Yoshihito Nomoto

Comparison of prognostic value of MRI and FIGO stage among patients with cervical carcinoma treated with radiotherapy.

PURPOSE To compare the efficacy of MRI and FIGO stage, we performed retrospective multicenter analysis of patients with Stage II-III disease treated with radiation alone. METHODS AND MATERIALS From three institutions, 164 patients diagnosed with cervical carcinoma were entered into the study. The majority of this cohort received intracavitary brachytherapy combined with external beam radiotherapy (n = 161). Uni- and multivariate analyses were performed to identify the prognostic factors for overall survival (OAS), disease-free survival (DFS), pelvic control (PC), and distant metastasis-free survival (DMFS). RESULTS The 5-year OAS, DFS, PC, and DMFS rates were 68.8%, 60.4%, 77.4%, and 71.7%, respectively. Using uni- and multivariate analyses, both large tumor size/volume and positive lymph node enlargement (LN) showed a significantly unfavorable influence on survival and local and/or distant failure (p < 0.05). Using these two prognostic factors, patients were divided into three subgroups; the 5-year DFS rates of patients with risk 0 (volume </=50 cc and negative LN), 1 (volume >50 cc or positive LN), and 2 (volume >50 cc and positive LN) were 72.9%, 53.3%, and 26.1%, respectively (p < 0.0001). Among patients with volume </=50 cc, disease stage proved to be a significantly prognostic factor of OAS, DFS, and PC (p < 0.05). However, these correlations were not observed in the large volume group (p > 0.05). CONCLUSION MRI will provide more useful and practical information than will FIGO stage classification for patients with bulky disease, although this will remain a prognostic factor for patients with nonbulky disease (volume </=50 cc). With the aid of MRI, accurate and practical evaluation of clinical outcome could be achieved.

Complications after lung radiofrequency ablation: Risk factors for lung inflammation

This retrospective study was conducted to review the complications of lung radiofrequency (RF) ablation and to clarify the effects of inflammation after lung RF ablation on mortality and morbidity. Complications were evaluated by reviewing medical records on an RF session basis. The C-reactive protein (CRP) value was used as an indicator of inflammation and was measured before and every 1-2 days during the hospital stay after RF ablation. The relationships between CRP values and patient baselines were evaluated to identify factors affecting lung inflammation. 130 patients who underwent 327 lung RF ablation sessions were enrolled in this study. The major complication rate was 18.3% (60/327). Inflammation-related complications such as interstitial pneumonia (n = 2) and aseptic pleuritis (n = 2) developed in four sessions (1.2%). Death occurred in two patients with interstitial pneumonia (0.6%). The mean CRP value increased significantly from 1.3+/-2.6 mg dl(-1) to 3.4+/-5.6 mg dl(-1) (p<0.01) after RF ablation. Large tumour size (>or=2 cm) and previous external-beam radiotherapy were significant factors associated with an increased CRP value in both univariate and multivariate analyses. In conclusion, although the incidence rate is low, fatal lung inflammation may develop after lung RF ablation. Large tumour size and previous external-beam radiotherapy are risk factors for severe lung inflammation.

Clinical assessment by MRI for patients with Stage II cervical carcinoma treated by radiation alone in multicenter analysis: are all patients with Stage II disease suitable candidates for chemoradiotherapy?

