Unilateral Fourth Nerve Palsy due to Presumed Metastatic Melanoma.

ABSTRACT: An 81-year-old man with a history of metastatic melanoma presented with sudden onset of painless, binocular vertical diplopia. The clinical examination was consistent with a right fourth nerve palsy. An MRI of the head revealed a mass dorsal to the right tectum at the level of the inferior colliculus. An MRI just 4 months prior did not show a lesion in that location. An MRA of the head did not show an aneurysm. This is a rare case of an isolated fourth nerve palsy believed to be due to metastatic melanoma compressing the nerve along the dorsal midbrain.

Reproducibility of a novel, vacuum-assisted immobilization for breast stereotactic radiotherapy.

A novel, breast-specific stereotactic radiotherapy device has been developed for delivery of highly conformal, accelerated partial breast irradiation. This device employs a unique, vacuum-assisted, breast cup immobilization system that applies a gentle, negative pressure to the target breast with the patient in the prone position. A device-specific patient loader is utilized for simulation scanning and device docking. Prior to clinical activation, a prospective protocol enrolled 25 patients who had been or were to be treated with breast conservation surgery and adjuvant radiotherapy for localized breast cancer. The patients underwent breast cup placement and two separate CT simulation scans. Surgical clips within the breast were mapped and positions measured against the device's integrated stereotactic fiducial/coordinate system to confirm reproducible and durable immobilization during the simulation, treatment planning, and delivery process for the device. Of the enrolled 25 patients, 16 were deemed eligible for analysis. Seventy-three clips (median, 4; mean, 4.6; range, 1-8 per patient) were mapped in these selected patients on both the first and second CT scans. X, Y, and Z coordinates were determined for the center point of each clip. Length of vector change in position was determined for each clip between the two scans. The mean displacement of implanted clips was 1.90 mm (median, 1.47 mm; range, 0.44-6.52 mm) (95% CI, 1.6-2.20 mm). Additional analyses stratified clips by position within the breast and depth into the immobilization cup. Overall, this effort validated the clinically utilized 3-mm planning target volume margin for accurate, reliable, and precise employment of the device.

Utilization of hypofractionated whole-breast radiation therapy in patients receiving chemotherapy: a National Cancer Database analysis.

PURPOSE: Results from four major hypofractionated whole-breast radiotherapy (HF-WBRT) trials have demonstrated equivalence in select patients with early-stage breast cancer when compared with conventionally fractionated WBRT (CF-WBRT). Because relatively little data were available on patients receiving neoadjuvant or adjuvant chemotherapy, consensus guidelines published in 2011 did not endorse the use of HF-WBRT in this population. Our goal is to evaluate trends in utilization of HF-WBRT in patients receiving chemotherapy. METHODS AND MATERIALS: We retrospectively analyzed data from 2004 to 2013 in the National Cancer DataBase on breast cancer patients treated with HF-WBRT who met the clinical criteria proposed by consensus guidelines (i.e., age >0 years, T1-2N0, and breast-conserving surgery), regardless of receipt of chemotherapy. We employed logistic regression to delineate and compare clinical and demographic factors associated with utilization of HF-WBRT and CF-WBRT. RESULTS: A total of 56,836 women were treated with chemotherapy and WBRT (without regional nodal irradiation) from 2004 to 2013; 9.0% (n = 5093) were treated with HF-WBRT. Utilization of HF-WBRT increased from 4.6% in 2004 to 18.2% in 2013 (odds ratio [OR] 1.21/year; P < 0.001). Among patients receiving chemotherapy, factors most dramatically associated with increased odds of receiving HF-WBRT on multivariate analysis were academic facilities (OR 2.07; P < 0.001), age >80 (OR 2.58; P < 0.001), west region (OR 1.91; P < 0.001), and distance >50 miles from cancer reporting facility (OR 1.43; P < 0.001). Factors associated with decreased odds of receiving HF-WBRT included white race, income <$48,000, lack of private insurance, T2 versus T1, and higher grade (all P < 0.02). CONCLUSIONS: Despite the absence of consensus guideline recommendations, the use of HF-WBRT in patients receiving chemotherapy has increased fourfold (absolute = 13.6%) over the last decade. Increased utilization of HF-WBRT should result in institutional reports verifying its safety and efficacy.

