Toshinori Soejima

PROSPECTIVE TRIAL OF COMBINED TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION AND THREE-DIMENSIONAL CONFORMAL RADIOTHERAPY FOR PORTAL VEIN TUMOR THROMBUS IN PATIENTS WITH UNRESECTABLE HEPATOCELLULAR CARCINOMA

PURPOSE We conducted a prospective trial of combined transarterial chemoembolization (TACE) and three-dimensional conformal radiotherapy (3D-CRT) for portal vein tumor thrombus (PVTT) in unresectable hepatocellular carcinoma (HCC). The aim of the present study was to investigate the efficacy and toxicity of this trial regime. METHODS AND MATERIALS Patients with unresectable HCC complicated with tumor thrombus in the first branch of portal vein were selected as eligible for this study. TACE was performed using Lipiodol, epirubicin hydrochloride, and mitomycin, followed by gelatin sponge cubes. The 3D-CRT was performed targeting the clinical target volume (CTV) defined as PVTT only to a total dose of 60 Gy using 10-MV accelerator. RESULTS A total of 19 patients were enrolled in this study. Survival rates at 1 and 2 years were 40.6% and 10.2%, respectively. The median survival time was 7.0 months. An objective response was observed in 11 of 19 cases (57.9%). Recanalization of the first portal branches was not observed; however, the protrusion of PVTT into the main portal trunk decreased in all cases. Growth of intrahepatic metastasis outside the 3D-CRT field was observed in 12 cases (63%). Deterioration of the Child-Pugh Score was observed in 5 of 6 cases with the percent volume of the total liver receiving a dose exceeding 30 Gy (V(30)) > or =40%, vs. 2 of 13 cases with a V(30) <40% (p < 0.01). CONCLUSION This combined therapy was feasible. Our results indicate that V(30) was a predictive test for deterioration of liver function. Further investigation of treatment modalities is needed to prevent the growth of intrahepatic metastasis.

Angiosarcoma treated with radiotherapy: impact of tumor type and size on outcome

PURPOSE Angiosarcoma is a rare and highly malignant vascular neoplasm. The purpose of this study was to elucidate the tumor characteristics and evaluate the efficacy of radiotherapy (RT) for angiosarcoma. MATERIALS AND METHODS Thirty patients with angiosarcoma (20 males and 10 females, age range 4-89 years, median 66) who received RT from 1986 to 1999 were enrolled in the study. Twenty-four patients had angiosarcoma of the face and scalp (AFS), and 6 patients had angiosarcomas at other sites. AFS was classified into two categories (according to the macroscopic features): nodular AFS (14 patients) and endophytic AFS (10 patients). The median prescribed irradiation dose was 68 Gy. Surgery had been previously performed in 9 patients, and adjuvant immunotherapy using recombinant interleukin-2 (rIL-2) was combined during and after RT in 20 patients. Univariate analyses and calculation of survival by Kaplan-Meier methods were performed. RESULTS Local tumor control was obtained in 17 patients (57%). However, 7 (47%) of them developed distant metastases. The median survival time for all patients was 8 months (7 months for AFS), and the 13-year overall survival rate was 25% (20% for AFS). Twenty-one patients died of angiosarcoma, with the cause of death local failure in 7 patients, distant failure in 7, and both in 7. Tumor type and size were found to be significant prognostic factors (p = 0.004 and p = 0.007, respectively), and age, total amount of rIL-2, gender, radiation dose, and surgery were not. Six patients (4 with nodular AFS and 2 with angiosarcoma in other parts) survived >2 years. No patient with endophytic AFS survived >2 years. Ten patients (33%) died of respiratory failure secondary to pulmonary metastases. High-dose rIL-2 administration suppressed the occurrence of distant metastases (p = 0.006). Two patients developed radiation dermatitis (Radiation Therapy Oncology Group Grade 4). CONCLUSION RT, combined with complete resection or adjuvant rIL-2 immunotherapy, could be a promising treatment strategy, leading to prolonged survival in patients with angiosarcoma.

Severe complications in advanced esophageal cancer treated with radiotherapy after intubation of esophageal stents: a questionnaire survey of the Japanese Society for Esophageal Diseases.

PURPOSE A questionnaire survey was performed to evaluate the complications and prognosis of esophageal cancer treated with esophageal intubation before or during radiotherapy. METHODS AND MATERIALS Clinical data were accumulated on a total of 47 patients treated at 17 institutions in Japan. Five patients had Stage II, 30 Stage III, and 11 Stage IV, and the stage was unknown in 1 patient. Covered expandable metallic stents were inserted in 30 patients, uncovered expandable metallic stents in 13, plastic or silicon prosthesis in 3, and an unknown type in 1 patient. Esophageal stenting was performed before the start of RT for 23 patients and during the course of RT for 24 patients. The reasons for the stenting were severe stricture in 32 patients (Group 1) and esophageal fistula in 15 patients (Group 2). RESULTS The most frequent toxicity was formation or worsening of esophageal fistulas in 13 patients (28%), followed by massive hematemesis or GI bleeding in 10 patients (21%). In total, 24 patients (51%), including 10 patients with possible treatment-related deaths (Grade 5), had nonhematologic toxicities of Grade 3-5. The interval from the start of RT to the nonhematologic toxicity ranged from 16 to 312 days (median 78). The incidence of toxicities was higher for Group 1 (59%) than for Group 2 (33%), although the difference was not statistically significant. The median survival time for those with Stage II-III and Stage IV was 5 and 3.5 months, respectively. CONCLUSIONS Patients with esophageal intubation before or during RT have a high risk of life-threatening complications, especially for those with severe esophageal stricture. Because long survival is expected for a substantial proportion of patients with locally advanced esophageal cancer after chemoradiotherapy, palliative intubation should be delayed until radiotherapy or chemoradiotherapy appears to have failed.

