The incidence of brain metastases in breast cancer according to molecular subtype and stage: a 10-year single institution analysis.

BACKGROUND: Breast cancer (BC) is the second most common etiology of brain metastases (BrM). We aimed to examine the incidence of BrM among all BC patients presenting to a large tertiary cancer centre over one decade. METHODS: We included all BC patients presenting consecutively between 2009 and 2019 and cross referenced that cohort to a radiotherapy database, identifying patients treated for BrM at any time following their initial presentation. Cumulative incidences (CI) of BrM diagnoses were calculated using death as a competing risk and compared using the Fine-Gray method. Overall survival was estimated using the Kaplan Meier method. RESULTS: We identified 12,995 unique patients. The CI of BrM in patients who initially presented with Stage 0-4 disease was 2.1%, 3.7%, 9.4%, 10.6%, and 28.7%, respectively at 10 years. For 8,951 patients with available molecular subtype data, 6,470 (72%), 961 (11%), 1,023 (11%), and 497 (6%) had hormone-receptor (HR)-positive/ERBB2-, HR-negative/ERBB2-, HR-positive/ERBB2 + , and HR-negative/ERBB2 + disease, respectively; the CI of BrM in each was 7.6%, 25.3%, 24.1%, and 26.6%, at 10 years following BC diagnosis, respectively. Median overall survival (OS) following BC diagnosis and BrM diagnosis was 28 years 95% CI [25, 32] and 10 months 95% CI [9, 12], respectively. CONCLUSIONS: From a large, registry-based study, we observed that patients with ERBB2 + and triple negative BC have the highest incidence of BrM. Our data supports prospective surveillance brain MRI studies. Given advancements in BrM treatment, clinicians should have a low threshold for brain imaging in BC patients with high risk subtypes.

Toxicity and outcomes of melanoma brain metastases treated with stereotactic radiosurgery: the risk of subsequent symptomatic intralesional hemorrhage exceeds that of radiation necrosis.

PURPOSE: We aimed to assess the outcomes and patterns of toxicity in patients with melanoma brain metastases (MBM) treated with stereotactic radiosurgery (SRS) with or without immunotherapy (IO). METHODS: From a prospective registry, we reviewed MBM patients treated with single fraction Gamma Knife SRS between 2008 and 2021 at our center. We recorded all systemic therapies (chemotherapy, targeted therapy, or immunotherapy) administered before, during, or after SRS. Patients with prior brain surgery were excluded. We captured adverse events following SRS, including intralesional hemorrhage (IH), radiation necrosis (RN) and local failure (LF), as well as extracranial disease status. Distant brain failure (DBF), extracranial progression-free survival (PFS) and overall survival (OS) were determined using a cumulative Incidence function and the Kaplan-Meier method. RESULTS: Our analysis included 165 patients with 570 SRS-treated MBM. Median OS for patients who received IO was 1.41 years versus 0.79 years in patients who did not (p = 0.04). Ipilimumab monotherapy was the most frequent IO regimen (30%). In the absence of IO, the cumulative incidence of symptomatic (grade 2 +) RN was 3% at 24 months and remained unchanged with respect to the type or timing of IO. The incidence of post-SRS g2 + IH in patients who did not receive systemic therapy was 19% at 1- and 2 years compared to 7% at 1- and 2 years among patients who did (HR: 0.33, 95% CI 0.11-0.98; p = 0.046). Overall, neither timing nor type of IO correlated to rates of DBF, OS, or LF. Among patients treated with IO, the median time to extracranial PFS was 5.4 months (95% IC 3.2 - 9.1). CONCLUSION: The risk of g2 + IH exceeds that of g2 + RN in MBM patients undergoing SRS, with or without IO. IH should be considered a critical adverse event following MBM treatments.

Anatomical and surgical characteristics correlate with pachymeningeal failure in patients with brain metastases after neurosurgical resection and adjuvant stereotactic radiosurgery.

