Patterns of care and outcomes in small cell carcinoma of the prostate: A national cancer database analysis.

BACKGROUND: Small cell carcinoma (SCC) of the prostate is a rare, aggressive disease. Evidence is limited; however, the current standard of care is chemotherapy. The benefit of local treatment modalities is unknown. METHODS: We queried the National Cancer Database identifying all SCC/neuroendocrine cases of the prostate, excluding those with unknown nodal or metastatic status, unknown treatment, or those not receiving chemotherapy. Overall survival (OS) was calculated using Kaplan-Meier curves. Multivariable Cox proportional hazards model was used to identify factors associated with survival. A further subgroup analysis was performed on the utility of local therapy on survival in the nonmetastatic setting. RESULTS: Our final cohort included 657 patients with a median age of 68. Most patients had positive lymph nodes (60.1%) and metastatic disease (70.0%). Median survival was 12 months (95% confidence interval [95% CI], 11.1-13.3 months) with a median follow-up of 11.8 months. Metastatic disease, age greater than or equal to 70, omission of androgen deprivation therapy (ADT), and lower income (P < .05 for all) were all associated with reduced OS. Patients with prostate-specific antigen (PSA) greater than or equal to 33 ng/mL and those receiving ADT had better survival (P < .05). Those with nonmetastatic disease were more likely to undergo prostatectomy and/or prostatic/pelvic radiation (P < .0001). Prostatic/pelvic radiation in the nonmetastatic setting was associated with longer survival (P = .02). Though well powered, our study is limited by the selection bias inherent to all observational studies, despite the statistical methods utilized to reduce this effect. CONCLUSIONS: Although chemotherapy is the mainstay of treatment, radiation to the prostate/pelvis may be beneficial in the nonmetastatic setting. In addition to chemotherapy, ADT may benefit patients with an elevated PSA.

Management of brain metastases from large cell neuroendocrine carcinoma of the lung: improved outcomes with radiosurgery.

OBJECTIVES: Large cell neuroendocrine carcinoma (LCNEC) of the lung is a rare pulmonary tumor, having similar natural history and management strategy as small cell lung cancer. Therefore, the management of brain metastases in these patients has mirrored that of SCLC through the use of whole brain radiation therapy (WBRT). We used the National Cancer Database (NCDB) to look at predictors of stereotactic radiosurgery (SRS) and any potential differences in outcomes for patients with brain metastases from LCNEC. MATERIAL AND METHODS: We queried the NCDB from 2004 to 2015 for patients with LCNEC of the lung with brain metastases that received brain radiation. Univariable and multivariable analyses were performed to identify factors predictive of SRS use and overall survival (OS). Propensity-adjusted Cox proportional hazard ratios for survival were used to account for indication bias. RESULTS: Out of 9970 patients with LCNEC of the lung we identified 348 with brain metastases. Sixty-eight patients were treated with upfront SRS and 280 were treated with WBRT. Patients that were treated at an academic facility or received chemotherapy as part of upfront treatment were more likely to receive SRS. Univariable analysis revealed improved outcomes with SRS compared to WBRT, with a median OS of 11 months compared to 6 months, respectively (p = .007). Multivariable Cox regression with propensity score confirmed SRS to have improved survival (HR: 0.68, 95%CI: 0.51-0.91, p = .0093). Multivariable Cox regression with propensity score also identified younger age, receipt of chemotherapy, absence of extracranial disease and non-rural locations as additional predictors of improved OS. CONCLUSIONS: Treatment of brain metastases from LCNEC of the lung with SRS was associated with improved survival. For the appropriate patients, upfront treatment of limited brain metastases with SRS may be appropriate.

Utilization Patterns of Single-Fraction and Short-Course Radiotherapeutic Schedules in the Management of Bone Metastases.