Endoscopic findings of radiation esophagitis in concurrent chemoradiotherapy for intrathoracic malignancies

BACKGROUND AND PURPOSE The incidence and extent of radiation esophagitis were assessed endoscopically in patients treated with concurrent chemoradiotherapy. PATIENTS AND METHODS Eighty-two patients who received thoracic radiotherapy for lung, thymic, or esophageal cancer were investigated endoscopically from July 1991 to the end of 1997. Among them, 23 esophageal cancer patients were treated with radiation alone, and the others were treated with concurrent chemoradiotherapy. Esophageal endoscopy was performed during or just after radiotherapy. The presence of radiation esophagitis was assessed and assigned an endoscopic score (i.e. grade 0 for normal, 1 for erythema, 2 for erosion or sloughing, 3 for ulcer, hemorrhage, or stricture). The symptomatic grade was assessed using the RTOG (Radiation Therapy Oncology Group) acute radiation morbidity score. RESULTS A correlation was seen between endoscopic and RTOG scores. However, even some patients with RTOG grade 0 to 1 had endoscopic grade 3 esophagitis. Endoscopic grade 3 was observed in 16 (27.1%) patients in the concurrent chemoradiotherapy group, whereas it did not occur in any patient in the radiation alone group (P=0.004). CONCLUSIONS Our results suggest that (1) RTOG score correlates closely to esophageal mucosal damage, and (2) more severe esophagitis occurs in those undergoing concurrent chemoradiotherapy than those undergoing radiotherapy alone [corrected].

Clinical significance of serum pulmonary surfactant proteins A and D for the early detection of radiation pneumonitis

PURPOSE Radiation pneumonitis (RP) is one of the most serious complications for patients who receive thoracic irradiation. To avoid this, early diagnosis of radiation pneumonitis is extremely important. The purpose of the present study is to investigate whether serum pulmonary surfactant proteins A and D (SP-A and SP-D, respectively) could be useful markers for RP. METHODS AND MATERIALS Eighty-six patients (lung cancer: 42 [primary: 39, metastatic: 3], breast cancer: 23, esophageal cancer: 21) who underwent radiation therapy were prospectively studied. Radiation doses ranged from 30-76 Gy (median, 58 Gy). Serum SP-A and SP-D levels were evaluated sequentially by a sandwich enzyme-linked immunosorbent assay (ELISA) method before, during, and throughout the follow-up period until the development of symptomatic RP or until one year after completion of radiotherapy. Specificity of the ELISA results was confirmed by Western blot analysis. Patients symptomatic for RP were graded according to the Common Toxicity Criteria. RESULTS RP occurred in 19 patients. Serum SP-D levels of patients with RP were sequentially higher than those in patients without RP. In the monitoring, serum SP-D levels at 50-60 Gy showed greater sensitivity and positive predictive values for RP detection (74% and 68%, respectively) than SP-A (26% and 21%, respectively). Western blot analysis showed that the development of RP was due to overproduction, but not proteolysis of surfactant proteins. CONCLUSION We confirm that serum SP-A and SP-D monitoring is a practical and useful diagnostic method for the early detection of RP.

Combined Analysis of V20, VS5, Pulmonary Fibrosis Score on Baseline Computed Tomography, and Patient Age Improves Prediction of Severe Radiation Pneumonitis After Concurrent Chemoradiotherapy for Locally Advanced Non-Small-Cell Lung Cancer

Introduction: We aimed to develop a more accurate model for predicting severe radiation pneumonitis (RP) after concurrent chemoradiotherapy for non–small-cell lung cancer. Methods: We retrospectively analyzed data from 122 patients with locally advanced non–small-cell lung cancer treated with concurrent chemoradiotherapy. Several dose-volume histogram metrics including absolute lung volume spared from a 5 Gy dose (VS5) were analyzed for an association with RP above NCI-CTC grade 3 (RP ≥ G3). Clinical factors including pulmonary fibrosis score (PFS) and pulmonary emphysema score on baseline chest computed tomography (CT) were also analyzed. Results: Fourteen patients (11.4%) developed RP greater than or equal to G3. On univariate analysis, all dose-volume histogram metrics, sex, and PFS on baseline CT were significantly (p < 0.05) associated with occurrence of RP greater than or equal to G3. Multivariate analysis revealed that V20 greater than or equal to 26%, VS5 less than 1500 cc, age greater than or equal to 68 years, and PFS on baseline CT greater than or equal to 2 were significant risk factors. Thus, we defined a new predictive risk score (PRS) that combines these factors. The cumulative incidence of RP greater than or equal to G3 at 12 months were 0%, 7.8%, 26.6%, and 71.4% when the PRS was 0, 3–5, 6–8, and 9–14, respectively (p < 0.001). This PRS was superior at predicting RP than both V20 and VS5 combined, or V20 alone by receiver operating characteristic analysis (area under the curve, 0.888 versus 0.779 versus 0.678). Conclusions: V20, VS5, age, and PFS on baseline CT are independent and significant risk factors for occurrence of severe RP. Combining these factors may improve the predictability of severe RP.