Increasing utilization of regional nodal irradiation in elderly node-positive women and declining emphasis on demographic factors.

PURPOSE: To evaluate the practice patterns for the use of regional nodal irradiation (RNI) in treatment of elderly women with low volume node-positive breast cancer in the setting of breast conservation surgery (BCS). METHODS: Women aged 70-89 diagnosed with unilateral, pathologic T1-2N1M0 breast cancer from 2004 to 2013, who underwent BCS and received radiotherapy were identified from the National Cancer Database. In 2011, two major trials were presented that helped define indications for RNI. Patients were dichotomized into "early", i.e. diagnosed up to 2010, and "late" cohorts. Patient and treatment characteristics were compared between the cohorts and logistic regression used to determine independent factors associated with the receipt of RNI. RESULTS: 7228 women met inclusion criteria; 4330 (59.9%) in early and 2898 (40.1%) in late cohorts. Utilization of RNI increased from 33.9% in early to 42.5% in late cohorts (P ≤ 0.001) and was independent of a general increase in RNI utilization. RNI in the early and late cohorts was not different between the study population and younger women (P > 0.05). RNI utilization increased in both cohorts with increasing number of positive lymph nodes. In the early cohort, RNI was also associated with higher grade, white race and lower income. In the late cohort, RNI increased with the presence of multiple, predefined risk factors. CONCLUSIONS: There was an increase in utilization of RNI for elderly patients from 2004 to 2013. In more recent years, the primary factors associated with receipt of RNI were tumor related with declining importance of demographic factors.

Delineation of recurrent glioblastoma by whole brain spectroscopic magnetic resonance imaging.

BACKGROUND: Glioblastoma (GBM) cellularity correlates with whole brain spectroscopic MRI (sMRI) generated relative choline to N-Acetyl-Aspartate ratio (rChoNAA) mapping. In recurrent GBM (rGBM), tumor volume (TV) delineation is challenging and rChoNAA maps may assist with re-RT targeting. METHODS: Fourteen rGBM patients underwent sMRI in a prospective study. Whole brain sMRI was performed to generate rChoNAA maps. TVs were delineated by the union of rChoNAA ratio over 2 (rChoNAA > 2) on sMRI and T1PC. rChoNAA > 2 volumes were compared with multiparametric MRI sequences including T1PC, T2/FLAIR, diffusion-restriction on apparent diffusion coefficient (ADC) maps, and perfusion relative cerebral blood volume (rCBV). RESULTS: rChoNAA > 2 (mean 27.6 cc, range 6.6-79.1 cc) was different from other imaging modalities (P ≤ 0.05). Mean T1PC volumes were 10.7 cc (range 1.2-31.4 cc). The mean non-overlapping volume of rChoNAA > 2 and T1PC was 29.2 cm3. rChoNAA > 2 was 287% larger (range 23% smaller-873% larger) than T1PC. T2/FLAIR volumes (mean 111.7 cc, range 19.0-232.7 cc) were much larger than other modalities. rCBV volumes (mean 6.2 cc, range 0.2-19.1 cc) and ADC volumes were tiny (mean 0.8 cc, range 0-3.7 cc). Eight in-field failures were observed. Three patients failed outside T1PC but within rChoNAA > 2. No grade 3 toxicities attributable to re-RT were observed. Median progression-free and overall survival for re-RT patients were 6.5 and 7.1 months, respectively. CONCLUSIONS: Treatment of rGBM may be optimized by sMRI, and failure patterns suggest benefit for dose-escalation within sMRI-delineated volumes. Dose-escalation and radiologic-pathologic studies are underway to confirm the utility of sMRI in rGBM.

Assessment of IMPT versus VMAT plans using different uncertainty scenarios for prostate cancer.

