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It is desirable to estimate the degree of the decrease in pulmonary function before lung stereotactic body radiation therapy (SBRT) especially for patients with poor pulmonary function. The purpose of this study was to investigate whether decreases in pulmonary function after SBRT may be predicted from radiation dose–volume parameters. A total of 70 patients undergoing SBRT were evaluated for changes in pulmonary function. Of these, 67 had primary lung cancer and 3 had lung metastasis. Twenty-six (37%) patients had chronic obstructive pulmonary disease. Pulmonary function tests (PFTs) were performed shortly before and at 18–24 months after SBRT. Radiation pneumonitis was Grade 2 in 10 patients and Grade 3 in 1. Mean forced vital capacity (FVC) decreased from 2.67 to 2.51 L (P 5 Gy) and %V40Gy. Although the correlation was not significant, the %V20Gy value was the closest to the percent reduction in predicted FVC; %V20Gy of 10% tended to be associated with ~10% reduction in predicted FVC. Patients with poor pulmonary function did not necessarily show greater decreases in each PFT parameter. Decreases in FVC and FEV1 were within previously reported ranges. PTV was associated with decreases in FVC. The %V20Gy value was closest to the percentage decrease in predicted FVC.

To investigate whether surgery and stereotactic body radiotherapy (SBRT) yield comparable outcomes for clinical stage (c-stage) I non-small-cell lung cancer (NSCLC), propensity score-matching (PSM) analysis was conducted. This single-institutional retrospective study included patients who underwent surgery (n = 574) or SBRT (n = 182) between 2004 and 2014. PSM was performed based on tumor diameter, age, sex, performance status, forced expiratory volume, Charlson comorbidity index, and ground glass nodules (GGN) defined as cTis or cT1mi according to the 8th TNM classification. The median follow-up durations for the surgery and SBRT groups were 66 and 69 months, respectively. The multivariate analysis revealed that non-GGN was a significant factor for poorer overall survival (OS) and disease-free survival (DFS): hazard ratio (HR) 19.95% confidence interval (CI) 4.7–79, P

Definitive chemoradiotherapy (dCRT) is the standard treatment for unresectable esophageal cancer. Induction chemotherapy has been actively investigated for borderline-resectable and unresectable disease, but the superiority over dCRT has yet to be confirmed. The purpose of this study was to evaluate the outcome of dCRT with special interest in borderline-resectable disease. Patients with esophageal cancer treated with dCRT between January 2004 and November 2016 were included in this retrospective analysis. Chemotherapy consisted of two cycles of cisplatin (70–75 mg/m2) on day 1 and 5-fluorouracil (700–1000 mg/m2 per day) on days 1–4 or low-dose cisplatin (10 mg/m2 per day) and 5-fluorouracil (175 mg/m2 per day) for 20 days. Radiotherapy was given with a daily fraction of 1.8–2 Gy to a total dose of 50–70 Gy. A total of 104 patients were included: 34 were resectable, 35 were borderline-resectable and 35 were unresectable. Complete response was achieved in 44 patients (42%). Eighteen patients (17%) suffered Grade 2 or greater cardiopulmonary toxicity and seven patients (7%) suffered Grade 3 cardiopulmonary toxicity. At the time of this analysis, 59 patients were dead and 45 were censored. The 3-year overall survival proportions for resectable, borderline-resectable and unresectable patients were 64%, 46% and 21%, respectively. The overall survival for borderline-resectable patients with complete response and noncomplete response was significantly different (P

We retrospectively reviewed the effect of stereotactic body radiation therapy (SBRT) in patients with stage I lung cancer whose lung tumor showed a nodular appearance of ground glass opacity, so-called ground glass nodule (GGN). A total of 84 patients (42 men, 42 women; mean age, 75 years) with stage I lung cancer with GGN accompanying a solid component

