Masashi Koto

Carbon ion radiotherapy for stage I non-small cell lung cancer.

BACKGROUND AND PURPOSE Heavy ion radiotherapy is a promising modality because of its excellent dose localization and high biological effect on tumors. Using carbon beams, a dose escalation study was conducted for the treatment of stage I non-small cell lung cancer (NSCLC) to determine the optimal dose. MATERIALS AND METHODS The first stage phase I/II trial using 18 fractions over 6 weeks for 47 patients and the second one using nine fractions over 3 weeks for 34 patients were conducted by the dose escalation method from 59.4 to 95.4 Gray equivalents (GyE) in incremental steps of 10% and from 68.4 to 79.2 GyE in 5% increments, respectively. The local control and survival rates were obtained using the Kaplan-Meier method. RESULTS Radiation pneumonitis at grade III occurred in three of 81 patients, but they fully recovered. This was not a dose-limiting factor. The local control rates in the first and second trials were 64% and 84%, respectively. The total recurrence rate in both trials was 23.2%. The infield local recurrence in the first trial was significantly dependent on carbon dose. The doses greater than 86.4 GyE at 18 fractions and 72 GyE at nine fractions achieved a local control of 90% and 95%, respectively. The 5 year overall and cause-specific survivals in 81 patients were 42% and 60%, respectively. CONCLUSIONS With our dose escalation study, the optimum safety and efficacy dose of carbon beams was determined. Carbon beam therapy attained almost the same results as surgery for stage I NSCLC although this was a I/II study.

Characteristics of patients who developed radiation pneumonitis requiring steroid therapy after stereotactic irradiation for lung tumors.

BACKGROUND To find possible risk factors for symptomatic radiation pneumonitis (RP) after stereotactic irradiation (STI) for peripheral non-small cell lung cancer (NSCLC), pre-treatment pulmonary function test and dose volume statistics in patients who developed RP requiring steroid intake were retrospectively compared with statistics of those who did not develop RP. MATERIALS AND METHODS From 1996 to 2002, 156 patients with Stage I NSCLC received STI at 5 hospitals in Japan. Of those patients, 12 were medicated with steroids for RP after treatment (RP group). For comparison, 31 patients were randomly selected from the remaining 144 patients who received STI but did not receive steroids (control group). RESULTS There were no statistical differences in age, sex, tumor size, performance status, forced expiratory volume in 1 sec (FEV 1.0 %), or percent vital capacity (%VC) between patients medicated with steroids for RP and those who did not have RP and received no steroids. V 20 (%) was 7 to 18% (median 8%) in patients medicated with steroids for RP and 2 to 16% (median 7%) in those who did not have RP No difference was observed in V 20 , the biologically effectively dose (BED) at the periphery of the planning target volume, or the dose per fraction between the two groups. CONCLUSIONS Pre-treatment pulmonary function test (%VC, FEV 1.0 %), and dose volume statistics (V 20 , total dose, BED, dose per fraction, peripheral dose) were not predictive of RP requiring steroid intake after STI for stage I NSCLC.

