Utility of 68Ga-DOTATATE PET-MRI for Gamma Knife® stereotactic radiosurgery treatment planning for meningioma.

OBJECTIVES: To investigate the impact of adding 68Ga-DOTATATE PET/MRI to standard MRI for target volume delineation in Gamma Knife® stereotactic radiosurgery (GKSRS) for meningioma. METHODS: Seventeen patients with 18 lesions undergoing GKSRS for WHO grade 1 meningioma were enrolled in a prospective study. All patients underwent pre-treatment 68Ga-DOTATATE PET/MRI examination in addition to standard procedures. Five clinicians independently contoured the gross tumour volume (GTV) based on standard MRI (GTVMRI) and PET/MRI (GTVPET/MRI) on separate occasions. Interobserver agreement was evaluated using Cohen's Kappa statistic (CKS), Dice similarity coefficient (DC), and Hausdorff distance (HD). Statistical analysis was performed with paired t-test and Wilcoxon signed rank test. RESULTS: The addition of PET/MRI significantly increased GTV contour volume (mean GTVPET/MRI 3.59 cm3 versus mean GTVMRI 3.18 cm3, P = .008). Using the treating clinician's pre-treatment GTVMRI as the reference, median CKS (87.2 vs 77.5, P = .006) and DC (87.2 vs 77.4, P = .006) were significantly lower, and median HD (25.2 vs 31.0, P = .001) was significantly higher with the addition of PET/MRI. No significant difference was observed in interobserver contouring reproducibility between GTVMRI and GTVPET/MRI. CONCLUSION: The addition of 68Ga-DOTATATE PET/MRI for target volume delineation in GKSRS for meningioma is associated with an increase in GTV volume and greater interobserver variation. PET/MRI did not affect interobserver contouring reproducibility. ADVANCES IN KNOWLEDGE: This study provides novel insights into the impact of 68Ga-DOTATATE PET/MRI on GTV delineation and interobserver agreement in meningioma GKSRS, highlighting its potential for improving GKSRS treatment accuracy.

The impact of local control on widespread progression and survival in oligometastasis-directed SBRT: Results from a large international database.

PURPOSE: We investigated the impact of local control (LC) on widespread progression (WSP) and overall survival (OS) in patients treated to all extracranial oligometastases (OMs) at presentation to SBRT in this retrospective review across 6 international centers. MATERIALS/METHODS: Relationships between LC status of SBRT-directed OMs and OS and WSP (>5 new active/untreated lesions) were explored using Cox and Fine-Gray regression models, adjusting for radioresistant histology and pre-SBRT systemic therapy receipt. The association between LC and dosimetric predictors was analyzed with competing risk regression using death as a competing risk and across a wide range of simulated α/ßratios. RESULTS: In total, 1700 OMs in 1033 patients were analyzed, with 25.2% NSCLC, 22.7% colorectal, 12.8% prostate, and 8.1% breast histology. Patients who failed locally in any SBRT-directed OM within 6 mo were at 3.6-fold higher risk of death and 2.7-fold higher risk of WSP compared to those who remained locally-controlled (p < 0.001). Similar associations existed for each duration of LC investigated through 3 yrs post-SBRT. There was no significant difference in risk of WSP or death between patients who failed in a subset of SBRT-treated lesions vs. patients who failed in all lesions. Minimum dose (Dmin) to the GTV/ITV was most predictive of LC when compared to prescription dose, PTV Dmin, and PTV Dmax. Sensitivity analysis for achieving 1-yr LC > 95% found thresholds of 41.2 Gy and 55.2 Gy in 5 fractions for smaller (< 27.7 cc) and larger radioresistant lesions, respectively. CONCLUSION: This large multinational cohort suggests that the duration of LC following OM-directed SBRT strongly correlates with WSP and OS.

Gamma Knife® stereotactic radiosurgery for intracranial cavernous malformations.

