Normal tissue dose and risk estimates from whole and partial breast radiation techniques.

PURPOSE: To compare radiation dose to organs at risk in patients with early-stage breast cancer treated with lumpectomy and intraoperative radiation therapy with CT-guided HDR brachytherapy (precision breast IORT; PB-IORT) and those treated with external beam whole breast irradiation (WB-DIBH) or partial breast irradiation (PB-DIBH) with deep inspiratory breath hold. METHODS: We retrospectively identified 52 consecutive patients with left-sided breast cancers treated with either PB-IORT (n = 17, 76% outer breast) on a phase I clinical trial, adjuvant PB-DIBH (n = 18, 56% outer breast, 6% cavity boost), or WB-DIBH (n = 17, 76% outer breast, 53% with lumpectomy cavity boost). Conventional (2 Gy/fraction) or moderate hypofractionation (2.66 Gy/fraction) was prescribed for the external beam cohorts and 12.5 Gy in 1 fraction to 1 cm from the balloon surface was prescribed to the HDR brachytherapy cohort. CT-based planning was used for all patients. Organ at risk doses and excess risk ratios (ERR) for secondary lung cancers, contralateral breast cancers, and cardiac toxicity were compared between treatment techniques. RESULTS: Compared to WB-DIBH and PB-DIBH, PB-IORT resulted in lower ipsilateral lung V5, V10, V20, mean, and max dose (P < .05). Mean ipsilateral lung BED3Gy was as follows: 1.32 Gy for PB-IORT, 4.33 Gy for WB-DIBH, 3.35 Gy for PB-DIBH. The ERR for lung cancer was lowest for PB-IORT (P < .001). There was significantly higher contralateral breast max dose but lower mean BED3Gy for WB-DIBH compared with PB-IORT (P = .012, P = .011, respectively). Mean contralateral breast BED3Gy was as follows: 0.10 Gy for PB-IORT, 0.06 Gy for WB-DIBH, and 0.08 Gy for PB-DIBH. The ERR for contralateral breast cancer was low for all breast techniques, but WB-DIBH showed lower ERR compared to PB-IORT (P = .019). Mean heart BED2Gy was higher with PB-IORT at 1.26 Gy compared to 0.48 Gy and 0.24 Gy for WB-DIBH and PB-DIBH, respectively (P < .001). CONCLUSIONS: Patients with early-stage breast cancer treated with PB-IORT and with tissue-sparing external beam techniques all received low organ at risk doses, but PB-IORT resulted in far lower ipsilateral lung dose compared with external beam techniques. Our data indicate the lowest mean contralateral breast BED in the WB-DIBH group, likely due to the simplicity of the field design in low-risk patients using tangential whole breast radiation. External beam using DIBH results in lowest heart dose, but all techniques were well within recommended heart constraints.

Leptomeningeal disease following stereotactic radiosurgery for brain metastases from breast cancer.

Leptomeningeal disease (LMD) is a highly aggressive and usually rapidly fatal condition. The purpose of this study is to identify clinical factors that can serve to predict for LMD at the time of stereotactic radiosurgery (SRS) for brain metastases from breast carcinoma. We conducted a retrospective review of patients with brain metastases from breast cancer treated with SRS from 1995 to 2014 at our institution. Clinical, radiographic, and dosimetric data were collected. LMD was diagnosed by cerebrospinal fluid (CSF) cytology or MRI demonstrating CSF seeding. Comparative statistical analyses were conducted using Cox proportional hazards regression, binary logistic regression, and/or log-rank test. 126 patients met inclusion criteria. Eighteen patients (14 %) developed LMD following SRS. From the time of SRS, the actuarial rate of LMD at 12 months from diagnosis of brain metastasis was 9 % (11 patients). Active disease in the chest at the time of SRS was associated with development of LMD (p = 0.038). Factors including receptor status, tumor size, number of intra-axial tumors, cystic tumor morphology, prior WBRT, active bone metastases, and active liver metastases were not significantly associated with the development of LMD. In patients with brain metastasis from breast cancer that undergo SRS, there is a relatively low rate of LMD. We found that while tumor hormonal status, bone metastases, and hepatic metastases were not associated with the development of LMD, active lung metastases at SRS was associated with LMD. Further research may help to delineate a causative relationship between metastatic lung disease and LMD.

