Radionecrosis (RN) in patients with brain metastases treated with stereotactic radiosurgery (SRS) and immunotherapy.

OBJECTIVES: Limited data exist regarding radionecrosis (RN) rates when patients receive immunotherapy (IT) and SRS for brain metastases. This study assesses the influence of such treatments on the rate of RN. METHODS: We retrospectively reviewed 352 lesions from 105 patients with metastatic melanoma or NSCLC treated with SRS and IT from 2012 to 2018. Lesions were excluded from analysis if patients had received WBRT or prior GK to the same lesion, if RN occurred before IT, or if IT had been discontinued >6 months pre-SRS or initiated >1 year post-SRS. IT was delivered concurrently (±30 days of SRS) or sequentially. Overall survival and RN rates were assessed with Kaplan-Meier analysis. Univariate analysis and multivariate analysis were performed to identify characteristics predicting RN. RESULTS: Of 195 lesions from 63 patients included in analysis, the median prescription dose, IDL, lesion volume, and maximum tumor dimension (MTD) were 19 Gy, 50%, 0.15 cc and 0.8 cm, respectively. RN rates at 1, 2, and 3 years were 7.3%, 10.4% and 10.4%. On UVA, RN risk increased with, isodose volume (IDV), MTD, and tumor volume (TV) whereas conformity index was associated with a trend toward decreased RN risk. Two-year RN rates increased with TV ≥ 0.3 cc (16% vs 1.1% p = 0.001), MTD ≥ 1.3 cm (19.1% vs 1.8% p < 0.003), and IDV ≥ 1.5 cc (19.6% vs 1.7% p = 0.001). Concurrent vs sequential timing of IT did not predict for RN. CONCLUSIONS: Patients who received IT and SRS had acceptably low rates of RN. Timing of IT did not predict for RN. Further investigation is warranted to define RN risk with combined SRS and IT.

Using previously registered cone beam computerized tomography images to facilitate online computerized tomography to cone beam computerized tomography image registration in lung stereotactic body radiation therapy.

PURPOSE: In our conventional image registration workflow, the four-dimensional (4D) CBCT was directly registered to the reference helical CT (HCT) using a dual registration approach within the Elekta XVI software. In this study, we proposed a new HCT-CBCT auto-registration strategy using a previously registered CBCT (CBCTpre) as the reference image and tested its clinical feasibility. METHODS: From a previous CBCT session, the registered average 4D CBCT was selected as CBCTpre and the HCT-CBCTpre registration vector from the clinician's manual registration result was recorded. In the new CBCT session, auto-registration was performed between the new average 4D CBCT (CBCTtx) and CBCTpre (CBCTpre-CBCTtx). The overall HCT-CBCTtx registration result was then derived by combing the results from two registrations (i.e., HCT-CBCTpre + CBCTpre-CBCTtx). The results from the proposed method were compared with clinician's manually adjusted HCT-CBCTtx registration results ("ground truth") to evaluate its accuracy using a test dataset consisting of 32 challenging registration cases. RESULTS: The uncertainty of the proposed auto-registration method was -0.1 ± 0.5, 0.1 ± 1.0, and -0.1 ± 0.7 mm in three translational directions (lateral, longitudinal, and vertical) and 0.0° ± 0.9°, 0.3° ± 0.9°, and 0.4° ± 0.7° in three rotation directions, respectively. Two patients (6.3%) had translational uncertainty > 2 mm (max = 3.1 mm) and both occurred in the longitudinal direction. Meanwhile, the uncertainty of the conventional direct HCT-CBCTtx auto-registration was -0.4 ± 2.6, -0.2 ± 7.4, -1.4 ± 3.6 mm for translations and -0.3° ± 1.2°, 0.0° ± 1.6°, and 0.1 ± 1.1° for rotations. Eleven patients (34.4%) had translation uncertainty > 2 mm (max = 26.2 mm) in at least one direction. Accuracy in translation was improved with the new method, while rotation accuracy stayed in the same order. CONCLUSION: We demonstrated the feasibility of incorporating prior clinical registration knowledge into the online HCT-CBCT registration process. The proposed auto-registration method provides a quick and reliable starting solution for online HCT-CBCT registration.

