The impact of initial tumor bulk in DLBCL treated with DA-EPOCH-R vs. R-CHOP: a secondary analysis of alliance/CALGB 50303.

The ideal treatment paradigm for bulky diffuse large B-cell lymphoma (DLBCL) remains uncertain. We investigated the impact of tumor bulk in patients treated with systemic therapy alone through Alliance/CALGB 50303. Data from this trial were obtained from the National Cancer Institute's NCTN/NCORP Data Archive. The study assessed the size of nodal sites and estimated progression-free survival (PFS) using Cox proportional hazards models. Stratified analysis factored in International Prognostic Index (IPI) risk scores. Out of 524 patients, 155 had pretreatment scans. Using a 7.5 cm cutoff, 44% were classified as bulky. Bulk did not significantly impact progression-free survival (PFS), whether measured continuously or at thresholds of >5 or >7.5 cm (p = 0.10-p = 0.99). Stratified analyses by treatment group and IPI risk group were also non-significant. In this secondary analysis, a significant association between bulk and PFS was not identified.

The prognosis of upfront tumor bulk in DLBCL remains unclear. In this secondary analysis of a phase III trial comparing DA-EPOCH-R to R-CHOP, a significant association between upfront tumor bulk and PFS was not identified.

Unilateral Neck Treatment with either Surgery and/or Radiotherapy for Squamous Cell Carcinoma for the Tonsil.

INTRODUCTION: Strategies for treatment of tonsil carcinoma are under active investigation. Limiting surgical and radiation treatment volumes to the primary tumor and ipsilateral neck in appropriately selected patients are one such approach. Here, we present our institutional experience with treatment through ipsilateral surgical or radiotherapeutic neck management. METHODS: We retrospectively reviewed our institutional database of patients with tonsil carcinoma treated from 2012 to 2020. Patients were included for analysis if they received definitive radiation therapy (RT), definitive surgery (S), or surgery with postoperative radiation therapy (S-PORT) and whose treatment volumes were limited to the primary tumor and involved/elective ipsilateral neck. Patients who received radiation and/or surgery to the contralateral neck (including those with bilateral nodal involvement), as well as patients with metastatic disease, were excluded. Clinical factors including T- and N-stage (AJCC 7th edition), and HPV status (by p16 and/or HPV DNA PCR) were recorded, as were pathologic factors (when applicable) including margin status, extracapsular extension (ECE), lymphovascular invasion (LVSI), and perineural invasion (PNI). Overall survival (OS), progression-free survival (PFS), and locoregional control (LRC) at 2 years were estimated using the Kaplan-Meier method. RESULTS: In total, 71 patients were treated with unilateral neck approaches: S (n = 49), RT (n = 10), and S+PORT (n = 12). Among these patients, 32, 36, and 3 had T1, T2, and T3 disease, respectively. N-stage was N0, N1, N2a, N2b, and N3 in 22, 20, 5, 23, and 1 patient(s), respectively. Concurrent chemotherapy was administered in 12 patients. From those with recorded risk factors, 86% were HPV positive, 20% had LVSI, 7% had PNI, 13% had ECE, and 5% had positive margins. From a median follow-up of 27 months, local, regional, and distant failures occurred in 5, 6, and 5 patients, respectively. No contralateral neck failures were recorded. At 2 years, OS, PFS, and LRC were 92% (95% CI 85-99%), 85% (95% CI 75-95%), and 88% (95% CI 80-98%), respectively. CONCLUSIONS: In patients with early T-stage tonsil carcinoma, treatment of the primary tumor and ipsilateral neck is associated with acceptable OS, PFS, and LRC. In this population, the risk of contralateral neck failure is likely very low regardless of primary treatment modality. Additional prospective studies are needed to determine the impact of limiting treatment extent, either surgical or radiotherapeutic, to the unilateral neck.

Treatment Options for Brain Metastases.

OPINION STATEMENT: Therapies for brain metastasis continue to evolve as the life expectancies for patients have continued to prolong. Novel advances include the use of improved technology for radiation delivery, surgical guidance, and response assessment, along with systemic therapies that can pass through the blood brain barrier. With increasing complexity of treatments and the increased need for salvage treatments, multi-disciplinary management has become significantly more important.

