Natsuo Tomita

Invasive Thymoma: Postoperative Mediastinal Irradiation, and Low-Dose Entire Hemithorax Irradiation in Patients with Pleural Dissemination

Introduction: We evaluated the results of postoperative mediastinal radiotherapy (MRT) for invasive thymoma and low-dose entire hemithorax radiotherapy (EHRT) for pleural dissemination. Methods: Sixty patients were treated with a nearly uniform policy. Generally, we administered 30 to 40 Gy MRT after surgery at 2 Gy daily fractions for Masaoka stage II tumors or suspected residual diseases, and 50 to 55 Gy MRT for stage III tumors and for highly-suspected or macroscopic residual diseases. Since 1992, we have administered EHRT in patients with pleural dissemination, with 11.2 Gy in 7 fractions or 15 to 16 Gy in 10 fractions after removal of disseminated lesions in addition to MRT. We treated 52 patients with MRT alone and 8 with EHRT and MRT. In addition, we gave EHRT to four patients who developed pleural dissemination later. Results: For all 60 patients, the overall and cause-specific survival and local and pleural-dissemination control rates at 5 years were 79, 87, 86, and 69%, respectively. Both Masaoka stage and tumor resectability were associated with prognosis. In stage IVa patients, pleural dissemination control rate was 71% at 3 years after EHRT, whereas it was 49% in patients receiving MRT alone (p = 0.38). Grade 2 or higher radiation pneumonitis was observed in only 3 of 52 patients (5.8%) undergoing MRT initially. In 12 patients who underwent EHRT, 3 patients (25%) experienced grade 2 or 4 pneumonitis. Conclusions: Postoperative MRT appeared to prevent local recurrence with acceptable toxicity. EHRT is generally safe and may contribute to control of pleural dissemination.

Stereotactic body radiotherapy for stage I lung cancer and small lung metastasis: evaluation of an immobilization system for suppression of respiratory tumor movement and preliminary results

BackgroundIn stereotactic body radiotherapy (SBRT) for lung tumors, reducing tumor movement is necessary. In this study, we evaluated changes in tumor movement and percutaneous oxygen saturation (SpO2) levels, and preliminary clinical results of SBRT using the BodyFIX immobilization system.MethodsBetween 2004 and 2006, 53 consecutive patients were treated for 55 lesions; 42 were stage I non-small cell lung cancer (NSCLC), 10 were metastatic lung cancers, and 3 were local recurrences of NSCLC. Tumor movement was measured with fluoroscopy under breath holding, free breathing on a couch, and free breathing in the BodyFIX system. SpO2 levels were measured with a finger pulseoximeter under each condition. The delivered dose was 44, 48 or 52 Gy, depending on tumor diameter, in 4 fractions over 10 or 11 days.ResultsBy using the BodyFIX system, respiratory tumor movements were significantly reduced compared with the free-breathing condition in both craniocaudal and lateral directions, although the amplitude of reduction in the craniocaudal direction was 3 mm or more in only 27% of the patients. The average SpO2 did not decrease by using the system. At 3 years, the local control rate was 80% for all lesions. Overall survival was 76%, cause-specific survival was 92%, and local progression-free survival was 76% at 3 years in primary NSCLC patients. Grade 2 radiation pneumonitis developed in 7 patients.ConclusionRespiratory tumor movement was modestly suppressed by the BodyFIX system, while the SpO2 level did not decrease. It was considered a simple and effective method for SBRT of lung tumors. Preliminary results were encouraging.

Estimation of Errors Associated With Use of Linear-Quadratic Formalism for Evaluation of Biologic Equivalence Between Single and Hypofractionated Radiation Doses: An In Vitro Study