PURPOSE: Neurosurgery (NS) is an essential modality for large brain metastases (BM). Postoperative stereotactic radiosurgery (SRS) is the standard of care adjuvant treatment. Pachymeningeal failure (PMF) is a newly described entity, distinct from classical leptomeningeal failure (LMF), that is uniquely observed in postoperative patients treated with adjuvant SRS. We sought to identify risk factors for PMF in patients treated with NS + SRS. METHODS: From a prospective registry (2009 to 2021), we identified all patients treated with NS + SRS. Clinical, imaging, pathological, and treatment factors were analyzed. PMF incidence was evaluated using a competing risks model. RESULTS: 144 Patients were identified. The median age was 62 (23-90). PMF occurred in 21.5% (31/144). Female gender [Hazard Ratio (HR) 2.65, p = 0.013], higher Graded Prognostic Assessment (GPA) index (HR 2.4, p < 0.001), absence of prior radiation therapy (HR N/A, p = 0.018), controlled extracranial disease (CED) (HR 3.46, p = 0.0038), and pia/dura contact (PDC) (HR 3.30, p = 0.0053) were associated with increased risk for PMF on univariate analysis. In patients with PDC, wider target volumes correlated with reduced risk of PMF. Multivariate analysis indicated PDC (HR 3.51, p = 0.0053), piecemeal resection (HR 2.38, p = 0.027), and CED (HR 3.97, p = 0.0016) independently correlated with PMF risk. PMF correlated with reduced OS (HR 2.90, p < 0.001) at a lower rate compared to LMF (HR 10.15, p < 0.001). CONCLUSION: PMF correlates with tumor PDC and piecemeal resection in patients treated with NS + SRS. For unclear reasons, it is also associated with CED. In tumors with PDC, wider dural radiotherapy coverage was associated with a lower risk of PMF.

Brain Metastases: A Modern Multidisciplinary Approach.

Brain metastases (BM) are the most common intracranial neoplasm and represent a major clinical challenge across many medical disciplines. The incidence of BM is increasing, largely due to improvements in primary disease therapeutics conferring greater systemic control, and advancements in neuroimaging techniques and availability leading to earlier diagnosis. In recent years, the landscape of BM treatment has changed significantly with the advent of personalized targeted chemotherapies and immunotherapy, the adoption of focal radiotherapy (RT) for higher intracranial disease burden, and the implementation of new surgical strategies. The increasing permutations of options available for the treatment of patients diagnosed with BM necessitate coordinated care by a multidisciplinary team. This review discusses the current treatment regimens for BM as well as examines the salient features of a modern multidisciplinary approach.

Retrospective assessment of patterns of recurrence relative to radiotherapy volumes for adjuvant conformal chemoradiotherapy in gastric cancer.

BACKGROUND: Since the Intergroup 0116 study was published in 2000, adjuvant postoperative chemoradiotherapy using CT-planned and 3D conformal/intensity-modulated radiotherapy has been offered routinely to fit patients with resected gastric cancer at Princess Margaret Hospital .The objective of this study was to analyze patterns of disease recurrence with respect to the radiotherapy volumes. METHODS: For the date and site (local, locoregional, or distant) of the first recurrence, medical records were reviewed for all patients treated at Princess Margaret Hospital with adjuvant chemoradiotherapy for resected gastric adenocarcinoma (January 1, 2000 to November 30, 2009). Patients whose recurrences were limited to local and/or regional sites were selected for further analysis. Available diagnostic imaging of the recurrence site was registered to the original planning radiotherapy dataset for contouring. If necessary to respect changes in anatomy, the contour was translocated on the basis of anatomic descriptors. The center of mass for each recurrence was identified as a point and its location was categorized according to the isodose encompassing it; in field (90 % or more), marginal (50-89 %), or out of field (less than 50 %). RESULTS: Of all 197 patients, 14 (7 %) had isolated locoregional failure, constituting 20 % of all 71 patients with a recurrence. Successful fusions were feasible in five cases. Of these recurrences, four were in field and one was marginal. In a further four cases, visual inspection was used, showing one in-field recurrence, one marginal recurrence, and two out-of-field recurrences. In five patients, either a useable original dataset or diagnostic imaging of the recurrence was not available. CONCLUSIONS: The rates of isolated local/locoregional tumor recurrence in this study were low. Of the small number of recurrences available for analysis, most (five of nine) were in field. Further studies involving a larger cohort of patients might allow a more meaningful analysis of trends in the recurrence site with evolving radiotherapy techniques.

