Retrospective assessment of HDR brachytherapy dose calculation methods in locally advanced cervical cancer patients: AcurosBV vs. AAPM TG43 formalism.

PURPOSE: This retrospective analysis was completed to investigate the use of a model-based dose calculation algorithm (MBDCA) AcurosBV, for use in HDR BT treatments for locally advanced cervical cancer treated with tandem and ovoid applicators with interstitial needles. METHODS: A cohort of 32 patients receiving post-EBRT HDR brachytherapy boost with a prescription dose of 5.5 Gy × 5 fractions to the high-risk clinical target volume (CTVHR) were selected for this study. For standard TG43 dose calculation, applicators were manually digitized on the planning images, while for AcurosBV calculations, solid renderings of Titanium Fletcher Suite Delclos (FSD) applicators included in BrachyVision were matched to those used clinically and Ti needles were manually digitized. The dose was recalculated using Varian's AcurosBV 13.5 and dose-to-medium-in-medium (Dm,m) was reported. EQD2 values for targets and organs at risk were compared between dose calculation formalisms. D90% and D98% values were reported for the high and intermediate-risk CTVs, and D 2 c m 3 ${\mathrm{\ D}}_{{\mathrm{2\ c}}{{\mathrm{m}}}^{\mathrm{3}}}$ values were reported for OARs including bladder, rectum, sigmoid, bowel, and vagina. Due to variability within the patient cohort, the dosimetric impact of AcurosBV was investigated corresponding to planning image modality (CT vs. CBCT), presence of Ti needles, and contrast within vaginal balloons used to stabilize implants. AcurosBV showed lower dosimetric values for all plans compared to TG43. RESULTS: The average ± standard deviation of dosimetric reduction in D90% was 4.33 ± 0.09% for CTVHR and 4.12 ± 0.09% for CTVIR. The reduction to OARs D 2 c m 3 ${\mathrm{\ D}}_{{\mathrm{2\ c}}{{\mathrm{m}}}^{\mathrm{3}}}$ was: 4.99 ± 0.15% for bladder, 7.87 ± 0.16% for rectum, 5.79 ± 0.17% for sigmoid, 6.91 ± 0.14% for bowel, and 4.55 ± 0.14% for vagina. CONCLUSIONS: AcurosBV should be utilized for HDR BT GYN cases, treated with tandem and ovoid applicators, with high degrees of heterogeneity and calculated in tandem with TG43.

A novel multi-modality imaging phantom for validating interstitial needle guidance for high dose rate gynecological brachytherapy.

PURPOSE: To design, manufacture, and validate a female pelvic phantom for multi-modality imaging (CT, MRI, US) to benchmark a commercial needle tracking system with application in HDR gynecological (GYN) interstitial procedures. MATERIALS AND METHODS: A GYN needle-tracking phantom was designed using CAD software to model an average uterus from a previous patient study, a vaginal canal from speculum dimensions, and a rectum to accommodate a transrectal ultrasound (TRUS) probe. A target volume (CTVHR ) was designed as an extension from the cervix-uterus complex. Negative space molds were created from modeled anatomy and 3D printed. Silicone was used to cast the anatomy molds. A 3D printed box was constructed to house the manufactured anatomy for structural integrity and to accommodate the insertion of a speculum, tandem, needles, and TRUS probe. The phantom was CT-imaged to identify potential imperfections that might impact US visualization. Free-hand TRUS was used to guide interstitial needles into the phantom. The commercial tracking system was used to generate a 3D US volume. After insertion, the phantom was imaged with CT and MR and the uterus and CTVHR dimensions were verified against the CAD model. RESULTS/CONCLUSIONS: The manufactured phantom allows for accurate visualization with multiple imaging modalities and is conducive to applicator and needle insertion. The phantom dimensions from the CAD model were verified with those from each imaging modality. The phantom is low cost and can be reproducibly manufactured with the 3D printing and molding processes. Our initial experiments demonstrate the ability to integrate the phantom with a commercial tracking system for future needle tracking validation studies.

Effect of COVID-19 on Gynecologic Oncology Care: A Survey of Practicing Gynecologic Radiation Oncologists in the United States.