Local failure after stereotactic radiosurgery (SRS) for intracranial metastasis: analysis from a cooperative, prospective national registry.

INTRODUCTION: Stereotactic radiosurgery (SRS) has been increasingly employed to treat patients with intracranial metastasis, both as a salvage treatment after failed whole brain radiation therapy (WBRT) and as an initial treatment. "Several studies have shown that SRS may be as effective as WBRT with the added benefit of preserving neuro-cognition". However, some patients may have local failure following SRS for intracranial metastasis, defined as increase in total lesion volume by 25% after at least 3 months of follow up. METHODS: The SRS registry, established by the Neuro point alliance (NPA) under the auspices of the American Association of Neurological Surgeons (AANS), was queried for patients with intracranial metastasis receiving SRS at the participating sites. Demographic, clinical symptoms, tumor, and treatment characteristics as well as follow up status were summarized for the cohort. A multivariable explanatory cox- regression was performed to evaluate the impact of each of the factors on time to local failure.at last follow-up. RESULTS: A total of 441 patients with 1255 intracranial metastatic lesions undergoing SRS were identified. The most common primary cancer histology was non-small cell lung cancer (43.8%, n = 193). More than half of the cohort had more than 1 metastatic lesion (2-3 lesions: 29.5%, n = 130; more than 3 lesions: 25.2% (n = 111). The average duration of follow-up for the cohort was found to be 8.4 months (SD = 7.61). The mean clinical treatment volume (CTV), after adding together the volume of each lesion for each patient was 5.39 cc (SD = 7.6) at baseline. A total of 20.2% (n = 89) had local failure (increase in volume by > 25%) with a mean time to progression of 7.719 months (SD = 6.09). The progression free survival (PFS) for the cohort at 3, 6 and 12 months were found to be 94.9%, 84.3%, and 69.4%, respectively. On multivariable cox regression analysis, factors associated with increased hazard of local failure included male gender (HR 1.65, 95% CI 1.03-2.66, p = 0.037), chemotherapy at or before SRS (HR = 2.39, 95% CI 1.41-4.05, p = 0.001), WBRT at or before SRS (HR = 2.21, 95% CI 1.16- 4.22, p = 0.017), while surgical resection (HR 0.45, 95% CI 0.21-0. 97, p = 0.04) and immunotherapy (0.34, 95% CI 0.16-0.50, p = 0.014) were associated with lower hazard of local failure. CONCLUSION: Factors found to be predictive of local failure included higher RPA score and those receiving chemotherapy, while patients undergoing surgical resection and those with occipital lobe lesions were less likely to experience local failure. Our analyses not only corroborate those previously reported but also demonstrate the utility of a multi-institutional registry to advance real-world SRS research for patients with intracranial metastatic lesions.

Functional avoidance-based intensity modulated proton therapy with 4DCT derived ventilation imaging for lung cancer.

The primary objective is to evaluate the potential dosimetric gains of performing functional avoidance-based proton treatment planning using 4DCT derived ventilation imaging. 4DCT data of 31 patients from a prospective functional avoidance clinical trial were evaluated with intensity modulated proton therapy (IMPT) plans and compared with clinical volumetric modulated arc therapy (VMAT) plans. Dosimetric parameters were compared between standard and functional plans with IMPT and VMAT with one-way analysis of variance and post hoc paired student t-test. Normal Tissue Complication Probability (NTCP) models were employed to estimate the risk of two toxicity endpoints for healthy lung tissues. Dose degradation due to proton motion interplay effect was evaluated. Functional IMPT plans led to significant dose reduction to functional lung structures when compared with functional VMAT without significant dose increase to Organ at Risk (OAR) structures. When interplay effect is considered, no significant dose degradation was observed for the OARs or the clinical target volume (CTV) volumes for functional IMPT. Using fV20 as the dose metric and Grade 2+ pneumonitis as toxicity endpoint, there is a mean 5.7% reduction in Grade 2+ RP with the functional IMPT and as high as 26% in reduction for individual patient when compared to the standard IMPT planning. Functional IMPT was able to spare healthy lung tissue to avoid excess dose to normal structures while maintaining satisfying target coverage. NTCP calculation also shows that the risk of pulmonary complications can be further reduced with functional based IMPT.

