Atsushi Motegi

Accelerated radiotherapy for T1 to T2 glottic cancer

Accelerated fractionation radiotherapy (RT) was administered in an attempt to improve the local control rates in patients with T1/T2 N0 glottic cancer.

Proton beam therapy for olfactory neuroblastoma

PURPOSE To clarify the efficacy and feasibility of proton beam therapy (PBT) for olfactory neuroblastoma (ONB). METHODS AND MATERIALS We retrospectively reviewed 42 consecutive patients who received PBT with curative intent for ONB at National Cancer Center Hospital East from November 1999 to March 2012. RESULTS Five patients (12%) had Kadish A disease, nine (21%) had Kadish B, and twenty-eight (67%) had Kadish C. All patients except one received a total dose of 65Gy (relative biological effectiveness: RBE) in 26 fractions. Twenty-four patients (57%) received induction and/or concurrent chemotherapy. The median follow-up for all eligible patients was 69months (7-186). The 5-year overall survival (OS) and progression-free survival (PFS) rates were 100% and 80% for Kadish A, 86 and 65% for Kadish B, and 76% and 39% for Kadish C, respectively. The sites of the first progression were local in six patients (30%), regional in eight (40%), distant in two (10%), local and regional in two (10%), and local and distant in two (10%). Late adverse events of grade 3-4 were seen in six patients (ipsilateral visual impairment, 3; bilateral visual impairment, 1; liquorrhea, 1; cataract, 1). CONCLUSION PBT was a safe and effective modality for ONB.

Post-mastectomy radiation therapy without usage of a bolus may be a reasonable option.

To clarify the efficacy and toxicity of post-mastectomy radiation therapy (PMRT) without usage of a bolus, we identified 129 consecutive patients who received PMRT at the National Cancer Center Hospital East between 2003 and 2012. Seven of the 129 patients who received breast reconstruction before PMRT were excluded. All patients received PMRT of 6 MV photons, without usage of a bolus. The median follow-up duration for all eligible patients was 47.7 months (range: 4.0–123.2). Local, locoregional and isolated locoregional recurrence was found in 12 (9.8%), 14 (11%) and 5 patients (4.1%), respectively. The 3- and 5-year cumulative incidence of local recurrence, locoregional recurrence and isolated locoregional recurrence was 9.2 and 10.7%, 10.8 and 12.4%, and 4.3 and 4.3%, respectively. Although Grade 2 dermatitis was found in 11 patients (9.0%), no Grade 3–4 dermatitis was found. On univariate analysis, only a non-luminal subtype was a significant predictor for local recurrence (P < 0.001). On multivariate analysis, a non-luminal subtype remained as an independent predictor for local recurrence (P = 0.003, odds ratio: 10.9, 95% confidence interval: 2.23–53.1). In conclusion, PMRT without usage of a bolus resulted in a low rate of severe acute dermatitis without an apparent increase in local recurrence. PMRT without usage of a bolus may be reasonable, especially for patients with a luminal subtype.

Acute and Progressive Tracheal Stenosis after Proton Beam Therapy with Concurrent Chemotherapy for Non–Small Cell Lung Cancer

Acute and Progressive Tracheal Stenosis after Proton Beam Therapy with Concurrent Chemotherapy for Non–Small Cell Lung Cancer Yoshitaka Zenke, MD, Shigeki Umemura, MD, PhD,* Atsushi Motegi, MD, Kinya Furukawa, MD, Keisuke Kirita, MD, Shingo Matsumoto, MD, Kiyotaka Yoh, MD, Seiji Niho, MD, Hironobu Ohmatsu, MD, Masahiro Tsuboi, MD, Tetsuo Akimoto, MD, Koichi Goto, MD Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan Division of Radiation Oncology and Particle Therapy, National Cancer Center Hospital East, Kashiwa, Chiba, Japan Tokyo Medical University, Ibaraki Medical Center, Inashiki-gun, Ibaraki, Japan

Locoregional control after intensity-modulated radiotherapy for nasopharyngeal carcinoma with an anatomy-based target definition.

