TARGIT-R (Retrospective): North American Experience with Intraoperative Radiation Using Low-Kilovoltage X-Rays for Breast Cancer.

BACKGROUND: Single-dose intraoperative radiotherapy (IORT) is an emerging treatment for women with early stage breast cancer. The objective of this study was to define the frequency of IORT use, patient selection, and outcomes of patients treated in North America. METHODS: A multi-institutional retrospective registry was created, and 19 institutions using low-kilovoltage IORT for the treatment of breast cancer entered data on patients treated at their institution before July 31, 2013. Patient selection, IORT treatment details, complications, and recurrences were analyzed. RESULTS: From 2007 to July 31, 2013, a total of 935 women were identified and treated with lumpectomy and IORT. A total of 822 patients had at least 6 months' follow-up documented and were included in the analysis. The number of IORT cases performed increased significantly over time (p < 0.001). The median patient age was 66.8 years. Most patients had disease that was <2 cm in size (90 %) and was estrogen positive (91 %); most patients had invasive ductal cancer (68 %). Of those who had a sentinel lymph node procedure performed, 89 % had negative sentinel lymph nodes. The types of IORT performed were primary IORT in 79 %, secondary IORT in 7 %, or planned boost in 14 %. Complications were low. At a median follow-up of 23.3 months, crude in-breast recurrence was 2.3 % for all patients treated. CONCLUSIONS: IORT use for the treatment of breast cancer is significantly increasing in North America, and physicians are selecting low-risk patients for this treatment option. Low complication and local recurrence rates support IORT as a treatment option for selected women with early stage breast cancer.

Correlation of HOXD3 promoter hypermethylation with clinical and pathologic features in screening prostate biopsies.

BACKGROUND: Molecular markers that can discriminate indolent cancers from aggressive ones may improve the management of prostate cancer and minimize unnecessary treatment.Aberrant DNA methylation is a common epigenetic event in cancers and HOXD3 promoter hypermethylation (H3PH) has been found in prostate cancer. Our objective was to evaluate the relationship between H3PH and clinicopathologic features in screening prostate biopsies. METHODS: Ninety-two patients who underwent a prostate biopsy at our institution between October 2011 and May 2012 were included in this study. The core with the greatest percentage of the highest grade disease was analyzed for H3PH by methylation-specific PCR. Correlational analysis was used to analyze the relationship between H3PH and various clinical parameters. Chi-square analysis was used to compare H3PH status between benign and malignant disease. RESULTS: Of the 80 biopsies with HOXD3 methylation status assessable, 66 sets were confirmed to have cancer. In the 14 biopsies with benign disease there was minimal H3PH with the mean percentage of methylation reference (PMR) of 0.7%. In contrast, the HOXD3 promoter was hypermethylated in 16.7% of all cancers and in 50% of high risk tumors with an average PMR of 4.3% (P=0.008). H3PH was significantly correlated with age (P=0.013), Gleason score (P=0.031) and the maximum involvement of the biopsy core (P=0.035). CONCLUSIONS: H3PH is associated with clinicopathologic features. The data indicate that H3PH is more common in older higher risk patients. More research is needed to determine the role of this marker in optimizing management strategies in men with newly diagnosed prostate cancer.

Improved efficacy of endobronchial ultrasound-guided fine-needle aspiration biopsy in comparison to endobronchial ultrasound-guided miniforceps biopsy.

OBJECTIVE: Endobronchial ultrasound-guided fine-needle aspiration (EBUS-FNA) cytology and EBUS-miniforceps biopsy (MFB) have emerged as less invasive tools for evaluating mediastinal lymph nodes and pulmonary lesions. The aim of this study is to compare the diagnostic yields of EBUS-FNA cytology to EBUS-MFB. STUDY DESIGN: A retrospective cohort study was performed by reviewing the database at our institution between December 12, 2010, and August 10, 2012. A total of 476 consecutive cases were identified. Of these, 227 patients had concurrent FNA and MFB taken during the procedure. The results and diagnostic yields of both techniques are calculated. RESULTS: Of the 476 cases, the mean age was 62 ± 14 years with 53% being males. In 453 of the total cases, the less invasive FNA technique alone produced enough diagnostic cytology material negating the need for concurrent MFB. Of these FNA cases, 280 were diagnosed as malignant neoplasms. The diagnostic yield of EBUS-FNA cytology was comparable to EBUS-MFB (95% FNA and 94% MFB). There were discordant diagnoses between cytology and histology in 19 of the 227 (∼8.4%) cases. CONCLUSIONS: EBUS-FNA cytology is a more efficacious diagnostic modality compared to EBUS-MFB.