BACKGROUND: To assess the impact of systematic setup and range uncertainties for robustly optimized (RO) intensity modulated proton therapy (IMPT) and volumetric modulated arc therapy (VMAT) plans in patients with localized prostate cancer. METHODS: Twenty-six localized prostate patients previously treated with VMAT (CTV to PTV expansion of 3-5 mm) were re-planned with RO-IMPT with 3 mm and 5 mm geometrical uncertainties coupled with 3% range uncertainties. Robust evaluations (RE) accounting for the geometrical uncertainties of 3 and 5 mm were evaluated for the IMPT and VMAT plans. Clinical target volume (CTV), anorectum, and bladder dose metrics were analyzed between the nominal plans and their uncertainty perturbations. RESULTS: With geometric uncertainties of 5 mm and accounting for potential inter-fractional perturbations, RO-IMPT provided statistically significant (p < 0.05) sparing at intermediate doses (V4000cGy) to the anorectum and bladder and high dose sparring (V8000cGy) to the bladder compared to VMAT. Decreasing the RO and RE parameters to 3 mm improved IMPT sparing over VMAT at all OAR dose levels investigated while maintaining equivalent coverage to the CTV. CONCLUSIONS: For localized prostate treatments, if geometric uncertainties can be maintained at or below 3 mm, RO-IMPT provides clear dosimetric advantages in anorectum and bladder sparing compared to VMAT. This advantage remains even under uncertainty scenarios. As geometric uncertainties increase to 5 mm, RO-IMPT still provides dosimetric advantages, but to a smaller magnitude.

Factors associated with the use of salvage whole brain radiation therapy versus salvage stereotactic radiosurgery after initial stereotactic radiosurgery for brain metastases.

Objectives: Patients undergoing stereotactic radiosurgery (SRS) for brain metastases require additional radiation for relapse. Our objective is to determine the factors associated with salvage SRS versus whole brain radiation therapy (WBRT) for salvage of first intracranial failure (ICF) after upfront SRS. Method: We identified a cohort of 110 patients with brain metastases treated with SRS in the definitive or postoperative setting followed by subsequent salvage WBRT or SRS at least one month after initial SRS. Clinical and demographic characteristics were retrospectively recorded. Results: 78 Patients received SRS and 32 patients received WBRT at the time of first ICF. On multivariate analysis (MVA) factors associated with decreased use of salvage SRS were male gender (p=0.044) and local progression (p<0.001). Conclusions: Local progression and male gender were the strongest factors associated with selection of salvage WBRT. Possible etiologies of this difference could be provider or patient driven, but warrant further exploration.

Survival and Yield of Surveillance Imaging in Long-Term Survivors of Brain Metastasis Treated with Stereotactic Radiosurgery.

OBJECTIVES: The optimal frequency of surveillance brain magnetic resonance imaging (MRI) in long-term survivors with brain metastases after stereotactic radiosurgery (SRS) is unknown. Our aim was to identify the optimal frequency of surveillance imaging in long-term survivors with brain metastases after SRS. METHODS: Eligible patients were identified from a cohort treated with SRS definitively or postoperatively at our institution from 2014 to 2019 with no central nervous system (CNS) failure within 12 months from SRS. Time to CNS disease failure diagnosis and cost per patient were estimated using theoretical MRI schedules of 2, 3, 4, and 6 months starting 1 year after SRS until CNS failure. Time to diagnosis was calculated from the date of CNS progression to the theoretical imaging date on each schedule. RESULTS: This cohort included 55 patients (median follow-up from SRS: 2.48 years). During the study period, 20.0% had CNS disease failure (median: 2.26 years from SRS treatment). In this cohort, a theoretical 2-month, 3-month, 4-month, and 6-month MRI brain surveillance schedule produced a respective estimated time to diagnosis of CNS disease failure of 1.11, 1.74, 1.65, and 3.65 months. The cost of expedited diagnosis for the cohort (dollars/month) for each theoretical imaging schedule compared with a 6-month surveillance schedule was $6600 for a 2-month protocol, $4496 for a 3-month protocol, and $2180 for a 4-month protocol. CONCLUSIONS: Based on cost-benefit, a 4-month MRI brain schedule should be considered in patients with metastatic disease to the brain treated definitively or postoperatively with SRS without evidence of CNS recurrence at 1 year.

Early Magnetic Resonance Imaging After Gamma Knife Radiosurgery of Brain Metastases.

