Preliminary results of reduced myocardial blood flow in the subacute phase after radiation therapy for thoracic esophageal cancer: A quantitative analysis with stress dynamic myocardial computed tomography perfusion imaging.

BACKGROUND AND PURPOSE: Late adverse cardiac events after radiation therapy (RT) for thoracic malignancies are known, but the underlying mechanisms are poorly understood. This study aimed to determine the radiation dose that can cause MBF alterations in the subacute phase after RT for thoracic esophageal cancer using stress dynamic myocardial computed tomography perfusion imaging (CTP). MATERIALS AND METHODS: Twenty-five patients with esophageal cancer scheduled for RT were prospectively enrolled. The quantitative analysis of MBF by CTP was performed before and 3 months after RT. The mean radiation dose and hyperemic MBF in 15 segments of the left ventricular (LV) myocardium were determined. ΔMBF was calculated in each segment as MBFafter RT - MBFbeforeRT. The myocardial segments were classified into the following 5 groups according to the mean radiation dose: group A, <10 Gy; B1, 10-15 Gy; B2, 15-20 Gy; C, 20-30 Gy; and D, >30 Gy. RESULTS: The final cohort included 22 patients who completed pre- and post-RT CTP. A one-way analysis of variance revealed a significant difference (p=0.005) in ΔMBF among the five groups of LV segments classified by the mean radiation dose. ΔMBF was significantly lower in group C (-7.7 ± 28.9 mL/min/100 g, p=0.020) and group D (-8.4 ± 34.8 mL/min/100 g, p=0.004) in comparison to ΔMBF in group A (4.9 ± 26.1 mL/min/100 g). CONCLUSIONS: This study using CTP early after RT demonstrated a significant reduction of the MBF in the LV segments with ≥20 Gy of radiation. The results might provide important insights into preventing radiotherapy-induced cardiac events.

Initial Experience of Intra-Arterial Chemotherapy Using a Novel External Carotid Arterial Sheath System Combined with Radiotherapy and Systemic Chemotherapy for Locally Advanced Tongue Cancer.

We retrospectively evaluated the safety and effectiveness of an external carotid arterial sheath (ECAS) for intra-arterial chemotherapy (IACT) for locally advanced tongue cancer. Thirty-one patients with the Union for International Cancer Control's 8th TNM stage III-IV tongue cancer underwent IACT using the ECAS combined with RT and systemic chemotherapy with either cisplatin and fluorouracil (FP) or docetaxel, cisplatin, and fluorouracil (TPF) between October 2015 and February 2021. The ECAS was inserted retrogradely via the superficial temporal artery, and the tip was placed in the external carotid artery between the maxillary and facial arteries. A microcatheter was inserted into each tumor-feeding artery through the ECAS under fluoroscopy, wherein cisplatin 50 mg/m2 was administered. IACT was performed weekly with neutralization using sodium thiosulfate. Complete response of the primary lesion was achieved in 28/31 (90%) patients. The median follow-up for all patients was 39 months. The 3-year overall survival, progression-free survival, and local control rates were 81.6%, 74.2%, and 83.4%, respectively. Grade 3 and greater toxicities included oral mucositis (45%), neutropenia (39%), nausea (13%), anemia (10%), thrombocytopenia (10%), dry mouth (10%), and fever (3%). There were no severe complications associated with IACT. In conclusion, the ECAS is feasible and effective for locally advanced tongue cancer.

Tenascin C in radiation-induced lung damage: Pathological expression and serum level elevation.

Radiation-induced lung damage (RILD) is a critical problem in lung cancer radiotherapy, and it is difficult to predict its severity. Although no biomarkers for RILD have been established, tenascin C (TNC) is an extracellular matrix glycoprotein involved in the remodeling of damaged tissues and has been implicated in inflammation and fibrosis. We report the unique case of a 36-year-old man with adenocarcinoma of the lung, Union for International Cancer Control stage IIIB, who was treated with radiotherapy before lung surgery. The surgical specimen showed histopathological expression of TNC in the region where radiation pneumonitis was observed radiographically. Serum TNC levels were elevated after radiotherapy. In this case, TNC is suggested to be implicated in RILD and may be a potential candidate as a biomarker for the onset and severity of the condition.

Intra-arterial chemoradiotherapy for locally advanced buccal mucosal cancer in an elderly patient with multiple comorbidities: A case report.

BACKGROUND: The management of locally advanced oral cavity squamous cell carcinoma (LA-OCScc) in elderly patients with multiple comorbidities is difficult. CASE: We report the case of an elderly patient with buccal mucosal squamous cell carcinoma as well as chronic renal dysfunction, hepatic cirrhosis, rheumatoid arthritis, and metachronous diffuse large B-cell lymphoma. We performed radiation therapy (a total dose of 70 Gy in 35 fractions) and six cycles of intra-arterial chemotherapy with 40 mg/m2 cisplatin per week. After treatment, the tumor completely disappeared, and there was no recurrence or deterioration of comorbidities during the 12-month follow-up period. CONCLUSION: Intra-arterial chemoradiotherapy may be a good treatment option for LA-OCScc in elderly patients with multiple comorbidities.

Proton beam therapy for children and adolescents and young adults (AYAs): JASTRO and JSPHO Guidelines.