Purpose: The COVID-19 pandemic has placed demands and limitations on the delivery of health care. We sought to assess the effect of COVID-19 on the delivery of gynecologic oncologic care from the perspective of practicing radiation oncologists in the United States. Methods and Materials: An anonymous online survey was created and distributed to preidentified radiation oncologists in the United States with clinical expertise in the management of gynecologic patients. The survey consisted of demographic questions followed by directed questions to assess specific patterns of care related to the COVID-19 pandemic. Results: A total of 47 of 96 invited radiation oncologists responded to the survey for a response rate of 49%. Fifty-six percent of respondents reported an increase in locally advanced cervical cancer with no similar increase for endometrial, vulvar, or vaginal patients. Most respondents (66%) reported a pause in surgical management, with a duration of 1 to 3 months being most common (61%). There was a reported increased use of shorter brachytherapy regimens during the pandemic. Most providers (61%) reported caring for at least 1 patient with a positive COVID-19 test. A pause or delay in treatment due to COVID-19 positivity was reported by 45% of respondents, with 55% reporting that patients chose to delay their own care because of COVID-19-related concerns. Total treatment times >8 weeks for patients with cervical cancer were observed by 33% of respondents, but occurred in >25% of patients. Conclusions: Data from this prospectively collected anonymous survey of practice patterns among radiation oncologists reveal that the COVID-19 pandemic resulted in delays initiating care, truncated brachytherapy treatment courses, and a reported increase in locally advanced cervical cancer cases at presentation. These data can be used as a means of self-assessment to ensure appropriate decision making for gynecologic patients during the endemic phase of COVID-19.

What is appropriate target delineation for MRI-based brachytherapy for medically inoperable endometrial cancer?

PURPOSE: For medically inoperable endometrial cancer (MIEC), the volumetric target of image-guided brachytherapy (IGBT) techniques is not well established. We propose a high-risk CTV (HRCTV) concept and report associated rates of local control and toxicity. METHODS AND MATERIALS: For all MIEC patients receiving definitive external beam radiotherapy (EBRT) followed by MRI-based IGBT at a single institution, BT dose was prescribed to HRCTV defined as GTV plus endometrial cavity with a planning goal of a summed EQD2 D90 of ≥85 Gy. Freedom from local progression (FFLP) and overall survival (OS) were estimated via Kaplan Meier method. RESULTS: Thirty two MIEC patients received EBRT followed by MRI-based IGBT between December 2015 and August 2020. Median follow up was 19.8 months. A total of 75% of patients had FIGO stage I/II disease, 56% endometrioid histology, and 50% grade 3 disease. OS was 73.6% (95% CI 57.8%-89.3%) at 12 months and 65.8% (95% CI 48.4%-83.2%) at 24 months. FFLP was 93.8% (95% CI 85.3%-100%) at 12 months and 88.8% (95% CI 86.6%-91.0%) at 24 months. 23 (72%) patients experienced no RT-related toxicity, while 2 of 32 patients (6%) experienced late grade 3+ toxicities (grade 3 refractory vomiting; grade 5 GI bleed secondary to RT-induced proctitis). CONCLUSIONS: Patients with MIEC receiving definitive EBRT followed by MRI-based IGBT prescribed to the MRI-defined HRCTV demonstrated favorable long-term local control with an acceptable toxicity profile.

Initial analysis of the dosimetric benefit and clinical resource cost of CBCT-based online adaptive radiotherapy for patients with cancers of the cervix or rectum.