INTRODUCTION: Gamma Knife® stereotactic radiosurgery (GKSRS) is a non-invasive alternative to surgical resection for cerebral cavernous malformations (CCMs), especially in eloquent locations. METHODOLOGY: A retrospective review was performed on an Australian cohort of patients receiving GKSRS for CCMs at a single institution. All patients exhibited symptoms and/or radiological evidence of haemorrhage before therapy. The minimum follow-up was 1-year post-GKSRS. McNemar's test was used for differences in matched-pair outcomes pre- and post-GKSRS with an α = 0.05. A systematic review and meta-analysis was additionally performed to synthesise the current published evidence on the clinical efficacy of stereotactic radiosurgery in reducing haemorrhage risk in CCMs using a DerSimonian and Laird random effects model. RESULTS: Thirty-five patients (39 cavernomas) underwent GKSRS. 87.2 % of patients had evidence of at least one haemorrhage before GKSRS and the remainder exhibited seizures. The median dose was 12.5 Gy in a single fraction (IQR 12-13). The median follow-up duration from GKSRS was 809 days (IQR 536-960). There was a significant reduction in matched annual bleed rate from pre-GKSRS (52.1 %) compared to after SRS (12.3 %) (p < 0.001) [OR = 0.07, 95 % 0.008-0.283] There was no statistically significant difference in seizure incidence pre- (30.7 %) versus post-GKSRS (17.9 %) (p = 0.13) [OR = 0.167, 95 %CI 0.004-1.37]. One patient (3 %) with a brainstem lesion experienced long-term treatment-related oedema with persistent ipsilateral weakness and tremors. On meta-analysis of 25 pooled studies, radiosurgery for the treatment of CCMs was associated with a statistically significantly relative risk (RR) reduction in haemorrhage events [random effects RR 0.12 (95 % CI 0.074-0.198), p < 0.001)], with most of the proportionate risk reduction occurring in the initial 2 years following SRS. CONCLUSION: GKSRS significantly reduces the annual rate of haemorrhage for intracranial cavernomas in this cohort and on meta-analysis, particularly in the first 2 years following treatment. The overall risk of treatment-related morbidity is low.

Stereotactic radiosurgery for melanoma brain metastases: Concurrent immune checkpoint inhibitor therapy associated with superior clinicoradiological response outcomes.

INTRODUCTION/PURPOSE: This study assessed long-term clinical and radiological outcomes following treatment with combination stereotactic radiosurgery (SRS) and immunotherapy (IT) for melanoma brain metastases (BM). METHODS: A retrospective review was performed in a contemporary cohort of patients with melanoma BM at a single tertiary institution receiving Gamma Knife® SRS for melanoma BM. Multivariate Cox proportional-hazards modelling was performed with a P <0.05 for significance. RESULTS: 101 patients (435 melanoma BM) were treated with SRS between January-2015 and June-2019. 68.3% of patients received IT within 4 weeks of SRS (concurrent) and 31.7% received SRS alone or non-concurrently with IT. Overall, BM local control rate was 87.1% after SRS. Median progression free survival was 8.7 months. Median follow-up was 29.2 months. On multivariate analysis (MVA), patients receiving concurrent SRS-IT maintained a higher chance of achieving a complete (CR) or partial response (PR) [HR 2.6 (95% CI: 1.2-5.5, P = 0.012)] and a reduced likelihood of progression of disease (PD) [HR 0.52 (95% CI: 0.16-0.60), P = 0.048]. Any increase in BM volume on the initial MRI 3 months after SRS predicted a lower likelihood of achieving long-term CR or PR on MVA accounting for concurrent IT, BRAF status and dexamethasone use [HR = 0.048 (95% CI: 0.007-0.345, P = 0.0026)]. Stratified volumetric change demonstrated a sequential relationship with outcomes on Kaplan-Meier analysis. CONCLUSION: Concurrent SRS-IT has favourable clinical and radiological outcomes with respect to CR, PR and a reduced likelihood of PD. Changes in BM volume on the initial MRI 3 months after SRS were predictive of long-term outcomes for treatment response.

An analysis of a large multi-institutional database reveals important associations between treatment parameters and clinical outcomes for stereotactic body radiotherapy (SBRT) of oligometastatic colorectal cancer.