Purpose: Bone metastases are common, occurring in 60% to 70% of patients with advanced malignancies. Historically, bone-directed radiation therapy regimens of 30 Gy over 10 fractions were used. However, prospective randomized data suggest equivalent pain relief with shorter-course regimens. The American Society for Radiation Oncology Choosing Wisely Campaign encourages clinicians to consider shorter-course palliative regimens in patients with limited prognosis. A retrospective analysis was performed to assess patterns of short-course and single-fraction radiation therapy during the past 5 years. Methods and Materials: We queried our electronic medical record (MOSAIQ) from 2016 to 2020 for patients with bone metastases who received palliative radiation therapy. Patients receiving >10 fractions or Medicare-approved palliative courses of radiation (30 Gy/10 fractions, 24 Gy/6 fractions, 20 Gy/5 fractions, 8 Gy/1 fraction) were included. Treatment department was defined as academic (n = 2) versus community (n = 12). Short-course treatment was defined as <6 fractions, whereas long-course included patients receiving >10 fractions. Patients were subdivided based on age and disease site. Physicians were grouped according to their year of residency completion. Multivariable logistic regression analysis identified predictors of short-course and single-fraction treatment. Results: We identified 1004 patients with 1768 bony metastases meeting inclusion criteria. The spine was the most common site, followed by pelvis/hip, extremity, and other site. Use of short-course treatment increased from 40% in 2016 to 50% in 2020. Single-fraction treatment increased from 7% in 2016 to 11% in 2020. Predictors of shorter courses included treatment at academic centers, more recent treatment, patient age >76 years, and nonspine anatomic site. Predictors of single-fraction treatment included treatment at academic centers, treating physician residency completion after 2010, patient age >76 years, and treatment to extremity or other site. Conclusions: Rates of short-course and single-fraction bone-directed radiation therapy increased within our health system over time. Treatment receipt at academic centers was associated with both short-course and single-fraction regimens. Physicians completing residency after 2010 were more likely to deliver single-fraction therapy.

Dosimetric benefits of dynamic conformal arc therapy-combined with active breath-hold in lung stereotactic body radiotherapy.

To test the hypothesis that dynamic conformal arc therapy (DCAT) in Monaco, compared with volumetric modulated arc therapy (VMAT), maintains plan quality with higher delivery efficiency for lung stereotactic body radiotherapy (SBRT) and to investigate dosimetric benefits of DCAT with active breath-hold (DCAT+ABH), compared with free-breathing (DCAT+FB) for varying tumor sizes and motions. Fifty DCAT plans were used for lung SBRT. Randomly selected 17 DCAT plans were evaluated with respect to the retrospectively generated volumetric modulated arc therapy (VMAT) plans. The maximum dose at 2 cm from planning target volume (PTV) in any direction (D2cm/Rx), the ratio of 50% prescription isodose volume to the PTV (R50%), conformity index (CI), the lung volume receiving ≥20 Gy (V20), and monitor unit (MU) were evaluated. A t-test was used to evaluate the difference of plan quality between DCAT and VMAT. Internal target volume (ITV)/integrated-gross target volume (GTV) attributed by intra-fraction motion and lung V20 were stratified for DCAT+ABH and DCAT+FB across varying GTVs. DCAT maintained plan quality (p = 0.154 for D2cm/Rx, p = 0.089 for R50%, p = 0.064 for CI, and p = 0.780 for lung V20) while reducing MUs up to 30% (p <0.001) from 2748 MU (VMAT) to 1868 MU (DCAT). DCAT+ABH, compared to DCAT+FB, reduced tumor motion, resulting in 19% volume reduction of PTV and 60% reduction in lung V20, on average. The difference in lung V20 between DCAT+ABH and DCAT+FB increased as the target size increased. The DCAT is a favorable approach compared with VMAT. These results support the utility of DCAT as a routine planning platform for lung SBRT, especially when utilized with respiratory motion management using the ABH.

Treatment of recalcitrant Darier's disease with electron beam therapy.

Darier's disease (DD) is difficult to treat and has no cure. Although many modalities have been investigated, treatment options to date are largely unsatisfactory. Side-effect profiles have limited the use of many of these therapies, as has their ability to target only limited areas of disease. Furthermore, the effectiveness of most available treatments seems to be highly individualized, varying with disease severity and offering little alteration in the natural course of the disease. The present study reports a case of severe DD that was poorly responsive to known therapeutic modalities but responded to electron beam radiotherapy, and recommends this therapeutic modality for localized areas of severe, recalcitrant symptomatic disease.

Trends in Radiation Fractionation for Bone Metastases: A Contemporary Nationwide Analysis.