Risk of Brain Arteriovenous Malformation Hemorrhage Before and After Stereotactic Radiosurgery.

Background and Purpose- Understanding the hemorrhage risks associated with brain arteriovenous malformations (AVMs) before and after stereotactic radiosurgery (SRS) is important. The aims of this multicenter, retrospective cohort study are to evaluate and compare the rates of pre- and post-SRS AVM hemorrhage and identify risk factors. Methods- We pooled AVM SRS data from 8 institutions participating in the International Radiosurgery Research Foundation. Predictors of post-SRS hemorrhage were determined using a multivariate logistic regression model. Pre- and post-SRS hemorrhage rates were compared using Fisher exact test. Ruptured and unruptured AVMs were matched in a 1:1 ratio using propensity scores, and their outcomes were compared. Results- The study cohort comprised 2320 AVM patients who underwent SRS. Deep AVM location (odds ratio, 1.86; 95% CI, 1.19-2.92; P=0.007), the presence of an AVM-associated arterial aneurysm (odds ratio, 2.44; 95% CI, 1.63-3.66; P<0.001), and lower SRS margin dose (odds ratio, 0.93; 95% CI, 0.88-0.98; P=0.005) were independent predictors of post-SRS hemorrhage. The post-SRS hemorrhage rate was lower for obliterated versus patent AVMs (6.0 versus 22.3 hemorrhages/1000 person-years; P<0.001). The AVM hemorrhage rate decreased from 15.4 hemorrhages/1000 person-years before SRS to 11.9 after SRS ( P=0.001). The outcomes of the matched ruptured versus unruptured AVM cohorts were similar. Conclusions- SRS appears to reduce the risk of AVM hemorrhage, although this effect is predominantly driven by obliteration. Deep-seated AVMs are more likely to rupture during the latency period after SRS. AVM-associated aneurysms should be considered for selective occlusion before SRS of the nidus to ameliorate the post-SRS hemorrhage rate of these lesions.

Stereotactic Radiosurgery for Unruptured Versus Ruptured Pediatric Brain Arteriovenous Malformations.

Background and Purpose- The effects of prior hemorrhage on stereotactic radiosurgery (SRS) outcomes for pediatric arteriovenous malformations (AVMs) are not well defined. The aim of this multicenter, retrospective cohort study is to compare the SRS outcomes for unruptured versus ruptured pediatric AVMs. Methods- The International Radiosurgery Research Foundation pediatric AVM database from 1987 to 2018 was reviewed retrospectively. Favorable outcome was defined as AVM obliteration, no post-SRS hemorrhage, and no permanently symptomatic radiation-induced changes. Associations between prior hemorrhage and outcomes were adjusted for baseline differences, inverse probability weights, and competing risks. Results- The study cohort comprised 153 unruptured and 386 ruptured AVMs. Favorable outcome was achieved in 48.4% and 60.4% of unruptured and ruptured AVMs, respectively (adjusted odds ratio, 1.353; P=0.190). Cumulative AVM obliteration probabilities were 51.2%, 59.4%, 64.2%, and 70.0% for unruptured and 61.0%, 69.3%, 74.0%, and 79.3% for ruptured AVMs at 4, 6, 8, and 10 years, respectively (subhazard ratio, 1.311; P=0.020). Cumulative post-SRS hemorrhage probabilities were 4.5%, 5.6%, 5.6%, and 9.8% for unruptured and 4.7%, 6.1%, 6.1%, and 10.6% for ruptured AVMs at 4, 6, 8, and 10 years, respectively (subhazard ratio, 1.086; P=0.825). Probabilities of AVM obliteration (adjusted subhazard ratio, 0.968; P=0.850) and post-SRS hemorrhage (adjusted subhazard ratio, 1.663; P=0.251) were comparable between the 2 cohorts after inverse probability weight adjustments. Symptomatic (15.8% versus 8.1%; adjusted odds ratio, 0.400; P=0.008) and permanent (9.2% versus 5.0%; adjusted odds ratio, 0.441; P=0.045) radiation-induced change were more common in unruptured AVMs. Conclusions- The overall outcomes after SRS for unruptured versus ruptured pediatric AVMs are comparable. However, symptomatic and permanent radiation-induced change occur more frequently in pediatric patients with unruptured AVMs.

