Saiji Ohga

Radiation Therapy for Recurrent Esophageal Cancer after Surgery: Clinical Results and Prognostic Factors

OBJECTIVE To evaluate the outcome of radiotherapy for recurrent esophageal cancer after surgery and to determine the prognostic factors. METHODS From 1987 through 2002, 82 patients treated with radiotherapy for loco-regional recurrences of esophageal cancer after surgery were retrospectively reviewed. The stage at initial surgery was I in 16, II in 41, III or higher in 24 and unknown in 1. The median size of recurrent tumors was 3.5 cm in diameter. Fifty-two patients were treated with radiotherapy alone, and 30 were treated with radiotherapy combined with chemotherapy. The median total dose of external radiotherapy given was 50.4 Gy in 28 fractions. RESULTS The median survival period after recurrence was 7.0 months. The 2- and 5-year overall survival rate for all patients was 22 and 11%, respectively. In univariate analysis, the patients with performance status (PS) = 0-1, or tumor size <3.5 cm, and those treated with total dose >/=50 Gy showed a better survival outcome than each the other groups. The patients with a history of previous radiotherapy showed a poorer survival outcome in univariate analysis than each the other groups. In multivariate analysis, tumor size, PS and radiation dose were independent prognostic factors for overall survival. CONCLUSION The prognosis of patients with post-operative loco-regional recurrence of esophageal cancer is poor. However, a long-term survival may be expected by definitive radiotherapy for the patients with small-size tumors and with a good PS.

Prediction of Local Failures with a Combination of Pretreatment Tumor Volume and Apparent Diffusion Coefficient in Patients Treated with Definitive Radiotherapy for Hypopharyngeal or Oropharyngeal Squamous Cell Carcinoma

Diffusion-weighted magnetic resonance imaging/Apparent diffusion coefficient/Hypopharyngeal squamous cell carcinoma/Oropharyngeal squamous cell carcinoma. Purpose: Th e purpose of this study was to investigate the clinical factors for predicting local failure after definitive radiotherapy in oropharyngeal or hypopharyngeal squamous cell carcinoma. Materials and Methods: Between July 2006 and December 2008, 64 consecutive patients with squamous cell carcinoma of the hypopharynx or the oropharynx treated with definitive radiotherapy were included in this study. Clinical factors, such as pretreatment hemoglobin (Hb) level, T-stage, gross tumor volume of primary tumors (pGTV), and maximum standardized uptake value (SUVmax) on FDG-PET, were evaluated for the correlation with local failure. A subset analysis of 32 patients with MR images including diffusionweighted images (DWI) as a pretreatment evaluation was also performed. The Kaplan-Meier curves, the log-rank test, and the Cox proportional hazards model were used to evaluate these clinical factors. Results: Eleven of 64 patients experienced local recurrence, with a median follow-up time of 15 months. In the univariate analysis, Hb level (p = 0.0261), T-stage (p = 0.012), pGTV (p = 0.0025), and SUVmax (p = 0.024) were significantly associated with local failure. In the multivariate analysis, pGTV (p = 0.0070) remained an adverse factor for local control. In the subset analysis of 32 patients with DWI, the median apparent diffusion coefficient (ADC) value of primary tumors on DWI was 0.79 × 10 –3 mm 2 /s (range, 0.40–1.60 × 10 –3 mm 2 /s). Patients with a high ADC value (> 0.79 × 10 –3 mm 2 /s) had a significantly lower local control rate than patients with a low ADC value (100% vs. 44%, p = 0.0019). The rate of local failure among patients with a large pGTV and a high ADC value was 55% (6/11), whereas no local failures occurred (0%, 0/21) among patients with a small pGTV or a low ADC. Co nclusions: These results suggest that a combination of a large tumor volume and a high ADC value could be predictive of local recurrence after definitive radiotherapy in hypopharyngeal or oropharyngeal squamous cell carcinoma.

Postoperative radiotherapy in patients with salivary duct carcinoma: clinical outcomes and prognostic factors

This study sought to investigate the clinical outcome and the role of postoperative radiotherapy for patients with salivary duct carcinoma (SDC) who had undergone surgery and postoperative radiotherapy. We performed a retrospective analysis of 25 SDC patients treated between 1998 and 2011 with surgery and postoperative radiotherapy. The median prescribed dose was 60 Gy (range, 49.5–61.4 Gy). The clinical target volume (CTV) was defined as the tumor bed in four patients, the tumor bed and ipsilateral neck in 14 patients, and the tumor bed and bilateral neck in six patients. Local control (LC), disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and prognostic variables were analyzed with the log-rank test. The 5-year LC, DFS and OS were 67%, 45% and 47%, respectively. Disease recurrence was found in 12 patients: seven as local, four as regional and eight as distant failure. Perineural and lymphovascular invasion was a significant prognostic factor for LC (P = 0.03). Local failure was common, and the presence of local recurrence significantly affected the OS (P < 0.05). We conclude that surgery and postoperative radiotherapy is expected to decrease the risk of local failure and contribute to good prognoses for patients with SDC. It might be advisable to have the CTV include the cranial nerves involved and the corresponding parts of the skull base in cases of pathologically positive perineural invasion.