BACKGROUND: Gamma knife radiosurgery (GKRS) is often performed to treat brain metastases (BrMs). Widely referenced guidelines have suggested post-treatment imaging studies at 3-month intervals. However, clinicians frequently obtain magnetic resonance imaging (MRI) studies at <3 months after GKRS. METHODS: We performed a retrospective medical record review study to assess the utility of early (<3 months) MRI after GKRS in patients with BrMs. RESULTS: A total of 415 GKRS procedures were performed. For 325 patients, early MRI studies were obtained. A total of 31 patients had new or worsened neurological symptoms. The early MRI studies showed adverse findings in 25 patients (78%), which in 23 (72%) had resulted in a change in treatment. For 294 patients, no new or worsened neurological symptoms were found on early MRI studies. Of these 294 patients, 86 (29%) had ≥1 adverse finding on MRI, and 60 (20%) had a change in management as a result. However, no rapidly growing tumors or other emergent adverse findings were seen. CONCLUSIONS: Early MRI (within 3 months) after post GKRS will frequently show adverse findings even in asymptomatic patients, more often in patients aged <65 years and patients with multiple treated BrMs. However, according to the nature of the adverse findings observed in our retrospective study, it is unlikely that the clinical outcomes would have been affected if the post-GKRS MRI studies had been deferred to 3 months after treatment. Our data support deferring post-GKRS MRI to 3 months after treatment in the absence of new neurological signs or symptoms.

Assessment of single isocenter linear accelerator radiosurgery for metastases and base of skull lesions.

BACKGROUND: Newer technology for stereotactic radiosurgery (SRS) should be assessed for different multi-leaf collimators (MLC). OBJECTIVE: Assess plan quality of an automated, frameless, linear accelerator based (linac) planning and delivery system (HyperArc) for SRS using both standard MLC (SMLC) and high definition MLC (HDMLC) compared to a cobalt-60 based SRS system (Gamma Knife, GK). METHODS: We re-planned twenty GK Perfexion-treated SRS patients (27 lesions) for HyperArc using SMLC and HDMLC. We assessed plan quality using the following metrics: gradient index (GI), Paddick and RTOG conformity indices (CIPaddick, CIRTOG), volume receiving half of prescription isodose (PIVhalf) and maximum dose to 0.03 cc for brainstem, optic chiasm and optic nerves, and V12Gy for brain-GTV. RESULTS: Linac plans had better conformity with HDMLC being most conformal. GK exhibited better GI. PIVhalf demonstrated no statistically significant difference between HDMLC and GK, and SMLC was nominally worse than GK. Mean PIVhalf was generally 0.85 cc larger for SMLC than HDMLC. For TV > 1.0 cc, the relative differences in CIRTOG, GI, and PIVhalf for SMLC vs. HDMLC were less than 21%. For TV less than < 1.0 cc, there were more obvious relative differences for SMLC vs. HDMLC in CIRTOG (mean 146%, max 700%), GI (mean 49%, max 162%), and PIVhalf (mean 77%, max 522%). Organ at risk doses were met in all plans. CONCLUSIONS: New linac-based plans positively compare to GK plans overall. HDMLC should be strongly considered for treatment of lesions < 1.0 cc given the significant improvements in conformity and PIVhalf over SMLC.

Knowledge-Based Planning for Robustly Optimized Intensity-Modulated Proton Therapy of Head and Neck Cancer Patients.