A randomized trial evaluating a novel hydrogel packing system compared to standard packing during image-guided high-dose rate brachytherapy boost for cervical cancer.

INTRODUCTION: The purpose of this prospective randomized trial was to compare the use of a novel vaginal hydrogel packing system (BrachyGel) to standard vaginal packing (VP) during high dose rate (HDR) brachytherapy (BT) for locally advanced cervical cancer (LACC). METHODS: This cross-over study included LACC patients receiving HDR BT boost (intracavitary +/- interstitial). All patients received alternating gauze or BrachyGel VP on Arms A and B. Patients, physicians, and physicists evaluated BT characteristics via a 4-point Likert scale. Adverse events (AEs) were prospectively collected and scored per CTCAE. RESULTS: The 20 patients enrolled. The mean bladder D2cc difference between gauze and BrachyGel in Arm A was 0.117 Gray (Gy) and in Arm B 0.013 Gy. The mean difference in rectum D2cc in Arm A and Arm B was -0.189 Gy and -0.191 Gy, respectively. The mean dose to 90% of the high-risk clinical target volume (HR-CTV) for gauze compared to BrachyGel was -0.032 Gy (95% CI: 0.472, 0.409). Patient-reported discomfort was similar with BrachyGel and gauze ("mild/moderate" 70.0% vs 74.0%, respectively). The clarity of VP was similar between BrachyGel and gauze (86.8% vs 89.7%, respectively). The completeness of VP was more frequently "excellent/good" with BrachyGel (79.0%) compared to gauze (56.4%). The ease of packing was more frequently "extremely easy" with BrachyGel (21.2% vs 0%). No serious AEs were reported. CONCLUSION: This randomized trial found no clinically significant difference in OAR or HR-CTV dosimetry between BrachyGel and standard VP. BrachyGel performed well compared to gauze for the patient and physician use experience.

Evaluating the relationship between vaginal apex "dog ears" and patterns of recurrence in endometrial cancer following adjuvant image guided vaginal cuff brachytherapy.

PURPOSE: The aim of this investigation is to characterize vaginal apex "dog ears" and their association with patterns of treatment failure in patients with endometrial cancer treated with adjuvant high-dose-rate (HDR) single-channel vaginal cuff brachytherapy (VCB). METHODS: A retrospective review of patients treated with HDR VCB from 2012 to 2021 for medically operable endometrial cancer at a single institution was conducted. Dog ears, defined as tissue at the apex extending at least 10 mm from the brachytherapy applicator were identified on CT simulation images. Fisher exact test and a multivariate logistic regression model evaluated the association between factors of interest with treatment failure. Vaginal cuff failure free survival (VCFFS) was calculated from first brachytherapy to vaginal cuff recurrence (VCR). RESULTS: A total of 219 patients were reviewed. In this sample, 57.5% of patients met criteria for having dog ears. In total, 13 patients (5.9%) developed a VCR. There was no statistically significant difference in the rate of VCR between patients with and without dog ears (7.1% vs. 4.3%, p = 0.56). There was a trend toward increased risk of recurrence with higher grade histology identified in the multivariate logistic regression model (p = 0.085). The estimated 3-year probability of VCFFS was 86%. CONCLUSIONS: Vaginal apex dog ears are prevalent but are not found to statistically increase the risk of VCR after VCB in our single institution experience. However, while local failure remains low in this population, we report an absolute value of over twice as many VCRs in patients with dog ears, indicating that with improved dog ear characterization this may remain a relevant parameter for consideration in treatment planning.

Demystifying radiation oncology clinical trial concerns for protocol scientific review and institutional review board committee members.

