What is the current approach to radiation therapy for small cell lung cancer (SCLC) in 2025?

Radiation Therapy for Small Cell Lung Cancer: 2025 Update

Limited-Stage SCLC

For limited-stage SCLC, deliver early concurrent chemoradiotherapy starting with cycle 1 or 2 of platinum-etoposide chemotherapy, using either 45 Gy in 1.5 Gy twice-daily fractions over 3 weeks (preferred for survival benefit) or 60-70 Gy once-daily if twice-daily is not feasible. 1, 2

Timing and Concurrent Delivery

• Early concurrent radiotherapy (starting with cycle 1-2 of chemotherapy) significantly improves overall survival compared to late or sequential approaches 1
• Meta-analyses demonstrate that early concurrent thoracic radiation with platinum-based chemotherapy increases both 2-year and 5-year overall survival 1
• Sequential radiotherapy is inferior and should be avoided when concurrent therapy is feasible 1

Dose and Fractionation

• Twice-daily radiotherapy (45 Gy in 1.5 Gy fractions BID over 3 weeks) provides superior survival compared to once-daily regimens (median survival 23 vs 19 months, P=0.04; 5-year survival 26% vs lower rates) 1
• The survival advantage of twice-daily fractionation comes at the cost of higher grade 3/4 esophagitis 1
• Once-daily radiotherapy to 60-70 Gy is an acceptable alternative when twice-daily treatment is not feasible due to logistics or toxicity concerns 2

Consolidation Immunotherapy

• Following chemoradiotherapy, consolidation durvalumab immunotherapy has recently demonstrated improved outcomes, with median survival reaching up to 55.9 months in limited-stage disease 3
• This represents a major advance in the 2025 treatment paradigm 3

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Extensive-Stage SCLC

For extensive-stage SCLC patients achieving very good partial response or better to platinum-etoposide chemotherapy, deliver consolidative thoracic radiotherapy to 30 Gy in 10 fractions (once-daily) targeting post-chemotherapy residual disease volumes. 2

Patient Selection

• Consolidative thoracic RT is recommended specifically for patients with extensive-stage disease who achieved excellent response (very good partial response or better) to first-line chemotherapy 2
• This approach has gained increasing recognition as standard practice for responding patients 4

Dose and Target Volume

• The European Society for Medical Oncology recommends 30 Gy in 10 fractions once-daily 2
• Target post-chemotherapy volumes (residual disease), NOT pre-chemotherapy volumes 2
• Include residual hilar nodes, any sites of initial involvement not completely resolved, and post-chemotherapy mediastinal N2 nodal regions if there was significant initial involvement 2
• Treating post-chemotherapy volumes is appropriate because patients have already received 6 cycles of systemic therapy with excellent response; pre-chemotherapy volumes would unnecessarily increase toxicity without proven benefit 2

Timing

• Deliver consolidative thoracic RT after completion of chemotherapy and confirmation of response, typically within 4-6 weeks of completing systemic therapy 2

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Prophylactic Cranial Irradiation (PCI)

Offer PCI to all patients with limited-stage or extensive-stage SCLC who achieve significant radiological response to initial therapy. 5

Rationale and Benefits

• PCI reduces brain metastases in responding patients 5
• For extensive-stage SCLC with very good partial response, the European Society for Medical Oncology strongly recommends PCI as it reduces brain metastases and improves survival 2
• PCI does not significantly improve overall survival but does reduce CNS recurrences with minimal long-term sequelae 6

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Key Distinctions Between Limited and Extensive Stage

• Limited-stage requires higher-dose concurrent chemoradiotherapy (45 Gy BID or 60-70 Gy once-daily) delivered early with chemotherapy 1, 2
• Extensive-stage receives lower-dose consolidative (sequential) thoracic RT (30 Gy in 10 fractions) after chemotherapy completion, only in responding patients 2
• The fundamental difference is concurrent high-dose RT for limited disease versus sequential moderate-dose RT for responding extensive disease 2

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Common Pitfalls to Avoid

• Do not delay radiotherapy in limited-stage disease - early concurrent therapy (cycle 1-2) is critical for survival benefit 1
• Do not use sequential therapy when concurrent is feasible in limited-stage disease 1
• Do not treat pre-chemotherapy volumes in extensive-stage disease - this increases toxicity without benefit 2
• Do not omit consolidative thoracic RT in extensive-stage patients with excellent response - this is now standard practice 2, 4
• Do not give myeloid growth factors concurrently with thoracic radiotherapy 7