PURPOSE: This provides a benchmark of dosimetric benefit and clinical cost of cone-beam CT-based online adaptive radiotherapy (ART) technology for cervical and rectal cancer patients. METHODS: An emulator of a CBCT-based online ART system was used to simulate more than 300 treatments for 13 cervical and 15 rectal cancer patients. CBCT images were used to generate adaptive replans. To measure clinical resource cost, the six phases of the workflow were timed. To evaluate the dosimetric benefit, changes in dosimetric values were assessed. These included minimum dose (Dmin) and volume receiving 95% of prescription (V95%) for the planning target volume (PTV) and the clinical target volume (CTV), and maximum 2 cc's (D2cc) of the bladder, bowel, rectum, and sigmoid colon. RESULTS: The average duration of the workflow was 24.4 and 9.2 min for cervical and rectal cancer patients, respectively. A large proportion of time was dedicated to editing target contours (13.1 and 2.7 min, respectively). For cervical cancer patients, the replan changed the Dmin to the PTVs and CTVs for each fraction 0.25 and 0.25 Gy, respectively. The replan changed the V95% by 9.2 and 7.9%. The D2cc to the bladder, bowel, rectum, and sigmoid colon for each fraction changed -0.02, -0.08, -0.07, and -0.04 Gy, respectively. For rectal cancer patients, the replan changed the Dmin to the PTVs and CTVs for each fraction of 0.20 and 0.24 Gy, respectively. The replan changed the V95% by 4.1 and 1.5%. The D2cc to the bladder and bowel for each fraction changed 0.02 and -0.02 Gy, respectively. CONCLUSIONS: Dosimetric benefits can be achieved with CBCT-based online ART that is amenable to conventional appointment slots. The clinical significance of these benefits remains to be determined. Managing contours was the primary factor affecting the total duration and is imperative for safe and effective adaptive radiotherapy.

Patterns of Care and Outcomes for Small Cell Carcinoma of the Cervix: A National Retrospective Analysis of 542 Cases.

PURPOSE: Small cell carcinoma of the cervix (SCCC) represents 1% to 5% of cervical cancers, with limited data on management and outcomes. We evaluated patterns of care and outcomes for SCCC using the National Cancer Database. METHODS AND MATERIALS: This retrospective cohort study of SCCC (2004-2011) included 542 cases. Patient demographic, diagnosis, treatment information, and overall survival (OS) were compared with descriptive statistics, logistic regression, Kaplan-Meier, and Cox models. Clinical reasoning was used to select variables for multivariable models to avoid overfitting. RESULTS: SCCC had more comorbidities, higher grade, and advanced stage than other histologies. SCCC received neoadjuvant chemotherapy (36%) more often than squamous cell carcinoma (23%) and adenocarcinoma (13%, P < .001). SCCC had worse OS across all stages (P < .001). Looking at SCCC alone, patients who received chemoradiation (CRT) (with external beam and brachytherapy) and those who received chemotherapy and surgery (without RT) had similar OS (median OS 44 vs 47 months; P = .7) on Kaplan-Meier. Patients receiving CRT were more likely to have stage II or III and N+ disease (P < .001). When evaluating chemoradiation, the addition of brachytherapy resulted in improved median OS (35 vs 19 months; P = .001) regardless of surgical resection status and controlling for age and stage. Even after controlling for stage, age, and comorbidities, the addition of brachytherapy was associated with a 40% improvement in OS (hazard ratio 1.4, 95% confidence interval 1.0-2.0). CONCLUSIONS: SCCC patients benefit from chemotherapy with aggressive local treatment. Patients who receive CRT that included brachytherapy did as well as patients who received chemotherapy followed by surgery. Brachytherapy remains an essential component in the treatment of SCCC with CRT.

Effect at One Year of Adjuvant Trastuzumab for HER2+ Breast Cancer Combined with Radiation or an Anthracycline on Left Ventricular Ejection Fraction.

To determine the impact of radiation therapy (XRT) in addition to trastuzumab (TZB) adjuvant chemotherapy for HER2+ breast cancer on left ventricular systolic function, we assessed demographics, oncologic treatment history including XRT exposure, and serial measurements of left ventricular ejection fraction (LVEF) in 135 consecutively identified women receiving TZB for treatment of adjuvant breast cancer. Longitudinal mixed effects models were fit to identify baseline to treatment changes in LVEF among those receiving TZB with or without concomitant anthracycline or XRT. Women averaged 53 ± 3 years in age, 77% were white, 62% patients had 1 or more cardiovascular risk factors at baseline, and mean duration of TZB was 11 ± 5 months. Seventy-seven women were treated with XRT and received between 4000 and 5500 cGy of radiation. The LVEF declined by an average of 3.4% after 1 year for those in the study. Relative to baseline upon completion of adjuvant TZB, LVEF remained reduced for those receiving anthracycline with or without XRT (p=0.002 for both), or XRT alone (p=0.002), but not in those without these therapies. Amongst patients treated only with XRT and TZB, LVEF declined 3.1% on average in those with left-sided disease and 6.9% on average in those with right-sided disease (p= 0.06, p= 0.008 respectively). Among women receiving TZB for adjuvant treatment of HER-2 positive breast cancer, the administration of XRT, anthracycline, or the combination of the 2 is associated with a persistent post-treatment as opposed to a temporary treatment related decline in LVEF.

