¿Más es Mejor en Cáncer de Pulmón?

Standard-Dose Radiation Bests High-Dose Radiation in Advanced NSCLC

IMNG Medical Media, 2013 May 16, P Wendling

Standard-dose radiation produced better overall survival and locoregional control than did high-dose radiation when given with concurrent chemotherapy in patients with newly diagnosed stage III non–small cell lung cancer in the phase III, randomized RTOG 0617 trial.

Patients on the high dose had a 56% greater risk of death than those on a standard 60 Gy dose. Median overall survival times were 18.5 months with high-dose radiation and 28.7 months with a standard dose (hazard ratio, 1.56;P = .0007).

The risk of local failure also was increased by 37% in the high-dose arm (HR, 1.37; P = .03).

“At this point, there is no clear reason for the poor outcome we experienced on the high-dose arm,” lead author Dr. Jeffrey Bradley said in a press briefing highlighting studies to be presented at the upcoming annual meeting of the American Society of Clinical Oncology (ASCO).

The most likely culprit is unreported toxicities, although other possible explanations are increased heart dose, longer duration of therapy, or a combination of these factors, he said.

The results are surprising because conventional thinking has been that higher doses of radiation would more effectively kill the tumor and thereby improve survival.

A phase-III trial in the 1970s established the standard radiation dose of 60 Gy in this setting but, over time, several radiation dose-ranging phase-II studies have reported promising results and improved median survival times with radiation doses up to 74 Gy, explained Dr. Bradley, professor of radiation oncology and chief of the thoracic service at Washington University, St. Louis.

At the same time, improvements in technology such as three-dimensional radiation therapy (RT) and intensity-modulated RT techniques have made RT delivery more precise, allowing organs and tissues sensitive to radiation to receive less radiation while the tumor receives more. This technique was explored in Radiation Therapy Oncology Group (RTOG) 0617.

“This is a very surprising result, especially when using these special radiation techniques that were designed to be more precise, you would expect that the outcome would be better,” ASCO president Sandra Swain, medical director of the Washington (D.C.) Cancer Institute, told reporters. “This should really put an end to higher-dose treatments, given the better outcomes in the standard-dose arms.”

Dr. Bradley said, “A lot of phase-III trials turn out negative when phase-II trials look good, so I think it was good to do a phase-III trial and get this answered.”

RTOG 0617 randomly assigned 464 patients with newly diagnosed, unresected stage-III non–small cell lung cancer to conformal RT to 60 Gy, five times per week for 6 weeks or to 74 Gy five times per week for 7.5 weeks. All patients received concurrent chemotherapy with weekly paclitaxel (Taxol) and carboplatin, with a second randomization for patients to receive consolidation chemotherapy with or without cetuximab (Erbitux).

Among the 419 patients available for analysis at 18 months, local failure rates were 25% with standard-dose RT and 34.3% with high-dose RT (P = .03, as noted above), Dr. Bradley reported.

Median 18-month overall survival rates were 67% with the standard radiation dose vs. 54% with the high dose.

Median overall survival times in both groups were higher than expected, but “the overall survival benefit of 60 Gy is independent of the cetuximab question,” he said. Data from that portion of the trial are expected to be reported in 2014.

Finally, the only significant difference in physician-reported side effects was a slightly higher rate of esophagitis in the high-dose arms (21% vs. 7%).

Full details of RTOG 0617 (abstract 7501) will be reported 10:15 a.m. on June 4 at ASCO’s annual meeting in Chicago.

The study was supported by the National Cancer Institute. Dr. Bradley reported having no relevant financial disclosures. A coauthor reported research funding from the NCI.

Clinical Outcomes of Biological Effective Dose-Based Fractionated Stereotactic Radiation Therapy for Metastatic Brain Tumors From Non-Small Cell Lung Cancer

International Journal of Radiation Oncology-Biology-Physics Volume 85, Issue 4, Pages A1-A16, e165-e199, 891-1150 (15 March 2013)