Improving dosimetric outcome for hippocampus and cochlea sparing whole brain radiotherapy using spot-scanning proton arc therapy.

This feasibility study shows that Spot-scanning Proton Arc therapy (SPArc) is able to significantly reduce the dose to the hippocampus and cochlea compared to both Volumetric Modulated Arc Photon Therapy (VMAT) and the robust optimized Intensity Modulated Proton Therapy (ro-IMPT) plans in whole brain radiotherapy. Furthermore, SPArc not only improves plan robustness but could potentially deliver a treatment as efficient as ro-IMPT when proton system's energy layer switch time is less than 1 s.

Intrafraction 4D-cone beam CT acquired during volumetric arc radiotherapy delivery: kV parameter optimization and 4D motion accuracy for lung stereotactic body radiotherapy (SBRT) patients.

PURPOSE: Elekta XVI 5.0 allows for four-dimensional cone beam computed tomography (4D CBCT) image acquisition during treatment delivery to monitor intrafraction motion. These images can have poorer image quality due to undersampling of kV projections and treatment beam MV scatter effects. We determine if a universal intrafraction preset can be used for stereotactic body radiotherapy (SBRT) lung patients and validate the accuracy of target motion characterized by XVI intrafraction 4D CBCT. METHODS: The most critical parameter within the intrafraction preset is the nominal AcquisitionInterval, which controls kV imaging acquisition frequency. An optimal value was determined by maximizing the kV frame number acquired up to 1000 frames, typical of pretreatment 4D CBCT. CIRS motion phantom intrafraction phase images for 16 SBRT beams were obtained. Mean target position, time-weighted standard deviation, and amplitude for these images as well as target motion for three SBRT lung patients were compared to respective pretreatment 4D CBCTs. Evaluation of intrafraction 4D CBCT reconstruction revealed inclusion of MV only images acquired to remove MV scatter effects. A workaround to remove these images was developed. RESULTS: AcquisitionInterval of 0.1°/frame was optimal. The number of kV frames acquired was 567-1116 and showed strong linear correlation with beam monitor unit (MUs). Phantom target motion accuracy was excellent with average differences in target position, standard deviation and amplitude range of ≤0.5 mm. Target tracking for SBRT patients also showed good agreement. Evaluation of phase sorting wave forms showed that inclusion of MV only images significantly impacts intrafraction image reconstruction for patients and use of workaround is necessary. CONCLUSIONS: A universal intrafraction imaging preset can be used safely for SBRT lung patients. The number of kV projections with MV delivery parameters varies; however images with fewer kV projections still provided accurate target position information. Impact of the reconstruction workaround was significant and is mandated for all 4D CBCT intrafraction imaging performed at our institution.

Stereotactic Radiosurgery for Pediatric Versus Adult Brain Arteriovenous Malformations.

Background and Purpose- The aim of this international, multicenter, retrospective matched cohort study is to directly compare the outcomes after stereotactic radiosurgery (SRS) for brain arteriovenous malformations (AVM) in pediatric versus adult patients. Methods- We performed a retrospective review of patients with AVM who underwent SRS at 8 institutions participating in the International Gamma Knife Research Foundation from 1987 to 2014. Patients were categorized into pediatric (<18 years of age) and adult (≥18 years of age) cohorts and matched in a 1:1 ratio using propensity scores. Favorable outcome was defined as AVM obliteration, no post-SRS hemorrhage, and no permanently symptomatic radiation-induced changes. Results- From a total of 2191 patients who were eligible for inclusion in the overall study cohort, 315 were selected for each of the matched cohorts. There were no significant differences between matched pediatric versus adult cohorts with respect to the rates of favorable outcome (59% versus 58%; P=0.936), AVM obliteration (62% versus 63%; P=0.934), post-SRS hemorrhage (9% versus 7%; P=0.298), radiological radiation-induced changes (26% versus 26%; P=0.837), symptomatic radiation-induced changes (7% versus 9%; P=0.383), or permanent radiation-induced changes (2% versus 3%; P=0.589). The all-cause mortality rate was significantly lower in the matched pediatric cohort (3% versus 10%; P=0.003). Conclusions- The outcomes after SRS for comparable AVMs in pediatric versus adult patients were not found to be appreciably different. SRS remains a reasonable treatment option for appropriately selected pediatric patients with AVM, who harbor a high cumulative lifetime hemorrhage risk. Age seems to be a poor predictor of AVM outcomes after SRS.

