ESTRO 2020 Abstract book

S694 ESTRO 2020

When combined with ipi at 10 mg/kg, the MTD of RT was 9 Gy. This combination of ipi + RT appeared to be associated with antitumor activity. Ipi + RT could increase CD4+ and CD8+ ICOS+ T cells. Increased CD8+ was significantly associated to PFS. Thus, immune biomarkers may be useful for early response evaluation. ΔTGR non-irr lesions could be more important than for irradiated lesion in responding pts and may be related to abscopal effect. PO-1228 Stereotactic radiosurgery with concurrent immunotherapy in malignant melanoma brain metastases J. Liermann 1 , M. Syed 1 , U. Neuberger 2 , D. Reuss 3 , R. El Shafie 1 , W. Julia 4 , J. Debus 1 , J. Hassel 4 , S. Rieken 5 1 Heidelberg University Hospital, Department of Radiation Oncology, Heidelberg, Germany ; 2 Heidelberg University Hospital, Department of Neuroradiology, Heidelberg, Germany ; 3 Heidelberg University Hospital, Institue of Pathology, Heidelberg, Germany ; 4 Heidelberg University Hospital, Department of Dermatology, Heidelberg, Germany ; 5 Goettingen University Hospital, Department of Radiation Oncology, Goettingen, Germany Purpose or Objective Stereotactic radiosurgery (SRS) is an established treatment for brain metastases in the management of malignant melanoma. The increasing use of checkpoint inhibitors in melanoma therapy leads to combined treatment schemes consisting of immunotherapy and SRS that need to be evaluated regarding safety and feasibility. Material and Methods We retrospectively analysed 36 patients suffering from malignant melanoma with brain metastases. Between November 2011 and May 2016, a total of 66 brain metastases were treated with single-fraction SRS (22.5-25 Gy prescribed to the 80% isodose) in combination with a checkpoint inhibitor (Ipilimumab: 82%, Pembrolizumab: 14% or Nivolumab: 4%), applied within 3 months before or after SRS. Toxicity was evaluated with focus on the incidence of radiation-induced cerebral necrosis. Overall survival (OS) and intracranial Progression free survival (PFS) were analysed using the Kaplan-Meier method. Results The median follow-up was 24.9 months (range: 1.9-115.5 months). SRS was well tolerated. No clear SRS-induced CTCAE °III or °IV toxicity could be seen. Severe neurological symptoms (seizures, aphasia or neurocognitive deficiency) were either due to tumor progression or a result of additional whole brain radiotherapy before (11%) or after (22%) SRS. During follow-up, seven of the growing contrast-enhanced lesions were resected, revealing three cases of radiation-induced necrosis and four cases of local tumor progression. Altogether, the observed radiation necrosis rate of the irradiated metastases was 6-18% (the range is due to the radiologically challenging differentiation between radiation necrosis and tumor progression). Median OS was 22.2 months. Intracranial median PFS was 5.8 months. Conclusion In the presented cohort, the combination of SRS and checkpoint inhibitors in the management of malignant melanoma brain metastases was safe and effective. To gain resilient data, prospective trials are needed.

