Toxicity After Stereotactic Body Radiation Therapy for Prostate Cancer in Patients With Inflammatory Bowel Disease: A Multi-institutional Matched Case-Control Series.

PURPOSE: To evaluate the safety of stereotactic body radiation therapy (SBRT) for prostate cancer in men with inflammatory bowel disease (IBD). METHODS AND MATERIALS: We queried a consortium database for patients with IBD receiving SBRT for prostate cancer between 2006 and 2012. Identified patients were matched with patients without a history of IBD in a 3:1 fashion based on dose, fractionation, use of androgen deprivation therapy, and age distribution. Logistic regression was used to evaluate the association between having IBD and experiencing acute and late gastrointestinal (GI) and genitourinary (GU) toxicities as scored on the Common Terminology Criteria for Adverse Events scale. Time to late toxicity was evaluated using proportional hazard Cox models. Our study was limited by absence of data on prostate size, baseline International Prostate Symptom Score, and rectal dose-volume histogram parameters. RESULTS: Thirty-nine patients with flare-free IBD at time of treatment (median follow-up 83.9 months) and 117 matched controls (median follow-up 88.7 months) were identified. A diagnosis of IBD was associated with increased odds of developing any late grade GI toxicity (odds ratio [OR] 6.11, P <.001) and GU toxicity (odds ratio 6.14, P < .001), but not odds of developing late grade ≥2 GI (P = .08) or GU toxicity (P = .069). Acute GI and GU toxicity, both overall and for grade ≥2 toxicities, were more frequent in men with IBD (P < .05). Time to late GI and GU toxicity of any grade was significantly shorter in patients with IBD (P < .001). Time to late grade ≥2 GU, but not grade ≥2 GI toxicity, was also shorter in patients with IBD (P = .044 for GU and P = .144 for GI). CONCLUSIONS: Patients with IBD who received SBRT for PCa had a higher likelihood of developing acute GI and GU toxicity, in addition to experiencing lower grade late toxicities that occurred earlier. However, patients with IBD did not have a higher likelihood for late grade ≥2 GI or GU toxicity after SBRT compared with the control cohort. Interpretation of this data are limited by the small sample size. Thus, men with IBD in remission should be properly counseled about these risks when considering SBRT.

A Three-Dimensional Bioabsorbable Tissue Marker for Volume Replacement and Radiation Planning: A Multicenter Study of Surgical and Patient-Reported Outcomes for 818 Patients with Breast Cancer.

BACKGROUND: Accurate identification of the tumor bed after breast-conserving surgery (BCS) ensures appropriate radiation to the tumor bed while minimizing normal tissue exposure. The BioZorb® three-dimensional (3D) bioabsorbable tissue marker provides a reliable target for radiation therapy (RT) planning and follow-up evaluation while serving as a scaffold to maintain breast contour. METHODS: After informed consent, 818 patients (826 breasts) implanted with the BioZorb® at 14 U.S. sites were enrolled in a national registry. All the patients were prospectively followed with the BioZorb® implant after BCS. The data collected at 3, 6, 12, and 24 months included all demographics, treatment parameters, and provider/patient-assessed cosmesis. RESULTS: The median follow-up period was 18.2 months (range, 0.2-53.4 months). The 30-day breast infection rate was 0.5 % of the patients (n = 4), and re-excision was performed for 8.1 % of the patients (n = 66), whereas 2.6 % of the patients (n = 21) underwent mastectomy. Two patients (0.2 %) had local recurrence. The patient-reported cosmetic outcomes at 6, 12, and 24 months were rated as good-to-excellent by 92.4 %, 90.6 %, and 87.3 % of the patients, respectively and similarly by the surgeons. The radiation oncologists reported planning of target volume (PTV) reduction for 46.2 % of the patients receiving radiation boost, with PTV reduction most commonly estimated at 30 %. CONCLUSIONS: This report describes the first large multicenter study of 818 patients implanted with the BioZorb® tissue marker during BCS. Radiation oncologists found that the device yielded reduced PTVs and that both the patients and the surgeons reported good-to-excellent long-term cosmetic outcomes, with low adverse effects. The BioZorb® 3D tissue marker is a safe adjunct to BCS and may add benefits for both surgeons and radiation oncologists.

Long-term Outcomes of Stereotactic Body Radiotherapy for Low-Risk and Intermediate-Risk Prostate Cancer.

