Simultaneous boost radiotherapy versus conventional dose radiotherapy for patients with newly diagnosed glioblastoma: a multi-institutional analysis.

We compared survival outcomes of high-dose concomitant boost radiotherapy (HDCBRT) and conventional dose radiotherapy (CRT) for newly diagnosed glioblastoma (GB). Patients treated with intensity-modulated radiation therapy for newly diagnosed GB were included. In HDCBRT, specific targets received 69, 60, and 51 Gy in 30 fractions, while 60 Gy in 30 fractions was administered with a standard radiotherapy method in CRT. Overall survival (OS) and progression-free survival (PFS) were compared using the Log-rank test, followed by multivariate Cox analysis. The inverse probability of treatment weighting (IPTW) method was also applied to each analysis. Among 102 eligible patients, 45 received HDCBRT and 57 received CRT. With a median follow-up of 16 months, the median survival times of OS and PFS were 21 and 9 months, respectively. No significant differences were observed in OS or PFS in the Kaplan-Meier analyses. In the multivariate analysis, HDCBRT correlated with improved OS (hazard ratio, 0.49; 95% confidence interval, 0.27-0.90; P = 0.021), and this result remained consistent after IPTW adjustments (P = 0.028). Conversely, dose suppression due to the proximity of normal tissues and IMRT field correlated with worse OS and PFS (P = 0.008 and 0.049, respectively). A prospective study with a stricter protocol is warranted to validate the efficacy of HDCBRT for GB.

Late genitourinary toxicity in salvage radiotherapy for prostate cancer after radical prostatectomy: impact of daily fraction doses.

OBJECTIVE: To evaluate the impact of daily fraction doses on late genitourinary (GU) toxicity after salvage radiotherapy (SRT) for prostate cancer. METHODS: This multi-institutional retrospective study included 212 patients who underwent SRT between 2008 and 2018. All patients received image-guided intensity-modulated SRT at a median dose of 67.2 Gy in 1.8-2.3 Gy/fraction. The cumulative rates of late grade ≥2 GU and gastrointestinal (GI) toxicities were compared using Gray test, stratified by the ≤2.0 Gy/fraction (n = 137) and ≥2.1 Gy/fraction groups (n = 75), followed by multivariate analyses. The total dose was represented as an equivalent dose in 2-Gy fractions (EQD2) with α/ß = 3 Gy. RESULTS: After a median follow-up of 63 months, the cumulative rates of 5-year late grade ≥2 GU and GI toxicities were 14% and 2.5%, respectively. The cumulative rates of 5-year late grade ≥2 GU toxicity in the ≥2.1 Gy/fraction and ≤2.0 Gy/fraction groups were 22% and 10%, respectively (P = .020). In the multivariate analysis, ≥2.1 Gy/fraction was still associated with an increased risk of late grade ≥2 GU toxicity (hazard ratio, 2.37; 95% confidence interval, 1.12-4.99; P = .023), while the total dose was not significant. CONCLUSION: The present results showed that ≥2.1 Gy/fraction resulted in a higher incidence of late grade ≥2 GU toxicity in SRT. ADVANCES IN KNOWLEDGE: The impact of fraction doses on late GU toxicity after SRT remains unknown. The results suggest that higher fraction doses may increase the risk of late GU toxicity in SRT.

Impact of radiation doses on clinical relapse of biochemically recurrent prostate cancer after prostatectomy.

The relationship between radiation doses and clinical relapse in patients receiving salvage radiotherapy (SRT) for biochemical recurrence (BCR) after radical prostatectomy (RP) remains unclear. We identified 292 eligible patients treated with SRT between 2005 and 2018 at 15 institutions. Clinical relapse-free survival (cRFS) between the ≥ 66 Gy (n = 226) and < 66 Gy groups (n = 66) were compared using the Log-rank test, followed by univariate and multivariate analyses and a subgroup analysis. After a median follow-up of 73 months, 6-year biochemical relapse-free survival, cRFS, cancer-specific survival, and overall survival rates were 58, 92, 98, and 94%, respectively. Six-year cRFS rates in the ≥ 66 Gy and < 66 Gy groups were 94 and 87%, respectively (p = 0.022). The multivariate analysis revealed that Gleason score ≥ 8, seminal vesicle involvement, PSA at BCR after RP ≥ 0.5 ng/ml, and a dose < 66 Gy correlated with clinical relapse (p = 0.015, 0.012, 0.024, and 0.0018, respectively). The subgroup analysis showed the consistent benefit of a dose ≥ 66 Gy in patients across most subgroups. Doses ≥ 66 Gy were found to significantly, albeit borderline, increase the risk of late grade ≥ 2 GU toxicity compared to doses < 66 Gy (14% vs. 3.2%, p = 0.055). This large multi-institutional retrospective study demonstrated that a higher SRT dose (≥ 66 Gy) resulted in superior cRFS.