Dosimetric analysis of patients receiving volumetric-modulated arc palliative radiotherapy to the thoracic spine: A comparison with conventional mono-isocentric parallel opposed pair treatment.

PURPOSE: Volumetric modulated arc therapy (VMAT) has allowed for dose escalation and a decrease in radiation-induced toxicities for a variety of treatment sites, including spinal metastases. This article will compare the dosimetric impacts on normal lung tissue in patients treated with both VMAT and conventional treatment to the thoracic spine and determine if any significant difference exists among patient reported Edmonton Symptom Assessment System (ESAS) scores. METHODS: This retrospective quality assurance study identified 288 patients who received palliative radiotherapy to the thoracic spine using VMAT or conventional planning techniques with various palliative dose fractionation schemes. V5 lung dose levels, treated planning target volume (PTV) cord length, patient-reported ESAS scores at the time of radiation oncology consultation, 3 months' post-treatment, and 6 months' post-treatment were analyzed. All symptoms on the ESAS survey were investigated, but shortness of breath (SOB) scores were the main focus of this study. Date of death for each patient was also included for analysis. RESULTS: Patients treated with a VMAT technique had significantly higher V5 lung dose levels compared to those treated conventionally (right lung: p = 1.67e-14; left lung: p = 1.33e-6). Despite this, no significant differences were observed for SOB scores at all time points between groups and conventionally treated patients reported significantly worse pain, tiredness, depression, and wellbeing scores. A moderate correlation was observed between PTV length and nausea, SOB, appetite, and drowsiness scores in the VMAT group. Treatment technique was not found to have a significant impact on patient lifespan. CONCLUSIONS: Despite higher V5 lung dose levels associated with a VMAT technique, no significant differences were found in patient-reported ESAS scores compared to patients treated with conventional techniques. This demonstrates that palliation of thoracic spinal metastases is feasible and safe using a VMAT technique.

Rate of pachymeningeal failure following adjuvant WBRT vs SRS in patients with brain metastases.

Background: Stereotactic radiosurgery (SRS) has supplanted whole brain radiotherapy (WBRT) as standard-of-care adjuvant treatment following surgery for brain metastasis (BrM). Concomitant with the adoption of adjuvant SRS, a new pattern of failure termed "Pachymeningeal failure" (PMF) has emerged. Methods: We reviewed a prospective registry of 264 BrM patients; 145 and 119 were treated adjuvantly with WBRT and SRS, respectively. The Cox proportional hazards model was used to identify variables correlating to outcomes. Outcomes were calculated using the cumulative incidence (CI) method. Univariate (UVA) and multivariate analyses (MVA) were done to identify factors associated with PMF. Results: CI of PMF was 2 % and 18 % at 12 months, and 2 % and 23 % at 24 months for WRBT and SRS, respectively (p < 0.001). The CI of classic leptomeningeal disease (LMD) was 3 % and 4 % at 12 months, and 6 % and 6 % at 24 months for WBRT and SRS, respectively (P = 0.67). On UVA, adjuvant SRS [HR 9.75 (3.43-27.68) (P < 0.001)]; preoperative dural contact (PDC) [HR 6.78 (1.64-28.10) (P = 0.008)]; GPA score [HR 1.64 (1.11-2.42) (P = 0.012)]; and lung EGFR/ALK status [HR 3.11 (1.02-9.45) (P = 0.045)]; were associated with PMF risk. On MVA, adjuvant SRS [HR 8.15 (2.69-24.7) (P < 0.001)]; and PDC [HR 6.28 (1.51-26.1) (P = 0.012)] remained associated with PMF. Conclusions: Preoperative dural contact and adjuvant SRS instead of adjuvant WBRT were associated with an increased risk of PMF. Strategies to improve pachymeningeal radiation coverage to sterilize at risk pachymeninges should be investigated.