Breath-hold monitoring and visual feedback for radiotherapy using a charge-coupled device camera and a head-mounted display: system development and feasibility

PurposeThe aim of this study was to present the technical aspects of the breath-hold technique with respiratory monitoring and visual feedback and to evaluate the feasibility of this system in healthy volunteers.Methods and materialsTo monitor respiration, the vertical position of the fiducial marker placed on the patient’s abdomen was tracked by a machine vision system with a charge-coupled device camera. A monocular head-mounted display was used to provide the patient with visual feedback about the breathing trace. Five healthy male volunteers were enrolled in this study. They held their breath at the end-inspiration and the end-expiration phases. They performed five repetitions of the same type of 15-s breath-holds with and without a head-mounted display, respectively. A standard deviation of five mean positions of the fiducial marker during a15-s breath-hold in each breath-hold type was used as the reproducibility value of breath-hold.ResultsAll five volunteers well tolerated the breath-hold maneuver. For the inspiration breath-hold, the standard deviations with and without visual feedback were 1.74 mm and 0.84 mm, respectively (P = 0.20). For the expiration breath-hold, the standard deviations with and without visual feedback were 0.63 mm and 0.96 mm, respectively (P = 0.025).ConclusionOur newly developed system might help the patient achieve improved breath-hold reproducibility.

Prediction of outcome with FDG-PET in definitive chemoradiotherapy for esophageal cancer

The purpose of this study was to assess the efficacy of 18F-fluoro-2-deoxy-glucose uptake positron emission tomography (FDG-PET) for the prediction of outcome in definitive chemoradiotherapy (CRT) for esophageal cancer. We enrolled 56 patients with esophageal cancer treated with definitive CRT and examined by FDG-PET before treatment. We examined the correlation of the maximum standardized uptake value (SUVmax) in FDG-PET of the primary tumor with overall survival (OS), progression-free survival (PFS), local control (LC) and response of the primary tumor. After definitive CRT, 30 patients had a clinical complete response (CR), making the CR rate 54%. For all 56 patients, the 2-year OS rate, PFS rate and LC rates were 64%, 38% and 51%, respectively. We divided the patients into two groups according to SUVmax: SUVmax < 10 (low-SUV) and ≥10 (high-SUV). The 2-year OS rates in the low- and high-SUV groups were 100% and 41%, the PFS rates were 73% and 19%, the LC rates were 71% and 39%, and the CR rates were 100% and 32%, respectively. A univariate analysis revealed significant differences between the low- and high-SUV group in OS, PFS, LC and response (P = 0.0005, 0.0002, 0.048, and <0.0001, respectively). SUVmax and T stage were significantly associated with OS, PFS, LC and response. A multivariate analysis showed significant differences between the SUVmax <10 and ≥10 groups in overall survival and response (P < 0.05). Our result suggests that the SUVmax in FDG-PET of the primary tumor before treatment may have prognostic value for esophageal cancer.

A clinical evaluation of visual feedback-guided breath-hold reproducibility of tumor location

The purpose of this study was to evaluate the reproducibility of visual feedback-guided breath-hold using a machine vision system with a charge-coupled device camera and a monocular head-mounted display. Sixteen patients with lung tumors who were treated with stereotactic radiotherapy were enrolled. A machine vision system with a charge-coupled device camera was used for monitoring respiration. A monocular head-mounted display was used to provide the patient with visual feedback about the breathing trace. The patients could control their breathing so that the breathing waveform would fall between the upper and lower threshold lines. Planning and treatment were performed under visual feedback-guided expiratory breath-hold. Electronic portal images were obtained during treatment. The range of cranial-caudal motion of the tumor location during each single breath-hold was calculated as the intra-breath-hold (intra-BH) variability. The maximum displacement between the two to five averaged tumor locations of each single breath-hold was calculated as the inter-breath-hold (inter-BH) variability. All 16 patients tolerated the visual feedback-guided breath-hold maneuvers well. The intra- and inter-BH variability of all patients was 1.5 +/- 0.6 mm and 1.2 +/- 0.5 mm, respectively. A visual feedback-guided breath-hold technique using the machine vision system is feasible with good breath-hold reproducibility.

Esophageal stenosis associated with tumor regression in radiotherapy for esophageal cancer: Frequency and prediction