PURPOSE From recent randomized trials, patients with Stage II cervical carcinoma are thought to be candidates for chemoradiotherapy. To refine the strategy for Stage II patients, we performed a retrospective multi-institutional analysis using MRI. METHODS AND MATERIALS From three institutions, 84 patients with Stage II cancer diagnosed by MRI were entered into the study. All patients received intracavitary brachytherapy with (n = 83) or without (n = 1) external beam radiotherapy. Uni- and multivariate analyses were performed to identify the prognostic factors for overall survival (OAS), disease-free survival (DFS), pelvic control (PC), and distant metastasis-free survival (DMFS). RESULTS The 5-year DFS rate of patients with maximal tumor size (D(max)) > or =50 mm (46.2%) was significantly lower than that for patients with D(max) <50 mm (88.0%; p <0.0001). Large size or volume and lymph node swelling were also significant prognostic factors of OAS, DFS, PC, and DMFS. In the multivariate model, size or volume was a significant prognostic factor of OAS, DFS, PC, and DMFS, and lymph node swelling was a prognostic factor for DFS, PC, and DMFS. Using these two prognostic factors, patients were divided into 3 subgroups. The 5-year DFS rate of patients with risk 0 (D(max) <50 mm and negative lymph node swelling), 1 (D(max) > or =50 mm or positive lymph node swelling), and 2 (D(max) > or =50 mm and positive lymph nodes) was 93.2%, 53.3%, and 25.0%, respectively (p <0.0001). CONCLUSION In this stage-limiting analysis, we clarified the stratification according to clinical risk with the aid of MRI. For patients with low-risk factors, especially for elderly patients, radiation alone would probability be a feasible option. In the future, a randomized trial using criteria with MRI would help to identify the optimal strategy for patients with Stage II disease.

High dose rate endobronchial brachytherapy using a new applicator

BACKGROUND AND PURPOSE To obtain adequate spatial dose distribution for endobronchial brachytherapy, we applied reference dose points according to the bronchial diameter. For this purpose, we devised a new applicator of which the source transfer tube is contained in the center of the lumen for high dose rate (HDR) brachytherapy. MATERIALS AND METHODS Thirty-nine patients with endobronchial cancer underwent endobronchial brachytherapy using an HDR afterloading machine with an Ir-192 source. In the nine patients treated with curative intent, treatment consisted of external beam radiotherapy with 40-60 Gy for 4-6 weeks and endobronchial brachytherapy with three fractions of 6 Gy. The 30 patients treated with palliative intent received one fraction of 10 Gy with or without external beam irradiation. The reference dose points were prescribed according to bronchial diameter, which was measured by the applicators radiopaque wing expansion reflecting the bronchial caliber. RESULTS The new applicator could be placed at the intended site in 37 lesions. Of 12 lesions which were treated with curative intent, eight (67%) disappeared after brachytherapy. The overall survival at 3 years of all patients and of the patients treated with curative intent was 22 and 64%, respectively. CONCLUSIONS The source should be positioned in the center of the lumen; this technique is helpful in reducing side-effects caused by inhomogeneous dose distribution of endobronchial brachytherapy.

Multi-Institutional Analysis of Early Glottic Cancer from 2000 to 2005

BackgroundThe purpose of this study is to analyze the outcome of patients with early glottic cancer (GC) treated with radiotherapy (RT) with or without chemotherapy at 10 institutions in the Tokai District, Japan.MethodsTen institutions combined data from 279 patients with T1-T2 GC treated with RT with or without chemotherapy between 2000 and 2005. The overall survival rate, disease-specific survival rate, and local control rate were evaluated in 270 patients, except for incomplete cases due to issues such as discontinuation, using the method of Kaplan-Meier and compared using the log-rank test. Results were considered statistically significant at the level of p < 0.05.ResultsFor 122 patients, the tumors were classified as T1a, while 64 patients had T1b tumors, and 84 patients had T2 tumors. In three cases of T1 tumors, the subtype was unknown. Combined chemoradiotherapy (CRT) was administered during each stage, and various chemotherapy drugs and regimens were used. The median follow-up period was 55.4 months. The 5-year LC rates for T1a, Tb, and T2 tumors in all patients were 87.9%, 82.7%, and 74.1%, respectively. The difference between T1a and T2 was statistically significant (p = 0.016). The 5-year LC rates for T1a, Tb, and T2 with CRT were 92.7%, 78.6%, and 80.7%, respectively, while the rates with radiation alone were 86.5%, 83.8%, and 64.4%, respectively. The difference between CRT and RT alone was not statistically significant in each stage.ConclusionsIn this survey, CRT was performed for early GC at most institutions in clinical practice. Our data showed no statistical difference in the LC rates between CRT and RT alone in each stage. However, there was a tendency for the LCRs of the CRT group to be more favorable than those of the RT group in the T2-stage.