Background To evaluate the long-term efficacy and toxicity of radiation therapy in patients with Stage IE primary ocular adnexal mucosa-associated lymphoid tissue lymphoma. Methods We designed a retrospective analysis to evaluate 81 patients with ocular adnexal mucosa-associated lymphoid tissue lymphoma treated with radiation therapy between 2006 and 2016. The median radiation dose was 30 Gy (range, 30–36 Gy in 15–18 fractions). Local control, progression-free survival, overall survival, and cumulative incidence of Grade 3 cataract were calculated by using the Kaplan–Meier method. Result The median follow-up time was 74 months (range, 4–157 months). The 5-year local control was 100%. Although local relapse was suspected in 3 patients after radiation therapy, 2 patients were pathologically diagnosed as IgG4-related inflammation and in 1 patient as intense inflammatory cell infiltration. The 5-year progression-free survival was 94.4%. Five patients had relapse at distant sites. The 5-year overall survival was 98.8%. Twenty patients had Grade 3 cataract. The 5-year cumulative incidences of Grade ≥ 3 and Grade ≥ 2 cataract for 58 patients treated without a lens shield were 38 and 40%, respectively. The incidence of Grade ≥ 3 cataract was 42% for 50 patients treated with 6-MV X-rays (estimated lens dose: 29 Gy) and 17% for 8 patients treated with 9-MeV electrons (estimated lens dose: 24 Gy). Conclusions Radiation therapy alone yielded excellent local control and long-term survival in Stage IE ocular adnexal mucosa-associated lymphoid tissue lymphoma. Long-term observation with careful attention to relapse at distant sites is necessary. In the case of suspected local relapse, IgG4-related disease should be carefully ruled out.

With the newly-developed static-port forward-planning (FP) mode of tomotherapy, the ratio of the dose of the planning target volume (PTV) periphery to the maximum dose can be easily adjusted by modifying leaf margins when planning stereotactic body radiotherapy (SBRT). The purpose of this study was to evaluate the characteristics of FP plans compared to helical intensity-modulated radiotherapy (IMRT) and helical 3D conformal radiotherapy (3DCRT) plans of SBRT for lung tumors. The three plans were created for 14 tumors in 11 patients. For 13 tumors, 60 Gy in 7.5-Gy fractions was prescribed for a minimum coverage dose of 95% of the PTV (D95). The prescribed isodose line (PIL) was intended to be 60–80% of the maximum dose. Nine angles were used for the FP plans. The median D98 and D50 of the internal target volume for FP, helical-IMRT and helical-3DCRT plans were 70.4, 71.4 and 60.5 Gy, respectively (P

AIM We aimed to identify the optimal candidates for early salvage radiotherapy (SRT) among patients with biochemical recurrence (BCR) after radical prostatectomy (RP). METHODS This multi-institutional retrospective study included 371 patients treated using SRT after RP. The median (range) PSA level at BCR was 0.36 (0.10-2.00) ng/mL. The association between early SRT (ie, starting PSA level

The safety and efficacy of dose-escalated radiotherapy with intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT) remain unclear in salvage radiotherapy (SRT) after radical prostatectomy. We examined the impact of these advanced radiotherapy techniques and dose intensification on the toxicity of SRT. This multi-institutional retrospective study included 421 patients who underwent SRT at the median dose of 66 Gy in 2-Gy fractions. IMRT and IGRT were used for 225 (53%) and 321 (76%) patients, respectively. At the median follow-up of 50 months, the cumulative incidence of late grade 2 or higher gastrointestinal (GI) and genitourinary (GU) toxicities was 4.8% and 24%, respectively. Multivariate analysis revealed that the non-use of either IMRT or IGRT, or both (hazard ratio [HR] 3.1, 95% confidence interval [CI] 1.8–5.4, p p = 0.048) were associated with late GI toxicity, whereas a higher dose ≥68 Gy was the only factor associated with GU toxicities (HR 3.1, CI 1.3–7.4, p = 0.012). This study suggested that the incidence of GI toxicities can be reduced by IMRT and IGRT in SRT, whereas dose intensification may increase GU toxicity even with these advanced techniques.