PURPOSE: In recent years, stereotactic body radiotherapy (SBRT) has emerged as an effective treatment for oligometastatic cancers. Here, we report radiation treatment parameters and clinical outcomes for patients with oligometastatic colorectal cancer (CRC) treated with SBRT using a large multi-institutional database. METHODS: Patients with extra-cranial oligometastatic CRC (≤5 lesions) treated with SBRT at six large academic cancer centers were included. The primary outcome was local recurrence while secondary outcomes included overall survival (OS) progression free survival, oligo-progression, and widespread progression. Survival outcomes were estimated using the Kaplan-Meier method. Univariable and multivariable analyses were performed to determine the relationship between patient and treatment characteristics and clinical outcomes. RESULTS: We identified 235 patients with a total of 381 oligometastatic CRC lesions. The 1- and 5-year local recurrence rate was 13.6% and 44.3% respectively. The median OS was 49 months with a 2-and 5-year OS of 76.1% and 35.9%, respectively. On multivariable analysis, a BED10 of ≥120 Gy, and lung versus liver metastases were associated with a reduction in local recurrence. Larger total PTV size (≥17.5 cc) was associated with worse overall survival, progression free survival, and widespread progression. CONCLUSION: This large multi-institutional analysis found that the use of SBRT for oligometastatic colorectal cancer resulted in favorable overall survival. However, local recurrence is higher than expected for ablative radiation treatment. An increase in BED10 should be considered if feasible and safe.

Volumetric burden of metastatic lesions drives outcomes in patients with extracranial oligometastatic disease.

BACKGROUND: We hypothesized that the total volume of metastases at initial oligometastatic (OM) presentation to stereotactic body radiation therapy (SBRT) is an important prognostic factor that can refine the definition of OM disease. METHODS: Patients with extracranial oligometastatic cancer (≤5 lesions) treated with SBRT were included in an international multi-institutional database. Multivariable Cox and competing risks regression models were used to determine the relationship between distant progression-free survival (DPFS), widespread progression (WSP), and overall survival (OS) with the total planning target volume (PTV) at initial OM presentation to SBRT. All models were adjusted for histology, pre-SBRT systemic therapy, osseous-only lesions, and number of metastases. RESULTS: In total, 961 patients were included. The median follow-up was 24.4 months (IQR: 13.8-37.5). Total PTV had a significant effect on DPFS in the first 18 months after SBRT and was most profound in the first 6 months, when each twofold increase in total PTV conferred a 40.6% increased risk of distant progression (p < 0.001). Each twofold increase in total PTV increased the risk of WSP by 45.4% in the first 6 months (p < 0.001). Total PTV had a significant effect on OS in the first 2 years after SBRT, with each twofold PTV change increasing the risk of death by 60.7% during the first 6 months (p < 0.001) and by 34% thereafter (p < 0.001). Exploratory gross tumor volume (GTV) analysis confirmed the PTV-based observations. CONCLUSION: The total volumetric burden of metastases at initial OM presentation to SBRT is strongly and independently prognostic for the risk of distant and widespread progression and survival. We propose that this metric should drive the definition of OM disease and guide treatment decision-making.

An international pooled analysis of SBRT outcomes to oligometastatic spine and non-spine bone metastases.

PURPOSE: There is a paucity of data on SBRT to non-spine bone (NSB) lesions compared to spine metastases. We report local recurrence (LR), widespread progression (WSP), and overall survival (OS) for oligometastatic patients treated to bone lesions with SBRT and investigate the hypothesis that outcomes are different between patients with spine and non-spine bone oligometastatic disease. METHODS: Patients with oligometastatic disease (≤5 cumulative extracranial metastases) treated with bone SBRT at 6 international institutions from 2007 to 2016 were reviewed. Fine and Gray competing risks and Cox regressions were used to analyze univariable and multivariable relationships between disease/treatment factors and outcomes. RESULTS: In total, 288 spine and 233 NSB lesions are reported in 356 patients. Cumulative incidence of LR across all bone lesions was 6.3%, 12.6% and 19.3% at 6 mo, 1 yr and 2 yrs. While univariable analysis suggested inferior LC and OS in spine patients, this did not hold true in multivariable analysis. The final regression model for LR in NSB lesions included PTV ≥ median of 31.8 cc (HR 5.02, p = 0.014) and primary histology, with RCC and NSCLC conferring a 10.8- and 6.5-fold increased risk of LR compared to prostate histology, respectively. The spine LR model included radioresistant histology (HR 2.11, p = 0.0051), PTV Dmin (BED10) ≥ median of 19.1 Gy (HR 0.46, p = 0.0085), and epidural disease (HR 1.99, p = 0.016). CONCLUSION: This large multi-institutional series reports comparably excellent response to SBRT for a balanced distribution of oligometastatic NSB and spine lesions. Dose escalation for large and/or radioresistant NSB lesions should be explored, given the typical lack of an immediately adjacent dose-limiting critical structure.