Comparative analysis of plan quality and delivery efficiency: ZAP-X vs. CyberKnife for brain metastases treatment.

Purpose/Objectives: ZAP-X, a novel and dedicated radiosurgery (SRS) system, has recently emerged, while CyberKnife has solidified its position as a versatile solution for SRS and stereotactic body radiation therapy over the past two decades. This study aims to compare the dosimetric performance and delivery efficiency of ZAP-X and CyberKnife in treating brain metastases of varying target sizes, employing circular collimation. Methods and materials: Twenty-three patients, encompassing a total of 47 brain metastases, were included in the creation of comparative plans of ZAP-X and CyberKnife for analysis. The comparative plans were generated to achieve identical prescription doses for the targets, while adhering to the same dose constraints for organs at risk (OAR). The prescription isodose percentage was optimized within the range of 97-100% for each plan to ensure effective target-volume coverage. To assess plan quality, indices such as conformity, homogeneity, and gradient (CI, HI, and GI) were computed, along with the reporting of total brain volumes receiving 12Gy and 10Gy. Estimated treatment time and monitor units (MUs) were compared between the two modalities in evaluating delivery efficiency. Results: Overall, CyberKnife achieved better CI and HI, while ZAP-X exhibited better GI and a smaller irradiated volume for the normal brain. The superiority of CyberKnife's plan conformity was more pronounced for target size less than 1 cc and greater than 10 cc. Conversely, the advantage of ZAP-X's plan dose gradient was more notable for target sizes under 10 cc. The homogeneity of ZAP-X plans, employing multiple isocenters, displayed a strong correlation with the target's shape and the planner's experience in placing isocenters. Generally, the estimated treatment time was similar between the two modalities, and the delivery efficiency was significantly impacted by the chosen collimation sizes for both modalities. Conclusion: This study demonstrates that, within the range of target sizes within the patient cohort, plans generated by ZAP-X and CyberKnife exhibit comparable plan quality and delivery efficiency. At present, with the current platform of the two modalities, CyberKnife outperforms ZAP-X in terms of conformity and homogeneity, while ZAP-X tends to produce plans with a more rapid dose falloff.

Prognostic utility of biopsy-based PTEN and ERG status on biochemical progression and overall survival after SBRT for localized prostate cancer.

Introduction/background: Phosphatase and tensin homolog (PTEN) genomic deletions and transmembrane protease, serine 2/v-ets avian erthyroblastosis virus E26 oncogene homolog (ERG) rearrangements are two of the most common genetic abnormalities associated with prostate cancer. Prior studies have demonstrated these alterations portend worse clinical outcomes. Our objective is to evaluate the impact of biopsy-determined PTEN losses and TMPRSS2-ERG fusion on biochemical progression-free survival (bPFS) and overall survival (OS) in patients who receive SBRT for localized prostate cancer. Methods/materials: Patients received SBRT for localized prostate cancer on a prospective quality-of-life (QoL) and cancer outcomes study. For each patient, the single biopsy core with the highest grade/volume of cancer was evaluated for PTEN and ERG abnormalities. Differences in baseline patient and disease characteristics between groups were analyzed using ANOVA for age and χ2 for categorical groupings. bPFS and OS were calculated using the Kaplan Meier (KM) method with Log-Rank test comparison between groups. Predictors of bPFS and OS were identified using the Cox proportional hazards method. For all analyses, p <0.05 was considered statistically significant. Results: Ninety-nine consecutive patients were included in the analysis with a median follow-up of 72 months. A statistically significant improvement in bPFS (p = 0.018) was observed for wild type ERG patients with an estimated 5-year bPFS of 94.1% vs. 72.4%. Regarding PTEN mutational status, significant improvements in were observed in both bPFS (p = 0.006) and OS (p < 0.001), with estimated 5-year bPFS rates of 91.0% vs. 67.9% and 5-year OS rates of 96.4% vs. 79.4%. When including both ERG and PTEN mutational status in the analysis, there were statistically significant differences in both bPFS (p = 0.011) and OS (p < 0.001). The estimated 5-year bPFS rates were 100%, 76.6%, 72.9%, and 63.8% for patients with ERG+/PTEN+, ERG-/PTEN+, ERG+/PTEN-, and ERG-/PTEN- phenotypes respectively. The estimated 5-year OS rates were 93.9%, 100%, 80.0%, and 78.7% for patients with ERG+/PTEN+, ERG-/PTEN+, ERG+/PTEN-, and ERG-/PTEN- phenotypes respectively. Conclusion: ERG rearrangements and PTEN deletions detected on biopsy samples are associated with poorer oncologic outcomes in prostate cancer patients treated with SBRT and merit further study in a dedicated prospective trial.