OBJECTIVE The objective of the study was to evaluate locoregional control after intensity-modulated radiotherapy for nasopharyngeal cancer using a target definition along with anatomical boundaries. METHODS Forty patients with biopsy-proven squamous cell or non-keratinizing carcinoma of the nasopharynx who underwent intensity-modulated radiotherapy between April 2006 and November 2009 were reviewed. There were 10 females and 30 males with a median age of 48 years (range, 17-74 years). More than half of the patients had T3/4 (n = 21) and/or N2/3 (n = 24) disease. Intensity-modulated radiotherapy was administered as 70 Gy/33 fractions with or without concomitant chemotherapy. The clinical target volume was contoured along with muscular fascia or periosteum, and the prescribed radiotherapy dose was determined for each anatomical compartment and lymph node level in the head and neck. RESULTS One local recurrence was observed at Meckels cave on the periphery of the high-risk clinical target volume receiving a total dose of <63 Gy. Otherwise, six locoregional failures were observed within irradiated volume receiving 70 Gy. Local and nodal control rates at 3 years were 91 and 89%, respectively. Adverse events were acceptable, and 25 (81%) of 31 patients who were alive without recurrence at 2 years had xerostomia of ≤Grade 1. The overall survival rate at 3 years was 87%. CONCLUSIONS Target definition along with anatomically defined boundaries was feasible without compromise of the therapeutic ratio. It is worth testing this method further to minimize the unnecessary irradiated volume and to standardize the target definition in intensity-modulated radiotherapy for nasopharyngeal cancer.

Dosimetric comparison between proton beam therapy and photon radiation therapy for locally advanced esophageal squamous cell carcinoma

BackgroundThe purpose of this study was to perform a dosimetric comparison between proton beam therapy (PBT) and photon radiation therapy in patients with locally advanced esophageal squamous cell carcinoma (ESCC) who were treated with PBT in our institution. In addition, we evaluated the correlation between toxicities and dosimetric parameters, especially the doses to normal lung or heart tissue, to clarify the clinical advantage of PBT over photon radiation therapy.MethodsA total of 37 consecutive patients with Stage III thoracic ESCC who had received PBT with or without concurrent chemotherapy between October 2012 and December 2015 were evaluated in this study. The dose distributions of PBT were compared with those of dummy 3-dimensional conformal radiation therapy (3DCRT) and Intensity Modulated Radiation Therapy (IMRT), focusing especially on the doses to organs at risk, such as normal lung and heart tissue.ResultsOf the 37 patients, the data from 27 patients were analyzed. Among these 27 patients, four patients (15%) developed grade 2 pericardial effusion as a late toxicity. None of the patients developed grade 3 or worse acute or late pulmonary and cardiac toxicities. When the dosimetric parameters between PBT and planned 3DCRT were compared, all the PBT domestic variables for the lung dose except for lung V10 GyE and V15 GyE were significantly lower than those for the dummy 3DCRT plans, and the PBT domestic variables for the heart dose were also significantly lower than those for the dummy 3DCRT plans. When the PBT and IMRT plans were compared, all the PBT domestic variables for the doses to the lung and heart were significantly lower than those for the dummy IMRT plans. Regarding the correlation between the grades of toxicities and the dosimetric parameters, no significant correlation was seen between the occurrence of grade 2 pericardial effusion and the dose to the heart.ConclusionsWhen the dosimetric parameters of the dose distributions for the treatment of patients with locally advanced stage III ESCC were compared between PBT and 3DCRT or IMRT, PBT enabled a significant reduction in the dose to the lung and heart, compared with 3DCRT or IMRT.

Radiotherapy increases plasma levels of tumoral cell-free DNA in non-small cell lung cancer patients

We investigated the plasma levels of tumor-specific cell-free DNA (cfDNA) in 17 stage I–II (early) and IV (advanced) non-small cell lung cancer (NSCLC) patients who underwent radiotherapy. Digital polymerase chain reaction (PCR) and targeted sequencing showed that total and tumor-specific cfDNA levels increased in response to radiotherapy in both early- and advanced-stage NSCLC patients. We detected high copy numbers of epidermal growth factor receptor mutations (L858R and T790M) in the cfDNA samples from stage IV NSCLC patients who underwent stereotactic body radiation therapy to treat brain metastasis related to tyrosine kinase inhibitor (TKI) treatment failure. In conclusion, our study demonstrates that radiotherapy increases tumoral cfDNA levels in the plasma and shows potential to serve as an indicator for diagnosing drug-resistant tumor-related gene mutations in early-stage NSCLC patients or those undergoing molecular targeted therapy.