A matched-pair analysis of stereotactic body radiotherapy (SBRT) for oligometastatic lung tumors from colorectal cancer versus early stage non-small cell lung cancer.

BACKGROUND: The use of stereotactic body radiotherapy (SBRT) for early-stage primary non-small cell lung cancer (NSCLC) reported excellent local control rates. But the optimal SBRT dose for oligometastatic lung tumors (OLTs) from colorectal cancer (CRC) has not yet been determined. This study aimed to evaluate whether SBRT to a dose of 48-60 Gy in 4-5 fractions could result in similar local outcomes for OLTs from CRC as compared to early-stage NSCLC, and to examine potential dose-response relationships for OLTs from CRC. METHODS: OLTs from CRC and primary NSCLCs treated with SBRT to 48-60 Gy in 4-5 fractions at a single institution were evaluated, and a matched-pair analysis was performed. Local recurrence-free survival (LRFS) was estimated by the Kaplan-Meier method. Univariate Cox regression was performed to identify significant predictors. RESULTS: There were 72 lung lesions in 61 patients (24 OLTs from CRC in 15 patients and 48 NSCLCs in 46 patients) were analyzed with a median follow-up of 30 months. LRFS for OLTs from CRC was significantly worse than that of NSCLC when treated with 48-60 Gy/4-5 fx (p = 0.006). The 1, 3 and 5-year LRFS of OLTs from CRC vs NSCLC were 80.6% vs. 100%, 68.6% vs. 97.2%, and 68.6% vs. 81.0%, respectively. On univariate analysis, OLTs from CRC treated with higher dose (BED10 = 132 Gy) exhibited significantly better local recurrence-free survival than those treated to lower doses (BED10 ≤ 105.6 Gy) (p = 0.0022). The 1 and 3-year LRFS rates for OLTs treated to a higher dose (BED10 = 132 Gy) were 88.9% and 81.5%, vs 33.3%, and not achieved for lower doses (BED10 ≤ 105.6 Gy). CONCLUSION: The LRFS of OLTs from CRC after SBRT of 48-60 Gy/4-5 fx was significantly worse than that of primary NSCLC. Lower dose SBRT appeared to have inferior control for OLTs of CRC in this cohort. Further studies with larger sample sizes are needed.

Prognostic significance of corticotroph staining in radiosurgery for non-functioning pituitary adenomas: a multicenter study.

Silent corticotroph staining pituitary adenoma (SCA) represents an uncommon subset of Non-Functioning adenomas (NFAs), hypothesized to be more locally aggressive. In this retrospective multicenter study, we investigate the safety and effectiveness of Stereotactic Radiosurgery (SRS) in patients with SCA compared with other non-SCA NFA's. Eight centers participating in the International Gamma-Knife Research Foundation (IGKRF) contributed to this study. Outcomes of 50 patients with confirmed SCAs and 307 patients with confirmed non-SCA NFA's treated with SRS were evaluated. Groups were matched. SCA was characterized by a lack of clinical evidence of Cushing disease, yet with positive immunostaining for corticotroph. Median age was 55.2 years (13.7-87). All patients underwent at least one trans-sphenoidal tumor resection prior to SRS. SRS parameters were comparable as well. Median follow-up 40 months (6-163). Overall tumor control rate (TCR) 91.2% (n = 280). In the SCA group, TCR were 82% (n = 41) versus 94.1% (n = 289) for the control-NFA (p = 0.0065). The SCA group showed a significantly higher incidence of new post-SRS visual deficit (p < 0.0001) assigned to tumor progression and growth, and post-SRS weakness and fatigue (p < 0.0001). In univariate and multivariate analysis, only the status of silent corticotroph staining (p = 0.005, p = 0.009 respectively) and margin dose (p < 0.0005, p = 0.0037 respectively) significantly influenced progression rate. A margin dose of ≥17 Gy was noted to influence the adenoma progression rate in the entire cohort (p = 0.003). Silent corticotroph staining represents an independent factor for adenoma progression and hypopituitarism after SRS. A higher margin dose may convey a greater chance of TCR.