Delayed Imaging Changes 18 Months or Longer After Stereotactic Radiosurgery for Brain Metastases: Necrosis or Progression.

OBJECTIVE: Imaging changes after stereotactic radiosurgery (SRS) can occur for years after treatment, although the available data on the incidence of tumor progression and adverse radiation effects (ARE) are generally limited to the first 2 years after treatment. METHODS: A single-institution retrospective review was conducted of patients who had >18 months of imaging follow-up available. Patients who had ≥1 metastatic brain lesions treated with Gamma Knife SRS were assessed for the time to radiographic progression. Those with progression ≥18 months after the initial treatment were included in the present study. The lesions that progressed were characterized as either ARE or tumor progression based on the tissue diagnosis or imaging characteristics over time. RESULTS: The cumulative incidence of delayed imaging radiographic progression was 35% at 5 years after the initial SRS. The cumulative incidence curves of the time to radiographic progression for lesions determined to be ARE and lesions determined to be tumor progression were not significantly different statistically. The cumulative incidence of delayed ARE and delayed tumor progression was 17% and 16% at 5 years, respectively. Multivariate analysis indicated that the number of metastatic brain lesions present at the initial SRS was the only factor associated with late radiographic progression. CONCLUSIONS: The timing of late radiographic progression does not differ between ARE and tumor progression. The number of metastatic brain lesions at the initial SRS is a risk factor for late radiographic progression.

Prognostication methods for patients treated with palliative radiotherapy: a narrative review.

BACKGROUND AND OBJECTIVE: Palliative radiotherapy (PRT) practice patterns among radiation oncologists are heterogeneous. Appropriate selection of PRT regimen must balance symptom/disease control with patient quality of life. The aim of this review is to summarize prognostic scoring systems for PRT in order to help guide clinical decision making and selection of appropriate PRT regimens. METHODS: A PubMed search was conducted for articles published between 01/2000 and 07/2023. Standardized search terms including "palliative", "radiotherapy" and "survival" were used. Only English-language, peer-reviewed articles that presented a prognostic scoring system of PRT were included in this review. KEY CONTENT AND FINDINGS: In this study, we review the published literature on prognostic scoring systems for patients treated with PRT. Multiple models have been developed and each pertains to a specific patient population or primary tumor type. While they are specific to a particular patient population, all models incorporate patients' clinical characteristics such as primary site, performance status, location of metastatic disease, and indication for PRT to estimate overall survival (OS) after PRT. For each model, the salient points of the scoring system are described. Based on survival estimates from each prognostic system, different PRT regimens are recommended. CONCLUSIONS: PRT scoring systems can be used to help clinicians assess patient prognosis. With the information provided by the included studies, radiation oncologists will be better prepared to formulate an optimal, individualized treatment plan for patients to be treated with PRT.

Survival and Swallowing Function after Primary Radiotherapy versus Transoral Robotic Surgery for Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma.

INTRODUCTION: The aim of this study was to investigate the impact of primary transoral robotic surgery (TORS) versus radiotherapy (RT) on progression-free survival (PFS), overall survival (OS), and 1-year swallowing function for patients with early-stage HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). METHODS: Patients with stage I-II (AJCC 8th Ed.) HPV-associated OPSCC treated with TORS followed by risk-adapted adjuvant therapy or (chemo)radiotherapy between 2014 and 2019 were identified. PFS, OS, and swallowing outcomes including gastrostomy tube (GT) use/dependence, and Functional Oral Intake Scale (FOIS) change over 1 year were compared. RESULTS: One hundred sixty-seven patients were analyzed: 116 treated with TORS with or without adjuvant RT and 51 treated with RT (50 chemoRT). The RT group had more advanced tumor/nodal stage, higher comorbidity, and higher rates of concurrent chemotherapy. There were no differences in 3-year PFS (88% TORS vs. 75% RT) or OS (90% vs. 81%) between groups, which persisted after adjusting for stage, age, and comorbidity. GT use/dependence rates were higher in the RT group. Mean (SD) FOIS scores in the TORS group were 6.9 (0.4) at baseline and 6.4 (1.0) at 1 year, compared with 6.7 (0.6) and 5.6 (1.7) for the RT group. Only clinical nodal stage was found to be significantly associated with FOIS change from baseline to 1 year. CONCLUSION: There were no differences in PFS or OS between patients treated with primary TORS or RT for early-stage HPV-associated OPSCC. Clinical N2 status is associated with FOIS change at 1 year and may be the major factor affecting long-term swallowing function, irrespective of primary treatment modality.