PURPOSE: Radiation therapy remains an important palliative tool for patients with bone metastases. The guidelines from the American Society for Therapeutic Radiation Oncology recommend the use of fewer fractions based on randomized data. We used the National Cancer Database to examine trends in radiation fractionation for patients with bone metastases. METHODS AND MATERIALS: We queried breast, prostate, and non-small cell lung cancer in the National Cancer Database from 2010 to 2015 for patients with bone metastases at the time of diagnosis who received bone-directed radiation therapy of 8 Gy in 1 fraction, 20 Gy to 24 Gy in 5 to 6 fractions, 30 Gy in 10 fractions, or >30 Gy in 10 fractions. We tabulated the baseline characteristics, and a multivariable logistic regression analysis was used to identify predictors of single-fraction treatment. RESULTS: We identified 17,859 patients who met the study criteria. The median patient age was 67 years, and the majority of patients (67%) had primary prostate cancer. Most patients (62%) received spine treatment. Single-fraction treatment increased over time from 3% in 2010 to 7% by 2015. Use of more protracted courses (>30 Gy in 10 fractions) decreased from 34% to 15% over the same interval. The most commonly used regimen (50%-60% of cases) remained 30 Gy in 10 fractions. Predictors of single-fraction treatment included increased age, no systemic therapy, increasing distance from facility, treatment at an academic center, nonspine/nonskull metastasis, and more recent treatment year. CONCLUSIONS: Use of single-fraction radiation for bone metastases has increased steadily but still accounts for <10% of palliative courses. The use of more protracted regimens has decreased significantly, although 30 Gy in 10 fractions remains the most widely used regiment.

Utilization of Stereotactic Ablative Body Radiation Therapy for Intact Renal Cell Carcinoma: Trends in Treatment and Predictors of Outcome.

PURPOSE: Surgery is the standard-of-care treatment in patients with localized renal cell carcinoma (RCC), offering excellent chance of cure. However, there is a subset of patients who are ineligible for surgery and instead manage with ablative therapies, such as stereotactic ablative body radiation therapy (SABR). We used the National Cancer Database to examine trends in the use of SABR for inoperable RCC and identify any predictors of outcome. METHODS AND MATERIALS: We queried the National Cancer Database for patients with unresected RCC between 2004 and 2016 who were treated with SABR. Kaplan-Meier analyses were used to determine overall survival. Multivariable Cox regression was used to identify predictors of survival. RESULTS: We identified 347 patients meeting eligibility criteria. Median age was 74, and the majority of patients were clinical stage T1-2 (80%) and N0 (97%). The median tumor size was 3.8 cm (interquartile range [IQR], 2.8-5.2 cm). Six percent of patients received systemic therapy. The median dose of SABR was 45 Gy (IQR, 35-54 Gy) in 3 fractions (IQR, 1-5 fractions). The median follow-up was 36 months (IQR, 1-156 months). Predictors of decreased survival were age >74, larger tumors, and N1 or M1 disease. Median survival across the entire cohort was 58 months. Median survival was 92 months, 88 months, 44 months, and 26 months for primary tumors ≤2.5 cm, 2.6-3.5 cm, 3.5-5.0 cm, and >5.0 cm, respectively (P < .0001). CONCLUSIONS: SABR is being increasingly used for renal cell carcinoma across the United States with excellent outcomes in smaller tumors.

Adaptation of a Gamma Knife Icon stereotactic radiosurgery program in the face of the COVID-19 pandemic.

Objective: The COVID-19 pandemic necessitated drastic and rapid changes throughout the field of radiation oncology, some of which were unique to the discipline of radiosurgery. Guidelines called for reduced frame use and reducing the number of fractions. Our institution implemented these guidelines, and herein we show the resultant effect on patient treatments on our Gamma Knife Icon program. Methods: In early March 2020 we rapidly implemented suggested changes according to ASTRO and other consensus guidelines as they relate to stereotactic radiosurgery in the COVID-19 era. We reviewed the GK Icon schedule at our institution between January 01 and April 30, 2020. We documented age, condition treated, technique (frame vs. mask), and number of fractions. We then tabulated and graphed the number of patients, framed cases, and fractions delivered. Results: Seventy-seven patients were treated on the GK Icon over that period, for a total of 231 fractions. The number of unique patients varied from 18 (April) to 22 (January). Of the 77 patients only 5 were treated using a frame. The number of fractions per month decreased significantly over time, from 70 in January to 36 in April. Likewise, the percentage of single fraction cases increased from 4.5% per month in January to 67% in April. Conclusions: The results presented here show that it is possible to quickly and efficiently change work flows to allow for reduced fractionation and frame use in the time of a global pandemic. Multidisciplinary cooperation and ongoing communication are integral to the success of such programs.

