Chemotherapy-immunotherapy-based Split-course Adaptive Hypofractionated Radiotherapy for Extensive-stage SCLC

Inclusion Criteria:

1. Any pathologic confirmation of ES-SCLC at any site, either primary or metastases.
2. Patients must have measurable disease and 3 or fewer observable liver metastases.
3. If there is a pleural effusion, patients will be eligible if thoracentesis is cytologically negative or if pleural fluid is too small a volume to effectively sample by thoracentesis and does not show increased metabolic activity on CT/PET imaging
4. Age greater than or equal to 18 years.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
6. Adequate normal organ and bone marrow function
7. The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
8. Life expectancy greater than six (6) months
9. If the autoimmune disease is not active for over 3 years and the patient is not receiving immunosuppressive treatment such as methotrexate or steroids above a dose equivalent to 10 mg prednisone daily, the patient is eligible.
10. Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone are eligible.
11. Patients with controlled type 1 diabetes mellitus on a stable insulin regimen are eligible.
12. Patients with eczema, psoriasis, lichen simplex chronicus or vitiligo with dermatologic manifestations are excluded only if they have active disease with acute exacerbation and on immunosuppressive medications within the 12 months prior to enrollment. They are eligible otherwise.
13. Severe, active co-morbidity defined as follows: Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of radiation, chemotherapy and ICIs or that may affect the interpretation of the results or render the patient at high risk from treatment complications;
14. Active tuberculosis;
15. Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease.
16. Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen \[HBsAg\] test and a positive anti-HBc \[antibody to hepatitis B core antigen\] antibody test) are eligible.

Exclusion Criteria:

1. Metastatic disease invading the liver (\> 3 metastases)
2. Patients with malignant pleural and/or pericardial effusions
3. Prior radiotherapy in the thorax that would result in overlapping RT fields
4. Active autoimmune disease, including, but not limited to: systemic lupus erythematosus; rheumatoid arthritis; inflammatory bowel disease (e.g. Crohn's, ulcerative colitis); vascular thrombosis associated with antiphospholipid syndrome; Wegener's granulomatosis; Sjogren's syndrome; Guillain-Barre syndrome; multiple sclerosis; vasculitis; or glomerulonephritis.
5. Known immunosuppressive disease, for example history of bone marrow transplant or chronic lymphocytic leukemia (CLL);
6. Chronic obstructive pulmonary disease (COPD) requiring chronic oral steroid therapy of \> 10 mg prednisone daily or equivalent at the time of registration. Inhaled corticosteroids are not exclusionary;
7. Unstable angina and/or congestive heart failure requiring hospitalization within the last 3 months;
8. History of recent myocardial infarction within 6 months prior to registration.
9. Clinically significant interstitial lung disease;
10. History of allogeneic organ transplant;
11. Patients positive for human immunodeficiency virus (HIV) on effective anti-retroviral therapy with undetectable viral load within 6 months and a stable regimen of highly active anti-retroviral (HAART) HIV-positive patients must have no requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections.