Shinsaku Yamaguchi

Stereotactic body radiotherapy for lung tumors in patients with subclinical interstitial lung disease: The potential risk of extensive radiation pneumonitis

PURPOSE To evaluate the toxicity and efficacy of thoracic stereotactic body radiotherapy (SBRT) in patients with subclinical interstitial lung disease (ILD). METHODS AND MATERIALS One hundred patients with 124 lung tumors were treated with SBRT at our institution according to our own protocols; patients with subclinical (untreated and oxygen-free) ILD were treated with SBRT, while those with clinical ILD (post- or under treatment) were not. The administration of 48 Gy in four fractions was used in 103 (83%) of the 124 tumors. The presence of subclinical ILD in the pre-SBRT CT findings was reviewed by two chest radiologists. The relationships between radiation pneumonitis (RP) and clinical factors were investigated. RESULTS Subclinical ILD was recognized in 16 (16%) of 100 patients. Grade 2-5 RP was recognized in 13 (13%) of 100 patients. Grade 2-5 RP was observed in three (19%) of 16 patients with subclinical ILD. Subclinical ILD was not found to be a significant factor influencing Grade 2-5 RP; however, extensive RP beyond the irradiated field, including the contralateral lung, was recognized in only three patients with subclinical ILD, and the rate of extensive RP was significantly high in the patients with subclinical ILD. Grade 4 or 5 extensive RP was recognized in only two patients with subclinical ILD. Dosimetric factors of the lungs (V5, V10, V15, V20, V25, MLD) were significantly associated with Grade 2-5 RP. The three-year overall survival and local control rates of all patients were 53% and 86%, respectively. No significant differences were seen in either overall survival or local control rates between the patients with ILD and those without ILD. CONCLUSIONS Subclinical ILD was not found to be a significant factor for Grade 2-5 RP or clinical outcomes in the current study; however, uncommon extensive RP can occur in patients with subclinical ILD.

Deep regional hyperthermia for the whole thoracic region using 8 MHz radiofrequency-capacitive heating device: Relationship between the radiofrequency-output power and the intra-oesophageal temperature and predictive factors for a good heating in 59 patients

Purpose: To assess the relationship between the radiofrequency (RF) output power and the intra-oesophageal temperature for hyperthermia of the whole thoracic region, and also to evaluate the patients’ characteristics associated with adequate heating. Materials and methods: Fifty-nine patients with thoracic cancer treated with radiotherapy plus hyperthermia were retrospectively analysed. The 8-MHz RF capacitive heating device was applied, both the upper and lower electrodes were 300 mm in diameter, placed on opposite sides of the whole thoracic region. All the patients also underwent intra-oesophageal temperature measurements. Results: All thermal parameters, Tmin, Tmax, Tave, and %T ≥ 41°C, of the intra-oesophageal temperature highly correlated with the median RF output power (p < 0.0001), and the relations were independent in the multivariable analyses including clinical characteristics (p < 0.01). The performance status showed a statistically significant association on Tmax, Tave and %T ≥ 41°C (p < 0.05). The patient age and subcutaneous fat at some levels were inversely correlated with the thermal parameters (p < 0.05). Conclusion: The RF output power was significantly correlated with the intra-oesophageal temperature; it could be used as a promising parameter to assess the efficacy of hyperthermia for the whole thoracic region. Higher intra-oesophageal temperature may be achieved in patients with good performance status, younger age and thinner subcutaneous fat.

Epithelial ovarian cancer: definitive radiotherapy for limited recurrence after complete remission had been achieved with aggressive front-line therapy

The purpose of this study was to assess the efficacy and toxicity of definitive radiotherapy (RT) for the recurrence of epithelial ovarian cancer, which is limited to one or two gross regions, after complete remission had been achieved with aggressive front-line therapy. Twenty-seven patients were treated with definitive RT and were retrospectively analyzed. Their median tumor size was 3.0 cm. Twenty-six (96%) patients received external irradiation at a median total dose of 60 Gy, and a median daily dose of 2 Gy. Only two patients received intracavitary brachytherapy. Twenty (74%) of the 27 patients received systemic chemotherapy for the treatment of a limited recurrent tumor followed by definitive RT. Six (22%) of the patients received concurrent chemotherapy and seven (26%) of the patients also underwent regional hyperthermia during definitive RT. Twenty-two (82%) patients had an objective response (CR: 11, PR: 11). The 2-year overall survival, progression-free survival and local (in-field) control rates after RT were 53%, 39% and 96%, respectively. The toxicities were mild, no Grade 3 or higher toxicity was observed in any of the patients. The tumor size( < 3 cm), period between front-line therapy and RT (≥2 year) and objective tumor response (CR) were significant prognostic factors of the overall survival rate. In conclusion, definitive RT for limited recurrence of epithelial ovarian cancer achieves a better local control rate without severe toxicity, and it may therefore be a potentially effective modality for inducing long-term survival in selected patients.