Cancer Stem Cell Chemotherapeutics Assay for Prospective Treatment of Recurrent Glioblastoma and Progressive Anaplastic Glioma: A Single-Institution Case Series.

BACKGROUND: Chemotherapy-resistant cancer stem cells (CSC) may lead to tumor recurrence in glioblastoma (GBM). The poor prognosis of this disease emphasizes the critical need for developing a treatment stratification system to improve outcomes through personalized medicine. METHODS: We present a case series of 12 GBM and 2 progressive anaplastic glioma cases from a single Institution prospectively treated utilizing a CSC chemotherapeutics assay (ChemoID) guided report. All patients were eligible to receive a stereotactic biopsy and thus undergo ChemoID testing. We selected one of the most effective treatments based on the ChemoID assay report from a panel of FDA approved chemotherapy as monotherapy or their combinations for our patients. Patients were evaluated by MRI scans and response was assessed according to RANO 1.1 criteria. RESULTS: Of the 14 cases reviewed, the median age of our patient cohort was 49 years (21-63). We observed 6 complete responses (CR) 43%, 6 partial responses (PR) 43%, and 2 progressive diseases (PD) 14%. Patients treated with ChemoID assay-directed therapy, in combination with other modality of treatment (RT, LITT), had a longer median overall survival (OS) of 13.3 months (5.4-NA), compared to the historical median OS of 9.0 months (8.0-10.8 months) previously reported. Notably, patients with recurrent GBM or progressive high-grade glioma treated with assay-guided therapy had a 57% probability to survive at 12 months, compared to the 27% historical probability of survival observed in previous studies. CONCLUSIONS: The results presented here suggest that the ChemoID Assay has the potential to stratify individualized chemotherapy choices to improve recurrent and progressive high-grade glioma patient survival. IMPORTANCE OF THE STUDY: Glioblastoma (GBM) and progressive anaplastic glioma are the most aggressive brain tumor in adults and their prognosis is very poor even if treated with the standard of care chemoradiation Stupp's protocol. Recent knowledge pointed out that current treatments often fail to successfully target cancer stem cells (CSCs) that are responsible for therapy resistance and recurrence of these malignant tumors. ChemoID is the first and only CLIA (clinical laboratory improvements amendment) -certified and CAP (College of American Pathologists) -accredited chemotherapeutic assay currently available in oncology clinics that examines patient's derived CSCs susceptibility to conventional FDA (Food and Drugs Administration) -approved drugs. In this study we observed that although the majority of our patients (71.5%) presented with unfavorable prognostic predictors (wild type IDH-1/2 and unmethylated MGMT promoter), patients treated with ChemoID assay-directed therapy had an overall response rate of 86% and increased median OS of 13.3 months compared to the historical median OS of 9.1 months (8.1-10.1 months) previously reported [1] suggesting that the ChemoID assay may be beneficial in personalizing treatment strategies.

Stereotactic radiosurgery boost to the resection bed for oligometastatic brain disease: challenging the tradition of adjuvant whole-brain radiotherapy.

