Outcomes of MR-guided Stereotactic Body Radiotherapy (SBRT) or yttrium-90 Transarterial Radioembolization for Hepatocellular Carcinoma Treated at an Urban Liver Transplant Center

Background: There are overlapping indications for both stereotactic body radiotherapy (SBRT) and yttrium-90 (Y90) trans-arterial radioembolization as locoregional treatments for hepatocellular cancer, though most centers preferentially use one modality over the other. MR-guided radiation allows both effective on-table localization and integrated motion management as compared with many traditional linear accelerators, allowing SBRT to be done more easily. Y90 radioembolization has been a well-established modality to deliver highly conformal dose due to the localization of the microspheres to the vascular supply of a tumor. We looked at patient characteristics and treatment outcomes for patients receiving MR-guided SBRT or Y90 at an urban transplant center. Objectives: To compare patient characteristics and treatment outcomes of MR-guided SBRT with Y90 transarterial radioembolization in a liver transplant center. Methods: This retrospective single-institution study analyzed patients with HCC treated with SBRT or Y90 from August 2017 to September 2020. To select a patient population eligible for either treatment modality, any Y90 procedures for lesions \u3e 10 cm or for treatment volumes \u3e 1000 cc were omitted from the cohort. A total of 239 patients were included in the analysis, receiving a total of 98 courses of SBRT and 187 courses of Y90 treatment. Local control (LC), freedom from liver progression (FFLP), and overall survival (OS) rates were measured from treatment completion date to death date or last follow-up. All outcomes were censored at time of loss to follow-up; LC and FFLP were censored at time of liver transplant if applicable. Cox regression models were used for survival, with significant factors on the univariate analysis further analyzed with a multivariate model. Results: Median time to follow-up was 11 months (0-44 mo). The mean size of lesions treated with SBRT were smaller than those treated with Y90 (2.7 cm vs 4.3 cm, P\u3c0.01). The groups of patients differed in liver disease characteristics, with SBRT patients having fewer Child-Pugh A disease (62% vs 80%, P\u3c0.01), more having received locoregional treatments to the liver in the past (81% v 35%, P\u3c0.01), and more disease in previously treated liver (57% vs 25%, P\u3c0.01). Dose of radiation for SBRT was 45-50 Gy administered in 5 fractions; dose of Y90 radiation to tumor was prescribed to a median of 235.2 Gy (range 55.8-512.3 Gy). There was a higher rate of one year LC in the SBRT cohort (77% vs 57%, P\u3c0.01), while median FFLP (9 mo vs 8 mo, P=NS) and median OS were not significantly different (24 mo vs 21 mo, P=NS). Multivariate analysis revealed size of largest lesion (P\u3c0.01) was correlated with decreased local control; a 1 cm increase in tumor size was associated with a 25% increased risk of local failure. Subsequent transplant (P\u3c0.01) was the remaining significant factor. Treatment modality did not remain an independent predictor of LC. Predictors of OS in multivariate analysis included age (P=0.01), prior liver treatments (HR 2.86, P\u3c0.01), size of largest lesion (P\u3c0.01), Child-Pugh stage (P\u3c0.01), portal vein thrombosis (HR 1.6, P=0.04), and subsequent liver transplant (HR 0.08, P\u3c0.01). Conclusions: These findings support the effectiveness of both MR-guided SBRT and Y90 transarterial radioembolization in locoregional management of HCC at a single institution despite clear differences in the patient cohorts. Though survival outcomes were comparable, local control differences favored the cohort treated by SBRT, in large part due to differences in tumor size. This data supports further investigation in a randomized study between SBRT and Y90

Survival Outcomes and Patterns of Recurrence After Adjuvant Vaginal Cuff Brachytherapy and Chemotherapy in Early-Stage Uterine Serous Carcinoma