Importance: Stereotactic body radiotherapy harnesses improvements in technology to allow the completion of a course of external beam radiotherapy treatment for prostate cancer in the span of 4 to 5 treatment sessions. Although mounting short-term data support this approach, long-term outcomes have been sparsely reported. Objective: To assess long-term outcomes after stereotactic body radiotherapy for low-risk and intermediate-risk prostate cancer. Design, Setting, and Participants: This cohort study analyzed individual patient data from 2142 men enrolled in 10 single-institution phase 2 trials and 2 multi-institutional phase 2 trials of stereotactic body radiotherapy for low-risk and intermediate-risk prostate cancer between January 1, 2000, and December 31, 2012. Statistical analysis was performed based on follow-up from January 1, 2013, to May 1, 2018. Main Outcomes and Measures: The cumulative incidence of biochemical recurrence was estimated using a competing risk framework. Physician-scored genitourinary and gastrointestinal toxic event outcomes were defined per each individual study, generally by Radiation Therapy Oncology Group or Common Terminology Criteria for Adverse Events scoring systems. After central review, cumulative incidences of late grade 3 or higher toxic events were estimated using a Kaplan-Meier method. Results: A total of 2142 men (mean [SD] age, 67.9 [9.5] years) were eligible for analysis, of whom 1185 (55.3%) had low-risk disease, 692 (32.3%) had favorable intermediate-risk disease, and 265 (12.4%) had unfavorable intermediate-risk disease. The median follow-up period was 6.9 years (interquartile range, 4.9-8.1 years). Seven-year cumulative rates of biochemical recurrence were 4.5% (95% CI, 3.2%-5.8%) for low-risk disease, 8.6% (95% CI, 6.2%-11.0%) for favorable intermediate-risk disease, 14.9% (95% CI, 9.5%-20.2%) for unfavorable intermediate-risk disease, and 10.2% (95% CI, 8.0%-12.5%) for all intermediate-risk disease. The crude incidence of acute grade 3 or higher genitourinary toxic events was 0.60% (n = 13) and of gastrointestinal toxic events was 0.09% (n = 2), and the 7-year cumulative incidence of late grade 3 or higher genitourinary toxic events was 2.4% (95% CI, 1.8%-3.2%) and of late grade 3 or higher gastrointestinal toxic events was 0.4% (95% CI, 0.2%-0.8%). Conclusions and Relevance: In this study, stereotactic body radiotherapy for low-risk and intermediate-risk disease was associated with low rates of severe toxic events and high rates of biochemical control. These data suggest that stereotactic body radiotherapy is an appropriate definitive treatment modality for low-risk and intermediate-risk prostate cancer.

Multicenter Trial of Stereotactic Body Radiation Therapy for Low- and Intermediate-Risk Prostate Cancer: Survival and Toxicity Endpoints.

PURPOSE: The radiobiology of prostate cancer may favor the extreme hypofractionation inherent in stereotactic body radiation therapy (SBRT); however, data from a large multicenter study are lacking. We therefore examined the hypothesis that dose-escalated SBRT can be safely administered across multiple institutions, with favorable 5-year disease-free survival (DFS) rates compared with historical controls. METHODS AND MATERIALS: Twenty-one centers enrolled 309 patients with prostate adenocarcinoma: 172 with low-risk (LR) and 137 with intermediate-risk (IR) disease. All were treated with a non-coplanar robotic SBRT platform using real-time tracking of implanted fiducials. The prostate was prescribed 40 Gy in 5 fractions of 8 Gy. We assessed toxicities using Common Terminology Criteria for Adverse Events (CTCAE) version 3 and biochemical failure using the "nadir + 2" definition. The study population yielded 90% power to identify excessive (>10%) rates of grade ≥3 genitourinary (GU) or gastrointestinal toxicities and, in the LR group, 80% power to show superiority in DFS over a 93% historical comparison rate. RESULTS: At a median follow-up of 61 months, 2 LR patients (1.2%) and 2 IR patients (1.5%) experienced grade 3 GU toxicities, far below the 10% toxicity rate deemed excessive (upper limits of 95% confidence interval, 3.5% and 4.3%, respectively). No grade 4 or 5 toxicities occurred. All grade 3 toxicities were GU, occurring 11 to 51 months after treatment. For the entire group, the actuarial 5-year overall survival rate was 95.6% and the DFS rate was 97.1%. The 5-year DFS rate was 97.3% for LR patients (superior to the 93% DFS rate for historical controls; P = .0008; lower limit of 95% confidence interval, 94.6%) and 97.1% for IR patients. CONCLUSIONS: Dose-escalated prostate SBRT was administered with minimal toxicity in this multi-institutional study. Relapse rates compared favorably with historical controls. SBRT is a suitable option for LR and IR prostate cancer.

