When should radiotherapy be administered in combination with chemotherapy?

The authors aimed to determine when radiotherapy should be administered, during chemotherapy-radiotherapy adjuvant treatment in patients with limited small-cell lung cancer (SCLC). They concluded that radiotherapy increases the survival rate if it is administered early during chemotherapy treatment.

For SCLC, chemotherapy is the first line of treatment regardless of the stage of the disease. For patients with limited disease (that has not spread), chemotherapy can fail. Combining chemotherapy with radiotherapy has since become standard care in an attempt to increase the rate of survival of these patients. The perfect time to administer radiotherapy during chemotherapy treatment for this type of cancer remains undefined.

The authors analyzed 9 clinical trials with a total of 2305 patients that had stage 1-3B limited SCLC. These trials looked at the benefit of combining radiotherapy with chemotherapy. The trials administered radiotherapy either early (9 weeks before the third cycle of chemotherapy) or later. The trials looked at overall survival (OS; time from beginning trial to death from any cause) and progression free survival (PFS; time from beginning trial to disease progression).

Overall, the authors found no difference in OS or PFS between early or late administration of radiotherapy.

In patients who received 100% of the planned chemotherapy treatment, early radiotherapy was associated with a 21% increase in the odds of a longer OS, a 5.6% increase in the odds of a longer 5-year PFS, and a 7.7% increased 5-year survival rate. Patients who received 100% of the planned chemotherapy had 44% better odds of a longer OS and 30% better odds of a longer PFS than those who did not.

For patients who did not receive the original planned chemotherapy, radiotherapy delivered later was associated with a 19% increase in the odds of a longer OS.

Patients who received radiotherapy early had more toxic side effects, including inflammation of the esophagus.

The authors recommended that radiotherapy should be administered early with planned chemotherapy, however increased survival comes at the expense of more toxic side effects.