Potent radiation treatment provides tumor control for patients with inoperable lung cancer

Robert Timmerman, M.D., of the University of Texas Southwestern Medical Center, Dallas, presented the findings of the study at a JAMA media briefing.

Patients with inoperable early stage lung cancer are generally offered conventional radiation treatment (most commonly given during 20-30 outpatient treatments) or observed without specific cancer therapy. "Outcomes are not ideal with either approach. Conventional radiotherapy fails to durably control the primary lung tumor in 60 percent to 70 percent of patients. More than half of patients ultimately die specifically from progressive lung cancer with observation, and 2-year survival is less than 40 percent with either approach," the authors write. Stereotactic body radiation therapy (SBRT) is a noninvasive cancer treatment in which numerous small, highly focused, and accurate radiation beams are used to deliver potent doses in 1 to 5 treatments to tumor targets.

Dr. Timmerman and colleagues conducted the Radiation Therapy Oncology Group (RTOG) 0236 trial, the first North American multicenter, cooperative group study to test SBRT in treating medically inoperable patients with early stage non-small cell lung cancer. The Phase 2 study included patients 18 years or older with biopsy-proven peripheral T1-T2N0M0 non-small cell tumors (measuring less than 5 cm. in diameter) and medical conditions that would not allow surgical treatment. Radiation treatment lasted between 1.5 and 2 weeks. The study opened May 2004 and closed October 2006, with data analyzed through August 2009. The final study population included 55 patients (44 with T1 tumors and 11 patients with T2 tumors), with a median (midpoint) follow-up of 34.4 months.

The primary outcome measured for the study was 2-year actuarial primary tumor control; secondary end points were disease-free survival (i.e., primary tumor, involved lobe, regional, and disseminated recurrence [the reappearance or return of a cancer in multiple areas of the body]), treatment-related toxicity and overall survival.

Of all the patients in the study, only one experienced a documented tumor recurrence or progression at the primary site. The 3-year primary tumor control rate was 97.6 percent. Three patients had recurrence within the involved lobe; the 3-year primary tumor and involved lobe (local) control rate was 90.6 percent. Combining local and regional failures, the 3-year local-regional control rate was 87.2 percent. Disseminated recurrence as some component of recurrence was reported in 11 patients. The 3-year rate of disseminated failure was 22.1 percent with 8 such failures occurring prior to 24 months.

Disease-free survival and overall survival at 3 years were 48.3 percent and 55.8 percent, respectively. Median disease-free survival and overall survival for all patients were 34.4 months and 48.1 months, respectively. Seven patients (12.7 percent) and 2 patients (3.6 percent) were reported to experience protocol-specified treatment-related grade 3 and 4 adverse events, respectively. No grade 5 treatment-related adverse events were reported. Higher grades indicate greater severity of adverse event, with grade 5 indicating death.

"The main finding in this prospective study was the high rate of primary tumor control (97.6 percent at 3 years). Primary tumor control is an essential requirement for the cure of lung cancer," the authors write. "Stereotactic body radiation therapy as delivered in RTOG 0236 provided more than double the rate of primary tumor control than previous reports describing conventional radiotherapy."

"The RTOG 0236 trial demonstrated that technologically intensive treatments like SBRT can be performed in a cooperative group so long as the proper infrastructure and support are put in place. The RTOG will be building on RTOG 0236 to (l) design a trial to address the rather high rate of disseminated failure observed after treatment, (2) complete a trial to determine a safe and effective dose for central lung tumors and (3) complete a trial to refine the dose of SBRT for peripheral tumors."