scholarly journals Integration of Systemic Therapy and Stereotactic Radiosurgery for Brain Metastases

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3682
Author(s):  
Raees Tonse ◽  
Martin C. Tom ◽  
Minesh P. Mehta ◽  
Manmeet S. Ahluwalia ◽  
Rupesh Kotecha
Keyword(s):  
Stereotactic Radiosurgery ◽  
Systemic Therapy ◽  
Checkpoint Inhibitors ◽  
Tumor Biology ◽  
Treatment Strategies ◽  
Whole Brain Radiotherapy ◽  
Cancer Therapeutics ◽  
Optimal Timing ◽  
The Impact ◽  
Systemic Therapies

Brain metastasis (BM) represents a common complication of cancer, and in the modern era requires multi-modal management approaches and multi-disciplinary care. Traditionally, due to the limited efficacy of cytotoxic chemotherapy, treatment strategies are focused on local treatments alone, such as whole-brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), and resection. However, the increased availability of molecular-based therapies with central nervous system (CNS) penetration now permits the individualized selection of tailored systemic therapies to be used alongside local treatments. Moreover, the introduction of immune checkpoint inhibitors (ICIs), with demonstrated CNS activity has further revolutionized the management of BM patients. The rapid introduction of these cancer therapeutics into clinical practice, however, has led to a significant dearth in the published literature about the optimal timing, sequencing, and combination of these systemic therapies along with SRS. This manuscript reviews the impact of tumor biology and molecular profiles on the management paradigm for BM patients and critically analyzes the current landscape of SRS, with a specific focus on integration with systemic therapy. We also discuss emerging treatment strategies combining SRS and ICIs, the impact of timing and the sequencing of these therapies around SRS, the effect of corticosteroids, and review post-treatment imaging findings, including pseudo-progression and radiation necrosis.

scholarly journals RADI-13. Systemic Therapy Type and Timing Effects on Radiation Necrosis Risk in HER2+ Breast Cancer Brain Metastases Patients Treated with Stereotactic Radiosurgery

2021 ◽  
Vol 3 (Supplement_3) ◽  
pp. iii20-iii20
Author(s):  
Christine Park ◽  
Evan Buckley ◽  
Amanda Van Swearingen ◽  
Will Giles ◽  
James Herndon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stereotactic Radiosurgery ◽  
Systemic Therapy ◽  
Radiation Necrosis ◽  
Standard Of Care ◽  
Current Standard ◽  
Her2 Breast Cancer ◽  
Breast Cancer Brain Metastasis ◽  
The Impact ◽  
Systemic Therapies

Abstract Background Current standard of care options for HER2+ breast cancer brain metastasis (BCBrM) include radiation therapy, brain permeable systemic therapies, and in select cases, neurosurgical resection. There is a concern that HER2-directed systemic therapies when administered concurrently with stereotactic radiosurgery (SRS) may increase the risk of radiation necrosis (RN). This study explores the impact of timing and type of systemic therapies on the development of RN in patients treated with SRS for HER2+ BCBrM. Methods This was a single-institution, retrospective study including patients ≥18 years of age with HER2+ BCBrM who received SRS between 2013 and 2018 with at least 12-month post-SRS follow-up. Presence of RN was determined at one-year post-SRS. Demographics, radiotherapy parameters, and timing (“during” defined as four weeks before/after SRS) and type of systemic therapy were evaluated. Results Among 46 patients with HER2+ BCBrM who received SRS, 28 (60.9%) developed RN and 18 (39.1%) did not. Age (mean 53.3 vs 50.4 years, respectively), radiotherapy parameters (dose, fraction, CTV, GTV, CI, V12Gy, all p>0.05), and receipt of any type of systemic therapy during SRS (60.7% vs 55.6%, p = 0.97) did not differ between patients who did or did not develop RN. However, patients who developed RN more commonly received more than one line of HER2-directed therapy independent of SRS timing compared to those who did not develop RN (75.0% vs 44.4%, p = 0.08). In fact, a significantly higher proportion of those who developed RN received more than one line of HER2-directed therapy during a given SRS treatment compared to those did not develop RN (35.7% vs 5.6%, p<0.05). Conclusions Patients with HER2+ BCBrM who receive multiple lines of HER2-directed therapy during SRS for BCBrM may be at higher risk of RN. Collectively, this data supports a practice of holding HER2-directed therapy during treatment with SRS if medically acceptable.