PURPOSE: To assess the performance of a proton-specific knowledge-based planning (KBP) model in the creation of robustly optimized intensity-modulated proton therapy (IMPT) plans for treatment of advanced head and neck (HN) cancer patients. METHODS: Seventy-three patients diagnosed with advanced HN cancer previously treated with volumetric modulated arc therapy (VMAT) were selected and replanned with robustly optimized IMPT. A proton-specific KBP model, RapidPlanPT (RPP), was generated using 53 patients (20 unilateral cases and 33 bilateral cases). The remaining 20 patients (10 unilateral and 10 bilateral cases) were used for model validation. The model was validated by comparing the target coverage and organ at risk (OAR) sparing in the RPP-generated IMPT plans with those in the expert plans. To account for the robustness of the plan, all uncertainty scenarios were included in the analysis. RESULTS: All the RPP plans generated were clinically acceptable. For unilateral cases, RPP plans had higher CTV_primary V100 (1.59% ± 1.24%) but higher homogeneity index (HI) (0.7 ± 0.73) than had the expert plans. In addition, the RPP plans had better ipsilateral cochlea Dmean (-5.76 ± 6.11 Gy), with marginal to no significant difference between RPP plans and expert plans for all other OAR dosimetric indices. For the bilateral cases, the V100 for all clinical target volumes (CTVs) was higher for the RPP plans than for the expert plans, especially the CTV_primary V100 (5.08% ± 3.02%), with no significant difference in the HI. With respect to OAR sparing, RPP plans had a lower spinal cord Dmax (-5.74 ± 5.72 Gy), lower cochlea Dmean (left, -6.05 ± 4.33 Gy; right, -4.84 ± 4.66 Gy), lower left and right parotid V20Gy (left, -6.45% ± 5.32%; right, -6.92% ± 3.45%), and a lower integral dose (-0.19 ± 0.19 Gy). However, RPP plans increased the Dmax in the body outside of CTV (body-CTV) (1.2 ± 1.43 Gy), indicating a slightly higher hotspot produced by the RPP plans. CONCLUSION: IMPT plans generated by a broad-scope RPP model have a quality that is, at minimum, comparable with, and at times superior to, that of the expert plans. The RPP plans demonstrated a greater robustness for CTV coverage and better sparing for several OARs.

Proton therapy for thoracic malignancies: a review of oncologic outcomes.

Introduction: Radiotherapy is an integral component in the treatment of the majority of thoracic malignancies. By taking advantage of the steep dose fall-off characteristic of protons combined with modern optimization and delivery techniques, proton beam therapy (PBT) has emerged as a potential tool to improve oncologic outcomes while reducing toxicities from treatment.Areas covered: We review the physical properties and treatment techniques that form the basis of PBT as applicable for thoracic malignancies, including a brief discussion on the recent advances that show promise to enhance treatment planning and delivery. The dosimetric advantages and clinical outcomes of PBT are critically reviewed for each of the major thoracic malignancies, including lung cancer, esophageal cancer, mesothelioma, thymic cancer, and primary mediastinal lymphoma.Expert opinion: Despite clear dosimetric benefits with PBT in thoracic radiotherapy, the improvement in clinical outcomes remains to be seen. Nevertheless, with the incorporation of newer techniques, PBT remains a promising modality and ongoing randomized studies will clarify its role to determine which patients with thoracic malignancies receive the most benefit. Re-irradiation, advanced disease requiring high cardio-pulmonary irradiation volume and younger patients will likely derive maximum benefit with modern PBT.

MR-Guided Radiotherapy for Brain and Spine Tumors.

MRI is the standard modality to assess anatomy and response to treatment in brain and spine tumors given its superb anatomic soft tissue contrast (e.g., T1 and T2) and numerous additional intrinsic contrast mechanisms that can be used to investigate physiology (e.g., diffusion, perfusion, spectroscopy). As such, hybrid MRI and radiotherapy (RT) devices hold unique promise for Magnetic Resonance guided Radiation Therapy (MRgRT). In the brain, MRgRT provides daily visualizations of evolving tumors that are not seen with cone beam CT guidance and cannot be fully characterized with occasional standalone MRI scans. Significant evolving anatomic changes during radiotherapy can be observed in patients with glioblastoma during the 6-week fractionated MRIgRT course. In this review, a case of rapidly changing symptomatic tumor is demonstrated for possible therapy adaptation. For stereotactic body RT of the spine, MRgRT acquires clear isotropic images of tumor in relation to spinal cord, cerebral spinal fluid, and nearby moving organs at risk such as bowel. This visualization allows for setup reassurance and the possibility of adaptive radiotherapy based on anatomy in difficult cases. A review of the literature for MR relaxometry, diffusion, perfusion, and spectroscopy during RT is also presented. These techniques are known to correlate with physiologic changes in the tumor such as cellularity, necrosis, and metabolism, and serve as early biomarkers of chemotherapy and RT response correlating with patient survival. While physiologic tumor investigations during RT have been limited by the feasibility and cost of obtaining frequent standalone MRIs, MRIgRT systems have enabled daily and widespread physiologic measurements. We demonstrate an example case of a poorly responding tumor on the 0.35 T MRIgRT system with relaxometry and diffusion measured several times per week. Future studies must elucidate which changes in MR-based physiologic metrics and at which timepoints best predict patient outcomes. This will lead to early treatment intensification for tumors identified to have the worst physiologic responses during RT in efforts to improve glioblastoma survival.