A randomized phase II trial of veliparib, radiotherapy, and temozolomide in patients with unmethylated MGMT glioblastoma: the VERTU study.

BACKGROUND: Temozolomide offers minimal benefit in patients with glioblastoma with unmethylated O6-methylguanine-DNA methyltransferase (MGMT) promoter status, hence, the need for novel therapies. This study evaluated whether veliparib, a brain-penetrant poly(ADP-ribose) polymerase (PARP) inhibitor, acts synergistically with radiation and temozolomide. METHODS: VERTU was a multicenter 2:1 randomized phase II trial in patients with newly diagnosed glioblastoma and MGMT-unmethylated promotor status. The experimental arm consisted of veliparib and radiotherapy, followed by adjuvant veliparib and temozolomide. The standard arm consisted of concurrent temozolomide and radiotherapy, followed by adjuvant temozolomide. The primary objective was to extend the progression-free survival rate at six months (PFS-6m) in the experimental arm. RESULTS: A total of 125 participants were enrolled, with 84 in the experimental arm and 41 in the standard arm. The median age was 61 years, 70% were male, 59% had Eastern Cooperative Oncology Group (ECOG) performance status of 0, and 87% underwent macroscopic resection. PFS-6m was 46% (95% confidence interval [CI]: 36%-57%) in the experimental arm and 31% (95% CI: 18%-46%) in the standard arm. Median overall survival was 12.7 months (95% CI: 11.4-14.5 months) in the experimental arm and 12.8 months (95% CI: 9.5-15.8 months) in the standard arm. The most common grade 3-4 adverse events were thrombocytopenia and neutropenia, with no new safety signals. CONCLUSION: The veliparib-containing regimen was feasible and well tolerated. However, there was insufficient evidence of clinical benefit in this population. Further information from correlative translational work and other trials of PARP inhibitors in glioblastoma are still awaited.

Multi-institutional Analysis of Prognostic Factors and Outcomes After Hypofractionated Stereotactic Radiotherapy to the Resection Cavity in Patients With Brain Metastases.

IMPORTANCE: For brain metastases, the combination of neurosurgical resection and postoperative hypofractionated stereotactic radiotherapy (HSRT) is an emerging therapeutic approach preferred to the prior practice of postoperative whole-brain radiotherapy. However, mature large-scale outcome data are lacking. OBJECTIVE: To evaluate outcomes and prognostic factors after HSRT to the resection cavity in patients with brain metastases. DESIGN, SETTING, AND PARTICIPANTS: An international, multi-institutional cohort study was performed in 558 patients with resected brain metastases and postoperative HSRT treated between December 1, 2003, and October 31, 2019, in 1 of 6 participating centers. Exclusion criteria were prior cranial radiotherapy (including whole-brain radiotherapy) and early termination of treatment. EXPOSURES: A median total dose of 30 Gy (range, 18-35 Gy) and a dose per fraction of 6 Gy (range, 5-10.7 Gy) were applied. MAIN OUTCOMES AND MEASURES: The primary end points were overall survival, local control (LC), and the analysis of prognostic factors associated with overall survival and LC. Secondary end points included distant intracranial failure, distant progression, and the incidence of neurologic toxicity. RESULTS: A total of 558 patients (mean [SD] age, 61 [0.50] years; 301 [53.9%] female) with 581 resected cavities were analyzed. The median follow-up was 12.3 months (interquartile range, 5.0-25.3 months). Overall survival was 65% at 1 year, 46% at 2 years, and 33% at 3 years, whereas LC was 84% at 1 year, 75% at 2 years, and 71% at 3 years. Radiation necrosis was present in 48 patients (8.6%) and leptomeningeal disease in 73 patients (13.1%). Neurologic toxic events according to the Common Terminology Criteria for Adverse Events grade 3 or higher occurred in 16 patients (2.8%) less than 6 months and 24 patients (4.1%) greater than 6 months after treatment. Multivariate analysis identified a Karnofsky Performance Status score of 80% or greater (hazard ratio [HR], 0.61; 95% CI, 0.46-0.82; P < .001), 22 to 33 days between resection and radiotherapy (HR, 1.50; 95% CI, 1.07-2.10; P = .02), and a controlled primary tumor (HR, 0.69; 95% CI, 0.52-0.90; P = .007) as prognostic factors associated with overall survival. For LC, a single brain metastasis (HR, 0.57; 95% CI, 0.35-0.93; P = .03) and a controlled primary tumor (HR, 0.59; 95% CI, 0.39-0.92; P = .02) were significant in the multivariate analysis. CONCLUSIONS AND RELEVANCE: To date, this cohort study includes one of the largest series of patients with brain metastases and postoperative HSRT and appears to confirm an excellent risk-benefit profile of local HSRT to the resection cavity. Additional studies will help determine radiation dose-volume parameters and provide a better understanding of synergistic effects with systemic and immunotherapies.

