Prospective external validation of radiomics-based predictive model of distant metastasis after dynamic tumor tracking stereotactic body radiation therapy in patients with non-small-cell lung cancer: A multi-institutional analysis.

BACKGROUND AND PURPOSE: This study aims to externally validate a predictive model for distant metastasis (DM) with computed tomography (CT)-based radiomics features in prospectively enrolled non-small-cell lung cancer patients undergoing dynamic tumor-tracking stereotactic body radiation therapy (DTT-SBRT). MATERIALS AND METHODS: The study collected retrospective data from 567 patients across 11 institutions as the training dataset and prospectively enrolled 42 patients from four institutions as the external test dataset. Four clinical features were collected, and 944 CT-based radiomic features were extracted from gross tumor volumes. After standardization and feature selection, DM predictive models were developed using fine and gray regression (FG) and random survival forest (RSF), incorporating clinical and radiomic features, and their combinations within the training dataset. Then, the model was applied to the test dataset, dividing patients into high- and low-risk groups based on medians of risk scores. Model performance was assessed using the concordance index (C-index), and the statistical significance between groups was evaluated using Gray's test. RESULTS: In the training dataset, 122 of 567 patients (21.5%) developed DM, compared to 9 of 42 patients (21.4%) in the test dataset. In the test dataset, the C-indices of the clinical, radiomics, and hybrid models with FG were 0.559, 0.544, and 0.560, respectively, whereas those with RSF were 0.576, 0.604, and 0.627, respectively. The hybrid model with RSF, which exhibited the best predictive performance of all models, identified 7 of 23 patients (30.4%) as high risk and 2 of 19 patients (10.5%) as low risk for DM incidence in the test dataset (p = 0.116). CONCLUSION: Although predictive models for DM lack significance when applied to prospectively enrolled cases undergoing DTT-lung SBRT, the model with RSF exhibits a consistent capacity to effectively classify patients at a high risk of developing DM.

Population-based asymmetric margins for moving targets in real-time tumor tracking.

BACKGROUND: Both geometric and dosimetric components are commonly considered when determining the margin for planning target volume (PTV). As dose distribution is shaped by controlling beam aperture in peripheral dose prescription and dose-escalated simultaneously integrated boost techniques, adjusting the margin by incorporating the variable dosimetric component into the PTV margin is inappropriate; therefore, geometric components should be accurately estimated for margin calculations. PURPOSE: We introduced an asymmetric margin-calculation theory using the guide to the expression of uncertainty in measurement (GUM) and intra-fractional motion. The margins in fiducial marker-based real-time tumor tracking (RTTT) for lung, liver, and pancreatic cancers were calculated and were then evaluated using Monte Carlo (MC) simulations. METHODS: A total of 74 705, 73 235, and 164 968 sets of intra- and inter-fractional positional data were analyzed for 48 lung, 48 liver, and 25 pancreatic cancer patients, respectively, in RTTT clinical trials. The 2.5th and 97.5th percentiles of the positional error were considered representative values of each fraction of the disease site. The population-based statistics of the probability distributions of these representative positional errors (PD-RPEs) were calculated in six directions. A margin covering 95% of the population was calculated using the proposed formula. The content rate in which the clinical target volume (CTV) was included in the PTV was calculated through MC simulations using the PD-RPEs. RESULTS: The margins required for RTTT were at most 6.2, 4.6, and 3.9 mm for lung, liver, and pancreatic cancer, respectively. MC simulations revealed that the median content rates using the proposed margins satisfied 95% for lung and liver cancers and 93% for pancreatic cancer, closer to the expected rates than the margins according to van Herk's formula. CONCLUSIONS: Our proposed formula based on the GUM and motion probability distributions (MPD) accurately calculated the practical margin size for fiducial marker-based RTTT. This was verified through MC simulations.

Dynamic tumor-tracking stereotactic body radiotherapy with real-time monitoring of liver tumors using a gimbal-mounted linac: A multi-institutional phase II study.