Assessment of intra-fraction motion during automated linac-based SRS treatment delivery with an open face mask system.

PURPOSE/OBJECTIVE: To evaluate intra-fraction target shift during automated mono-isocentric linac-based stereotactic radiosurgery with open-face mask system and optical real-time tracking. MATERIALS/METHODS: Ninety-five patients were treated using automated linac-based stereotactic radiosurgery in 1-5 fractions with single isocenter for a total of 195 fractions. During treatment, patient positioning was tracked real-time with optical surface guidance and immobilized with a rigid open-face mask. Patients were re-positioned if optical surface guidance error exceeded 1 mm magnitude or 1°. Translational and rotational intra-fractional changes were determined by post-treatment CBCT matched to the planning CT. Target specific error was calculated by translation and rotation matrices applied to isocenter and target spatial coordinates. RESULTS: For 132 fractions with isocenter within a single target, the median shift magnitude was 0.40 mm with a maximum shift of 1.17 mm. A total of 398 targets treated for plans having multiple or single targets that lied outside isocenter, resulted in a median shift magnitude of 0.46 mm, with median translational shifts of 0.20 mm and 0.20° rotational shifts. A 1 mm PTV margin was insufficient in 18% of targets at a distance greater than 6 cm away from isocenter, but sufficient for 96% of targets within 6 cm. CONCLUSIONS: The findings of this study support 1 mm PTV expansion due to intra-fraction motion to ensure target coverage for plans with isocenter placement less than 6 cm away from the targets.

Assessment of daily dose accumulation for robustly optimized intensity modulated proton therapy treatment of prostate cancer.

PURPOSE: To implement a daily CBCT based dose accumulation technique in order to assess ideal robust optimization (RO) parameters for IMPT treatment of prostate cancer. METHODS: Ten prostate cancer patients previously treated with VMAT and having daily CBCT were included. First, RO-IMPT plans were created with ± 3 mm and ± 5 mm patient setup and ± 3% proton range uncertainties, respectively. Second, the planning CT (pCT) was deformably registered to the CBCT to create a synthetic CT (sCT). Both daily and weekly sampling strategies were employed to determine optimal dose accumulation frequency. Doses were recalculated on sCTs for both ± 3 mm/±3% and ± 5 mm/±3% uncertainties and were accumulated back to the pCT. Accumulated doses generated from ± 3 mm/±3% and ± 5 mm/±3% RO-IMPT plans were evaluated using the clinical dose volume constraints for CTV, bladder, and rectum. RESULTS: Daily accumulated dose based on both ± 3mm/±3% and ±5 mm/±3% uncertainties for RO-IMPT plans resulted in satisfactory CTV coverage (RO-IMPT3mm/3% CTVV95 = 99.01 ± 0.87% vs. RO-IMPT5mm/3% CTVV95 = 99.81 ± 0.2%, P = 0.002). However, the accumulated dose based on ± 3 mm/3% RO-IMPT plans consistently provided greater OAR sparing than ±5 mm/±3% RO-IMPT plans (RO-IMPT3mm/3% rectumV65Gy = 2.93 ± 2.39% vs. RO-IMPT5mm/3% rectumV65Gy = 4.38 ± 3%, P < 0.01; RO-IMPT3mm/3% bladderV65Gy = 5.2 ± 7.12% vs. RO-IMPT5mm/3% bladderV65Gy = 7.12 ± 9.59%, P < 0.01). The gamma analysis showed high dosimetric agreement between weekly and daily accumulated dose distributions. CONCLUSIONS: This study demonstrated that for RO-IMPT optimization, ±3mm/±3% uncertainty is sufficient to create plans that meet desired CTV coverage while achieving superior sparing to OARs when compared with ± 5 mm/±3% uncertainty. Furthermore, weekly dose accumulation can accurately estimate the overall dose delivered to prostate cancer patients.