scholarly journals RADI-18. Survival and disease control after upfront stereotactic radiosurgery for brain metastases from breast cancer

2021 ◽  
Vol 3 (Supplement_3) ◽  
pp. iii21-iii22
Author(s):  
Yan Wang ◽  
Ran An ◽  
Fuchenchu Wang ◽  
Chao Gao ◽  
Akshara Singareeka Raghavendra ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Hormone Therapy ◽  
Stereotactic Radiosurgery ◽  
Systemic Therapy ◽  
Molecular Subtypes ◽  
Treatment Strategies ◽  
Metastatic Breast ◽  
Factors Associated ◽  
Cox Proportional Hazard Regression

Abstract Background As systemic therapy for metastatic breast cancer (BC) improves, the survival benefit from hormonal and targeted therapy urges treatment of brain metastases (BMs) with minimal toxicity and less systemic therapy interruption. Here we assessed clinical outcomes in BC patients who received upfront stereotactic radiosurgery (SRS). Methods We identified 236 patients who received upfront SRS with/without surgery for BMs from metastatic BC from 06/2007 to 05/2018. Twenty-four patients who received SRS for surgical cavity were excluded for analysis. Overall survival (OS) and salvage radiation-free survival (SRFS) were estimated using Kaplan-Meier analysis. Cox proportional hazard regression was used to identify prognostic factors. Results At a median follow-up time of 15.4 months (range, 0.8–119.6), the estimated median OS was 18.5 mo (95% CI, 14.9–21). Factors associated with OS on multivariate analysis (MVA) were molecular subtypes (12.2 months for triple-negative [n=68], 13.3 months for HR+/HER2- [n=66], 36.4 months for HR+/HER2+ [n=46], and 28.1 months for HER2+ [n=32], p=0.002), KPS >80 (p<0.0001), receipt of chemotherapy (p=0.016) or anti-HER2 therapy (p=0.029) after diagnosis of BM, and type of salvage radiation (p<0.0001). OS was comparable in patients who received upfront SRS to less or more than 4 lesions (19.3 months for <4 [n=162] vs. 17.8 months for >/= 4 [n=50], p=0.36). The 12-month salvage RT rate was 25% for WBRT and 26.4% for SRS. The median SRFS was 7.4 months (95% CI, 6.5‒8.3). Factors associated with SRFS on MVA were subtypes (p=0.002), KPS (p=0.011), and receipt of hormone therapy after diagnosis of BM (p=0.031). Conclusions The median OS for BC patients who developed BM is over 15 months. Molecular subtypes (HER2+ and HR+/HER2+), good KPS, and anti-HER2 or hormone therapy predicted better OS and SRFS. Prospective studies are needed to verify these results and refine the best treatment strategies for these patients.

Effect of type and timing of systemic therapy on risk of radiation necrosis in patients with HER2+ breast cancer brain metastases.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14002-e14002
Author(s):  
Christine Park ◽  
Evan Buckley ◽  
Amanda E.D. Van Swearingen ◽  
Will Giles ◽  
James Emmett Herndon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Systemic Therapy ◽  
Radiation Necrosis ◽  
Treatment Modalities ◽  
Conformity Index ◽  
Her2 Breast Cancer ◽  
Breast Cancer Brain Metastasis ◽  
The Impact ◽  
Systemic Therapies