Background and purpose: This prospective multicenter phase II study aimed to evaluate the safety and efficacy of dynamic tumor tracking (DTT) stereotactic body radiotherapy (SBRT) with real-time monitoring of liver tumors using a gimbal-mounted system. Materials and methods: Patients with < 4 primary or metastatic liver tumors with diameters ≤ 50 mm and expected to have a respiratory motion of ≥ 10 mm were eligible. The prescribed dose was 40 Gy in five fractions. The primary endpoint was local control (LC) at 2 years. The secondary endpoints were overall survival (OS), progression-free survival (PFS), treatment-related toxicity, and tracking accuracy. Results: Between September 2015 and March 2019, 48 patients (48 lesions) with a median age of 74 years were enrolled from four institutions. Of these, 39 were diagnosed with hepatocellular carcinoma and nine with metastatic liver cancer. The median tumor diameter was 17.5 mm. DTT-SBRT was successfully performed in all patients; the median treatment time was 28 min/fraction. The median follow-up period was 36.5 months. The 2-year LC, OS, and PFS rates were 98.0 %, 88.8 %, and 55.1 %, respectively. Disease progression was observed in 33 (68.8 %) patients. One patient (0.2 %) had local recurrence, 31 (64.6 %) developed new hepatic lesions outside the irradiation field, and nine (18.8 %) had distant metastases (including overlap). Grade 3 late adverse events were observed in seven patients (14.5 %). No grade 4 or 5 treatment-related toxicity was observed. The median tracking accuracy was 2.9 mm. Conclusion: Employing DTT-SBRT to treat liver tumors results in excellent LC with acceptable adverse-event incidence.

Organs-at-risk dose constraints in head and neck intensity-modulated radiation therapy using a dataset from a multi-institutional clinical trial (JCOG1015A1).

BACKGROUND: JCOG1015A1 is an ancillary research study to determine the organ-specific dose constraints in head and neck carcinoma treated with intensity-modulated radiation therapy (IMRT) using data from JCOG1015. METHODS: Individual patient data and dose-volume histograms of organs at risk (OAR) were collected from 74 patients with nasopharyngeal carcinoma treated with IMRT who enrolled in JCOG1015. The incidence of late toxicities was evaluated using the cumulative incidence method or prevalence proportion. ROC analysis was used to estimate the optimal DVH cut-off value that predicted toxicities. RESULTS: The 5-year cumulative incidences of Grade (G) 1 myelitis, ≥ G1 central nervous system (CNS) necrosis, G2 optic nerve disorder, ≥ G2 dysphagia, ≥ G2 laryngeal edema, ≥ G2 hearing impaired, ≥ G2 middle ear inflammation, and ≥ G1 hypothyroidism were 10%, 5%, 2%, 11%, 5%, 26%, 34%, and 34%, respectively. Significant associations between DVH parameters and incidences of toxicities were observed in the brainstem for myelitis (D1cc ≥ 55.8 Gy), in the brain for CNS necrosis (D1cc ≥ 72.1 Gy), in the eyeball for optic nerve disorder (Dmax ≥ 36.6 Gy), and in the ipsilateral inner ear for hearing impaired (Dmean ≥ 44 Gy). The optic nerve, pharyngeal constrictor muscle (PCM), and thyroid showed tendencies between DVH parameters and toxicity incidence. The prevalence proportion of G2 xerostomia at 2 years was 17 versus 6% (contralateral parotid gland Dmean ≥ 25.8 Gy vs less). CONCLUSIONS: The dose constraint criteria were appropriate for most OAR in this study, although more strict dose constraints might be necessary for the inner ear, PCM, and brainstem.

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.

Multi-institutional phase II study on the safety and efficacy of dynamic tumor tracking-stereotactic body radiotherapy for lung tumors.

