Online

ESTRO 2020

Session Item

Poster highlights 9 CL: Lung
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Poster Highlights
Clinical
09:33 - 09:41
Phase 2 Study of Novel Partial Tumor Irradiation for Sparing Peri-Tumoral Immune Microenvironment.
Slavisa Tubin, Austria
PH-0282

Abstract

Phase 2 Study of Novel Partial Tumor Irradiation for Sparing Peri-Tumoral Immune Microenvironment.
Authors: Branislav Jeremic.(Research Institute of Clinical Medicine- Tbilisi- Georgia- and BioIRC- R&D Center for Biomedical Research- Kragujevac- Serbia, Department of Radiation Oncology, Tbilisi, Georgia), Mohammad K. Khan.(Emory University School of Medicine- Winship Cancer Institute, Department of Radiation Oncology, Atlanta- GE, USA), Waleed F. Mourad.(Markey Cancer Center- University of Kentucky Lexington ky, Department of Radiation Medicine, Lexington KY, USA), Gerardo Salerno.(Universita´ La Sapienza Roma- Ospedale Sant´ Andrea, Department of Neurosciences- Mental Health and Sensory Organs / Department of Clinical and Molecular Medicine, Rome- RM, Italy), Slavisa Tubin.(Landeskrankenhaus Klagenfurt, Strahlentherapie und Radioonkologie, Klagenfurt, Austria), Weisi Yan.(Thomas Jefferson University- Philadelphia, Department of Radiation Oncology, Philadelphia- PA, USA)
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Purpose or Objective

Patients with unresectable bulky NSCLC continue to be a therapeutic dilemma because the radical conventional radiotherapy (RT) techniques including SBRT are technically difficult to apply to such a large lesions due to the limited surrounding normal tissue tolerance.
The immunomodulatory effects of RT have been questioned by many scientists in the era of immunotherapy (IT), with a renewed focus on the immune-mediated abscopal effects (AE) as well as on the depletion of lymphocytes. RT-induced lymphopenia may be limiting the success of therapy and could also negatively affect the ability of immune system in mediating the bystander effect (BE) and AE. A novel SBRT-based PArtial Tumor irradiation of HYpoxic clonogenic cells (SBRT-PATHY) for induction of the tumoricidal BE and AE by sparing the peritumoral immune microenvironment and regional circulating lymphocytes has been developed at our institute to enhance RT therapeutic ratio of unresectable bulky NSCLC. The aim of this retrospective review of prospectively collected mono-institutional phase 2 study was to compare the outcomes between unconventional SBRT-PATHY and standard of care in unresectable bulky NSCLC.

Material and Methods

60 patients with stage IIIB/IV bulky NSCLC considered inoperable or unsuitable for radical radio-chemotherapy were treated at our cancer center with: SBRT-PATHY to the bulky NSCLC (group I, n=20 patients), recommended standard of care CHT (group II, n=20 patients), and conventional palliative 3Gy x 10 RT to the bulky NSCLC (group III, n=20 patients). For the purpose of SBRT-PATHY planning each bulky tumor was divided into 4 segments using a combination of contrast-enhanced CT and FDG-PET: 1) peripheral hypervascularized-hypermetabolic („normoxic“) bulky segment, 2) central necrotic („anoxic”) tumor region, 3) hypovascularized-hypometabolic (SUVmax<3, „hypoxic“) segment, 4) peri-tumoral immune microenvironment created by adding a uniform 1 cm margin around the GTV. SBRT-PATHY dose of 10-12Gy x 1-3 (based on bulky site and volume) was delivered to hypoxic segment 3 considering the following dose constraints for segment 4: Dmin<1Gy/fraction, Dmax<5Gy/fraction, Dmean<3Gy/fraction.

Results

Median follow-up was 13 months. SBRT-PATHY showed improved treatment outcomes in terms of survival, tumor and symptom control, and toxicity compared to standard of care. Table 1 and Figure 1, respectively summarize the main clinical results. Multi-variate analysis for cancer specific survival was significant for treatment effect with SBRT-PATHY (p < 0.001) independent of age, sex, performance status, histology, stage, treated bulky site and tumor diameter.

Conclusion

We present a novel concept of SBRT-PATHY to treat unresectable bulky NSCLC patients which showed improved RT therapeutic ratio compared to standard of care in this phase 2 study with 60 patients. A larger prospective trial is ongoing to provide additional hope and promise for bulky, unresectable NSCLC patients, especially in the context of emerging IT combinations.