Radiosurgery for Cerebral Arteriovenous Malformations in A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA)-Eligible Patients: A Multicenter Study.

BACKGROUND AND PURPOSE: The benefit of intervention for patients with unruptured cerebral arteriovenous malformations (AVMs) was challenged by results demonstrating superior clinical outcomes with conservative management from A Randomized Trial of Unruptured Brain AVMs (ARUBA). The aim of this multicenter, retrospective cohort study is to analyze the outcomes of stereotactic radiosurgery for ARUBA-eligible patients. METHODS: We combined AVM radiosurgery outcome data from 7 institutions participating in the International Gamma Knife Research Foundation. Patients with ≥12 months of follow-up were screened for ARUBA eligibility criteria. Favorable outcome was defined as AVM obliteration, no postradiosurgery hemorrhage, and no permanently symptomatic radiation-induced changes. Adverse neurological outcome was defined as any new or worsening neurological symptoms or death. RESULTS: The ARUBA-eligible cohort comprised 509 patients (mean age, 40 years). The Spetzler-Martin grade was I to II in 46% and III to IV in 54%. The mean radiosurgical margin dose was 22 Gy and follow-up was 86 months. AVM obliteration was achieved in 75%. The postradiosurgery hemorrhage rate during the latency period was 0.9% per year. Symptomatic and permanent radiation-induced changes occurred in 11% and 3%, respectively. The rates of favorable outcome, adverse neurological outcome, permanent neurological morbidity, and mortality were 70%, 13%, 5%, and 4%, respectively. CONCLUSIONS: Radiosurgery may provide durable clinical benefit in some ARUBA-eligible patients. On the basis of the natural history of untreated, unruptured AVMs in the medical arm of ARUBA, we estimate that a follow-up duration of 15 to 20 years is necessary to realize a potential benefit of radiosurgical intervention for conservative management in unruptured patients with AVM.

Post-radiosurgical edema associated with parasagittal and parafalcine meningiomas: a multicenter study.

Stereotactic radiosurgery (SRS) offers a high degree of tumor control for benign meningiomas. However, radiosurgery can occasionally incite edema or exacerbate pre-existing peri-tumoral edema. The current study investigates the incidence, timing, and extent of edema around parasagittal or parafalcine meningiomas following SRS. A retrospective multicenter review was undertaken through participating centers in the International Gamma Knife Research Foundation (previously the North American Gamma Knife Consortium or NAGKC). All included patients had a parafalcine or parasagittal meningioma and a minimum of 6 months follow up. The median follow up was 19.6 months (6-158 months). Extent of new or worsening edema was quantitatively analyzed using volumetric analysis; edema indices were longitudinally computed following radiosurgery. Analysis was performed to identify prognostic factors for new or worsening edema. A cohort of 212 patients comprised of 51.9 % (n = 110) females, 40.1 % upfront SRS and 59.9 % underwent adjuvant SRS for post-surgical residual tumor. The median tumor volume at SRS was 5.2 ml. Venous sinus compression or invasion was demonstrated in 25 % (n = 53). The median marginal dose was 14 Gy (8-20 Gy). Tumor volume control was determined in 77.4 % (n = 164 out of 212 patients). Tumor edema progressed and then regressed in 33 % (n = 70), was stable or regressed in 52.8 % (n = 112), and progressively worsened in 5.2 % (n = 11). Tumor location, tumor volume, venous sinus invasion, margin, and maximal dose were found to be significantly related to post-SRS edema in multivariate analysis. SRS affords a high degree of tumor control for patients with parasagittal or parafalcine meningiomas. Nevertheless, SRS can lead to worsening peritumoral edema in a subset of patients such as those with larger tumors (>10 cc) and venous sinus invasion/compression. Long-term follow up is required to detect and appropriately manage post-SRS edema.

