Nobutaka Mizoguchi

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.

Long-term Results of Carbon Ion Radiation Therapy for Locally Advanced or Unfavorably Located Choroidal Melanoma: Usefulness of CT-based 2-Port Orthogonal Therapy for Reducing the Incidence of Neovascular Glaucoma

PURPOSE To determine the long-term results of carbon ion radiation therapy (C-ion RT) in patients with choroidal melanoma, and to assess the usefulness of CT-based 2-port irradiation in reducing the risk of neovascular glaucoma (NVG). METHODS AND MATERIALS Between January 2001 and February 2012, a total of 116 patients with locally advanced or unfavorably located choroidal melanoma received CT-based C-ion RT. Of these patients, 114 were followed up for more than 6 months and their data analyzed. The numbers of T3 and T2 patients (International Union Against Cancer [UICC], 5th edition) were 106 and 8, respectively. The total dose of C-ion RT varied from 60 to 85 GyE, with each dose given in 5 fractions. Since October 2005, 2-port therapy (51 patients) has been used in an attempt to reduce the risk of NVG. A dose-volume histogram analysis was also performed in 106 patients. RESULTS The median follow-up was 4.6 years (range, 0.5-10.6 years). The 5-year overall survival, cause-specific survival, local control, distant metastasis-free survival, and eye retention rates were 80.4% (95% confidence interval 89.0%-71.8%), 82.2% (90.6%-73.8%), 92.8% (98.5%-87.1%), 72.1% (81.9%-62.3%), and 92.8% (98.1%-87.5%), respectively. The overall 5-year NVG incidence rate was 35.9% (25.9%-45.9%) and that of 1-port group and 2-port group were 41.6% (29.3%-54.0%) and 13.9% (3.2%-24.6%) with statistically significant difference (P<.001). The dose-volume histogram analysis showed that the average irradiated volume of the iris-ciliary body was significantly lower in the non-NVG group than in the NVG group at all dose levels, and significantly lower in the 2-port group than in the 1-port group at high dose levels. CONCLUSIONS The long-term results of C-ion RT for choroidal melanoma are satisfactory. CT-based 2-port C-ion RT can be used to reduce the high-dose irradiated volume of the iris-ciliary body and the resulting risk of NVG.

Treatment outcomes of definitive chemoradiotherapy for patients with hypopharyngeal cancer

We analyzed the efficacy of definitive chemoradiotherapy (CRT) for patients with hypopharyngeal cancer (HPC). Subjects comprised 97 patients who were treated with definitive CRT from 1990 to 2006. Sixty-one patients (62.9%) with resectable disease who aimed to preserve the larynx received induction chemotherapy (ICT), whereas 36 patients (37.1%) with resectable disease who refused an operation or who had unresectable disease received primary alternating CRT or concurrent CRT (non-ICT). The median dose to the primary lesion was 66 Gy. The median follow-up time was 77 months. The 5-year rates of overall survival (OS), progression-free survival (PFS), local control (LC), and laryngeal preservation were 68.7%, 57.5%, 79.1%, and 70.3%, respectively. The T-stage was a significant prognostic factor in terms of OS, PFS and LC in both univariate and multivariate analyses. The 5-year rates of PFS were 45.4% for the ICT group and 81.9% for the non-ICT group. The difference between these groups was significant with univariate analysis (P = 0.006). Acute toxicity of Grade 3 to 4 was observed in 34 patients (35.1%). Grade 3 dysphagia occurred in 20 patients (20.6%). Twenty-nine (29.8%) of 44 patients with second primary cancer had esophageal cancer. Seventeen of 29 patients had manageable superficial esophageal cancer. The clinical efficacy of definitive CRT for HPC is thought to be promising in terms of not only organ preservation but also disease control. Second primary cancer may have a clinical impact on the outcome for HPC patients, and special care should be taken when screening at follow-up.

Retrospective analysis of definitive radiotherapy for patients with superficial esophageal carcinoma: Consideration of the optimal treatment method with a focus on late morbidity

PURPOSE To evaluate the clinical efficacy of definitive radiotherapy for patients with superficial esophageal cancer. MATERIAL AND METHODS From 1990 through 2006, 97 patients with stage I disease were treated with radiotherapy with or without chemotherapy. All patients were diagnosed with panesophagoscopy and computed tomography. Chemotherapy was added in 61 patients, and intra-cavitary brachytherapy (ICBT) was used in 27 patients. RESULTS The patients were 90 men and seven women with a median age of 65.7 years (range; 41-89). At last follow-up with a median follow-up duration of 35.7 months, 3 year-overall and progression-free survival (PFS) rates were 81.5% (95% C.I. = 73.3-89.7%) and 55.8% (95% C.I. = 45.2-66.4%), respectively. Shorter tumor length was a significantly favorable factor for the PFS rate (P = 0.02) and local failure-free (LFF) rate (P = 0.007) on both univariate and multivariate analyses. Although the addition of ICBT had no apparent benefit for survival or tumor control, the rate of severe adverse effects including lethal esophageal ulcers, showed a higher tendency in patients receiving ICBT. CONCLUSIONS Our results regarding efficacy from the viewpoint of organ preservation are promising. Special care would be taken for the use of ICBT for patients with superficial esophageal cancer, especially if they have received chemoradiotherapy.