Combining Adjuvant Radiotherapy With Capecitabine in Chemotherapy-resistant Breast Cancer: Feasibility, Safety, and Toxicity.

BACKGROUND: In a randomized trial (CREATE-X), patients with residual disease after standard neoadjuvant chemotherapy had improved survival with the addition of adjuvant capecitabine. For patients who required radiotherapy (RT), capecitabine was given sequentially. Concurrent capecitabine-RT might be more efficacious. We hypothesized that the safety, feasibility, and toxicity of adjuvant capecitabine-RT would not be significantly different compared with adjuvant RT alone. PATIENT AND METHODS: We retrospectively studied the data from patients with stage I-III invasive mammary carcinoma. Patients who had received capecitabine-RT were matched 1:3 with control patients who had received RT alone. Logistic regression analysis was used to evaluate the predictors of radiation dermatitis. RESULTS: A total of 64 patients were enrolled, including 16 who had received capecitabine-RT and 48 who had received RT alone. The cohorts were balanced regarding the clinicopathologic factors. No treatment in either cohort resulted in hospitalization, short-term disability, or fatality. Most toxicities of capecitabine-RT were related to radiation dermatitis. Radiation dermatitis was not significantly different between the capecitabine-RT and RT cohort at either grade 2 (odds ratio [OR], 1.36; 95% confidence interval [CI], 0.38-4.93; P = .63) or grade 3 (OR, 3.00; 95% CI, 0.85-10.63; P = .09) or after multivariable analysis. However, the capecitabine-RT group was more likely to require modifications in the RT schedule, including treatment breaks or cancelled fractions (44% vs. 17%; OR, 3.89; 95% CI, 1.12-13.52; P = .03). CONCLUSION: Capecitabine-RT appears to be safe in the adjuvant treatment of breast cancer with comparable toxicity to RT alone. It might require more treatment adjustments. Prospective studies are needed to evaluate the safety and tolerability of this combination.

Multi-institutional validation of brain metastasis velocity, a recently defined predictor of outcomes following stereotactic radiosurgery.

INTRODUCTION: Brain metastasis velocity (BMV) is a prognostic metric that describes the recurrence rate of new brain metastases after initial treatment with radiosurgery (SRS). We have previously risk stratified patients into high, intermediate, and low-risk BMV groups, which correlates with overall survival (OS). We sought to externally validate BMV in a multi-institutional setting. METHODS: Patients from nine academic centers were treated with upfront SRS; the validation cohort consisted of data from eight institutions not previously used to define BMV. Patients were classified by BMV into low (<4 BMV), intermediate (4-13 BMV), and high-risk groups (>13 BMV). Time-to-event outcomes were estimated using the Kaplan-Meier method. Cox proportional hazards methods were used to estimate the effect of BMV and salvage modality on OS. RESULTS: Of 2829 patients, 2092 patients were included in the validation dataset. Of these, 921 (44.0%) experienced distant brain failure (DBF). Median OS from initial SRS was 11.2 mo. Median OS for BMV < 4, BMV 4-13, and BMV > 13 were 12.5 mo, 7.0 mo, and 4.6 mo (p < 0.0001). After multivariate regression modeling, melanoma histology (ß: 10.10, SE: 1.89, p < 0.0001) and number of initial brain metastases (ß: 1.52, SE: 0.34, p < 0.0001) remained predictive of BMV (adjusted R2 = 0.06). CONCLUSIONS: This multi-institutional dataset validates BMV as a predictor of OS following initial SRS. BMV is being utilized in upcoming multi-institutional randomized controlled trials as a stratification variable for salvage whole brain radiation versus salvage SRS after DBF.

