Data presented by Dr. Gomez, however, suggest that a mean delivered esophageal dose of above 40 Gy may be predictive of high-grade inflammation regardless of whether proton beams, IMRT or 3D-CRT is used. This research might eventually help develop dosing guides for clinicians to use in routine practice, he suggested.
"Patients receiving IMRT had a higher rate of esophagitis in all grades, including grade 3," Dr. Gomez said. In contrast, "patients receiving proton therapy had lower rates of esophagitis at all grades." The incidence of grade 3 or higher esophagitis was 14% (n = 65) for 3D-CRT, 27% (n = 33) for IMRT, and 6% (n = 6) for proton beam therapy.
Dr. Gomez also reported that grade 3 or higher esophagitis was more likely in patients who received concurrent chemotherapy than in those who did not (18.4% vs. 7.4%, P less than .001). The mean esophageal dose of radiation delivered to patients given concurrent chemotherapy also was, significantly higher (32.2 Gy vs. 15.8 Gy, P less than .001), however.
The M.D. Anderson investigators said they have just finished (May 12) recruiting patients into a phase III trial (Radiation Therapy Oncology Group [RTOG] 0617) that will compare conventional (60 Gy in 6 weeks) vs. high dose (74 Gy in 7.5 weeks) radiation therapy in combination with paclitaxel and carboplatin, with or without the addition of cetuximab (Erbitux) in 500 patients with NSCLC.
Although the trial is not directly comparing the type of radiation treatment used, it should still be possible to retrospectively analyze the results to determine the individual effects of the radiation modalities used at each participating center, Dr. Komaki noted.
"When we started this trial, it was not acquiring patients because some of the radiation and medical oncologists said that it was obvious that patients given 60 Gy would do worse compared to 74 Gy," she added in the interview. "When we included cetuximab based on the results of the RTOG 0324 trial, however, recruitment started to rocket." The RTOG 0324 trial showed the feasibility of combining cetuximab with chemoradiation in NSCLC (J. Clin. Oncol. 2011 May 9 [Epub ahead of print, doi: 10.1200/JCO.2010.31.7875]).
Discussing the downsides of proton beam therapy vs. IMRT, Dr. Komaki conceded that the newer method involved a lot more sophisticated planning and was more expensive. There is also concern that the sharp drop-off of radiation received with proton beam therapy might mean that important areas of the tumor are missed – although this may explain the lower rate of side effects seen with PBT to date. "There is no give," Dr. Komaki said.
As relatively few proton beam facilities are in operation, large cooperative trials are difficult to perform. The prospective phase II trial comparing proton beam therapy and IMRT now being conducted at M.D. Anderson and the Massachusetts General Hospital will be the proof that such trials are possible, and provide valuable information on the comparative safety and efficacy of the two procedures.
Dr. Komaki and Dr. Gomez said they had no financial conflicts of interest.