Definitive radiotherapy plus regional hyperthermia with or without chemotherapy for superior sulcus tumors: A 20-year, single center experience

PURPOSE To assess the efficacy and toxicity of definitive radiotherapy (RT) plus regional hyperthermia (HT) in treating superior sulcus tumors (SSTs), and to identify predictors of positive outcomes. METHODS AND MATERIALS Twenty-four patients with SSTs treated with definitive RT plus regional HT were retrospectively analyzed. The median total dose of RT was 70 Gy. All patients were treated with an 8-MHz RF-capacitive heating device. Twelve of 24 (50%) patients also underwent chemotherapy. Those with either subcutaneous fat measuring 2.5 cm or greater, or any other serious complications did not undergo this therapy. RESULTS Overall survival, local control, and distant metastasis-free survival rates at 3 years were 47%, 55%, and 71%, respectively. Chemotherapy and younger age (<65 years) were significant predictors of the overall survival rate. Clinical stage (IIB) was a statistically significant prognostic indicator for local control survival rate. Toxicities were mild, with Grade 3 dermatitis seen in one patient. CONCLUSIONS Definitive RT plus regional HT with chemotherapy may be a promising treatment for SSTs. The results justify further evaluation with detailed treatment protocols in a large number of patients.

Re-irradiation plus regional hyperthermia for recurrent non-small cell lung cancer: A potential modality for inducing long-term survival in selected patients

PURPOSE The purpose of this study was to assess the toxicity and efficacy of re-irradiation plus regional hyperthermia for recurrent NSCLC and to identify the predictors of long-term survival. METHODS AND MATERIALS A total of 33 patients with recurrent NSCLC treated with re-irradiation plus regional hyperthermia were retrospectively analyzed. The median total dose of initial radiotherapy and re-irradiation were 70 Gy and 50 Gy, respectively. A median of 5 hyperthermia treatments using an 8-MHz radiofrequency-capacitive device were applied during re-irradiation in all patients. RESULTS Toxicity of Grade 3 was seen in 3 (9%) patients, and no Grade 4 or 5 toxicity was observed. The median overall survival, local control, and disease progression-free survival times after re-irradiation were 18.1, 12.1, and 6.7 months, respectively. Eight patients achieved a long-term survival (more than 3 years after re-irradiation), and 4 of them underwent a third round of irradiation for re-recurrent tumors. Univariate analyses showed that a smaller tumor size (<4 cm) and the absence of distant metastases were significant predictors for a better overall survival. The absence of distant metastases was also found to be a significant predictor for better disease progression-free survival in the univariate analyses. In the subset analyses of 23 patients treated with hyperthermia using electrodes of 30 cm in diameter, the use of a higher radiofrequency-output power tended to be associated with a better prognosis in terms of the local control rate. CONCLUSIONS Re-irradiation plus regional hyperthermia for recurrent NSCLC appears feasible, with acceptable toxicity, and may be a promising treatment that can result in the long-term survival of patients without distant metastasis and larger recurrent tumors.

Definitive 3D-CRT for clinically localized prostate cancer: modifications of the clinical target volume following a prostate MRI and the clinical benefits

PurposeTo evaluate the modifications of the tumor stage and clinical target volume following a prostate magnetic resonance imaging (MRI) to evaluate the tumor (T) staging, and the clinical benefits for prostate cancer.MethodsA total of 410 patients with newly diagnosed and clinically localized prostate cancer were retrospectively analyzed. The patients were treated with definitive three-dimensional conformal radiotherapy (3D-CRT). In all of the patients, digital rectal examination, transrectal ultrasound, prostate biopsy and computed tomography were performed to evaluate the clinical stage. Of the 410 patients, 189 patients had undergone a prostate MRI study to evaluate the T staging, and 221 patients had not.ResultsModification of the T stage after the prostate MRI was seen in 39 (25%) of the 157 evaluable patients, and a modification of the risk group was made in 14 (9%) patients. Eventually, a modification of the CTV in 3D-CRT planning was made in 13 (8%) patients, and 10 of these had extracapsular disease. Most of the other modifications of the T staging were associated with intracapsular lesions of prostate cancer which did not change the CTV. There were no significant differences in the biological relapse-free survival between the patients with and without a prostate MRI study.ConclusionsModification of the CTV were recognized in only 8% of the patients, most of whom had extracapsular disease, although that of the T stage was seen in approximately one-quarter of the patients. Prostate MRI should only be selected for patients with a high probability of extracapsular involvement.

Definitive radiotherapy plus regional hyperthermia for high-risk and very high-risk prostate carcinoma: Thermal parameters correlated with biochemical relapse-free survival.

