Association of platinum-based chemotherapy with live birth and infertility in female survivors of adolescent and young adult cancer.

OBJECTIVE: To estimate the effect of platinum-based chemotherapy on live birth (LB) and infertility after cancer, in order to address a lack of treatment-specific fertility risks for female survivors of adolescent and young adult cancer, which limits counseling on fertility preservation decisions. DESIGN: Retrospective cohort study. SETTING: US administrative database. PATIENTS: We identified incident breast, colorectal, and ovarian cancer cases in females aged 15-39 years who received platinum-based chemotherapy or no chemotherapy and matched them to females without cancer. INTERVENTION: Platinum-based chemotherapy. MAIN OUTCOME MEASURES: We estimated the effect of chemotherapy on the incidence of LB and infertility after cancer, overall, and after accounting for competing events (recurrence, death, and sterilizing surgeries). RESULTS: There were 1,287 survivors in the chemotherapy group, 3,192 in the no chemotherapy group, and 34,147 women in the no cancer group, with a mean age of 33 years. Accounting for competing events, the overall 5-year LB incidence was lower in the chemotherapy group (3.9%) vs. the no chemotherapy group (6.4%). Adjusted relative risks vs. no chemotherapy and no cancer groups were 0.61 (95% confidence interval [CI] 0.42-0.82) and 0.70 (95% CI 0.51-0.93), respectively. The overall 5-year infertility incidence was similar in the chemotherapy group (21.8%) compared with the no chemotherapy group (20.7%). The adjusted relative risks vs. no chemotherapy and no cancer groups were 1.05 (95% CI 0.97-1.15) and 1.42 (95% CI 1.31-1.53), respectively. CONCLUSIONS: Cancer survivors treated with platinum-based chemotherapy experienced modestly increased adverse fertility outcomes. The estimated effects of platinum-based chemotherapy were affected by competing events, suggesting the importance of this analytic approach for interpretations that ultimately inform clinical fertility preservation decisions.

Maternal comorbidity and adverse perinatal outcomes in survivors of adolescent and young adult cancer: A cohort study.

OBJECTIVE: To evaluate risks of preterm birth (PTB) and severe maternal morbidity (SMM) in female survivors of adolescent and young adult cancer and assess maternal comorbidity as a potential mechanism. To determine whether associations differ by use of assisted reproductive technology (ART). DESIGN: Retrospective cohort. SETTING: Commercially insured females in the USA. SAMPLE: Females with live births from 2000-2019 within a de-identified US administrative health claims data set. METHODS: Log-binomial regression models estimated relative risks of PTB and SMM by cancer status and tested for effect modification. Causal mediation analysis evaluated the proportions explained by maternal comorbidity. MAIN OUTCOME MEASURES: PTB and SMM. RESULTS: Among 46 064 cancer survivors, 2440 singleton births, 214 multiple births and 2590 linked newborns occurred after cancer diagnosis. In singleton births, the incidence of PTB was 14.8% in cancer survivors versus 12.4% in females without cancer (aRR 1.19, 95% CI 1.06-1.34); the incidence of SMM was 3.9% in cancer survivors versus 2.4% in females without cancer (aRR 1.44, 95% CI 1.13-1.83). Cancer survivors had more maternal comorbidities before and during pregnancy; 26% of the association between cancer and PTB and 30% of the association between cancer and SMM was mediated by maternal comorbidities. Tests for effect modification of cancer status on perinatal outcomes by ART were non-significant. CONCLUSIONS: Preterm birth and SMM risks were modestly increased after cancer. Significant proportions of elevated risks may result from increased comorbidities. ART did not significantly modify the association between adolescent and young adult cancer and adverse perinatal outcomes. The prevention and treatment of comorbidities provides an opportunity to improve perinatal outcomes among cancer survivors.

Long-term antimüllerian hormone patterns differ by cancer treatment exposures in young breast cancer survivors.