The declining role of post-treatment neck dissection in human papillomavirus-associated oropharyngeal cancer.

BACKGROUND AND PURPOSE: Human papillomavirus-associated oropharyngeal cancer (HPV+ OPC) with regional lymph node metastases has a good prognosis following (chemo)radiation therapy (C/RT) but lymph nodes may remain detectable for several months. Delayed [18F]-Fluorodeoxyglucose positron emission tomography/computed tomography (PET) can identify patients who may avoid post-treatment neck dissection (PTND). We investigated the rate of PTND in HPV+ OPC treated with C/RT and delayed PET-directed management of the neck. MATERIALS AND METHODS: This is a retrospective cohort study from a prospectively updated institutional database. Eligible patients were treated between January 2005 and July 2017 with a minimum of 18 months follow up, had node-positive, non-distant metastatic HPV+ OPC and were treated with RT (70 Gy/35#/5 per week) with concurrent Cisplatin or Cetuximab, or accelerated RT alone (68 Gy/34#/6 per week). The primary endpoint was rate of PTND. Secondary endpoints were locoregional failure free survival (LRFFS), regional failure free survival (RFFS), distant metastatic failure free survival (DMFFS), overall survival (OS) and oropharyngeal cancer-specific survival (CSS). RESULTS: 418 patients were eligible. Nineteen patients (4.5%) received a PTND. None of the tested variables were associated with an increased risk of PTND. Five-year probabilities for LRFFS, RFFS, DMFS, OS and CSS were, 91.2% (95% CI 88.3-94.2), 93.4% (95% CI 90.8-96.0), 91.2% (95% CI 88.3-94.2), 86.4% (95% CI 83.0-90.1) and 90.2% (95% CI 87.1-93.4), respectively. CONCLUSION: In a large cohort with good median follow up and protocolized C/RT, delayed PET-directed management of the neck affords a lower rate of PTND than reported in historical series without compromising disease control and survival.

Evidence of dose-response following hypofractionated stereotactic radiotherapy to the cavity after surgery for brain metastases.