Pelvic insufficiency fractures after preoperative radiotherapy for rectal carcinoma

Insufficiency fractures of the pelvic bones are rare complications of radiotherapy, but they can cause significant morbidity. We report a patient who developed pelvic insufficiency fractures because of preoperative hypofractionated radiotherapy with chemotherapy for rectal carcinoma. She was treated with a four-field box technique, receiving 20 Gy in four fractions, and she underwent concurrent pharmacokinetic modulating chemotherapy (PMC; intravenous infusion of 5-fluorouracil [FU], 750 mg/body per 24 h and oral administration of uracil and futrafur [UFT] 400 mg/day) over a 1-week period. She developed severe buttock and femoral pain 10 months after this preoperative therapy. Physical examination at this time was unremarkable, with an absence of neurological signs, and radiographic examination was also normal, resulting in the patient initially being undiagnosed. However, 2 months after the onset of her initial pain, she was diagnosed as having pelvic insufficiency fractures on conventional radiographs. Although preoperative chemoradiotherapy has been widely accepted for improving local control and survival in patients with primary rectal carcinoma, surgeons need to be aware of this rare complication that can arise even 10 months after preoperative chemoradiotherapy.

Radiation-induced organizing pneumonia after stereotactic body radiotherapy for lung tumor

The aim of this retrospective study was to investigate characteristics of organizing pneumonia (OP) after stereotactic body radiotherapy (SBRT) for lung tumor. Between September 2010 and June 2014, patients who were diagnosed as Stage I lung cancer and treated with SBRT at our institution were included in this study. A total of 78 patients (47 males with a median age of 80 years) were analyzed. The median follow-up period was 23 months. Five patients (6.4%) developed OP at 6–18 months after SBRT. The cumulative incidence of OP was 4.3% (95% confidence interval [CI], 1.1–11.0) and 8.2% (95% CI, 2.9–17.0) at 1 and 2 years, respectively. Tumor location (superior and middle lobe vs inferior lobe) was shown to be a borderline significant factor for the occurrence of OP (P = 0.069). In the subgroup analysis of patients with a radiographic follow-up period at least 6 months, or who died within 6 months after SBRT, 7 of 72 patients (9.7%) developed Grade 2 or 3 radiation pneumonitis (G2/3 RP) at 2–4 months after SBRT. A statistically significant association between G2/3 RP in the subacute phase and OP was shown (P = 0.040). In two of the five patients who developed OP, the symptoms and radiographic change were improved rapidly by corticosteroid administration. One patient had relapsed OP after suspending the treatment and re-administration was required. Three patients with minor symptoms were managed without corticosteroid administration and OP resolved without any relapse. The radiation-induced OP should be considered as one of the late lung injuries after SBRT for lung tumors.

Clinical evaluation using magnetic resonance imaging for patients with stage III cervical carcinoma treated by radiation alone in multicenter analysis: its usefulness and limitations in clinical practice.