OBJECT: Whole-brain radiation therapy (WBRT) has been the traditional approach to minimize the risk of intracranial recurrence following resection of brain metastases, despite its potential for late neurotoxicity. In 2007, the authors demonstrated an equivalent local recurrence rate to WBRT by using stereotactic radiosurgery (SRS) to the operative bed, sparing 72% of their patients WBRT. They now update their initial experience with additional patients and more mature follow-up. METHODS: The authors performed a retrospective review of all cases involving patients with limited intracranial metastatic disease (< or = 4 lesions) treated at their institution with SRS to the operative bed following resection. No patient had prior cranial radiation and WBRT was used only for salvage. RESULTS: From November 2000 to June 2009, 52 patients with a median age of 61 years met inclusion criteria. A single metastasis was resected in each patient. Thirty-four of the patients each had 1 lesion, 13 had 2 lesions, 3 had 3 lesions, and 2 had 4 lesions. A median dose of 1500 cGy (range 800-1800 cGy) was delivered to the resection bed targeting a median volume of 3.85 cm(3) (range 0.08-22 cm(3)). With a median follow-up of 13 months, the median survival was 15.0 months. Four patients (7.7%) had a local recurrence within the surgical site. Twenty-three patients (44%) ultimately developed distant brain recurrences at a median of 16 months postresection, and 16 (30.7%) received salvage WBRT (8 for diffuse disease [> 3 lesions], 4 for local recurrence, and 4 for diffuse progression following salvage SRS). The median time to WBRT administration postresection was 8.7 months (range 2-43 months). On univariate analysis, patient factors of a solitary tumor (19.0 vs 12 months, p = 0.02), a recursive partitioning analysis (RPA) Class I (21 vs 13 months, p = 0.03), and no extracranial disease on presentation (22 vs 13 months, p = 0.01) were significantly associated with longer survival. Cox multivariate analysis showed a significant association with longer survival for the patient factors of no extracranial disease on presentation (p = 0.01) and solitary intracranial metastasis (p = 0.02). Among patients with no extracranial disease, a solitary intracranial metastasis conferred significant additional survival advantage (43 vs 10.5 months, p = 0.05, log-rank test). No factor (age, RPA class, tumor size or histological type, disease burden, extent of resection, or SRS dose or volume) was related to the need for salvage WBRT. CONCLUSIONS: Adjuvant SRS to the metastatic intracranial operative bed results in a local recurrence rate equivalent to adjuvant WBRT. In combination with SRS for unresected lesions and routine imaging surveillance, this approach achieves robust overall survival (median 15 months) while sparing 70% of the patients WBRT and its potential acute and chronic toxicity.

Alternative Medicine and Oncology: Erroneous Biochemical Failure Following Herbal Supplementation in Early-Stage Prostate Cancer.

Prostate-specific antigen (PSA) levels are routinely surveilled after oncologic intervention in patients with prostate cancer. Occasionally, PSA levels are elevated because of factors unrelated to disease recurrence, such as herbal supplement use. False-positive PSA elevations may confound the clinical picture and subsequent decision-making processes, potentially leading to unnecessary diagnostic and therapeutic interventions. In this case report, a patient with low-risk prostate cancer who was treated with low-dose-rate interstitial brachytherapy presented several years after treatment with an erroneously elevated PSA level after taking an herbal supplement. This case highlights the importance of a holistic approach to patient care, whereby tactful assessment of the psychosocial and spiritual aspects of health led to the identification of an uncommon but potentially morbid entity.

Linear Accelerator-Based Stereotactic Radiotherapy for Low-Grade Meningiomas: Improved Local Control With Hypofractionation.

BACKGROUND AND PURPOSE: Meningioma is a common type of benign tumor that can be managed in several ways, ranging from close observation, surgical resection, and various types of radiation. We present here results from a 10-year experience treating meningiomas with a hypofractionated approach. MATERIALS AND METHODS: We reviewed the charts of 56 patients treated with stereotactic radiosurgery (SRS) or hypofractionated stereotactic radiotherapy (SRT) from 2008 to 2017. A total of 46 (82%) patients had WHO Grade 1 disease and 10 (18%) had Grade 2. Outcomes that were analyzed included local control rates and the rate and grade of any reported toxicity. RESULTS: A total of 38 women and 18 men underwent SRS to a median dose of 15 Gy (n = 24) or hypofractionated SRT with a median dose of 25 Gy in five fractions (n = 34). Of the 56 patients, 22 had surgery before receiving treatment. The median follow-up was 36 (6-110) months. Local control at 2 and 5 years for all patients was 90% and 88%, respectively. Comparing fractionated to single-fraction treatment, there was improved local control with fractionation (91% vs 80% local control at 2 years, P = .009). There was one episode of late radionecrosis on imaging with associated symptoms after single-fraction treatment and one patient requiring resection of meningioma related to worsening symptoms (and local recurrence) after five-fraction SRT. CONCLUSIONS: This study provides further evidence for high rates of local control and minimal toxicity using a hypofractionated SRT approach, with improvement in local control through use of hypofractionation.

Tumor localization accuracy for high-precision radiotherapy during active breath-hold.

