Age-related changes in static balance in older women aged in their early sixties to their late eighties: different aging patterns in the anterior-posterior and mediolateral directions.

Objective: The aim of this study was to cross-sectionally investigate how static balance changes throughout the aging process in older women aged from their early sixties to their late eighties. Methods: Forty-six older women (aged 62-89 years) were requested to stand barefoot and quietly on a force platform for 30 s with their eyes either open or closed. During the trials, the position of the center of foot pressure (CoP) and the acceleration of the body's center of mass (ACC) were measured. The root mean square (RMS) of the CoP and ACC values was calculated to evaluate the amplitude of postural sway and the level of regulatory activity, respectively. The mean power frequency of the ACC was also calculated to represent the temporal characteristics of regulatory activity. Results: In the anterior-posterior direction, there was no significant relationship between the RMS of CoP and the participants' age, whereas the RMS of ACC significantly increased with increasing age. In the mediolateral direction, however, the RMS of CoP significantly increased with increasing age, whereas the RMS of ACC did not change with age. The mean power frequency of ACC did not exhibit any age-related change in either the anterior-posterior or the mediolateral direction. Conclusion: The results indicate that static balance in older women aged in their early sixties to their late eighties exhibits distinctly contrasting aging patterns between the anterior-posterior and mediolateral directions. To prevent falls in older women, it is necessary to elucidate the physiological mechanisms responsible for the increase in mediolateral sway that occurs throughout old age.

Complete response and long­term survival after stereotactic body radiotherapy in a patient with liver metastasis from α­fetoprotein­producing gastric cancer: A case report.

α-Fetoprotein (AFP)-producing gastric carcinoma (GC) (AFPGC) is a special subtype of GC that is clinically characterized by a high incidence of liver metastasis and poor prognosis. The present study reported the case of a patient with AFPGC who showed complete response (CR) after stereotactic body radiotherapy (SBRT) for liver metastasis. A 76-year-old male patient underwent total gastrectomy with D2 lymph node dissection for GC. The excised tumor was diagnosed as AFPGC due to the patient's high serum AFP level (3,763 ng/ml) and AFP expression on immunohistochemistry. The patient was diagnosed with liver metastasis two months after the surgery. 18F-fluorodeoxyglucose positron emission tomography indicated that the metastasis was a single recurrent focus. Although the patient underwent seven cycles of chemotherapy with S-1-based regimens, the metastatic tumor showed only a minor response despite the decrease in serum AFP levels. To realize high-quality disease control, SBRT was performed on the liver tumor (total dose of 48 Gy in four fractions). The metastasis showed a significant response two weeks after the completion of SBRT and CR two years later. CR was sustained and the patient survived with no evidence of recurrence 62 months after the diagnosis of liver metastasis. Literature data on the efficacy of radiotherapy for liver metastasis from AFPGC remain scarce. The present case report suggests that SBRT has high efficacy for oligometastatic diseases and may be included as an indication for the treatment of liver metastasis from AFPGC.

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.

Long-Term Follow-up of a Randomized Controlled Trial on Accelerated Radiation Therapy Versus Standard Fractionated Radiation Therapy for Early Glottic Cancer (JCOG0701A3).

PURPOSE: We previously reported the primary results of JCOG0701, a randomized, multicenter, phase 3, noninferiority trial comparing accelerated fractionation (Ax) to standard fractionation (SF) for early glottic cancer. In the primary results, although the similar efficacy of 3-year progression-free survival and toxicity of Ax compared with SF was observed, the noninferiority of Ax was not confirmed statistically. To evaluate the long-term follow-up results of JCOG0701, we conducted JCOG0701A3 as an ancillary study of JCOG0701. METHODS AND MATERIALS: In JCOG0701, 370 patients were randomly assigned to receive SF of 66 to 70 Gy (33-35 fractions; n = 184) or Ax of 60 to 64.8 Gy (25-27 fractions; n = 186). The data cutoff date for this analysis was in June 2020. Overall survival, progression-free survival, and late adverse events including central nervous system ischemia were analyzed. RESULTS: With a median follow-up period of 7.1 years (range, 0.1-12.4), progression-free survival of the SF and Ax arms were 76.2% and 78.2% at 5 years and 72.7% and 74.8% at 7 years (P = .44). OS of the SF and Ax arms were 92.7% and 89.6% at 5 years and 90.8% and 86.5% at 7 years (P = .92). Among 366 patients with a protocol treatment, the cumulative incidence of late adverse events of the SF and Ax arms were 11.9% and 7.4% at 8 years (hazard ratio, 0.53; 95% CI, 0.28-1.01; P = .06). Central nervous system ischemia of grade 2 or higher was observed in 4.1% for the SF arm and 1.1% for the Ax arm (P = .098). CONCLUSIONS: After long-term follow-up, Ax showed comparable efficacy to SF and a tendency for better safety. Ax may be suitable for early glottic cancer because of its convenience in minimizing treatment time, cost, and labor.