Background Cutaneous adverse reactions are frequently induced by mogamulizumab. Cases of Stevens-Johnson syndrome, toxic epidermal necrolysis and severe photosensitivity related to mogamulizumab have been reported. This study investigated whether severe radiation-induced dermatitis occurred in patients undergoing radiotherapy after the administration of mogamulizumab for adult T-cell leukaemia/lymphoma. Methods We retrospectively reviewed 46 courses of radiotherapy administered to 15 consecutive patients with adult T-cell leukaemia/lymphoma (acute, n = 7; lymphoma, n = 7; smouldering, n = 1) who received mogamulizumab before or during radiotherapy at three institutions between 2012 and 2017. Results During 43 of the 46 radiotherapy courses, patients developed Grade ≤1 radiation-induced dermatitis. No patient developed Grade ≥3 radiation-induced dermatitis. No patient was prescribed ointments as prophylactic treatment for radiation-induced dermatitis. Development of radiation-induced dermatitis was not significantly associated with the number of days since the administration of mogamulizumab prior to radiotherapy (P = 0.85), frequency of administration of mogamulizumab before/during radiotherapy (P = 0.33), administration of mogamulizumab during radiotherapy (P = 0.41) or types of lesions in adult T-cell leukaemia/lymphoma cases (cutaneous vs. non-cutaneous, P = 0.74). Development of radiation-induced dermatitis was significantly related to the total cutaneous dose (mean, 31.9 Gy [95% confidence interval: 26.6-37.1 Gy] vs. 19.7 Gy [95% confidence interval: 16.2-23.2 Gy], P = 0.0004) and total prescribed dose (mean, 31.5 Gy [95% confidence interval: 26.2-36.8 Gy] vs. 18.5 Gy [95% confidence interval: 15.0-22.0 Gy], P = 0.0002). Conclusion None of the 15 patients who received moderate-dose radiotherapy developed severe radiation-induced dermatitis during the 46 courses of radiotherapy after mogamulizumab administration.

To treat local recurrence of brain metastases after gamma knife radiosurgery (GKS), we have used fractionated stereotactic radiotherapy (SRT). The purpose of this study was to evaluate the efficacy and toxicity of SRT in these patients.Fifty locally recurrent metastatic brain tumors in 47 patients were treated with SRT. The median prescribed dose of GKS was 20 Gy at the periphery. The median interval between the GKS (the last session in cases in which multiple GKS procedures were performed) and recurrence was 7.5 (range 1-33) months. Several dose-fractionation protocols were used for SRT, depending on the size and location of the tumor and previous GKS dose. The median prescribed dose of the SRT at the isocenter was 30 Gy with a median of ten fractions.Among the 50 lesions treated with SRT, 26 did not recur locally before the patient's death or the last follow-up examination, and 24 recurred locally. The median follow-up period for the surviving patients was 24 months after the first GKS procedure, and the overall survival rate was 80% at 1 year and 57% at 2 years. The median time to local re-recurrence after the SRT (16 months) was significantly longer than the median interval between the last GKS and recurrence (7.5 months; P 0.001). Only two patients developed ≥grade 2 radiation necrosis.Stereotactic radiotherapy appeared to be an effective treatment for recurrent metastatic brain tumors and yielded relatively good local control. The associated adverse events were generally acceptable.

Stereotactic body radiotherapy (SBRT) is widely used as a curative treatment option for stage I non-small-cell lung cancer, but for patients with stage I small-cell lung cancer, the role of stereotactic body radiotherapy is unclear. In this study, we retrospectively analyzed the outcomes of a subset of patients with stage I small-cell lung cancer treated with stereotactic body radiotherapy in the database of the Japanese Radiological Society-Multi-Institutional stereotactic body radiotherapy Study Group. The 43 patients treated with stereotactic body radiotherapy for stage I small-cell lung cancer between 2004 and 2012 at 11 Japanese institutions were studied: median age = 77 years; 32 (74%) males and 11 females; and 80% were medically inoperable. The clinical stage was IA in 31 and IB in 12. In all patients, the lung tumors were pathologically proven as small-cell lung cancer. A total dose of 48 to 60 Gy was administered in 4 to 8 fractions. The median biologically effective dose (α/β = 10 Gy) was 105.6 Gy. Chemotherapy and prophylactic cranial irradiation were administered in only 8 patients, respectively. The median follow-up time was 23.2 months. The 2-year overall survival, progression-free survival, and distant metastasis-free survival rates were 72.3%, 44.6%, and 47.2%, respectively. The 2-year local control was 80.2%. Regarding the patterns of failure, distant metastasis, lymph node metastasis, and local recurrence were observed in 47%, 28%, and 16% of patients, respectively. No ≥grade 3 stereotactic body radiotherapy-related toxicities were observed. Although stereotactic body radiotherapy was thus revealed to be effective for the local control of stage I small-cell lung cancer, the incidence of distant metastases was high. Further investigations of larger cohorts are needed, including analyses of the effects of combined chemotherapy.

