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Key Words

Small-cell lung cancer, prophylactic cranial irradiation. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary.)

Summary

Radiation therapy to the head, given to patients who had responded to chemotherapy for advanced small-cell lung cancer, reduced by about two-thirds the risk that patients’ tumors would spread to the brain, thus extending patients’ lives. These findings are likely to change the standard of care for this group of patients.

Source

American Society of Clinical Oncology (ASCO) annual meeting, Chicago, June 2, 2007 (see the meeting abstract).

Background

Lung cancer is the leading cause of cancer death among both men and women. Small-cell lung cancer (SCLC) accounts for about 15 percent of lung cancer cases in the United States. It tends to grow quickly and to spread widely through the body. At diagnosis, about two-thirds of patients with SCLC have disease that has spread beyond the chest cavity.

It is common for SCLC to spread, or metastasize, to the brain. In about 20 percent of patients, the disease has already spread to the brain at diagnosis; after two years, more than 50 percent of patients have brain metastases. With currently available treatments, patients with brain metastases of SCLC survive for a median of six months to a year.

In studies published in the early 1990s, radiation therapy to the head (known as prophylactic cranial irradiation, or PCI) reduced the risk of tumors spreading to the brain and improved survival among patients with early-stage SCLC whose tumors had disappeared after chemotherapy. PCI had not been tested, however, in patients with advanced SCLC.

The Study

A total of 286 patients with SCLC took part in the study, which began in May 2001. All of them had already been treated with chemotherapy. Although their tumors had shrunk in response to the chemotherapy, 75 percent still had tumors in their lungs and in 70 percent the disease had spread to other organs, although not yet to the brain.

The patients were assigned at random to receive either PCI or no additional treatment (the control group). Those assigned to PCI were treated with doses of radiation comparable to those used to treat brain metastases after they develop.

The study’s principal investigator was Ben Slotman, M.D., Ph.D., of VU University Medical Center in Amsterdam, the Netherlands. (See the protocol summary.)

Results

After one year, 14.6 percent of the patients treated with PCI had developed symptomatic brain metastases compared with 40.4 percent of the patients in the control group. Moreover, 27.1 percent of patients in the PCI group were alive after one year, compared with 13.3 percent of those in the control group.

PCI caused some side effects, including headache, nausea, vomiting, and fatigue, but for the most part these adverse effects were mild. Quality of life was similar in both the PCI and control groups. PCI adversely affected patients’ cognitive abilities (that is, the ability to think and reason) in less than 10 percent of cases, noted Andrew T. Turrisi, M.D., of the Karmanos Cancer Institute at Wayne State University in Detroit, Michigan, in a discussion at the ASCO meeting.

(Note: final results from this trial were published in the Aug. 16, 2007, New England Journal of Medicine; see the journal abstract.)

Comments

“Based on the results of this study, patients with [advanced SCLC] who respond to chemotherapy should routinely be offered prophylactic cranial irradiation,” principal investigator Slotman concluded at an ASCO press briefing.

The study’s findings are likely “almost immediately” to change the standard of care for patients with advanced SCLC, added Roy L. Herbst, M.D., Ph.D., of the University of Texas M.D. Anderson Cancer Center in Houston, who moderated the press briefing.

Janet E. Dancey, M.D., of the National Cancer Institute’s Cancer Therapy Evaluation Program, agreed. “The magnitude of the effect [of PCI] is striking,” she said. “Relatively few side effects were seen and these were manageable and did not have an apparent effect on patients’ quality of life.”

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