Sequential Diffusion Tensor Imaging and Magnetic Resonance Spectroscopy in Patients Undergoing Reirradiation for Progressive Diffuse Intrinsic Pontine Glioma.

PURPOSE: Diffusion tensor imaging for evaluation of white matter tracts is used with magnetic resonance spectroscopy (MRS) to improve management of diffuse intrinsic pontine glioma (DIPG). Changes in the apparent diffusion coefficient (ADC), fractional anisotropy (FA), and tumor metabolite ratios have been reported after initial radiation for DIPG, but these markers have not been studied sequentially in patients undergoing reirradiation for progressive DIPG. Here, we report a case series of 4 patients who received reirradiation for progressive DIPG on a prospective clinical trial in which we evaluated quantitative changes in FA, ADC, and tumor metabolites and qualitative changes in white matter tracts. METHODS AND MATERIALS: The median reirradiation dose was 25.2 Gy (24-30.8 Gy). Fiber tracking was performed using standard tractography analysis. The FA and ADC values for the corticospinal and medial lemniscus tracts were calculated before and after reirradiation. Multivoxel MRS was performed. Findings were correlated with clinical features and conventional MRI of tumors. RESULTS: All patients had an initial response to reirradiation as shown by a decrease in tumor size. In general, FA increased with disease response and decreased with progression, whereas ADC decreased with disease response and increased with progression. At second progression, the FA fold change relative to values during disease response decreased in both patients with available imaging at second progression. Visualization of tracts demonstrated robust reconstitution of previously disrupted paths during tumor response; conversely, there was increased fiber tract disruption and infiltration during tumor progression. The MRS analysis revealed a decrease in choline:creatinine and choline:N-acetylaspartate ratios during tumor response and increase during progression. CONCLUSIONS: Distinct changes in white matter tracts and tumor metabolism were observed in patients with DIPG undergoing reirradiation on a prospective clinical trial. Changes related to tumor response and progression were observed after 24 to 30.8 Gy reirradiation.

Survival impact of prolonged postoperative radiation therapy for patients with glioblastoma treated with combined-modality therapy.

BACKGROUND: Though conventionally fractionated chemoradiation (CRT) is well tolerated by selected patients with newly diagnosed glioblastoma (GBM), adverse health-related and nonhealth-related factors can lead to unplanned interruptions in treatment. The effects of prolonged time to completion (TTC) of radiation therapy (RT) on overall survival (OS) for these patients are unclear. METHODS: The National Cancer Database (NCDB) was queried for all adult patients with newly diagnosed GBM undergoing surgical resection followed by adjuvant CRT with conventionally fractionated RT (6000-6600 cGy in 30-33 fractions) from 2005 to 2012. TTC was defined as the interval from first to last fraction of RT. Recursive partitioning analysis (RPA) was used to determine a threshold for TTC of adjuvant RT. Cox proportional hazards modeling was used to identify covariates associated with OS. RESULTS: A total of 13489 patients were included in our cohort. Patients who completed adjuvant RT within the RPA-defined threshold of 46 days from initiation of RT (median OS: 14.0 months, 95% confidence interval (CI) 13.7 to 14.3 months) had significantly improved OS compared to patients with TTC of 47 days or greater (median OS: 12.0 months, 95% CI 11.4 to 12.6 months, P < .001). Delays in completing adjuvant RT were relatively common, with 15.0% of patients in our cohort having a TTC of RT of 47 days or greater. CONCLUSIONS: Delays in completing adjuvant RT were associated with a worse survival outcome. Any unnecessary delays in completing adjuvant RT should be minimized while ensuring the safe delivery of therapy.

The impact of timing of adjuvant therapy on survival for patients with glioblastoma: An analysis of the National Cancer Database.

The optimal timing of adjuvant chemoradiation after surgical resection of glioblastoma remains unknown. The National Cancer Database was queried for all patients diagnosed with glioblastoma from 2004 to 2012 who underwent surgical resection followed by adjuvant chemoradiation. Cox proportional hazards modeling was used to determine factors influencing survival. Optimal thresholds for time to initiation (TTI) of adjuvant therapy were determined using recursive partitioning analysis (RPA). A total of 16,335 patients were included. The RPA model identified an optimal threshold of 61 days to initiation of adjuvant therapy which was confirmed with randomly selected training and validation sets using conditional inference trees repeated 1000 times for robustness. Compared to patients who initiated adjuvant therapy within 61 days (median overall survival: 14.1 months, 95% CI 13.8-14.3 months), patients who initiated adjuvant therapy after day 61 (MOS: 12.0, CI: 10.7-12.9) had higher risk of death (p < 0.0001). For patients with glioblastoma, large increases in time to the initiation of adjuvant therapy leads to inferior survival with a threshold of 61 days or less following surgical resection.