Radiographic pulmonary and pleural changes after carbon ion irradiation

PURPOSE For the treatment of Stage I non-small-cell lung cancers, a Phase I/II study of carbon ion irradiation was undertaken. In the present study, we focus on posttreatment radiographic lung damage: specifically, its timing, features, and relation to dose-volume factors. MATERIALS AND METHODS Forty-three patients with 44 Stage I non-small-cell lung cancers were treated with carbon ion irradiation ranging from 59.4 to 95.4 photon Gy equivalent dose (GyE) in 18 fractions over 6 weeks, according to our dose escalation protocols. Primary lesions were irradiated by 2-4 portals. Follow-up evaluation with computed tomography (CT) was sequentially performed to assess changes in the lung. CT findings were classified into two categories: pulmonary reaction and pleural reaction. A dose-volume histogram for each patient was calculated, using a three-dimensional CT planning system. Statistical analysis was conducted using Spearmans rank test. RESULTS The median appearance period of pulmonary reactions was 3 months after the start of carbon ion irradiation, whereas the maximum period was 6 months. The severity of pulmonary reactions statistically correlated with lung volumes irradiated no less than 20 GyE (vol. 20) and 40 GyE (vol. 40) (p = 0.017 and p = 0.0089). Geometrically unique findings in the irradiated fields were observed in 7 patients (16%). The median appearance period of pleural reactions was 4 months after the start of carbon ion irradiation. The occurrence of pleural reactions significantly correlated with planning target volume (p = 0.000098), vol. 20 (p = 0.00011), and vol. 40 (p = 0.00097). CONCLUSIONS Lung damage after carbon ion irradiation was observed in the parenchyma and in the pleura. The severity of pulmonary reactions was correlated with dose-volume factors. These findings might provide useful information in the planning and management of carbon ion irradiation.

Prognostic factors for local control of stage I non-small cell lung cancer in stereotactic radiotherapy: a retrospective analysis

BackgroundThe purpose of this study is to investigate the prognostic factors of stereotactic radiotherapy for stage I NSCLC to improve outcomes.MethodsStage I non-small cell lung cancer patients who were treated with stereotactic radiotherapy between 2005 and 2009 at our hospital were enrolled in this study. The primary endpoint was local control rate. Survival estimates were calculated from the completion date of radiotherapy using the Kaplan-Meier method. The prognostic factors including patients’ characteristics and dose-volume histogram parameters were evaluated using Cox’s proportional hazard regression model.ResultsEighty patients (81 lesions) treated with 3 dose levels, 48 Gy/4 fractions, 60 Gy/8 fractions and 60 Gy/15 fractions, were enrolled in this study. Median follow-up was 30.4 months (range, 0.3 – 78.5 months). A Cox regression model showed T factor (p = 0.013), biological effective dose calculated from prescribed dose (BED10) (p = 0.048), and minimum dose for PTV (p = 0.013) to be prognostic factors for local control. Three-year overall survival rate and local control rate were 89.9% (T1: 86.8%, T2: 100%) and 89.0% (T1: 97.9%; T2: 64.8%), respectively. When the 3-year local control rates were examined by prescribed doses, they were 100% for the dose per fraction of 48 Gy /4 fractions (105.6 Gy BED10), 82.1% for 60 Gy/8 fractions (105 Gy BED10), and 57.1% for 60 Gy/15 fractions (84 Gy BED10). The median value of the minimum dose for PTV (%) was 89.88 (%), and the 3-year local control rates were 100% in those with the minimum dose for PTV (%) ≥ 89.88% and 79.2% in those with the minimum dose for PTV (%) < 89.88%.ConclusionsOur results suggest that T factor, BED10, and minimum dose for PTV influence the local control rate. Local control rate can be improved by securing the minimum dose for PTV.

Long-Term Results of Radiochemotherapy for Solitary Lymph Node Metastasis After Curative Resection of Esophageal Cancer

PURPOSE To evaluate the long-term efficacy and toxicity of definitive radiochemotherapy for solitary lymph node metastasis after curative surgery of esophageal cancer. METHODS AND MATERIALS We performed a retrospective review of 35 patients who underwent definitive radiochemotherapy at Tohoku University Hospital between 2000 and 2009 for solitary lymph node metastasis after curative esophagectomy with lymph node dissection for esophageal cancer. Radiotherapy doses ranged from 60 to 66 Gy (median, 60 Gy). Concurrent chemotherapy was platinum based in all patients. The endpoints of the present study were overall survival, cause-specific survival, progression-free survival, irradiated-field control, overall tumor response, and prognostic factors. RESULTS The median observation period for survivors was 70.0 months. The 5-year overall survival was 39.2% (median survival, 39.0 months). The 5-year cause-specific survival, progression-free survival, and irradiated-field control were 43.3%, 31.0% and 59.9%, respectively. Metastatic lesion, size of the metastatic lymph node, and performance status before radiochemotherapy were significantly correlated with prognosis. Complete response and partial response were observed in 22.9% and 57.1% of the patients, respectively. There was no Grade 3 or higher adverse effect based on the Common Terminology Criteria for Adverse Events (CTCAE v3.0) in the late phase. CONCLUSIONS Based on our study findings, approximately 40% of patients with solitary lymph node metastasis after curative resection for esophageal cancer have a chance of long-term survival with definitive radiochemotherapy.