OBJECTIVE: To compare antimüllerian hormone (AMH) patterns by cancer status and treatment exposures across 6 years after incident breast cancer using administrative data. DESIGN: In a cross-sectional design, AMH levels in patients who developed incident breast cancer between ages 15-39 years during 2005-2019 were matched 1:10 to levels in females without cancer in the OptumLabs Data Warehouse. Modeled AMH patterns were compared among cyclophosphamide-based chemotherapy, non-cyclophosphamide-based chemotherapy, no chemotherapy, and no breast cancer groups. SETTING: Commercially insured females in the United States. PATIENT(S): Females with and without breast cancer. EXPOSURE(S): Breast cancer, cyclophosphamide- and non-cyclophosphamide-based chemotherapy. MAIN OUTCOME MEASURE(S): AMH levels. RESULT(S): A total of 233 patients with breast cancer (mean age, 34 years; standard deviation, 3.7 years) contributed 278 AMH levels over a median of 2 years (range, 0-6.7 years) after diagnosis; 52% received cyclophosphamide-based chemotherapy, 17% received non-cyclophosphamide-based chemotherapy (80% platinum-based), and 31% received no chemotherapy. A total of 2,777 matched females without cancer contributed 2,780 AMH levels. The pattern of AMH levels differed among the 4 groups. Among females without cancer and breast cancer survivors who did not undergo chemotherapy, AMH declined linearly over time. In contrast, among those who received cyclophosphamide-based and noncyclophosphamide-based chemotherapy, a nonlinear pattern of AMH level of initial fall during chemotherapy, followed by an increase over 2-4 years, and then by a plateau over 1-2 years before a decline was observed. CONCLUSION(S): In breast cancer survivors, AMH levels from administrative data supported ovarian toxicity of non-cyclophosphamide-based chemotherapy in breast cancer and efficiently depicted the timing and duration of changes in ovarian reserve to reflect the residual reproductive lifespan.

Mental Health Outcomes in Adolescent and Young Adult Female Cancer Survivors of a Sexual Minority.

Purpose: Sexual minority (SM) individuals experience higher rates of anxiety and depression. Previous research on mental health disparities for SM cancer survivors has largely focused on adult survivors; however, studies are limited in the adolescent and young adult (AYA) population. This study's objective is to compare depression and anxiety symptoms between AYA, female cancer survivors who identify as an SM and those who identify as heterosexual. Methods: A cross-sectional analysis of 1025 AYA survivors aged 18-40 years (2015-2017) was performed. Patients self-reported SM identification and depression and anxiety symptoms, as measured by the Patient Health Questionnaire (PHQ8) and Generalized Anxiety Disorder Scale (GAD7), respectively. Multivariable logistic regression tested associations between SM identification and depression and anxiety. Results: Sixty-four participants (6%) identified as an SM. In adjusted analyses, SM participants had 1.88 higher odds of anxiety (odds ratio [OR] 1.88, confidence interval [95% CI] 1.05-3.35, p = 0.033) compared with heterosexual participants. SM participants did not have significantly higher odds of depression (OR 1.36, CI 0.75-2.47, p = 0.31). More social support was significantly associated with lower odds of depression (OR 0.91, CI 0.89-0.93, p < 0.001) and anxiety (OR 0.93, CI 0.91-0.94, p < 0.001). Conclusions: AYA cancer survivors identifying as an SM had nearly twice the odds of anxiety, with social support that is protective for both anxiety and depression. While mental health screening is recommended throughout the cancer care continuum, these data support the need for reliable screening, clinician awareness of increased vulnerability in the AYA, SM survivor population, and clinician training on culturally competent care and generation of evidence-based interventions.

Role of pregnancy and female sex steroids on aneurysm formation, growth, and rupture: a systematic review of the literature.