e14002 Background: It is estimated that 30% of patients with metastatic human epidermal growth factor receptor 2-positive (HER2+) breast cancer will develop brain metastases. Current standard of care options for HER2+ breast cancer brain metastasis (BCBrM) includes radiation therapy (stereotactic radiosurgery [SRS] or whole brain radiation), brain permeable systemic therapies, and in select cases, neurosurgical resection. A multimodal approach combining these different treatment modalities has improved the overall survival and functional outcomes of patients with BCBrM. Some HER2-directed systemic therapies, however, may increase the risk of radiation necrosis (RN), a longer-term consequence of SRS. This study explores the impact of timing and type of systemic therapies on the development of RN in patients treated with SRS for HER2+ BCBrM. Methods: This was a single-institution, retrospective study including patients ≥18 years of age with HER2+ BCBrM who received SRS between 2013 and 2018 at Duke University with at least 12-month post-SRS follow-up. Presence of RN was determined at one-year post-SRS. Demographics, radiotherapy parameters (total dose, fractions, clinical target volume [CTV], gross tumor volume [GTV], conformity index [CI], volume receiving 12 gray [V12Gy]), and timing (during [within 4 weeks of SRS] vs. not during SRS) and type of systemic therapy (HER2-directed therapy, mitosis inhibitors, DNA synthesis inhibitors, others) were evaluated. Results: Among 46 patients with HER2+ BCBrM who received SRS, 28 (60.9%) developed RN and 18 (39.1%) did not. Age at time of SRS did not differ between those who developed RN and those who did not (mean 53.3 vs 50.4 years, respectively). There was a higher percentage of African Americans in the RN group (28.6% vs 11.1%, p = 0.3). There were no significant differences between the measured radiotherapy parameters—including dose, fraction, CTV, GTV, CI, V12Gy—between the two groups (all p > 0.05). Receipt of any type of systemic therapy during SRS did not differ between patients who did or did not develop RN (60.7% vs 55.6%, p = 0.97). However, patients who developed RN more commonly received more than one line of HER2-directed therapy independent of SRS timing compared to those who did not develop RN (75.0% vs 44.4%, p = 0.08). In fact, a significantly higher proportion of those who developed RN received more than one line of HER2-directed therapy during SRS compared to those did not develop RN (35.7% vs 5.6%, p<0.05). Conclusions: Patients with HER2 BCBrM who receive multiple lines of HER2-directed therapy during SRS for BCBrM may be at higher risk of RN. This data supports a practice of holding HER2-directed therapy during SRS if medically acceptable. Further investigation of next generation HER2-directed therapies in a larger cohort of patients should be investigated to help guide best practice to minimize RN.

scholarly journals The impact of sequencing PD-1/PD-L1 inhibitors and stereotactic radiosurgery for patients with brain metastasis

2019 ◽  
Vol 21 (8) ◽  
pp. 1060-1068 ◽  
Author(s):  
Rupesh Kotecha ◽  
Joseph M Kim ◽  
Jacob A Miller ◽  
Aditya Juloori ◽  
Samuel T Chao ◽  
...  
Keyword(s):  
Stereotactic Radiosurgery ◽  
Checkpoint Inhibitors ◽  
Combined Modality Therapy ◽  
Objective Response ◽  
Complete Response ◽  
Substantial Effect ◽  
Durable Response ◽  
Best Response ◽  
Programmed Cell Death 1 ◽  
The Impact

Abstract Background The response of brain metastases (BM) treated with stereotactic radiosurgery (SRS) and immune checkpoint inhibitors (ICIs; programmed cell death 1 and its ligand) is of significant interest. Methods Patients were divided into cohorts based on ICI sequencing around SRS. The primary outcome was best objective response (BOR) that was lesion specific. Secondary outcomes included overall objective response (OOR), response durability, radiation necrosis (RN), and overall survival (OS). Results One hundred fifty patients underwent SRS to 1003 BM and received ICI. Five hundred sixty-four lesions (56%) treated with concurrent ICI (±5 half-lives) demonstrated superior BOR, OOR, and response durability compared with lesions treated with SRS and delayed ICI. Responses were best in those treated with immediate (±1 half-life) ICI (BOR: −100 vs −57%, P < 0.001; complete response: 50 vs 32%; 12-month durable response: 94 vs 71%, P < 0.001). Lesions pre-exposed to ICI and treated with SRS had poorer BOR (−45%) compared with ICI naive lesions (−63%, P < 0.001); best response was observed in ICI naive lesions receiving SRS and immediate ICI (−100%, P < 0.001). The 12-month cumulative incidence of RN with immediate ICI was 3.2% (95% CI: 1.3–5.0%). First radiographic follow-up and best intracranial response were significantly associated with longer OS; steroids were associated with inferior response rates and poorer OS (median 10 vs 25 mo, P = 0.002). Conclusions Sequencing of ICI around SRS is associated with overall response, best response, and response durability, with the most substantial effect in ICI naive BM undergoing immediate combined modality therapy. First intracranial response for patients treated with immediate ICI and SRS may be prognostic for OS, whereas steroids are detrimental.