Focal dose escalation using FDG-PET-guided intensity-modulated radiation therapy boost for postoperative local recurrent rectal cancer: a planning study with comparison of DVH and NTCP

BackgroundTo evaluate the safety of focal dose escalation to regions with standardized uptake value (SUV) >2.0 using intensity-modulated radiation therapy (IMRT) by comparison of radiotherapy plans using dose-volume histograms (DVHs) and normal tissue complication probability (NTCP) for postoperative local recurrent rectal cancerMethodsFirst, we performed conventional radiotherapy with 40 Gy/20 fr. (CRT 40 Gy) for 12 patients with postoperative local recurrent rectal cancer, and then we performed FDG-PET/CT radiotherapy planning for those patients. We defined the regions with SUV > 2.0 as biological target volume (BTV) and made three boost plans for each patient: 1) CRT boost plan, 2) IMRT without dose-painting boost plan, and 3) IMRT with dose-painting boost plan. The total boost dose was 20 Gy. In IMRT with dose-painting boost plan, we increased the dose for BTV+5 mm by 30% of the prescribed dose. We added CRT boost plan to CRT 40 Gy (summed plan 1), IMRT without dose-painting boost plan to CRT 40 Gy (summed plan 2) and IMRT with dose-painting boost plan to CRT 40 Gy (summed plan 3), and we compared those plans using DVHs and NTCP.ResultsDmean of PTV-PET and that of PTV-CT were 26.5 Gy and 21.3 Gy, respectively. V50 of small bowel PRV in summed plan 1 was significantly higher than those in other plans ((summed plan 1 vs. summed plan 2 vs. summed plan 3: 47.11 ± 45.33 cm3 vs. 40.63 ± 39.13 cm3 vs. 41.25 ± 39.96 cm3(p < 0.01, respectively)). There were no significant differences in V30, V40, V60, Dmean or NTCP of small bowel PRV.ConclusionsFDG-PET-guided IMRT can facilitate focal dose-escalation to regions with SUV above 2.0 for postoperative local recurrent rectal cancer.

Feasibility of carbon ion radiotherapy for locally advanced sinonasal adenocarcinoma.

BACKGROUND AND PURPOSE To evaluate the safety and efficacy of carbon ion radiotherapy (CIRT) for locally advanced sinonasal adenocarcinoma. MATERIAL AND METHODS Twenty-two patients with sinonasal adenocarcinoma were treated with CIRT. CIRT was the primary treatment for 16 patients. Four patients received CIRT for local recurrence after surgery and two for residual tumour after surgery or chemotherapy. At the start of CIRT, 1 patient had T-classification (T) 2 disease, 2 had T3 disease, 5 had T4a disease, and 14 had T4b disease. Fourteen patients were treated with 57.6 Gy equivalent (GyE)/16 fractions, and 8, with 64.0 GyE/16 fractions. RESULTS The median follow-up period was 43 months for all patients. The 3-year local control and loco-regional control rates for all patients were 76.9% (95% confidence interval [CI]=56.7-97.1%) and 61.3% (95% CI=38.5-84.1%), respectively. The 3-year overall survival and disease-specific survival rates were 59.1% (95% CI=38.6-79.6%) and 65.6% (95% CI=44.9-86.3%), respectively. Acute reactions of grade 3 of the skin and mucosa were observed in 2 and 4 patients, respectively. Late reactions included lateral visual loss (5 patients), mucosal ulceration (1 patient), and brain necrosis with clinical symptoms (1 patient). In the 5 patients who developed visual loss, the optic nerve was close to the tumour. CONCLUSIONS CIRT was effective and generally safe for locally advanced sinonasal adenocarcinoma.