Telepathology in cytopathology: challenges and opportunities.

OBJECTIVE: Telepathology in cytopathology is becoming more commonly utilized, and newer technologic infrastructures afford the laboratory a variety of options. The options and design of a telepathology system are driven by the clinical needs. This is primarily focused on providing rapid on-site evaluation service for fine needle aspiration. STUDY DESIGN: The clinical requirements and needs of a system are described. Available tools to design and implement a telepathology system are covered, including methods of image capture, network connectivity and remote viewing options. RESULTS: The primary telepathology method currently used and described involves the delivery via a network connection of a live video image to a remote site which is passively viewed by an internet web-based browser. By utilizing live video information and a voice connection to the on-site location, the remote viewer can collect clinical information and direct their view of the slides. CONCLUSIONS: Telepathology systems for use in cytopathology can be designed and implemented with commercially available infrastructure. It is necessary for the laboratory to validate the designed system and adhere to the required regulatory requirements. Telepathology for cytopathology can be reliably utilized by adapting existing technology, and newer advances hold great promise for further applications in the cytopathology laboratory.

Serous cystadenoma of the pancreas with endoscopic ultrasound fine needle aspiration biopsy and surgical correlation.

OBJECTIVES: Endoscopic ultrasound (EUS) fine needle aspiration (FNA) biopsies are commonly used to diagnose tumors of the pancreas. Serous cystadenoma (SCA) is a benign neoplasm that is uncommon and accounts for 1-2% of all pancreatic neoplasms. STUDY DESIGN: Surgically excised SCAs with preoperative EUS FNA biopsy over a 10-year span were identified. Clinical data were collected, and cytomorphologic features reviewed retrospectively and correlated with surgical excision data. Original cytopathologic diagnoses and retrospectively reviewed cytomorphology features were recorded. RESULTS: Seventeen patients were identified. Original EUS FNA interpretation included 1 'unsatisfactory', 9 'negative for malignancy' and 7 'atypical' or greater; however, all cases were categorized as benign/negative or nondiagnostic on retrospective review. The cases were hypocellular and possessed variable (rare to few-moderate) groups of bland cuboidal epithelial cells embedded in granular debris. Mucosal sampling was present (7/17) and cell blocks were acellular (5/17). CONCLUSION: This is a large series of pancreas SCAs subjected exclusively to EUS FNA biopsy where all cases had surgical excision confirmation. The 17 cases had hypocellular aspirate smears with the majority showing few bland epithelial cells; however, this can limit definitive diagnosis based on the cytomorphologic evaluation alone. The aspirate smear pattern of EUS FNA of SCAs of the pancreas supports a benign/negative or nondiagnostic categorization.

Utilization of p40 (ΔNp63) with p63 and cytokeratin 5/6 immunohistochemistry in non-small cell lung carcinoma fine-needle aspiration biopsy.