Five-year survivors from brain metastases treated with stereotactic radiosurgery: Biology, improving treatments, or just plain luck?

Background: Improvements in therapies have led to an increasing number of long-term survivors of brain metastases. The present series compares a population of 5-year survivors of brain metastases to a generalized brain metastases population to assess for factors attributable to long-term survival. Methods: A single institution retrospective review was performed to identify 5-year survivors of brain metastases who received stereotactic radiosurgery (SRS). A historical control population of 737 patients with brain metastases was used to assess similarities and differences between the long-term survivor population and the general population treated with SRS. Results: A total of 98 patients with brain metastases were found to have survived over 60 months. No differences between long-term survivors and controls were identified with regards to the age at first SRS (P = .19), primary cancer distribution (P = .80), and the number of metastases at first SRS (P = .90). Cumulative incidence of neurologic death at 6, 8 and 10 years for the long-term survivor cohort was 4.8%, 16%, and 16% respectively. In the historical controls, cumulative incidence of neurologic death reached a plateau at 40% after 4.9 years. A significant difference in the distribution of burden of disease at the time of the first SRS was found between the 5-year survivors and the control (P = .0049). 58% of 5-year survivors showed no evidence of clinical disease at the last follow-up. Conclusion: Five-year survivors of brain metastases represent a diverse histologic population, suggesting a small population of oligometastatic and indolent cancers exist for each cancer type.

Long term survivors of stereotactic radiosurgery for brain metastases: do distant brain failures reach a plateau and what factors are associated with a brain metastasis velocity of zero?

PURPOSE: Life expectancy continues to increase for patients with brain metastases treated with stereotactic radiosurgery (SRS). The present study sought to retrospectively analyze brain metastasis patients who have survived 2 years or more, and assess for what factors may predict for a final brain metastasis velocity (BMV) of zero. METHODS: This was a single-institution retrospective study of 300 patients treated with SRS from 2001 to 2019 for brain metastases who survived greater than 2 years after first SRS. Final BMV is calculated by summing all metastases through the observed time divided by the total time in years. A BMV of zero is defined as at least 2 years of imaging follow-up without distant brain failure (DBF). RESULTS: Median age at first SRS is 61 (IQR: 53, 70). Kaplan-Meier estimated median overall survival is 4.9 years and time to DBF is 1.5 years (95% CI 1.2, 2.0). Twenty-eight (9.3%) patients underwent subsequent WBRT. One hundred and one (33.7%) patients never had any further brain metastases (BMV = 0) at a median follow-up time of 3.3 years. Median BMV is 0.4 (IQR: 0, 1.4). Distant brain failures reach a plateau at 4 years where the cumulative incidence of DBF is 82%. 70% of first time DBFs have occurred by 2 years. Factors significantly associated with a BMV of zero include fewer brain metastases at first SRS (HR 1.1; p = 0.0004) and Caucasian race (HR 1.5; p = 0.03). CONCLUSION: Approximately one third of brain metastasis patients who live beyond 2 years after initial SRS have a BMV of zero. DBFs appear to reach a plateau at 4 years. Factors significantly associated with a BMV of zero include Caucasian race and having had a single brain metastasis at first SRS.

Upfront immunotherapy leads to lower brain metastasis velocity in patients undergoing stereotactic radiosurgery for brain metastases.