Multicenter retrospective study of stereotactic body radiotherapy for patients with previously untreated initial small hepatocellular carcinoma.

AIM: We aimed to verify the therapeutic efficacy and safety of stereotactic body radiotherapy (SBRT) for previously untreated initial small hepatocellular carcinoma (HCC) in a multicenter, retrospective study. METHODS: Patients who underwent SBRT for HCC at the Japanese Society of Clinical Oncology (JCOG) member hospitals in Japan between July 2013 and December 2017 and met the following eligibility criteria were included: (1) initial HCC; (2) ≤3 nodules, ≤5 cm in diameter; (3) Child-Pugh score of A or B; and (4) unsuitability for or refusal of standard treatment. We analyzed the overall survival, recurrence-free survival, and cumulative incidence of local recurrence rate, and adverse events directly related to SBRT. RESULTS: Seventy-three patients with 79 lesions from 14 hospitals were analyzed. The median age was 77 years (range: 50-89 years), and the median tumor size was 23 mm (range: 6-50 mm). The median radiation dose was 40 Gy (range: 35-60 Gy) in five fractions (range: 4-8). The median follow-up period was 45 months (range: 0-103 months). The 3-year overall survival, recurrence-free survival, and cumulative incidence of local recurrence rates were 69.9% (95% CI: 58.7%-81%), 57.9% (95% CI: 45.2%-70.5%), and 20.0% (95% CI: 11.2%-30.5%), respectively. Four cases (5.5%) of adverse events of grade 3 or higher were reported: three cases of grade 3 and one case of grade 4 (duodenal ulcer). No grade 5 toxicities were observed. CONCLUSION: SBRT is a promising treatment modality, particularly for small HCCs, as they are not suitable for standard treatment.

Reduced-dose WBRT combined with SRS for 1-4 brain metastases aiming at minimizing neurocognitive function deterioration without compromising brain tumor control.

Background and purpose: To minimize cognitive decline without increasing brain tumor recurrence (BTR) by reduced-dose whole-brain radiotherapy (RD-WBRT) (25 Gy, 10 fractions) + stereotactic radiosurgery (SRS) in patients with ≤ 4 brain metastases. Materials and methods: Eligible patients with ≤ 4 brain metastases on contrast-enhanced MRI and Karnofsky Performance Status ≥ 70. The primary endpoint was the non-inferiority of BTR at distant sites in the brain (BTR-distant)-free survival at 6 months compared to that of the standard dose (SD)-WBRT (30 Gy, 10 fractions) + SRS arm in a randomized clinical trial (JROSG99-1) of SRS with/without SD-WBRT. Secondary endpoints included BTR at any brain sites (BTR-all) and neurocognitive function assessed by a six-test standardized battery. Results: Forty patients from seven institutions were enrolled (median age 69 years). The primary tumor site was a lung in 28 patients; 20 patients had a solitary brain metastasis. The median survival time was 19.0 months (95 %CI: 13.8 %-27.5 %). The BTR-distant-free survival at 6 months was 76.9 % (59.5 %-87.7 %), which is comparable to that of historical control although predetermined non-inferiority (>71 %) could not be confirmed (p = 0.16). The cumulative incidence of BTR-all at 6 months accounting for the competing risk of death was 23.0 % (11.4-37.1), which was not worse than that of historical control (p = 0.774). The frequency of the cumulative incidence of persistent cognitive decline at 6 months was 48.6 % under the [>2.0 SD in ≥ 1 test] definition. Conclusions: RD-WBRT may yield comparable intracranial tumor control when combined with SRS, and may reduce the risk of neurocognitive decline compared to that after SD-WBRT.

