Adediran, Samuel, MD

Nair, Suresh G., MD

Naziri, Jason, BS

English

Lehigh Valley Health Network: LVHN Scholarly Works

Lehigh Valley Health NetworkLVHN Scholarly WorksUSF-LVHN SELECTMetastatic Cancers Treated with Concurrent PD-1Inhibition and Stereotactic Ablative Radiotherapy(SABR)Jason Naziri BSSamuel Adediran MDLehigh Valley Health Network, Samuel.Adediran@lvhn.orgSuresh G. Nair MDLehigh Valley Health Network, suresh.nair@lvhn.orgFollow this and additional works at: https://scholarlyworks.lvhn.org/select-programPart of the Medical Education CommonsThis Poster is brought to you for free and open access by LVHN Scholarly Works. It has been accepted for inclusion in LVHN Scholarly Works by anauthorized administrator. For more information, please contact LibraryServices@lvhn.org.Published In/Presented AtNaziri, J. Adediran, S. Nair, S. (2018, March). Metastatic Cancers Treated with Concurrent PD-1 Inhibition and Stereotactic AblativeRadiotherapy (SABR). Poster Presented at: 2018 SELECT Capstone Posters and Presentations Day. Kasych Family Pavilon, LehighValley Health Network, Allentown, PA.© 2018 Lehigh Valley Health NetworkLehigh Valley Health Network, Allentown, Pennsylvania• In the setting of oligometastatic disease for solid malignancies including renal cell carcinoma, melanoma, and NSCLC, SABR and PD-1 inhibitor concurrent therapy may offer improved outcomes without significant additional toxicity. Given the poor outcomes of these patients, randomized clinical studies are needed to clarify and better define the most appropriate combination of RT with check point inhibitorsMetastatic Cancers Treated with Concurrent PD-1 Inhibitionand Stereotactic Ablative Radiotherapy (SABR)References• We identified 12 patients who have received concurrent therapy with SABR and PD-1 inhibitors• All patients had metastatic disease of various sites and refractory to at least a first line chemotherapeutic agent. No patients were lost to follow up. Of the 12 patients, three (25%) were treated with concurrent therapy twice. Of the 15 total PD-1 inhibitor treatments, 10 (67%) were with nivolumab while 5 with pembrolizumab (33%)• Median time from initial cancer diagnosis was 21 months (range: 11-38 months) with a median follow-up of 14 months (range: 6-19 months). The median treatment dose and fractions were 40.5 Gy (range 24-54 Gy) and 5 fr (range 3-9) respectively• Four lesions (27%) were noted to undergo local progression at time of analysis. In these patients, local progression was noted a median of 3.5 months following radiation (range 1-8 months)• A total of five patients had died at the time of study analysis (42%). Median OS for all patients from the date of primary cancer diagnosis was 72 months• In this novel analysis of solid tumor oligometastases treated with SABR concurrently with anti-PD-1 therapy, we found no increased toxicity with combination therapy• Studies using mouse models in the preclinical setting have provided strong evidence to support combination treatments in patients with multiple solid tumors• This potential immunogenic effect of ablative radiation doses may potentially a path to improve overall survival and progression free survival in future cancer therapies. Given our remarkable OS with such dismal malignancies, we find that treatment in the concurrent setting has the potential to upregulate the tumor specific antigenic exposure and improve both local control and potentially distal control• Multiple other recent clinical studies have confirmed improved OS with the use of PD-1 therapy and radiation. Nevertheless, the optimal sequence and dosage of both SABR as well as PD-1 inhibitors has yet to be established. Given our findings as well as the promising data of other cohorts, further prospective analyses should be pursued• This was an IRB approved retrospective cohort study of patients with solid tumor metastases• We gathered tumor registry data of patients who received concurrent SABR and anti-PD-1 between January 1 2015 and December 31 2016• Local progression was assessed using response evaluation criteria in solid tumors (RECIST) and categorized as partial, stable, or progressive• Overall survival was also calculated using the Kaplan–Meier method, with the log-rank test, Tarone-Ware, and Breslow used to test differences between groups. Cox proportional hazard model analyses were also carried outJason Naziri BS, Samuel Adediran MD, Suresh Nair MDIntroductionMethodsResultsDiscussionConclusionsAvailable upon request• Metastatic solid tumor disease portends poor outcomes and is often refractory to first line therapy. Immune therapy has become a viable alternative• In recent years, check point inhibitors have become a paradigm shifting modality of treatment in malignancy trailblazing a new class of cancer treatment. Ablative radiotherapy has been shown to increase response rates by virtue of creating a more penetrative tumor microenvironment thus exposing certain malignant-specific antigens and further recruitment of immune responsive cells• Novel evidence has shown the synergistic effect of checkpoint inhibitors and ablative radiotherapy. Our institution has been treating patients with concurrent SABR and PD-1 therapy for multiple solid tumor malignancies including renal, melanomatous, and lung cancersVariable n %No. of Patients 12  No. of PD-1 Treatments 15  Type of PD-1 Inhibitor    Pembrolizumab       5  33%Nivolumab     10  67%Age (years)  Median 65.5  Range 44-83  Gender    Male 7 58.0%Female 5 42.0%Primary Tumor Resected  Y 6 50.0%N 6 50.0%Alive    Y 7 58.0%N 5 42.0%Enrolled on clinical trial  Y 5 42%N 7 58%Figure 3 Overall Survival from Initial Cancer DiagnosisFigure 2 Local Control Following 15 SABR SessionsVariable n %FU from RadioembolizationMedian (months) 14  Range (months) 6-19  Time from Primary Diagnosis to RadioembolizationMedian (months) 21  Range (months) 11-38  Treatment Dose (Gy)Median 40.5  Range 24-54  Number of FractionsMedian 5  Range 3-9  Treated SiteSegmental 7Lobar 19• The purpose of this study is to assess the toxicities and health outcomes in all patients concurrently treated with SABR and anti-PD-1 therapy for solid tumorsProblem StatementTable 1 Patient CharacteristicsFigure 1 Immunogenic Cell Death Stress Induced by Radiation Leads to Antigen Exposure to the Adaptive Immune SystemTable 2 Lesion Characteristics

Metastatic Cancers Treated with Concurrent PD-1 Inhibition and Stereotactic Ablative Radiotherapy (SABR)

https://scholarlyworks.lvhn.org/cgi/viewcontent.cgi?article=1235&context=select-program

Metastatic Cancers Treated with Concurrent PD-1 Inhibition and Stereotactic Ablative Radiotherapy (SABR)

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