A total inverse planning paradigm: Prospective clinical trial evaluating the performance of a novel MR-based 3D-printed head immobilization device.

Background and purpose: Brain radiotherapy (cnsRT) requires reproducible positioning and immobilization, attained through redundant dedicated imaging studies and a bespoke moulding session to create a thermoplastic mask (T-mask). Innovative approaches may improve the value of care. We prospectively deployed and assessed the performance of a patient-specific 3D-printed mask (3Dp-mask), generated solely from MR imaging, to replicate a reproducible positioning and tolerable immobilization for patients undergoing cnsRT. Material and methods: Patients undergoing LINAC-based cnsRT (primary tumors or resected metastases) were enrolled into two arms: control (T-mask) and investigational (3Dp-mask). For the latter, an in-house designed 3Dp-mask was generated from MR images to recreate the head positioning during MR acquisition and allow coupling with the LINAC tabletop. Differences in inter-fraction motion were compared between both arms. Tolerability was assessed using patient-reported questionnaires at various time points. Results: Between January 2020 - July 2022, forty patients were enrolled (20 per arm). All participants completed the prescribed cnsRT and study evaluations. Average 3Dp-mask design and printing completion time was 36 h:50 min (range 12 h:56 min - 42 h:01 min). Inter-fraction motion analyses showed three-axis displacements comparable to the acceptable tolerance for the current standard-of-care. No differences in patient-reported tolerability were seen at baseline. During the last week of cnsRT, 3Dp-mask resulted in significantly lower facial and cervical discomfort and patients subjectively reported less pressure and confinement sensation when compared to the T-mask. No adverse events were observed. Conclusion: The proposed total inverse planning paradigm using a 3D-printed immobilization device is feasible and renders comparable inter-fraction performance while offering a better patient experience, potentially improving cnsRT workflows and its cost-effectiveness.

Factors correlating with survival following adjuvant or definitive radiosurgery for large brain metastases.

BACKGROUND: We sought to identify variates correlating with overall survival (OS) in patients treated with surgery (S) plus adjuvant stereotactic radiosurgery (SRS) versus definitive SRS for large (>4 cc) brain metastases (BrM). METHODS: We used univariate (UVA) and multivariate analyses (MVA) to identify survival correlates among eligible patients identified from a prospective registry and compared definitive SRS to S+ adjuvant SRS cohorts using propensity score-matched analysis (PSMA). Secondary outcomes were measured using the cumulative incidence (CI) method. RESULTS: We identified 364 patients; 127 and 237 were treated with S+SRS and definitive SRS, respectively. On UVA, SRS alone [HR1.73 (1.35,2.22) P < .001), BrM quantity [HR 1.13 (1.06-1.22) (P < .001)]; performance status (PS) [HR 2.78 (1.73-4.46) (P < .001)]; extracranial disease (ECD) [HR 1.82 (1.37,2.40) (P < .001)]; and receipt of systemic treatment after BrM therapy, [HR 0.58 (0.46-073) (P < .001)] correlated with OS. On MVA, SRS alone [HR 1.81 (1.19,2.74) (P < .0054)], SRS target volume [HR 1.03 (1.01,1.06) (P < .0042)], and receipt of systemic treatment [HR 0.68 (0.50,0.93) (P < .015)] correlated with OS. When PSMA was used to balance ECD, BrM quantity, PS, and SRS target volume, SRS alone remained correlated with worsened OS [HR 1.62 (1.20-2.19) (P = 0.0015)]. CI of local failure requiring resection at 12 months was 3% versus 7% for S+SRS and SRS cohorts, respectively [(HR 2.04 (0.89-4.69) (P = .091)]. CI of pachymeningeal failure at 12 months was 16% versus 0% for S+SRS and SRS. CONCLUSION: SRS target volume, receipt of systemic therapies, and treatment with S+SRS instead of definitive SRS correlated with improved survival in patients with large BrM.

Multiplicity does not significantly affect outcomes in brain metastasis patients treated with surgery.

Background: Brain metastasis quantity may be a negative prognostic factor for patients requiring resection of at least one lesion. Methods: We retrospectively reviewed patients who underwent surgical resection of brain metastases from July 2018 to June 2019 at our institution, and examined outcomes including overall survival (OS), progression free survival (PFS), and rates of local failure (LF). Patients were grouped according to the number of metastases at the time of surgery (single vs multiple). Results: We identified 130 patients who underwent surgical resection as the initial treatment modality. At the time of surgery, 87 patients had only one lesion (control) and 43 had multiple (>1). Two-year OS for the entire cohort was 46%, with equal rates in both the multiple metastases group and the control group (P = .335). 2-year PFS was 27%; 21% in the multiple metastases group and 31% in the control group (P = .766). The rate of LF at 2 years was 32%, with equal rates in both the multiple lesion group and control group (P = .889). On univariate analysis, multiplicity was not significantly correlated to OS (HR = 0.80, 95% CI: 0.51-1.26, P = .336), PFS (HR = 1.06, 95% CI: 0.71-1.59, P = .766) or LF (HR = 1.06, 95% CI: 0.57-1.97, P = .840). Multivariate analysis revealed preoperative tumor volume of the resected lesion to be the single correlate for OS (P = .0032) and PFS (P = .0081). Conclusions: Having more than one metastasis does not negatively impact outcomes in patients treated with surgery. In carefully selected patients, especially those with large tumors, surgery should be considered regardless of the total number of lesions.

Clinicopathologic and Treatment Features of Long-Term Surviving Brain Metastasis Patients.

BACKGROUND: The purpose of our study was to characterize clinical features among brain metastasis (BM) patients who were long term survivors (LTS). METHODS: We reviewed a registry of BM patients referred to our multidisciplinary BM clinic between 2006 and 2014 and identified 97 who lived ≥ 3 years following BM diagnosis. The clinical and treatment characteristics were obtained from a prospectively maintained database, and additional information was obtained through review of electronic medical records and radiologic images. Survival analyses were performed using the Kaplan-Meier method. RESULTS: Median follow up for LTS was 67 months (range 36-181). Median age was 54 years, 65% had single BM, 39% had stable extracranial disease at the time of BM treatment, and brain was the first site of metastasis in 76%. Targetable mutations were present in 39% of patients and 66% received treatment with targeted-, hormonal-, or immuno-therapy. Brain surgery at the time of diagnosis was performed in 40% and stereotactic radiosurgery (SRS) or whole brain radiotherapy (alone or combination) in 52% and 56%, respectively. Following initial BM treatment, 5-year intracranial disease-free survival was 39%, and the cumulative incidence of symptomatic radio-necrosis was 16%. Five and ten-year overall survival was 72% and 26%, respectively. CONCLUSION: Most LTS were younger than 60 years old and had a single BM. Many received treatment with surgery or targeted, immune, or hormonal therapy.

Impact of EGFR mutation on outcomes following SRS for brain metastases in non-small cell lung cancer.