Evaluation of breast cosmetic changes with a computer-software; the breast cancer conservative treatment cosmetic results (BCCT. core) in hypofractionated whole breast irradiation after breast-conserving surgery-supplementary analysis of multicenter single-arm confirmatory trial: JCOG0906.

BACKGROUND: A good cosmetic outcome has been defined as an important endpoint in breast-conserving therapy (BCT). Various evaluation methods have been studied, but the optimal method has yet to be identified. The present supplementary analysis of JCOG0906 focused on comparing evaluation methods for breast cosmetic outcomes following hypofractionated whole breast irradiation (HFWBI) to examine whether a computer-software (the Breast Cancer Conservative Treatment cosmetic results [BCCT. core])-based program evaluation (CE) can be used for Asian women in clinical trials of BCT. METHODS: Of 306 women, 292 underwent institutional evaluation (IE) for breast cosmetic outcomes before (pre) and 3 years after (post) HFWBI using a 4-point scale (excellent/good/fair/poor), and they were evaluated by CE and a central panel evaluation (PE) on the same scale using 292 pairs of pre/post-HFWBI photographs. PE was performed twice by consensus of the same two experts with a 3-year interval. CE was assessed individually by two radiation oncologists, an expert and a non-expert. Intra-observer variability and inter-observer variability were calculated using the kappa (k) and weighted kappa (wk) statistics. RESULTS: The agreement between the first and second PE using pre/post-HFWBI photographs was moderate (k = 0.60, wk = 0.64. k = 0.53, wk = 0.60). The agreement between the expert and non-expert on CE was substantial (k = 0.72, wk = 0.76. k = 0.72, wk = 0.77). The inter-observer variability of CE was smaller than the intra-observer variability of PE. CONCLUSION: CE with BCCT. core was considered a reproducible and an appropriate evaluation method for Asian women in clinical trials of BCT, when breast cosmetic changes were compared between pre/post therapy.

A pictorial essay on radiological changes after stereotactic body radiation therapy for lung tumors.

Stereotactic body radiation therapy (SBRT) is a frequently used modality for the treatment of early stage non-small cell lung cancer and oligometastatic disease of the lung. The radiological changes observed in the lung after SBRT are likely to differ from those observed after conventional thoracic radiation therapy, primarily due to the small size of the target volume and highly conformal dose distributions with steep dose gradients from the target to surrounding normal lung tissues used in SBRT. Knowledge of the radiological changes that can occur after SBRT is required to correctly diagnose local failure. Herein, I report several radiological changes specific to SBRT that have been observed.

Final analysis of a Multicenter Single-Arm Confirmatory Trial of hypofractionated whole breast irradiation after breast-conserving surgery in Japan: JCOG0906.

OBJECTIVE: To evaluate the safety and efficacy of hypofractionated whole breast irradiation for Asian women after breast-conserving surgery. This is an updated report with 5-year follow-up. METHODS AND MATERIALS: Asian women who had invasive breast cancer with clinical tumor size ≤3 cm, pN0-1c and negative inked margins were enrolled. Hypofractionated whole breast irradiation of 42.56 Gy/16 fractions was delivered, and boost irradiation of 10.64 Gy/4 fractions was added when the surgical margin was ≤5 mm. The primary endpoint was the proportion of grade ≥ 2 late adverse reactions within 3 years. Secondary endpoints included early adverse events, overall survival, disease-free survival, ipsilateral breast relapse-free survival, late adverse reactions and cosmetic outcome. Toxicities were evaluated using CTCAE ver3.0. Cosmetic outcomes were assessed using a 4-point scale and CTCAE ver3.0 for hyper/hypopigmentation, breast nipple/areolar deformity and breast volume/deformity. RESULTS: Between February 2010 and August 2012, 312 patients were enrolled, and 306 received hypofractionated whole breast irradiation. Median follow-up was 70.5 (range 7.6-88.9) months. The proportion of grade ≥ 2 late adverse reactions within 3 years was 4.3% (90% confidence interval 2.5-6.7%). Grade 2 early adverse events occurred in 38 (12.4%); none had grade 3/4. Five-year overall survival, disease-free survival and ipsilateral breast relapse-free survival were 98.7, 95.4 and 98.0%, respectively. Of the 304 evaluable patients, 29 (9.5%; 95% confidence interval 6.5-13.4%) had grade 2/3 late adverse reactions; none had grade 4/5. At 5 years, 70/289 (24.2%) showed any worsening of breast cosmetic changes. CONCLUSIONS: Hypofractionated whole breast irradiation is considered a standard treatment for Asian women with margin-negative invasive breast cancer after breast-conserving surgery.