A Phase 1/2 Trial of Reirradiation for Diffuse Intrinsic Pontine Glioma.

PURPOSE: To identify an optimal dose for reirradiation (reRT) of diffuse intrinsic pontine glioma. METHODS AND MATERIALS: ReRT dose levels were selected using an adaptive utility-based dose-finding method. The coprimary endpoints were toxicity (mild, moderate, high, or severe) and efficacy, evaluated 1 month after reRT. Efficacy was defined as improvements in imaging, clinical status, and quality of life. Secondary endpoints were progression-free and overall survival. Utility of each dose level was calculated based on a combined toxicity/efficacy score, ranging from 0 for (severe toxicity, no efficacy) to 100 for (mild toxicity, all 3 efficacy improvements). RESULTS: Twelve patients completed reRT at 3 dose levels: 24 Gy in 12 fractions (6 patients), 26.4 Gy in 12 fractions (4 patients), and 30.8 Gy in 14 fractions (2 patients). One patient treated at dose level 3 developed a grade 3 acute toxicity. Five of the 6 patients receiving 24 Gy demonstrated improvement in 2 of 3 efficacy domains, and the sixth demonstrated improvement in all efficacy domains. Of 4 patients receiving 26.4 Gy, 1 demonstrated no improvement, and 1 patient each demonstrated improvement in 1, 2, and 3 efficacy domains. Of 2 patients receiving 30.8 Gy, 1 demonstrated improvement in 3 efficacy domains, and 1 did not complete the quality of life and was not assessed. Mean utilities were 88 for dose level 1, 76 for dose level 2, and 25 for dose level 3. For all patients, the median overall survival was 19.5 months from initial diagnosis (95% confidence interval, 15.6-21.1 months), and the median progression-free survival was 4.5 months from the start of reRT (95% confidence interval, 2.7-6.2 months). CONCLUSIONS: ReRT can safely be delivered for progressive diffuse intrinsic pontine glioma. Clinical improvement was seen in almost all patients. Utility analysis suggests that a regimen of 24 Gy in 12 fractions is preferred.

Effect of time to simulation and treatment for patients with oropharyngeal cancer receiving definitive radiotherapy in the era of risk stratification using smoking and human papillomavirus status.

BACKGROUND: The effect of increasing time to definitive radiotherapy (RT) for patients with oropharyngeal squamous cell carcinoma (SCC) is unknown. METHODS: Nodal tumor volumes at staging and simulation were compared for patients with oropharyngeal SCC. Time from staging to initiation of RT was tabulated. The primary endpoint of interest was nodal progression at simulation. RESULTS: Increasing time to simulation was associated with nodal progression in 144 patients (r = 0.474; P < .001). Patients with human papillomavirus (HPV)-associated oropharyngeal SCC were more likely to have nodal progression (50% vs 26%; P = .008). A threshold of 32 days was associated (sensitivity 77.9% and specificity 60.2%) with nodal progression (P < .001). Increasing time from staging to treatment initiation was associated with a greater risk of distant failure (hazard ratio [HR] 4.157; 95% confidence interval [CI] 1.170-14.764) but not progression-free survival (PFS; P = .179) or overall survival (OS; P = .474). CONCLUSION: Increasing time before RT for patients with oropharyngeal SCC is associated with nodal progression and increased hazard of distant failure, although not PFS or OS in our population.

Increasing time to postoperative stereotactic radiation therapy for patients with resected brain metastases: investigating clinical outcomes and identifying predictors associated with time to initiation.