Impact of prophylactic cranial irradiation on pattern of brain metastases as a first recurrence site for limited-disease small-cell lung cancer

Abstract This study sought to evaluate the impact of prophylactic cranial irradiation (PCI) on the pattern of brain recurrence after radical treatment in patients with limited-disease small-cell lung cancer (LD-SCLC). Patients treated with radiotherapy and chemotherapy between January 2006 and December 2014 at a single institution were retrospectively examined. Radiotherapy was performed using accelerated hyperfractionated radiotherapy (twice daily, 45 Gy in 30 fractions) or conventional fractionated radiotherapy (once daily, 50 Gy in 25 fractions). The chemotherapy regimen consisted of intravenous platinum–etoposide. A total of 162 patients were included and the median follow-up duration was 38 months. Ninety-three patients underwent PCI, and the 3-year overall survival (OS) rates were 14% among patients without PCI and 41% among those with PCI (P < 0.001). The frequency of brain metastases as a first recurrence site (BMFR) was significantly lower among patients who underwent PCI, compared with those who did not (P = 0.002). The median time to the l of BMFR was significantly shorter among patients without PCI than among those with PCI (P = 0.012). In addition, 68% of the BMFR patients who did not undergo PCI exhibited five or more lesions, while only 12% of BMFR patients who did undergo PCI exhibited five or more lesions (P < 0.001). PCI had a significant positive impact on patient prognosis after radical treatment for LD-SCLC, and the difference in the number of, and time to the appearance of, BMFR between patients treated with PCI and those treated without PCI might affect the clinical outcomes.

Late radiological changes after passive scattering proton beam therapy for Stage I lung cancer

Abstract This study aimed to examine late radiological changes after proton beam therapy (PBT) for early-stage non–small cell lung cancer (NSCLC) and to clarify correlations between mass-like radiological changes and patient characteristics. CT scans of patients who underwent passive scattering PBT for T1-2N0M0 NSCLC were analyzed retrospectively. Patients were considered eligible if follow-up CT was performed for at least 2 years, with no definite evidence of local recurrence. The following five periods were defined: (i) 6–12 months, (ii) 12–24 months, (iii) 24–36 months, (iv) 36–48 months and (v) 48–60 months after PBT. Late (≥6 months) radiological changes were scored by consensus of three radiation oncologists according to classifications set forth by Koenig (Radiation injury of the lung after three-dimensional conformal radiation therapy. AJR Am J Roentgenol 2002;178:1383–8.). CT scans of 113 patients (median follow-up, 36 months; range, 24–137 months) were evaluated. Late radiological changes during Periods (i), (ii), (iii), (iv) and (v) included modified conventional pattern (80%, 79%, 72%, 58% and 56%, respectively), mass-like changes (8%, 9%, 14%, 22% and 18%, respectively), scar-like changes (4%, 9%, 11%, 17% and 24%, respectively) and no increased density (8%, 3%, 3%, 2% and 2%, respectively). Mass-like changes were observed in 23 patients (20%). Among patients who developed mass-like changes, the median interval between the initiation of PBT and the onset of mass-like changes was 19 months (range, 6–62 months). In multivariate analysis, a peripheral location was found to be a significant factor (P = 0.035; odds ratio: 4.44; 95% confidence interval: 1.12–21.28). In conclusion, mass-like changes were observed in 20% of patients who underwent PBT. Patients with peripheral tumors showed a higher incidence of mass-like changes.

Palliative radiotherapy for breast cancer patients with skin invasion: a multi-institutional prospective observational study

Purpose To clarify the efficacy of palliative radiotherapy for the relief of symptoms due to skin invasion in patients with breast cancer. Materials and methods We conducted a multi-institutional prospective observational study of patients who received palliative radiotherapy for skin invasion due to a primary lesion or chest wall recurrence. Bleeding/discharge, offensive odor, pain and QOL scores were evaluated before and 1, 3 and 6 months after radiotherapy. Results Twenty-one patients were assessed. Sixteen patients (76%) received 36 Gy in 12 fractions. The mean (±1 SD) score of bleeding/discharge was 1.90 ± 0.89 before radiotherapy, 1.50 ± 0.74 at 1 month, 0.47 ± 0.58 at 3 months, and 0.82 ± 1.04 at 6 months (P = 0.001). The mean score of offensive odor was 1.21 ± 1.38 before radiotherapy, 0.71 ± 0.92 at 1 month, 0.20 ± 0.41 at 3 months, and 0.27 ± 0.62 at 6 months (P = 0.008). The mean score of pain was 2.90 ± 1.22 before radiotherapy, 3.05 ± 1.36 at 1 month, 3.29 ± 1.10 at 3 months, and 3.31 ± 1.54 at 6 months (P = 0.431). The mean total score of QOL-ACD/QOL-ACD-B was 126.2 ± 24.5 before radiotherapy, 130.3 ± 26.3 at 1 month, 136.2 ± 26.6 at 3 months, and 126.6 ± 32.8 at 6 months (P = 0.178). Conclusion Palliative radiotherapy for skin invasion in patients with breast cancer might be effective, especially for the relief of bleeding/discharge and offensive odor.