Prognostic Value of Epithelial Cell Adhesion Molecules in T1-2N0M0 Glottic Cancer.

OBJECTIVE: This is an ancillary study of a multi-institutional randomized non-inferiority phase III trial of accelerated fractionation (AF) versus standard fractionation (SF) radiation therapy for T1-2N0M0 glottic cancer (JCOG0701). Biopsy specimens of tumors from the patients enrolled in the JCOG0701 are collected and the association between clinical outcomes and histopathologic features such as expression of epithelial cell adhesion molecule (EpCAM), p53, and p16 were investigated. METHODS: Five slices of undyed slides from biopsy specimens were sent to the National Cancer Center Hospital and all the specimens were assessed for the expression of EpCAM, p53, and p16. The primary objective was to investigate the association between 3-year progression-free survival (PFS) and expression of EpCAM, p53, and p16. RESULTS: A total of 88 out of 370 patients were enrolled in this ancillary study. The 3-year PFS for tumors with strong expression of EpCAM was 70.6% (95% CI 43.1%-86.6%), while that of tumors without strong expression of EpCAM was 77.5% (95% CI 65.9%-85.5%) with no remarkable difference between groups (P = .67). Likewise, there was no significant difference in 3-year PFS between tumors regardless of p53 or p16 status. However, in a subgroup analysis for 17 patients with a strong expression of EpCAM, AF showed better 3-year PFS than SF (100% vs 54.5%, P = .07). CONCLUSIONS: From the current study, it could not be concluded that EpCAM, p16, and p53 were prognostic factors for early-stage glottic cancer after primary radiation therapy. AF might be an appropriate fractionation for tumors with a strong expression of EpCAM. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:1522-1527, 2021.

Factors related to primary cancer death and non-primary cancer death in patients treated with stereotactic body radiotherapy for pulmonary oligometastases.

Cancer-specific death (CSD) and non-cancer-specific death (non-CSD) after stereotactic body radiotherapy (SBRT) for pulmonary oligometastases have not been studied in detail. The aim of this study was to determine the cumulative incidences of CSD and non-CSD and to reveal prognostic factors. Data from a large survey of SBRT for pulmonary oligometastases were used for analyses, and patients with unknown cause of death were excluded from current analyses. CSD was primary cancer death and non-CSD was non-primary cancer death including a series of cancer treatment-related deaths. Cumulative incidences were calculated using the Kaplan-Meier method and a stratified Cox regression model was used for multivariate analyses (MVA). Fifty-two patients with an unknown death were excluded and a total of 1326 patients was selected. CSD and non-CSD occurred in 375 and 109 patients, respectively. The median OS period was 53.2 months and the cumulative incidences of 1-, 3-, and 5-year CSD vs. non-CSD rates were 6.5% vs. 2.3%, 29.5% vs. 8.6%, and 41.2% vs. 11.0%, respectively. In MVA, the incidence of CSD was related to performance status (1 vs. 0; p < 0.001, 2-3 vs. 0; p = 0.011), oligometastatic state (sync-oligometastases vs. oligo-recurrence, p = 0.026) and maximum tumor diameter (p = 0.009), and the incidence of non-CSD was related to age (p = 0.001), sex (p = 0.030), performance status (2-3 vs. 0; p = 0.002), and irradiated tumor-located lung lobe (left lower lobe vs. other lobes, p = 0.036). CSD was main cause of death, but non-CSD was not rare after SBRT. Prognostic factors for CSD and non-CSD were different, and an understanding of the factors would help in treatment.