Background: While immunotherapy has been shown to improve survival and decrease neurologic death in patients with brain metastases, it remains unclear whether this improvement is due to prevention of new metastasis to the brain. Method: We performed a retrospective review of patients presenting with brain metastases simultaneously with the first diagnosis of metastatic disease and were treated with upfront immunotherapy as part of their treatment regimen and stereotactic radiosurgery (SRS) to the brain metastases. We compared this cohort with a historical control population (prior to the immunotherapy era) who were treated with pre-immunotherapy standard of care systemic therapy and with SRS to the brain metastases. Results: Median overall survival time was improved in the patients receiving upfront immunotherapy compared to the historical cohort (48 months vs 8.4 months, p=0.001). Median time to distant brain failure was statistically equivalent (p=0.3) between the upfront immunotherapy cohort and historical control cohort (10.3 vs 12.6 months). Brain metastasis velocity was lower in the upfront immunotherapy cohort (median 3.72 metastases per year) than in the historical controls (median 9.48 metastases per year, p=0.001). Cumulative incidence of neurologic death at one year was 12% in the upfront immunotherapy cohort and 28% in the historical control cohort (p=0.1). Conclusions: Upfront immunotherapy appears to improve overall survival and decrease BMV compared to historical controls. While these data remain to be validated, they suggest that brain metastasis patients may benefit from concurrent immunotherapy with SRS.

Pilot study to assess sexual function, quality of life (QOL) and change in vaginal dimensions following vaginal brachytherapy (VBT).

METHODS: 63 patients with early stage endometrial carcinoma treated with VBT 30 Gy in three fractions to the vaginal surface were invited to participate. 18 patients enrolled. Vaginal length and diameter were measured using original VBT cylinders to assess change. Patients completed sexual function, QOL, and toxicity questionnaires. The assessment of patients' sexual function relative to national mean was calculated and reported by the Health Measures Scoring Service, a third party. RESULTS: Median length of time from VBT start until research visit was 3.6 years. Mean original vaginal length of the 18 women was 13.7 cm (Range: 11-18 cm); mean original diameter was 3.0 cm (Range: 2.5-3.5 cm). There was a significant decrease in vaginal length of 1.2 cm (p = 0.0005). There was a mean vaginal diameter decrease of 0.03 cm that was not significant. Toxicities were grade 1-2 and infrequent. There were no grade two acute toxicities, and 1 patient (5.6%) who had a chronic toxicity, diarrhea. 7 patients had evaluable sexual function responses. Reported sexual function was above the national mean in global satisfaction, interest, and lubrication (52.9, 50.2, and 56.2 percentile). Patients performed beneath national mean in the categories of orgasm and discomfort (3.1, 46.7 percentile) which was not correlated with the decrease in vaginal length. DISCUSSION/CONCLUSION: VBT resulted in significant vaginal shortening. Patients underperformed in the categories of orgasm and vaginal discomfort relative to national mean. This report adds to the scarce literature of objective data on sexual satisfaction and vaginal sequelae of VBT for endometrial carcinoma.

Local control outcomes for combination of stereotactic radiosurgery and immunotherapy for non-small cell lung cancer brain metastases.

BACKGROUND: Previous series have demonstrated CNS activity for immune checkpoint inhibitors, yet no prior data exists regarding whether this activity can improve outcomes of stereotactic radiosurgery. METHODS: In this single institution retrospective series, the clinical outcomes of 80 consecutive lung cancer patients treated with concurrent immune checkpoint inhibitors and stereotactic radiosurgery were compared to 235 in the historical control cohort in which patients were treated prior to immune checkpoint inhibition being standard upfront therapy. Overall survival was estimated using the Kaplan Meier method. Cumulative incidence of local progression was estimated using a competing risk model. RESULTS: Median overall survival time was improved in patients receiving upfront immunotherapy compared to the historical control group (40 months vs 8 months, p < 0.001). Factors affected overall survival include concurrent immunotherapy (HR 0.23, p < 0.0001) and KPS (HR 0.97, p = 0.0001). Cumulative incidence of local failure in the historical control group was 10% at 1 year, compared to 1.1% at 1 year in the concurrent immunotherapy group (p = 0.025). Factors affected local control included use of concurrent immunotherapy (HR 0.09, p = 0.012), and lowest margin dose delivered to a metastasis (HR 0.8, p = 0.0018). CONCLUSION: Local control and overall survival were both improved in patients receiving concurrent immune checkpoint inhibitors with radiosurgery compared to historical controls. While these data remain to be validated, they suggest that brain metastasis patients may benefit from concurrent use of immunotherapy with SRS.