INTRODUCTION: Patients with EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC) are at particularly high risk of developing brain metastases (BrM). In addition to EGFR targeting tyrosine kinase inhibitors (TKI), radiosurgery (SRS) has an important role in the management of EGFRm BrM. However, data specific to the response and toxicity of EGFRm BrM to SRS are sparse. We evaluated the incidence of local failure (LF) and toxicity of EGFRm and EGFR-wild-type (EGFRwt) BrM treated with SRS. METHODS: We analyzed a prospective registry of BrM patients treated at our centre between 2008 and 2017 and identified EGFRm and EGFRwt NSCLC patients treated with SRS ±â€¯systemic therapy for BrM. Incidences of local failure (LF) and radionecrosis (RN) were determined, and Cox regression was performed for univariate and multivariate analyses (MVAs). RESULTS: We analyzed data from 218 patients (615 lesions - 225 EGFRm and 390 EGFRwt). Median imaging follow-up per patient was 14.5 months (0.5-96.3). Prior to or concomitant with SRS, 62 % of EGFRm patients received TKI and 93 % received TKI post SRS. The 24-month incidence of LF was 6% and 16 % for EGFRm BrM and EGFRwt, respectively (0.43(0.19-0.95); p = 0.037). The 24-month incidence of RN was 4% and 6% for EGFRm and EGFRwt BrM, respectively (0.8(0.32-1.98) p = 0.63). On MVA, BrM size and prescription dose (PD) significantly correlated with a higher risk of LF and BrM size correlated with a higher risk of RN. CONCLUSION: We observed excellent rates of response and toxicity following SRS in EGFRm compared to EGFRwt NSCLC, suggesting that EGFRm BrM have a favourable risk benefit ratio compared to EGFRwt NSCLC.

Integrating Survivorship Care Into a Radiation Medicine Program.

Introduction An important but often overlooked component of caring for cancer patients is survivorship care, provided after the completion of active treatment in order to facilitate transition into the next surveillance phase. A survivorship program was developed to deliver a one-on-one education session on healthy lifestyle behaviours and available resources to help patients transition to their post-treatment life. This study reports the outcome of this pilot survivorship care program provided to breast cancer patients completing radiation therapy. Program delivery format and content were evaluated for effectiveness, applicability, and feasibility.  Methods and materials Between March 2017 and August 2018, 124 breast cancer patients, nearing completion of their curative intent radiation treatments, participated in this centre-specific survivorship program. The survivorship program entailed a one on one education session delivered to breast cancer patients within the last two weeks of their radiation treatment. Participants were provided a Microsoft PowerPoint presentation, information pamphlet, and evaluation form to provide feedback on materials and presentation. Survivorship education sessions were delivered by study staff or staff scheduled in the Pre-Radiotherapy Patient Assessment role. Follow-up phone calls were conducted post-session delivery to determine the ongoing applicability of survivorship material. Staff was also given an evaluation form upon completion of the trial to measure the session feasibility. Results Of the 124 participants in the study, 69 (56%) provided feedback. Results showed that 98% of participants felt the information provided either confirmed what they were already doing (44%) or encouraged them to consider a lifestyle change (54%). Additionally, 70% reported feeling more confident after completing the session. Staff survey results reported that 87.5% agreed or strongly agreed that these sessions were beneficial and valuable to patients Conclusions Delivering one-on-one education sessions to individual participants focusing on healthy lifestyle measures garnered a positive response from participants, increasing their confidence and knowledge for making lifestyle changes. While staff survey results pointed strongly in favour of continuing with the survivorship sessions, it was shown that the methods of delivery trialed in this study were not feasible to be implemented on a larger scale. With some workflow modification, implementing a survivorship care program in our cancer centre is a possible and important aspect of a patient's treatment journey.

A Phase II Study of Neoadjuvant Stereotactic Radiosurgery for Large Brain Metastases: Clinical Trial Protocol.

