Incorporation of vaginal brachytherapy to external beam radiotherapy in adjuvant therapy for high-risk early-stage cervical cancer: A comparative study.

PURPOSE: To examine trends, characteristics, and outcomes related to addition of vaginal brachytherapy (VBT) to external beam radiotherapy (EBRT) for adjuvant radiotherapy in high-risk early-stage cervical cancer. METHODS AND MATERIALS: This comparative study is a retrospective observational analysis of the National Cancer Institutes' Surveillance, Epidemiology, and End Results Program. Surgically treated women with stage T1-2 cervical cancer who had high-risk factors (nodal metastasis and/or parametrial invasion) and received adjuvant radiotherapy from 2000 to 2018 were examined. Propensity score inverse probability of treatment weighting was used to assess the survival estimates for addition of VBT use. RESULTS: Among 2470 women with high-risk factors receiving EBRT, 760 (30.8%) had additional VBT. During the study period, there was an increasing trend of VBT use from 27.4% to 36.1% (p< 0.001). In a multivariable analysis, year of diagnosis and high-risk tumor factors: parametrial involvement, large tumor size, and use of chemotherapy remained independent characteristics associated with VBT use (all, p< 0.05). In propensity score-weighted models, VBT use with EBRT and EBRT alone had comparable overall survival (5-year rates 73.8% vs. 77.4%, hazard ratio [HR] 1.07, 95% confidence interval [CI] 0.92-1.25). Nonsignificant association was also observed in squamous or nonsquamous tumors, young or old age, low or high nodal ratio, chemotherapy use, and simple or radical hysterectomy (all, p> 0.05). Lastly, the addition of VBT was not associated with cervical cancer-specific survival (subdistribution-HR 1.15, 95% CI 0.94-1.41). CONCLUSIONS: Utilization of VBT with EBRT for adjuvant radiotherapy in high-risk early-stage cervical cancer is increasing in the United States. Addition of VBT was associated with neither overall survival nor cancer-specific survival.

Association between definitive chemoradiotherapy wait-time and survival in locally-advanced cervical cancer: Implications during the coronavirus pandemic.

OBJECTIVE: The current coronavirus pandemic caused a significant decrease in cancer-related encounters resulting in a delay in treatment of cancer patients. The objective of this study was to examine the survival effect of delay in starting concurrent chemo-radiotherapy (CCRT) in women with locally-advanced cervical cancer. METHODS: This is a retrospective observational study querying the National Cancer Database from 2004 to 2016. Women with stage IB2-IVA squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix who received definitive CCRT with known wait-time for CCRT initiation after cancer diagnosis were eligible (N=13,617). Cox proportional hazard regression model with restricted cubic spline transformation was fitted to assess the association between CCRT wait-time and all-cause mortality in multivariable analysis. RESULTS: The median wait-time to start CCRT was 6 (IQR 4-8) weeks. In a multivariable analysis, older age, non-Hispanic black and Hispanic ethnicity, recent year of diagnosis, Medicaid and uninsured status, medical comorbidities, and absence of nodal metastasis were associated with longer CCRT wait-time (P<.05). Women with aggressive tumor factors (poorer differentiation, large tumor size, nodal metastasis, and higher cancer stage) were more likely to have a short CCRT wait-time (P<.05). After controlling for the measured covariates, CCRT wait-time of 6.1-9.8 weeks was not associated with increased risk of all-cause mortality compared to a wait-time of 6 weeks. Similar association was observed when the cohort was stratified by histology, cancer stage, tumor size, or brachytherapy use. CONCLUSION: An implication of this study for the current coronavirus pandemic is that in the absence of aggressive tumor factors, a short period of wait-time to start definitive CCRT may not be associated with increased risk of mortality in women with locally-advanced cervical cancer.

Tumor-specific outcome of metachronous uterine malignancy after pelvic irradiation for cervical cancer.

OBJECTIVE: To examine survival of women who develop metachronous uterine malignancy after definitive pelvic radiotherapy for cervical cancer. METHODS: This retrospective observational study examined the Surveillance, Epidemiology, End Results Program between 1973 and 2013. Women with cervical cancer who received definitive radiotherapy without hysterectomy were examined for the diagnosis of metachronous uterine malignancy (n = 5277). Survival was compared between metachronous and non-metachronous uterine malignancies according to tumor factors. RESULTS: The 10- and 20-year cumulative incidences of metachronous uterine malignancy were 0.6% and 1.2%, respectively. When compared to non-metachronous uterine malignancy, metachronous tumor were more likely to be non-endometrioid and advanced-stage (both, P < 0.001). As a whole cohort, metachronous uterine malignancy was significantly associated with decreased overall survival (OS) compared to non-metachronous tumors (hazard ratio [HR] 4.22, P < 0.001). OS was significantly worse in metachronous compared to non-metachronous malignancies, although the magnitude of statistical significance was greater for endometrioid tumors (HRs for endometrioid versus non-endometrioid: 6.17 versus 1.92). For grade 1-2 endometrial cancer, metachronous cases had significantly decreased OS compared to non-metachronous cases, a larger difference than that seen in higher grade tumors (HRs for grade 1-2 versus 3: 7.79 versus 2.15). Similarly, in early-stage endometrial cancer, metachronous cases had significantly decreased OS, with a greater HR compared to advanced-stage disease (HRs for stage I-II versus III-IV: 5.29 versus 2.29). CONCLUSION: Radiotherapy-associated metachronous uterine malignancy after cervical cancer is rare but commonly presents with aggressive tumor characteristics. The impact on survival is considerably high when metachronous uterine malignancy is endometrioid, low-grade, and early-stage.