Abstract Purpose: The aim of this study was to assess the efficacy of definitive radiotherapy (RT) plus regional hyperthermia (HT) and investigate the potential contribution of HT to clinical outcomes in patients with prostate carcinoma. Materials and methods: Following our institution’s treatment protocol, HT was combined with RT to improve clinical outcomes in selected patients with high-risk or very high-risk prostate cancer. Data from 82 patients treated with RT plus HT and 64 patients treated with RT alone were retrospectively analysed. Results: Median follow-up duration was 61 months. The 5-year biochemical disease-free survival (bDFS) rate for the 82 patients treated with RT plus HT was 78%, whereas bDFS for the 64 patients treated with RT alone was 72%; this difference was not significant. Among the 75 patients treated with RT plus HT who underwent intra-rectal temperature measurements, higher thermal parameters were significant prognostic indicators of improved bDFS by univariate analysis. A higher CEM43 °CT90 thermal parameter and a T stage of T1–2 were significant prognostic factors based on multivariate analysis. The 5-year bDFS rates for the 40 patients with a higher CEM43 °CT90 and the 64 patients treated with RT alone were significantly different, whereas 5-year bDFS for the 35 patients with a lower CEM43 °CT90 and the 64 patients treated with RT alone were not. Conclusions: The addition of HT with higher thermal parameters to RT may improve bDFS for patients with high-risk or very high-risk prostate cancer. These findings also demonstrate the importance of careful selection of treatable patients with higher thermal parameters.

Cancer of the pelvis: definitive three-dimensional conformal radiotherapy for patients with isolated recurrence in the para-aortic lymph nodes

The purpose of this study was to evaluate the outcome of definitive three-dimensional conformal radiotherapy (RT) for isolated para-aortic lymph node (LN) recurrence in patients with controlled primary cancer of the pelvis. Twenty-four consecutive patients with isolated para-aortic LN recurrence were retrospectively analyzed. The patients were included in this study if they were eligible to receive definitive RT for abdominal para-aortic LN recurrence with controlled primary cancer of the pelvis without other distant/recurrent diseases. The median time between the front-line therapy and RT for isolated para-aortic LN metastases was 21 months. Nineteen (79%) patients had an objective tumor response. In-field failure occurred in four patients (17%), while failure outside of the irradiated field was recognized in 12 patients (50%). The overall survival, progression-free survival and local control rates at 5 years were 56%, 29% and 72%, respectively. Statistically significant prognostic factors of the overall survival rate in the univariate analyses were an objective tumor response (P = 0.0098) and the time between front-line therapy and RT (P = 0.033). The maximum tumor size was a significant prognostic factor of the overall survival rates in the multivariate analyses (P = 0.046). The toxicities were mild; leukopenia of Grade 3 was detected in one patient, and no Grade 3 or higher non-hematological toxicity was observed. In conclusion, definitive three-dimensional RT for isolated abdominal para-aortic LN recurrence in patients with controlled primary cancer of the pelvis may be feasible, and can provide a relatively longer-term survival. The results justify further investigation of higher dose RT using modern RT planning techniques.

Salvage radiotherapy for second oligo-recurrence in patients with breast cancer

Abstract A new concept designated ‘oligo-recurrence (OR)’ has been proposed, which indicates one to several distant metastases/recurrences in one or more organs, which can be treated with local therapy, after the primary site of the cancer has been controlled. The purpose of this study was to assess the efficacy and toxicity of salvage radiotherapy (RT) for the second OR of breast cancer. The second OR was defined as once-salvaged patients with OR who had a second failure that was also detected as the state of OR. Twenty-one patients with second OR were treated with salvage RT and were retrospectively analyzed. The sites of the second OR were locoregional recurrence in 7 patients and distant metastasis in 14 patients. Salvage RT was performed at a median total dose of 60 Gy. Nineteen (90%) patients had an objective response. The median overall survival and progression-free survival (PFS) times were 41 and 24 months after salvage RT for the second OR, respectively. The 3-year local (in-field) control (LC) rates were 93%. The toxicities were mild; acute toxicities ≥Grade 3 were seen in one patient with Grade 3 dermatitis, and no late toxicity ≥Grade 2 was observed. In conclusion, salvage RT for the second OR was able to achieve a better LC rate and longer PFS time without inducing severe toxicity, and therefore may be a potentially effective modality for inducing long-term survival in select patients.

Salvage Radiotherapy for Solitary Metachronous Bone Metastasis in Patients with Breast Cancer

AIM We assessed the efficacy and toxicity of salvage radiotherapy for solitary metachronous bone metastasis (SMBM) in patients with breast cancer. PATIENTS AND METHODS We retrospectively analyzed 17 patients with SMBM who were treated with salvage radiotherapy. First failure was detected as SMBM in all patients. Salvage radiotherapy using three-dimensional treatment planning was performed at a median total dose of 50 Gy. Median daily dose was 2.0 Gy. RESULTS Median follow-up was 40 months. Local recurrence of SMBM was noted in only two patients. The 3-year overall survival, progression-free survival, and local control rates were 93%, 51%, and 85%, respectively. Median overall and progression-free survival were 74 and 30 months, respectively. Toxicities were mild, and bone fractures were not observed. CONCLUSION Salvage radiotherapy for SMBM was able to achieve higher local control rates without severe toxicity, as well as to provide longer progression-free survival; therefore, this may be an effective modality.