Carbon-ion radiotherapy for locally advanced primary or postoperative recurrent epithelial carcinoma of the lacrimal gland.

PURPOSE To evaluate the applicability of carbon ion beams for the treatment of carcinoma of the lacrimal gland with regard to normal tissue morbidity and local tumor control. METHODS AND MATERIALS Between April 2002 and January 2011, 21 patients with locally advanced primary epithelial carcinoma of the lacrimal gland were enrolled in a Phase I/II clinical trial of carbon-ion radiotherapy (CIRT) at the National Institute of Radiological Sciences. Acute radiation toxicity was the primary endpoint of this dose-escalation study and the late toxicity, local control, and overall survival were additionally evaluated as secondary endpoints. Of the 21 subjects enrolled, all patients were followed for more than 6 months and analyzed. RESULTS The radiation dose was increased from the initial dose of 48.0Gy equivalents (GyE)/12 fractions at 10% increments up to 52.8GyE. Of the 21 patients, five received a total dose of 48.0GyE, and 16 received a total dose of 52.8GyE. No patient developed grade 3 or higher skin toxicity. As late ocular/visual toxicity, three patients had grade 3 retinopathy and seven patients lost their vision. Among the 10 patients treated until May 2005, five patients had local recurrence, three of whom had marginal recurrence. Therefore, the margin for the CTV (clinical target volume) was set to a range according to the orbital exenteration since June 2005. After the application of the extended margin, no local recurrence has been observed. The three-year overall survival and local control rates were 82.2% and 79.0%, respectively. CONCLUSION CIRT can be applied for primary epithelial carcinoma of the lacrimal gland, with a borderline acceptable morbidity and sufficient antitumor effect when an extended margin is adopted.

Impact of combined modality treatment with radiotherapy and S-1 on T2N0 laryngeal cancer: Possible improvement in survival through the prevention of second primary cancer and distant metastasis.

BACKGROUND In patients with head and neck cancer, the management of second primary cancer (SPC) is particularly important for improving survival because of its high incidence and associated mortality. We evaluated the impact of combination chemotherapy on survival and SPC. METHOD We retrospectively analyzed data from 49 patients treated with definitive radiation therapy (RT) for T2N0M0 laryngeal squamous cell carcinoma between 2003 and 2011. Among them, 22 patients received combined modality treatment with radiotherapy and S-1 (RT+CT group). RESULTS The median follow-up period was 71months (32-111months). A significant difference in overall survival (OS, P<0.01) was observed between the RT+CT group (n=22) and the RT alone group (n=27) though no significant differences were observed in local control and disease specific survival. Univariate analyses showed that an older age (P<0.05) and a higher grade (P<0.05) were associated with OS. Multivariate analysis identified chemotherapy as the most significant predictor of survival (OR, 0.056; 95% CI, 0.008-0.353, P<0.01). A significantly lower incidence of distant metastasis (DM)+SPC (5-year incidence: 5% vs. 19%, P<0.05) and fewer deaths from these causes (1 vs. 8: P<0.05) were observed in the RT+CT group. Multivariate analysis showed that chemotherapy was the most significant factor for the incidence of DM+SPC (OR, 0.074; 95% CI, 0.0065-0.84; P<0.05). CONCLUSION The findings of this study suggest the possibility that combined modality treatment with radiotherapy and S-1 improve survival by preventing distant metastasis and second primary cancer.

The Ion-Beam Radiation Oncology Center in Kanagawa (i-ROCK) Carbon Ion Facility at the Kanagawa Cancer Center

The Kanagawa Cancer Center (KCC) is the core facility for cancer care in Kanagawa Prefecture. It serves a population of more than 9 million people. Planning for the ionbeam Radiation Oncology Center in Kanagawa (i-ROCK) started in 2015. The basic framework and design of i-ROCK was established in 2010, and it is the first cancercenter-based carbon ion radiation therapy facility in the world and the fifth carbon ion radiation therapy facility in Japan. The building was completed in August 2014 (Figure 1). The installation of beam delivery equipment has been completed. The start of clinical operation is planned for December 2015. An overview of i-ROCK is presented in this report.

Lacrimal Gland Tumors

Lacrimal gland carcinoma (LGC) is a very rare malignancy with no established treatment other than surgery [1]. If conservative surgery cannot be applied, orbital exenteration is the only treatment of choice with curative intent [2–6]. Therefore, effective and less invasive treatment methods are urgently needed. The National Institute of Radiological Sciences (NIRS) conducted a phase I/II dose-escalation study of carbon ion radiotherapy (C-ion RT) for LGC between 2002 and 2011 to establish a safe and effective treatment method using the carbon ion beam. Satisfactory results have been obtained with C-ion RT in 12 fractions over 3 weeks. An extended field was observed to be necessary for reducing the risks of marginal recurrence. In this chapter, the treatment method being performed at NIRS and up-to-date outcomes are described.