OBJECTIVE: Specific subclassification of pulmonary non-small cell carcinoma (NSCCA) is clinically necessary, and the aim of this study is to examine the utilization of p40 (ΔNp63) in fine-needle aspiration (FNA) biopsy for lung NSCCA. STUDY DESIGN: Database files of the Washington University Medical Center were searched. Patients who underwent endobronchial ultrasound and CT FNA of a primary lung neoplasia were selected and immunohistochemistry (IHC) was performed. A panel of markers was utilized, including p40, p63, cytokeratin (CK) 5/6, thyroid transcription factor, and napsin. RESULTS: One hundred patients were identified and comprised 38 squamous cell carcinomas (SCCA), 46 adenocarcinomas (AdCA), and 16 NSCCA. For SCCA, p40 was positive in 34/38 cases (89%) and negative in 4/38 cases (11%); p63 was positive in 33/38 cases (87%) and negative in 5/38 cases (13%); CK5/6 was positive in 38/38 cases. For AdCA cases, p40 was negative, p63 was positive in 2 cases (5%) and CK5/6 was negative in 43/46 cases (92%). CONCLUSION: For NSCCA, p40 had 89% sensitivity and 100% specificity compared to p63 with 86% sensitivity and 96% specificity and CK5/6 with 100% sensitivity and 96% specificity. In the evaluation of FNA biopsy for pulmonary NSCCA, p40 is a useful IHC marker for neoplastic subclassification, with better specificity in comparison to p63.

Testosterone as a Biomarker for Quality of Life (QOL) Following Androgen Deprivation Therapy (ADT) and Stereotactic Body Radiotherapy (SBRT).

BACKGROUND: Androgen deprivation therapy (ADT) causes fatigue and sexual dysfunction. The time to testosterone recovery depends on patient and treatment-specific characteristics. The kinetics of testosterone recovery in men treated with neoadjuvant ADT and stereotactic body radiotherapy (SBRT) is not well established. This study seeks to characterize testosterone recovery and evaluate its relationship with the improvement in patient-reported hormonal and sexual function. METHODS: Institutional review board (IRB) approval was obtained for retrospective review of prospectively collected data. All patients with localized prostate cancer treated with short-course ADT (3-6 months of Leuprolide) and robotic SBRT (35-36.25 Gy in five fractions) at a single institution were included in this analysis. Testosterone levels were measured at the start of radiation, every 3 months for the first year, and every 6 months thereafter. Total testosterone recovery was defined as a serum level of >230 ng/dL. Sexual and hormonal function was recorded using the Expanded Prostate Index Composite (EPIC)-26 prior to ADT initiation, the first day of SBRT, and at each follow-up. The EPIC-26 subdomain scores were transformed to a 0-100 scale with higher scores reflecting less bother. RESULTS: Between January 2009 and May 2018, 122 men with a median age of 72 years (range: 55-89 years) received ADT followed by SBRT. Thirty-two percent (N=39) were black and 27% [N=39 were obese (BMI > 30)]. The median pre-SBRT testosterone level was 15 ng/dL (range: 3-89 ng/dL). Around 77% (N=94) of patients received 3 months of ADT. The median pre-ADT EPIC-26 Hormone and Sexual Domain Scores were 94 and 41, respectively. At 12 months, 71% (N=87) of patients recovered to a eugonadal state with a mean recovery time of 4 months post-SBRT. Hormonal and sexual subdomain scores declined significantly following ADT but recovered to within the minimally important difference (MID) for sexual and hormonal domain scores by 12 months post-SBRT. CONCLUSIONS: Testosterone recovery following short-course ADT with leuprolide and SBRT occurs rapidly in the majority of patients within one year after treatment. Quality of life domain improvements followed the testosterone recovery trend closely. Testosterone testing at follow-up appointments would allow for anticipatory counseling that may limit the bother associated with temporary quality of life decrements.

High-Risk Non-Small Cell Lung Cancer Treated With Active Scanning Proton Beam Radiation Therapy and Immunotherapy.