Clinical trials are essential for evaluating advanced technologies and treatment approaches involving radiation therapy to improve outcomes for cancer patients. Clinical trials at cancer centers with designation from the National Cancer Institute must undergo scientific review in additional to Institutional Review Board approval. Given the highly specialized nature and rapidly advancing technologies of radiation therapy, and the small number of radiation oncology investigators at some centers, a lack of radiation oncology expertise among reviewers may present challenges at some cancer centers. This commentary aims to provide an overview of radiation therapy and special considerations for radiation oncology research that will serve as a helpful resource in the scientific review of clinical trials involving cancer patients.

Para-Aortic Nodal Radiation in the Definitive Management of Node-Positive Cervical Cancer.

OBJECTIVES: To investigate the safety and outcomes of elective para-aortic (PA) nodal irradiation utilizing modern treatment techniques for patients with node positive cervical cancer. METHODS: Patients with pelvic lymph node positive cervical cancer who received radiation were included. All patients received radiation therapy (RT) to either a traditional pelvic field or an extended field to electively cover the PA nodes. Factors associated with survival were identified using a Cox proportional hazards model, and toxicities between groups were compared with a chi-square test. RESULTS: 96 patients were identified with a mean follow up of 40 months. The incidence of acute grade ≥ 2 toxicity was 31% in the elective PA nodal RT group and 15% in the pelvic field group (Chi-square p = 0.067. There was no significant difference in rates of grade ≥ 3 acute or late toxicities between the two groups (p>0.05). The KM estimated 5-year OS was not statistically different for those receiving elective PA nodal irradiation compared to a pelvic only field, 54% vs. 73% respectively (log-rank p = 0.11). CONCLUSIONS: Elective PA nodal RT can safely be delivered utilizing modern planning techniques without a significant increase in severe (grade ≥ 3) acute or late toxicities, at the cost of a possible small increase in non-severe (grade 2) acute toxicities. In this series there was no survival benefit observed with the receipt of elective PA nodal RT, however, this benefit may have been obscured by the higher risk features of this population. While prospective randomized trials utilizing a risk adapted approach to elective PA nodal coverage are the only way to fully evaluate the benefit of elective PA nodal coverage, these trials are unlikely to be performed and instead we must rely on interpretation of results of risk adapted approaches like those used in ongoing clinical trials and retrospective data.

Recursive Partitioning Analysis for Local Control Achieved With Stereotactic Body Radiation Therapy for the Liver, Spine, or Lymph Nodes.

PURPOSE: This study aims to develop a local control risk stratification using recursive partitioning analysis (RPA) for patients receiving stereotactic body radiation therapy (SBRT) for metastatic cancer. METHODS AND MATERIALS: A single institutional database of 397 SBRT treatments to the liver, spine, and lymph nodes was constructed. All treatments required imaging follow-up to assess for local control. Cox proportional hazards analysis was implemented before the decision tree analysis. The data were split into training (70%), validation (10%), and testing (20%) sets for RPA to optimize the training set. RESULTS: In the study, 361 treatments were included in the local control analysis. Two-year local control was 71%. A decision tree analysis was used and the resulting model demonstrated 93.10% fidelity for the validation set and 87.67% for the test set. RPA class 3 was composed of patients with non-small cell lung cancer (NSCLC) primary tumors and treatment targets other than the cervical, thoracic, and lumbar spines. RPA class 2 included patients with primary cancers other than NSCLC or breast and treatments targets of the sacral spine or liver. RPA class 1 consisted of all other patients (including lymph node targets and patients with primary breast cancer). Classes 3, 2, and 1 demonstrated 3-year local controls rates of 29%, 50%, and 83%, respectively. On subgroup analysis using the Kaplan-Meier method, treatments for lymph nodes and primary ovarian disease demonstrated improved local control relative to other treatment targets (P < .005) and primary disease sites (P < .005), respectively. CONCLUSIONS: A local control risk stratification model for SBRT to sites of metastatic disease was developed. Treatment target and primary tumor were identified as critical factors determining local control. NSCLC primary lesions have increased local failure for targets other than the cervical, thoracic, or lumbar spines, and improved local control was identified for lymph node sites and breast or ovarian primary tumors.

