Akinori Takada

Dose-Volume Comparison of Proton Radiotherapy and Stereotactic Body Radiotherapy for Non-Small-Cell Lung Cancer

PURPOSE This study designed photon and proton treatment plans for patients treated with hypofractionated proton radiotherapy (PT) at the Southern Tohoku Proton Therapy Center (STPTC). We then calculated dosimetric parameters and compared results with simulated treatment plans for stereotactic body radiotherapy (SBRT), using dose--volume histograms to clearly explain differences in dose distributions between PT and SBRT. METHODS AND MATERIALS Twenty-one patients with stage I non-small-cell lung cancer (stage IA, n = 15 patients; stage IB, n = 6 patients) were studied. All tumors were located in the peripheral lung, and total dose was 66 Gray equivalents (GyE) (6.6 GyE/fraction). For treatment planning, beam incidence for proton beam technique was restricted to two to three directions for PT, and seven or eight noncoplanar beams were manually selected for SBRT to achieve optimal planning target volume (PTV) coverage and minimal dose to organs at risk. RESULTS Regarding lung tissues, mean dose, V5, V10, V13, V15, and V20 values were 4.6 Gy, 13.2%, 11.4%, 10.6%, 10.1%, and 9.1%, respectively, for PT, whereas those values were 7.8 Gy, 32.0%, 21.8%, 17.4%, 15.3%, and 11.4%, respectively, for SBRT with a prescribed dose of 66 Gy. Pearson product moment correlation coefficients between PTV and dose--volume parameters of V5, V10, V15, and V20 were 0.45, 0.52, 0.58, and 0.63, respectively, for PT, compared to 0.52, 0.45, 0.71, and 0.74, respectively, for SBRT. CONCLUSIONS Correlations between dose--volume parameters of the lung and PTV were observed and may indicate that PT is more advantageous than SBRT when treating a tumor with a relatively large PTV or several tumors.

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.

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.

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.

A new method using MRI to delineate areas of head and neck cancer targeted by intra-arterial infusion via a superficial temporal artery

To determine whether anticancer drugs delivered via arterial infusion can permeate entire tumors using a new MRI flow check method. We infused 20 ml of contrast medium (2 ml of Gd-GDPA plus 18 ml of normal saline) over a period of 10 min using a continuous injection pump, then immediately performed MRI using a 1.5 T unit. Images were obtained in 5-mm-thick continuous sections in two or three planes (axial, coronal, and sagittal) depending on the extent of the tumor, and enhanced fast gradient echo 3 D (EFGRE3D) images with a special inversion at lipids were photographed using a neurovascular array coil. The new MRI flow check method delineated an area of tongue cancer perfused with drugs more accurately than conventional methods.The MRI flow check method provides accurate information about areas of arterial infusion.

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.

Determination of the irradiation field for clinical T1-T3N0M0 thoracic/abdominal esophageal cancer based on the postoperative pathological results

OBJECTIVE In patients with thoracic/abdominal esophageal cancer with no clinical evidence of lymph node metastasis, there is no consensus about whether the irradiation field should include regional lymph nodes. In this study, the extent of the irradiation field for clinical stage T1-3N0M0 esophageal cancer was determined based on the postoperative pathological results. METHODS From July 1989 to June 2008, 103 patients diagnosed with clinical stage T1-3N0M0 thoracic/abdominal esophageal cancer underwent standard esophagectomy and regional lymph node dissection at the Aichi Cancer Center Hospital. Of these 103 patients, the pathological results of the resected specimens could be confirmed in 95 (92%) patients. The pathological lymphatic spread was reviewed retrospectively, and the extent of the irradiation field was determined based on the postoperative pathological results. RESULTS Of 95 patients with clinical stage T1-3N0M0 esophageal cancer, 40 (42.1%) had pathological lymph node metastases, and the frequency of nodal metastases was studied by tumor location. The rates of lymph node metastases for the upper, middle, lower and abdominal esophagus were 37.5%, 32.5%, 46% and 70%, respectively. CONCLUSIONS Pathological lymph nodes metastases are often seen after operation in clinical stage T1-3N0M0 esophageal cancer. In the present study, the optimal lymph nodes to be included in the irradiation field were determined according to the primary site in the esophagus.

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.

High-dose proton beam therapy for stage I non-small cell lung cancer: Clinical outcomes and prognostic factors

Abstract Background. Evidence has suggested that radiation therapy with a lower dose per fraction may be a reasonable option for the treatment of centrally located non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the safety and efficacy of two proton beam therapy (PBT) protocols for stage I NSCLC and to determine prognostic factors. Material and methods. This study included patients clinically diagnosed with stage I NSCLC. Based on the location of the tumor, one of the two PBT protocols was administered. Patients with peripherally located tumors were given 66 Gy relative biological dose effectiveness (RBE) over 10 fractions (Protocol A) while patients with centrally located tumors were given 80 Gy (RBE) over 25 fractions (Protocol B). Results. Between January 2009 and May 2012, 56 eligible patients were enrolled (protocol A: 32 patients; protocol B: 24 patients). The three-year overall survival (OS), progression-free survival (PFS), and local control (LC) rates were 81.3% [95% confidence interval (CI) 75.9–86.7%], 73.4% (95% CI 67.2–79.6%), and 96.0% (95% CI 93.2–98.8%), respectively. There were no significant differences in outcomes between the two protocols. Late grade 2 and 3 pulmonary toxicities were observed in nine patients (13.4%) and one patient (1.5%), respectively; no grade 4 or 5 toxicities were observed. Sex, age, performance status, T-stage, operability, and tumor pathology were not associated with OS and PFS. Only maximum standardized uptake value (SUVmax; < 5 vs. ≥ 5) was identified as a significant prognostic factor for OS and PFS. Conclusion. Both high-dose PBT protocols achieved high LC rates with tolerable toxicities in stage I NSCLC patients, and SUVmax was a significant prognostic factor.