Skeletal-Related Events After Surgery With or Without Radiotherapy for Bone Metastases to Weight-Bearing Bones.

Introduction In patients with metastatic disease involving weight-bearing bones, postoperative radiotherapy (PORT) is commonly administered following surgical stabilization of an impending or confirmed pathologic fracture to reduce the risk of a seeded local recurrence. The goal was to re-evaluate the beneficial effect of PORT in a modern cohort of patients and determine any potential clinical predictors of skeletal-related events (SREs) which were defined as a pathologic fracture or the necessity for radiation or surgery to the affected bone. Methods Consecutive patients undergoing surgical stabilization of metastatic disease to weight-bearing bones of the extremities between 2012 and 2019 were reviewed. Patient, disease, and treatment factors were abstracted. The cumulative incidence of SREs was determined using competing risks methodology; overall survival (OS) was estimated using the Kaplan-Meier method.  Results A total of 82 patients were identified, 74% of whom had undergone intramedullary nail fixation and 26% internal fixation or replacement. The femur was the most commonly involved bone (94%). A majority (78%) had an Eastern Cooperative Oncology Group (ECOG) performance status of 1-2. Bone-strengthening agents were given to 38% and PORT to 54%. The median PORT dose was 30 Gy in 10 fractions and the median percent coverage of surgical hardware was 100% (range, 25-100). SREs occurred in 10 of 82 patients. There were no differences between no RT and RT groups for the two-year cumulative incidence of SREs (8.2% vs 11.5%, p=0.59) or two-year cumulative incidence of local failure (10.8% vs 4.6%, p=0.53). The only identified predictors of SREs were the use of bone-strengthening agents (hazard ratio [HR] 0.22, 95% confidence interval [CI] 0.05-1.06, p=0.06) and malnutrition (HR 3.69, 95% CI 0.91-14.93, p=0.07). For patients treated with PORT, a biologically effective dose or percent coverage of surgical hardware was not associated with SREs. Conclusion In this series, the addition of PORT following surgery for metastatic disease involving weight-bearing bones does not significantly affect the rate of SREs. The use of bone-strengthening agents appears protective, and malnourished patients appear particularly at high risk for future SRE.

A Single-Institution Retrospective Study of Patients Treated With Laser-Interstitial Thermal Therapy for Radiation Necrosis of the Brain.

Object Laser-interstitial thermal therapy (LITT) has been proposed as an alternative treatment to surgery for radiation necrosis (RN) in patients treated with stereotactic radiosurgery (SRS) for brain metastases. The present study sought to retrospectively analyze LITT outcomes in patients with RN from SRS. Methods This was a single-institution retrospective study of 30 patients treated from 2011-2018 with pathologically-proven RN after SRS for brain metastases (n=28) or proximally treated extracranial lesions treated with external beam radiotherapy (n=2). Same-day biopsy was performed in all cases. Patients were prospectively followed with Functional Assessment of Cancer Therapy - Brain (FACT-Br), EuroQol-5 Dimension (EQ-5D), Hopkins Verbal Learning Test (HVLT) and clinical history and examination. Adjusted means, standard errors and tests comparing visits to pre-LITT were generated. Kaplan-Meier method was used to estimate time overall survival. Competing risk analysis was used to estimate cumulative incidence of LITT failure. Results In our patient population, median time from radiotherapy to LITT was 13.1 months. Median SRS dose and median LITT treatment target volume were 20 Gy (IQR 18-22) and 3.5 cc (IQR 2.2-4.6), respectively. Seventy-seven percent of our patients tapered off steroids within one month. There were only two instances of RN recurrence after LITT, with recurrence defined as recurrence of symptoms after initial improvement. These recurrences occurred at 1.9 and 3.4 months. The three-, six- and nine-month freedom from recurrence rates were 95.7%, 90.9%, and 90.9%. Median survival in our patient population with pathologically confirmed RN treated with LITT was 2.1 years. Regarding the quality of life questionnaires with which some patients were followed as part of different prospective studies, completion rates were 22/30 for FACT-Br, 16/30 for the EQ-5D and 8/30 for HVLT. Quality of life questionnaire results were overall stable from baseline. Mean FACT-Br scores were stable from baseline (17.9, 16.6, 21.4 and 22.8) to three months (18.8, 15.4, 18.4 and 23.4) (p=0.38, 0.53, 0.09 and 0.59). The mean EQ-5D Aggregate score was stable from baseline (7.1) to one month (7.6) (p=0.25). Mean HVLT-R Total Recall was stable from baseline (20.6) to three months (18.4) (p=0.09). There was a statistically significant decrease in mean Karnofsky Performance Scale (KPS) score from baseline (84) to three-month follow-up (75) (p=0.03). Conclusions LITT represents a safe and durably effective treatment option for RN in the brain. Results demonstrate a median survival of 2.1 years from LITT with only two recurrences, both within four months of treatment and salvageable. Patient-reported outcomes showed no severe declines after LITT. Quality of life questionnaires demonstrated stable well-being and functionality from baseline. LITT should be considered for definitive treatment of RN, especially in cases where patients have significant side effects from standards medical therapies such as steroids or if steroids are minimally effective.