Clinical Outcomes of Biological Effective Dose-Based Fractionated Stereotactic Radiation Therapy for Metastatic Brain Tumors From Non-Small Cell Lung Cancer Tomohiko Matsuyama, Kasei Kogo, Natsuo Oya Abstract  PurposeTo evaluate the efficacy and toxicity of fractionated stereotactic radiation therapy (FSRT) based on biological effective dose (BED), a novel approach to deliver a fixed BED irrespective of dose fractionation, for brain metastases from non-small cell lung cancer (NSCLC).Methods and MaterialsBetween March 2005 and March 2009 we treated 299 patients with 1 to 5 lesions from NSCLC (573 total brain metastases) with FSRT using Novalis. The dose fractionation schedules were individually determined to deliver a peripheral BED10 (α/β ratio = 10) of approximately 80 Gy10. The median number of fractions was 3 (range, 2-10), the median peripheral BED10 was 83.2 Gy (range, 19.1-89.6 Gy). Patients were followed up with magnetic resonance imaging (MRI) studies performed at 1- to 2-month intervals. The local tumor control rate and overall local progression-free and intracranial relapse-free survival were calculated by the Kaplan-Meier method.ResultsLocal control rates for all 573 lesions at 6 and 12 months were 96.3% and 94.5%, respectively. By multivariate analysis the tumor diameter was the only factor predictive of the local control rate (P=.001). The median overall survival, local progression-free survival, and intracranial relapse-free survival were 17.1, 14.9, and 4.4 months, respectively. The overall survival, local progression-free survival, and intracranial relapse-free survival rates at 6 and 12 months were 78.5% and 63.3%, 74.3% and 57.8%, and 41.0% and 21.8%, respectively. Six patients (2%) manifested progressive radiation injury to the brain even during therapy with corticosteroids; they underwent hyperbaric oxygen therapy, and follow-up MRI showed improvement. Conclusions This study showed that BED-based FSRT for brain metastases from NSCLC is a promising strategy that may yield excellent outcomes with acceptable toxicity. Criteria must be established to determine the optimal dose fractionation for individual patients.

Precision radiation therapy may improve survival rates of some lung cancer patients

Dr. Muñoz Carmona. Servicio de Oncología Radioterápica Huelva

March 16, 2010 -- A radiation therapy that uses multiple radiation beams to target tumors precisely has been shown to eliminate the primary tumor and ultimately may improve survival rates for lung-cancer patients unable to undergo surgery, according to UT Southwestern Medical Center physicians who led a national clinical trial of the treatment.
In a study appearing in the March 17 issue of The Journal of the American Medical Association, primary lung cancer did not recur in nearly 98 percent of the 55 participants who received stereotactic body radiation therapy (SBRT). More than half of these patients -- 56 percent ? were alive three years after diagnosis, while less than 20 percent ultimately died of metastatic lung cancer.
Dr. Robert Timmerman, vice chairman of radiation oncology at UT Southwestern, is lead author of the study and the principal investigator of the Radiation Therapy Oncology Group (RTOG) 0236 trial ? the first North American multicenter study to test SBRT in this patient population.
SBRT is a noninvasive procedure that delivers radiation beams to a tumor in a concentrated, extremely precise manner. Each of these beams is relatively weak and causes very little damage when traveling through the patient's body. When all the beams converge at the tumor, however, their cumulative effect delivers an extremely potent high dose aimed at destroying the target cells with great precision.
In this study, the 55 patients diagnosed with early-stage non-small cell lung (NSCL) cancer were unable to have their tumors surgically removed because of unrelated medical conditions, which left many of the subjects quite frail. Instead of conventional radiation therapy, which is often offered to such patients and is administered in 20 to 30 outpatient treatments, the participants were treated with SBRT during three outpatient treatments.
"Despite the high potency of the treatment, fewer than 20 percent of these extremely frail patients experienced a serious health decline," said Dr. Timmerman, who is considered one of the top international experts on stereotactic radiotherapy. "We believe these findings justify SBRT as a standard of care treatment for lung cancer in patients with serious medical problems like emphysema, heart disease and strokes.
"Primary tumor control is an essential requirement for the cure for lung cancer," he said. "SBRT as delivered in this clinical trial provided more than double the rate of primary tumor control as conventional radiotherapy described in earlier reports."
Dr. Timmerman said the patient outcomes in this study were better than researchers had expected and are similar to the risks for healthier patients who undergo radical surgery ? the standard treatment for early-stage NSCL cancer for the past century.
"The findings support ongoing clinical research that is investigating the use of SBRT in healthier patients who currently undergo surgery for their early-stage NSCL," Dr. Timmerman said. "SBRT is fast, convenient and very effective."
Dr. Timmerman and his team currently are conducting clinical studies using SBRT in healthier patients who would otherwise be candidates for surgery. Participants are still being recruited for the study.