BACKGROUND AND PURPOSE: This study aimed to evaluate the safety and efficacy of dynamic tumor tracking-stereotactic body radiotherapy (DTT-SBRT) for lung tumors. MATERIALS AND METHODS: Patients with cStage I primary lung cancer or metastatic lung cancer with an expected range of respiratory motion of ≥10 mm were eligible for the study. The prescribed dose was 50 Gy in four fractions. A gimbal-mounted linac was used for DTT-SBRT delivery. The primary endpoint was local control at 2 years. RESULTS: Forty-eight patients from four institutions were enrolled in this study. Forty-two patients had primary non-small-cell lung cancer, and six had metastatic lung tumors. DTT-SBRT was delivered for 47 lesions in 47 patients with a median treatment time of 28 min per fraction. The median respiratory motion during the treatment was 13.7 mm (range: 4.5-28.1 mm). The motion-encompassing method was applied for the one remaining patient due to the poor correlation between the abdominal wall and tumor movement. The median follow-up period was 32.3 months, and the local control at 2 years was 95.2% (lower limit of the one-sided 85% confidence interval [CI]: 90.3%). The overall survival and progression-free survival at 2 years were 79.2% (95% CI: 64.7%-88.2%) and 75.0% (95% CI: 60.2%-85.0%), respectively. Grade 3 toxicity was observed in one patient (2.1%) with radiation pneumonitis. Grade 4 or 5 toxicity was not observed. CONCLUSION: DTT-SBRT achieved excellent local control with low incidences of severe toxicities in lung tumors with respiratory motion.

Impact of pre-treatment C-reactive protein level and skeletal muscle mass on outcomes after stereotactic body radiotherapy for T1N0M0 non-small cell lung cancer: a supplementary analysis of the Japan Clinical Oncology Group study JCOG0403.

This study aimed to evaluate the impact of pretreatment C-reactive protein (CRP) and skeletal muscle mass (SMM) on outcomes after stereotactic body radiotherapy (SBRT) for T1N0M0 non-small cell lung cancer (NSCLC) as a supplementary analysis of JCOG0403. Patients were divided into high and low CRP groups with a threshold value of 0.3 mg/dL. The paraspinous musculature area at the level of the 12th thoracic vertebra was measured on simulation computed tomography (CT). When the area was lower than the sex-specific median, the patient was classified into the low SMM group. Toxicities, overall survival (OS) and cumulative incidence of cause-specific death were compared between the groups. Sixty operable and 92 inoperable patients were included. In the operable cohort, OS significantly differed between the CRP groups (log-rank test p = 0.009; 58.8% and 83.6% at three years for high and low CRP, respectively). This difference in OS was mainly attributed to the difference in lung cancer deaths (Gray's test p = 0.070; 29.4% and 7.1% at three years, respectively). No impact of SMM on OS was observed. The incidence of Grade 3-4 toxicities tended to be higher in the low SMM group (16.7% vs 0%, Fisher's exact test p = 0.052). In the inoperable cohort, no significant impact on OS was observed for either CRP or SMM. The toxicity incidence was also not different between the CRP and SMM groups. The present study suggests that pretreatment CRP level may provide prognostic information in operable patients receiving SBRT for early-stage NSCLC.

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.

Evaluation of Optimal Post-Injection Timing of Hypoxic Imaging with 18F-Fluoromisonidazole-PET/CT.

PURPOSE: Positron emission tomography (PET)/computed tomography (CT) using 18F-fluoromisonidazole (FMISO) has been used as an imaging tool for tumour hypoxia. However, it remains unclear whether they are useful when scanning is performed earlier, e.g. at 2-h post-injection with a high sensitivity PET scanner. This study aimed to investigate the relationship between quantitative values in 18F-fluoromisonidazole (18F-FMISO)-PET obtained at 2- and 4-h post-injection in patients with head and neck cancer. PROCEDURES: We enrolled 20 patients with untreated locally advanced head and neck cancer who underwent 18F-FMISO-PET/CT scan between August 2015 and March 2018 at our institute. Image acquisition was performed 2 h and 4 h after 18F-FMISO administration using a combined PET/CT scanner. The SUVmax, SUVmean, SUVpeak, tumour-to-blood ratio (TBR), tumour-to-muscle ratio (TMR), metabolic tumour volume (MTV), and total lesion hypoxia (TLH) were measured in the region of interest of the primary tumour. We evaluated the between-image Spearman's rank correlation coefficients and percentage differences in the quantitative values. The locations of the maximum uptake pixel were identified in both scans, and the distance between them was measured. RESULTS: The mean (SD) SUVmax at 2 h and 4 h was 2.2(0.7) and 2.4(0.8), respectively. The Spearman's rank correlation coefficients (ρ) and mean (SD) of the percentage differences of the measures were as follows: SUVmax (0.97; 7.0 [5.1]%), SUVmean (0.97; 5.2 [5.8]%), SUVpeak (0.94; 5.3 [4.7]%), TBR (0.96; 14.2 [9.8]%), TMR (0.96; 14.7 [8.4]%), MTV (0.98; 39.9 [41.3]%), and TLH (0.98; 40.1 [43.4]%). There were significant between-scan correlations in all quantitative values. The mean (SD) distance between the two maximum uptake pixels was 7.3 (5.3) mm. CONCLUSIONS: We observed a high correlation between the quantitative values at 2 h and 4 h. When using a combined high-quality PET/CT, the total examination time for FMISO-PET can be shortened by skipping the 4-h scan.