Radiosurgery plus whole-brain radiotherapy (WBRT) has been reported to be useful for patients with ≤ 4 brain metastases (BM), but we hypothesized that similar treatment may be applicable to patients with ≥ 5 BM with or without meningeal dissemination. The purpose of this study was to evaluate the efficacy and toxicity of low-dose Gamma Knife (GK) followed by WBRT for patients with advanced BM.Major eligibility criteria for this phase II study were: (1) ≥ 5 BM with or without meningeal dissemination and (2) the largest tumor diameter ≤ 4 cm. During 2013-2016, 40 patients (13 men and 27 women) entered the study. Nineteen had meningeal dissemination. The GK dose was 12 Gy at the periphery when the longest diameter was 3-4 cm and 14 Gy when it was 3 cm. The WBRT dose to the isocenter was 30 Gy in 10 fractions, or 37.5 Gy in 15 fractions for two patients, with an expected survival of 12 months. The median number of target BM was 17.5.After GK plus WBRT for 40 patients, 31 did not develop further intracranial recurrence until death or last follow-up, whereas 9 developed recurrence. With a follow-up period up to 24 months, the overall survival rate was 36% at 12 months and median survival time was 8 months. The cumulative incidence of intracranial recurrence was 25% at 12 months. Toxicity was considered acceptable.Treatment with low-dose GK followed by WBRT for advanced-stage BM appeared to contribute to local control.

The optimal treatment for hilar or mediastinal lymph node (LN) recurrence developing after stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer remains unclear. This study evaluated 5-year results of radiotherapy in such patients in comparison with those for postoperative LN metastases. Between 2004 and 2013, 27 patients with hilar and/or mediastinal LN metastases without local recurrence and distant metastasis after SBRT (n = 14) or surgery (n = 13) were treated with definitive conventional radiotherapy. The median total dose for treating metastatic LN was 60 Gy for the post-SBRT group and 66 Gy for the post-surgery group. The median follow-up for the 5 surviving patients was 62 months. The overall survival, cause-specific survival, progression-free survival, and local control rates at 5 years after mediastinal irradiation were 14%, 45%, 21%, and 58%, respectively, for the 14 patients in the post-SBRT group. These rates were 36%, 45%, 39%, and 92%, respectively for the post-surgery group (p = 0.066, 0.64, 0.38, and 0.41, respectively). Four patients in the post-SBRT group survived 3 or more years (range 36–92 months) after mediastinal irradiation. A proportion of patients in both groups achieved long-term survival by conventional radiotherapy.

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.

The outcomes of induction chemotherapy followed by radiotherapy for hypopharyngeal carcinoma were analyzed to determine whether response to induction chemotherapy could be a useful parameter for selecting candidates for organ-preserving therapy.Forty-three patients with hypopharyngeal carcinoma were treated with definitive radiotherapy with or without concurrent chemotherapy following induction chemotherapy. The predominant induction chemotherapy regimens involved cisplatin and 5-fluorouracil with or without docetaxel. The patients that responded to the induction chemotherapy received definitive organ-preserving treatment. Patients who did not respond to induction chemotherapy were considered for surgery, but only those patients who underwent definitive radiotherapy were analyzed in this study. Conventional radiotherapy was administered in all patients. The associations between clinical parameters including age, sex, performance status (PS), tumor site, T-category, N-category, stage, the regimen of induction chemotherapy, the response to induction chemotherapy, the presence/absence of concurrent chemotherapy, overall survival (OS), and local control (LC) were analyzed.Among the surviving patients, the follow-up period ranged from 10-145 months (median: 46 months). The 3-year OS and LC rates for all 43 patients were 61% and 70%, respectively. The 3-year OS and LC rates of the responders were 73% and 81%, respectively, whereas those of the non-responders were 29% and 40%, respectively. In multivariate analysis, only PS was correlated with overall survival (p=0.03). The complication rates were acceptable in all groups.Responders to induction chemotherapy appear to be good candidates for definitive organ-preserving treatment. Chemoselection appears to aid treatment selection in patients with hypopharyngeal carcinoma.

