Is Substantial Lymphovascular Space Invasion Prognostic in Patients With Pathologically Lymph Node-Negative Endometrial Cancer?

PURPOSE: Lymphovascular space invasion (LVSI) predicts for higher rates of recurrence and increased mortality in endometrial cancer. Using 3-tier LVSI scoring, a PORTEC-1 and -2 trials analysis demonstrated that substantial LVSI was associated with worse locoregional (LR-DFS) and distant metastasis disease-free survival (DM-DFS), and these patients possibly benefited from external beam radiation therapy (EBRT). Furthermore, LVSI is a predictor for lymph node (LN) involvement, but the significance of substantial LVSI is unknown in patients with a pathologically negative LN assessment. We aimed to evaluate clinical outcomes of these patients in relation to the 3-tier LVSI scoring system. METHODS AND MATERIALS: We performed a single-institutional retrospective review of patients with stage I endometrioid-type endometrial cancer who underwent surgical staging with pathologically negative LN evaluation from 2017 to 2019 with 3-tier LVSI scoring (none, focal, or substantial). Clinical outcomes (LR-DFS, DM-DFS, and overall survival) were analyzed using the Kaplan-Meier method. RESULTS: A total of 335 patients with pathologically LN-negative stage I endometrioid-type endometrial carcinoma were identified. Substantial LVSI was present in 17.6% of patients; 39.7% of patients received adjuvant vaginal brachytherapy and 6.9% of patients received EBRT. Adjuvant radiation treatment varied by LVSI status. In patients with focal LVSI, 81.0% received vaginal brachytherapy. Among patients with substantial LVSI, 57.9% received vaginal brachytherapy alone, and 31.6% of patients received EBRT. The 2-year LR-DFS rates were 92.5%, 98.0%, and 91.4% for no LVSI, focal LVSI, and substantial LVSI, respectively. The 2-year DM-DFS rates were 95.5%, 93.3%, and 93.8% for no LVSI, focal LVSI, and substantial LVSI, respectively. CONCLUSIONS: In our institutional study, patients with pathologically LN-negative stage I endometrial cancer with substantial LVSI had similar rates of LR-DFS and DM-DFS compared with patients with none or focal LVSI. These findings highlight the need for multi-institutional studies to validate the prognostic value of substantial LVSI in this patient population.

Concurrent immunoradiation for HPV-associated oropharyngeal squamous cell carcinoma.

OBJECTIVES: Current trials for HPV-associated oropharyngeal SCCs (OP-SCCs) are evaluating treatment de-escalation including use of concurrent immunotherapy with radiation therapy (I-RT). Given limited prospective data following I-RT, we aimed to examine this question utilizing the National Cancer Data Base (NCDB). METHODS: The NCDB was queried for patients with HPV-associated OP-SCCs eligible for current de-escalation studies with AJCC 7th edition T1-T2/N1-N2b and T3/N0-N2b disease. Patients were stratified into I-RT, concurrent chemoradiation (C-RT), and radiation therapy alone (RT) arms. Kaplan-Meier analysis was utilized to compare overall survival (OS) between treatment arms followed by a Cox multivariate (MVA) proportional hazards model controlling for tumor and patient characteristics and propensity-score analyses with inverse probability treatment weighting (IPTW). RESULTS: We identified 4768 patients; 313 received I-RT, 3660 patients received C-RT, and 795 received RT. Median age was 62 years (range 27-90) with a median Charlson-Deyo co-morbidity score of 0 (range: 0-3). The vast majority were cN1-N2a (88.8%) and 26.5% were cT3. On MVA, inferior 3-year and 8-year OS was noted following I-RT (81.6% and 70.5%) vs. C-RT (90.6% and 79.4%) (HR = 1.69 (95% CI: 1.29-2.21); p < 0.0001) with no significant difference vs. RT (88.1% and 75.8%) (HR = 1.07; p = 0.80). This was also maintained on IPTW-analysis (HR = 1.62 (95% CI: 1.23-2.15); p = 0.001). CONCLUSIONS: I-RT was associated with significantly poorer OS vs. C-RT with no benefit compared to RT for HPV-associated OP-SCCs. I-RT is not recommended outside of currently accruing clinical trials.

A multi-institutional analysis of outcomes following stereotactic body radiation therapy for management of metastases from squamous cell carcinomas of the head and neck.

Background: There is limited data on clinical outcomes following SBRT for patients with metastatic head and neck squamous cell carcinoma (mHNC). Method: An international SBRT registry was utilized to identify patients. LC and OS were evaluated with the Kaplan-Meier method and a Cox-proportional hazards model for multivariate analysis (MVA) to assess potential prognostic factors. Results: We identified 81 patients with 98 lesions treated with SBRT. Areas treated included the lung (53.0%), non-regional lymph nodes (16.0%), and spine (12.3%). OS rates at 1 year and 2 years were 66.4% and 43.1%, respectively. Utilizing KPS, spinal disease, and GTV, 1-year OS estimates were 90.9%, 70.4%, 54.5%, and 25% for patients with 0-3 of these factors, respectively (p = 0.002). One-year and 2-year LC rates were both 93.3%. Roughly 17% of patients reported toxicities (none Grade 3+). Conclusions: SBRT resulted in promising LC for mHNC patients. Spinal disease, GTV, and KPS should be considered in selecting patients with mHNC that may benefit from SBRT.

