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CHICAGO -- Individualized, volume-adapted radiotherapy for lung cancer led to good disease control and a favorable safety profile, a researcher reported.

Patients with newly diagnosed lung cancer, recurrent disease, or lung metastases had better than 90% freedom from recurrence at 1 year with the individualized approach. Median overall survival was 57 months.

The results question the need for a high biologically effective dose (BED) to achieve local disease control, as suggested by earlier studies, said Michael Gensheimer, MD, of Stanford University in California, during the American Society for Radiation Oncology (ASTRO) meeting.

"The individualized dosing strategy appeared to be successful," said Gensheimer. "The primary local control endpoint was made in all three patient groups, with generally low toxicity. The dosing of 25 Gy per fraction seems to be a convenient and cost-effective option for small peripheral tumors. The results question the need for high doses greater than 100 Gy volume dose for all non-small cell lung cancers [NSCLCs]."

Stereotactic ablative radiotherapy (SABR) is the standard of care for inoperable early-stage NSCLC, as well as an emerging standard for oligometastatic lung tumors, Gensheimer said in the introduction to the study. have suggested a dose exceeding 100 Gy BED is required for local control. However, high-dose treatment carries a risk of serious toxicities, including pulmonary hemorrhage and severe chest wall pain.

Early experience at Stanford with SABR showed that a dose of 15-30 Gy in a single fraction is , he continued. Additional studies showed that , with BED ≥100 Gy reserved for gross tumor volume ≥12 cc, offered promising results and warranted further study. Colorectal cancer lung metastases appeared to require for local control.

With that background, investigators conducted a phase II single-arm trial to test the hypothesis that individualizing SABR dose and fractionation by tumor size, location, and histology would produce good local control with acceptable toxicity. The primary outcome was per-tumor freedom from local recurrence at 1 year. The trial would be considered successful if the lower bound of 90% confidence intervals exceeded 80%.

Investigators enrolled patients with lung tumors that fell into one of three categories: newly diagnosed early NSCLC (T1-3 N0 M0), synchronous NSCLC or new NSCLC after prior early lung cancer, or lung metastases from NSCLC or other primary site. Tumors could be operable or inoperable.

Dosing was individualized by tumor volume, location, and histology. Tumors with small volume (<10 cc) received 25 Gy in one fraction if peripherally located, 40 Gy in four fractions if centrally located, and 50 Gy in four fractions if colorectal in origin. Tumors 10-30 cc received 50 Gy in four fractions whether located peripherally or centrally. Larger tumors were treated with 50 Gy in three fractions if peripheral and 60 Gy in eight fractions if central.

The study included 240 patients, 79 with primary NSCLC, 82 with synchronous NSCLC or a new primary, and 79 with lung metastases. A total of 285 tumors were treated, 211 of which had peripheral location. Small tumors accounted for 68% of the total, medium-size tumors for 20%, large tumors for 7%, and colorectal metastases for 6%.

The local recurrence rate was <10% overall and in each of the three subgroups. The trial also met the statistical requirements for success.

"The treated-tumor recurrence was low for tumors in each of the six size and location categories that determined the dosing, with no statistically significant difference between the six categories," said Gensheimer.

Grade 2 toxicity occurred in 13% of patients, grade 3 in 3%, grade 4 in 0.5%, and one patient (0.5%) had a fatal pulmonary hemorrhage that was possibly related to SABR. The patient had a large centrally located tumor treated with a 60-Gy radiation dose.

The trial showed that individualized dosing is successful, as the primary local control endpoint was met in all three patient groups and achieved with low rates of toxicity, said ASTRO invited discussant Charles Simone II, MD, of Memorial Sloan Kettering Cancer Center in New York City. The results also showed that 25 Gy in one fraction is convenient, cost-effective, and a reasonable option for small peripheral lung tumors. Additionally, the results reinforced three prior studies comparing single- and multifraction SABR.

"This tells us that for small peripheral tumors, you probably don't need to get over 100 BED, whether that's a single fraction or a multifraction regimen," said Simone. "Peripheral small tumors probably can have very, very good local control without it."

The trial did not address the interaction of SABR with chemotherapy or immunotherapy, how that might affect toxicity, and whether toxicity might change dose-fractionation recommendations, he added. Additional studies evaluating SABR with systemic therapy are needed.

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