Variation in Management of Extremity Soft-Tissue Sarcoma in Younger vs Older Adults.

Importance: A large proportion of extremity soft-tissue sarcomas (ESS) occur among young adults, yet this group is underrepresented in clinical trials, resulting in limited data on this population. Younger patients present many complex challenges that affect clinical management. Objective: To investigate variations in treatment management in young adults vs older adults with ESS. Design, Setting, and Participants: This multicenter retrospective cohort study used the National Cancer Data Base (NCDB) to identify patients 18 years and older with ESS who received definitive treatment (ie, limb-sparing surgery [LSS] or amputation) between 2004 and 2014. Data analysis was conducted in November 2019. Exposures: Treatment regimen received among young adults (aged 18-39 years) and older adults (≥40 years) after diagnosis with ESS. Main Outcomes and Measures: To detect unique factors associated with treatment decisions in young adults with ESS, multivariable analyses used logistic regressions for patterns of treatment and their association with demographic factors and tumor characteristics. Results: Overall, 8953 patients were identified, and among these, 1280 (14.3%) were young adults. From the full cohort, 4796 patients (53.6%) identified as male and 6615 (73.9%) identified as non-Hispanic White. More young adults than older adults underwent amputation (age 18-39 years, 104 of 1280 [8.1%]; age 40-64 years, 217 of 3937 [5.5%]; aged ≥65 years, 199 of 3736 [5.3%]), but the association was not statistically significant (age ≥65 years, odds ratio [OR], 1.49; 95% CI, 1.00-2.23; P = .05). Young adults were more likely to receive chemotherapy than older patients (age 40-65 years, OR, 0.52; 95% CI, 0.45-0.60; P = .001; ≥65 years, OR, 0.16; 95% CI, 0.12-0.20; P = .001). Conversely, young adults were less likely to receive radiation therapy compared with older patients (age 40-65 years, OR, 1.40; 95% CI, 1.22-1.61; P = .001; ≥65 years, OR, 1.33; 95% CI, 1.10-1.61; P = .003). Unique to younger adults, clinical stage II disease vs stage I and positive surgical margins were not associated with use of radiation therapy (stage II disease: OR, 1.25; 95% CI, 0.81-1.91; P = .31; positive surgical margins: OR, 1.43; 95% CI, 0.93-2.22; P = .11). White Hispanic young adults were less likely than non-Hispanic White young adults to receive radiation therapy (OR, 0.53; 95% CI, 0.36-0.78; P = .002). Conclusions and Relevance: In this study, young adults with ESS were more likely to receive chemotherapy and less likely to receive radiation therapy than older adults. Further study is warranted to identify the clinical outcomes of these practice disparities.

CBCT-Based Adaptive Assessment Workflow for Intensity Modulated Proton Therapy for Head and Neck Cancer.

PURPOSE: Anatomical changes and patient setup uncertainties during intensity modulated proton therapy (IMPT) of head and neck (HN) cancers demand frequent evaluation of delivered dose. This work investigated a cone-beam computed tomography (CBCT) and deformable image registration based therapy workflow to demonstrate the feasibility of proton dose calculation on synthetic computed tomography (sCT) for adaptive IMPT treatment of HN cancer. MATERIALS AND METHODS: Twenty-one patients with HN cancer were enrolled in this study, a retrospective institutional review board protocol. They had previously been treated with volumetric modulated arc therapy and had daily iterative CBCT. For each patient, robust optimization (RO) IMPT plans were generated using ±3 mm patient setup and ±3% proton range uncertainties. The sCTs were created and the weekly delivered dose was recalculated using an adaptive dose accumulation workflow in which the planning computed tomography (CT) was deformably registered to CBCTs and Hounsfield units transferred from the planning CT. Accumulated doses from ±3 mm/±3% RO-IMPT plans were evaluated using clinical dose-volume constraints for targets (clinical target volume, or CTV) and organs at risk. RESULTS: Evaluation of weekly recalculated dose on sCTs showed that most of the patient plans maintained target dose coverage. The primary CTV remained covered by the V95 > 95% (95% of the volume receiving more than 95% of the prescription dose) worst-case scenario for 84.5% of the weekly fractions. The oral cavity accumulated mean dose remained lower than the worst-case scenario for all patients. Parotid accumulated mean dose remained within the uncertainty bands for 18 of the 21 patients, and all were kept lower than RO-IMPT worst-case scenario for 88.7% and 84.5% for left and right parotids, respectively. CONCLUSION: This study demonstrated that RO-IMPT plans account for most setup and anatomical uncertainties, except for large weight-loss changes that need to be tracked throughout the treatment course. We showed that sCTs could be a powerful decision tool for adaptation of these cases in order to reduce workload when using repeat CTs.