We sought to determine the impact of time to initiation (TTI) of post-operative radiosurgery on clinical outcomes for patients with resected brain metastases and to identify predictors associated with TTI. All patients with resected brain metastases treated with postoperative SRS or fractionated stereotactic radiation therapy (fSRT) from 2012 to 2016 at a single institution were reviewed. TTI was defined as the interval from resection to first day of radiosurgery. Receiver operating characteristic (ROC) curves were used to identify an optimal threshold for TTI with respect to local failure (LF). Survival outcomes were estimated using the Kaplan-Meier method and analyzed using the log-rank test and Cox proportional hazards models. Logistic regression models were used to identify factors associated with ROC-determined TTI covariates. A total of 79 resected lesions from 73 patients were evaluated. An ROC curve of LF and TTI identified an optimal threshold for TTI of 30.5 days, with an area under the curve of 0.637. TTI > 30 days was associated with an increased hazard of LF (HR 4.525, CI 1.239-16.527) but was not significantly associated with survival (HR 1.002, CI 0.547-1.823) or distant brain failure (DBF, HR 1.943, CI 0.989-3.816). Fifteen patients (20.5%) required post-operative inpatient rehabilitation. Post-operative rehabilitation was associated with TTI > 30 days (OR 1.48, CI 1.142-1.922). In our study of resected brain metastases, longer time to initiation of post-operative radiosurgery was associated with increased local failure. Ideally, post-op SRS should be initiated within 30 days of resection if feasible.

Neck dissection for unknown cancer of the head and neck in the era of chemoradiation.

PURPOSE: To report outcomes for patients with cervical lymph node metastases from an unknown primary site of the head and neck treated with either non-operative therapy or neck dissection followed by adjuvant therapy. MATERIALS AND METHODS: All patients with squamous cell carcinoma of an unknown primary site of the head or neck seen between 2003 and 2013 were reviewed. The Kaplan-Meier method was used to estimate overall survival, local recurrence free survival, loco-regional recurrence free survival, and progression free survival. The log-rank test and proportional hazards regression were used to analyze factors influencing outcomes. RESULTS: Of 2258 patients with a new diagnosis of head and neck cancer, no primary site was identified in 66 patients. Twenty-nine patients were treated with definitive non-operative therapy (15 with chemoradiation and 14 with radiation alone). Thirty-seven patients received an upfront neck dissection followed by adjuvant radiation or chemoradiation. Three-year loco-regional recurrence free survival, progression free survival, and overall survival were 55.9%, 55.4%, and 69.4% respectively. Patients treated with preoperative neck dissection had improved local recurrence free survival (96.7% vs 54.1%, p=0.003) and loco-regional recurrence free survival (82.2% vs 46.4%, p=0.068) compared to patients treated with definitive chemoradiation with no difference in overall survival (p=0.641). CONCLUSIONS: Neck dissection improved local and regional control but not overall survival in patients with unknown primary squamous cell carcinoma of the head and neck over non-operative therapy alone.

Patterns of care and predictors of adjuvant therapies in elderly patients with glioblastoma: An analysis of the National Cancer Data Base.

BACKGROUND: The objectives of this study were to characterize patterns of care and to identify predictors for adjuvant therapy in elderly patients with glioblastoma in the modern era. METHODS: The National Cancer Data Base was queried for patients aged 70 years and older with glioblastoma diagnosed from January 1, 2004 through December 31, 2012. Multinomial logistic regression was used to identify predictors for receiving adjuvant therapy. Survival outcomes were estimated using the Kaplan-Meier method and were analyzed using Cox regression models and the log-rank test. RESULTS: In total, 14,886 patients were identified. Of these, 8214 patients (55.2%) received combined-modality therapy with chemotherapy and radiation (CRT), 3955 (26.6%) received no adjuvant therapy, 2065 (13.9%) received radiation therapy (RT) alone, and 652 (4.4%) received chemotherapy (CT) alone after undergoing resection. The receipt of CRT increased in frequency over the study interval, from 40.3% in 2004 to 59.8% in 2012. Younger patients (ages 70-75 years) were more likely to receive CRT than no adjuvant therapy (P < .0001 for all other age groups) or adjuvant RT alone (P < .0001 for all other age groups). Combined-modality therapy with adjuvant CRT produced improved survival outcomes, and the highest median overall survival was 9.2 months. CONCLUSIONS: In this analysis of elderly patients who had glioblastoma diagnosed from 2004 through 2012, a significant increase in the receipt of combined-modality therapy was observed. Combined-modality treatment produces improved survival outcomes and should be considered as adjuvant treatment for carefully selected elderly patients. Cancer 2017;123:3277-84. © 2017 American Cancer Society.

High-dose versus weekly cisplatin definitive chemoradiotherapy for HPV-related oropharyngeal squamous cell carcinoma of the head and neck.

