T. Takaoka

Stereotactic Body Radiotherapy Using a Radiobiology-Based Regimen for Stage I Non–Small-Cell Lung Cancer: Five-Year Mature Results

Introduction: Although the protocol of 48 Gy in four fractions over 4 days has been most often employed in stereotactic body radiotherapy (SBRT) for stage I non–small-cell lung cancer in Japan, higher doses are necessary to control larger tumors, and interfraction intervals should be longer than 24 hours to take advantage of reoxygenation. We report the final results of our study testing the following regimen: for tumors less than 1.5, 1.5–3, and greater than 3 cm in diameter, 44, 48, and 52 Gy, respectively, were given in four fractions with interfraction intervals of greater than or equal to 3 days. Methods: Among 180 histologically proven patients entered, 120 were medically inoperable and 60 were operable. The median patient age was 77 years (range, 29–89). SBRT was performed with 6-MV photons using four noncoplanar and three coplanar beams. Isocenter doses of 44, 48, and 52 Gy were given to four, 124, and 52 patients, respectively. Results: The 5-year overall survival rate was 52.2% for all 180 patients and 66% for 60 operable patients. The 5-year local control rate was 86% for tumors less than or equal to 3 cm (44/48 Gy) and 73% for tumors greater than 3 cm (52 Gy; p = 0.076). Grade greater than or equal to 2 radiation pneumonitis developed in 13% (10% for the 44/48-Gy group and 21% for the 52-Gy group; p = 0.056). Other grade 2 toxicities were all less than 4%. Conclusions: Our first prospective SBRT study yielded reasonable local control and overall survival rates and acceptable toxicity. Refinement of the protocol including dose escalation may lead to better outcome.

Biological effects of hydrogen peroxide administered intratumorally with or without irradiation in murine tumors

Despite insufficient laboratory data, radiotherapy after intratumoral injection of hydrogen peroxide (H2O2) is increasingly being used clinically for radioresistant tumors. Especially, this treatment might become an alternative definitive treatment for early and advanced breast cancer in patients who refuse any type of surgery. The purpose of this study was to investigate the biological effects and appropriate combination methods of irradiation and H2O2 in vivo. SCCVII tumor cells transplanted into the legs of C3H/HeN mice were used. Chronological changes of intratumoral distribution of oxygen bubbles after injection of H2O2 were investigated using computed tomography. The effects of H2O2 alone and in combination with single or five‐fraction irradiation were investigated using a growth delay assay. The optimal timing of H2O2 injection was investigated. Immunostaining of tumors was performed using the hypoxia marker pimonidazole. Oxygen bubbles decreased gradually and almost disappeared after 24 h. Administration of H2O2 produced 2–3 days’ tumor growth delay. Tumor regrowth was slowed further when H2O2 was injected before irradiation. The group irradiated immediately after H2O2 injection showed the longest tumor growth delay. Dose‐modifying factors were 1.7–2.0 when combined with single irradiation and 1.3–1.5 with fractionated irradiation. Pimonidazole staining was weaker in tumors injected with H2O2. H2O2 injection alone had modest antitumor effects. Greater tumor growth delays were demonstrated by combining irradiation and H2O2 injection. The results of the present study could serve as a basis for evaluating results of various clinical studies on this treatment.

Efficacy of stereotactic radiotherapy for brain metastases using dynamic jaws technology in the helical tomotherapy system

Objective: Dynamic jaws (DJ) are expected to be useful in stereotactic radiotherapy (SRT) for brain metastases (BM). The efficacy and optimal dose fractionation were investigated. Methods: In a planning study, 63 treatment plans were generated for the following 3 conditions: 1.0-cm fixed jaws (FJ), 2.5-cm FJ and 2.5-cm DJ. In a clinical study, 30 Gy/3 fr, 35 Gy/5 fr or 37.5 Gy/5 fr were prescribed depending on tumour size. Clinical results of groups treated with 2.5-cm DJ plans and 1.0-cm FJ were compared. Results: In the planning study, the treatment times in 2.5-cm DJ and FJ plans were less than that in 1.0-cm FJ plans (p < 0.001). The brain doses in 1.0-cm FJ plans and 2.5-cm DJ plans were smaller than those in 2.5-cm FJ plans (p < 0.05). In the clinical study, 34 patients with 68 BM were treated with SRT. Of those, 15 patients with 34 BM were treated with 2.5-cm DJ plans and 19 patients with 34 BM were treated with 1.0-cm FJ plans. The overall survival and local tumour control (LC) rates were 52 and 93% at 12 months, respectively. The DJ system achieved favourable LC and 29% shorter treatment time compared with the FJ system (p < 0.001). Grade 2 or 3 necrosis occurred more frequently in patients with 15 cc or larger tumour volumes (p = 0.05). Conclusion: DJ technology enables treatment time to be reduced without worsening the dose distribution and clinical efficacy. The prescribed doses in this study may be acceptable for patients with small tumour volumes. Advances in knowledge: DJ technology enables treatment time to be reduced without worsening the dose.