Technological advances in and increased availability of radiation therapy, along with the changing demographics of lung cancer, are producing advances in lung cancer radiotherapy.1 Shifting patterns in lung cancer survival have led to recent calls for a renewed emphasis on radiotherapy for older patients. Lung cancer mortality has decreased among patients younger than 50 years, but it continues to increase among those older than 70 years.2-3 Lung cancer remains a leading cause of cancer mortality in the United States and around the world, and more than two-thirds of lung cancer cases are diagnosed when the patient is 65 or older.2-3
Radiation therapy can be curative for lung tumors, especially when they are diagnosed in early, localized stages. For elderly patients, the 10- to 20-year latency period between radiation exposure and the onset of secondary cancers and heart disease means that the risk-to-benefit ratio is more favorable than might be the case with younger patients.4-5
Secondary cancer risks aside, the primary risk of radiation therapy for lung cancer—as with most cancers—has long been the toxic effects of radiation to healthy tissues. Impaired lung function has been the inevitable downside of radiation therapy approaches to cancer treatment.
“The only problem in radiotherapy is minimizing the side-effects,” Dr Christian Siedschlag (Netherlands Cancer Institute Radiotherapy Department, Amsterdam) told an audience at the second European Lung Cancer Conference (Geneva, Switzerland, April 28-May 1, 2010). “If one could hit the tumor with arbitrarily high doses without having to worry about (patient) complications, all tumor cells could be killed with 100% certainty.”
Recent advances in the timing and targeting of radiation therapy promise to help minimize the “collateral damage” radiotherapy inflicts on healthy tissues—trends that were on display at the second European Lung Cancer Conference. More than 1,600 attendees learned about advances in gene therapies aimed at preventing the spread of lung cancer to other organs, chemotherapeutic advances—and the rapidly evolving role of radiation therapies.
A central theme of the conference was how best to address the need to maintain lung function while aggressively attacking tumor tissue.
“The ultimate aim is to precisely irradiate the target and protect the surrounding tissues from radiation,” Dr Corina Udrescu (Centre Hospitalier Lyon Sud, Lyon, France) told conference-goers. “Then we get the optimal ratio of tumor benefit to normal tissue damages.”
TIMING AND FRACTIONATION
How a given total target radiation dose is administered can be modified by altering fractionation of the dose—changing the number of irradiation sessions and the fraction of the dose delivered at each session. Hyperfractionated (or accelerated) radiotherapy involves administering smaller doses more frequently, giving tumor tissue less time to recover or to develop reduced radiosensitivity.
Randomized studies of survival benefits of hyperfractionation in lung cancer radiotherapy have yielded contradictory results. But pooling study data from 10 trials confirmed a modest overall 5-year survival benefit of 3% for patients with both non-small cell and small cell lung cancers, conference-goers heard from Dr Cecile Le Pechoux (Institut Gustave Roussy, Villejuif, France).
The findings will not yield immediate changes in clinical practice, but they will spark new research into optimized fractionation schedules, Dr Le Pechoux suggested. “Interest in modified fractionation was uncertain before the meta-analysis,” she said. “[The] current results will lead to renewed interest in this research field.”
Dr Le Pechoux also reported a new meta-analysis comparing combined (concomitant) versus sequentially-administered radio-chemotherapy for locally advanced non-small cell lung cancer.6 Pooling data from six studies, the meta-analysis suggested that simultaneous radio-chemotherapy improved 3- and 5-year survival times by 5.7% and 4.5%, respectively, over sequential radiation and chemotherapy-apparently because of improved control of local and regional tumor growth.6 Unfortunately, metastasis to distant sites was not affected, and local tumor control benefits came at the cost of significantly increased rates of acute, grade 3 to 4 esophageal toxicity (from 4% to 18% of patients).6