ObjectThe Basic Score for Brain Metastases (BSBM) proposed by Lorenzoni and colleagues is one of the best grading systems for predicting survival periods after stereotactic radiosurgery (SRS) for brain metastases. However, it includes no brain factors and cannot predict neurological outcomes, such as preservation of neurological function and prevention of neurological death. Herein, the authors propose a modified BSBM, adding 4 brain factors to the original BSBM, enabling prediction of neurological outcomes, as well as of overall survival, in patients undergoing SRS.MethodsTo serve as neurological prognostic scores (NPSs), the authors scored 4 significant brain factors for both preservation of neurological function (qualitative survival) and prevention of neurological death (neurological survival) as 0 or 1 as described in the following: > 10 brain tumors = 0 or ≤ 10 = 1, total tumor volume > 15 cm3 = 0 or ≤ 15 cm3 = 1, MRI findings of localized meningeal dissemination (yes = 0 or no = 1), and neurological symptoms (yes = 0 or no = 1). According to the sum of NPSs, patients were classified into 2 subgroups: Subgroup A with a total NPS of 3 or 4 and Subgroup B with an NPS of 0, 1, or 2. The authors defined the modified BSBM according to the NPS subgroup classification applied to the original BSBM groups. The validity of this modified BSBM in 2838 consecutive patients with brain metastases treated with SRS was verified.ResultsPatients included 1868 with cancer of the lung (including 1604 with non–small cell lung cancer), 355 of the gastrointestinal tract, 305 of the breast, 176 of the urogenital tract, and 134 with other cancers. Subgroup A had 2089 patients and Subgroup B 749. Median overall survival times were 2.6 months in BSBM 0 (382 patients), 5.7 in BSBM 1 (1143), 11.4 in BSBM 2 (1011) and 21.7 in BSBM 3 (302), and pairwise differences between the BSBM groups were statistically significant (all p < 0.0001). One-year qualitative survival rates were 64.6% (modified BSBM 0A, 204 patients), 45.0% (0B, 178), 82.5% (1A, 825), 63.3% (1B, 318), 86.4% (2A, 792), 73.7% (2B, 219), 91.4% (3A, 268), and 73.5% (3B, 34). One-year neurological survival rates were 82.6% (0A), 52.4% (0B), 90.5% (1A), 78.1% (1B), 91.1% (2A), 83.2% (2B), 93.9% (3A), and 76.3% (3B), where A and B identify the subgroup. Statistically significant differences in both qualitative and neurological survivals between Subgroups A and B were detected in all BSBM groups.ConclusionsThe authors' new index, the modified BSBM, was found to be excellent for predicting neurological outcomes, independently of life expectancy, in SRS-treated patients with brain metastases.

Despite insufficient laboratory data, radiotherapy after intratumoral injection of hydrogen peroxide (H2 O2 ) 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 H2 O2 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 H2 O2 were investigated using computed tomography. The effects of H2 O2 alone and in combination with single or five-fraction irradiation were investigated using a growth delay assay. The optimal timing of H2 O2 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 H2 O2 produced 2-3 days' tumor growth delay. Tumor regrowth was slowed further when H2 O2 was injected before irradiation. The group irradiated immediately after H2 O2 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 H2 O2 . H2 O2 injection alone had modest antitumor effects. Greater tumor growth delays were demonstrated by combining irradiation and H2 O2 injection. The results of the present study could serve as a basis for evaluating results of various clinical studies on this treatment.

The aim of this study was to examine the applicability of the linear-quadratic (LQ) model to single and fractionated irradiation in EMT6 cells. First, the α/β ratio of the cells was determined from single-dose experiments, and a biologically effective dose (BED) for 20 Gy in 10 fractions (fr) was calculated. Fractional doses yielding the same BED were calculated for 1-, 2-, 3-, 4-, 5-, 7-, 15- and 20-fraction irradiation using LQ formalism, and then irradiation with these schedules was actually given. Cell survival was determined by a standard colony assay. Differences in cell survival between pairs of groups were compared by t-test. The α/β ratio of the cells was 3.18 Gy, and 20 Gy in 10 fr corresponded to a BED3.18 of 32.6 Gy. The effects of 7-, 15- and 20-fraction irradiation with a BED3.18 of 32.6 Gy were similar to those of the 10-fraction irradiation, while the effects of 1- to 5-fraction irradiation were lower. In this cell line, the LQ model was considered applicable to 7- to 20-fraction irradiation or doses per fraction of 2.57 Gy or smaller. The LQ model might be applicable in the dose range below the α/β ratio.

