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Purpose: Non-melanoma skin cancers of the face are at high-risk for local recurrence and metastatic spread. While surgical interventions such as Mohs microsurgery are considered the standard of care, this modality has the potential for high rates of toxicity in sensitive areas of the face. Catheter flap high-dose-rate (HDR) brachytherapy has shown promising results, with high rates of local control and acceptable cosmetic outcomes. Material and methods: Patients with non-melanoma skin cancers (NMSC) located on the face were treated with 40 Gy in 8 fractions, given twice weekly via catheter flap HDR brachytherapy. Clinical target volume (CTV) included the visible tumor plus a margin of 5 mm in all directions, with no additional planning target volume (PTV) margin. Results: Fifty patients with 53 lesions on the face were included, with a median follow-up of 15 months. All were considered high-risk based on NCCN guidelines. Median tumor size and thickness were 18 mm and 5 mm, respectively. Median PTV volume and D90 were 1.7 cc and 92%, respectively. Estimated rate of local control at twelve months was 92%. Three patients (5%) experienced acute grade 2 toxicity. Two patients (4%) continued to suffer from chronic grade 1 skin toxicity at 12 months post-radiotherapy (RT), with an additional two patients (4%) experiencing chronic grade 2 skin toxicity. Forty-nine lesions (92%) were found to have a good or excellent cosmetic outcome with complete tumor remission. Conclusions: CT-based flap applicator brachytherapy is a valid treatment option for patients with NMSC of the face. This modality offers high rates of local control with acceptable cosmetic outcomes and low rates of toxicity. [ABSTRACT FROM AUTHOR]

Background: Patients with head and neck cancer (HNC) who are not candidates for definitive treatment represent an increasing challenge, with limited data to guide management. Conventional local therapies such as surgery and chemoradiation can significantly impact quality of life (QoL). There has been limited data published using stereotactic body radiotherapy (SBRT) as primary treatment in previously unirradiated patients. We hypothesize that SBRT provides high rates of control while limiting toxicity. Methods: A total of 66 medically unfit previously unirradiated patients with HNC were treated with SBRT, consisting of 35‐40 Gy to gross tumor volume and 30 Gy to clinical target volume in five fractions. Results: Median age was 80 years. Local control (LC) and overall survival (OS) at 1 year were 73% and 64%. Two patients experienced grade 3 toxicity. Conclusion: SBRT shows acceptable outcomes with relatively low toxicity in previously unirradiated patients with HNC who are medically unfit for conventional treatment. SBRT may provide an aggressive local therapy with high rates of LC and OS while maintaining QoL. [ABSTRACT FROM AUTHOR]

Purpose: To present a retrospective analysis of the efficacy, toxicity, and quality of life (QoL) of patients treated with OAR Extreme -sparing stereotactic body radiotherapy (SBRT) in previously-irradiated head and neck cancer. Materials/Methods: From 11/2012 to 7/2015, 60 patients with in-field recurrence of head and neck cancer underwent re-irradiation with SBRT. Retreatment sites included the aerodigestive tract (43%), lateral neck (22%), and skull base (35%). The median prior RT dose was 63.6 Gy with a median time from prior irradiation of 16.5 months. The median volume treated was 61.0 cc. Patients were treated with 40 Gy in the definitive setting or 35 Gy in the post-operative setting in five fractions. Dose constraints to the OAR Extreme were calculated with a BED calculator using an alpha/beta ratio of 3 to reduce the risk of late toxicities. QoL data was collected from patients at the time of consultation and at subsequent follow up appointments using the MD Anderson Dysphagia Inventory (MDADI) and Symptom Inventory (MDASI). Results: The 1- and 2- year rates of local, regional, and distant control and overall survival were 79/79, 74/70, 74/71, and 59/45%, respectively. Late grade 3 toxicities were seen in 3% in the group treated to the aerodigestive tract and 1% in the group treated to the skull base. No grade 4 or 5 toxicities were observed. Patients with skull base re-irradiation maintained a stable QoL score after radiation treatment, while patients treated to the aerodigestive tract demonstrated a slight impairment associated with worsening dysphagia, compared to their pretreatment baseline. All groups experienced an increase in xerostomia. Conclusions: OAR Extreme -sparing SBRT is able to achieve excellent tumor coverage while protecting the organs at highest risk of re-irradiation-related complications. The potential for lower toxicities and maintained QoL with this treatment makes it a promising option for salvage of recurrent head and neck cancer. Summary: Local control and overall survival rates for recurrent head and neck cancer remain poor, despite the use of local therapy. In addition, re-irradiation with conventional radiation therapy confers a high rate of grade 3 and higher late toxicities. SBRT appears to improve the therapeutic ratio in this patient population, and treatment planning with a focus on sparing OAR Extreme may further decrease the rates of morbidity in these patients. [ABSTRACT FROM AUTHOR]

