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.

The recently developed dynamic jaw technology of tomotherapy can reduce craniocaudal dose spread without much prolonging the treatment time. This study aimed to investigate the efficacy of the dynamic jaw mode for tomotherapy of breast cancer. Static tomotherapy plans of the whole breast and supraclavicular regional lymph nodes, and plans for the whole breast only were generated in 25 patients with left-sided breast cancer. Plans with a field width of 2.5 or 5 cm with the dynamic or fixed jaw modes were made for each patient. The prescribed dose was 50 Gy in 25 fractions. In whole breast and supraclavicular nodal radiotherapy, dose distributions and homogeneity of the planning target volume (PTV) with the dynamic jaw mode were slightly inferior to those with the fixed jaw mode with a 5-cm field width (P < .05). However, lung low-dose volumes and mean doses of the larynx, thyroid, skin, and all the healthy tissues combined were smaller with the dynamic jaw mode than with the fixed jaw mode with a 5-cm field width (P < .001). In whole breast radiotherapy, mean doses of the skin and healthy tissues were lower with the dynamic jaw mode than with the fixed jaw mode with a 5-cm field width (P < .001) without significant differences in PTV dose distributions, homogeneity, and conformity. The dynamic jaw mode provided better sparing of organs at risks with minimal disturbance of dose–volume indices of PTV. Considering the treatment time, the 5-cm-field dynamic jaw mode is more efficient than the 2.5-cm fixed jaw mode.

BackgroundEfficacy of stereotactic body radiotherapy (SBRT) in stage I non–small-cell lung cancer (NSCLC) has almost been established. In Japan, the protocol of 48 Gy in 4 fractions over 4 days has been most often employed, but higher doses may be necessary to control large tumors. Previously, we conducted a clinical study using SBRT for stage I NSCLC employing different doses depending on tumor diameter, which was closed in 2008. Thereafter, a new study employing higher doses has been conducted, which is reported here. The purpose of this study was to review the safety and effectiveness of the higher doses.MethodsWe escalated the total dose for the improvement of local control for large tumors. In this study, 71 patients underwent SBRT between December 2008 and April 2014. Isocenter doses of 48, 50, and 52 Gy were administered for tumors with a longest diameter of < 1.5 cm, 1.5–3 cm, and > 3 cm, respectively. It was recommended to cover 95% of the PTV with at least 90% of the isocenter dose, and in all but one cases, 95% of the PTV received at least 80% of the prescribed dose. Treatments were delivered in 4 fractions, giving 2 fractions per week. SBRT was performed with 6-MV photons using 4 non-coplanar and 3 coplanar beams.ResultsThe median follow-up period was 44 months for all patients and 61 months for living patients. Overall survival (OS) was 65%, progression-free survival (PFS) was 55%, and cumulative incidence of local recurrence (LR) was 15% at 5 years. The 5-year OS was 69% for 57 stage IA patients and 53% for 14 stage IB patients (p = 0.44). The 5-year PFS was 55 and 54%, respectively (p = 0.98). The 5-year cumulative incidence of LR was 11 and 31%, respectively (p = 0.09). The cumulative incidence of Grade ≥ 2 radiation pneumonitis was 25%.ConclusionsOur newer SBRT study yielded reasonable local control and overall survival and acceptable toxicity, but escalating the total dose did not lead to improved outcomes.Trial registration UMIN000027231, registered on 3 May 2017. Retrospectively registered.

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.

Radiation doses to the heart are potentially high in patients undergoing radiotherapy for thymoma or thymic carcinoma because of their origin site and propensity for pericardial invasion. We investigated potential relationships between radiation pneumonitis (Rp) and the dosimetric parameters of lung and heart substructures in patients with thymic epithelial tumors. this retrospective study included 70 consecutive patients who received definitive or postoperative radiotherapy at a median dose of 58.3 Gy. Heart substructures were delineated according to a published atlas. The primary end point of ≥ grade 2 RP was observed in 13 patients (19%) despite a low lung dose; median lung V20 (i.e. percentage of the volume receiving at least 20 Gy) was only 16.6%. In a univariate analysis, four lung parameters, heart V35, three pulmonary artery (PA) parameters, two left ventricle parameters, and left atrium V35 were associated with the development of RP. In a multivariate analysis, only PA V35 remained significant (hazard ratio 1.04; 95% CI 1.01-1.07, p = 0.007). PA V35 of the RP versus non-RP groups were 84.2% versus 60.0% (p = 0.003). The moderate dose sparing of PA could be a candidate as a planning constraint for reducing the risk of Rp in thoracic radiotherapy. Thymic epithelial tumors (TET) generally originate within the thymus of the anterior mediastinal region, and these advanced tumors are more likely to invade the pericardial space. When patients with advanced thymoma or thymic carcinoma receive radiotherapy (RT), doses to the heart may be markedly higher than in those with locally advanced (LA) non-small-cell lung cancer (NSCLC). The RTOG 0617 study recently reported a relationship between heart doses and overall survival (OS) in LANSCLC patients treated with chemoradiotherapy (CRT) 1. Thus, heart V5 and V30 (i.e. the percentage of the normal structure volume receiving more than the indicated dose) were both identified as important predictors of OS 1. Similar findings were reported by Speirs et al. 2 ; the heart dose was associated with both OS and cardiac toxicity in LANSCLC patients treated with CRT. Potential relationships between doses to heart substructures and non-cancer death have also been investigated in early-stage NSCLC patients treated with stereotactic body radiation therapy (SBRT) 3. However, these studies left one shared question unanswered: the uncertainty of the cause of death. Difficulties are often associated with distinguishing among death due to RT-associated cardiac toxicity, other treatment-related death, and death due to comorbidities, particularly in retrospective studies 2,3. Several types of RT-associated cardiac toxicities have been identified: e.g. ischemic, pericardial, valvular, and arrhythmic 4,5. Each type of RT-associated cardiac toxicity has a different underlying mechanism 4,5 ; however, tissue fibrosis is a common mediator. For example, patients with breast cancer and lymphoma are at risk of ischemic