Analyses of local control and survival after stereotactic body radiotherapy for pulmonary oligometastases from colorectal adenocarcinoma.

This study is a subset analysis of a retrospective multicenter study performed in Japan and its purpose was to investigate the effectiveness of stereotactic body radiotherapy (SBRT) for pulmonary oligometastases from colorectal cancer. Local control (LC), freedom from further metastases, relapse-free survival and overall survival (OS) after SBRT were retrospectively analyzed. The Kaplan-Meier method was used to estimate lifetime data and the log-rank test was performed as univariate analyses. The Cox proportional hazards model was applied in multivariate analyses. Data for 330 patients with 371 tumors were used for analyses. The median follow-up period was 25.0 months. The 3-year LC, freedom from further metastases, relapse-free survival and OS rates were 64.9, 34.9, 24.9 and 63.4%, respectively. The results of multivariate analyses showed that a higher LC rate was associated with no history of local therapy for oligometastases (P = 0.01), SBRT without concurrent chemotherapy (P < 0.01), type B calculation algorithm (P < 0.01) and higher biological effective radiation doses (≥115 Gy, P = 0.04). A longer OS was associated with no history of local therapy for oligometastases (P = 0.04), a more recent period of SBRT (2010-15, P = 0.02), tumor located in the upper or middle lobe (P < 0.01) and higher biological effective radiation doses (≥115 Gy, P = 0.01). In conclusion, OS after SBRT was good, but LC rate was relatively low. The use of high biological effective radiation doses can improve both LC and OS outcomes.

Stereotactic Body Radiotherapy for Pulmonary Oligometastases from Esophageal Cancer: Results and Prognostic Factors.

BACKGROUND/AIM: The aim of this multi-center retrospective study was to investigate the results of stereotactic body radiotherapy (SBRT) for pulmonary oligometastases from esophageal cancer. PATIENTS AND METHODS: Oligometastases from the esophagus were identified from a dataset of a Japanese survey. The Kaplan-Meier method and Cox regression were applied to perform analyses. RESULTS: A total of 114 patients with 132 pulmonary oligometastases were collected. The 3-year local control rate, freedom from further metastasis (FFFM) rate and overall survival (OS) rate were 70.2%, 25.3% and 37.5%, respectively. Performance status (PS) (PS 1 vs. PS 0, p<0.01), disease-free interval (p=0.03) and history of local therapy for metastasis (p=0.01) had significant relationships with FFFM and only PS was an independent prognostic factor for OS (PS 1 vs. PS 0, p=0.02; PS 2-3 vs. PS 0, p=0.04). CONCLUSION: SBRT for pulmonary oligometastases from esophageal cancer provided good local control and survival.

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.

Pulmonary Oligometastases Treated by Stereotactic Body Radiation Therapy: A Nationwide Survey of 1,378 Patients.

AIM: This study was performed to confirm the superior overall survival (OS) after pulmonary oligo-recurrence compared to pulmonary sync-oligometastases in a large nationwide study. PATIENTS AND METHODS: Patients that met the following criteria were included: 1 to 5 lung-only metastases at the beginning of stereotactic body radiation therapy (SBRT) was performed between January 2004 and June 2015, and the biological effective dose (BED) of SBRT was 75 Gy or more. The parameters included in the analyses were age, gender, ECOG PS, primary lesion, pathology, oligoetastatic state, SBRT date, chemotherapy before SBRT, chemotherapy concurrent SBRT, chemotherapy after SBRT, maximum tumor diameter, number of metastases, field coplanarity, dose prescription, BED10, OTT of SBRT. RESULTS: In total, 1,378 patients with 1,547 tumors were enrolled. Oligo-recurrence occurred in 1,016 patients, sync-oligometastases in 118, and unclassified oligometastases in 121. The three-year OS was 64.0% for oligo-recurrence and 47.5% for sync-oligometastasis (p<0.001). In the multivariate analysis, the hazard ratio (HR) for sync-oligometastases versus oligo-recurrence was 1.601 (p=0.014). Adverse events of Grade 5 were occurred in 3 patients. CONCLUSION: This is the first nationwide to indicate that the OS of patients with pulmonary oligo-recurrence is better than that of patients with sync-oligometastases.