Predictors of Adverse Radiation Effect in Brain Metastasis Patients Treated With Stereotactic Radiosurgery and Immune Checkpoint Inhibitor Therapy.

PURPOSE: Immune checkpoint inhibitor (ICI) therapy has recently been found to improve survival in patients with a number of cancers, including those with metastatic disease. There is an association of adverse radiation effect (ARE) in patients with brain metastases who have been treated with stereotactic radiosurgery (SRS) and ICIs. METHODS AND MATERIALS: Single-institution retrospective review identified 1118 brain metastases treated with SRS between 2013 and 2018 that had received ICI therapy and 886 metastases that did not receive ICI. Toxicity grading was done via the Common Terminology Criteria for Adverse Events v4.0 grading criteria. Cumulative incidence of ARE was estimated using competing risks methodology; univariate and multivariable regression models were generated to estimate the subdistribution hazard (sHR) of ARE. RESULTS: Two-year cumulative incidence of ARE was 4.5% and 2.1% in patients treated with and without ICI, respectively (Gray's P = .004). Of the 52 metastases exhibiting ARE during the follow-up period, ARE severity by Common Terminology Criteria for Adverse Events v4 was grade 1 in 14 patients, grade 2 in 15, grade 3 in 9, and grade 4 in 14. There were no grade 5 events. Factors associated with an increased sHR of ARE on univariate analysis included ICI, metastasis volume, SRS dose, prescription isodose line, cavity-directed SRS, and V12. Multivariable analysis revealed prescription isodose line (sHR 0.95, P < .01) and ICI (sHR 2.58, P < .01) as significant predictors of ARE. Increasing V12 was associated with a rapidly increasing risk of adverse radiation effect in patients who received ICI. CONCLUSIONS: Our findings suggest that patients receiving ICI have an increased risk of ARE after radiosurgery for brain metastases, with large metastases being at particularly high risk.

Impact of brain metastasis velocity on neurologic death for brain metastasis patients experiencing distant brain failure after initial stereotactic radiosurgery.

PURPOSE: Patients with high rates of developing new brain metastases have an increased likelihood of dying of neurologic death. It is unclear, however, whether this risk is affected by treatment choice following failure of primary stereotactic radiosurgery (SRS). METHODS: From July 2000 to March 2017, 440 patients with brain metastasis were treated with SRS and progressed to have a distant brain failure (DBF). Eighty-seven patients were treated within the immunotherapy era. Brain metastasis velocity (BMV) was calculated for each patient. In general, the institutional philosophy for use of salvage SRS vs whole brain radiotherapy (WBRT) was to postpone the use of WBRT for as long as possible and to treat with salvage SRS when feasible. No further treatment was reserved for patients with poor life expectancy and who were not expected to benefit from salvage treatment. RESULTS: Two hundred and eighty-five patients were treated with repeat SRS, 91 patients were treated with salvage WBRT, and 64 patients received no salvage radiation therapy. One-year cumulative incidence of neurologic death after salvage SRS vs WBRT was 15% vs 23% for the low- (p = 0.06), 30% vs 37% for the intermediate- (p < 0.01), and 31% vs 48% (p < 0.01) for the high-BMV group. Salvage WBRT was associated with increased incidence of neurologic death on multivariate analysis (HR 1.64, 95% CI 1.13-2.39, p = 0.01) when compared to repeat SRS. One-year cumulative incidence of neurologic death for patients treated within the immunotherapy era was 9%, 38%, and 38% for low-, intermediate-, and high-BMV groups, respectively (p = 0.01). CONCLUSION: Intermediate and high risk BMV groups are predictive of neurologic death. The association between BMV and neurologic death remains strong for patients treated within the immunotherapy era.