Clinical Outcomes of Radiation Therapy for Choroidal Metastases and A Literature Review.

INTRODUCTION: Radiation therapy (RT) for choroidal metastasis (CM) aims to preserve vision and achieve local control (LC), thereby maintaining quality of life. The present study reports the clinical outcomes of RT for CM and reviews the literature. METHODS: We retrospectively collected data on 11 patients with CM; their primary tumors were breast cancer (n=3), lung cancer (n=3), leukemia (n=2), lymphoma (n=2), and gastric cancer (n=1). Four patients had bilateral CM. The median radiation dose was 39 Gy in 13 fractions (range, 20-50 Gy in 10-25 fractions). We investigated changes in visual acuity, tumor responses, morbidities, LC, and overall survival (OS). A systematic review of literature published between 1990 and 2020 was performed using the PubMed database. RESULTS: One, 1, and 6 patients had improved, stabilized, and worse visual acuity, respectively (data missing for 3 patients). Nevertheless, eight patients considered their visual acuity to have improved or remained the same after RT. Among 15 lesions in 11 patients, complete and partial responses were observed in 2 and 6, respectively (data missing for 7 lesions in 4 patients). Three-year LC and OS rates were 100 and 32%, respectively. Grade ≥ 3 morbidities were not observed. In the literature review, the most common primary cancer was breast cancer followed by lung cancer. Improvements in or the stabilization of visual acuity was observed in 80% of patients (range, 47-100), and the median survival time was 11 months (range, 4.9-23). CONCLUSION: RT is an efficient and safe palliative treatment for CM without severe toxicity.

Real-World Results of Stereotactic Body Radiotherapy for 399 Medically Operable Patients with Stage I Histology-Proven Non-Small Cell Lung Cancer.

Surgery is the standard treatment for stage I non-small cell lung cancer (NSCLC); however, no clear randomized trial demonstrates its superiority to stereotactic body radiotherapy (SBRT) regarding survival. We aimed to retrospectively evaluate the treatment outcomes of SBRT in operable patients with stage I NSCLC using a large Japanese multi-institutional database to show real-world outcome. Exactly 399 patients (median age 75 years; 262 males and 137 females) with stage I (IA 292, IB 107) histologically proven NSCLC (adenocarcinoma 267, squamous cell carcinoma 96, others 36) treated at 20 institutions were reviewed. SBRT was prescribed at a total dose of 48-70 Gy in 4-10 fractions. The median follow-up period was 38 months. Local progression-free survival rates were 84.2% in all patients and 86.1% in the T1, 78.6% in T2, 89.2% in adenocarcinoma, and 70.5% in squamous cell subgroups. Overall 3-year survival rates were 77.0% in all patients: 90.7% in females, 69.6% in males, and 41.2% in patients with pulmonary interstitial changes. Fatal radiation pneumonitis was observed in two patients, all of whom had pulmonary interstitial changes. This real-world evidence will be useful in shared decision-making for optimal treatment, including SBRT for operable stage I NSCLC, particularly in older patients.

Comparative Analysis of Photon Stereotactic Radiotherapy and Carbon-Ion Radiotherapy for Elderly Patients with Stage I Non-Small-Cell Lung Cancer: A Multicenter Retrospective Study.