Patient compliance for postoperative radiotherapy and survival outcome of women with stage I endometrioid endometrial cancer.

BACKGROUND AND OBJECTIVES: To examine characteristics and survival outcome of women with endometrial cancer who declined postoperative radiotherapy. METHODS: A retrospective study was conducted to examine surgically-treated grade 1-2 stage IB and grade 3 stage IA-IB endometrioid endometrial cancer in the Surveillance, Epidemiology, and End Results Program between 1983 and 2013 (n = 10 613). Associations of patient declination for guideline-based postoperative radiotherapy and clinico-pathological demographics or survival outcome were examined on multivariable analysis. RESULTS: There were 323 (3.0%) women who declined adjuvant radiotherapy. Women who declined postoperative radiotherapy were more likely to be older, White, Western U.S. residents, and register in recent years (all, adjusted-P < 0.05). On multivariable analysis, patient declination for guideline-based postoperative radiotherapy remained an independent prognostic factor for decreased endometrial cancer-specific survival in unstaged grade 1-2 stage IB or staged/unstated grade 3 stage IA-IB diseases (adjusted-hazard ratio 1.84, 95% confidence interval 1.34-2.51, P = 0.001). Association of patient declination for guideline-based postoperative radiotherapy and decreased overall survival remained independent in the entire cohort on multivariable analysis (adjuvant-hazard ratio 1.71, 95% confidence interval 1.44-2.02, P < 0.001). CONCLUSIONS: Our study suggested that patient compliance to guideline-based postoperative radiotherapy is a prognostic factor for women with stage I endometrioid endometrial cancer.

Extent of pelvic lymphadenectomy and use of adjuvant vaginal brachytherapy for early-stage endometrial cancer.

OBJECTIVE: To examine trends of adjuvant radiotherapy choice and to examine associations between pelvic lymphadenectomy and radiotherapy choice for women with early-stage endometrial cancer. METHODS: The Surveillance, Epidemiology, and End Results Program was used to identify surgically treated stage I-II endometrial cancer between 1983 and 2012 (type 1 n=79,474, and type 2 n=25,020). Piecewise linear regression models were used to examine temporal trends of intracavitary brachytherapy (ICBT) and whole pelvic radiotherapy (WPRT) use, pelvic lymphadenectomy rate, and sampled node counts. Multivariable binary logistic regression models were used to identify independent predictors for ICBT use. RESULTS: There was a significant increase in ICBT use and decrease in WPRT use during the study period. ICBT use exceeded WPRT use in 2003 for type 1 stage IA, and in 2007 for type 1 stage IB and type 2 stage IA diseases. In addition, number of sampled pelvic nodes significantly increased over time in type 1-2 stage I-II diseases (mean, 7.0-12.7 in 1988 to 15.2-17.6 in 2012, all P<0.001). On multivariable analysis, extent of sampled pelvic nodes was significantly associated with ICBT use for type 1 cancer: adjusted-odds ratios for 1-10 and >10 nodes versus no lymphadenectomy in stage IA (1.38/2.40), IB (2.75/6.32), and II (1.36/2.91) diseases. Similar trends were observed for type 2 cancer: adjusted-odds ratios for stage IA (1.69/3.73), IB (2.25/5.65), and II (1.36/2.19) diseases. CONCLUSION: Our results suggest that surgeons and radiation oncologists are evaluating the extent of pelvic lymphadenectomy when counseling women with early-stage endometrial cancer for adjuvant radiotherapy.

Pulmonary homograft monocusp reconstruction of the right ventricular outflow tract: outcomes to the intermediate term.

BACKGROUND: There is limited information on longer-term outcomes of pulmonary homograft monocusp (PHM) reconstruction of the right ventricular outflow tract (RVOT). METHODS: A retrospective review of 131 consecutive patients undergoing RVOT reconstruction with PHM was completed. RESULTS: Median age was 7.6 months (range, 1 day to 14 years) and weight was 7.3 kg (range, 2 to 65 kg). Most patients (108 of 131; 82%) underwent repair for Tetralogy. After PHM, median duration of mechanical ventilation was 1 day (range, 0 to 89) and hospital stay was 6.5 days (range, 2 to 137). Hospital mortality was 2% (3 of 131) with 1 patient undergoing early replacement of PHM. Echocardiogram at hospital discharge demonstrated peak RVOT gradient of 16 mm Hg (range, 4 to 64 mm Hg); and pulmonary insufficiency was absent/trivial in 40%, mild in 42%, moderate in 16%, and severe in 2%. Follow-up is completed in 91% of hospital survivors at a median of 5 years (range, 1 to 12). There were 5 late deaths, with an actuarial survival of 96% +/- 3.7%, 94% +/- 4.6%, and 89% +/- 9.2% at 1 year, 5 years, and 10 years, respectively. There were 24 reinterventions, including 10 pulmonary valve replacements. Median time to valve replacement was 1.9 years (range, 0.4 to 4.6). Actuarial freedom from pulmonary valve replacement was 97% +/- 3.0%, 90% +/- 6.1%, and 85% +/- 10.3% at 1 year, 5 years, and 10 years, respectively. Echocardiogram at last follow-up demonstrated no increase in RVOT gradient compared with hospital discharge (16 mm Hg), but there was significant increase in pulmonary insufficiency (mild 27%, moderate 39%, severe 34%). CONCLUSIONS: Pulmonary homograft monocusp reconstruction is an alternative strategy for RVOT reconstruction and provides early but gradually diminishing protection against pulmonary insufficiency without a risk of stenosis. As expected, PHM function decreases over time as the RVOT grows and the homograft tissue undergoes structural deterioration.