Initial SRS for Patients With 5 to 15 Brain Metastases: Results of a Multi-Institutional Experience.

PURPOSE: Several studies evaluating stereotactic radiosurgery (SRS) for patients with >4 brain metastases (BM) demonstrated similar outcomes after treatment of 1, 2 to 4, and 5 to 15 BM; others found clinically significant survival decrements in the latter group. In this review of 8 academic centers, we compared outcomes of patients undergoing initial SRS for 1, 2 to 4, and 5 to 15 BM. METHODS AND MATERIALS: A total of 2089 patients treated with initial SRS for BM were included. Overall survival (OS) was estimated using the Kaplan-Meier method and compared using the log-rank test. Patient and disease characteristics were evaluated for association with OS and cumulative incidence of distant brain failure (DBF) using stepwise multivariable Cox proportional hazards and competing risk regression modeling. RESULTS: In this series, 989 (47%) patients had 1 metastasis, 882 (42%) had 2 to 4 metastases, and 212 (10%) had 5 to 15 metastases treated. Median OS for the 1, 2 to 4, and 5 to 15 BM groups was 14.6, 9.5, and 7.5 months, respectively (log-rank P < .01). Univariate and multivariable analyses revealed no difference in survival between 2 to 4 and 5 to 15 BM. DBF at 1 year was 30%, 41%, and 50%, respectively (Gray's P < .01). Two-year cumulative incidence of salvage SRS decreased with increasing number of BM (1: 21% vs 2-4: 19% vs 5-15: 13%; P < .01), but no difference in salvage whole brain radiation therapy was observed (1: 12% vs 2-4: 15% vs 5-15: 16%, P = .10). At the time of DBF, median brain metastasis velocity was 3.9, 6.1, and 11.7 new metastases per year in the 1, 2 to 4, and 5 to 15 BM groups, respectively (P < .01). CONCLUSIONS: Patients treated with initial SRS for 5 to 15 BM experienced survival similar to that in patients with 2 to 4 BM. Lower rates of salvage SRS were observed in the 5 to 15 BM group, with no difference in rates of salvage whole brain radiation therapy.

Classification for long-term survival in oligometastatic patients treated with ablative radiotherapy: A multi-institutional pooled analysis.

BACKGROUND: Radiotherapy is increasingly used to treat oligometastatic patients. We sought to identify prognostic criteria in oligometastatic patients undergoing definitive hypofractionated image-guided radiotherapy (HIGRT). METHODS: Exclusively extracranial oligometastatic patients treated with HIGRT were pooled. Characteristics including age, sex, primary tumor type, interval to metastatic diagnosis, number of treated metastases and organs, metastatic site, prior systemic therapy for primary tumor treatment, prior definitive metastasis-directed therapy, and systemic therapy for metastasis associated with overall survival (OS), progression-free survival (PFS), and treated metastasis control (TMC) were assessed by the Cox proportional hazards method. Recursive partitioning analysis (RPA) identified prognostic risk strata for OS and PFS based on pretreatment factors. RESULTS: 361 patients were included. Primary tumors included non-small cell lung (17%), colorectal (19%), and breast cancer (16%). Three-year OS was 56%, PFS was 24%, and TMC was 72%. On multivariate analysis, primary tumor, interval to metastases, treated metastases number, and mediastinal/hilar lymph node, liver, or adrenal metastases were associated with OS. Primary tumor site, involved organ number, liver metastasis, and prior primary disease chemotherapy were associated with PFS. OS RPA identified five classes: class 1: all breast, kidney, or prostate cancer patients (BKP) (3-year OS 75%, 95% CI 66-85%); class 2: patients without BKP with disease-free interval of 75+ months (3-year OS 85%, 95% CI 67-100%); class 3: patients without BKP, shorter disease-free interval, ≤ two metastases, and age < 62 (3-year OS 55%, 95% CI 48-64%); class 4: patients without BKP, shorter disease-free interval, ≥ three metastases, and age < 62 (3-year OS 38%, 95% CI 24-60%); class 5: all others (3-year OS 13%, 95% CI 5-35%). Higher biologically effective dose (BED) (p < 0.01) was associated with OS. CONCLUSIONS: We identified clinical factors defining oligometastatic patients with favorable outcomes, who we hypothesize are most likely to benefit from metastasis-directed therapy.