Comparison of initial computed tomography-based target delineation and subsequent magnetic resonance imaging-based target delineation for cervical cancer brachytherapy.

PURPOSE: For cervical brachytherapy planning, magnetic resonance imaging (MRI) is preferable to computed tomography (CT) for target delineation. However, due to logistical and financial restrictions, in-room MRI is sometimes not routinely available in brachytherapy centers. Our institution has created a workflow that integrates MRI-based target delineation with an in-room CT scanner, with the aim of improving target coverage and conformality. This study reports the initial dosimetric results with using this workflow. MATERIAL AND METHODS: A retrospective review was performed on 46 consecutive patients who received definitive chemoradiation with 5 fraction intracavitary high-dose-rate (HDR) brachytherapy for cervical cancer. Fraction 1 was planned from CT only. Outpatient MRI was obtained after Smit sleeve placement and first insertion to assess concurrent chemoradiotherapy tumor response. This MRI was registered to the CT for planning fractions 2-5. The median prescription dose for the cohort was 25 Gy (range, 25-29 Gy). RESULTS: The D90 to the high-risk clinical target volume (HR-CTV) and D2cc rectal dose were increased from fraction 1 to fraction 2-5 averaged (p < 0.05). Among the 18 patients with complete volumetric data, there was no significant difference in HR-CTV size, with an average decrease of 1.73 cc (p > 0.05) with MRI fusion. Eleven out of 18 patients had changes in high-risk target volume greater than 20%, with an absolute average change in volume of 31.5%. CONCLUSIONS: The use of asynchronous MRI for target delineation, with co-registration to CT for each fraction of brachytherapy was associated with higher D90 to the HR-CTV. We observed slightly higher D2cc rectal doses with MRI, but cumulative rectal doses were within accepted thresholds. High-risk target volumes were not consistently increased or decreased, but MRI fusion was associated with target volume changes greater than 20% in over half of the treated patients.

Time-driven activity-based costing of adjuvant vaginal cuff brachytherapy for uterine cancer in an integrated brachytherapy suite.

PURPOSE: Adjuvant vaginal cuff brachytherapy is well tolerated and reduces the risk of local recurrence in endometrial cancer. However, there is provider variation in the number of radiation treatments, which ranges from three to six fractions. Using time-driven activity-based costing, we calculated the cost to deliver three vs six fractions to determine the value of each regimen at our brachytherapy suite with CT-on-rails. METHODS AND MATERIALS: Process maps were created to represent each step from initial consult to completion of therapy. Components of care included personnel, equipment, and consumable supplies. The capacity cost rate was determined for each resource and calculated for each regimen. RESULTS: The total direct costs to deliver three- and six-fraction treatment courses were $1,415 and $2,227, respectively. Personnel cost accounted for 63% of overall expenditures. Computed tomography simulation and planning, required for the first fraction, cost $232 for both regimens. Duties of the procedural nurse (scheduling, patient setup, and turnover) consumed the most time at 35% of total personnel minutes. CONCLUSIONS: Time-driven activity-based cost analysis revealed a 57% relative increase, but modest absolute increase, in delivery costs for six vs three fractions of brachytherapy at our institution. This current analysis may influence considerations of the relative value between the two treatment schedules, but this methodology should not be interpreted as informative for reimbursement policy evaluation.

STAT RAD: Prospective Dose Escalation Clinical Trial of Single Fraction Scan-Plan-QA-Treat Stereotactic Body Radiation Therapy for Painful Osseous Metastases.