PURPOSE To investigate the reliability of the linear-quadratic (LQ) formalism and the magnitude of errors associated with its use in assessing biologic equivalence between single, high radiation doses and hypofractionated radiation doses. METHODS AND MATERIALS V79 and EMT6 single cells received single doses of 2-12 Gy or two or three fractions of 4 or 5 Gy, each at 4-h intervals. Single and fractionated doses to actually reduce the cell survival to the same level were determined by a colony assay. The alpha/beta ratio was obtained from the cell survival curves. Using the alpha/beta ratio and the LQ formalism, equivalent single doses for the hypofractionated doses were calculated. They were then compared with the actually determined equivalent single doses for the hypofractionated doses. The V79 spheroids received single doses of 5-26 Gy or two to five fractions of 5-12 Gy at 2 or 4-h interval, and then were assayed for cell survival. Next, equivalent single doses for the hypofractionated doses were determined, as were done for the single cells. RESULTS The alpha/beta ratio was 5.1 Gy for the V79 single cells and 0.36 Gy for EMT6. In V79, the equivalent single doses for the hypofractionated doses calculated using the LQ formalism were 12-19% lower than the actually measured biologically equivalent single doses. In the EMT6 cells, this trend was also seen, but the differences were not significant. In the V79 spheroids, the calculated doses were 18-30% lower than the measured doses. CONCLUSION Conversion of hypofractionated radiation doses to single doses using the LQ formalism could underestimate the effect of hypofractionated radiation by < or =30%.

Favorable outcomes of radiotherapy for early-stage mucosa-associated lymphoid tissue lymphoma

PURPOSE The aim of this study was to evaluate the efficacy of radiation therapy (RT) for early-stage mucosa-associated lymphoid tissue (MALT) lymphoma. MATERIALS AND METHODS Patients with stage IotaE (n=48) and stage capital PE, CyrillicE (n=2) MALT lymphoma treated with RT were reviewed. The primary tumor originated in the stomach in 20 patients, in the orbit in 9 patients, in the conjunctiva or eyelid and the parotid glands in 6 patients each, and 9 patients in the others. The median total RT dose was 32Gy (range, 25.6-50Gy). The median follow-up time was 50 months. RESULTS Although disease did not recur in the RT field in any patient regardless of the total dose, disease recurred outside the RT field in the seven patients. As all recurrences were localized, salvage RT was performed for each recurrence and achieved complete response without recurrence in the field. The 5-year overall survival, local control, and progression-free survival rates were 96.6%, 100%, and 82.2%, respectively. CONCLUSIONS A total dose of 25-30Gy is appropriate for local control of MALT lymphoma. RT is also an effective salvage therapy in cases of localized recurrence.

Clinical Usefulness of [(18)F] Fluoro-2-Deoxy-d-Glucose Uptake in 178 Head-and-Neck Cancer Patients With Nodal Metastasis Treated With Definitive Chemoradiotherapy: Consideration of Its Prognostic Value and Ability to Provide Guidance for Optimal Selection of Patients for Planned Neck Dissection

PURPOSE To evaluate the clinical effectiveness of pretreatment [18F] fluoro-2-deoxy-D-glucose-positron emission tomography for head-and-neck squamous cell carcinoma patients with nodal metastasis treated with chemoradiotherapy. METHODS AND MATERIALS Between March 2002 and December 2006, 178 patients with head-and-neck squamous cell carcinoma and nodal metastasis underwent fluoro-2-deoxy-D-glucose positron emission tomography before chemoradiotherapy. Fluoro-2-deoxy-D-glucose uptake by both the primary lesion and the neck node was measured using the standard uptake value (SUV). The overall survival, disease-free survival, local control, nodal progression-free survival, and distant metastasis-free survival rates were calculated, and several prognostic factors were evaluated. RESULTS The patients with a nodal SUV≥6.00 had a significantly lower 3-year disease-free survival rate than those with a lower SUV (44% vs. 69%, p=.004). On multivariate analysis, a high SUV of nodal disease also proved to be a significantly unfavorable factor for disease-free survival (p=.04, 95% confidence interval [CI], 1.02-3.23), nodal progression-free survival (p=.05; 95% CI, 1.00-4.15), and distant metastasis-free survival (p=.016; 95% CI, 1.25-8.92). Among the patients with a greater nodal SUV (≥6.00), those treated with planned neck dissection had better nodal progression-free survival than those in the observation group (p=.04, hazard ratio, 2.36; 95% CI, 1.00-5.85). CONCLUSION Among head-and-neck squamous cell carcinoma patients treated with chemoradiotherapy, the pretreatment SUV of nodal disease was one of the strongest prognostic factors and also provided important information for the selection of patients suitable for planned neck dissection.