Radiation Therapy in Patients with Implanted Cardiac Pacemakers and Implantable Cardioverter Defibrillators: A Prospective Survey in Japan

Radiotherapy/Pacemaker/ICD/Malfunction. Patients with implanted cardiac pacemakers (ICPs) or implantable cardioverter defibrillators (ICDs) ar e increasing in number, and the incidence of treating these patients with radiation therapy also is increasing. Thus, a prospective survey was conducted of patien ts with these devices receiving radiation therapy. A prospective survey of patients with ICPs or ICDs treated with radiation therapy was conducted on methods of radiation therapy, status of ICP/ICD, and management of patients before, during, and after radiation th erapy. After completion of radiation therapy, study participants were registered via mail, fax, or e-mail. Sixty-two patients from 29 institutions were registered from September 2006 to December 2008. Sixty patients had an ICP and 2 had an ICD. The total dose was estimated before radiation therapy by dosevolume histogram in 26 patients (42%) and by measurement of actual doses in 9 (15%). In one patient, the maximum total dose was 2069 cGy; however, in the other patients, the ICP/ICD dose did not exceed 478 cGy. Function of ICPs and ICDs was checked before radiation therapy in 38 patients (61%), after radiation therapy in 32 (52%), and both before and after radiation ther apy in 29 (47%). ICP malfunction occurred in a patient with prostate cancer treated by intensity-modulated radiation therapy to the prostate. Even when an ICP or ICD is not within the field of radiation, malfunction of the device may still occur. To minimize the risk to patients, precautions must be taken during the planning and administration of radiation therapy.

Nuclear factor-κB expression as a novel marker of radioresistance in early-stage laryngeal cancer†‡

The aim of this study was to evaluate the significance of nuclear factor‐kappa B (NF‐κB) expression as a marker of radioresistance in early‐stage laryngeal cancer.

White matter changes on magnetic resonance imaging following whole-brain radiotherapy for brain metastases

PurposeThe purpose of this study was to evaluate white matter (WM) abnormalities induced by WBRT.Materials and methodsTwenty-four patients (11 men and 13 women; age range 38–74 years, median 60 years) who survived for more than 1 year after completion of WBRT (radiation dose range 30–40 Gy, median 35 Gy) at our institution between January 2000 and June 2003 were followed up with magnetic resonance (MR) scans for 11–51 months (median 19 months). We evaluated WM changes attributable to WBRT as grade 0–6 and assessed possible contributing factors by statistical analysis.ResultsWM changes were found in 20 patients: Eight were assessed as grade 2, three as grade 3, and nine as grade 5. In total, 12 patients developed grade 3 or higher WM changes. Age (<60 vs ≥60 years), sex, radiation dose (≤35 vs >35 Gy), chemotherapy (with CDDP vs without CDDP), biologically effective dose (≤120 vs >120 Gy1), and head width (<16.3 vs ≥16.3 cm) were found not to be relevant to the incidence or severity of the WM changes.ConclusionLong-term survivors who have under-gone WBRT may have a higher incidence of WM abnormalities.

Pelvic insufficiency fracture after definitive radiotherapy for uterine cervical cancer: retrospective analysis of risk factors

The purpose of this study is to determine the incidence, clinical characteristics and risk factors of postradiation pelvic insufficiency fracture (PIF) in women with uterine cervical cancer. We reviewed the medical records of 126 patients who received definitive radiotherapy (RT) for uterine cervical cancer between 2003 and 2009 at our institution. Among them, 99 patients who underwent at least one computed tomography (CT) or magnetic resonance imaging of the pelvis during their follow-up at more than 6 months were included in this analysis. The relationship between the incidence of PIF and several patient- and treatment-related factors was analyzed. The median follow-up period was 21 months. Of the 126 patients, 33 (with a total of 50 lesions) were diagnosed with PIF. The 2-year cumulative incidence was 32%. Univariate analysis showed that age ≥70 years (P= 0.0010), postmenopausal state (P = 0.0013), and lower CT density of bone and bone marrow (P= 0.020) significantly related to PIF. In a multivariate analysis, of the 59 patients whose CT densities were evaluable, lower CT density was the only significant factor associated with PIF (P = 0.0026). In conclusion, postradiation PIFs were detected in a considerable number of patients after definitive RT for cervical cancer. Predisposing factors were older age, postmenopausal state, and decreased density of bone and bone marrow on CT.