Emergent Radiotherapy for Leukemia-Induced Cranial Neuropathies Refractory to Intrathecal Therapy.

Neurologic symptoms from leukemic infiltration of the central nervous system are an oncologic emergency, and expeditious treatment is required to preserve function. We report the case of a 44-year-old patient with relapsed acute myeloid leukemia (AML) who developed sub-acute cranial neuropathies refractory to treatment with intrathecal (IT) chemotherapy. The patient was therefore treated with an emergent course of whole-brain radiotherapy, resulting in immediate improvement and subsequent resolution of cranial neuropathies. This case illustrates that while central nervous system involvement by AML is rare, radiotherapy remains an effective modality to avoid long-term morbidity in patients failing to respond to systemic or IT chemotherapy.

Spatially Fractionated Radiotherapy (GRID) Prior to Standard Neoadjuvant Conventionally Fractionated Radiotherapy for Bulky, High-Risk Soft Tissue and Osteosarcomas: Feasibility, Safety, and Promising Pathologic Response Rates.

Spatially fractionated radiotherapy (GRID) has been utilized primarily in the palliative and definitive treatment of bulky tumors. Delivered in the modern era primarily with megavoltage photon therapy, this technique offers the promise of safe dose escalation with potential immunogenic, bystander and microvasculature effects that can augment a conventionally fractionated course of radiotherapy. At the University of Maryland, an institutional standard has arisen to incorporate a single fraction of GRID radiation in large (>8 cm), high-risk soft tissue and osteosarcomas prior to a standard fractionated course. Herein, we report on the excellent pathologic responses and apparent safety of this regimen in 26 consecutive patients.

Patterns of Care and Survival in Stage III NSCLC Among Black and Latino Patients Compared With White Patients.

BACKGROUND: Race and socioeconomic status have continued to affect the survival and patterns of care of patients with non-small-cell lung cancer (NSCLC). However, data evaluating these associations in patients with stage III disease remain limited. Therefore, we investigated the patterns of care and overall survival (OS) of black and Latino patients with locally advanced NSCLC compared with white patients, using the National Cancer Database. MATERIALS AND METHODS: All patients with stage III NSCLC from 2004 to 2013 who had undergone external beam radiotherapy (RT) alone, RT with chemotherapy (bimodality), or RT with chemotherapy followed by surgery (trimodality) were analyzed within the National Cancer Database according to race (n = 113,945). Univariate associations among the demographic, disease, and treatment characteristics within the 3 cohorts were assessed using χ2 tests. The OS between cohorts were analyzed using the log-rank test and multivariate Cox proportional hazards regression. RESULTS: The black and Latino patients were younger at diagnosis, had lower median household incomes, and were less likely to be insured than were the white patients. The black patients were more likely to receive RT alone (19.3% vs. 18%; P < .001) and less likely to have undergone concurrent chemo-RT (53.6% vs. 56.1%; P < .001) compared with the white patients. Black patients had improved OS (P < .001). In contrast, the Latino patients had survival equivalent to that of the white patients (P = .920). CONCLUSIONS: Despite epidemiologic differences and a propensity for less aggressive treatment, black patients with locally advanced NSCLC had better OS than white patients and Latino patients had equivalent outcomes. Additional research is needed to elucidate this finding, perhaps focusing on biological differences among the cohorts.