Purpose: Non-small cell lung cancer (NSCLC) is a deadly malignancy that is frequently diagnosed in patients with significant medical comorbidities. When delivering local and regional therapy, an exceedingly narrow therapeutic window is encountered, which often precludes patients from receiving aggressive curative therapy. Radiation therapy advances including particle therapy have been employed in an effort to expand this therapeutic window. Here we report outcomes with the use of proton therapy with curative intent and immunotherapy to treat patients diagnosed with high-risk NSCLC. Methods and Materials: Patients were determined to be high risk if they had severe underlying cardiopulmonary dysfunction, history of prior thoracic radiation therapy, and/or large volume or unfavorable location of disease (eg, bilateral hilar involvement, supraclavicular involvement). As such, patients were determined to be ineligible for conventional x-ray-based radiation therapy and were treated with pencil beam scanning proton beam therapy (PBS-PBT). Patients who demonstrated excess respiratory motion (ie, greater than 1 cm in any dimension noted on the 4-dimensional computed tomography simulation scan) were deemed to be ineligible for PBT. Toxicity was reported using the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Overall survival and progression-free survival were calculated using the Kaplan-Meier method. Results: A total of 29 patients with high-risk NSCLC diagnoses were treated with PBS-PBT. The majority (55%) of patients were defined as high risk due to severe cardiopulmonary dysfunction. Most commonly, patients were treated definitively to a total dose of 6000 cGy (relative biological effectiveness) in 30 fractions with concurrent chemotherapy. Overall, there were a total of 6 acute grade 3 toxicities observed in our cohort. Acute high-grade toxicities included esophagitis (n = 4, 14%), dyspnea (n = 1, 3.5%), and cough (n = 1, 3.5%). No patients developed grade 4 or higher toxicity. The majority of patients went on to receive immunotherapy, and high-grade pneumonitis was rare. Two-year progression-free and overall survival was estimated to be 51% and 67%, respectively. COVID-19 was confirmed or suspected to be responsible for 2 patient deaths during the follow-up period. Conclusions: Radical PBS-PBT treatment delivered in a cohort of patients with high-risk lung cancer with immunotherapy is feasible with careful multidisciplinary evaluation and rigorous follow-up.

Endoscopic ultrasound fine needle aspiration biopsy of celiac ganglia.

OBJECTIVE: Celiac ganglia are normal anatomic structures located in the region of the celiac artery and can vary in size from 5 mm to 4.5 cm. These nodules can be visualized by endoscopic ultrasound (EUS) and be subject to fine needle aspiration (FNA) biopsy. They can be identified in patients with and without underlying pathology and present a challenge in accurate interpretation. STUDY DESIGN: The hospital database was retrospectively searched for patients who had undergone EUS FNA and where a diagnosis of 'ganglia' was rendered. Clinical and demographic data were collected and the cases reviewed for cytomorphologic features. RESULTS: Aspirate smears were generally hypocellular with variable cellularity between aspirate passes, showing dispersed single large epithelioid cells with cytoplasmic pigmentation, small groups of bland stroma and spindled cells, as well as 'grape-like' groups with peripheral epithelioid cells and central stroma with spindled elements. CONCLUSION: EUS cannot always definitively identify celiac lesions and the use of EUS FNA can help to accurately classify these cases. In patients with known or suspected malignancy, the accurate identification of celiac ganglia by EUS FNA can have important patient management implications. EUS FNA can identify celiac ganglia and show the distinctive features of large pigmented epithelioid ganglion cells and background neural elements.

Chest CT for Breast Cancer Diagnosis.

Background: We report the results of our retrospective analysis of the ability of standard chest CT scans to correctly diagnose cancer in the breast. Methods: Four hundred and fifty-three consecutive women with chest CT scans (contrast and non-contrast) preceding mammograms within one year comprise the study population. All chest CT images were reviewed by an experienced fellowship-trained chest radiologist and mammograms by an experienced fellowship-trained mammographer without the benefit of prior or ancillary studies; only four mammographic views were included for analysis. The size, location, and shape of breast masses were documented; on CT, the average Hounsfield units were measured. On both imaging modalities, the presence of lymphadenopathy, architectural distortion, skin thickening, and microcalcifications were recorded. Ultimately, the interpreting radiologist was asked to decide if a biopsy was indicated, and these recommendations were correlated with the patient's outcome. Findings: Nineteen of four hundred and fifty-three patients had breast cancer at the time of the mammography. Breast masses were the most common finding on chest CT, leading to the recommendation for biopsy. Hounsfield units were the most important feature for discerning benign from malignant masses. CT sensitivity, specificity, and accuracy of CT for breast cancer detection was 84.21%, 99.3%, and 98.68% compared to 78.95%, 93.78%, and 93.16% for four-view mammography. Chest CT scans with or without contrast had similar outcomes for specificity and accuracy, but sensitivity was slightly less without contrast. Chest CT alone, without the benefit of prior exams and patient recall, correctly diagnosed cancer with a p-value of <0.0001 compared to mammography with the same limitations. Conclusion: Chest CT accurately diagnosed breast cancer with few false positives and negatives and did so without the need for patient recall for additional imaging.