BACKGROUND: Conventionally fractionated and stereotactic body radiation therapy (SBRT) for thoracoabdominal tumors may utilize breath-hold techniques. However, there are concerns that differential amounts of inspired airflow may result in unplanned tumor dislocation and underdosing. Thus, we investigated tumor localization accuracy associated with lung volume variations during breath-hold treatment via an automated-gating interface. METHODS: Twelve patients received breath-hold treatment with the active breathing coordinator (ABC) through an automated-gating interface. All breath-hold volumes were recorded at CT simulation, setup imaging, and during treatment, and analyzed as a function of airflow rate into the ABC. The variation of breath-hold volumes was calculated for each fraction over entire course. Intrafraction target motion related to the breathing variation was investigated based on daily imaging acquired before the breath-hold treatment. Correlation between target location and breath-hold variation was statistically analyzed. RESULTS: The air volume held by the ABC increased as the airflow rate increased on inhalation and decreased on exhalation. The mean range of airflow rate was 0.77 L/s and 0.29 L/s in the conventionally fractionated and SBRT patients, respectively. The maximum air volume difference with respect to the reference volume at the CT simulation was 1.0 L for conventional fractionation and 0.16 L for SBRT. The target dislocation caused by 0.25 L of air volume difference was 6 mm for SBRT. Three patients showed significant correlation between the target location and breath-hold variations. CONCLUSIONS: This investigation shows that because variations in the breath-hold volume may cause target dislocation, patient-specific breath-hold setting is required to improve tumor localization accuracy.

Linear accelerator-based radiosurgery and hypofractionated stereotactic radiotherapy for brain metastasis secondary to gynecologic malignancies: A single institution series examining outcomes of a rare entity.

OBJECTIVE: The use of SRS and fSRT to determine overall survival, tumor control, and local-disease free progression in patient diagnosed with gynecologic brain metastasis. METHODS: In this retrospective review, 11 patients aged 50 to 85 (median age of 71) were treated with linear accelerator-based SRS and hypofractionated SRT for brain metastasis secondary to gynecologic malignancies. In total, 16 tumors were treated from 2007 to 2017. Patients were treated to a median dose of 24 Gy (range 15 to 30 Gy) in 3 Fx (range 1 to 5). Median follow-up from SRS or SRT was 4 months (range 3-38 months). RESULTS: The actuarial 1-year overall survival rate was 26% with a median overall survival of 8 months. In addition, 1-year actuarial local control rate was 83.3% and the 1-year distant brain control rate was 31%. One patient experienced toxicity that presented as seizures after 7 months (due to minimal edema) that required anticonvulsants. There was no other acute or late treatment-related toxicity.Conclusion: Linear-accelerator based SRS or fSRT is safe and effective for control of local tumor growth in brain metastases secondary to gynecologic malignancies. The course of disease remains aggressive as seen by poor overall survival and distant failure rate.

A 10-year experience of linear accelerator-based stereotactic radiosurgery/radiotherapy (SRS/SRT) for paraganglioma: A single institution experience and review of the literature.

OBJECTIVE: Patients with paragangliomas were treated with LINAC-SRS/SRT in this retrospective review to evaluate tumor control, clinical control, and toxicity. METHODS: 16 patients (median age = 65) with paragangliomas were treated with LINAC-SRS/SRT. Patients were treated to a median dose of 25 Gy in 5 Fx and were evaluated for long-term tumor control, symptom control, and toxicity. Median follow-up was 44 months. RESULTS: 16 paragangliomas with a median PTV of 11.7 cc were treated as above. All but 2 lesions were controlled at last follow-up, with a 5-year control rate of 88%. Eighty-one percent of patients reported improved or resolved symptoms after treatment. Toxicities included grade 2 vertigo in 1 patient and grade 3 headache from hydrocephalus requiring ventriculoperitoneal shunt. DISCUSSION: Linear accelerator based SRS/SRT appears to be an effective treatment option for paragangliomas. Recurrences in this cohort occurred 4-5 years after treatment, highlighting the importance of long term follow up.

IMRT planning and delivery incorporating daily dose from mega-voltage cone-beam computed tomography imaging.