Antibiotic use and outcomes with systemic therapy in metastatic renal cell carcinoma (mRCC).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 607-607 ◽  
Author(s):  
Aly-Khan A. Lalani ◽  
Wanling Xie ◽  
Xun Lin ◽  
John A. Steinharter ◽  
Dylan J. Martini ◽  
...  
Keyword(s):  
Systemic Therapy ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Mtor Inhibitors ◽  
Risk Groups ◽  
Antibiotic Use ◽  
Vegf Inhibitors ◽  
Logistic Regression Models ◽  
The Impact

607 Background: Antibiotic (Abx) use is shown to alter commensal gut microbiota, a key regulator of immune homeostasis. We conducted the largest investigation to date on the impact of Abx use on outcomes in mRCC patients treated with systemic agents. Methods: Two cohorts were analyzed: an institutional cohort (DFCI, n = 146) of patients receiving PD-1/PD-L1-based immune checkpoint inhibitors (ICI), and an external cohort from pooled phase II/III clinical trials (Pfizer, n = 4144) of patients treated with interferon (IFN, n = 510), mTOR inhibitors (n = 660), and VEGF inhibitors (n = 2974). Abx use was defined as Abx treatment at any time between 8-weeks pre- and 4-weeks post the start of systemic therapy. We examined the associations of Abx use and objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) using Cox/logistic regression models, adjusted for prognostic factors including risk groups. Results: In the DFCI cohort, 15% had non-clear cell histology, 43% had first-line ICI, 45% had combotherapy. Baseline characteristics were balanced between Abx users (n = 31, 21%) and non-users (p > 0.15). Abx users had a lower ORR (12.9 vs 34.8%, p = 0.026) and shorter PFS compared to non-users (Table). In the external cohort, Abx users (n = 709) had lower ORR (19.3 vs 24.2%, p = 0.005). IFN treated patients (current or prior cytokines) had worse OS if they received Abx compared to those who did not. However, there was no OS difference by Abx use in mTOR or VEGF treated patients without prior cytokines. Conclusions: Abx use was independently associated with worse outcomes in mRCC patients receiving contemporary ICI or historic cytokine immunotherapy. We hypothesize that concurrent use of Abx may reduce the efficacy of ICI due to a complex interplay with the host microbiome. [Table: see text]

scholarly journals Novel immunotherapy approaches to follicular lymphoma

Hematology ◽  
2018 ◽  
Vol 2018 (1) ◽  
pp. 194-199 ◽  
Author(s):  
Christopher R. Flowers ◽  
John P. Leonard ◽  
Loretta J. Nastoupil
Keyword(s):  
Follicular Lymphoma ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Antibody Therapy ◽  
Treatment Strategies ◽  
Careful Consideration ◽  
Optimal Timing ◽  
Phosphatidylinositol 3 Kinase ◽  
Anti Cd20

AbstractFollicular lymphoma (FL) remains a lymphoma subtype that is remarkably sensitive to immunotherapy-based treatment strategies. Anti-CD20 antibody therapy administered as a single agent and in combination as a first-line treatment and at relapse continues to be the most broadly used therapy for this disease. Autologous and allogeneic stem cell transplantation provide meaningful durable remissions for patients with FL. However, identifying the most suitable patients and the optimal timing for these approaches has become increasingly challenging with the advent of novel therapies. Lenalidomide and phosphatidylinositol 3-kinase inhibitors are emerging as agents that can be applied in the relapsed setting. Other immunotherapy approaches, including checkpoint inhibitors and chimeric antigen receptor T cells, appear promising but remain experimental. Utilization of all forms of immunotherapy requires careful consideration of the unique toxicities associated with these agents and the means to mitigate them by selection of appropriate patients, optimal timing, and the use of supportive care.