Rationale for Utilization of Hydrogel Rectal Spacers in Dose Escalated SBRT for the Treatment of Unfavorable Risk Prostate Cancer.

In this review we outline the current evidence for the use of hydrogel rectal spacers in the treatment paradigm for prostate cancer with external beam radiation therapy. We review their development, summarize clinical evidence, risk of adverse events, best practices for placement, treatment planning considerations and finally we outline a framework and rationale for the utilization of rectal spacers when treating unfavorable risk prostate cancer with dose escalated Stereotactic Body Radiation Therapy (SBRT).

Allele-specific PCR with competitive probe blocking for sensitive and specific detection of BRAF V600E in thyroid fine-needle aspiration specimens.

OBJECTIVE: To detect BRAF V600E mutation in thyroid fine-needle aspiration (FNA) slides and needle rinses (NR). STUDY DESIGN: Tumor-enriched DNA was extracted from FNA smears, formalin-fixed paraffin-embedded (FFPE) sections, or NR specimens from 37 patients with confirmed papillary thyroid carcinoma or benign findings. An allele-specific primer selectively amplified the 1799 T>A BRAF mutation while simultaneously blocking amplification of wild-type (WT) BRAF with an unlabeled probe during PCR. Mutation detection was accomplished by melting analysis of the probe. RESULTS: Allele-specific/blocking probe PCR confirmed the BRAF mutation status for 20 of 24 paired FNA/FFPE samples previously tested by fluorescent probe real-time PCR. For the other 4 cases, the sensitive PCR method detected the BRAF mutation in all paired FNA/FFPE samples. Previously, the mutation had been detected in only the FFPE samples. The BRAF mutation was also detected in some NR specimens. CONCLUSION: Treatment of patients with thyroid nodules is guided by FNA biopsy, which can be scantly cellular, necessitating a sensitive test that can detect low levels of BRAF V600E mutation in a WT background. We report increased detection of BRAF V600E in FNA specimens using allele-specific/blocking probe PCR, which has an analytical sensitivity of 0.01%.

Lobar Gross Endobronchial Disease Predicts for Overall Survival and Grade 5 Pulmonary Toxicity in Medically Inoperable Early Stage Non-Small Cell Lung Cancer Patients Treated With Stereotactic Body Radiation Therapy.