Hippocampal dose volume histogram predicts Hopkins Verbal Learning Test scores after brain irradiation.

PURPOSE: Radiation-induced cognitive decline is relatively common after treatment for primary and metastatic brain tumors; however, identifying dosimetric parameters that are predictive of radiation-induced cognitive decline is difficult due to the heterogeneity of patient characteristics. The memory function is especially susceptible to radiation effects after treatment. The objective of this study is to correlate volumetric radiation doses received by critical neuroanatomic structures to post-radiation therapy (RT) memory impairment. METHODS AND MATERIALS: Between 2008 and 2011, 53 patients with primary brain malignancies were treated with conventionally fractionated RT in prospectively accrued clinical trials performed at our institution. Dose-volume histogram analysis was performed for the hippocampus, parahippocampus, amygdala, and fusiform gyrus. Hopkins Verbal Learning Test-Revised scores were obtained at least 6 months after RT. Impairment was defined as an immediate recall score ≤15. For each anatomic region, serial regression was performed to correlate volume receiving a given dose (VD(Gy)) with memory impairment. RESULTS: Hippocampal V53.4Gy to V60.9Gy significantly predicted post-RT memory impairment (P < .05). Within this range, the hippocampal V55Gy was the most significant predictor (P = .004). Hippocampal V55Gy of 0%, 25%, and 50% was associated with tumor-induced impairment rates of 14.9% (95% confidence interval [CI], 7.2%-28.7%), 45.9% (95% CI, 24.7%-68.6%), and 80.6% (95% CI, 39.2%-96.4%), respectively. CONCLUSIONS: The hippocampal V55Gy is a significant predictor for impairment, and a limiting dose below 55 Gy may minimize radiation-induced cognitive impairment.

Prediction of new brain metastases after radiosurgery: validation and analysis of performance of a multi-institutional nomogram.

Stereotactic radiosurgery (SRS) without whole brain radiotherapy (WBRT) for brain metastases can avoid WBRT toxicities, but with risk of subsequent distant brain failure (DBF). Sole use of number of metastases to triage patients may be an unrefined method. Data on 1354 patients treated with SRS monotherapy from 2000 to 2013 for new brain metastases was collected across eight academic centers. The cohort was divided into training and validation datasets and a prognostic model was developed for time to DBF. We then evaluated the discrimination and calibration of the model within the validation dataset, and confirmed its performance with an independent contemporary cohort. Number of metastases (≥8, HR 3.53 p = 0.0001), minimum margin dose (HR 1.07 p = 0.0033), and melanoma histology (HR 1.45, p = 0.0187) were associated with DBF. A prognostic index derived from the training dataset exhibited ability to discriminate patients' DBF risk within the validation dataset (c-index = 0.631) and Heller's explained relative risk (HERR) = 0.173 (SE = 0.048). Absolute number of metastases was evaluated for its ability to predict DBF in the derivation and validation datasets, and was inferior to the nomogram. A nomogram high-risk threshold yielding a 2.1-fold increased need for early WBRT was identified. Nomogram values also correlated to number of brain metastases at time of failure (r = 0.38, p < 0.0001). We present a multi-institutionally validated prognostic model and nomogram to predict risk of DBF and guide risk-stratification of patients who are appropriate candidates for radiosurgery versus upfront WBRT.

Brain Metastasis Velocity: A Novel Prognostic Metric Predictive of Overall Survival and Freedom From Whole-Brain Radiation Therapy After Distant Brain Failure Following Upfront Radiosurgery Alone.