Achieving PSA < 0.2 ng/ml before Radiation Therapy Is a Strong Predictor of Treatment Success in Patients with High-Risk Locally Advanced Prostate Cancer.

BACKGROUND: To predict long-term treatment outcome of radiation therapy (RT) plus androgen deprivation therapy (ADT) for high-risk locally advanced prostate cancer. METHODS: In total, 204 patients with the National Comprehensive Cancer Network (NCCN) high risk locally advanced prostate cancer (PSA > 20 ng/ml, Gleason score ≧ 8, clinical T stage ≧ 3a) were treated with definitive RT with ADT. Median follow up period was 113 months (IQR: 95-128). Median neoadjuvant ADT and total ADT duration were 7 months (IQR: 6-10) and 27 months (IQR: 14-38), respectively. RESULTS: PSA recurrence-free survival (PSA-RFS), cancer specific survival (CSS), and overall survival (OS) rates at 5 years were 84.1%, 98.5%, and 93.6%, respectively, and 67.9%, 91.2%, and 78.1%, respectively, at 10 years. Pre-RT PSA less than 0.2 ng/ml was associated with superior outcomes of PSA-RFS (HR = 0.42, 95% CI: 0.25-0.70, p = 0.001), CSS (HR = 0.27, 95% CI: 0.09-0.82, p = 0.013), and OS (HR = 0.48, 95% CI: 0.26-0.91, p = 0.021). On multivariate analysis, age (≥70 y.o.) and pre-RT PSA (≥0.2 ng/ml) were factors predictive of poorer OS (p = 0.032) , but iPSA, T stage, Gleason score, number of NCCN high-risk criteria, a combination with anti-androgen therapy and neoadjuvant ADT duration were not predictive of treatment outcome. CONCLUSION: In patient with high-risk prostate cancer, RT plus ADT achieved good oncologic outcomes. PSA < 0.2 ng/ml before radiation therapy is a strong independent predictor for long overall survival.

A primary analysis of a multicenter, prospective, single-arm, confirmatory trial of hypofractionated whole breast irradiation after breast-conserving surgery in Japan: JCOG0906.

OBJECTIVE: To evaluate the safety of hypofractionated whole breast irradiation in Japanese women after breast-conserving surgery. METHODS: Japanese women who had invasive breast cancer with a clinical tumor size ≤3 cm, pN0-1c and a negative inked margin were enrolled. Hypofractionated whole breast irradiation (42.56 Gy/16 fractions) was delivered, adding boost irradiation (10.64 Gy/4 fractions) when the surgical margin was ≤5 mm. The treatment course was meant to be completed within 29 days or 33 days (plus boost irradiation). The primary endpoint was the proportion of grade ≥2 of pre-specified late adverse reactions, including telangiectasia, ulceration, fibrosis, fracture, pneumonitis, cardiac ischemia/infarction, pericardial effusion and breast pain, within 3 years. A sample size of 310 patients was set, with one-sided alpha of 0.05, beta of 0.1, threshold value of 8% and expected value of 4%. Secondary endpoints included the proportion of treatment completion within the recommended period and early adverse events within 90 days. Adverse events/adverse reactions were evaluated using CTCAE-3.0. RESULTS: Between 2010 and 2012, 312 women were enrolled; 306 received hypofractionated whole breast irradiation, but 6 chose conventional fractionated WBI, with 301 patients (96.5%) treated within the recommended period. Grade 2 early adverse events were found in 38 patients (12.4%); none had grade 3/4. Among the 303 evaluable patients, 13 (4.3%; 90% CI 2.6-6.7) had grade 2/3 late adverse reactions, including one with grade 3 pneumonitis, which was under the threshold value. CONCLUSION: Hypofractionated whole breast irradiation is considered to be safe and one of the standard treatments for Japanese women with margin-negative invasive breast cancer after breast-conserving surgery.

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.