Risk factors for brain injury after carbon ion radiotherapy for skull base tumors

BACKGROUND AND PURPOSE This study aimed to determine the risk factors for radiation-induced brain injury (RIBI) after carbon ion radiotherapy (CIRT) for treating skull base tumors. MATERIALS AND METHODS Between April 1997 and January 2009, CIRT at a total dose of 48.0-60.8Gy equivalent (GyE) was administered in 16 fractions to 47 patients with skull base tumors. Of these patients, 39 who were followed up with magnetic resonance imaging (MRI) for more than 24months were analyzed. RIBI was assessed according to the MRI findings based on the Late Effects of Normal Tissue-Subjective, Objective, Management, Analytic criteria; clinical symptoms were assessed according to the Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer tables. The correlations of clinical and dosimetric parameters with incidence of ⩾grade 2 RIBI were retrospectively analyzed. RESULTS The median follow-up period was 67months. The 5-year actuarial likelihoods of ⩾grade 2 RIBI and ⩾grade 2 clinical symptoms were 24.5% and 7.0%, respectively. Multivariate analysis demonstrated that the brain volume receiving more than 50GyE (V50) was a significant risk factor for the development of ⩾grade 2 RIBI (p=0.004). CONCLUSION V50 was a significant risk factor for ⩾grade 2 RIBI after CIRT using a 16-fraction regimen.

Carbon ion radiotherapy for locally advanced squamous cell carcinoma of the external auditory canal and middle ear

The prognosis of advanced squamous cell carcinoma (SCC) of the external auditory canal and middle ear remains poor. Carbon ion radiotherapy (C‐ion RT) has shown promise for locally advanced head and neck cancer. Therefore, we evaluated the safety and efficacy of C‐ion RT for locally advanced SCC of the external auditory canal and middle ear.

Preoperative carbon ion radiotherapy for non-small cell lung cancer with chest wall invasion—pathological findings concerning tumor response and radiation induced lung injury in the resected organs

The purpose of this study was to make a pathological evaluation of the tumor response and the lung injury of non-small cell lung cancer (NSCLC) patients after carbon ion therapy. We enrolled four NSCLC patients with chest wall invasion but without nodal and distant metastasis (T3N0M0). Only primary lesions were irradiated with carbon ions, followed by surgical resection. The patients consisted of three males and one female varying by age from 54 to 73 (average 66.3). Total treatment dose was 59.4 and 64.8 GyE, respectively, administered in 18 fractions over 6 weeks, or 72.0 GyE in 16 fractions over 4 weeks. Resection after radiation therapy was performed as a combination of lobectomy, lymph node dissection and chest wall surgery. After fixation, the lung was sliced into thin sections to match the CT image. Each slice was anatomically identified and the slices were compared with each other subjected to pathological analysis. No tumor cells were observed in two cases. The other two cases exhibited only a few tumor cells sparsely distributed in the lung tissue. There was evidence of dense pulmonary fibrosis in the limited space surrounding primary tumors, but its density was found to rapidly decrease in the narrow area toward the outside. The rate at which its density subsided mirrored the rapid decrease in the planning CT dose distribution. Microscopy showed no evidence of fibrosis in any of the fields irradiated with less than 15 GyE. Microscopy confirmed an outstanding tumor response with limited pulmonary fibrosis. This substantiates the superior dose localization and strong biological effect of carbon ion beams with a Bragg peak in the lung. The pathological findings have thus provided evidence of the safety and effectiveness of carbon beam therapy in the treatment of NSCLC.