Higher dose 3D-CRT improves local control of lung cancer

November is National Lung Cancer Awareness Month, and 2004 marks the debut of www.lcam.org, an Internet forum for lung cancer survivors. Unfortunately, not all lung cancer patients will have the opportunity to tell their stories: According to projections by the American Cancer Society, more than 160,000 people in the U.S. will die from the disease this year. Over the past decade, lung cancer has claimed more than 1.5 million lives.

Despite advances in lung carcinoma treatment, such as the dynamic duo of chemotherapy and radiation therapy, the overall survival rate for these patients remains less than ideal. One possible reason for this poor outcome is that current radiation doses are insufficient for local disease control, according to researchers from Memorial Sloan-Kettering Cancer Center in New York City. But the solution involves more than just upping the dosage and curing the disease, they added.

"Evidence suggests that there is a direct relationship between dose and tumor control, and that increasing tumor dose results in an improvement of local control," wrote Dr. Ramesh Rengan, Ph.D., and colleagues (International Journal of Radiation Oncology, Biology, Physics, November 2004, Vol. 60:3, pp. 741-747). Rengan is from the center's department of radiation oncology. His co-authors are from the departments of epidemiology and biostatistics, as well as medical physics.

However, they stated, "One of the principal roadblocks to dose escalation has been toxicity secondary to the irradiation of normal lung."

Rengan's group studied 72 patients with biopsy-proven stage III non-small cell lung carcinoma (NSCLC) and gross tumor volumes (GTV) of 100 cc or higher. All the patients were treated with 3D conformal radiotherapy (3D-CRT). The planning target volume (PTV) was constructed from the GTV by an automatic margining tool. For treatment delivery, megavoltage linear accelerator x-rays of 6 MV or higher energy were used. Doses were prescribed to the maximum isodose level that encompassed the PTV.

The majority of patients first underwent 2-4 cycles of cisplatin-based chemotherapy. They were then divided into two groups: Group 1 (37 patients) was treated with radiation doses of less than 64 Gy, while group 2 (35 patients) received doses of 64 Gy or higher. The dose levels ranged from 50 Gy to 84 Gy. Radiotherapy was followed with physical exams and chest CT up to two years after the completion of therapy.

"Overall survival and local failure-free survival were assessed from the start of radiation until the time of recurrence, death, or date of most recent follow-up," the authors explained.

According to the results, the median survival time for those who received doses of 64 Gy or higher was 20 months, compared to 15 months for those who received lower doses. The two-year local failure rate for patients treated to 70 Gy or higher was 64%, less than the 75% for those treated to less than 70 Gy. The two-year local failure rate was 49% for stage III patients with GTV of 200 cc or higher and who were treated with a minimum 70 Gy dose. For those treated with less than 70 Gy, the local failure rate was 92%.

"Dose was an independent predictor of local failure-free survival," the group wrote. "A 10 Gy incremental increase in dose resulted in a 36% decreased risk of local failure."

In addition, there were no cases of grade 4-5 esophageal cancer in either group. However, the incidence of grade 2 or higher pulmonary toxicity was increased in the high-dose group. One patient in group 2 died of radiation pneumonitis.

While an optimum radiation dose for NSCLC treatment remains undefined, the authors pointed out that "based on our study, an increase in dose by 4 Gy might account for a 15% improvement in local control."

A number of presentations at the 2004 Radiological Society of North America (RSNA) conference in Chicago will explore radiotherapy for lung cancer. Dr. Ritsuko Komaki will lead a refresher course on the multimodality management of lung carcinoma, including ways to reduce severe acute normal tissue toxicities (RC119B). Several scientific papers will address such topic as reradiation for locoregional relapse of NSCLC (SSA19-03), 3D conformal therapy versus 4D respiratory-gated radiotherapy (SSA19-07), and MR analysis of lung motion and intrathoracic tumor mobility for radiotherapy (SSA19-09).

By Shalmali Pal
AuntMinnie.com staff writer
November 8, 2004

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