OBJECTIVE: Women have been shown to have a higher risk of cerebral aneurysm formation, growth, and rupture than men. The authors present a review of the recently published neurosurgical literature that studies the role of pregnancy and female sex steroids, to provide a conceptual framework with which to understand the various risk factors associated with cerebral aneurysms in women at different stages in their lives. METHODS: The PubMed database was searched for "("intracranial" OR "cerebral") AND "aneurysm" AND ("pregnancy" OR "estrogen" OR "progesterone")" between January 1980 and February 2019. A total of 392 articles were initially identified, and after applying inclusion and exclusion criteria, 20 papers were selected for review and analysis. These papers were then divided into two categories: 1) epidemiological studies about the formation, growth, rupture, and management of cerebral aneurysms in pregnancy; and 2) investigations on female sex steroids and cerebral aneurysms (animal studies and epidemiological studies). RESULTS: The 20 articles presented in this study include 7 epidemiological articles on pregnancy and cerebral aneurysms, 3 articles reporting case series of cerebral aneurysms treated by endovascular therapies in pregnancy, 3 epidemiological articles reporting the relationship between female sex steroids and cerebral aneurysms through retrospective case-control studies, and 7 experimental studies using animal and/or cell models to understand the relationship between female sex steroids and cerebral aneurysms. The studies in this review report similar risk of aneurysm rupture in pregnant women compared to the general population. Most ruptured aneurysms in pregnancy occur during the 3rd trimester, and most pregnant women who present with cerebral aneurysm have caesarean section deliveries. Endovascular treatment of cerebral aneurysms in pregnancy is shown to provide a new and safe form of therapy for these cases. Epidemiological studies of postmenopausal women show that estrogen hormone therapy and later age at menopause are associated with a lower risk of cerebral aneurysm than in matched controls. Experimental studies in animal models corroborate this epidemiological finding; estrogen deficiency causes endothelial dysfunction and inflammation, which may predispose to the formation and rupture of cerebral aneurysms, while exogenous estrogen treatment in this population may lower this risk. CONCLUSIONS: The aim of this work is to equip the neurosurgical and obstetrical/gynecological readership with the tools to better understand, critique, and apply findings from research on sex differences in cerebral aneurysms.

Perioperative Risk Factors Associated With Morbidity and Mortality Following Pediatric Inpatient Sinus Surgery.

OBJECTIVES:: Pediatric sinus surgery is indicated for a wide range of sinonasal and skull base pathologies, but it is most commonly performed for recalcitrant chronic rhinosinusitis or complicated acute sinusitis. The authors aim to report medical risk factors of morbidity and mortality following inpatient sinus surgery in the pediatric population. METHODS:: Using data from the Kids' Inpatient Database from 2003 to 2012, patients with International Classification of Diseases, Ninth Revision, procedure codes for primary sinus surgery were identified. Mixed-effect multivariable logistic regression was used to identify risk factors of inpatient postoperative morbidity and mortality. RESULTS:: The final sample included a weighted estimate of 4965 pediatric patients. The rates of inpatient morbidity and mortality were 6% and 1%, respectively. Respiratory complications (2.5%) were the most prevalent postoperative adverse events. The most prevalent comorbidities were chronic sinusitis (59.8%), acute sinusitis (27.8%), and cystic fibrosis (26.4%). Compared with patients who did not experience any morbidity, patients with inpatient morbidity had higher rates of pneumonia, mycoses, and nasal or paranasal benign neoplasm ( P < .05). The odds of inpatient morbidity and mortality were highest for patients with leukemia (odds ratio, 2.74; 95% confidence interval, 1.59-4.72; P < .001) and mycoses (odds ratio, 15.84; 95% confidence interval, 6.45-38.89; P < .001), respectively. CONCLUSIONS:: This study is the first to report the national comorbidity burden and risk factors for postoperative adverse events following inpatient sinus surgery. Knowledge of the comorbidities and independent factors associated with morbidity and mortality will help in directing preoperative optimization and counseling. LEVEL OF EVIDENCE:: 2c.