BACKGROUND: Brain metastases which require resection are treated with surgery followed by whole brain radiation therapy or postoperative cavity boost stereotactic radiosurgery (POCBS). Recently a novel strategy using neoadjuvant stereotactic radiosurgery (NaSRS) followed by resection was reported, demonstrating lower rates of postoperative leptomeningeal dissemination (LMD) and symptomatic radiation toxicity compared to a comparative cohort of patients treated with postoperative SRS. OBJECTIVE: To determine if the rate of symptomatic radiation toxicity at 1 yr in patients who receive NaSRS differs significantly from historical rates for patients treated with POCBS. METHODS: This is a multi-center, non-randomized, open phase II clinical trial. A total of 30 patients with up to 10 brain metastases, at least 1 of which is appropriate for surgical resection, will be enrolled for over 4 yr. All enrolled patients will be assigned to receive NaSRS followed by surgery. EXPECTED OUTCOME: This study will clarify whether symptomatic radiation toxicity caused by NaSRS is significantly decreased compared to historical rates associated with POCBS. Secondary endpoints will include 1-yr local control (LC) of the treated lesion, 1-yr rates of LMD, median survival and 2-yr rates of progression-free and overall survival. Tertiary analyses will include correlation between LC and radiation toxicity with pretreatment clinical factors, serum markers, radiomic features, and molecular assessments of the resected tumors. DISCUSSION: This prospective study will determine the toxicity associated with NaSRS and provide additional quantitative metrics of efficacy for future comparative trials.

Neurological Death is Common in Patients With EGFR Mutant Non-Small Cell Lung Cancer Diagnosed With Brain Metastases.

PURPOSE: Brain metastases (BrM) are common in patients with epidermal growth factor receptor (EGFRm) mutant non-small cell lung cancer (NSCLC). We sought to determine the rate of neurologic death (ND) in this population. METHODS AND MATERIALS: We analyzed data from 198 patients who received a diagnosis of BrM from EGFRm NSCLC between 2004 and 2016, comparing patients whose initial treatment for BrM was stereotactic radiosurgery with or without tyrosine kinase inhibitors (TKI), whole brain radiation therapy (WBRT) with or without TKI, or TKI alone. The incidence of ND was determined using a competing risks analysis. Univariate and multivariate analyses were used to identify clinical variables associated with this outcome. RESULTS: The percentage of patients who initially received stereotactic radiosurgery, whole brain radiation therapy, or TKI alone was 22%, 61%, and 17%, respectively. Median overall survival in these subgroups was 31.1, 14.6, and 24.6 months, respectively (P = .0016). The 5-year incidence of ND among all patients was 40% and did not significantly vary according to treatment group. In a multivariable model, only leptomeningeal disease at any point in a patient's disease course significantly correlated with ND (hazard ratio 4.75, P <.001). CONCLUSIONS: Among our cohort of patients with BrM from EGFRm NSCLC, the incidence of ND was significantly higher than suggested by previous reports. BrM should be considered a driver of mortality in many patients with EGFRm NSCLC, and treatments providing better control of BrM, lower neurocognitive side effects, and maintenance of quality of life are needed.

Prospective evaluation of pretreatment and intratreatment FDG PET-CT SUV stability in primary head and neck cancer.

PURPOSE: To evaluate standardized uptake value (SUV) stability on pretreatment and intratreatment 18-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) in patients undergoing definitive CRT for head and neck cancer (HNC). METHODS: Primary tumor and nodal volumes of interest (VOIs) from HNC patients were contoured on the pretreatment and intratreatment PET-CT by two independent observers. SUV stability was measured with intersection calculations (DICE, overlap fraction, center to center) between the VOIs at threshold levels of 50%, 60%, 70%, 80%, and 90% of the SUV maximum. RESULTS: The mean calculated DICE of the 50%, 60%, 70%, 80%, 90% SUV threshold was 0.53, 0.48, 0.41, 0.28, and 0.12, respectively. The mean calculated overlap fraction was 0.71, 0.65, 0.58, 0.43, and 0.2, respectively. Center-center difference demonstrates spatial variability of 7.8, 8.2, 8.6, 9.5, and 11.2 mm for these SUV subvolumes of interest. CONCLUSIONS: HNC subvolumes defined by SUV thresholding technique in FDG PET-CT imaging do not remain physically stable during (chemo)RT. HIGHLIGHTS: All pretreatment and intratreatment SUV thresholds (50%-90%) overlap indexes are low during the course of (chemo)radiation. Pretreatment and intratreatment center to center variation further corroborates that all FDG threshold volumes do not remain stable during treatment. No difference in SUV threshold stability was seen between p16 positive and negative tumors.