PURPOSE To determine clinical factors for predicting the frequency and severity of esophageal stenosis associated with tumor regression in radiotherapy for esophageal cancer. METHODS AND MATERIALS The study group consisted of 109 patients with esophageal cancer of T1-4 and Stage I-III who were treated with definitive radiotherapy and achieved a complete response of their primary lesion at Kyushu University Hospital between January 1998 and December 2007. Esophageal stenosis was evaluated using esophagographic images within 3 months after completion of radiotherapy. We investigated the correlation between esophageal stenosis after radiotherapy and each of the clinical factors with regard to tumors and therapy. For validation of the correlative factors for esophageal stenosis, an artificial neural network was used to predict the esophageal stenotic ratio. RESULTS Esophageal stenosis tended to be more severe and more frequent in T3-4 cases than in T1-2 cases. Esophageal stenosis in cases with full circumference involvement tended to be more severe and more frequent than that in cases without full circumference involvement. Increases in wall thickness tended to be associated with increases in esophageal stenosis severity and frequency. In the multivariate analysis, T stage, extent of involved circumference, and wall thickness of the tumor region were significantly correlated to esophageal stenosis (p = 0.031, p < 0.0001, and p = 0.0011, respectively). The esophageal stenotic ratio predicted by the artificial neural network, which learned these three factors, was significantly correlated to the actual observed stenotic ratio, with a correlation coefficient of 0.864 (p < 0.001). CONCLUSION Our study suggested that T stage, extent of involved circumference, and esophageal wall thickness of the tumor region were useful to predict the frequency and severity of esophageal stenosis associated with tumor regression in radiotherapy for esophageal cancer.

Long-term local control of recurrent adenoid cystic carcinoma in the parotid gland with radiotherapy and intraarterial infusion chemotherapy

We report a case of postoperative recurrence of adenoid cystic carcinoma in the left parotid gland treated with radiotherapy and arterial infusion chemotherapy. A 52-year-old woman had a history of surgical resection for an adenoid cystic carcinoma arising from the left parotid gland 25 years before. Despite two reoperations for local recurrence after the initial surgery, she had a third local recurrence in the remnant of the left parotid gland. The patient was treated with a concurrent combination of radiotherapy (60 Gy/30F) and intraarterial infusion chemotherapy with carboplatin (750 mg/30 days) from which she obtained a complete response. The patient has remained free of local progression 54 months after treatment. Radiotherapy and arterial infusion chemotherapy is effective treatment for local recurrence of adenoid cystic carcinoma in the head and neck.

Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced MR finding of radiation-induced hepatic injury: Relationship to absorbed dose and time course after irradiation

PURPOSE To evaluate if Gd-EOB-DTPA-enhanced MRI could identify liver tissue damage caused by radiation exposure in patients undergoing external beam radiation therapy. MATERIALS AND METHODS We enrolled 11 patients who underwent Gd-EOB-DTPA-enhanced MRI during or after radiotherapy in which the radiation field included the liver. External beam radiotherapy was delivered through multiple fields using a 10-MV linear accelerator. The hepatobiliary phase images of Gd-EOB-DTPA-enhanced MRI were qualitatively evaluated for the presence of a decreased uptake of Gd-EOB-DTPA in the irradiated area in the liver. Next, signal intensity (SI) ratio of the irradiated area to the non-irradiated liver parenchyma was also calculated. The absorbed dose of the irradiated area in the liver was standardized using equivalent dose in 2Gy fraction (EQD2) and biological effective dose (BED). The results of qualitative analysis were compared with EQD2 or BED, and linear regression analysis was performed between EQD2 or BED and SI ratio. RESULTS Twenty-two irradiated areas were evaluated. Qualitative analysis revealed a decreased uptake of Gd-EOB-DTPA in 14 areas and no decreased uptake of Gd-EOB-DTPA in eight areas. The thresholds of EQD2 and BED causing a decreased uptake of Gd-EOB-DTPA were considered to be 24 to 29Gy and 29 to 35Gy, respectively. Quantitatively, SI ratio decreased as EQD2 or BED increased (r=0.89, p<0.001), and the inverse relationship between signal enhancement and the absorbed dose in the irradiated area was obtained. One area with EQD2 of 50Gy and BED of 60Gy showed a slightly decreased uptake of Gd-EOB-DTPA on the 40th day but a clearly decreased uptake of Gd-EOB-DTPA on the 123rd day from initiation of radiotherapy. CONCLUSIONS Gd-EOB-DTPA-enhanced MRI described RLI as a decreased uptake of Gd-EOB-DTPA matching the irradiated area. The occurrence of this finding was significantly correlated with the absorbed dose of the irradiated area in the liver.

Can a belly board reduce respiratory-induced prostate motion in the prone position? - Assessed by cine-magnetic resonance imaging

The purpose of this study is to evaluate the real-time respiratory motion of the prostate and surrounding tissues/organs in the supine and prone positions and to investigate, using cine-MRI, whether a belly board can reduce respiratory-induced motion in the prone position. Cine-MRI scans were made of 13 volunteers in the supine and prone positions on a flat board and in two different prone positions using a belly board. Images in cine mode were recorded for 20 seconds. For each session, the points of interest (POIs) were located at the apex, base, mid-anterior surface and mid-posterior surface of the prostate; the tip of the seminal vesicle; the pubic symphysis; and the sacrum. The maximum range and standard deviation (SD) of the displacement from the mean value were calculated. The SDs for each of the four different positions were compared using a paired t-test. Respiratory-induced prostate motion was significantly larger in the prone position than in the supine position. However, when a belly board was used in the prone position, motion in the prostate and surrounding tissues/organs was significantly reduced. There were no significant differences between the two different positions using a belly board in any of the POIs.