The emergence of an aging society and technological advances have made radiotherapy, especially stereotactic body radiotherapy (SBRT), a common alternative to surgery for elderly patients with early stage non-small-cell lung cancer (NSCLC). Carbon-ion radiotherapy (CIRT) is also an attractive treatment option with potentially lower toxicity for elderly patients with comorbidities. We compared the clinical outcomes of the two modalities using Japanese multicenter data. SBRT (n = 420) and single-fraction CIRT (n = 70) data for patients with stage I NSCLC from 20 centers were retrospectively analyzed. Contiguous patients ≥ 80 years of age were enrolled, and overall survival (OS), disease-specific survival (DSS), local control (LC), and adverse event rates were compared. The median age was 83 years in both groups and the median follow-up periods were 28.5 and 42.7 months for SBRT and CIRT, respectively. The 3-year OS, DSS, and LC rates were 76.0% vs. 72.3% (p = 0.21), 87.5% vs. 81.6% (p = 0.46), and 79.2% vs. 78.2% (p = 0.87), respectively, for the SBRT vs. CIRT groups. Regarding toxicity, 2.9% of the SBRT group developed grade ≥ 3 radiation pneumonitis, whereas none of the CIRT group developed grade ≥ 2 radiation pneumonitis. SBRT and CIRT in elderly patients showed similar survival and LC rates, although CIRT was associated with less severe radiation pneumonitis.

Clinical Outcomes of Radiation Therapy for Angiosarcoma of the Scalp and Face: A Multi-Institutional Observational Study.

Angiosarcoma of the scalp and face (ASF) is a rare, aggressive tumor often treated with multimodal therapy, including radiation therapy (RT). This study assessed RT outcomes for ASF and identified prognostic factors. Data from 68 non-metastatic ASF patients undergoing RT with or without other therapies were analyzed. Median radiation dose was 66 Gy in 33 fractions (interquartile range (IQR) 60-70 Gy in 28-35 fractions). Local control (LC), progression-free survival (PFS), and overall survival (OS) rates were calculated using Kaplan-Meier analysis. Multivariate analyses and adverse event evaluation were conducted. Median patient age was 75 years (IQR 71-80 years), with a median follow-up of 17 months (IQR 11-42 months). One-/three-year LC rates were 57/37%, PFS rates were 44/22%, and OS rates were 81/44%. Multivariate analyses showed that an equivalent dose in a 2 Gy fraction (EQD2) >66 Gy correlated with improved LC (HR 2.35, 95% CI 1.03-5.32, p = 0.041). Combining chemotherapy (HR 2.43, 95% CI 1.08-5.46, p = 0.032) or surgery (HR 2.41, 95% CI 1.03-5.59, p = 0.041) improved PFS. No factors influenced OS. Late grade 3+ toxicities occurred in 1%, with one patient developing a grade 4 skin ulcer. These findings suggest that EQD2 > 66 Gy and combining chemotherapy or surgery can enhance LC or PFS in ASF. Further prospective studies are needed to determine the optimal treatment strategy for this rare malignancy, particularly in elderly patients.

Changes in pulmonary function and their correlation with dose-volume parameters in patients undergoing stereotactic body radiotherapy for lung cancer.

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 < 0.01) and mean forced expiratory volume in 1 s (FEV1) decreased from 1.80 to 1.72 L (P < 0.01). Planning target volume (PTV) was correlated with changes in FVC. Changes in percent predicted FVC were correlated with %V5Gy (% of lung volume receiving > 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.

Stereotactic body radiotherapy using the forward-planned static-port tomotherapy for lung cancer: a novel planning technique with the newly-developed mode.

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 < 0.001), and 77.7, 75.7 and 62.3 Gy, respectively (P < 0.0001). The median PIL and the lung volume receiving ≥20 Gy (V20) were 73.4, 73.4 and 94.3%, respectively (P < 0.0001), and 4.7, 4.0 and 5.7%, respectively (P < 0.0001). These parameters were not significantly different between the FP and helical-IMRT plans. The median beam-on times were 238.6, 418.9 and 197.1 s, respectively (P < 0.0001). The FP plans reduced the beam-on time by 43% compared to the helical-IMRT plans. The dose distribution of the FP plans was comparable to that of the helical-IMRT plans. The helical-3DCRT plans could not adjust PIL to be 60-80%.

Early salvage radiotherapy in patients with biochemical recurrence after radical prostatectomy: Its impact and optimal candidate.