Aichi Cancer Center Initial Experience of Intensity Modulated Radiation Therapy for Nasopharyngeal Cancer Using Helical Tomotherapy

PURPOSE To assess the feasibility of helical tomotherapy (HT) for patients with nasopharyngeal carcinoma. METHODS AND MATERIALS From June 2006 to June 2007, 20 patients with nasopharyngeal carcinoma were treated with HT with (n = 18) or without (n = 2) systemic chemotherapy. The primary tumor and involved lymph node (PTV1) were prescribed 70 Gy and the prophylactic region 54 Gy at D95, respectively. The majority of patients received 2 Gy per fraction for PTV1 in 35 fractions. Parotid function was evaluated using quantitative scintigraphy at pretreatment, and posttreatment at 3 months and 1 year later. RESULTS The median patient age was 53 years, ranging from 15 to 83. Our cohort included 5, 8, 4, 2, and 1 patients with disease Stages IIB, III, IVA, IVB, and IVC, respectively. Histopathological record revealed two for World Health Organization Type I and 18 for Type 2 or 3. The median duration time for treatment preparation was 9.5 days, and all plans were thought to be acceptable regarding dose constraints of both the planning target volume and organ at risk. All patients completed their treatment procedure of intensity-modulated radiation therapy (IMRT). All patients achieved clinical remission after IMRT. The majority of patients had Grade 3 or higher toxicity of skin, mucosa, and neutropenia. At the median follow-up of 10.9 months, two patients recurred, and one patient died from cardiac disease. Parotid gland function at 1 year after completion of IMRT was significantly improved compared with that at 3 months. CONCLUSION HT was clinically effective in terms of IMRT planning and utility for patients with nasopharyngeal cancer.

A comparison of radiation treatment plans using IMRT with helical tomotherapy and 3D conformal radiotherapy for nasal natural killer/T-cell lymphoma

The purpose of this study was to compare radiation treatment plans (RTPs) that used intensity-modulated radiation therapy (IMRT) with helical tomotherapy (HT) or three-dimensional conformal radiation therapy (3D-CRT) for nasal natural killer/T-cell lymphoma (NNKTL). We created RTPs that used IMRT with HT or 3D-CRT for eight NNKTL patients previously treated at our institution and conducted a pilot comparison between the two modalities using the parameters of the target coverage and homogeneity for the planning target volume (PTV) and the maximum and mean doses for organs at risk (OARs). The clinical target volume (CTV) included the gross tumour volume with an additional margin of 1.5 cm and the nasopharynx, palates and nasal cavity; the PTV with the CTV plus a 2 mm margin received a total dose of 50 Gy. IMRT achieved significantly better PTV coverage, with more than 99% of the PTV receiving 90% and 95% of the prescribed dose, whereas 3D-CRT could not provide adequate coverage of the PTV, with 89.1+/-2.6% and 84.5+/-2.7% of the PTV receiving 90% and 95% of the prescribed dose, respectively (both p <0.0001). The homogeneity index was 0.29+/-0.06 for IMRT and 0.046+/-0.022 for 3D-CRT, which was statistically significant (p <0.0001). IMRT tended to provide equivalent or slightly better OAR avoidance than 3D-CRT. In conclusion, 3D-CRT could not provide adequate coverage of the PTV because the PTV was close to many OARs. IMRT should be used for NNKTL because a lack of optimal RTPs could cause local failure.