PURPOSE: Radiation therapy is a well-established treatment for symptomatic bone metastases. Despite continued advances in both planning techniques and treatment delivery, the standard workflow has remained relatively unchanged, often requiring 1 to 3 weeks and resulting in patient inconvenience and delayed palliation. We developed an expedited method wherein computed tomography simulation, treatment planning, quality assurance, and treatment delivery are performed in 1 day. This prospective pilot clinical trial evaluates the safety, efficacy, and patient satisfaction of this rapid workflow. METHODS AND MATERIALS: Patients with 1 to 3 painful bone metastases were prospectively enrolled and treated with 1 fraction of stereotactic body radiation therapy, using a same-day Scan-Plan-QA-Treat workflow, termed STAT RAD, in a phase 1/2 dose escalation trial from 8 Gy to 15 Gy per fraction. Bone pain, opioid use, patient satisfaction, performance status, and quality of life were evaluated before and at 1, 4, 8, 12, 26, and 52 weeks after treatment. Outcomes and treatment-related toxicity were analyzed. RESULTS: A total of 49 patients were enrolled, and 46 patients with 60 bone metastases were treated per the protocol. Partial or greater pain response occurred in 50% of patients at 1 week, 75% of patients at 8 weeks, 68.7% of patients at 6 months, and 33.3% of patients at 12 months. There were 2 grade-3 toxicities, including 1 spinal fracture associated with disease progression and hyperbilirubinemia. Reirradiation was required in 16.7% of treated lesions at a median time to retreatment of 4.9 months. Most patient responses (78.6%) indicated that patients would choose this workflow again. CONCLUSIONS: The results demonstrate that treating bone metastases with palliative stereotactic body radiation therapy via a single-fraction, patient-centric workflow is feasible and safe with doses up to 15 Gy. However, pain response decreased at 12 months and was associated with a 16.7% retreatment rate, which suggests that further dose escalation is warranted.

The vaginal cylinder: Misunderstood, misused, or trivial? An in-depth dosimetric and multiinstitutional outcome investigation.

PURPOSE: The purpose of the study was to investigate the impact on dose distribution and radiobiological metrics of common high-dose-rate vaginal brachytherapy treatment parameters and to analyze multiinstitutional data for clinically significant impact on outcomes in early-stage endometrial cancer. METHODS AND MATERIALS: Treatment plans were created for all combinations of prescription parameters and used to quantify the dosimetric impact of each parameter and to estimate the dose delivered using common voxel-integrated radiobiological metrics. A rating system, based on risk grouping from GOG and PORTEC trials, was used to consolidate staging information into a cancer "aggressiveness" measure. Correlations between the rating, toxicity, disease recurrence, and plan parameters were investigated. RESULTS: When prescribing to 5 mm depth, the variation caused by the diameter was very large across all dose metrics, ranging from 51% to 175% increase with the most divergence in BEDmax. For surface prescription, changing the cylinder diameter from 4 cm to 2 cm caused the dose metrics of BEDmin, Dmin, and gBEUD (a = -3) to increase by 117%, 67%, and 52%, respectively. Prescription to 5-mm depth caused changes across all dose metrics of 260% compared with surface prescription for a 2-cm cylinder. Deeper prescription point (p = 0.005) and longer treatment length (p = 0.01) were correlated with increased stenosis rates. No correlation between recurrence and any plan parameter was found. CONCLUSIONS: Dramatic differences in dose distributions arise by small variations of plan parameters, with large impact on rates of vaginal stenosis, but no clear relation with local recurrence. To help radiation oncologists interpret the magnitude of these effects for their patients, we created a tool that allows comparison between dose and fractionation parameters.

The Effect of Receptor Status on Mastectomy and Contralateral Prophylactic Mastectomy Rates in Early Stage Invasive Breast Carcinoma.