Palliative radiation therapy for children with cancer.

Radiation therapy (RT) is often used as a palliative treatment for children with recurrent malignant disease to ameliorate or prevent symptoms. However, no guidelines exist regarding the clinical indications or dose fractionation for palliative RT. The goal of this report is to provide guidelines for the use of palliative RT in children with cancer. In this guideline, appropriate indications for palliative RT, recommended dose-fractionation schedules, relevant toxicities, and avenues for future research are explored. RT is an effective palliative treatment for bone, brain, liver, lung, abdominopelvic and head-and-neck metastases, spinal cord compression, superior vena cava syndrome, and bleeding. Single-fraction regimens (8 Gy in one fraction) for children with short life expectancy are recommended for simple, uncomplicated bone metastases and can be considered for some patients with lung or liver metastases. A short, hypofractionated regimen (20 Gy in five fractions) may be used for other indications to minimize overall burden of therapy. There are little data supporting use of more prolonged fractionation regimens, though they may be considered for patients with very good performance status. Future research should focus on response and outcomes data collection, and to rigorously evaluate the role of stereotactic body RT in well-designed, prospective studies.

Supportive care for toxicities in children undergoing radiation therapy.

Radiation therapy (RT) is an integral part of the management of many pediatric tumors; however, it is associated with both acute and permanent adverse events that can significantly impact a child's quality of life, lead to treatment delays, and potentially affect outcomes of cancer therapy. Prevention, early detection, and optimal management of these adverse effects will help reduce their impact on the patients' quality of life and overall well-being. Unfortunately, there has not been a coordinated effort to study the etiology, evaluate risk factors, and explore novel treatments for these conditions. Studies of supportive care for children undergoing RT are often small and uncontrolled. This review will focus on the impact of irradiation on the different organ systems and their current management. Further studies are required to improve our understanding of the contributing factors and explore novel treatment options for these adverse effects and to enable children and their families to better cope with some of the unavoidable toxicities following multimodality therapy.

Stereotactic body radiation therapy (SBRT) for metastatic renal cell carcinoma: A multi-institutional experience.

Objectives: Examine local control(LC), overall survival(OS), and toxicity following stereotactic body radiation therapy(SBRT) for patients with metastatic renal cell carcinoma(mRCC). Methods: A multi-institutional registry was queried. Potential predictive factors of LC and OS were evaluated with a Cox-proportional hazards model for multivariate analysis(MVA). Results: We identified 115 mRCC patients with 181 lesions. Median biologically effective dose (BED7) was 72.9 Gy7 (range: 42.9-231.4 Gy7) with a median dose/fraction of 10 Gy (range: 5-24 Gy). Utilizing both Karnofsky Performance Score (KPS) and presence of osseous metastatic disease as prognostic indicators, estimated 2-year OS rates were 67.7% (95% CI: 49.9-89.5%), 31.8% (95% CI: 19.0-45.3%), and 20% (95% CI: 1.4-54.7%; p=0.0012). One- and 2-year LC rates were 88.2% and 82.7%, respectively, with no prognostic factors identified. Roughly 13% of patients reported toxicities with one Grade 3-5 toxicity. Conclusion: SBRT was well-tolerated with promising LC. Both KPS and osseous metastatic disease should be considered in determining which patients with mRCC may preferentially benefit from SBRT.

Cancer antigen 125 is associated with disease status in uterine carcinosarcoma.

Uterine carcinosarcoma is a rare and aggressive tumor with poor outcomes. Cancer antigen 125 is routinely used to track the disease course of ovarian cancer and has been suggested as a biomarker in other aggressive forms of uterine cancer. We sought to characterize cancer antigen 125 as a potential biomarker of disease status in uterine carcinosarcoma. Clinical and pathological data were abstracted for patients who had surgical staging for a pathologically confirmed uterine carcinosarcoma at our institution from January 2000 to March 2014. Non-parametric tests were used to compare changes in cancer antigen 125. Elevated cancer antigen 125 (>35 U/mL) as a predictor of survival was assessed via Kaplan-Meier curves. Among the 153 patients identified, 66 patients had at least one paired measure of cancer antigen 125 drawn preoperatively, post-treatment, or at the time of disease recurrence, and 19 patients had cancer antigen-125 levels at all three time points. Analysis of the 51 patients with both preoperative and post-treatment values found a significant drop in cancer antigen 125 (p < 0.001). Among the 30 patients who had end-of-treatment and recurrence levels, a significant increase was noted (p = 0.001). There was no significant difference in cancer antigen-125 levels preoperatively compared to at recurrence among the 23 patients with levels at both time-points (p = 0.99). Elevated preoperative cancer antigen 125 was not associated with overall survival (p = 0.12); elevated post-treatment cancer antigen 125 was associated with a worse overall survival (p < 0.001). Based on this dataset, there seems to be utility in trending a cancer antigen-125 level in patients with uterine carcinosarcoma. A cancer antigen-125 level could predict recurrence and provide prognostic information regarding survival.