Immunotherapy is associated with improved survival and decreased neurologic death after SRS for brain metastases from lung and melanoma primaries.

BACKGROUND: The effect of immunotherapy on brain metastasis patients remains incompletely understood. Our goal was to evaluate its effect on survival, neurologic death, and patterns of failure after stereotactic radiosurgery (SRS) without prior whole-brain radiation therapy (WBRT) in patients with lung and melanoma primaries metastatic to the brain. METHODS: We performed a retrospective analysis of 271 consecutive lung or melanoma patients treated with upfront SRS for brain metastases between 2013 and 2018. Of these patients, 101 (37%) received immunotherapy and 170 (63%) did not. Forty-three percent were treated with nivolumab. Thirty-seven percent were treated with pembrolizumab. Fifteen percent were treated with ipilimumab. One percent were treated with a combination of nivolumab and ipilimumab. One percent were treated with atezolizumab. Three percent were treated with another immunotherapy regimen. Survival was estimated by the Kaplan-Meier method and cumulative incidences of neurologic death, and local and distant brain failure were estimated using death as a competing risk. RESULTS: The median overall survival (OS) of patients treated with immunotherapy vs without was 15.9 (95% CI: 13.3 to 24.8) vs 6.1 (95% CI: 5.1 to 8.8) months (P < .01). The 1-year cumulative incidence of neurologic death was 9% in patients treated with immunotherapy vs 23% in those treated without (P = .01), while nonneurologic death was not significantly different (29% vs 41%, P = .51). Median brain metastasis velocity (BMV) did not differ between groups, and rates of salvage SRS and WBRT were similar. CONCLUSIONS: The use of immunotherapy in patients with lung cancer or melanoma metastatic to the brain treated with SRS is associated with improved OS and decreased incidence of neurologic death.

Potential prognostic markers for survival and neurologic death in patients with breast cancer brain metastases who receive upfront SRS alone.

PURPOSE/OBJECTIVES: Stereotactic radiosurgery (SRS) is used as a treatment option for breast cancer brain metastases. It is unclear what factors predict neurologic death for these patients. MATERIALS/METHODS: A total of 128 patients with breast cancer brain metastases were treated with upfront SRS alone in this study. Survival was estimated using the Kaplan-Meier method. Clinicopathologic factors evaluated included age, ER/PR status, Her2 status, numbers of brain metastases treated, minimum SRS dose, disease-specific GPA, extracranial disease status and systemic disease burden. RESULTS: ER or PR positivity was associated with a trend towards decreased neurologic death (subdistribution hazard ratio (sHR) = 0.54, p=0.06). Factors associated with non-neurologic death include extracranial disease status (sHR = 2.02, p=0.02) and dose (sHR = 1.11, p=0.02); Her2-positivity was associated with reduced hazard of non-neurologic death (sHR 0.52, p=0.05). CONCLUSIONS: ER/PR positivity was associated with a trend towards less neurologic death. HER2 positivity was associated with a trend towards less non-neurologic death.

Impact of diabetes mellitus on outcomes in patients with brain metastasis treated with stereotactic radiosurgery.