Background: Urinary symptoms and sexual dysfunction are the two most common complaints following prostate radiotherapy. The impact of hypofractionated treatment on sexual function, irritative symptoms, and voiding symptoms has not been determined within the same patient population. Here we present our institutional data on sexual function, voiding function, irritative symptoms, and treatment response following SBRT. Methods: This retrospective analysis includes 102 non-metastatic patients treated with SBRT at a single institution between May 2008 and September 2014. The course of radiotherapy consisted of 36.25 Gy (range 35-40) over five daily fractions. International Prostate Symptom Score (IPSS), Sexual Health Inventory for Men (SHIM), and PSA were recorded at baseline, 1, 3, 6, 9, 12, 18, 24, and 36 months after treatment. Results: Median patient age was 72 years old with a median follow-up of 4.3 years. Pretreatment IPSS-I score was 5.21, increasing to 6.97 (p < .001) after 1 month. The mean IPSS-I score returned close to baseline after 3 months to 5.86 and decreased to below baseline after 2 years to 5.09. At 3 months, 9 months, and 2 years, 47.5, 76.2, and 91.1 % of patients had reached IPSS-I resolution. The mean IPSS-O score prior to treatment was 5.31 and there was an increase in the score to 6.45 (p = 0.344) at 1 month. The score remained close to baseline and decreased to 4.00 at 2 years and significantly decreased to 3.74 (p = 0.035) at 3 years. 64.4, 82.1, and 96.0 % of patients had IPSS-O resolution by 3 months, 9 months, and 2 years. The mean SHIM score prior to treatment was 13.52 and continually decreased to below baseline a year after treatment to 10.56 (p < .001). SHIM score began to improve at 18 months, but was still significantly less than baseline at 12.12 (p = .01). Conclusions: While an increase in AUA/IPSS score initially occurred, all patients resume normal activities immediately following treatment and the AUA/IPSS symptoms improved from baseline. Irittative symptoms take longer to resolve when compared to obstructive voiding symptoms in patients treated with SBRT. Three year PSA response, reported toxicity, erectile function preservation, and urinary function improvement, shows favorable results. [ABSTRACT FROM AUTHOR]

Purpose: Accelerated partial breast irradiation (APBI) with balloon and strut adjusted volume implants (SAVI) show promising results with excellent tumor control and minimal toxicity. Knowing the factors that contribute to a high skin dose, rib dose, and D95 coverage may reduce toxicity, improve tumor control, and help properly predict patient outcomes following APBI. Methods and materials: A retrospective analysis of 594 patients treated with brachytherapy based APBI at a single institution from May 2008 to September 2014 was grouped by applicator subtype. Patients were treated to a total of 34 Gy (3.4 Gy x 10 fractions over 5 days delivered BID) targeting a planning target volume (PTV) 1.0 cm beyond the lumpectomy cavity using a high dose rate source. Results: SAVI devices had the lowest statistically significant values of DmaxSkin (81.00 ± 29.83), highest values of D90 (101.50 ± 3.66), and D95 (96.09 ± 4.55). SAVI-mini devices had the lowest statistically significant values of DmaxRib (77.66 ± 32.92) and smallest V150 (18.01 ± 3.39). Multi-lumen balloons were able to obtain the smallest V200 (5.89 ± 2.21). Strut-based applicators were more likely to achieve a DmaxSkin and a DmaxRib less than or equal to 100 %. The effect of PTV on V150 showed a strong positive relationship (p < .001). PTV and DmaxSkin showed a weak negative relationship in multi-lumen applicators (p = .016) and SAVI-mini devices (p < .001). PTV and DmaxRib showed a weak negative relationship in multi-lumen applicators (p = .009), SAVI devices (p < .001), and SAVI-mini devices (p < .001). Conclusion: PTV volume is strongly correlated with V150 in all devices and V200 in strut based devices. Larger PTV volumes result in greater V150 and V200, which could help predict potential risks for hotspots and resulting toxicities in these devices. PTV volume is also weakly negatively correlated with max skin dose and max rib dose, meaning that as the PTV volumes increase one can expect slightly smaller max skin and rib doses. Strut based applicators are significantly more effective in keeping skin and rib dose constraints under 125 and 100 % when compared to any balloon based applicator. [ABSTRACT FROM AUTHOR]