The technology of online mega-voltage cone-beam (CB) computed tomography (MV-CBCT) imaging is currently used in many institutions to generate a 3D anatomical dataset of a patient in treatment position. It utilizes an accelerator therapy beam, delivered with 200 degrees gantry rotation, and captured by an electronic portal imager to account for organ motion and setup variations. Although the patient dose exposure from a single volumetric MV-CBCT imaging procedure is comparable to that from standard double-exposure orthogonal portal images, daily image localization procedures can result in a significant dose increase to healthy tissue. A technique to incorporate the daily dose, from a MV-CBCT imaging procedure, in the IMRT treatment planning optimization process was developed. A composite IMRT plan incorporating the total dose from the CB was optimized with the objective of ensuring uniform target coverage while sparing the surrounding normal tissue. One head and neck cancer patient and four prostate cancer patients were planned and treated using this technique. Dosimetric results from the prostate IMRT plans optimized with or without CB showed similar target coverage and comparable sparing of bladder and rectum volumes. Average mean doses were higher by 1.6 +/- 1.0 Gy for the bladder and comparable for the rectum (-0.3 +/- 1.4 Gy). In addition, an average mean dose increase of 1.9 +/- 0.8 Gy in the femoral heads and 1.7 +/- 0.6 Gy in irradiated tissue was observed. However, the V65 and V70 values for bladder and rectum were lower by 2.3 +/- 1.5% and 2.4 +/- 2.1% indicating better volume sparing at high doses with the optimized plans incorporating CB. For the head and neck case, identical target coverage was achieved, while a comparable sparing of the brain stem, optic chiasm, and optic nerves was observed. The technique of optimized planning incorporating doses from daily online MV-CBCT procedures provides an alternative method for imaging IMRT patients. It allows for daily treatment modifications where other volumetric tomographic imaging techniques may not be feasible and/or available and where accurate patient localization with a high degree of precision is required.

Hypofractionated image guided radiation therapy followed by prostate seed implant boost for men with newly diagnosed intermediate and high risk adenocarcinoma of the prostate: Preliminary results of a phase 2 prospective study.

PURPOSE: A phase 2 protocol was designed and implemented to assess the toxicity and efficacy of hypofractionated image guided intensity modulated radiation therapy (IG-IMRT) combined with low-dose rate 103Pd prostate seed implant for treatment of localized intermediate- and high-risk adenocarcinoma of the prostate. METHODS AND MATERIALS: This is a report of an interim analysis on 24 patients enrolled on an institutional review board-approved phase 2 single-institution study of patients with intermediate- and high-risk adenocarcinoma of the prostate. The median pretreatment prostate-specific antigen level was 8.15 ng/mL. The median Gleason score was 4 + 3 = 7 (range, 3 + 4 = 7 - 4 + 4 = 8), and the median T stage was T2a. Of the 24 patients, 4 (17%) were high-risk patients as defined by the National Comprehensive Cancer Network criteria, version 2016. The treatment consisted of 2465 cGy in 493 cGy/fraction of IG-IMRT to the prostate and seminal vesicles. This was followed by a 103Pd transperineal prostate implant boost (prescribed dose to 90% of the prostate volume of 100 Gy) using intraoperative planning. Five patients received neoadjuvant, concurrent, and adjuvant androgen deprivation therapy. RESULTS: The median follow-up was 18 months (range, 1-42 months). The median nadir prostate-specific antigen was 0.5 ng/mL and time to nadir was 16 months. There was 1 biochemical failure associated with distant metastatic disease without local failure. Toxicity (acute or late) higher than grade 3 was not observed. There was a single instance of late grade 3 genitourinary toxicity secondary to hematuria 2 years and 7 months after radiation treatment. There were no other grade 3 gastrointestinal or genitourinary toxicities. CONCLUSIONS: Early results on the toxicity and efficacy of the combination of hypofractionated IG-IMRT and low-dose-rate brachytherapy boost are favorable. Longer follow-up is needed to confirm safety and effectiveness.

Estimating the additive benefit of surgical excision to stereotactic radiosurgery in the management of metastatic brain disease.