Cumulative volumetric analysis as a key criterion for the treatment of brain metastases.

BACKGROUND: Recent studies have demonstrated diminished cognitive function, worse quality of life, and no overall survival benefit from the addition of adjuvant whole brain radiation therapy (WBRT) to stereotactic radiosurgery (SRS) in the management of brain metastases. This study analyzes the treatment outcome of SRS, specifically CyberKnife Radiosurgery, based on the total tumor volume compared to the absolute number of lesions. METHODS: A retrospective analysis of hospital records at Virginia Hospital Center for patients with brain metastases who underwent CyberKnife Radiosurgery between June 2008 and June 2014 was performed. Previous treatment history, metastatic tumor dimensions, and outcomes were recorded. Predictors of neurological defects, local tumor progression, and overall survival were assessed with univariate and multivariate analysis. RESULTS: We identified 130 adult patients with a median age of 61.5years and a median follow-up of 7.1months. Unfavorable outcomes such as death, tumor progression, or neurological defect showed correlation with cumulative tumor volume greater than the median volume of 7cc (p<0.05). Worsening neurological defects showed an association with an increased number of lesions (p<0.02) and age (p<0.05). For local tumor progression, patients who have received WBRT were less likely to progress (.74, 95% CI, .48, 1.10), while those who received chemotherapy (1.48 95% CI, .98, 2.26), or surgery (1.56 95%, CI .98, 2.47) without WBRT were more likely to progress. CONCLUSIONS: Our data suggest that a cumulative tumor volume greater than 7cc correlates with worse outcomes following CyberKnife Radiosurgery. In addition, WBRT appears to have a role in improved survival for patients with increased tumor burden. A prospective study is warranted to validate these findings.

Comparative dosimetric findings using accelerated partial breast irradiation across five catheter subtypes.

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.

Sexual, irritative, and voiding outcomes, following stereotactic body radiation therapy for prostate cancer.

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.

Hypofractionated stereotactic body radiation therapy for elderly patients with stage IIB-IV nonsmall cell lung cancer who are ineligible for or refuse other treatment modalities.

OBJECTIVE: In elderly patients with stage IIB-IV nonsmall cell lung cancer who cannot tolerate chemotherapy, conventionally fractionated radiotherapy is the treatment of choice. We present our experience with hypofractionated stereotactic body radiation therapy (SBRT) in the treatment of this patient population. METHODS: Thirty-three patients with a median age of 80 years treated with fractionated SBRT were retrospectively analyzed. Most patients were smokers and had preexisting lung disease and either refused treatment or were ineligible. A median prescribed dose of 40 Gy was delivered to the prescription isodose line over a median of five treatments. The majority of patients (70%) did not receive chemotherapy. RESULTS: With a median follow-up of 9 months (range: 4-40 months), the actuarial median overall survival (OS) and progression-free survival were 12 months for both. One year actuarial survival outcomes were 75%, 58%, 44%, and 48% for local control, regional control, progression-free survival, and OS, respectively. Increased volume of disease was a statistically significant predictor of worse OS. Three patients developed a grade 1 cough that peaked 3 weeks after treatment and resolved within 1 month. One patient developed grade 1 tracheal mucositis and three patients developed grade 1 pneumonitis. Both resolved 6 weeks after treatment. Three patients died within the first month of treatment, but the cause of death did not appear to be related to the treatment. CONCLUSION: Hypofractionated SBRT is a relatively safe and convenient treatment option for elderly patients with inoperable stage IIB-IV nonsmall cell lung cancer. However, given the small sample size and the heterogeneity of the patient population, larger studies are needed before adopting this treatment option into clinical practice.

Dose escalation with stereotactic body radiation therapy boost for locally advanced non small cell lung cancer.

