Is high-dose thoracic radiation therapy with 60 Gy to 70 Gy a better option than the standard of care for limited-stage SCLC?

No level-one evidence supports it

Currently, the standard-of-care fractionation schemes delivered concurrently with chemotherapy are conventional once-a-day fractionation over five weeks and accelerated hyperfractionation twice-a-day over three weeks. Both of these approaches have been tested in randomized phase-3 trials.

Once daily fractionation (45 Gy in five weeks) is certainly more convenient for patients but was shown to be inferior to accelerated hyperfractionation radiotherapy (45 Gy twice-a-day in three weeks). Other fractionation schemes are being tested under clinical trial.

The rationale for the superiority of the accelerated hyperfractionation approach is based on the rapid growth of SCLC. One common approach is to increase the dose higher than 45 Gy if the patient is receiving daily fractionation radiotherapy.

Bin Teh

There is no level-one evidence yet that high-dose TRT is better than the standard dose. Ongoing intergroup trials are testing high-dose daily TRT (70 Gy) over seven weeks against standard of care 45 Gy twice daily over three weeks. The other arm is a concomitant boost approach 61.2 Gy over five weeks.

A few important considerations are 1) early rather than delayed thoracic irradiation, and 2) continuous rather than split-course thoracic irradiation.

Other important issues being investigated are sequencing of chemotherapy with radiotherapy; for example, neoadjuvant newer chemotherapy agents followed by concurrent standard chemoradiotherapy as well as testing newer chemotherapy agents — including paclitaxel, topotecan and irinotecan — in comparison to the standard agents of platinum and etoposide.

Bin Teh, MD, is a Radiation Oncologist at The Methodist Hospital, Houston.

It is feasible and promising; more data needed

Escalated doses of radiation may be beneficial in NSCLC, and the RTOG 0617 trial is studying this concept in a randomized fashion.

Definitive thoracic radiation therapy with concurrent chemotherapy, followed by prophylactic cranial irradiation in complete responders, is the standard of care for limited stage small cell lung cancer. Of the thoracic radiation delivery schedules that have been studied in this setting, the one that is considered by many to be the standard of care, in that its use is supported by the highest level of clinical evidence — a randomized clinical trial — is 45 Gy given over three weeks in 1.5 Gy fractions delivered twice per day, starting concurrently with chemotherapy.

Many academic centers including Stanford use this treatment regimen because of these results, but the minority of patients overall receive hyperfractionated accelerated treatment because of the logistical difficulties in most treatment centers of administering radiation twice a day.

Once-a-day treatment to a total dose of at least 60 Gy is generally considered an acceptable alternative but has not been shown to be equivalent to hyperfractionated accelerated treatment in a direct comparison.

In limited-stage SCLC, the CALGB conducted a series of studies establishing once-per-day radiation therapy to a total dose of 70 Gy over seven weeks as a feasible treatment regimen to give concurrently with chemotherapy.

Billy W. Loo Jr.

Similarly, the RTOG has conducted a series of studies employing an accelerated fractionation regimen of 61.2 Gy in 1.8 Gy fractions delivered over five weeks with concurrent chemotherapy, with twice-per-day treatments during the latter part of the course, demonstrating its feasibility.

Both of these regimens demonstrated promising outcomes relative to the historical results with 45 Gy hyperfractionated accelerated treatment and are now being tested against this standard in a randomized trial (CALGB 30610/RTOG 0538).

Patients with extensive stage SCLC are generally treated with chemotherapy alone, followed by PCI in responders. However, a small randomized study found that patients who had a very good response to chemotherapy alone benefited from consolidative thoracic radiation (given on a hyperfractionated accelerated schedule). I offer this treatment to well-selected patients with extensive-stage SCLC.

Billy W. Loo Jr., MD, PhD, DABR, is an Assistant Professor and Thoracic Radiation Oncology Program Leader at Stanford University & Cancer Center.