Background: Uterine serous carcinoma (USC) is a relatively rare histology that portends a poor prognosis. The optimal adjuvant therapy for early-stage USC remains controversial; however, adjuvant vaginal cuff brachytherapy (VB) and chemotherapy is a commonly utilized strategy. Objectives: We sought to characterize predictors of survival endpoints and determine recurrence patterns in women with early-stage USC who received adjuvant VB and chemotherapy. Methods: We queried our prospectively maintained database for patients with 2009 FIGO stages I-II USC who underwent adequate surgical staging at our institution and received adjuvant chemotherapy with carboplatin and paclitaxel along with VB. We excluded women with synchronous malignancies. Overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) were assessed by Kaplan-Meier and log-rank tests. Univariate (UVA) and multivariate analyses (MVA) were performed to identify statistically significant predictors of survival endpoints. Variables with P\u3c0.1 on UVA were included in a MVA and any variable with P\u3c0.05 was considered statistically significant. Results: We identified 77 women who met our inclusion criteria who underwent surgical staging between 1991 and 2018. The median follow-up time was 36 months (range 6-125). The median age was 66 years. Of the cohort, 70% were FIGO stage IA, 17% were stage IB, and 13% were stage II. The median number of dissected lymph nodes (LN) was 22. There were 10 women (13%) diagnosed with a recurrence with a median time to recurrence of 12.0 months. The main site of initial recurrence was distant in seven patients (70%) with the remaining recurrences being pelvic/para-aortic. The 5-year RFS for patients who experienced a distant recurrence was 87% (95% Confidence Interval [CI] 0.75-0.94). For the entire cohort, 5-year OS, DSS, and RFS were 83% (95% CI 0.68-0.91), 92% (95% CI 0.78-0.97), and 83% (95% CI 0.71-0.91), respectively. The sole predictor of 5-year OS on UVA was receipt of omentectomy (P=0.09). The predictors of 5-year DSS on UVA were presence of positive peritoneal cytology (P=0.03), number of LN examined (Hazard Ratio [HR] 1.10, 95% CI 1.00-1.21, P=0.05), and number of para-aortic LN examined (HR 1.16 [95% CI 1.01-1.32], P=0.03). The sole independent predictor of DSS was the presence of positive peritoneal cytology (HR 0.03 [95% CI 0.00-0.72], P=0.03). Predictors of five-year RFS on UVA were robotic vs open surgery technique (P=0.06), presence of positive peritoneal cytology (P=0.01), percent myometrial invasion (HR 5.59 [95% CI 0.84-37.46], P=0.08), and presence of lymphovascular space invasion (LVSI) (P=0.05). Conclusions: Five-year survival outcomes were promising in this cohort of women with early-stage USC treated with adjuvant chemotherapy and VB; however, this study shows that the predominant pattern of relapse in this population is distant, suggesting the need to optimize systemic therapy. Possible predictors of worse outcomes include positive peritoneal cytology, deep myometrial invasion, and presence of LVSI. Multi-institutional pooled analyses are warranted to confirm our study results

Racial Differences in Treatments and Toxicity in Non-Small Cell Lung Cancer Patients Treated with Thoracic Radiation Therapy

Background: Racial disparities are of particular concern for lung cancer patients given historical differences in surgery rates for African-American lung cancer patients that resulted in lower overall survival and higher recurrence rates compared with rates in White patients. Objectives: The overall objective of this study was to examine racial differences in thoracic radiation therapy (RT) treatments and toxicities in a large cohort of patients from a multi-institutional consortium database of non-small cell lung cancer (NSCLC) patients. Methods: A large multi-institutional statewide prospectively collected patient-level database of locally advanced (stage II or III) NSCLC patients who received thoracic RT from March 2012 to November 2019 was analyzed to assess the associations between race and treatment and toxicity variables. Race (White or African-American) was defined by patient self-report or if not available then by the electronic medical record system classification. Race categories other than White or African-American comprised a small minority of patients and were excluded from this analysis. Patient-reported toxicity was determined by validated tools including the Functional Assessment of Cancer Therapy-Lung (FACT-L) quality of life instrument. Provider-reported toxicity was determined by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Uni-variable and multi-variable regression models were then fitted to assess relationships between primary outcomes by race and indicators of high-quality treatment and secondary analysis of symptoms. Spearman rank correlation coefficients were calculated between provider reported toxicity and similar patient reported outcomes for each race category. Results: A total of 1441 patients from 24 institutions with mean age of 68 years (range 38-94) were evaluated; 226 patients were African-American, of whom 61% were treated at three facilities. Race was not significantly associated with RT treatment approach, use of concurrent chemotherapy, or the dose to the planning target volume (PTV) or organs at risk including the heart and lungs. However, there was increased patient-reported general pain in African-American patients (compared with White patients) at several time points including pre-RT (22% (vs 15%), P=0.02) and at the end of RT (30% (vs 17%), P=0.001). African-American patients were significantly less likely to have provider-reported grade 2+ radiation pneumonitis (odds ratio (OR) 0.36, P=0.03), despite similar levels of patient-reported respiratory toxicities such as cough and shortness of breath and even after controlling for known patient and treatment-related factors. Correlation coefficients between provider- and patient-reported toxicities were generally similar across race categories. Conclusions: In this large multi-institutional observational study, we reassuringly found no evidence of differences in radiation treatment or chemotherapy approaches by race, in contrast to historical differences by race in surgical care that led to worse survival and outcomes in minority race patients. However, we did unexpectedly find that African-American race was associated with lower odds of provider-reported grade 2+ radiation pneumonitis despite similar patient-reported toxicities of shortness of breath and cough. There are several possibilities for this finding including that pneumonitis is a multifactorial diagnosis that relies on clinical as well as radiologic information and clinical information alone may be insufficient. The Spearman correlation analysis also revealed stronger correlations between patient- and provider-reported toxicities in White patients compared with African-American patients, particularly for trouble swallowing/esophagitis. These findings together for pneumonitis and esophagitis discouragingly suggest possible under-recognition of symptoms in black patients. Further investigation is now warranted to better understand how these findings impact the care of racially diverse lung cancer patients