Regional collaboration to improve quality of radiation therapy in Asia.

In Asia, several challenges hinder the delivery of high-quality cancer treatment, especially radiation therapy (RT). Many Asian countries face large-scale shortage of RT centres and treatment machines. Additionally, there is also a significant technological gap, with many RT centres in Asia still using outdated technology. There is an urgent need to improve radiation treatment quality in Asia. The Federation of Asian Organizations for Radiation Oncology (FARO) was set up to foster regional collaboration, which we believe can help to identify and solve some of these issues collectively. This report describes the background and rationale of starting FARO, and puts forth some of the early achievements of the group, including fact-finding and educational activities. Finally, we discuss future possibilities, including strategic proposals that may benefit the RT community and our patients in Asia.

Hypofractionated intensity-modulated radiotherapy with concurrent chemotherapy for elderly patients with locally advanced pancreatic carcinoma.

BACKGROUND: It is important to understand how elderly patients with locally advanced pancreatic carcinoma (LAPC) should be treated, since the number of elderly cancer patients will increase. However, the optimal treatment for elderly patients with LAPC remains unclear. The purpose of this study was to evaluate the efficacy and safety of hypofractionated intensity-modulated radiotherapy (IMRT) with concurrent gemcitabine for elderly patients with LAPC. METHODS: We retrospectively analysed the data from LAPC patients aged ≥ 75 years treated with hypofractionated IMRT (48 Gy in 15 fractions) with concurrent weekly gemcitabine at our institution from February 2013 to December 2018. Overall survival (OS), progression-free survival (PFS), locoregional progression-free survival (LRPFS), distant metastasis-free survival (DMFS), and the pattern of recurrence and toxicity were analysed. RESULTS: Fifteen patients received treatment during the study period. The median age was 78 years (range 75-86 years), and the Eastern Cooperative Oncology Group (ECOG) performance status (PS) of all patients was 0-1. The median survival time (MST) and median PFS were 20.4 [95% confidence interval (CI) 10.3-36.8] and 13.5 (95% CI 6.4-20.3) months, respectively, and the 1-year OS and PFS rates were 80.0% (95% CI 50-93.1%) and 66.7% (95% CI 37.5-84.6%), respectively. The median LRPFS and median DMFS were 15.6 (95% CI 6.4-36.8) and 14.9 (95% CI 7.0-20.5) months, respectively, and the 1-year LRPFS and DMFS rates were 73.3% (95% CI 43.6-89.1%) and 66.7% (95% CI 37.5-84.6%), respectively. Non-haematologic grade 3 toxicity was observed in three cases, of which only one was induced by radiotherapy, whereas grade 4-5 non-haematologic acute or late toxicities were not observed. CONCLUSIONS: The OS and PFS of elderly patients with LAPC treated using hypofractionated IMRT with concurrent gemcitabine were favourable and without the occurrence of severe toxicity. This treatment strategy is feasible and promising for elderly LAPC patients with good PS.

Outcome measures reported in abstracts of randomized controlled trials in leading clinical journals: A bibliometric study.