Helical Tomotherapy for Brain Metastases: Dosimetric Evaluation of Treatment Plans and Early Clinical Results:

The purpose of this study was to evaluate the feasibility and treatment plans of intensity-modulated radiation therapy using helical tomotherapy (HT) for brain metastases. Twenty-three patients with 1 to 4 brain metastases were treated with H T. In combination with whole-brain radiotherapy (simultaneous plans), metastatic lesions, and the whole brain were treated with 50 Gy and 30 Gy, respectively, in 10 fractions, with a simultaneous integrated boost technique. In patients treated for brain metastases alone (focal plans), metastatic lesions were treated with 35 or 37.5 Gy in 5 fractions. The treatment plans were compared regarding the conformation number (CN) and homogeneity index (HI), and differences in these indexes between simultaneous and focal plans were examined by Students t-test. Seven and 16 patients were treated with simultaneous plans and focal plans, respectively. The mean ± SD of CN and HI values were 0.75 ± 0.13 and 0.063 ± 0.042, respectively, for simultaneous plans, and 0.73 ± 0.12 and 0.052 ± 0.023, respectively, for focal plans. The CN and HI between the two plans were not significantly different. Response rates in 13 patients with follow-up imaging were approximately 90% for both plans and the local control rate at 1 year was 69%. One patient with a huge tumor (34.0 cc) and WHO performance status 3 treated with focal plans experienced severe headache, requiring prolongation of the treatment time, and died at 8 days after completion of treatment. The exact cause of deterioration was uncertain as no radiological investigation was performed in this patient. No late complications were observed during follow-up periods up to 20 months. HT is a viable non-invasive technique for treatment of brain metastases and achieves high accuracy in terms of dose conformity and homogeneity.

Alternating chemoradiotherapy in patients with nasopharyngeal cancer: prognostic factors and proposal for individualization of therapy

The purpose of this study is to assess the efficacy of alternating chemoradiation in patients with nasopharyngeal cancer. From 1990–2006, 100 patients with nasopharyngeal cancer were treated with alternating chemoradiation at the Aichi Cancer Center. Of these, 4, 2, 23, 34, 13 and 23 patients were staged as I, IIA, IIB, III, IVA and IVB, respectively. The median radiation doses for primary tumors and metastatic lymph nodes were 66.6 Gy (range, 50.4–80.2 Gy) and 66 Gy (range, 40.4–82.2 Gy), respectively. A total of 82 patients received chemotherapy with both cisplatin and 5-fluorouracil (5-FU), while 14 patients received nedaplatin (CDGP) and 5-FU. With a median follow-up of 65.9 months, the 5-year rates of overall survival (OAS) and progression-free survival (PFS) were 78.1% and 68.3%, respectively. On multivariate analysis (MVA), elderly age, N3, and WHO type I histology proved to be significantly unfavorable prognostic factors of OAS. As for PFS, there were T4, N3, and WHO type I histology in MVA. Acute toxicities of hematologic and mucositis/dermatitis ≥ Grade 3 were relatively high (32%); however, they were well-managed. Late toxicities of ≥ Grade 3 were three (3%) mandibular osteomyelitis and one (1%) lethal mucosal bleeding. Results for alternating chemoradiation for nasopharyngeal carcinoma are promising. In order to improve outcomes, usage of intensity-modulated radiation therapy and application of active anticancer agents are hopeful treatments, especially for groups with poor prognosis factors with WHO type I histopathology, T4 and/or N3 disease.

Chemoradiotherapy for Locally Recurrent Nasopharyngeal Carcinoma: Treatment Outcome and Prognostic Factors

OBJECTIVE To evaluate the treatment outcome of patients with locally recurrent nasopharyngeal carcinoma (NPC) treated with re-irradiation and chemotherapy. METHODS Between 1991 and 2004, 36 patients with locally recurrent NPC received re-irradiation and chemotherapy. The median re-irradiation dose was 37.9 Gy; the median total dose of prior irradiation and re-irradiation was 104.4 Gy. The outcome is studied retrospectively and also evaluated the prognostic factors and toxicities. RESULTS With a median follow-up of 40 months, 3-year overall survival (OS) was 58.3% and 3-year progression-free survival (PFS) was 25.0%. Patients aged <50 and of early stage at recurrence had a significantly better OS and PFS. Over Grade 3 of late toxicities were seen in patients received a total dose of >110 Gy. CONCLUSIONS Age and stage at recurrence were identified as prognostic factors for OS and PFS. Patients received external beam radiation therapy at a total dose of more than 110 Gy should be careful for severe late toxicities, and it is thought to be the optimal dose for recurrent tumor.