BACKGROUND AND OBJECTIVE: A retrospective review of consecutive patients between January 2012 and December 2018 receiving hypofractionated stereotactic radiotherapy (HSRT) to the cavity after resection for brain metastases was performed. METHODS: Treatment was delivered using an appropriately commissioned linear accelerator. The primary outcome was time to radiological or histological confirmation of local recurrence following completion of HSRT. Dose-fractionation regimens were converted to biologically 2 Gy-equivalent doses assuming α/ß = 10 (EQD2[10]). Multivariate Cox proportional hazards modelling was performed to determine hazard ratios (HR) with respective 95% confidence intervals (CI). The Log-rank test was used to determine p values taking statistical significance p < 0.05. RESULTS: There were 134 patients and 144 cavities identified. The most common primary histologies were melanoma (n = 49) and lung (n = 32). 116 patients (87%) underwent a gross total resection. Median planning target volume (PTV) was 28 cm3 (range 2.4-149.2). Median EQD2[10] was 38.4 Gy (range 22.3-59.7) and 24 Gy in 3 fractions was the most common regimen. 12 (9%) patients demonstrated local recurrence at median interval 215 days (range 4-594). 7 (5%) patients experienced grade 3 or higher toxicities. In multivariate analysis, EQD2[10] was associated with local failure such that increased equivalent doses improved local control [HR = 0.79 and 95% CI 0.65-0.96, p = 0.0192]. There were no significant associations for primary histology, patient age, volume of residual disease, PTV volume or location. CONCLUSION: This large series demonstrates that HSFRT to the surgical resection cavity for brain metastases has improved local control with increasing dose. Rates of grade 3 or higher toxicity were low overall.

Extent of surrounding edema does not correlate with acute complications after radiosurgery for melanoma brain metastases.

AIM: To assess whether extent of surrounding edema correlates with acute adverse clinical outcomes within 3 months after stereotactic radiosurgery (SRS) for melanoma brain metastases (BM). METHODS: Patients with melanoma BM treated with SRS were included in a single center retrospective analysis. A contrast-enhanced magnetic resonance image (MRI) brain was acquired on the day of treatment and used to calculate the volume of the largest lesion (the index BM) and total volume of all BM. Their corresponding volume of surrounding edema was defined based on the fluid attenuated inversion recovery (FLAIR) sequence. After SRS, MRI was performed every 3 months for at least 2 years if the patient remained well enough to do so. Adverse neurologic events after SRS were defined using common terminology criteria for adverse events (CTCAE) version 5.0. Multivariate regression analyses assessed for associations between BM size and edema at baseline with increasing edema and neurologic adverse events within 3 months after SRS. RESULTS: Mean volume of the index BM reduced from 2.2 to 0.5 cm3 at 3 months after SRS (p = 0.03). Mean volume of edema surrounding the index BM was 6.4 cm3 at baseline, 10.2 cm3 at 3 months and 5.5 cm3 at 6 months. There were 7/43 (16%) patients that experienced an adverse neurological event within 3 months (attributable to any cause) and 4/43 (9%) were associated with an increase in BM edema. On univariate and multivariate analyses, there were no correlations between any baseline factors and volume of edema at 3 months. However, SRS dose delivered and systemic therapy use within 4 weeks of SRS both correlated with a reduction in edema surrounding the index BM. CONCLUSION: A transient increase in mean volume of edema was apparent at 3 months after SRS. However, this resolved by 6 months and did not correlate with adverse events or dexamethasone requirement. Thus, the clinical significance is uncertain.

Re-irradiation for recurrent high-grade gliomas: a systematic review and analysis of treatment technique with respect to survival and risk of radionecrosis.

BACKGROUND: Re-irradiation may be considered for select patients with recurrent high-grade glioma. Treatment techniques include conformal radiotherapy employing conventional fractionation, hypofractionated stereotactic radiotherapy (FSRT), and single-fraction stereotactic radiosurgery (SRS). METHODS: A pooled, population-weighted, multiple linear regression analysis of publications from 1992 to 2016 was performed to evaluate the relationships between re-irradiation technique and median overall survival (OS) and radionecrosis outcomes. RESULTS: Seventy published articles were analyzed, yielding a total of 3302 patients. Across all studies, initial treatment was external beam radiotherapy to a median dose of 60 Gy in 30 fractions, with or without concurrent chemotherapy. On multivariate analysis, there was a significant correlation between OS and radiotherapy technique after adjusting for age, re-irradiation biologically equivalent dose (EQD2), interval between initial and repeat radiotherapy, and treatment volume (P < .0001). Adjusted mean OS was 12.2 months (95% CI, 11.8-12.5) after SRS, 10.1 months (95% CI, 9.7-10.5) after FSRT, and 8.9 months (95% CI, 8.4-9.4) after conventional fractionation. There was also a significant association between radionecrosis and treatment technique after adjusting for age, re-irradiation EQD2, interval, and volume (P < .0001). Radionecrosis rate was 7.1% (95% CI, 6.6-7.7) after FSRT, 6.1% (95% CI, 5.6-6.6) after SRS, and 1.1% (95% CI, 0.5-1.7) after conventional fractionation. CONCLUSIONS: The published literature suggests that OS is highest after re-irradiation using SRS, followed by FSRT and conventionally fractionated radiotherapy. Whether this represents superiority of the treatment technique or an uncontrolled selection bias is uncertain. The risk of radionecrosis was low for all modalities overall. Re-irradiation is a feasible option in appropriately selected patients.