BACKGROUNDS: The CONSORT for Abstracts checklist published in 2008 recommends that authors report effect size for their studies. Meanwhile, the FDA strongly recommends reporting both ratio and difference measures. However, the measures of effect used in recent clinical trial reports remain unknown. This study is aimed to reveal trends regarding the measures of effect of interventions described in abstracts of recent randomized controlled trials (RCTs) in leading journals. METHODS: A bibliometric analysis of data was obtained by electronic searches. Human RCTs published in 2016 in the following five journals were searched using PubMed: Annals of Internal Medicine, British Medical Journal, Journal of American Medical Association, The Lancet, and New England Journal of Medicine. Main outcome is numbers of studies reporting each measure in their abstracts. RESULTS: Among abstracts of 334 articles, measures most frequently used were relative risk alone (n = 169), followed by absolute risk alone (n = 92), and raw data alone (n = 58). Reporting of the following measures was relatively limited: both ratio and difference measures (n = 8), raw data with ratio measures (n = 5), and raw data with difference measures (n = 2). None of the studies reported raw data with both ratio and difference measures. Only 15 articles described multiple measures of effect in their abstracts. CONCLUSIONS: More than half of the RCT abstracts published in the five leading journals in 2016 reported risk ratio alone to indicate effect size. Even abstracts in the five leading journals did not adhere fully to the CONSORT for Abstracts or FDA recommendations.

The gimbaled-head radiotherapy system: Rise and downfall of a dedicated system for dynamic tumor tracking with real-time monitoring and dynamic WaveArc.

A gimbaled-head radiotherapy device was developed by industry-academic collaborations, with a concept of robust structures whilst maintaining high flexibilities, and its clinical application started in 2008. The unique structures with multi-image guidance functions initiated 2 new treatment modalities. One is dynamic tumor tracking radiotherapy with real time monitoring (DTTRM), which enables 4-D radiotherapy without prolongation of radiotherapy treatment time. This treatment has become clinically feasible for stereotactic body radiotherapy (SBRT) of lung cancers and liver tumors, and intensity-modulated radiotherapy (IMRT) for pancreatic cancers. The second one is Dynamic WaveArc therapy (DWA), the non-coplanar versatility of the SBRT system by combining the gantry-ring synchronized rotation with dynamic multileaf collimator optimization. DWA opens the possibility to create patient-individualized treatment plans, allowing additional flexibility in organ at risk sparing while preserving dosimetric robust delivery. The clinical usefulness of the DWA has been preliminary shown for those tumors in the prostate, breast and skull base. Prospective clinical trials are under way with a support of the national funding of Japan for DTTRM and DWA, respectively. Marketing of the system was terminated in 2016 due to a commercial decision. However, lessons can be learned from the development process of this device that might be useful for those who have interests in new technologies and clinical applications in radiation oncology. This review article aims to summarize the developments and achievements of a gimbaled-head radiotherapy device with a focus on DTTRM and DWA.

Influence of chemoradiotherapy on nutritional status in locally advanced rectal cancer: Prospective multicenter study.

OBJECTIVE: The aim of this study was to investigate the influence of chemoradiotherapy (CRT) on nutritional status and the association between changes in nutritional status and clinical outcomes (treatment completion, adverse events, perioperative complications, and relapse-free survival [RFS]) in patients with locally advanced rectal cancer (LARC). METHODS: In this multicenter, phase II study, 41 patients with LARC underwent CRT for 5 wk, followed by a 6- to 8-wk interval before surgery. Body weight, body mass index (BMI), lean body mass, serum albumin, and prealbumin levels were measured before (pre-), during, and after CRT, and before surgery. Changes in these data and scores on the Malnutrition Universal Screening Tool (MUST) were calculated based on pre-CRT status. RESULTS: Twelve patients (29.3%) experienced body weight loss (BWL) ≥5% (defined as malnutrition) after CRT (P < 0.001) and before surgery (P = 0.035). Significant changes were seen in serum albumin levels and BMI during and after CRT (P < 0.001), and in MUST scores after CRT (P = 0.003) and before surgery (P = 0.035). Treatment completion was significantly associated with BWL (P = 0.028), MUST score (P = 0.013), and decreased serum albumin level (P = 0.001) after CRT. Regarding adverse events, MUST score before surgery (P = 0.009) and serum albumin level after CRT (P = 0.002) were significantly associated with diarrhea severity. Serum albumin level during CRT was associated with the onset of neutropenia (P = 0.005). No association was found between BWL and RFS. CONCLUSIONS: These findings suggest that malnutrition and changes in nutritional status are not only commonly observed after CRT, but also associated with treatment completion and adverse events.

