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Small-Cell Lung Cancer

How do I treat patients presenting with limited-stage small cell lung cancer (LS-SCLC)?

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Key concept

Chemotherapy is an integral component of the treatment of patients with LS-SCLC, because of the high likelihood of early dissemination. Radiation therapy is also important, because treatment with chemotherapy alone in LS-SCLC can be associated with a high risk of local progression. Surgery plays a role only in T1-2N0M0 disease.

Clinical scenario

A 52-year-old man with a history of heavy smoking presents for worsening shortness of breath. CT of the chest revealed large mediastinal and right hilar lymph nodes. Endobronchial ultrasound is positive for small-cell lung cancer. An MRI of the brain is normal, and PET/CT scan shows a fluorodeoxyglucose (FDG)-avid, large mediastinal mass and bilateral hilar lymph nodes but no distant metastasis. What will be the next step in the management of this patient?

Action items
  • The backbone of LS-SCLC treatment consists of concurrent chemotherapy and radiation therapy followed by prophylactic cranial irradiation if the patient has a good response

  • Patients with T1-2N0M0 disease might benefit from surgery followed by adjuvant treatment (chemotherapy with or without radiation for nodal disease)

  • Thoracic radiation therapy must be administered with the first or second cycle of chemotherapy

  • Standard dose of radiation therapy is 45 Gy (1.5 Gy twice daily for 3 weeks)

  • Alternative radiation therapy dose is 60–70 Gy (2 Gy daily for 6 weeks)

  • Chemotherapy consists of 4–6 cycles of platinum doublet (ie, cisplatin and etoposide or cisplatin and irinotecan). Cisplatin is the preferred platinum agent to be used during radiation therapy

Discussion

A meta-analysis has shown that chest radiation therapy, when added to chemotherapy, improves the survival in LS-SCLC, with a 3-year overall survival (OS) rate of 14.3% for the bimodality approach vs. 8.9% for chemotherapy only.1 Another important randomized controlled study has proved that concurrent chemoradiation is superior to sequential chemotherapy–radiation therapy in LS-SCLC, with a median average survival of 27.2 months for concurrent therapy vs. 19.7 months for sequential therapy.2 Another meta-analysis showed that early initiation of radiation therapy correlated with better OS than late initiation of radiation therapy.3 A hyperfractionated accelerated radiation therapy regimen (45 Gy/1.5 Gy twice daily over 3 weeks) proved superior to standard fractionation of 50 Gy (2 Gy daily over 5 weeks).4 Whether this regimen is superior to 60 Gy (2 Gy daily over 6 weeks) is being assessed in an ongoing trial. Finally, the addition of prophylactic cranial irradiation (PCI) following chemoradiation has been shown to decrease the incidence of brain metastasis and improve OS in LS-SCLC.5

Pearls

For patients with LS-SCLC, treatment consists primarily of concurrent chemotherapy (cisplatin-based regimen) and radiation therapy. Radiotherapy preferably should be initiated before cycle 2 of chemotherapy. Patients with a good response to treatment should be offered PCI. In the rare scenario of LS-SCLC with low tumor burden and absence of ...

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