OBJECTIVES: To compare the outcomes and toxicity of high-dose cisplatin (HDC) versus weekly cisplatin (WC) definitive chemoradiotherapy (CRT) for patients with human papillomavirus (HPV) related oropharyngeal squamous cell carcinoma (SCCOPx). METHODS: All patients with p16 positive SCCOPx treated with definitive CRT with cisplatin between 2010 and 2014 at a single institution were retrospectively reviewed. CTCAE v 4.03 toxicity criteria were used. The Kaplan-Meier method was used to estimate event-free survival (EFS) and the overall survival (OS). RESULTS: Of the 55 patients included, 22 were patients treated with HDC at dose of 100mg/m2 on days 1 and 22; and the remaining 33 patients were treated with WC at 40mg/m2. Both cohorts received a median total dose of cisplatin of 200mg/m2. At median follow-up of 31months, there was one local failure and no distant failures in the HDC cohort. In the WC group, there were 6 total failures (2 local, 4 distant). Estimated 2-year EFS was better in HDC cohort as compared to WC (96% vs. 75%; p=0.04). There was no significant difference in 2-year OS (95% vs. 94%; p=0.40). Weight loss, gastric tube dependence at six months, acute renal injury and grade 3 or 4 hematological toxicity were all similar between both groups. CONCLUSIONS: HPV-related SCCOPx treated with definitive CRT with either HDC or WC had similar toxicity profile. HDC had better EFS when compared with WC and this seems to be driven by increased distant failure rates, although the OS was similar.

Peri-SRS Administration of Immune Checkpoint Therapy for Melanoma Metastatic to the Brain: Investigating Efficacy and the Effects of Relative Treatment Timing on Lesion Response.

OBJECTIVE: To investigate the efficacy of immune checkpoint therapy (ICT) administered with stereotactic radiosurgery (SRS) and determine the effects of relative treatment timing on lesion response. METHODS: A prospective institutional database of all patients with intact brain metastases treated with SRS from 2008 to 2015 was reviewed for patients diagnosed with malignant melanoma. Lesion response was determined using a modified RECIST v1.1 criteria. Patients were grouped according to if they received ICT and the timing of ICT relative to SRS. Cox regression was used to identify predictors of lesion failure (LF) and distant brain failure (DBF). The Wilcoxon rank-sum test was used to compare median lesion regression after SRS between treatment groups. RESULTS: Fifty-one patients with 167 metastases were evaluated. Eighteen patients (59 lesions) were treated with peri-SRS ICT with anticytotoxic T-lymphocyte-associated protein 4 or antiprogrammed cell death protein 1 therapy. Peri-SRS ICT was a significant favorable predictor for reduced hazard of LF (hazard ratio, 0.131; confidence interval, 0.028-0.610). Concurrent ICT given with SRS (hazard ratio, 0.364; confidence interval, 0.161-0.825) significantly predicted freedom from DBF. When quantitative lesion response was examined, peri-SRS ICT resulted in a significantly greater median percent lesion regression than did SRS alone at 1.5 (-30.7% vs. -14.6%; P = 0.018), 4 (-42.3% vs. -18.8%; P = 0.031), and 5 months after SRS (-52.01 vs. -14.9%; P = 0.002). CONCLUSIONS: ICT combined with SRS was associated with greater lesion regression of melanoma brain metastases and decreased LF. When given concurrently, combined SRS and ICT may result in improved freedom from DBF.

A Dose-Volume Response Model for Brain Metastases Treated With Frameless Single-Fraction Robotic Radiosurgery: Seeking to Better Predict Response to Treatment.

Purpose/Objective(s): To establish a dose-volume response relationship for brain metastases treated with single-fraction robotic stereotactic radiosurgery and identify predictors of local control. MATERIALS/METHODS: We reviewed a prospective institutional database of all patients treated for intact brain metastases with stereotactic radiosurgery alone using the CyberKnife robotic radiosurgery system from 2012 to 2015. Tumor response was determined based on Response Evaluation Criteria In Solid Tumors version 1.1. Survival was estimated using the Kaplan-Meier method. Logistic regression modeling was used to identify predictors of outcome and establish a dose-volume response relationship. Receiver operating characteristic curves were constructed to evaluate the predictive capability of the relationship. RESULTS: There were 357 metastases evaluated in 111 patients with a median diameter of 8.14 mm (2.00-40.77 mm). At 6 and 12 months, local control was 86.9% and 82.2%, respectively. For lesions of similar volumes, higher maximum dose, mean dose, and minimum dose (all P values <.05) predicted for better local control. Tumor volume and diameter were strongly correlated, and a dose-volume response relationship was constructed using mean dose per lesion diameter (Gy/mm) that was predictive of local control (odds ratio: 1.34, 95% confidence interval: 1.06-1.70). Area under the receiver operating characteristic curve for local control and mean dose by volume was 0.6199 with a threshold of 2.05 Gy/mm (local failure 7.6% above and 17.3% below 2.05 Gy/mm). CONCLUSION: A dose-volume response relationship exists for brain metastases treated with robotic stereotactic radiosurgery. Mean dose per volume is strongly predictive of local control and can be potentially useful during stereotactic radiosurgery plan evaluation while respecting previously established dose constraints.

Optimal epidural analgesia for patients diagnosed as having gynecologic cancer undergoing interstitial brachytherapy.

STUDY OBJECTIVE: To determine the optimal epidural analgesia for patients receiving interstitial brachytherapy (ISBT) for gynecologic cancers. DESIGN: Retrospective analysis. SETTING: Operating room and hospital ward. PATIENTS: Seventy-three patients diagnosed as having gynecologic cancer and undergoing ISBT. INTERVENTIONS: Twelve patients received ropivacaine alone, 14 patients received ropivacaine with fentanyl, and 45 patients received ropivacaine with hydromorphone by epidural infusion. MEASUREMENTS: Numeric Rating Scale pain scores, amounts of nonnarcotic and narcotic pain medications used in intravenous morphine equivalents (IVMEs), and amount of antiemetic or antipruritic medications used. MAIN RESULTS: Patients receiving ropivacaine alone had higher pain scores the morning of day 2 (4.2 vs 1.71 vs 0.6, P=.001), the afternoon of day 2 (4.9 vs 2.5 vs 1.7, P=.005), and the night of day 2 (2.4 vs 2.0 vs 0.6, P<.001). Patients receiving opioids in their epidural had lower pain scores on the night of placement (P=.050), the morning of day 2 (P<.001), the afternoon of day 2 (P=.002), and the night of day 2 (P<.001). Patients receiving ropivacaine alone used more oral narcotics than did those receiving ropivacaine with fentanyl or ropivacaine with hydromorphone on day 3 (5.9 vs 3.8 vs 2.8mg IVME) and received more intravenous opioids day 1 (5.8 vs 0.0 vs 0.7mg IVME, P=.004) and day 2 (20.6 vs 4.8 vs 1.0mg IVME, P=.042). There were no differences in antiemetic or diphenhydramine usage at any time point. No epidural complications occurred. CONCLUSIONS: For patients receiving ISBT for gynecologic cancer, epidural analgesia provides safe and effective pain control. Combined modality epidural analgesia improves pain control and lessens oral and intravenous opioid requirements without increased risk of adverse effects compared with epidural analgesia with local anesthetic alone.

Distribution of Cervical Lymph Node Metastases From Squamous Cell Carcinoma of the Oropharynx in the Era of Risk Stratification Using Human Papillomavirus and Smoking Status.

PURPOSE/OBJECTIVE(S): To investigate the factors contributing to the clinical presentation of oropharyngeal squamous cell carcinoma (OPSCC) in the era of risk stratification using human papilloma virus (HPV) and smoking status. METHODS AND MATERIALS: All patients with OPSCC presenting to our institutional multidisciplinary clinic from January 2009 to June 2015 were reviewed from a prospective database. The patients were grouped as being at low risk, intermediate risk, and high risk in the manner described by Ang et al. Variance in clinical presentation was examined using χ(2), Kruskal-Wallis, Mann-Whitney, and logistic regression analyses. RESULTS: The rates of HPV/p16 positivity (P<.001), never-smoking (P=.016), and cervical lymph node metastases (P=.023) were significantly higher for patients with OPSCC of the tonsil, base of tongue (BOT), or vallecula subsites when compared with pharyngeal wall or palate subsites. Low-risk patients with tonsil, base of tongue, or vallecula primary tumors presented with nodal stage N2a at a much higher than expected frequency (P=.007), and high-risk patients presented with tumor stage T4 at a much higher than expected frequency (P=.003). Patients with BOT primary tumors who were never-smokers were less likely to have clinically involved ipsilateral neck disease than were former smokers (odds ratio 1.8; P=.038). The distribution of cervical lymph node metastases was not associated with HPV/p16 positivity, risk group, or subsite. When these data were compared with those in historical series, no significant differences were seen in the patterns of cervical lymph node metastases for patients with OPSCC. CONCLUSIONS: For patients with OPSCC differences in HPV status, smoking history and anatomic subsite were associated with differences in clinical presentation but not with distribution of cervical lymph node metastases. Historical series describing the patterns of cervical lymph node metastases in patients with OPSCC remain clinically relevant.