INTRODUCTION: Low survival outcomes have been reported for the treatment of locally advanced non small cell lung cancer (LA-NSCLC) with the standard of care treatment of concurrent chemoradiation (cCRT). We present our experience of dose escalation using stereotactic body radiosurgery (SBRT) following conventional cCRT for patients with LA-NSCLC. METHODS: Sixteen patients with a median age of 67.5 treated with fractionated SBRT from 2010 to 2012 were retrospectively analyzed. Nine (56%) of the patients had stage IIIB, 6 (38%) has stage IIIA, and 1 (6%) had recurrent disease. Majority of the patients (63%) presented with N2 disease. All patients had a PET CT for treatment planning. Patients received conventional cCRT to a median dose of 50.40 Gy (range 45-60) followed by an SBRT boost with an average dose of 25 Gy (range 20-30) given over 5 fractions. RESULTS: With a median follow-up of 14 months (range, 1-14 months), 1-year overall survival (OS), progression free survival (PFS), local control (LC), regional control (RC), and distant control (DC) rates were, 78%, 42%, 76%, 79%, and 71%, respectively. Median times to disease progression and regional failure were 10 months and 18 months, respectively. On univariate analysis, advanced age and nodal status were worse prognostic factors of PFS (p < 0.05). Four patients developed radiation pneumonitis and one developed hemoptysis. Treatment was interrupted in one patient who required hospitalization due to arrhythmias and pneumonia. CONCLUSION: Risk adaptive dose escalation with SBRT following external beam radiotherapy is possible and generally tolerated treatment option for patients with LA-NSCLC.

Robotic stereotactic body radiation therapy for elderly medically inoperable early-stage non-small cell lung cancer.

INTRODUCTION: Stereotactic body radiation therapy (SBRT) is being increasingly applied in the treatment of non-small cell lung cancer (NSCLC) because of its high local efficacy. This study aims to examine survival outcomes in elderly patients with inoperable stage I NSCLC treated with SBRT. METHODS: A total of 31 patients with single lesions treated with fractionated SBRT from 2008 to 2011 were retrospectively analyzed. A median prescribed dose of 48 Gy was delivered to the prescription isodose line, over a median of four treatments. The median biologically effective dose (BED) was 105.6 (range 37.50-180), and the median age was 73 (65-90 years). No patient received concurrent chemotherapy. RESULTS: With a median follow up of 13 months (range, 4-40 months), the actuarial median overall survival (OS) and progression-free survival (PFS) were 32 months, and 19 months, respectively. The actuarial median local control (LC) time was not reached. The survival outcomes at median follow up of 13 months were 80%, 68%, and 70% for LC, PFS, and OS, respectively. Univariate analysis revealed a BED of >100 Gy was associated with improved LC rates (P = 0.02), while squamous cell histology predicted for worse LC outcome at median follow up time of 13 months (P = 0.04). Increased tumor volume was a worse prognostic indicator of both LC and OS outcomes (P < 0.05). Finally, female gender was a better prognostic factor for OS than male gender (P = 0.006). There were no prognostic indicators of PFS that reached statistical significance. No acute or subacute high-grade toxicities were documented. CONCLUSION: SBRT is a safe, feasible, and effective treatment option for elderly patients with inoperable early stage NSCLC. BED, histology, and tumor size are predictors of local control, while tumor size and gender predict OS.

Effect of tumor bulk on local control and survival of patients with T1 glottic cancer: a 30-year experience.

PURPOSE: To evaluate the effect of tumor bulk on local control and survival of patients with T1 glottic cancer. METHODS AND MATERIALS: Effects of tumor bulk, T-stage, anterior-commissure involvement, treatment duration, and fraction size were analyzed in 208 patients; 136 had small tumors and 72 had bulky tumors. Anterior-commissure was involved in 54 patients. Treatment duration ranged from 39 to 64 days and fraction size ranged from 1.8 to 2.0 Gy. Median follow-up was 5.1 years. RESULTS: Five-year actuarial local control rates were 86.1% and 91.4% after radiotherapy and salvage laryngectomy. On univariate analysis, local control rates were 92.6% and 73.6% for small and bulky tumors (p = 0.03), 89.6% and 75.9% for patients without and with anterior-commissure involvement (p = 0.01), 92.6% and 75.6% when treatment duration was 50 days (p = 0.04), and 90.2% and 76.4% with 2 Gy and 1.8 Gy (p = 0.02) per fraction. On multivariate analysis, tumor bulk was the only significant factor that affected local control (p = 0.007). Ultimate local control rates after salvage were 97.1% and 80.5% for patients with small and bulky tumors. Disease-free survival rates at 5 years for small and bulky tumors were 96.3% and 84.7% (p = 0.001). Median duration to recurrence for small tumors was 30 months as compared with 11 months for bulky tumors. CONCLUSION: Tumor bulk is a highly significant prognostic factor for radiation control of T1 glottic cancer. Patients with bulky tumors had lower local control and disease-free survival rates and shorter duration to recurrence than those with small tumors.