A phase II study of adaptive two-step intensity-modulated radiation therapy (IMRT) with chemotherapy for loco-regionally advanced nasopharyngeal cancer (JCOG1015).

BACKGROUND: A phase II study of adaptive two-step intensity-modulated radiotherapy (IMRT) with chemotherapy for nasopharyngeal cancer (NPC) (JCOG1015) was conducted to evaluate the efficacy and safety. METHODS: Patients aged 20-75 years with stages II-IVB NPC were enrolled. As adaptive two-step IMRT, computed tomography planning was performed twice before IMRT for the initial plan of 46 Gy/23 fractions and during treatment for the boost plan of 24 Gy/12 fractions with a total dose of 70 Gy. Chemotherapy (cisplatin 80 mg/m2/3-weeks × 3 courses) was administered concurrently with IMRT, followed by adjuvant chemotherapy (cisplatin at 70 mg/m2 with 5-FU 700 at mg/m2 for 5 days/4 weeks × 3 courses). RESULTS: Between 2011 and 2014, 75 patients were enrolled from 12 institutions. The 3-year overall survival (OS) for the 75 patients was 88%, and the upper and lower limits of the 95% CI of 78%-94% were higher than the expected 3-year OS of 75% for the target population adjusted by the actual proportion of stage II:III:IV = 21%:44%:35%. The 3-year progression-free survival (PFS) and loco-regional PFS were 71% [59-80%] and 77% [66-85%], respectively. Although no grade 4-5 late toxicities were observed, 15 patients (20%) developed grade 3 late toxicities. Grade 2 xerostomia was noted in 26%, 12%, and 9% at 1, 2, and 3 years after starting IMRT, respectively. CONCLUSIONS: Adaptive two-step IMRT for NPC demonstrated an excellent 3-year OS with acceptable toxicities. This method may be one treatment option for locally advanced NPC.

Radiotherapy planning techniques to reduce lung irradiation in head and neck cancer patients with mediastinal involvement.

The number of patients with head and neck squamous cell carcinoma (HNC) with mediastinal involvement is small, and appropriate treatment techniques have not been widely discussed. This study aimed to compare the efficacy of radiotherapy planning techniques in reducing lung irradiation while retaining target coverage. Among all HNC patients with mediastinal involvement who underwent radiotherapy between 2007 and 2014 at our hospital, seven consecutive patients were included in this study. Four different treatment plans were generated for each patient as follows: seven-field intensity-modulated radiation therapy (IMRT), modified IMRT in which the lateral beams avoided the lungs, three-full-arc volumetric-modulated arc therapy (VMAT), and VMAT with lung avoidance. We compared the outcomes of IMRT and VMAT plans using the paired t-test. After modifications were made to avoid lung irradiation, IMRT values for V5Gy and V20Gy decreased from 713.2 to 503.6 cm3 (p = 0.011) and from 338.8 cm3 to 267.0 cm3 (p = 0.058), respectively. In the case of VMAT, lung V5Gy and V20Gy values decreased from 754.8 to 601.0 cm3 (p = 0.004) and from 328.5 to 255.7 cm3 (p = 0.020), respectively. Other factors did not significantly differ between the plans. In both IMRT and VMAT planning, lung doses were significantly reduced following the modification of the beams that cross the lungs with target coverage maintenance.

The impact of age on the risk of ipsilateral breast tumor recurrence after breast-conserving therapy in breast cancer patients with a > 5 mm margin treated without boost irradiation.