BACKGROUND: There is an established relationship between hormone receptor (HR; estrogen and/or progesterone receptors) status, HER2 status, and locoregional recurrence. The purpose of this study was to analyze how HR and HER2 receptor status have influenced the surgical management trends among patients with early stage breast cancer. PATIENTS AND METHODS: The National Cancer Database was queried for patients with cT1 to cT3, cN0, and cM0 breast carcinoma from 2004 to 2012. Patients were grouped on the basis of receptor status and surgical management (mastectomy or breast-conserving surgery [BCS]). Multivariable analyses were performed to investigate factors associated with increased odds of receiving mastectomy over BCS. Among a subgroup of patients who underwent ipsilateral mastectomy, analyses were performed to determine any association between contralateral prophylactic mastectomy (CPM) and receptor status. RESULTS: We found 280,241 patients who met inclusion criteria for analyzing mastectomy or BCS surgical decision. Patients with HER2-positive (HER2+) tumors (HR+/HER+ and HR-/HER2+) were the most likely to undergo mastectomy (odds ratio [OR], 1.212 and 1.499 respectively, compared with HR+/HER2- patients, each P < .001). HR status alone did not affect ipsilateral surgical management as patients with HR+/HER2- and HR-/HER2- tumors demonstrated similar mastectomy rates (P = .391). Among the 108,018 who underwent mastectomy, 20% underwent CPM. After adjustment, patients with HR+/HER2+, HR-/HER2+, and HR-/HER2- were all more likely to undergo CPM (OR 1.356, 1.608, and 1.358, respectively compared with HR+/HER2- patients, each P < .001). CONCLUSION: This analysis indicates that patients with early stage breast cancer are more likely to undergo a mastectomy and CPM if they have HER2+ tumors.

Preliminary toxicity results using partial breast 3D-CRT with once daily hypo-fractionation and deep inspiratory breath hold.

BACKGROUND: To evaluate the clinical outcomes of patients treated with 3D conformal Hypo-fractionated, deep Inspiratory breath-hold (DIBH), Partial breast radiotherapy, termed "HIP." HIP was implemented to merge the schedule of once-daily breast hypofractionation with partial breast treatment. METHODS: We identified 38 breast cancers in 37 patients from 2013 to 2014 treated at our institution with HIP following lumpectomy for early stage breast cancer. Patients received a hypo-fractionated course (≤ 20 fractions) of once daily radiation to the partial breast (lumpectomy cavity + margin) utilizing DIBH regardless of laterality. Clinical and treatment-related characteristics were obtained, including target volume and organ at risk (OAR) dosimetric characteristics. Patients were followed clinically and with at least yearly mammograms for up to 36 months (range 5-36 months). Acute and late toxicity was scored using the Common Terminology Criteria for Adverse Events (CTCAE) v4.03. RESULTS: Patients received a median dose of 42.56 Gy in 16 Fractions (Fx) (range 40.05-53.2 Gy; and 15-20 Fx). OAR doses were low, with a mean heart dose of 0.37 Gy, an ipsilateral lung V20 mean of 4%, and a contralateral lung V5 of 1%. Acute toxicity (≤ grade 2) was present in 79% (n = 30) of the cases, with dermatitis being the most common finding (63%). Late grade 1-2 toxicity was present in 42% (n = 16) of the cases, with hyperpigmentation being the most common finding (n = 9). There were no severe acute or late toxicities (≥ grade 3). At a median follow up of 21 months, there were no local, regional, or distant failures. CONCLUSIONS: We report limited toxicity in this low risk cohort of patients with early stage breast cancer treated with HIP, a unique and logical combination of 3-D conformal external beam radiotherapy, moderate hypo-fractionation, and DIBH.

Integration of MRI target delineation into rapid workflow cervical cancer brachytherapy: Impact on clinical outcomes.