PURPOSE: Prior statistical models attempted to identify risk factors for time to distant brain failure (DBF) or time to salvage whole-brain radiation therapy (WBRT) to predict the benefit of early WBRT versus stereotactic radiosurgery (SRS) alone. We introduce a novel clinical metric, brain metastasis velocity (BMV), for predicting clinical outcomes after initial DBF following upfront SRS alone. METHODS AND MATERIALS: BMV was defined as the cumulative number of new brain metastases that developed over time since first SRS in years. Patients were classified by BMV into low-, intermediate-, and high-risk groups, consisting of <4, 4 to 13, and >13 new metastases per year, respectively. Histology, number of metastases at the time of first SRS, and systemic disease status were assessed for effect on BMV. RESULTS: Of 737 patients treated at our institution with upfront SRS without WBRT, 286 had ≥1 DBF event. A lower BMV predicted for improved overall survival (OS) following initial DBF (log-rank P<.0001). Median OS for the low, intermediate, and high BMV groups was 12.4 months (95% confidence interval [CI], 10.4-16.9 months), 8.2 months (95% CI, 5.0-9.7 months), and 4.3 months (95% CI, 2.6-6.7 months), respectively. Multivariate analysis showed that BMV remained the dominant predictor of OS, with a hazard ratio of 2.75 for the high BMV group (95% CI, 1.94-3.89; P<.0001) and a hazard ratio of 1.65 for the intermediate BMV group (95% CI, 1.18-2.30; P<.004). A lower BMV was associated with decreased rates of salvage WBRT (P=.02) and neurologic death (P=.008). Factors predictive for a higher BMV included ≥2 initial brain metastases (P=.004) and melanoma histology (P=.008). CONCLUSIONS: BMV is a novel metric associated with OS, neurologic death, and need for salvage WBRT after initial DBF following upfront SRS alone.

Multi-institutional Nomogram Predicting Survival Free From Salvage Whole Brain Radiation After Radiosurgery in Patients With Brain Metastases.

PURPOSE: Optimal patient selection for stereotactic radiosurgery (SRS) as the initial treatment for brain metastases is complicated and controversial. This study aimed to develop a nomogram that predicts survival without salvage whole brain radiation therapy (WBRT) after upfront SRS. METHODS AND MATERIALS: Multi-institutional data were analyzed from 895 patients with 2095 lesions treated with SRS without prior or planned WBRT. Cox proportional hazards regression model was used to identify independent pre-SRS predictors of WBRT-free survival, which were integrated to build a nomogram that was subjected to bootstrap validation. RESULTS: Median WBRT-free survival was 8 months (range, 0.1-139 months). Significant independent predictors for inferior WBRT-free survival were age (hazard ratio [HR] 1.1 for each 10-year increase), HER2(-) breast cancer (HR 1.6 relative to other histologic features), colorectal cancer (HR 1.4 relative to other histologic features), increasing number of brain metastases (HR 1.09, 1.32, 1.37, and 1.87 for 2, 3, 4, and 5+ lesions, respectively), presence of neurologic symptoms (HR 1.26), progressive systemic disease (HR 1.35), and increasing extracranial disease burden (HR 1.31 for oligometastatic and HR 1.56 for widespread). Additionally, HER2(+) breast cancer (HR 0.81) and melanoma (HR 1.11) trended toward significance. The independently weighted hazard ratios were used to create a nomogram to display estimated probabilities of 6-month and 12-month WBRT-free survival with a corrected Harrell's C concordance statistic of 0.62. CONCLUSIONS: Our nomogram can be used at initial evaluation to help select patients best suited for upfront SRS for brain metastases while reducing expense and morbidity in patients who derive minimal or no benefit.

Impact of radiosurgical management of geriatric patients with brain metastases: Clinical and quality of life outcomes.