Organ preservation with neoadjuvant chemoradiation in patients with orbit invasive sinonasal cancer otherwise requiring exenteration.

PURPOSE: We sought to determine if organ preservation (OP) with neoadjuvant chemoradiation (CRT) was feasible in patients with sinonasal cancer determined to require exenteration. MATERIALS AND METHODS: Twenty patients were determined to require exenteration for definitive treatment from 2005 to 2014. Fourteen patients underwent OP and 6 patients received exenteration with adjuvant CRT. Exenteration free survival (EFS), locoregional control (LRC), progression-free survival (PFS), and overall survival (OS) were estimated. RESULTS: Five patients (36%) receiving OP had complete disease response at time of surgery. With a median follow-up of 18.8 months, EFS was 62% at 2 years for patients undergoing OP. At 2 years, there were no significant differences in LRC, PFS or OS (all all p > 0.050) between the groups. Less grade 3 or greater toxicity was seen in patients undergoing OP (p = 0.003). Visual function was preserved in all patients undergoing OP. CONCLUSION: For patients with sinonasal cancer, OP may avoid exenteration, offering similar disease control and improved toxicity.

Stereotactic Ablative Radiotherapy for a Lung Metastasis in a Child With Ewing's Sarcoma.

Stereotactic ablative radiotherapy delivers a high dose of radiation to a small volume over several fractions. Although most commonly used as a treatment alternative to surgery in adult patients with primary lung cancer, its use has now been reported in children with metastatic disease to the lungs. We present the case of a child treated with stereotactic ablative radiotherapy to pulmonary metastases in preparation for a salvage stem cell transplant. The patient was treated to a dominant pulmonary nodule and successfully received his stem cell transplant, however he developed clinical and radiographic findings consistent with pneumonitis several months after treatment.

Computed tomography-planned interstitial brachytherapy for locally advanced gynecologic cancer: Outcomes and dosimetric predictors of urinary toxicity.

PURPOSE: To identify dosimetric predictors of outcome and toxicity in patients receiving CT-planned interstitial brachytherapy (ISBT) for gynecologic cancers. METHODS AND MATERIALS: Patients who received ISBT between 2009 and 2014 were reviewed. Demographic, disease specific, treatment, and toxicity data were collected. Logistic regression was used to model toxicity. A least absolute shrinkage and selection operator penalty was used to identify relevant predictors. Receiver operating characteristic curves were used to analyze the relation between dosimetric factors and urinary toxicity. RESULTS: Seventy-three patients received ISBT (21 at time of cancer recurrence and 52 at the first presentation). Thirty-six patients had cervical cancer, 16 had vaginal cancer, 13 had uterine cancer, and 8 had vulvar cancer. ISBT was performed using both high-dose-rate and low-dose-rate 192Ir sources (27 low dose rate and 46 high dose rate). With a median followup of 12 months, Grade 3 vaginal, urinary, and rectal toxicity occurred in 17.8%, 15.1%, and 6.8% of patients, respectively. No patients experienced Grade 4 or 5 toxicity. Dose to 0.1cc of urethra predicted for development of Grade 3 urinary toxicity (area under the curve of 0.81; 95% confidence interval: 0.66, 0.96). A 10% probability of a Grade 3 urinary toxicity associated with a dose of 23.1 equivalent dose in 2 Gy fractions (95% confidence interval: 9.51, 36.27 equivalent dose in 2 Gy fractions). CONCLUSIONS: ISBT is a safe treatment for gynecologic malignancies. The dose to 0.1cc significantly predicts for severe urinary toxicity. Our data suggests that dose to a small urethral volume may be the most significant predictor of urinary toxicity in patients receiving ISBT for gynecologic cancer.

Simultaneous integrated boost using stereotactic radiosurgery for resected brain metastases: rationale, dosimetric parameters, and preliminary clinical outcomes.

