Maiko Kozumi

Treatment outcome of high-dose image-guided intensity-modulated radiotherapy using intra-prostate fiducial markers for localized prostate cancer at a single institute in Japan

BackgroundSeveral studies have confirmed the advantages of delivering high doses of external beam radiotherapy to achieve optimal tumor-control outcomes in patients with localized prostate cancer. We evaluated the medium-term treatment outcome after high-dose, image-guided intensity-modulated radiotherapy (IMRT) using intra-prostate fiducial markers for clinically localized prostate cancer.MethodsIn total, 141 patients with localized prostate cancer treated with image-guided IMRT (76 Gy in 13 patients and 80 Gy in 128 patients) between 2003 and 2008 were enrolled in this study. The patients were classified according to the National Comprehensive Cancer Network-defined risk groups. Thirty-six intermediate-risk patients and 105 high-risk patients were included. Androgen-deprivation therapy was performed in 124 patients (88%) for a median of 11 months (range: 2–88 months). Prostate-specific antigen (PSA) relapse was defined according to the Phoenix-definition (i.e., an absolute nadir plus 2 ng/ml dated at the call). The 5-year actuarial PSA relapse-free survival, the 5-year distant metastasis-free survival, the 5-year cause-specific survival (CSS), the 5-year overall survival (OS) outcomes and the acute and late toxicities were analyzed. The toxicity data were scored according to the Common Terminology Criteria for Adverse Events, version 4.0. The median follow-up was 60 months.ResultsThe 5-year PSA relapse-free survival rates were 100% for the intermediate-risk patients and 82.2% for the high-risk patients; the 5-year actuarial distant metastasis-free survival rates were 100% and 95% for the intermediate- and high-risk patients, respectively; the 5-year CSS rates were 100% for both patient subsets; and the 5-year OS rates were 100% and 91.7% for the intermediate- and high-risk patients, respectively. The Gleason score (<8 vs. ≥8) was significant for the 5-year PSA relapse-free survival on multivariate analysis (p = 0.044). There was no grade 3 or 4 acute toxicity. The incidence of grade 2 acute gastrointestinal (GI) and genitourinary (GU) toxicities were 1.4% and 8.5%, respectively. The 5-year actuarial likelihood of late grade 2–3 GI and GU toxicities were 6% and 6.3%, respectively. No grade 4 GI or GU late toxicity was observed.ConclusionsThese medium-term results demonstrate a good tolerance of high-dose image-guided IMRT. However, further follow-up is needed to confirm the long-term treatment outcomes.

Metabolic tumor volume on FDG-PET/CT is a possible prognostic factor for Stage I lung cancer patients treated with stereotactic body radiation therapy: a retrospective clinical study

The aim of this study was to determine whether metabolic tumor volume (MTV) and total lesion glycolysis (TLG) are associated with outcomes in Stage I lung cancer patients treated with stereotactic body radiation therapy (SBRT). Thirty-eight patients underwent [18F] fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) within 60 days before SBRT at our institution between January 2001 and December 2011. The maximum standardized uptake value (SUVmax), MTV2, MTV4, MTV6, TLG40%, TLG50% and TLG60% were calculated. Prognostic factors for overall survival (OS) and local control (LC) were analyzed using Coxs proportional hazards model, and survival curves were calculated using the Kaplan–Meier method. Receiver operating characteristics (ROC) curves of PET parameters for OS and LC were calculated. The median follow-up period for survivors was 37.7 months. Three-year OS and LC rates were 56.4% and 70.5%, respectively, and 5-year OS and LC rates were 36.8% and 70.5%, respectively. In univariate analyses, tumor diameter (P = 0.019), single dose ≥10 Gy (P = 0.017), MTV2 (P = 0.030) and MTV4 (P = 0.048) were significant predictors for OS. Tumor diameter (P < 0.001), single dose ≥10 Gy (P = 0.007), SUVmax (P = 0.035), MTV2 (P < 0.001), MTV4 (P = 0.003), MTV6 (P = 0.017), TLG40% (P < 0.001), TLG50% (P = 0.001) and TLG60% (P = 0.003) were significant predictors for LC. SUVmax was not a significant predictor for OS. We made the ROC curves at PET parameters, and the largest area under the curve value for OS was MTV2 and for LC was TLG40%. Tumor diameter, single dose ≥10 Gy, MTV2 and MTV4 are prognostic factors for OS and LC rates and MTV2 is a better prognostic factor for OS than other PET parameters.