OBJECTIVES: Recent trials have shown that whole brain radiotherapy (WBRT) can worsen performance status, particularly in the geriatric population. We reviewed our institutional experience with geriatric patients (> 70 years) with brain metastases treated with radiosurgery (SRS) to determine clinical and quality of life (QOL) outcomes. METHODS: Between 7/2000 and 1/2013, a retrospective review was performed on 467 patients treated with SRS (114 geriatric patients). Overall survival (OS), cause of death, and WBRT were evaluated. A retrospective review of geriatric patients was performed with assessments of Karnofsky performance score (KPS, N=69), mini-mental status examinations (MMSE, N=39), and Spitzer QOL (SQOL, N=39) at initial interview, 6, and 12 months after SRS. Repeated Measures ANOVA was used to evaluate differences in quality of life values. Kaplan-Meier analysis estimated survival and time to WBRT. RESULTS: Geriatric patients had a shorter OS compared to non-geriatric patients (p<0.035). Fewer patients in the geriatric cohort received whole brain (p<0.001) or subsequent Gamma Knife stereotactic radiosurgery (GKRS) (p<0.025). No difference was seen in neurologic death rates (p<0.4). In geriatric patients, SQOL declined from 0 to 6 months (mean 6.5 to 5.9, respectively, p<0.02) and 0 to 12 months (mean 6.5 and 5.6, respectively, p<0.03). KPS and MMSE scores did not change over time. Grade 3 or 4 toxicity was 9% in geriatric patients. There was no grade 5 toxicity. CONCLUSION: Geriatric patients tolerate GKRS without a significant decline in KPS or MMSE and with acceptable toxicity profile. SRS also spares a significant proportion of geriatric patients from WBRT, and its associated toxicities.

Is a Clinical Target Volume (CTV) Necessary in the Treatment of Lung Cancer in the Modern Era Combining 4-D Imaging and Image-guided Radiotherapy (IGRT)?

OBJECTIVE: We hypothesized that omission of clinical target volumes (CTV) in lung cancer radiotherapy would not compromise control by determining retrospectively if the addition of a CTV would encompass the site of failure. METHODS: Stage II-III patients were treated from 2009-2012 with daily cone-beam imaging and a 5 mm planning target volume (PTV) without a CTV. PTVs were expanded 1 cm and termed CTVretro. Recurrences were scored as 1) within the PTV, 2) within CTVretro, or 3) outside the PTV. Locoregional control (LRC), distant control (DC), progression-free survival (PFS), and overall survival (OS) were estimated. RESULT: Among 110 patients, Stage IIIA 57%, IIIB 32%, IIA 4%, and IIB 7%. Eighty-six percent of Stage III patients received chemotherapy. Median dose was 70 Gy (45-74 Gy) and fraction size ranged from 1.5-2.7 Gy. Median follow-up was 12 months, median OS was 22 months (95% CI 19-30 months), and LRC at two years was 69%. Fourteen local and eight regional events were scored with two CTVretro failures equating to a two-year CTV failure-free survival of 98%. CONCLUSION: Omission of a 1 cm CTV expansion appears feasible based on only two events among 110 patients and should be considered in radiation planning.

Image guided radiation therapy may result in improved local control in locally advanced lung cancer patients.

PURPOSE: Image guided radiation therapy (IGRT) is designed to ensure accurate and precise targeting, but whether improved clinical outcomes result is unknown. METHODS AND MATERIALS: A retrospective comparison of locally advanced lung cancer patients treated with and without IGRT from 2001 to 2012 was conducted. Median local failure-free survival (LFFS), regional, locoregional failure-free survival (LRFFS), distant failure-free survival, progression-free survival, and overall survival (OS) were estimated. Univariate and multivariate models assessed the association between patient- and treatment-related covariates and local failure. RESULTS: A total of 169 patients were treated with definitive radiation therapy and concurrent chemotherapy with a median follow-up of 48 months in the IGRT cohort and 96 months in the non-IGRT cohort. IGRT was used in 36% (62 patients) of patients. OS was similar between cohorts (2-year OS, 47% vs 49%, P = .63). The IGRT cohort had improved 2-year LFFS (80% vs 64%, P = .013) and LRFFS (75% and 62%, P = .04). Univariate analysis revealed IGRT and treatment year improved LFFS, whereas group stage, dose, and positron emission tomography/computed tomography planning had no impact. IGRT remained significant in the multivariate model with an adjusted hazard ratio of 0.40 (P = .01). Distant failure-free survival (58% vs 59%, P = .67) did not differ significantly. CONCLUSION: IGRT with daily cone beam computed tomography confers an improvement in the therapeutic ratio relative to patients treated without this technology.