The aim of this study is to describe our initial experience with the VISICOIL, which is the first percutaneous fiducial marker approved for stereotactic body radiotherapy in Japan, and to evaluate its technical and clinical efficacy, and safety. Eight patients underwent this procedure under CT fluoroscopic guidance. One patient had two tumors, so the total number of procedures was nine. We evaluated the technical and clinical success rates of the procedure and the frequencies of complications. Technical success was defined as when the fiducial marker could be placed at the target site, and clinical success was defined as when stereotactic body radiotherapy could be performed without the marker dropping out of position. The technical success rate was 78% (7/9). In one of the two failed cases, we aimed to place the marker inside the tumor, but misplaced it beside the tumor. In the other failed case, we successfully placed the marker beside the tumor as planned; however, the marker migrated to near the pleura after the patient stopped holding their breath. None of the markers dropped out of place, so the clinical success rate was 100% (9/9). The complication rates were as follows: pneumothorax: 56% (5/9), pneumothorax necessitating chest tube placement: 44% (4/9), focal intrapulmonary hemorrhaging: 67% (6/9), hemoptysis: 11% (1/9), mild hemothorax 11% (1/9), air embolism 0% (0/9), and death 0% (0/9). In conclusion, this new percutaneous fiducial marker appears to be useful for stereotactic body radiotherapy due to its good stability.

To investigate the possible influences of various factors on tumor response to radiation, regression speeds and long‐term local control rates of primary adenocarcinoma and squamous cell carcinoma of the lung after stereotactic body radiotherapy were evaluated. Ninety‐one patients (65 men and 26 women) with a median age of 76 years were serially examined using computed tomography at 2, 4 and 6 months after treatment. Tumor histology was adenocarcinoma in 62 patients and squamous cell carcinoma in 29 patients. The prescribed dose was 48 Gy in four fractions given twice a week for T1 tumors (≤3 cm) and 52 Gy in four fractions given twice a week for T2 tumors (3–5 cm). Tumor shrinkage speed and 3‐year local control rates were similar between T1 and T2 tumors and between patients with normal pulmonary function and those with impaired function. Squamous cell carcinomas shrank faster than adenocarcinomas at 2 and 4 months after radiation, but mean relative tumor size at 6 months and local control rates at 3 years did not differ significantly between the two histologies. Tumors in patients with a higher hemoglobin level tended to shrink faster but the control rates were not different. It is concluded that, although squamous cell carcinoma shrinks faster than adenocarcinoma, the two types of lung cancer are of similar radiosensitivity in terms of long‐term control rates. Radiosensitivity should not be evaluated by early tumor response. (Cancer Sci 2013; 104: 130–134)

Pretreatment pulmonary interstitial change (PIC) has been indicated as a risk factor of severe radiation pneumonitis (RP) following stereotactic body radiation therapy (SBRT) for early-stage lung cancer, but details of its true effect remain unclear. This study aims to evaluate treatment outcomes of SBRT for stage I non-small cell lung cancer in patients with PIC. A total of 242 patients are included in this study (88% male). The median age is 77 years (range, 55&ndash, 92 years). A total dose of 40&ndash, 70 Gy is administered in 4 to 10 fractions during a 4-to-25 day period. One, two, and three-year overall survival (OS) rates are 82.1%, 57.1%, and 42.6%, respectively. Fatal RP is identified in 6.9% of all patients. The percent vital capacity &lt, 70%, mean percentage normal lung volume receiving more than 20 Gy (&gt, 10%), performance status of 2&ndash, 4, presence of squamous cell carcinoma, clinical T2 stage, regular use of steroid before SBRT, and percentage predicting forced expiratory volume in one second (&lt, 70%) are associated with worse prognoses for OS. Our results indicate that fatal RP frequently occurs after SBRT for stage I lung cancer in patients with PIC.