Elective nodal irradiation is not necessary in chemoradiotherapy for postoperative loco-regional recurrent esophageal cancer

Purpose The purposes of the present study were to evaluate prognostic factors for patients with postoperative loco-regional recurrent esophageal cancer treated with chemoradiotherapy by multivariate analysis and to determine which irradiation is better, involved field irradiation or elective nodal irradiation, by matched-pair analysis. Methods We reviewed records for 80 patients with postoperative loco-regional recurrent esophageal cancer treated by chemoradiotherapy between 2000 and 2014. The median follow-up period was 62.0 months. Thirty-one cases were treated with elective nodal irradiation and were randomly matched by risk factors to 49 cases treated with involved field irradiation (1:1). Results Fifty-one patients had disease recurrence again, and irradiated-field failure was observed in 26 patients. The 5-year overall survival rate was 30.5% with a median survival period of 26.5 months. Grade 3 or higher late toxicity was observed in only one patient. In multivariate analysis, short disease-free interval and anastomotic recurrence were statistically significant unfavorable prognostic factors for overall survival (hazard ratios: 2.1 and 2.5, respectively). Matched-pair analysis including disease-free interval, pattern of recurrence and number of recurrent regions revealed that overall survival rate and irradiated-field control rate in patients treated with involved field irradiation were significantly better than those in patients treated with elective nodal irradiation (P = 0.016 and P = 0.014, respectively). Conclusions Short disease-free interval and anastomotic recurrence are unfavorable factors and elective nodal irradiation is not necessary in chemoradiotherapy for patients with postoperative loco-regional recurrent esophageal cancer.

Oesophageal squamous cell carcinoma: histogram-derived ADC parameters are not predictive of tumour response to chemoradiotherapy

ObjectivesTo evaluate correlations between tumour response to definitive chemoradiotherapy (CRT) in oesophageal squamous cell carcinoma (SCC) and histogram-derived apparent diffusion coefficient (ADC) parameters on diffusion-weighted MR images.MethodsForty patients with clinical T3–4 oesophageal SCC underwent concurrent CRT. MR examination at 3 T was performed 1–3 days prior to CRT. Readout-segmented echo-planar diffusion imaging was used to acquire ADC maps. Pre- and post-treatment CT examinations were performed. Histogram parameters (mean, 10th, 25th, 50th, 75th, 90th percentiles, skewness and kurtosis) of the ADC values were compared with post-treatment disease status based on RECIST and the tumour regression ratio.ResultsNone of the ADC parameters showed significant correlation with post-treatment status (range of Spearman’s ρ values − 0.19 to 0.14, range of p values 0.22–0.47) or tumour regression ratio (range of Spearman’s ρ values − 0.045 to 0.18, range of p values 0.26–0.96). Neither progression-free survival (PFS) (p = 0.17) nor overall survival (OS) (p = 0.15) was significantly different between the two groups corresponding to the lower (< median) and upper arms (≥ median) of the mean ADC values.ConclusionsHistogram-derived pretreatment ADC parameters were not predictive imaging biomarkers for tumour response to CRT in patients with oesophageal SCC.Key Points• Apparent diffusion coefficient (ADC) values are derived from diffusion-weighted MR imaging.• High-resolution diffusion-weighted images are generated by readout-segmented echo-planar diffusion imaging.• Readout-segmented echo-planar diffusion-weighted imaging enabled evaluation of ADC parameters.• Pretreatment ADC parameters do not predict chemoradiotherapy response in patients with oesophageal carcinoma.

Prognostic Value of Radiation Pneumonitis After Stereotactic Body Radiotherapy: Effect of Pulmonary Emphysema Quantitated Using CT Images

Background The aim of this study was to determine the prognostic factors of radiation pneumonitis (RP) after stereotactic body radiotherapy (SBRT). Patients and Methods A total of 50 patients (36 male and 14 female) were treated with SBRT for 42 primary lung cancers and 8 metastatic lung cancers. SBRT was performed with 48 Gy in 4 fractions to the isocenter or with 40 Gy in 4 fractions covering 95% of the planning target volume. Percentage of low attenuation area (%LAA) was defined as percentage of the lung area with attenuation of −860 Hounsfield units (HU) or lower (%LAA‐860) or of −960 HU or lower (%LAA‐960). The dosimetric parameter of V20 Gy, which means percentage volume of the lung receiving 20 Gy or more, was recalculated. RP was assessed using Common Terminology Criteria for Adverse Events version 4.0. Results The median follow‐up period was 39.0 months (range, 7.2‐94.5 months). RP of Grade 0, Grade 1, and Grade 2 to 3 was diagnosed in 11, 29, and 10 patients, respectively. Multivariate analyses (MVA) for Grade 1 showed that higher %LAA‐860 and higher %LAA‐960 were significantly associated with a lower rate of Grade 1 RP. MVA for Grade 2 to 3 showed that lower Brinkman index and lower lung V20 Gy were significantly associated with a lower rate of Grade 2 to 3 RP, and, in contrast, %LAA‐860 and %LAA‐960 had no association with Grade 2 to 3 RP. Conclusion This result suggests that high %LAA is associated with radiological changes (Grade 1) but that %LAA has no correlation with Grade 2 to 3 RP because symptomatic RP might also be affected by other factors. Micro‐Abstract The prognostic role of pulmonary emphysema for radiation pneumonitis (RP) after stereotactic body radiotherapy was investigated. It is true that patients with pulmonary emphysema showed a lower rate of abnormal shadow, but there was no association with Grade 2 to 3 RP. This is because patients with pulmonary emphysema had a low tolerance for symptomatic RP because of poor pulmonary function.