PURPOSE: To determine the influence of diabetes mellitus (DM) on outcomes in patients with brain metastasis treated with stereotactic radiosurgery (SRS). METHODS: We retrospectively reviewed 498 patients with brain metastasis treated at our institution with SRS between January 2012 and March 2017. RESULTS: Eight-four patients (16.9%) held a diagnosis of DM prior to SRS treatment. Diabetics compared to nondiabetics had worse overall survival (OS). DM was found to be a significant predictor of OS on multivariate analysis (HR: 1.41, CI: 1.03-1.92, p = 0.03). When stratified by DM diagnosis, there were no significant differences in incidence of radiation necrosis (p = 0.82), radiation-induced edema (p = 0.88), cerebrospinal fluid leak (p = 0.49), or postoperative infection (p = 0.68). CONCLUSIONS: DM diagnosis was a significant predictor of poorer OS in patients treated for brain metastasis with SRS. Diabetics and nondiabetics experienced similar rates of radiation-associated brain toxicities.

Surgical resection and postoperative radiosurgery versus staged radiosurgery for large brain metastases.

PURPOSE: The purpose of this study was to retrospectively evaluate the new treatment paradigm of staged stereotactic radiosurgery (SRS) for the treatment of large brain metastases (BM) compared to the standard of surgical resection followed by SRS. METHODS: We evaluated 78 patients with large BM treated 2012-2017 with surgical resection and postoperative SRS (surgery + SRS) or staged SRS separated by 1 month. Overall survival (OS) was estimated using the Kaplan Meier method and compared across groups using the log-rank test. Cumulative incidence of neurologic death and local and distant brain failure (LF, DBF) were estimated using competing risk methodology. RESULTS: Forty patients were treated with surgery + SRS and 38 patients were treated with staged SRS. Median follow-up was 23.2 months (95% CI 20.5-39.3). Median OS was 13.2 months for staged SRS compared to surgery + SRS 9.7 months (p = 0.53). Cumulative incidence of neurologic death at 1 year was 23% after surgery + SRS, 27% after staged SRS (p = 0.69); cumulative incidence of LF at 1 year was 6% and 8% (p = 0.65) and 1-year DBF was 59% and 21% (p ≤ 0.01). Overall rates of leptomeningeal failure and radiation necrosis were similar between the groups (p = 0.63 and p = 1.0). CONCLUSIONS: Though surgery and postoperative SRS is the standard, staged SRS represents an attractive treatment paradigm for treating large BM without sacrificing LC or survival, and potentially decreases DBF. Prospective studies are needed to validate these findings.

Initial brain metastasis velocity: does the rate at which cancers first seed the brain affect outcomes?

PURPOSE/OBJECTIVE(S): Brain metastasis velocity (BMV) is a metric that describes the rate of development of new brain metastases (BM) after initial stereotactic radiosurgery (SRS). A limitation in the application of BMV is it cannot be applied until time of first BM failure after SRS. We developed initial BM velocity (iBMV), a new metric that accounts for the number of BM at first SRS and the time since initial cancer diagnosis. MATERIALS/METHODS: We reviewed patients with BM treated at our institution with upfront SRS without WBRT. iBMV was calculated as the number of BM at initial SRS divided by time (years) from initial cancer diagnosis to first SRS. We performed a linear regression to correlate BMV as a continuous variable and with low, intermediate, and high BMV risk groups. Kaplan-Meier estimation of OS was calculated from time of first SRS to death. iBMV was not calculated for patients who presented with BM at initial cancer diagnosis. RESULTS: 994 patients were treated with upfront SRS without WBRT between 2000 and 2017. Median OS was 8.5 mos. 595 (60%) patients developed BM after cancer diagnosis and median time to first SRS from time of initial diagnosis was 2.2 years. Median iBMV was 0.79 BM/year. iBMV correlated with BMV (ß = 1.57 p = 0.021) and independently predicted for mortality [Cox proportional hazard ratio (HR) 1.11, p = 0.036] after accounting for histology, number of initial brain metastases (HR 1.03, p = 0.32), time from cancer diagnosis to SRS (HR 0.98, p = 0.157) in a multivariate model. CONCLUSION: iBMV correlates with BMV and OS. With further validation, iBMV could serve as a metric to risk stratify patients for WBRT or SRS at time of first BM presentation.