Background After stereotactic body radiotherapy (SBRT) to the lung, radiation pneumonitis and fibrotic changes often develop, and the tumor shadow usually becomes indistinguishable from the fibrotic shadow. Occasionally, however, a residual mass in patients with no or mild radiation pneumonitis will be observed on serial computed tomography (CT) scans. The purpose of the present study was to evaluate the fate of such residual masses and, if possible, to determine the types of tumor at increased risk of local recurrence. Patients and Methods A total of 50 patients (underlying disease: primary lung cancer in 45, local recurrence in 2, and metastasis in 3) were selected because they had been followed up for > 2 years or until death and had observable CT changes and measurable tumor size for > 1 year, regardless of the influence of radiation pneumonitis. The patients' outcomes were compared according to various patient and tumor characteristics, including the presence and absence of emphysema, tumor size, and tumor shrinkage rate. The median follow-up period was 52 months. Results Of the 50 patients, only 8 developed local recurrence. The local control rate was 81% at 3 years and 73% at 5 years. The local control rates were similar between patients with a high tumor shrinkage rate and those with a low rate. The patients with emphysema exhibited a lower local control rate. Conclusion The persistence of lung masses for > 1 year after SBRT is not necessarily indicative of an increased risk of local recurrence. A low tumor shrinkage rate also was not predictive of recurrence.

In stereotactic body radiotherapy (SBRT), high doses per fraction are usually used and the dose delivery pattern is different from that of conventional radiation. The daily dose is usually given intermittently over a longer time compared to conventional radiotherapy. During prolonged radiation delivery, sublethal damage repair takes place, leading to the decreased effect of radiation. In in vivo tumors, however, this decrease in effect may be counterbalanced by rapid reoxygenation. Another issue related to high-dose-per-fraction radiotherapy is the mathematical model for dose evaluation and conversion. It has been suggested that the linear-quadratic (LQ) model and biologically effective dose (BED) are not applicable to high doses per fraction. The LQ model overestimates the effect of high fractional doses of radiation. BED is particularly incorrect when used for tumor responses in vivo, since it does not take reoxygenation into account. Correction of the errors associated with the use of the LQ model is necessary when it is used for SBRT. It has been reported that high fractional doses have effects against tumor vasculature and enhance host immunity, leading to increased antitumor effects. These observations, however, need to be confirmed in future studies. Since radioresistance of hypoxic tumor cells is more problematic in SBRT, trials of hypoxic cell sensitizers are encouraged.

Background: The overall treatment time of stereotactic body radiotherapy (SBRT) for non-small-cell lung cancer is usually 3 to over 10 days. If it is longer than 7 days, tumor volume expansion during SBRT may jeopardize the target dose coverage. In this study, volume change of stage I NSCLC during SBRT was investigated. Methods: Fifty patients undergoing 4-fraction SBRT with a total dose of 48 Gy (n= 36) or 52 Gy (n= 14) were analyzed. CT was taken for registration at the first and third SBRT sessions with an interval of 7 days in all patients. Patient age was 29–87 years (median, 77), and 39 were men. Histology was adenocarcinoma in 28, squamous cell carcinoma in 17, and others in 5. According to the UICC 7th classification, T-stage was T1a in 9 patients, T1b in 27, and T2a in 14. Tumor volumes on the first and 8th days were determined on CT images taken during the exhalation phase, by importing the data into the Dr. View/LINAX image analysis system. After determining the optimal threshold for distinguishing tumor from pulmonary parenchyma, the region above −250 HU was automatically extracted and the tumor volumes were calculated. Results: The median tumor volume was 7.3 ml (range, 0.5-35.7) on day 1 and 7.5 ml (range, 0.5-35.7) on day 8. Volume increase of over 10% was observed in 16 cases (32%); increases by >10 to ≤20%, >20 to ≤30%, and >30% were observed in 9, 5, and 2 cases, respectively. The increase in the estimated tumor diameter was over 2 mm in 3 cases and 1– 2m m in 6. Ad ecrease of 10% or more was seen in 3c ases. Among the 16 tumors showing av olume increase of over 10%, T-stage was T1a in 2 patients, T1b in 9, and T2a in 5. Histology was adenocarcinoma in 10 patients, squamous cell carcinoma in 5, and others in 1. Conclusions: Volume expansion >10% was observed in 32% of the tumors during the first week of SBRT, possibly due to edema or sustained tumor progression. When planning SBRT, this phenomenon should be taken into account.