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 < 0.50) and BCR after SRT was tested in each subgroup according to our own risk stratification. RESULTS: The median follow-up time was 51 months. By multivariate analysis, pT3b, Gleason score ≥ 8, negative surgical margins, PSA doubling time < 6 months, and non-early SRT were associated with BCR after SRT. Patients were stratified by four risk factors other than non-early SRT: (1) low risk (0 risk factor), (2) intermediate risk (1 risk factor), and (3) high risk (≥2 risk factors). The BCR-free survival was higher in the early SRT group than the nonearly SRT group in the high-risk subgroup (P = 0.020), whereas that was similar between two groups in the low-risk and intermediate-risk subgroups (P = .79 and .18, respectively). Multivariate analysis revealed that early SRT was beneficial for the high-risk subgroup (P = .032), whereas early SRT was not associated with improved outcomes in the low-risk and intermediate-risk subgroups (P = .92 and 1.0, respectively). CONCLUSIONS: This study suggested that early SRT seemed to contribute to better biochemical control for patients with more adverse features, whereas no benefit was observed in men with no adverse features.

Definitive chemoradiotherapy for squamous cell carcinoma of the esophagus: outcomes for borderline-resectable disease.

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 < 0.001), with 3-year survival of 70% and 8%, respectively. The overall survival for complete response patients with borderline-resectable disease was encouraging. Further investigation to find a subgroup fit for esophagus-preserving treatment is warranted.

Stereotactic body radiotherapy in patients with lung tumors composed of mainly ground-glass opacity.

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 <50% in diameter of the tumor and no metastases were studied. Concerning histology, 32 tumors were adenocarcinoma, 1 was squamous cell carcinoma, 2 were unclassified carcinoma and 49 cases were histology-unproven but increased in size or had a positive finding in 18F-FDG positron emission tomography (PET) examination. The median tumor size was 20 mm (range, 10-41 mm). All of the patients were treated with SBRT, and the total prescribed dose at the isocenter ranged between 48 Gy in four fractions and 84 Gy in ten fractions. Median follow-up duration was 33 months. No patient had local failure nor regional lymph node failure. The 3-year rate of distant failure was 2.6%. Two patients who experienced distant metastases had a past surgical history of initial lung cancer before SBRT. The rates of cause-specific and overall survival at 3 years were 98.2 and 94.6%, respectively. Treatment-related adverse events of ≥grade 4 were not reported. Although more cases and longer follow-ups are mandatory, SBRT may be one of the radical treatment options for patients with GGN.

Radiotherapy alone for stage IE ocular adnexal mucosa-associated lymphoid tissue lymphomas: long-term results.

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.

Impact of advanced radiotherapy techniques and dose intensification on toxicity of salvage radiotherapy after radical prostatectomy.

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 < 0.001) and use of whole-pelvic radiotherapy (HR 7.6, CI 1.0-56, 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.

Low-dose Gamma Knife radiosurgery plus whole-brain radiation therapy for patients with 5 or more brain metastases with or without meningeal dissemination.

PURPOSE/OBJECTIVE(S): 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. MATERIALS/METHODS: 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. RESULTS: 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. CONCLUSION: Treatment with low-dose GK followed by WBRT for advanced-stage BM appeared to contribute to local control.

Radiation-induced dermatitis after administration of mogamulizumab for adult T-cell leukaemia/lymphoma: a multi-institutional retrospective study.

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.

Definitive radiotherapy for hilar and/or mediastinal lymph node metastases after stereotactic body radiotherapy or surgery for stage I non-small cell lung cancer: 5-year results.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: A proportion of patients in both groups achieved long-term survival by conventional radiotherapy.

Stereotactic Body Radiation Therapy for Patients with Pulmonary Interstitial Change: High Incidence of Fatal Radiation Pneumonitis in a Retrospective Multi-Institutional Study.

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, 55⁻92 years). A total dose of 40⁻70 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 <70%, mean percentage normal lung volume receiving more than 20 Gy (>10%), performance status of 2⁻4, presence of squamous cell carcinoma, clinical T2 stage, regular use of steroid before SBRT, and percentage predicting forced expiratory volume in one second (<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.

Clinical Outcomes of Stereotactic Body Radiotherapy for Patients With Stage I Small-Cell Lung Cancer: Analysis of a Subset of the Japanese Radiological Society Multi-Institutional SBRT Study Group Database.

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/ß = 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.

Stereotactic body radiotherapy for stage I non-small-cell lung cancer using higher doses for larger tumors: results of the second study.

BACKGROUND: Efficacy 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. METHODS: We 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. RESULTS: The 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%. CONCLUSIONS: Our 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.