scholarly journals CMET-31. WHOLE BRAIN RADIOTHERAPY VERSUS STEREOTACTIC RADIOSURGERY IN POOR-PROGNOSIS PATIENTS WITH 1 – 10 BRAIN METASTASES: A RANDOMIZED FEASIBILITY STUDY

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi58-vi58
Author(s):  
Alan Nichol ◽  
Srinivas Raman ◽  
Benjamin Mou ◽  
Fred Hsu ◽  
Boris Valev ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Median Survival ◽  
Feasibility Study ◽  
Systemic Therapy ◽  
Poor Prognosis ◽  
Whole Brain Radiotherapy ◽  
Whole Brain ◽  
Brain Radiotherapy ◽  
Patients With Poor Prognosis

Abstract BACKGROUND The clinical advantage of stereotactic radiosurgery (SRS) over whole brain radiotherapy (WBRT) in patients with brain metastases and poor prognosis is controversial. To investigate the feasibility of a phase III clinical trial in a population of patients with poor prognosis, we conducted a randomized feasibility study of WBRT versus SRS. METHODS Patients with Karnofsky performance status (KPS) ≥ 70, life expectancy of 3–6 months, based on both Diagnosis-Specific Graded Prognostic Assessments and attending oncologist opinion, and 1– 10 brain metastases with a diameter ≤ 4 cm were enrolled at six Canadian cancer centers. Patients were randomly assigned to WBRT (20 Gy in 5 fractions) or SRS (15 Gy in 1 fraction). The primary endpoint was the rate of accrual. A secondary endpoint was the ratio of screened subjects to accrued subjects. This trial is registered with ClinicalTrials.gov (NCT02220491). RESULTS Between January 2015 and November 2017, 210 were screened to enroll 22 patients (9.5 screened/participant) and 20 patients were randomized. The accrual rate was 0.63 patients / month. The most common reasons for exclusion were: estimated median survival outside 3–6 months (n = 40), baseline KPS below 70 (n = 28), and > 10 brain metastases (n = 28). The median survival was 7.0 months. The overall survival was 9.5 months (n = 11) for patients who had subsequent systemic therapy, compared to 3.7 months (n = 9) in patients who had none. In both arms, the cumulative incidence of retreatment with brain radiotherapy was 40%. CONCLUSIONS Accrual was slow and the median survival was longer than expected, but a randomized trial evaluating WBRT vs SRS in patients with poor prognosis would likely be feasible by enrolling only patients with no remaining systemic therapy options.

scholarly journals CMET-36. IMMUNOTHERAPY VERSUS STANDARD OF CARE IN MELANOMA BRAIN METASTASES WITH KNOWN BRAF STATUS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi59-vi59
Author(s):  
Addison Barnett ◽  
Soumya Sagar ◽  
Adam Lauko ◽  
Wei (Auston) Wei ◽  
Samuel Chao ◽  
...  
Keyword(s):  
Median Survival ◽  
Systemic Therapy ◽  
Checkpoint Inhibitors ◽  
Tertiary Care ◽  
Local Therapy ◽  
Rank Test ◽  
Wild Type ◽  
Melanoma Patients ◽  
The Impact ◽  
Braf Mutant

Abstract INTRO/OBJECTIVE A mutation of the BRAF protein is seen in approximately 50% of melanoma patients. Immune checkpoint inhibitors (ICI) are standard therapy in melanoma patients independent of a patient’s BRAF status. The primary objective of this study is to investigate the impact of BRAF status in patients treated with ICI compared to non-ICI systemic therapy on overall survival (OS) in patients with melanoma brain metastasis (MBM). METHODS We reviewed 351 patients with MBM treated at our tertiary care center between 2000 and 2018. Of these, 144 had known BRAF status, 71 of which were BRAF mutant and 73 were BRAF wild-type. OS was calculated from the date of diagnosis of MBM to compare the efficacy of ICI to other systemic therapies. Many of these patients received multiple lines of treatment including targeted therapies at some point during their care. The log-rank test and Cox proportional hazard model was utilized to determine differences in OS. RESULTS Eighty-four percent of patients received local therapy that included either surgery, stereotactic radiosurgery, or whole brain radiation therapy. In BRAF wild-type patients, 40 received ICI and 33 underwent non-ICI systemic therapy with a median survival (5.6 vs 7.1 months) and 2-year survival (28% vs 32%), respectively (p=0.64). Of the BRAF mutant patients, 33 received ICI and 38 did not with a median survival (17.1 vs 9.0 months) and 2-year survival (36% and 19%), respectively (p=0.014). When controlling for age, KPS, ECM, and number of lesions, BRAF mutant MBM patients treated with ICI compared to non-ICI had an OS hazard ratio, HR=0.4 (95% CI=0.21 – 0.78, p=0.0069). CONCLUSION ICI therapy in BRAF mutant MBM patients results in improved OS compared to those with non-ICI systemic therapy. No such difference was observed in the BRAF wild-type cohort.