Intraoperative radiotherapy (IORT) for surgically resected brain metastases: outcome analysis of an international cooperative study.

BACKGROUND AND OBJECTIVE: The ideal delivery of radiation to the surgical cavity of brain metastases (BMs) remains the subject of debate. Risks of local failure (LF) and radiation necrosis (RN) have prompted a reappraisal of the timing and/or modality of this critical component of BM management. IORT delivered at the time of resection for BMs requiring surgery offers the potential for improved local control (LC) afforded by the elimination of delay in time to initiation of radiation following surgery, decreased uncertainty in target delineation, and the possibility of dose escalation beyond that seen in stereotactic radiosurgery (SRS). This study provides a retrospective analysis with identification of potential predictors of outcomes. METHODS: Retrospective data was collected on patients treated with IORT immediately following surgical resection of BMs at three institutions according to the approval of individual IRBs. All patients were treated with 50kV portable linear accelerator using spherical applicators ranging from 1.5 to 4.0 cm. Statistical analyses were performed using IBM SPSS with endpoints of LC, DBC, incidence of RN, and overall survival (OS) and p < 0.05 considered significant. RESULTS: 54 patients were treated with IORT with a median age of 64 years. The most common primary diagnosis was non-small cell lung cancer (40%) with the most common location in the frontal lobe (38%). Median follow-up was 7.2 months and 1-year LC, DBC, and OS were 88%, 58%, and 73%, respectively. LMD was identified in 2 patients (3%) and RN present in 4 patients (7%). The only predictor of LC was extent of resection with 1-year LC of 94% for GTR versus 62% for STR (p = 0.049). CONCLUSIONS: IORT is a safe and effective means of delivering adjuvant radiation to the BM resection cavities with high rates of LC and low incidence of RN. Further studies are warranted directly comparing LC outcomes to SRS.

Stereotactic radiosurgery and fractionated stereotactic radiosurgery for vestibular schwannomas: A comparison of clinical outcomes from the RSSearch patient registry.

PURPOSE: To compare clinical outcomes following stereotactic radiosurgery (SRS) and fractionated stereotactic radiosurgery (fSRS) for vestibular schwannomas (VS). MATERIALS/METHODS: We identified 64 VS patients from the RSSearch Patient Registry (12 treated with SRS and 52 patients treated with fSRS). Potential factors predictive of local control (LC) and toxicity were estimated using the Kaplan-Meier method, Cox proportional hazards model, and binary logistic regressions with propensity score weighting. RESULTS: SRS (100%) and fSRS (94.2%) resulted in similar LC (p = 0.33). fSRS was associated with a higher likelihood of experiencing toxicities (42.3% vs. 8.3%; p = 0.054 on time-to-event analysis) that was maintained following a propensity-score weighted binary logistic regression (p = 0.037) and propensity-score weighted Cox regression (p = 0.039; hazard ratio (HR) = 8.85 (95% CI: 1.1 - 70.1)). CONCLUSION: In a multi-institutional analysis, we note equivalent LC but higher toxicity with fSRS compared to SRS for VS.

Gender Differences in Musculoskeletal Lipid Metabolism as Assessed by Localized Two-Dimensional Correlation Spectroscopy.

Gender differences in lipid metabolism are poorly understood and difficult to study using conventional approaches. Magnetic resonance spectroscopy (MRS) permits non-invasive investigation of lipid metabolism. We employed novel two-dimensional MRS techniques to quantify intramyocellular (IMCL) and extramyocellular (EMCL) lipid compartments and their degree of unsaturation in normal weight adult male and female subjects. Using muscle creatine (Cr) for normalization, a statistically significant (p < 0.05) increase in IMCL/Cr (7.8 ± 1.6) and EMCL/Cr (22.5 ± 3.6) for female subjects was observed (n=8), as compared to IMCL/Cr (5.9 ± 1.7) and EMCL/Cr (18.4 ± 2.64) for male subjects. The degree of unsaturation within IMCL and EMCL was lower in female subjects, 1.3 ± 0.075 and 1.04 ± 0.06, respectively, as compared to that observed in males (n=8), 1.5 ± 0.08 and 1.12 ± 0.03, respectively (p < 0.05 male vs female for both comparisons). We conclude that certain salient gender differences in lipid metabolism can be assessed noninvasively by advanced MRS approaches.