INTRODUCTION: We evaluated the impact of MRI-based target delineation on toxicity and tumour control after implementation of a protocol to incorporate MRI while minimizing impact on overall procedural time. METHODS: We retrospectively reviewed outcomes for a cohort of 96 consecutive patients who received intracavitary brachytherapy for cervical cancer at our institution during 2012-2016. Starting in October 2014, an outpatient MRI was obtained for patients after Smit sleeve placement and first insertion to assess concurrent chemoradiotherapy tumour response. Then, for subsequent fractions, the MRI was co-registered by the Smit sleeve to the planning CT for target volume delineation. The primary and secondary outcomes were toxicity and local control, respectively. RESULTS: Median follow-up for the pre- (n = 50) and post-MRI-based (n = 46) planning groups was 24.6 and 14.7 months, respectively. Median treatment duration for patients before and after MRI implementation was 56 and 58 days (P = 0.052), respectively. Cumulative rectal D2 cc was less for those with MRI-based target delineation (P = 0.005). On multivariable analysis, patients with MRI-based target delineation experienced fewer severe late (CTCAE grade ≥ 3) toxicities (P = 0.025, hazard ratio = 0.25). Local control was 86% and 91% of the pre- and post-MRI groups, respectively (P = 0.959). CONCLUSIONS: Preliminary findings using this technique, which is applicable to other institutions without in-room MRI availability, are associated with lower radiation prescription doses, lower rectal doses and favourable toxicity rates while maintaining a rapid workflow. Longer follow-up is required to confirm equivalent local control.

High dose-rate tandem and ovoid brachytherapy in cervical cancer: dosimetric predictors of adverse events.

BACKGROUND: Brachytherapy (BT) is a vital component of the curative treatment of locally advanced cervical cancer. The American Brachytherapy Society has published guidelines for high dose rate (HDR) BT with recommended dose limits. However, recent reports suggest lower doses may be needed to avoid toxicity. The purpose of this study is to investigate incidence and predictive factors influencing gastrointestinal (GI) and genitourinary (GU) toxicity following HDR intracavitary brachytherapy for locally advanced cervical cancer. METHODS: We retrospectively evaluated a cohort of patients with locally advanced cervical cancer who received CT-based HDR BT. Cumulative doses were calculated using the linear-quadratic model. Statistical analyses were used to investigate clinical and dosimetric predictors of GI and GU toxicity following HDR brachytherapy according to CTCAE v4.0 grading criteria. RESULTS: Fifty-six women with FIGO IB1 - IVA cervical cancer were included. The overall rate of any GU adverse event (Grade 1+) was 23.3% (n = 13) and severe adverse events (Grade 3+) was 7.1% (n = 4). Of those, the bladder equivalent dose in 2- Gray (Gy) fractions (EQD2) D2cc was ≥80 for three of the four patients. The overall rate of any GI adverse event was 26.8% (n = 15) and the rate of severe adverse events was 14.3% (n = 8). Of those, six of the eight patients had a rectal EQD2 D2cc ≥ 65 Gy and seven patients had a sigmoid D2cc ≥ 65 Gy. Amongst clinically meaningful factors for development of adverse events (i.e. diabetes, smoking status, ovoid size, and treatment duration), there were no statistically significant prognostic factors identified. CONCLUSIONS: Severe adverse events are observed even with adherence to current ABS guidelines. In the era of recent multi-institutional study results, our data also supports more stringent dosimetric goals. We suggest cumulative D2cc dose limits of: less than 80 Gy for the bladder and less than 65 Gy for the rectum and sigmoid.

More than Just the Number of Brain Metastases: Evaluating the Impact of Brain Metastasis Location and Relative Volume on Overall Survival After Stereotactic Radiosurgery.

OBJECTIVE: Most evidence describing outcomes of patients with brain metastases is based on number of brain metastases, rather than location or volume. We evaluated the impact of tumor location and relative volume on overall survival (OS) among a large cohort of patients treated with stereotactic radiosurgery. METHODS: Clinical, radiographic, and dosimetric data were collected on patients treated with first (if multiple) stereotactic radiosurgery for brain metastases. Multivariate analyses were performed to investigate the impact of brain metastasis relative location and volume on OS after stereotactic radiosurgery. RESULTS: Analysis included 300 patients with 817 tumors (116 patients with single brain metastasis). The most common tumor locations were supratentorial (75% of tumors), cerebellar (19%), and brainstem (5%). Median tumor volume was 0.4 mL (range, 0.003-65.0 mL). Tumor-specific factors associated with inferior OS included brainstem location versus both supratentorial and cerebellum locations for particular assumed values of cube root tumor volume (P < 0.001 for each) and increasing total supratentorial tumor volume (P = 0.004). Patients with supratentorial tumors and cerebellar tumors demonstrated similar OS, and cube root total tumor volume within the cerebellum and brainstem did not predict for OS. CONCLUSIONS: The presence of brainstem metastases and cumulative supratentorial tumor volume are adverse features that result in inferior survival. These results can be used to inform patient prognosis and future clinical trial design.