BACKGROUND: The boost irradiation to the tumor bed following whole-breast irradiation (WBI) reduced the risk of ipsilateral breast tumor recurrence (IBTR). However, in Japan, almost all patients with a margin ≤5 mm receive boost irradiation to the tumor bed, but the decision to perform boost irradiation for those with a margin > 5 mm is dependent on the institution. Thus, institutional guidelines on utilizing boost irradiation for patients aged ≤40 or ≤ 50 years vary. We investigated the IBTR rate to assess the appropriate age for boost irradiation to the tumor bed with a margin > 5 mm. METHODS: From January 1993 to December 2010, 419 patients with early-stage breast cancer and negative margins (> 5 mm) after breast-conserving surgery received WBI without boost irradiation. The Gray test was used to compare the cumulative incidence of IBTR among patients aged ≤40, 41-50, and ≥ 51 years. Hazard ratios were estimated using the Fine and Gray models. Furthermore, as a subgroup analysis, we investigated whether IBTR depended on the use of systemic therapy, such as anthracycline or taxane regimens. RESULTS: The median follow-up time was 9.3 years. In multivariate analysis, only age predicted IBTR (p = 0.047). The 10-year IBTR rate was 15.7% in patients aged ≤40, 3.8% in those aged 41-50, and 2.0% in patients aged ≥51 years. The difference between patients aged ≤40 and 41-50 years was statistically significant (p = 0.045), whereas the difference between patients aged 41-50 and ≥ 51 years was not significant (p = 0.21). CONCLUSIONS: In our institutional surgical setting, when boost irradiation is performed only for patients with a margin ≤5 mm, the IBTR rate after WBI without boost irradiation was significantly higher in patients aged ≤40 years, suggesting that boost irradiation should be used for patients in this age group.

Single-isocenter volumetric-modulated Dynamic WaveArc therapy for two brain metastases.

PURPOSE: A new irradiation technique, volumetric-modulated Dynamic WaveArc therapy (VMDWAT), based on sequential non-coplanar trajectories, can be performed using the Vero4DRT. This planning study compared the dose distribution and treatment time between single-isocenter volumetric-modulated arc therapy (VMAT) with multiple straight non-coplanar arcs and single-isocenter VMDWAT in patients with two brain metastases. MATERIALS AND METHODS: Twenty patients with two planning target volumes exceeding 2.0 cm3 were included. Both VMAT and VMDWAT plans were created with single isocenter and a prescribed dose of 28 Gy delivered in five fractions. Target conformity was evaluated using indices modified from the RTOG-CI (mRTOG-CI) and IP-CI (mIP-CI). RESULTS: VMDWAT significantly improved both mRTOG-CI and mIP-CI and reduced the volume of normal brain tissue receiving 25 and 28 Gy compared to VMAT. The two modalities did not significantly differ in terms of the volume of normal brain tissue receiving 5, 10, 12, 15, and 20 Gy. The mean treatment time was significantly shorter in the VMDWAT group. CONCLUSION: VMDWAT significantly improved dose distribution in a shorter treatment time compared to VMAT in patients treated for two brain metastases. Single-isocenter VMDWAT may thus be a promising treatment for two brain metastases.

Factors associated with a preference for disclosure of life expectancy information from physicians: a cross-sectional survey of cancer patients undergoing radiation therapy.

PURPOSE: This study aimed to investigate experiences and preferences for disclosure of life expectancy, agreement between them, and the factors associated with preferences for disclosure of life expectancy with physicians among cancer patients undergoing radiation therapy. METHODS: Cancer patients aged 20 years or older were consecutively sampled when they started radiation therapy at two university hospitals. Patients completed self-administered questionnaires concerning their experiences of and preferences for disclosure of life expectancy, treatment decision-making, psychological distress, physical symptoms, sociodemographic and medical factors, physician's communication style, and provision of psychological, physical, and practical support. RESULTS: Among the 226 respondents (response rate: 58%) who responded, 54% experienced disclosure of life expectancy, and 45% preferred it. The agreement is 65%. Eighty-five percent recognized their aim of radiation therapy as curative. A univariate analysis indicated that having a full/part-time job and wishing to leave treatment decisions to doctors were significantly associated with preference for disclosure of life expectancy, but psychological distress was not. A multiple regression analysis revealed that having a full-time/part-time job was significantly associated with preference of communication about life expectancy. CONCLUSIONS: Fifty-four percent of the patients experienced and 45% of the patients preferred disclosure of life expectancy. The agreement is moderate. Our results show that there was a significant association between employment status and patient's preference for disclosure of life expectancy with physicians. Communication of prognosis is difficult but whether a patient continues to work or not may be an indicator of preference.

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.