Background: Irritative voiding symptoms are common in elderly men and following prostate radiotherapy. There is limited clinical data on the impact of hypofractionated treatment on irritative voiding symptoms. This study sought to evaluate urgency, frequency, and nocturia following stereotactic body radiation therapy (SBRT) for prostate cancer. Methods: Patients treated with SBRT monotherapy for localized prostate cancer from August 2007 to July 2011 at Georgetown University Hospital were included in this study. Treatment was delivered using the CyberKnife® with doses of 35-36.25 Gy in five fractions. Patient-reported urinary symptoms were assessed using the International Prostate Symptom Score (IPSS) before treatment and at 1, 3, 6, 9, and 12 months post-treatment and every 6 months thereafter. Results: Two hundred four patients at a median age of 69 years received SBRT with a median follow-up of 4.8 years. Prior to treatment, 50.0% of patients reported moderate to severe lower urinary tract symptoms (LUTS) and 17.7% felt that urinary frequency was a moderate to big problem. The mean prostate volume was 39 cc and 8% had prior procedures for benign prostatic hyperplasia. A mean baseline IPSS-irritative (IPSS-I) score of 4.8 significantly increased to 6.5 at 1 month (p<0.0001), however returned to baseline at 3 months (p=0.73). The IPSS-I score returned to baseline in 91% of patients by 6 months and 96% of patients by 2 years. Transient increases in irritative voiding symptoms were common at 1 year. The mean baseline IPSS-I score decreased to 4.4 at 24 months (p =0.03) and 3.7 at 36 months (p <0.0001). In men with moderate to severe LUTS (IPSS⁄8) at baseline, the mean IPSS-I decreased from a baseline score of 6.8-4.9 at 3 years post-SBRT. This decrease was both statistically (p <0.0001) and clinically significant (minimally important difference D1.45). Only 14.6% of patients felt that urinary frequency was a moderate to big problem at 3 years post-SBRT (p =0.23). Conclusion: Treatment of prostate cancer with SBRT resulted in an acute increase in irritative urinary symptoms that peaked within the first month post-treatment. Irritative voiding symptoms returned to baseline in the majority of patients by 3 months post-SBRT and were actually improved from baseline at 3 years post-SBRT. [ABSTRACT FROM AUTHOR]

The recent finding that the neuronal cadherin gene CDH2 confers a highly significant risk for canine compulsive disorder led us to investigate whether missense variants within the human ortholog CDH2 are associated with altered susceptibility to obsessive-compulsive disorder (OCD), Tourette disorder (TD) and related disorders. Exon resequencing of CDH2 in 320 individuals identified four non-synonymous single-nucleotide variants, which were subsequently genotyped in OCD probands, Tourette disorder probands and relatives, and healthy controls (total N=1161). None of the four variants was significantly associated with either OCD or TD. One variant, N706S, was found only in the OCD/TD groups, but not in controls. By examining clinical data, we found there were significant TD-related phenotype differences between those OCD probands with and without the N845S variant with regard to the co-occurrence of TD (Fisher's exact test P=0.014, OR=6.03). Both N706S and N845S variants conferred reduced CDH2 protein expression in transfected cells. Although our data provide no overall support for association of CDH2 rare variants in these disorders considered as single entities, the clinical features and severity of probands carrying the uncommon non-synonymous variants suggest that CDH2, along with other cadherin and cell adhesion genes, is an interesting gene to pursue as a plausible contributor to OCD, TD and related disorders with repetitive behaviors, including autism spectrum disorders. [ABSTRACT FROM AUTHOR]

PURPOSE: Peripheral nerve sheath tumors account for 5% to 10% of all soft tissue sarcomas. Recent data show that tumor diameter < 5 cm and/or gross total resection reduces hazard for death. The aim of this study was to review presentation, acute toxicity, and morbidity associated with surgery and radiation in the treatment of these favorable peripheral nerve sheath tumors at our institution. METHODS: We retrospectively reviewed the data of 27 patients treated at our institution from February 2010 to June 2015. Ten patients received stereotactic body radiation therapy (SBRT) in 4–6 fractions, 16 received gross total resections, and 1 received both surgery and radiation. Baseline characteristics gathered included race, age at diagnosis, body mass index (BMI), site, histology, grade, previous therapy, RT dose, duration of treatment, time to diagnosis, and presenting symptoms. Outcomes recorded focused on acute toxicities, local control, and overall survival. Toxicities were graded according to the Common Terminology Criteria for Adverse Events version 4.0. RESULTS: The median age at diagnosis was 53 years (range: 20–87 yr), median BMI (body mass index, kg/m2) was 28.9, median interval from onset of symptoms to diagnosis was 10 months (range: 0–32 mo), and median tumor size was 2.8 cm (range: 1.3–4.7 cm). Presenting symptoms included 41% of patients with lumbosacral plexopathy, 19% with mononeuropathy, 11% with incidental finding on imaging, 11% with a vestibular disturbance, 7% with brachial plexopathy, 7% with a gait disturbance, and 4% with a hip deformity. Toxicities were low, with 89% of patients experiencing grade 0/1 toxicity and 11% experiencing grade 2 toxicity. The local recurrence rate was 21% after a median of 18 months. There was no significant difference in outcomes between surgical treatment and RT. CONCLUSION: Both surgery and radiation are very well tolerated treatment regimens with limited and manageable toxicity in favorable patients. Outcomes in patients with peripheral nerve sheath tumors < 5 cm are promising. [ABSTRACT FROM AUTHOR]