scholarly journals Research on Anal Squamous Cell Carcinoma: Systemic Therapy Strategies for Anal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2180
Author(s):  
Ryan M. Carr ◽  
Zhaohui Jin ◽  
Joleen Hubbard
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Systemic Therapy ◽  
Checkpoint Inhibitors ◽  
Treatment Strategies ◽  
Standard Of Care ◽  
Treatment Modalities ◽  
Permanent Colostomy ◽  
Anal Squamous Cell Carcinoma

Anal squamous cell carcinoma (ASCC) is a rare malignancy, with most cases associated with human papilloma virus and an increased incidence in immunocompromised patients. Progress in management of ASCC has been limited not only due to its rarity, but also the associated lack of research funding and social stigma. Historically, standard of care for invasive ASCC has been highly morbid surgical resection, requiring a permanent colostomy. Surgery was associated with disease recurrence in approximately half of the patients. However, the use of chemotherapy (5-fluorouracil and mitomycin C) concomitantly with radiation in the 1970s resulted in disease regression, curing a subset of patients and sparing them from morbid surgery. Validation of the use of systemic therapy in prospective trials was not achieved until approximately 20 years later. In this review, advancements and shortcomings in the use of systemic therapy in the management of ASCC will be discussed. Not only will standard-of-care systemic therapies for locoregional and metastatic disease be reviewed, but the evolving role of novel treatment strategies such as immune checkpoint inhibitors, HPV-based vaccines, and molecularly targeted therapies will also be covered. While advances in ASCC treatment have remained largely incremental, with increased biological insight, an increasing number of promising systemic treatment modalities are being explored.

scholarly journals EXTH-12. RADIATION ENHANCES MELANOMA RESPONSE TO IMMUNOTHERAPY AND SYNERGIZES WITH BENZODIAZEPINES TO PROMOTE ANTI-TUMOR ACTIVITY

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi84-vi84
Author(s):  
Daniel Pomeranz Krummel ◽  
Tahseen Nasti ◽  
Benjamin Izar ◽  
Maxwell Xu ◽  
Lindsey Lowder ◽  
...  
Keyword(s):  
Gabaa Receptors ◽  
Checkpoint Inhibitors ◽  
Rna Seq ◽  
Treatment Groups ◽  
Combination Strategies ◽  
Melanoma Model ◽  
Melanoma Patients ◽  
The Impact ◽  
Anti Tumor Activity ◽  
Systemic Therapies

Abstract Melanoma brain metastases (MBM) occur in ~50% of advanced melanoma patients. It is unclear if systemic therapies synergize with radiotherapy (RT) and what the impact of RT timing has on efficacy. We find that RT followed by ICI (immune checkpoint inhibitors) (RTàICI) improves MBM patient survival compared to other combination strategies, also shown here in a murine melanoma model. RNA-seq of MBM tumors in the RTàICI group exhibit overrepresentation of genes implicated in NFKB signaling. There is also expression of GABAA receptor subunits across both treatment groups. We show that melanoma cells express functional GABAA receptors and that benzodiazepines impair tumor growth. Combination of sub-lethal RT doses with benzodiazepine results in significant ipsilateral and out of field abscopal anti-tumor activity, which is associated with enhanced tumor infiltration with poly-functional CD8 T-cells. This study provides evidence that RT enhances MBM response to ICI and synergizes with benzodiazepines to promote anti-tumor activity.

Sign in / Sign up

Export Citation Format

Share Document