To evaluate the ability of magnetic resonance imaging (MRI) to predict the clinical outcome, we perform retrospective multicenter analysis of patients with stage III disease treated with radiation alone. From three institutions, 80 patients with stage III disease diagnosed with MRI were entered in the study. Seventy-eight patients received intracavitary brachytherapy with external beam radiotherapy. Univariate and multivariate analyses were performed to identify the prognostic factors for overall survival (OAS), disease-free survival (DFS), pelvic control (PC), and distant metastasis-free survival (DMFS). The 5-year OAS, DFS, PC, and DMFS rates were 59.5%, 48.7, 74.2%, and 62.5%, respectively. Bilateral pelvic fixation to the pelvis (p = 0.001) and patient age 50 years or less (p < 0.0001) were significant adverse factors for OAS. As a function of DFS, these were positive lymph nodes (p = 0.02), bilateral fixation to the pelvis (p = 0.03), and younger patient age (p < 0.0001), respectively. Patient age 50 years or less proved to be the only significantly unfavorable factor for PC (p < 0.0001). Larger size/volume (p < 0.05), positive lymph nodes (p = 0.03), bilateral pelvic disease (p = 0.02), and younger patient age (p = 0.004) were significantly adverse factors for DMFS. Using multivariate analysis, patient age 50 years or less, disease with bilateral fixation, and calculated volume more than 100 ml proved to be significantly adverse factors for OAS and DFS. In the analysis of PC, only patient age 50 years or less was a significantly adverse factor (p = 0.0014, relative risk [RR] = 14.93). Bilateral fixation to the pelvis (p = 0.0055, RR = 4.032), positive lymph nodes (p = 0.0494, RR = 2.637), and large calculated volume (>100 ml; p = 0.0057, RR = 4.831) proved to be significantly adverse factors for DMFS. For patients with stage III disease, size/volume and lymph node status derived from MRI showed a significant correlation with the development of distant metastasis, but failed to predict locoregional control. In addition, size/volume analysis showed no apparent relationship with disease-free survival. For patients with stage III disease, MRI may provide beneficial information predicting distant metastasis, but not for local control.

Preliminary treatment results of proton beam therapy with chemoradiotherapy for stage I–III esophageal cancer

The effect of proton beam therapy (PBT) on various cancers is controversial. We aimed to evaluate the efficacy and safety of PBT with alternating chemoradiotherapy (ACRT) for patients with stage I–III esophageal cancer. Two cycles of systemic chemotherapy with a continuous infusion of 5‐fluorouracil (5‐FU) on days 1–5 and a 5h infusion of nedaplatin (NDP) on day 6 were accompanied by thoracic irradiation using X‐ray therapy and PBT. During the first half of the treatment, X‐rays were delivered to the prophylactic area. During the second half of the treatment, proton beams were used to irradiate the involved field. To reduce the dose of cardiac irradiation, proton beams were delivered with posterior and posterior oblique angles. Between January 2009 and December 2012, 47 patients were enrolled in this study. The median follow‐up duration was 29 months for all patients and 40 months for survivors. The 3 year overall survival rate, progression‐free survival rate, and local control rate were 59.2%, 56.3%, and 69.8%, respectively. With respect to grade 3–4 late toxicities, there were no pleural or pericardial effusions, but two patients (4.3%) had esophageal stenosis, one patient (2.1%) had fistula, and two patients (4.3%) developed radiation pneumonitis. PBT with ACRT might have the potential to reduce the risk of cardiac damage and might become one of the primary methods of esophageal cancer treatment.

DNA ploidy analysis performed prospectively using fresh tumor samples in early glottic carcinoma treatedwith radiotherapy

PURPOSE The correlation between the DNA content, determined using fresh tumor tissues, and the macroscopic presentation of the lesion was studied prospectively in patients with T1 glottic carcinoma. METHODS AND MATERIALS DNA flow cytometry and fiber-optic endoscopic examination were performed for 30 previously untreated patients with T1 glottic carcinoma. The patients received radical radiotherapy at Aichi Cancer Center Hospital. RESULTS In regard to the type of lesion, 4 (80%) were aneuploid, and 1 (20%) was diploid for the invasive type. There was a tendency to show an invasive appearance in aneuploid tumors. With respect to clinical outcome, there were 3 (43%) local recurrences among the aneuploid tumors that invaded the entire length of one vocal cord, 0 (0%) for medium-sized lesions, and 1 (17%) for small lesions. Aneuploid tumors showed a high correlation between lesion size and local control. CONCLUSIONS The correlation was not strong enough to conclude that DNA content can replace the macroscopic presentation of the lesion. However, the combination of DNA content and tumor size may help predict radiation sensitivity.