Background and Objective: Oligometastatic castration-sensitive prostate cancer (omCSPC) represents an early state in the progression of metastatic disease for which patients experience better outcomes in comparison to those with higher disease burden. Despite the generally more indolent nature, there is still much heterogeneity, with some patients experiencing a more aggressive clinical course unexplained by clinical features alone. Our aim was to investigate correlation of tumor genomics with the mode of progression (MOP) and pattern of failure (POF) following first treatment (metastasis-directed and/or systemic therapy) for omCSPC., Methods: We performed an international multi-institutional retrospective study of men treated for metachronous omCSPC who underwent tumor next-generation sequencing with at least 1 yr of follow-up after their first treatment. Descriptive MOP and POF results are reported with respect to the presence of genomic alterations in pathways of interest. MOP was defined as class I, long-term control (LTC; no radiographic progression at last follow-up), class II, oligoprogression (1-3 lesions), or class III, polyprogression (≥4 lesions). POF included the location of lesions at first failure. Genomic pathways of interest included TP53, ATM, RB1, BRCA1/2, SPOP, and WNT (APC, CTNNB1, RNF43). Genomic associations with MOP/POF were compared using χ 2 tests. Exploratory analyses revealed that the COSMIC mutational signature and differential gene expression were also correlated with MOP/POF. Overall survival (OS) was calculated via the Kaplan-Meier method from the time of first failure., Key Findings and Clinical Implications: We included 267 patients in our analysis; the majority had either one (47%) or two (30%) metastatic lesions at oligometastasis. The 3-yr OS rate was significantly associated with MOP (71% for polyprogression vs 91% for oligoprogression; p = 0.005). TP53 mutation was associated with a significantly lower LTC rate (27.6% vs 42.3%; p = 0.04) and RB1 mutation was associated with a high rate of polyprogression (50% vs 19.9%; p = 0.022). Regarding POF, bone failure was significantly more common with tumors harboring TP53 mutations (44.8% vs25.9%; p = 0.005) and less common with SPOP mutations (7.1% vs 31.4%; p = 0.007). Visceral failure was more common with tumors harboring either WNT pathway mutations (17.2% vs 6.8%, p = 0.05) or SPOP mutations (17.9% vs 6.3%; p = 0.04). Finally, visceral and bone failures were associated with distinct gene-expression profiles., Conclusions and Clinical Implications: Tumor genomics provides novel insight into MOP and POF following treatment for metachronous omCSPC. Patients with TP53 and RB1 mutations have a higher likelihood of progression, and TP53, SPOP, and WNT pathway mutations may have a role in metastatic organotropism., Patient Summary: We evaluated cancer progression after a first treatment for metastatic prostate cancer with up to five metastases. We found that mutations in certain genes were associated with the location and extent of further metastasis in these patients., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Chemoradiation therapy (CRT) is a treatment for muscle-invasive bladder cancer (MIBC). Using a novel transcriptomic profiling panel, we validated prognostic immune biomarkers to CRT using 70 pretreatment tumor samples from prospective trials of MIBC (NRG/RTOG 0524 and 0712). Disease-free survival (DFS) and overall survival (OS) were estimated via the Kaplan-Meier method and stratified by genes correlated with immune cell activation. Cox proportional-hazards models were used to assess group differences. Clustering of gene expression profiles revealed that the cluster with high immune cell content was associated with longer DFS (hazard ratio [HR] 0.53, 95% confidence interval [CI] 0.26-1.10; p = 0.071) and OS (HR 0.48, 95% CI 0.24-0.97; p = 0.040) than the cluster with low immune cell content. Higher expression of T-cell infiltration genes (CD8A and ICOS) was associated with longer DFS (HR 0.40, 95% CI 0.21-0.75; p = 0.005) and OS (HR 0.49, 95% CI 0.25-0.94; p = 0.033). Higher IDO1 expression (IFNγ signature) was also associated with longer DFS (HR 0.44, 95% CI 0.24-0.88; p = 0.021) and OS (HR 0.49, 95% CI 0.24-0.99; p = 0.048). These findings should be validated in prospective CRT trials that include biomarkers, particularly for trials incorporating immunotherapy for MIBC. PATIENT SUMMARY: We analyzed patient samples from two clinical trials (NRG/RTOG 0524 and 0712) of chemoradiation for muscle-invasive bladder cancer using a novel method to assess immune cells in the tumor microenvironment. Higher expression of genes associated with immune activation and high overall immune-cell content were associated with better disease-free survival and overall survival for patients treated with chemoradiation., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: Mindfulness, defined as awareness of the moment while acknowledging and accepting one's feelings, thoughts, and sensations, is the aim of mindfulness meditation. Our objective was to investigate the relationship between burnout, mindfulness, fulfillment, and other personal characteristics in radiation oncology (RO) residents/attendings compared with other specialties., Methods and Materials: From December 2019 to February 2020, residents and attendings in multiple specialties at a single tertiary care academic institution were sent surveys, including the mindfulness attention awareness scale, Stanford professional fulfillment index, and a personal questionnaire. A Pearson correlation was conducted on the relationship between mindfulness, fulfillment, disengagement, and exhaustion. To determine risk factors for burnout (overall burnout ≥ 1.33), a univariate analysis was conducted to yield odds ratios (ORs) on debt, specialty, income, sleep, exercise, marital status, number of children, work hours, mindfulness (mindfulness attention awareness scale ≥ 4), fulfillment (professional fulfillment ≥ 3), and time with family/friends. Significant factors on univariate analysis were entered into multivariate analysis., Results: There were 180 surveys completed by 60 residents and attendings across 17 specialties. Eighteen (30%) respondents were in RO. Mindfulness positively correlated with fulfillment ( P < .001, r = 0.534), negatively correlated with exhaustion ( P < .001, r = -0.578), and negatively correlated with disengagement ( P < .001, r = -0.483). Univariate analysis for factors associated with burnout was significant for mindfulness (OR = 0.065, P < .001), RO versus other specialty (OR = 0.024, P  = .044), working >60 h/wk (OR = 5.091, P  = .018), spending >10 h/wk with family or friends (OR = 0.120, P  = .001), and fulfillment (OR = 0.103, P < .001). Multivariate analysis showed mindfulness and fulfillment to significantly decrease odds of burnout., Conclusions: RO physicians experienced less burnout than physicians in other specialties at our institution. Mindfulness, professional fulfillment, moderate work hours, and spending time with loved ones protected against burnout. Further study of interventions to promote mindfulness and fulfillment may help us understand how best to improve the mental and emotional health of RO physicians., (© 2022 The Authors.)