PURPOSE: Stereotactic body radiation therapy (SBRT) is considered standard of care for medically inoperable early stage non-small cell lung cancer (ES-NSCLC). Central tumor location is a known risk factor for severe SBRT related toxicity. Bronchoscopy allows for visualization of the central airways prior to treatment. Five fraction SBRT approaches have been advocated to mitigate treatment induced toxicity. In this report, we examine the mature clinical outcomes of a diverse cohort of ES-NSCLC patients with both peripheral and central tumors treated with a conservative 5 fraction SBRT approach and evaluate the role of lobar gross endobronchial disease (LGED) in predicting overall survival and treatment-related death. METHODS: Medically inoperable biopsy-proven, lymph node-negative ES-NSCLC patients were treated with SBRT. Bronchoscopy was completed prior to treatment in all centrally located cases. The Kaplan-Meier method was used to estimate overall survival (OS), local control (LC), regional control (RC), distant metastasis free survival (DMFS) and disease-free survival (DFS). Overall survival was stratified based on clinical stage, histology, tumor location and LGED. Toxicities were scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0. RESULTS: From December 2010 to December 2015, 50 consecutive patients were treated uniformly with a 50 Gy in 5 fraction SBRT approach (tumor BED10 ≥ 100 Gy) and followed for a minimum of 5 years or until death. At a median follow up of 42 months for all patients, 3-year OS was 50%. Three-year OS did not statistically differ between stage I and stage II disease (51% vs. 47%; p=0.86), adenocarcinoma and squamous cell carcinoma (50% vs. 45%; p=0.68), or peripheral and central tumors (56% vs. 45%; p=0.46). Five central tumors were found to have LGED, and 3-year OS for this cohort was quite poor at 20%. Cox regression analysis identified LGED as a predictor of OS while controlling for age, stage and location (OR:4.536, p-value=0.038). Despite the relatively low dose delivered, treatment likely contributed to the death of 4 patients with central tumors. Lobar gross endobronchial disease was an independent predictor for grade 5 pulmonary toxicity (n=4, p=0.007). Specifically, 3 of the 5 patients with LGED developed fatal radiation-induced bronchial stricture. Three-year LC, RC, DMFS and DFS results for the group were similar to contemporary studies at 90%, 90%, 82% and 65%. CONCLUSIONS: Central location of ES-NSCLC is a well-established predictor for severe SBRT-related toxicity. Here we identify LGED as a significant predictor of poor overall survival and grade 5 pulmonary toxicity. The relatively high rates of severe treatment-related toxicity seen in patients with central ES-NSCLC may be due in part to LGED. Underlying LGED may cause irreparable damage to the lobar airway, unmitigated by SBRT treatment thus increasing the risk of severe treatment-related toxicity. These findings should be verified in larger data sets. Future prospective central ES-NSCLC clinical trials should require staging bronchoscopy to identify LGED and further assess its clinical significance.

Impact of Age on Patient-Reported Outcomes Following Stereotactic Body Radiation Therapy for Prostate Cancer.

Purpose Stereotactic body radiation therapy (SBRT) delivers large radiation doses to the prostate while minimizing exposure to adjacent normal tissues. Large fraction sizes may increase the risks of functional decrements. Elderly men may be at an increased risk of these toxicities due to poor baseline function and hence limited reserve. This study describes patient-reported outcomes following SBRT for clinically localized prostate cancer in the elderly. Methods Between 2007 and 2017, 179 hormone-naive elderly patients (≥ 70 years old) and 210 patients under 70 years old with clinically localized prostate cancer were treated with 35-36.25 Gy SBRT in five fractions utilizing the CyberKnife Radiosurgical System (Accuray Inc.). Quality of life (QOL) was assessed using the Expanded Prostate Index Composite-Short Form (EPIC-26) questionnaire at baseline and at 1, 3, 6, 12, 18, 24, 30, and 36 months following the completion of treatment. EPIC scores range from 0 to 100, with lower values representing worsening symptoms. Results EPIC scores in the elderly cohort mirrored those in the younger cohort. EPIC urinary obstructive/irritative scores declined at one month post-SBRT (mean change from baseline ≥70: -7.9; <70: -11.1) before returning to baseline at three months post-SBRT (mean change from baseline ≥70: -0.4; <70: -1.4). The EPIC urinary incontinence scores declined slowly over the three years following treatment without recovery (mean change from baseline ≥70: -6.6; <70: -4.8). EPIC Bowel scores transiently declined at one month post-SBRT (mean change from baseline ≥70: -8.5; <70: -9.1) and then experienced a second more protracted decline over the next three years without recovery (mean change from baseline ≥70: -4.5; <70: -1.8). Hormonal EPIC scores were not impacted by radiation treatment or age. Older men had lower baseline and post-treatment EPIC sexual summary scores at all time points. However, there was no clinically significant difference in the EPIC sexual bother score between younger and older men at baseline and following treatment. Conclusions In the first three years following treatment, the impact of SBRT treatment on patient-reported outcomes was minimal. Our findings suggest that SBRT for clinically localized prostate cancer should not be deferred in older men solely due to concerns of increased morbidity. Further studies should be conducted to evaluate the impact of age on outcomes or morbidity following SBRT.