Prospective Trial of Functional Lung Avoidance Radiation Therapy for Lung Cancer: Quality of Life Report.

PURPOSE: A novel form of lung function imaging has been developed that uses 4-dimensional computed tomography (4DCT) data to generate lung ventilation images (4DCT-ventilation). Functional avoidance uses 4DCT-ventilation to reduce doses to functional lung with the aim of reducing pulmonary side effects. A phase 2, multicenter 4DCT-ventilation functional avoidance clinical trial was completed. The purpose of this work was to quantify changes in patient-reported outcomes (PROs) for patients treated with functional avoidance and determine which metrics are predictive of PRO changes. MATERIALS AND METHODS: Patients with locally advanced lung cancer receiving curative-intent radiation therapy were accrued. Each patient had a 4DCT-ventilation image generated using 4DCT data and image processing. PRO instruments included the Functional Assessment of Cancer Therapy-Lung (FACT-L) questionnaire administered pretreatment; at the end of treatment; and at 3, 6, and 12 months posttreatment. Using the FACT-Trial Outcome Index and the FACT-Lung Cancer Subscale results, the percentage of clinically meaningful declines (CMDs) were determined. A linear mixed-effects model was used to determine which patient, clinical, dose, and dose-function metrics were predictive of PRO decline. RESULTS: Of the 59 patients who completed baseline PRO surveys. 83% had non-small cell lung cancer, with 75% having stage 3 disease. The median dose was 60 Gy in 30 fractions. CMD FACT-Trial Outcome Index decline was 46.3%, 38.5%, and 26.8%, at 3, 6, and 12 months, respectively. CMD FACT-Lung Cancer Subscale decline was 33.3%, 33.3%, and 29.3%, at 3, 6, and 12 months, respectively. Although an increase in most dose and dose-function parameters was associated with a modest decline in PROs, none of the results were significant (all P > .053). CONCLUSIONS: The current work presents an innovative combination of use of functional avoidance and PRO assessment and is the first report of PROs for patients treated with prospective 4DCT-ventilation functional avoidance. Approximately 30% of patients had clinically significant decline in PROs at 12 months posttreatment. The study provides additional data on outcomes with 4DCT-ventilation functional avoidance.

Predictors of Early Hospice or Death in Patients With Inoperable Lung Cancer Treated With Curative Intent.

INTRODUCTION: Treatment for inoperable stage II to III non-small cell lung cancer (NSCLC) involves chemo-radiotherapy (CRT). However, some patients transition to hospice or die early during their treatment course. We present a model to prognosticate early poor outcomes in NSCLC patients treated with curative-intent CRT. METHODS AND MATERIALS: Across a statewide consortium, data was prospectively collected on stage II to III NSCLC patients who received CRT between 2012 and 2019. Early poor outcomes included hospice enrollment or death within 3 months of completing CRT. Logistic regression models were used to assess predictors in prognostic models. LASSO regression with multiple imputation were used to build a final multivariate model, accounting for missing covariates. RESULTS: Of the 2267 included patients, 128 experienced early poor outcomes. Mean age was 71 years and 59% received concurrent chemotherapy. The best predictive model, created parsimoniously from statistically significant univariate predictors, included age, ECOG, planning target volume (PTV), mean heart dose, pretreatment lack of energy, and cough. The estimated area under the ROC curve for this multivariable model was 0.71, with a negative predictive value of 95%, specificity of 97%, positive predictive value of 23%, and sensitivity of 16% at a predicted risk threshold of 20%. CONCLUSIONS: This multivariate model identified a combination of clinical variables and patient reported factors that may identify individuals with inoperable NSCLC undergoing curative intent chemo-radiotherapy who are at higher risk for early poor outcomes.