Proceedings of the 2018 next-generation Gamma Knife research meeting.

In order to determine what areas of research are a clinical priority, a small group of young Gamma Knife investigators was invited to attend a workshop discussion at the 19th International Leksell Gamma Knife Society Meeting. Two areas of interest and the need for future radiosurgical research involving multiple institutions were identified by the young investigators working group: 1) the development of additional imaging sequences to guide the understanding, treatment, and outcome tracking of diseases such as tremor, radiation necrosis, and AVM; and 2) trials to clarify the role of hypofractionation versus single-fraction radiosurgery in the treatment of large lesions such as brain metastases, postoperative cavities, and meningiomas.

In response to Fogarty et al. and why adjuvant whole brain radiotherapy is not recommended routinely.

The routine use of adjuvant whole brain radiotherapy (AWBRT) after surgery or stereotactic radiosurgery is now discouraged by a number of international expert panels. Three decades of randomised studies have shown that, although AWBRT improves radiological measures of intracranial disease control, the clinical benefit is unclear and it is also associated with inferior quality of life and neurocognitive function. The number of patients with melanoma in these trials was low, but data suggesting that treatment-related side effects should vary according to histology of the primary malignancy are lacking. For metastatic melanoma, the role of AWBRT to control microscopic disease in the brain is also a less relevant concern because systemic therapies with intracranial activity are now available. Whether AWBRT is useful in select patients deemed at high risk of neurologic death remains undefined.

A multinational report of technical factors on stereotactic body radiotherapy for oligometastases.

AIM: Oligometastatic cancer is being increasingly managed with aggressive local therapy using stereotactic body radiation therapy (SBRT). However, few guidelines exist. We summarize the results of an international survey reviewing technical factors for extracranial SBRT for oligometastatic disease to guide safe management. MATERIALS & METHODS: Seven high-volume centers contributed. Levels of agreement were categorized as strong (6-7 common responses), moderate (4-5), low (2-3) or no agreement. RESULTS & CONCLUSION: We present the results of a multi-national and multi-institutional survey of technical factors of SBRT for extracranial oligometastases. Key methods including target delineation, prescription doses, normal tissue constraints, imaging and set-up for safe implementation and practice of SBRT for oligometastasis have been identified. This manuscript will serve as a foundation for future clinical evaluations.

A multi-national report on stereotactic body radiotherapy for oligometastases: Patient selection and follow-up.

Aims Stereotactic body radiotherapy (SBRT) for oligometastases is increasingly used with few evidenced-based guidelines. We conducted a survey to determine patient selection and follow-up practice patterns. Materials and methods Seven institutions from US, Canada, Europe, and Australia that recommend SBRT for oligometastases participated in a 72-item survey. Levels of agreement were categorized as strong (6-7 common responses), moderate (4-5), low (2-3), or no agreement. Results There was strong agreement for recommending SBRT for eradication of all detectable oligometastases with most members limiting the number of metastases to five (range 2-5) and three within a single organ (range 2-5). There was moderate agreement for recommending SBRT as consolidative therapy after systemic therapy. There was strong agreement for requiring adequate performance status and no concurrent chemotherapy. Additional areas of strong agreement included staging evaluations, primary diagnosis, target sites, and follow-up recommendations. Several differences emerged, including the use of SBRT for sarcoma oligometastases, treatment response evaluation, and which imaging should be performed during follow-up. Conclusion Significant commonalities and variations exist for patient selection and follow-up recommendations for SBRT for oligometastases. Information from this survey may serve to help clarify the current landscape.

Long-term results of positron emission tomography-directed management of the neck in node-positive head and neck cancer after organ preservation therapy.