Evaluating Quality of Life and Functional Outcomes in Salvage Surgery for Head and Neck Cancer

Background: Unique challenges surround treatment for residual or recurrent head and neck squamous cell carcinoma (HNSCC). Of the limited treatment options for residual or recurrent HNSCC, salvage surgery is often the best option. However, salvage surgery can result in significant morbidity, affecting both quality of life (QoL) and functional outcomes. Few studies have examined QoL outcomes following salvage surgery in the setting of HNSCC. Objectives: To analyze head and neck related quality of life and functional outcomes in patients with head and neck cancer who underwent salvage surgery. Methods: In this IRB approved study, FACT-HN Version 4 was administered pre-operatively and 6 months post-operatively to patients undergoing salvage surgery for HNSCC between November 4, 2014 and April 27, 2020. Retrospective cohort analysis was performed on this population with major outcome being postoperative QoL score. Functional outcomes included postoperative tracheostomy and feeding tube status. QoL outcomes were compared with paired t-tests. Univariate logistic regression was used to determine characteristics associated with presence of permanent tracheostomy and feeding tube, defined as presence greater than 30 days. Results: Overall, 25 patients undergoing salvage surgery for HNSCC were included in this analysis. Primary tumor sites were larynx/hypopharynx (44.0%), oral cavity (24.0%), oropharynx (20.0%), salivary (4.0%), skin (4.0%), and unknown primary (4.0%). Salvage surgeries consisted of total laryngectomy (36.0%), definitive neck dissection (24.0%), mandibulectomy (16.0%), parotidectomy (8.0%), with total laryngectomy/total glossectomy, radical tonsillectomy, TORS base of tongue excision, and transoral laser laryngeal excision all comprising 4% of cases. Total QoL scores were not significantly different preoperatively to postoperatively (mean 108.7, 95% CI=97.7 to 119.7 vs. 103.8, 95% CI: 93.1 to 114.5; P=0.436, with maximum total score of 148). Patients with lower preoperative Emotional Well-Being (EWB) subscores demonstrated significantly worse EWB subscores postoperatively (postoperative mean: 17.0, 95% CI: 14.5 to 19.4 vs. 21.7, 95% CI: 20.0 to 23.4; P=0.002). Of patients who underwent tracheostomy tube placement, 53.8% (N=7/13) remained tracheostomy dependent long-term (\u3e30 d). Of patients who underwent feeding tube placement, 81.0% (N=17/21) remained feeding tube dependent long-term (\u3e30 d). Tracheostomy and feeding tubes remained in place with median durations of 3.02 months (range 0.16 to 20.55) and 10.13 months (range 0 to 24.89), respectively. All patients with T3/4 disease undergoing salvage surgery required long-term feeding tube (N=6). Conclusions: This study provides important information about quality of life and functional outcomes for patients undergoing salvage surgery for HNSCC. There is a high rate of long-term tracheostomy and feeding tube dependence following salvage surgery. While no difference was found in head and neck related quality of life total score and sub-scores at 6 months postoperatively, general emotional well-being preoperatively was most associated with general emotional well-being postoperatively. This information should be taken into consideration when counseling and managing patients with residual or recurrent HNSCC