BACKGROUND: There are limited data on the benefits of surgical tumor resection plus stereotactic radiosurgery (SRS) in comparison with SRS alone for patients with oligometastatic brain disease. OBJECTIVE: To determine the benefit of adding resection to SRS. METHODS: We reviewed 162 consecutive patients with oligometastatic brain disease, who underwent surgical tumor resection and SRS boost (n = 49) or SRS alone (n = 113). Patients receiving prior whole brain radiation therapy were excluded. Factors related to patient survival and time-to-local recurrence (TTLR) were determined by Cox regression. The effect of complete resection + SRS boost on survival was further explored by propensity score matching. RESULTS: The average age of the cohort was 65.3 years, it was 49.4% female, and included 260 brain tumors, of which 119 tumors were single. Seventy-three brain tumors recurred (28%). TTLR was related to radiation-sensitive pathology (hazards ratio [HR] = 0.34, P = .001), treatment volume (HR = 1.078/mL, P = .002), and complete tumor resection (HR = 0.37, P = .015). Factors related to survival were age (HR = 1.21/decade, P = .037), Eastern Cooperative Oncology Group performance score (HR = 1.9, P = .001), and complete surgical resection (HR = 0.55, P = .01). Propensity score matched analysis of complete surgical resection + SRS boost (n = 40) vs SRS alone (n = 80) yielded nearly identical survival results (HR = 0.52, P = .030) compared with the initial unmatched sample. Incomplete tumor resection had both median survival and TTLR equivalent to SRS alone. CONCLUSION: Complete surgical resection + SRS boost is associated with improved survival and reduced likelihood of local tumor recurrence in comparison with SRS alone. Incomplete resection did not improve survival or TTLR compared with SRS alone.

Combination of IG-IMRT and permanent source prostate brachytherapy in patients with organ-confined prostate cancer: GU and GI toxicity and effect on erectile function.

PURPOSE: To assess toxicity outcomes of image-guided intensity-modulated radiation therapy (IG-IMRT) combined with permanent prostate seed implant in a cohort of patients with localized prostate cancer. METHODS AND MATERIALS: A retrospective analysis was performed on 67 patients with the median pretreatment prostate-specific antigen level of 5.4. The Gleason score was less than 7 in 7 patients, 7 in 52 patients, and greater than 7 in 8 patients. The median followup was 28.2 months (range, 12-89.5 months). Treatment consisted of 45 (n=65) or 50.4 Gy (n=2) at 1.8 Gy/fraction of IG-IMRT to the prostate and seminal vesicles. Eight patients had simultaneous irradiation of pelvic lymph nodes to 45 (n=65) or 50.4 Gy (n=2). After IG-IMRT, patients received transperineal prostate implant boost with either (103)Pd (n=65, the prescribed D(90) of 100 Gy) or (125)I (n=2, D(90) of 110 Gy). Eleven patients received androgen deprivation therapy with radiotherapy. RESULTS: Toxicity higher than Grade 3 was not observed. The combined incidence of acute and late Grade 3 genitourinary toxicity was 6%. The combined incidence of acute and late Grade 3 gastrointestinal toxicity was 3%. At least one episode of gastrointestinal bleeding on followup, which could be attributed to radiation, was recorded in 14.9% of patients. For patients achieving erections before radiation, the 3-year Kaplan-Meier potency preservation rate was 66.5%. CONCLUSIONS: The early toxicity of the combination of IG-IMRT and low-dose rate brachytherapy boost in this study was favorable.

Audiometric outcomes for acoustic neuroma patients after single versus multiple fraction stereotactic irradiation.

OBJECTIVE: To compare tumor control and changes in audiometric parameters of acoustic neuroma patients treated with either linac-based stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT) at Allegheny General Hospital. STUDY DESIGN: Twenty-three patients with acoustic neuroma were treated between February 2003 and April 2009 with either SRS (n = 13) or SRT (n = 10). The median age for all patients was 69 years and the median size of lesions was 1.2 cm (range 0.5-2.2 cm). The prescribed dose was a single dose of 1250 cGy for all SRS patients compared to 2500 cGy in 5 daily fractions for SRT patients. All patients had pre- and post-procedure audiometry including hearing acuity assessed using pure tone average (PTA), speech discrimination score (SDS), and speech reception threshold (SR). The results of treatment type and tumor variables resulting in hearing degradation were evaluated and compared. RESULTS: At a median follow-up of 13 months (range 3-36 months), only 1 of 13 patients treated with SRS and 2 of 10 patients treated with SRT develped progression of disease. However; all patients developed deterioration in PTA, SDS, or SR on the treated side. There were no statistically significant audiometric differences between patients treated with SRT or SRS and tumor response was similar regardless of irradiation technique. CONCLUSION: Both SRS and SRT provide excellent local control rates for the treatment of acoustic neuroma. While SRS demonstrated a trend toward worsening of SDS and the treatment of lesions >1.2 cm demonstrated a trend toward worsening of PTA, neither reached statistical significance. Our data suggest that single dose irradiation using the SRS technique should be considered primarily for patient convenience. All patients treated with radiotherapy for acoustic neuromas should undergo formal hearing testing before and after treatment.