OBJECTIVES: The current study presents the long-term results from a study designed to evaluate a restaging positron emission tomography (PET) directed policy whereby neck dissections were omitted in all node positive head and neck squamous cell carcinoma (N+HNSCC) patients with PET-negative lymph nodes after definitive radiotherapy (RT), with or without chemotherapy. METHODS: A post-therapy nodal response assessment with PET and computed tomography (CT) was performed in patients who achieved a complete response at the primary site after definitive radiotherapy. Patients with PET-negative lymph nodes were observed regardless of residual CT abnormalities. RESULTS: One hundred and twelve patients, the majority of whom (83 patients, 74%) had oropharyngeal primaries, were treated on protocol. Median follow-up was 62months. Negative and positive predictive values for the restaging PET was 97.1% and 77.8% respectively, with only one patient who was PET-negative after treatment experiencing an isolated nodal relapse. CONCLUSION: PET-guided management of the neck following organ preservation therapy effectively spares neck dissections in patients with N+HNSCC without compromising isolated nodal control or overall survival.

Melanoma brain metastases: the impact of nodal disease.

Brain metastases (BMs) are a major source of mortality and morbidity in patients with melanoma. This study assesses prognostic nodal factors in patients with nodal metastatic melanoma with respect to the development of BMs. The aim was to identify a high risk subset that may benefit from brain directed management. Prospective surgical and clinical trial databases identified patients who had had nodal dissections and were seen through the Princess Alexandra Hospital Melanoma clinic between August 1995 and June 2010. Patient data was collected and event data was updated from medical imaging and clinical records. The primary endpoint was the rate of development of BMs. 474 patients were identified as having nodal dissections. Two hundred and eighty-seven patients (61%) were male with a median age of 52 (39-66). The most common nodal dissection site was axilla 190 (40%), followed by groin 154 (32.5%) and neck 130 (27.5%). Adjuvant radiotherapy to the nodal basin was delivered to 134 patients (28%). BMs occurred in 61 patients (12.9%) with a median time of 13.87 months from dissection. No lymph node characteristics were significantly associated with the development of BMs including: nodal region (p=0.72), nodal size (p=0.08), number of involved nodes (p=0.36), presence of extra-capsular spread (p=0.47) and AJCC N stage. There was no significant association between primary ulceration (p=0.37) or location and development of BMs. It appears that for patients with resected stage III melanoma there is no histopathological lymph node feature associated with the development of BMs. This highlights the importance of identifying molecular markers in nodal melanoma which may predict for BMs to further direct site-specific therapy.

Stage III melanoma in the axilla: patterns of regional recurrence after surgery with and without adjuvant radiation therapy.

PURPOSE: To describe the anatomic distribution of regionally recurrent disease in patients with stage III melanoma in the axilla after curative-intent surgery with and without adjuvant radiation therapy. METHODS AND MATERIALS: A single-institution, retrospective analysis of a prospective database of 277 patients undergoing curative-intent treatment for stage III melanoma in the axilla between 1992 and 2012 was completed. For patients who received radiation therapy and those who did not, patterns of regional recurrence were analyzed, and univariate analyses were performed to assess for potential factors associated with location of recurrence. RESULTS: There were 121 patients who received adjuvant radiation therapy because their clinicopathologic features conferred a greater risk of regional recurrence. There were 156 patients who received no radiation therapy. The overall axillary control rate was 87%. There were 37 patients with regional recurrence; 17 patients had received adjuvant radiation therapy (14%), and 20 patients (13%) had not. The likelihood of in-field nodal recurrence was significantly less in the adjuvant radiation therapy group (P=.01) and significantly greater in sites adjacent to the axilla (P=.02). Patients with high-risk clinicopathologic features who did not receive adjuvant radiation therapy also tended to experience in-field failure rather than adjacent-field failure. CONCLUSIONS: Patients who received adjuvant radiation therapy were more likely to experience recurrence in the adjacent-field regions rather than in the in-field regions. This may not simply reflect higher-risk pathology. Using this data, it may be possible to improve outcomes by reducing the number of adjacent-field recurrences after adjuvant radiation therapy.