Outcomes following stereotactic radiosurgery for small to medium-sized brain metastases are exceptionally dependent upon tumor size and prescribed dose.

BACKGROUND: At our institution, we have historically treated brain metastasis (BM) ≤2 cm in eloquent brain with a radiosurgery (SRS) lower prescription dose (PD) to reduce the risk of radionecrosis (RN). We sought to evaluate the impact of this practice on outcomes. METHODS: We analyzed a prospective registry of BM patients treated with SRS between 2008 and 2017. Incidences of local failure (LF) and RN were determined and Cox regression was performed for univariate and multivariate analyses (MVAs). RESULTS: We evaluated 1533 BM ≤2 cm. Median radiographic follow-up post SRS was 12.7 months (1.4-100). Overall, the 2-year incidence of LF was lower for BM treated with PD ≥21 Gy (9.3%) compared with PD ≤15 Gy (19.5%) (sub-hazard ratio, 2.3; 95% CI: 1.4-3.7; P = 0.0006). The 2-year incidence of RN was not significantly higher for the group treated with PD ≥21 Gy (9.5%) compared with the PD ≤15 Gy group (7.5%) (P = 0.16). MVA demonstrated that PD (≤15 Gy) and tumor size (>1 cm) were significantly correlated (P < 0.05) with higher rates of LF and RN, respectively. For tumors ≤1 cm, when comparing PD ≤15 Gy with ≥21 Gy, the risks of LF and RN are equivalent. However, for lesions >1 cm, PD ≥21 Gy is associated with a lower incidence of LF without significantly increasing the risk of RN. CONCLUSION: Our results indicate that rates of LF or RN following SRS for BM are strongly correlated with size and PD. Based on our results, we now, depending upon the clinical context, consider increasing PD to 21 Gy for BM in eloquent brain, excluding the brainstem.

Active breathing control for patients receiving mediastinal radiation therapy for lymphoma: Impact on normal tissue dose.

PURPOSE: Active breathing control (ABC) is emerging as a tool to reduce heart and lung dose for lymphoma patients receiving mediastinal radiation therapy (RT). The objective of this study was to report our early institutional experience with this technique, with emphasis on quantifying the changes in normal tissue dose and exploring factors that could be used to select patients with the greatest benefit. METHODS AND MATERIALS: Patients receiving mediastinal involved-field RT (IFRT) for lymphoma were eligible. The ABC was performed using a moderate deep-inspiration breath-hold (mDIBH) technique. All patients were replanned with free-breathing (FB) computed tomographic data sets and comparisons of lung, cardiac, and female breast tissue doses were made between mDIBH and FB plans. Logistic regression models were used to identify factors associated with improvement in mean lung and heart dose with mDIBH. RESULTS: Forty-seven patients were analyzed; the majority (87.2%) had Hodgkin lymphoma. Median prescribed dose was 30 Gy (range, 20-36 Gy), with 78.7% of cases being treated with parallel-opposed beams. The use of mDIBH significantly improved average mean lung dose (FB: 11.0 Gy; mDIBH: 9.5 Gy; P < .0001), lung V20 (28% vs 22%; P < .0001), and mean heart dose (14.3 Gy vs 11.8 Gy; P = .003), but increased the mean breast dose (FB: 3.0 Gy; mDIBH 3.6 Gy; P = .0005). The magnitude of diaphragmatic excursion on the inhale scan was significantly associated with dosimetric improvement in both heart and lung dose with mDIBH. CONCLUSIONS: Mediastinal IFRT for lymphoma delivered with mDIBH can significantly reduce lung and heart dose compared with FB, although not for all patients, and may increase breast dose in females. Its implementation is achievable in both adult and pediatric populations. Further work is necessary to better predict which patients benefit from this technique.