The authors conducted validity testing of the 5 major reported indices for radiosurgically treated brain metastases- the original Radiation Therapy Oncology Group's Recursive Partitioning Analysis (RPA), the Score Index for Radiosurgery in Brain Metastases (SIR), the Basic Score for Brain Metastases (BSBM), the Graded Prognostic Assessment (GPA), and the subclassification of RPA Class II proposed by Yamamoto-in nearly 2500 cases treated with Gamma Knife surgery (GKS), focusing on the preservation of neurological function as well as the traditional endpoint of overall survival.The authors analyzed data from 2445 cases treated with GKS by the first author (T.S.), the primary surgeon. The patient group consisted of 1716 patients treated between January 1998 and March 2008 (the Chiba series) and 729 patients treated between April 2008 and December 2011 (the Tokyo series). The interval from the date of GKS until the date of the patient's death (overall survival) and impaired activities of daily living (qualitative survival) were calculated using the Kaplan-Meier method, while the absolute risk for two adjacent classes of each grading system and both hazard ratios and 95% confidence intervals were estimated using the Cox proportional hazards model.For overall survival, there were highly statistically significant differences between each two adjacent patient groups characterized by class or score (all p values0.001), except for GPA Scores 3.5-4.0 and 3.0. The SIR showed the best statistical results for predicting preservation of neurological function. Although no other grading systems yielded statistically significant differences in qualitative survival, the BSBM and the modified RPA appeared to be better than the original RPA and GPA.The modified RPA subclassification, proposed by Yamamoto, is well balanced in scoring simplicity with respect to case number distribution and statistical results for overall survival. However, a new or revised grading system is necessary for predicting qualitative survival and for selecting the optimal treatment for patients with brain metastasis treated by GKS.

BACKGROUND: The most common regimen of stereotactic body radiotherapy (SBRT) for stage I nonsmall cell lung cancer in Japan is 48 grays (Gy) in 4 fractions over 4 days. Radiobiologically, however, higher doses are necessary to control larger tumors, and interfraction intervals should be >24 hours to take advantage of reoxygenation. In this study, the authors tested the following regimen: For tumors that measured 3.0 cm in greatest dimension, radiation doses of 44 Gy, 48 Gy, and 52 Gy, respectively, were given in 4 fractions with interfraction intervals of ≥3 days. METHODS: Among 180 patients with histologically proven disease who entered the study, 120 were medically inoperable, and 60 were operable. The median patient age was 77 years (range, 29-92 years). SBRT was performed with 6-megavolt photons using 4 noncoplanar beams and 3 coplanar beams. Isocenter doses of 44 Gy, 48 Gy, and 52 Gy were received by 4 patients, 124 patients, and 52 patients, respectively. RESULTS: The overall survival rate for all 180 patients was 69% at 3 years and 52% at 5 years. The 3-year survival rate was 74% for operable patients and 59% for medically inoperable patients (P = .080). The 3-year local control rate was 86% for tumors ≤3 cm (44/48 Gy) and 73% for tumors >3 cm (52 Gy; P = .050). Grade ≥2 radiation pneumonitis developed in 13% of patients (10% of the 44-Gy/48-Gy group and 21% of the 52-Gy group; P = .056). All other grade 2 toxicities developed in

Materials/Methods: The charts of patients treated for single brain metastases from September 2005 to January 2012 were retrospectively reviewed. Cases were included if the size of themetastasis was greater than 2cm.Fortyone cases were identified. The median tumor size was 3.6cm (range, 2.3-7.5). All patients underwent microsurgical resection of their brain metastasis followed by WBRT and a 10 Gy radiosurgery boost to the surgical cavity. In 84% of cases, the WBRT schedule was 30 Gy in 10 fractions (range: 20 Gy in 5 to 37.5 Gy in 15). The radiosurgery was delivered using a variety of techniques, typically prescribed homogeneously (median prescription isodose 82%) at a 2mm margin from the cavity. Results: Non-small cell lung cancer was the diagnosis in 59%, breast in 17%. Median age was 59. The majority (65%) were in RTOG RPA Class II (10% Class I, 25% Class III). Average DS-GPA for the lung cancer patients was 2.67. Median overall survival was 17.6 months. The 5-year actuarial survival was 30.1%. Crude local control was 93%, 2-year actuarial local control was 84%. With a median follow-up of 22 months in living patients, the crude rate of new metastases (including leptomeningeal disease) was 15%. Three patients suffered symptomatic radiation necrosis. Conclusions: Tri-modality therapy with surgery, WBRT, and cavity radiosurgery appears safe and provided durable CNS control in a population where long-term survivors are common. Author Disclosure: D. Roberge: None. V. Panet-Raymond: None. K. Petrecca: None. L. Souhami: None.