BACKGROUND: Radiosurgery has been shown to reduce the rates of local recurrence in the postoperative bed after the resection of brain metastases, but the ideal radiation dose has not been well defined. OBJECTIVE: To present dosimetric parameters and preliminary clinical outcomes for patients undergoing postoperative stereotactic radiosurgery (SRS) with simultaneous integrated boost (SIB) for brain metastases. METHODS AND MATERIALS: 3 patients underwent surgery for a dominant metastatic focus and had residual or recurrent disease in the resection cavity. Our technique delivered a low dose to the resection cavity with an SIB dose to the gross tumor. Clinical target volume (CTV) was the magnetic resonance (MR)-defined resection cavity. Gross tumor volume (GTV) was the MR-defined residual disease. No additional margin was added to either the resection cavity or the residual disease area. Doses ranged from 14-15 Gy for CTV and 17-18 Gy for GTV prescribed to the 71%-78% isodose line. A traditional postoperative radiosurgery plan was constructed for each patient, and dosimetric values were compared using the paired t-test. RESULTS: 3 patients were treated at our institution using SRS with SIB. No patient experienced local recurrence. 2 patients developed distant brain failure (mean, 3.5 months). No grade 3 or greater toxicities were observed. The volume of brain receiving 12 Gy was significantly reduced using SIB compared with traditional postoperative SRS (𝑃 = .04). There were no differences in the maximum dose delivered to the tumor (𝑃 = .15) and cavity (𝑃 = .13). The average mean cavity dose was 16.20 Gy using the SIB plan, compared with 19.71 Gy using the traditional plan (𝑃 = .05). CONCLUSIONS: In patients with either recurrent or residual disease following surgical resection, SRS using SIB is technically feasible and safe.

Computed tomography planned interstitial brachytherapy for recurrent gynecologic cancer.

PURPOSE: To report outcomes and identify predictors of toxicity in patients undergoing reirradiation with interstitial brachytherapy (ISBT) for recurrent cancers of the female reproductive tract. METHODS AND MATERIALS: Twenty-one patients received ISBT performed using (192)Ir sources (10 low dose rate and 11 high dose rate) at our institution between 2009 and 2013. Demographic, disease specific, treatment, toxicity, and outcome data were collected. Kaplan-Meier and proportional hazard models were used to estimate survival and logistic regression to model toxicity. A least absolute shrinkage and selection operator penalty was used to identify relevant predictors of outcome and toxicity. RESULTS: Eleven patients had uterine cancer, 7 patients had cervical cancer, and 3 patients had vulvar cancer. One-year actuarial freedom from local-regional failure, progression-free survival (PFS), and overall survival were 71.5%, 66.0%, and 82.2%, respectively. Tumor size was a significant predictor of worse PFS and overall survival (1 cm increase in tumor size = hazard ratio [HR], 1.61; 95% confidence interval [CI]: 1.16, 2.62 for PFS; HR, 2.02; 95% CI: 1.21, 3.38). Grade 3 or higher vaginal, urinary, and rectal toxicity occurred in 28.5%, 9.5%, and 19% of patients, respectively. Urethra D0.1cc predicted for grade 2 or higher urinary toxicity (one equivalent dose in 2 Gy fraction increase = HR, 1.156; 95% CI: 1.001, 1.335). CONCLUSIONS: Reirradiation with ISBT is both safe and effective. In patients with recurrent cancer, urethra D0.1cc predicts for increased urinary toxicity. Increased tumor size is a negative prognostic factor in patients receiving ISBT for cancer recurrence.

Tumor bed radiosurgery: an emerging treatment for brain metastases.

While typically used for treating small intact brain metastases, an increasing body of literature examining tumor bed directed stereotactic radiosurgery (SRS) is emerging. There are now over 1000 published cases treated with this approach, and the first prospective trial was recently published. The ideal sequencing of tumor bed SRS is unclear. Current approaches include, a neoadjuvant treatment before resection, alone as an adjuvant after resection, and following surgery combined with whole brain radiotherapy either as an adjuvant or salvage treatment. Based on available evidence, adjuvant stereotactic radiosurgery improves local control following surgery, reduces the number of patients who require whole brain radiotherapy, and is well tolerated. While results from published series vary, heterogeneity in both patient populations and methods of reporting results make comparisons difficult. Additional prospective data, including randomized trials are needed to confirm equivalent outcomes to the current standard of care. We review the current literature, identify areas of ongoing contention, and highlight ongoing studies.