Whole-body total lesion glycolysis is an independent predictor in patients with esophageal cancer treated with definitive chemoradiotherapy

BACKGROUND AND PURPOSE To determine whether pretreatment whole-body total lesion glycolysis (TLGWB) and metabolic tumor volume (MTVWB) are associated with outcomes in patients with esophageal cancer treated with definitive chemoradiotherapy (dCRT). MATERIALS AND METHODS Ninety patients with stage II or III thoracic esophageal cancer who underwent FDG-PET/CT within 45 days before dCRT between 2005 and 2013 were reviewed. MTV and TLG of the primary lesion (MTVpri and TLGpri) and the sum of MTV and TLG for all lesions (MTVWB and TLGWB) were calculated. Predictors were analyzed using the Cox proportional hazards model. RESULTS The median follow-up period was 27.7 months. In multivariate analysis, MTVWB > median was an unfavorable predictor for OS (p = 0.027, hazard ratio [HR]: 2.15), LC (p = 0.039, HR: 1.98) and PFS (p = 0.041, HR: 1.96). TLGWB > median was an unfavorable predictor for OS (p = 0.019, HR: 2.26), LC (p = 0.015, HR: 2.36) and PFS (p = 0.014, HR: 2.33). SUVmax was not a predictor, and the HR of TLGWB was higher than that of MTVWB for OS, LC and PFS in multivariate analysis. CONCLUSION TLGWB and MTVWB are independent predictors in patients with esophageal cancer.

Clinical Factors Relating to Cervical Body Volume Reduction during Curative External Beam Radiation Therapy for Head and Neck Cancer

Purpose/Objectives: Substantial cervical body volume reduction (CBVR) occurs during fractionated external beam radiation therapy (EBRT) for head-and-neck cancer (HNC) and could have potential dosimetric influences. This study aims to investigate measurable clinical factors before treatment initiation correlating with CBVR during curative EBRT in HNC patients, and to determine which patients receive the great benefit from routine adaptive radiation therapy (ART). Materials/Methods: Fifty-six patients with oropharyngeal squamous cell carcinoma (OSCC) and 67 patients with hypopharyngeal squamous cell carcinoma (HSCC) had received curative EBRT between 2006 and 2013 were enrolled. For EBRT planning, computed tomography (CT) images were acquired before EBRT initiation and between two to seven weeks after the start of EBRT for replanning in each patient. A MATLAB program was used to evaluate the CBVR rate (CBVRR) between the initial and replanning CT imaging. The following factors were assessed for correlation with CBVRR: the T and N stage, induction and concurrent chemotherapy, the initial gross tumor volume (GTV), the GTV reduction rate (GTVRR) between the initial and replanning CT imaging, the initial body weight (BW) and the BW loss rate (BWLR) during the EBRT course. Results: In the OSCC group, the CBVRR ranged from 1.8 to 17.1% (median, 6.8%). In the HSCC group, the CBVRR ranged from 1.2 to 23.7% (median, 6.5%). In non-parametric univariate analysis, the N3 stage demonstrated a greater trend with the CBVRR than the N2c≥ stage in the HSCC group (p=0.023), whereas marginal inclination (p=0.096) was found in the OSCC group. The CBVRR was substantially related to the GTVRR (p=0.001) in the HSCC group.

Assessment of a Commercially Available Automatic Deformable Image Registration

Ventilation imaging can be performed using thoracic four dimensional computed tomography (4D-CT) images (max inhale phase and max exhale phase) and deformable image registration (DIR). If this method was administered in multi institution, some institution would use commercially available automatic DIR software. But, there are not many reports about commercially available automatic DIR. In this study, we evaluated the accuracy of a commercially available automatic deformable image registration (DIR) algorithm using 4D-CT images. For evaluating the accuracy of DIR, registration error was calculated by difference between manual displacement and automatic calculated displacement (DIR outputs). A B-spline DIR algorithm implemented in a Velocity AI ver. 2.7.0 software (Velocity Medial, GA, USA) was evaluated. 4D-CT images including 300 landmarks /case, throughout the lung, provided by DIR-lab (www.dir-lab.com). In this study, five patients were studied. The goal of DIR was to find a point to point correspondence between inhale image and exhale image. First, manual displacement was calculated by land mark points between max inhale phase and max exhale phase. Next, DIR outputs were calculated by a Velocity AI. After that, registration error was calculated by difference between manual displacement and DIR outputs. The mean 3D registration error (standard deviation) for the five cases was 2.70 (2.24) mm. Fewer large errors were seen, but the frequent histogram had a peak at 1.5mm of 3D error, and the frequencies decline as one moves away from the peak. The average 3D registration errors for case1 were 0.94 mm for 1.5 mm motion distance magnitude, 1.96 mm for 6.0 mm and 3.70 mm for 9.0 mm, respectively. Our result clearly shows that the accuracy of DIR in Velocity AI was within 3.0 mm. Therefore commercially available automatic DIR may be useful for image-guided radiation therapy, adaptive radiation therapy and ventilation imaging.