Treatment Interruptions During Stereotactic Body Radiotherapy for Prostate Cancer.

BACKGROUND: During the course of radiation treatment for prostate cancer, patients may have unintentional interruptions in their treatment course due to a wide variety of factors. Stereotactic body radiation therapy (SBRT) decreases the number of treatments compared to conventionally fractionated radiation; hence, it has the potential to decrease treatment delays and non-completion. This study sought to determine the incidence of treatment delay and characterize the etiology and length in a large cohort of men treated with SBRT for their prostate cancer. METHODS: One thousand three hundred and thirty-six patients treated with SBRT from 2008 to 2021 at the Georgetown University Hospital for prostate cancer were included in this retrospective study. A treatment delay was defined as a patient requiring longer than 14 days to complete 5 fractions of SBRT. Non-completion was defined as patients treated with less than 5 fractions. In the patients who experienced delays, chart review was performed to characterize the length and etiology of each delay. Multivariate analysis was performed via binary logistic regression modeling on PSPP. RESULTS: All individuals in the cohort eventually completed the planned 5-fraction regimen. Thirty-three patients experienced a treatment delay. Median length of time to complete treatment was 11 days (range 5-155 days). In patients who experienced a delay, nearly half (45.5%) experienced only a one-day delay. The most common reason for a delay was a technical issue (48.5%), including the machine maintenance, fiducial misalignment, or inadequate pretreatment bowel preparation. Other reasons included unplanned breaks due to acute side effects (21.2%), logistical issues (18.2%), non-treatment related health issues (9.1%), and inclement weather (3.0%). There were no significant sociodemographic, oncologic, or treatment variables that predicted treatment interruption on multivariate analysis. CONCLUSIONS: The incidence of treatment interruptions in patients undergoing SBRT for their prostate cancer was low. Most treatment delays were short.

Volume of Disease as a Predictor for Clinical Outcomes in Patients With Melanoma Brain Metastases Treated With Stereotactic Radiosurgery and Immune Checkpoint Therapy.

PURPOSE/OBJECTIVES: Clinical trials of anti-Programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein (CTLA-4) therapies have demonstrated a clinical benefit with low rates of neurologic adverse events in patients with melanoma brain metastases (MBMs). While the combined effect of these immunotherapies (ITs) and stereotactic radiosurgery (SRS) has yielded impressive results with regard to local control (LC) and overall survival (OS), it has also been associated with increased rates of radiation necrosis (RN) compared to historical series of SRS alone. We retrospectively reviewed patients treated with IT in combination with SRS to report on predictors of clinical outcomes. MATERIALS AND METHODS: Patients were included if they had MBMs treated with SRS within 1 year of receiving anti-PD-1 and/or CTLA-4 therapy. Clinical outcomes including OS, LC, intracranial death (ID), and RN were correlated with type and timing of IT with SRS, radiation dose, total volume, and size and number of lesions treated. RESULTS: Twenty-nine patients with 171 MBMs were treated between May 2012 and May 2018. Patients had a median of 5 lesions treated (median volume of 6.5 cm3) over a median of 2 courses of SRS. The median dose was 21 Gy. Most patients were treated with ipilimumab (n = 13) or nivolumab-ipilimumab (n = 10). Most patients underwent SRS concurrently or within 3 months of receiving immunotherapy (n = 21). Two-year OS and LC were 54.4% and 85.5%, respectively. In addition, 14% of patients developed RN; however, only 4.7% of the total treated lesions developed RN. The median time to development of RN was 9.5 months. Patients with an aggregate tumor volume >6.5 cm3 were found to be at increased risk of ID (p = 0.05) and RN (p = 0.03). There was no difference in OS, ID, or RN with regard to type of IT, timing of SRS and IT, number of SRS courses, SRS dose, or number of cumulative lesions treated. CONCLUSIONS: In our series, patients treated with SRS and IT for MBMs had excellent rates of OS and LC; however, patients with an aggregate tumor volume >6.5 cm3 were found to be at increased risk of ID and RN. Given the efficacy of combined anti-PD-1/CTLA-4 therapy for MBM management, further study of optimal selection criteria for the addition of SRS is warranted.