France ; 2 Gustave Roussy Cancer Campus, Laboratory Of Immunomonitoring In Oncology- University Paris-saclay- Faculty Of Pharmacy, Villejuif, France ; 3 Gustave Roussy Cancer Campus, Biostatistic And Epidemiology Unit, Villejuif, France ; 4 Gustave Roussy Cancer Campus, Dermatology Unit- Department Of Medicine, Villejuif, France ; 5 Gustave Roussy Cancer Campus, Department Of Radiation Oncology, Villejuif, France ; 6 Gustave Roussy Cancer Campus- Fondazione IRCCS Policlinico San Matteo, Department Of Radiation Oncology, Villejuif, France ; 7 Gustave Roussy Cancer Campus, Outpatient Clinic- Department Of Medicine, Villejuif, France ; 8 Gustave Roussy Cancer Campus, Ditep, Villejuif, France ; 9 Gustave Roussy Cancer Campus, Department Of Radiology, Villejuif, France ; 10 Gustave Roussy Cancer Campus, Laboratory Of Immunomonitoring In Oncology, Villejuif, France ; 11 Medimmune, Medimmune, Gaithersburg, France ; 12 Gustave Roussy Cancer Campus, Dermatology Unit- University Paris-saclay- Faculty Of Medicine- Inserm Unit U981, Villejuif, France ; 13 Gustave Roussy Cancer Campus, Department Of Radiation Oncology- Radiomics Team- Molecular Radiotherapy Inserm U1030- University Paris-saclay- Faculty Of Medicine, Villejuif, France Purpose or Objective A synergy between radiotherapy (RT) and anti-CTLA-4 antibody has been demonstrated preclinically. The Mel-Ipi- Rx phase 1 study aimed to: i) determine the maximum tolerated dose (MTD) and safety profile of RT combined with ipilimumab (ipi) in patients (pts) with metastatic melanoma, and ii) assess the impact of ipi + RT systemic immune antitumor response (SIAR) and tumor growth rate (TGR) variation (ΔTGR) of irradiated (TGR irr ) and non- irradiated (TGR non-irr ) lesions. Material and Methods A 3+3 dose escalation design was used with 9, 15, 18 and 24 Gy dose of RT at week 4 combined with 10 mg/kg ipi every 3 weeks for 4 doses. The adverse events (AEs) were graded according to the National Cancer Institute Common Terminology Criteria for AEs, version 4.0. Blood samples were collected at baseline, W4 (before 2nd ipi injection) and W6 (after ipi + RT) to phenotype T cells. TGR, defined as an increase in tumor volume during 1 month, was computed for TGR irr , and TGR non-irr in 2 periods: (i) Reference-TGR (REF-TGR) on baseline, and (ii) Experimental-TGR (EXP-TGR) between baseline and 1st evaluation. The ΔTGR between REF-TGR and EXP-TGR was used to assess the treatment effect. A negative value reflected a slowdown of disease progression. Results 19 pts received ipi between August 2011 and July 2015. Nine pts received the 4 doses of ipi. All pts received the combined RT. Grade 3 AEs occurred in 8 pts, the most common being colitis and hepatitis. No drug-related death occurred. DLT occurred in 2/6 pts in the cohort receiving 15 Gy. The MTD was 9 Gy dose. Two pts had complete response, 3 had partial response and 7 had stable disease, giving an objective response rate of 37%. Ipi alone could increase effector T cells (TEM), Treg and ICOS+ CD4+ T cells at W4. At W6, only TEM and ICOS+ CD4+ T cells significantly increased suggesting that combination could increase activated memory CD4+ T cells rather than Treg cells. CD8+ T cells did not increase at W4 while central memory T cells (TCM) and terminally differentiated (TEMRA) increased between W4 and W6, suggesting that RT + ipi could boost these CD8 + T populations. Increased CD8 from baseline to W4 was significantly correlated to progession-free survival (PFS) (p=0.0163). Interestingly, a higher effect of ipi+ RT seemed to be associated with a deeper ΔTGR non-irr than ΔTGR irr , although insignificant. The EXP-TGR non-irr was significantly associated with progressive disease. Conclusion

Poster: Clinical track: Sarcoma

PO-1229 Preliminary data on long term toxicity in young patients with chordoma: C.N.A.O. experience E. Scipilliti 1 , M.R. Fiore 2 , F. Cuccia 3 , S. Durante 4 , S. Ronchi 2 , M. Bonora 2 , A. Barcellini 2 , F. Valvo 2 1 University of Naples "Federico II", Department of Advanced Biomedical Science, Napoli, Italy ; 2 National Center of Oncological Hadrontherapy CNAO,