Clinical outcomes of helical conformal versus nonconformal palliative radiation therapy for axial skeletal metastases.

PURPOSE: Palliative radiation therapy (RT) for bone metastases has traditionally been delivered with conventional, nonconformal RT (NCRT). Conformal RT (CRT) is potentially more complex and expensive than NCRT, but may reduce normal tissue dose and subsequently toxicity. In this retrospective analysis, we compared CRT with NCRT to investigate the association between conformality and toxicity. METHODS AND MATERIALS: A retrospective analysis of patients receiving palliative RT for axial skeletal bone metastases from 2012 to 2014 was conducted. Patient and treatment characteristics were obtained including dosimetric variables, acute toxicity, and subjective pain during treatment and in the acute posttreatment period (≤60 days after completion). Statistical analyses included t tests, χ2 tests, and multivariate logistic regression. RESULTS: A total of 179 patients and 254 bone metastases were identified (142 CRT, 112 NCRT). The CRT and NCRT groups were well matched for baseline characteristics (number of fractions, field size, treatment sites, and concurrent chemotherapy). In multivariate logistic regression models, technique (CRT vs NCRT) was not associated with development of acute toxicity. Regarding toxicity, Eastern Cooperative Oncology Group performance status and total dose were significantly associated with a higher rate of acute toxicity during RT (odds ratios, 0.649 and 1.129 and P = .027 and .044, respectively), and only a higher number of vertebral bodies in the treatment field was significantly associated with acute toxicity post-treatment (odds ratios, 1.219, P = .028). CRT was associated with improvement in bone pain during and posttreatment (P = .049 and .045, respectively). CONCLUSIONS: Our results demonstrate no difference in acute toxicity following palliative RT with CRT compared with NCRT for painful bone metastases; however, treatment volume did predict for increased toxicity. Larger studies may further elucidate the value of CRT including the impact of dose escalation for bone metastases and differences in patient reported outcomes between RT techniques.

Choosing a Prescription Isodose in Stereotactic Radiosurgery for Brain Metastases: Implications for Local Control.

OBJECTIVE: Stereotactic radiosurgery (SRS) achieves excellent local control (LC) with limited toxicity for most brain metastases. SRS dose prescription variables influence LC; therefore, we evaluated the impact of prescription isodose line (IDL) on LC after SRS. METHODS: A retrospective analysis of patients with brain metastases treated on a Gamma Knife platform from 2004 to 2014 was conducted. Clinical, toxicity, radiographic, and dosimetric data were collected. Cox proportional hazards regression was used to determine progression-free survival (PFS) and competing risks analysis was used to determine predictive factors for LC. RESULTS: A total of 134 patients with 374 brain metastases were identified with a median survival of 8.7 months (range, 0.2-64.8). The median tumor maximum dimension was 8 mm (range, 2-62 mm), median margin dose was 20 Gy (range, 5-24 Gy), and 12-month LC rate was 88.7%. On multivariate analysis, PFS improved with increasing IDL (P = 0.003) and decreased with non-non-small-cell lung cancer histology (P = 0.001). Margin dose, tumor size, conformality, and previous whole-brain irradiation failed to independently affect PFS. When adjusting for death as a competing risk, the cumulative likelihood of LC improved with higher IDL (P = 0.04). The rate of SRS-induced radiographic and clinical toxicity was low (16.6% and 1.5%, respectively), and neither was affected by IDL. CONCLUSIONS: Our results confirm that SRS for brain metastases results in favorable LC, particularly for patients with smaller tumors. We noted that dose delivery to a higher prescription IDL is associated with small but measurable improvements in LC. This finding could be related to higher dose just beyond the radiographically apparent tumor.