Purpose: Stereotactic body radiation therapy (SBRT) is a common treatment option for patients with metastatic tumors of the spine. The optimal treatment-, tumor-, and patient-specific characteristics necessary to achieve durable outcomes remain less well understood given the heterogeneous nature of the patient population this modality typically serves. The objective of this analysis was to better understand the determinants underlying SBRT spine treatment outcomes., Methods and Materials: A total of 127 patients with 287 spine tumors were treated between March 2010 and May 2015. The median total doses for single-fraction and hypofractionated courses of treatment were 16 Gy (range, 16-20 Gy) and 24 Gy (range, 16-40 Gy), respectively. Radiologic local control and numeric pain score data were measured, and univariate and multivariate analyses were done to determine factors predictive of treatment response., Results: Median follow-up was 5.9 months (range, 1-61 months). Radiologic local control was achieved in 84.7% of patients at 6 months and in 74.7% of patients at 1 year. Local control was found to be affected by the Spinal Instability Neoplastic Score, and was worse in patients with scores ≥7 (hazard ratio [HR]: 4.25; 95% confidence interval [CI], 1.57-11.51). Patients who required upfront surgical intervention to alleviate spinal cord compression, address mechanical spinal instability, or both had worse local control than those who did not require surgery (HR: 2.32; 95% CI, 1.04-5.17). Patients treated with a hypofractionated course compared with a single fraction had worse radiologic local control (HR: 2.63; 95% CI, 1.27-5.45). No patients developed radiation-induced myelitis after treatment, and the vertebral compression fracture rate was 9.1% after SBRT., Conclusions: Patients with potentially unstable spines or needing upfront spinal surgery before SBRT are less likely to achieve durable radiologic local control. Additionally, patients treated with single-fraction regimens have improved local control compared with those treated with hypofractionated radiation.