Characterization of Pediatric Infratentorial Arteriovenous Malformations: A Retrospective, Multicenter Cohort Study.

BACKGROUND AND OBJECTIVES: Infratentorial arteriovenous malformations (AVMs) harbor different characteristics compared with supratentorial AVMs. This study aims to explore the unique characteristics of pediatric infratentorial AVMs and their response to single session stereotactic radiosurgery (SRS). METHODS: The International Radiosurgery Research Foundation database of pediatric patients with AVM (age <18 years) who underwent SRS was retrospectively reviewed. Baseline demographics, AVM characteristics, outcomes, and complications post-SRS were compared between infratentorial and supratentorial pediatric AVMs. Unfavorable outcome was defined as the absence of AVM obliteration, post-SRS hemorrhage, or permanent radiation-induced changes at last follow-up. RESULTS: A total of 535 pediatric AVMs managed with SRS with a median follow-up of 67 months (IQR 29.0-130.6) were included, with 69 being infratentorial and 466 supratentorial. The infratentorial group had a higher proportion of deep location (58.4% vs 30.3%, P = <.001), deep venous drainage (79.8% vs 61.8%, P = .004), and prior embolization (26.1% vs 15.7%, P = .032). There was a higher proportion of hemorrhagic presentation in the infratentorial group (79.7% vs 71.3%, P = .146). There was no statistically significant difference in the odds of an unfavorable outcome (odds ratio [OR] = 1.36 [0.82-2.28]), AVM obliteration (OR = 0.85 [0.5-1.43]), post-SRS hemorrhage (OR = 0.83 [0.31-2.18]), or radiologic radiation-induced changes (OR = 1.08 [0.63-1.84]) between both cohorts. No statistically significant difference on the rates of outcomes of interest and complications were found in the adjusted model. CONCLUSION: Despite baseline differences between infratentorial and supratentorial pediatric AVMs, SRS outcomes, including AVM obliteration and post-SRS hemorrhage rates, were comparable amongst both groups. SRS appears to have a similar risk profile and therapeutic benefit to infratentorial pediatric AVMs as it does for those with a supratentorial location.

Is individual perfusion dose-response different than ventilation dose-response for lung cancer patients treated with radiotherapy?

OBJECTIVE: Current ventilation and perfusion dose-response studies focus on single-modalities (ventilation or perfusion) and perform pulmonary-toxicity assessment related to radiotherapy on a population-based basis. This study aims at quantitative and clinical evaluation of intrapatient differences between ventilation and perfusion dose-responses among lung cancer patients treated with radiotherapy. METHODS: 20 patients enrolled on a prospective functional avoidance protocol underwent single photon emission computed tomography-CT ventilation and perfusion scans pre- and post-radiotherapy. Relative changes in pre- to post-treatment ventilation and perfusion in lung regions receiving ≥20 Gy were calculated. In addition, the slopes of the linear fit to the relative ventilation and perfusion changes in regions receiving 0-60 Gy were calculated. A radiologist read and assigned a functional defect score to pre- and post-treatment ventilation/perfusion scans. RESULTS: 25% of patients had a difference >35% between ventilation and perfusion pre- to post-treatment changes and 20-30% of patients had opposite directions for ventilation and perfusion pre- to post-treatment changes. Using a semi-quantitative scale, radiologist assessment showed that 20% of patients had different pre- to post-treatment ventilation changes when compared to pre- to post-treatment perfusion changes. CONCLUSION: Our data showed that ventilation dose-response can differ from perfusion dose-response for 20-30% of patients. Therefore, when performing thoracic dose-response in cancer patients, it is insufficient to look at ventilation or perfusion alone; but rather both modes of functional imaging may be needed when predicting for clinical outcomes. ADVANCES IN KNOWLEDGE: The significance of this study can be highlighted by the differences between the intrapatient dose-response assessments of this analysis compared to existing population-based dose-response analyses. Elucidating intrapatient ventilation and perfusion dose-response differences may be valuable in predicting pulmonary toxicity in lung cancer patients post-radiotherapy.