic breast cancer (N = 652,627) or papillary thyroid cancer (PTC) (N = 92,318) during 2000-2017 who survived ≥1-year. RESULTS: PTC risk was increased 1.3-fold [N = 1434; SIR = 1.32; 95 % confidence interval (CI) = 1.25-1.39] after breast cancer compared to the general population. PTC risk declined significantly with time since breast cancer (Poisson regression = Ptrend <0.001) and was evident only for tumors ≤2 cm in size. The SIRs for PTC were higher after hormone-receptor (HR)+ (versus HR-) and stage II or III (versus stage 0-I) breast tumors. Breast cancer risk was increased 1.2-fold (N = 2038; SIR = 1.21; CI = 1.16-1.26) after PTC and was constant over time since PTC but was only increased for stage 0-II and HR + breast cancers. CONCLUSION: Although some of the patterns by latency, stage and size are consistent with heightened surveillance contributing to the breast-thyroid association, we cannot exclude a role of shared etiology or treatment effects.

Local Therapy Decisional Regret in Older Women With Breast Cancer: A Population-Based Study.

PURPOSE: Older women with nonmetastatic breast cancer can often choose from several surgery and radiation treatment options. Little is known regarding how these choices contribute to decisional regret, which is a negative emotion reflecting the idea that another surgery or radiation decision might have been preferable. We sought to characterize the burden of and examine potential risk factors for local therapy decisional regret among a population-based cohort of older breast cancer survivors. METHODS AND MATERIALS: National Medicare claims for age ≥67 female breast cancer incident in 2009 identified patients treated with lumpectomy plus whole-breast irradiation, brachytherapy, or endocrine therapy or mastectomy with or without radiation. We sampled 330 patients per treatment group (N = 1650), of whom 1253 agreed to receive a paper survey including the Decisional Regret Scale and EQ-5D-3L Health-Utility Scale. Local therapy regret was defined as neutral or worse response to questions regarding surgery- or radiation-related decisional regret. Local therapy regret risk factors were evaluated using a multivariable generalized linear model. Association of local therapy regret with health utility was modeled using multivariable linear regression. RESULTS: The response rate was 30.2% (n = 498 of 1650); 421 surveys were included in this analysis. Median diagnosis age was 72 years, and surveys were completed 6 years after diagnosis. Overall, 23.8% of respondents (n = 100) reported experiencing local therapy decisional regret. Type of local therapy was not associated with local therapy regret. Predictors of increased regret included black race (risk ratio [RR], 2.09; 95% confidence interval [CI], 1.33-3.29), high school education or less (RR, 1.87; 95% CI, 1.27-2.75), and axillary nodal dissection (RR, 2.13; 95% CI, 1.33-3.41). Local therapy regret was not associated with health utility (P = .37). CONCLUSIONS: Local therapy regret afflicts nearly one quarter of our cohort of older breast cancer survivors, and it is associated with black race, less education, and more extensive nodal dissection, but not breast surgery. Regret is distinct from health utility, suggesting that it is a unique psychosocial construct that merits further study and mitigation strategies.