Children and adolescents and young adults (AYAs) with cancer are often treated with a multidisciplinary approach. This includes use of radiotherapy, which is important for local control, but may also cause adverse events in the long term, including second cancer. The risks for limited growth and development, endocrine dysfunction, reduced fertility and second cancer in children and AYAs are reduced by proton beam therapy (PBT), which has a dose distribution that decreases irradiation of normal organs while still targeting the tumor. To define the outcomes and characteristics of PBT in cancer treatment in pediatric and AYA patients, this document was developed by the Japanese Society for Radiation Oncology (JASTRO) and the Japanese Society of Pediatric Hematology/Oncology (JSPHO).

Endobronchial brachytherapy combined with surgical procedure for synchronous multiple primary lung cancer: A case report.

The management of synchronous multiple primary lung cancer is a challenge. In this report, we describe our experience in a patient with three synchronous multiple cancers. The first lesion was completely surgically removed, the second lesion received postoperative irradiation, and the third lesion was treated with radiotherapy alone. Radiation therapies were performed using a combination of external irradiation and endobronchial brachytherapy. Endobronchial brachytherapy is an effective radiation therapy for endobronchial tumors owing to its advantage of high-dose concentration. However, adverse events (AEs) such as hemoptysis or severe bronchitis are a problem. Thus, we have developed an applicator to keep the radioactive source in the center of the bronchial lumen. A total of 28 months after treatment, the patient had not experienced any relapses or AEs. Endobronchial brachytherapy using an applicator can be an alternative treatment for cases in which surgery is expected to lead to pulmonary dysfunction.

Proton beam therapy combined with retrograde intra-arterial infusion chemotherapy for an extremely rapid growing recurrent ameloblastic carcinoma: A case report.

Ameloblastic carcinoma (AC) is a very rare malignant odontogenic tumor. Although surgical resection is generally performed, treatment approaches have not been established for recurrent cases. Chemotherapy and radiotherapy are positioned as adjunctive therapies, and few studies investigated definitive non-operative therapy. We present the case of a 71-year-old male with recurrent secondary-type AC arising from the right maxilla, who was treated with proton beam therapy (PBT; 71.4 Gy relative biological effectiveness in 32 fractions) combined with continuous intra-arterial infusion of cisplatin (40 mg/m2) and docetaxel (8 mg/m2). The patient experienced acute grade 3 mucositis, dermatitis and neutropenia, which were resolved within 3 months of treatment. Late adverse events were grade 1 skin atrophy, and grade 2 right optic nerve disorder and retinopathy. After ~8 years of treatment, the patient died from another cause but did not experience any relapse or metastasis during the follow-up period of 94 months. To the best of our knowledge, this is the first report of recurrent AC treated with PBT and intra-arterial infusion chemotherapy without any severe late adverse events. This combination therapy approach may be considered as an effective therapeutic option for inoperable AC.

The Clinical Outcomes of Hemicortical Extracorporeal Irradiated Autologous Bone Graft After Tumor Resection of Bone and Soft Tissue Sarcoma.

BACKGROUND/AIM: We analyzed the process of healing at osteotomy sites and timing of achievement of full weight-bearing in sarcoma patients who underwent hemicortical or intercalary reconstruction using the extracorporeal irradiated autologous bone graft technique. PATIENTS AND METHODS: We studied 10 patients who had undergone tumor resection and reconstruction with hemicortical extracorporeal irradiated autologous bone graft at mid-shaft femur or tibia. The control group consisted of 30 patients who received the reconstruction using intercalary bone graft. RESULTS: Full weight-bearing was achieved in all 10 patients at a median time of 4.8 months. Function was excellent in all patients. When comparing the clinical outcome among the patients who received intercalary and hemicortical grafts, the duration to full weight-bearing achievement in patients who received hemicortical graft was shorter than that in those with intercalary graft. CONCLUSION: Early full weight-bearing may be achieved in patients undergoing hemicortical resection and reconstruction using extracorporeal irradiated autologous bone graft.

Proton Beam Therapy Combined with Intra-Arterial Infusion Chemotherapy for Stage IV Adenoid Cystic Carcinoma of the Base of the Tongue.

Adenoid cystic carcinoma (ACC) is a very rare epithelial tumor of the salivary glands. Surgical resection is considered to be a standard therapy. However, the optimal treatment strategy for managing advanced cases has not yet been established. This study evaluated the efficacy and toxicity of proton beam therapy (PBT) combined with selective intra-arterial infusion chemotherapy (IAIC) using weekly cisplatin for locally advanced ACC of the base of the tongue. Between March 2009 and February 2018, 15 patients were treated. The median follow-up duration was 56 (range: 15-116) months. The 5-year local control and overall survival rates were 89% and 76%, respectively. With regard to late toxicities, grade 2 osteoradionecrosis was found in one patient and grade 5 pharyngeal necrosis was observed in one patient. Considering most cases were significantly advanced and inoperable, this therapy was effective in controlling the primary tumor, preserving function and maintaining the quality of life. Although improvements are needed to reduce adverse events, PBT in combination with IAIC can be a treatment option for locally advanced ACC of the base of the tongue.

Long-term follow-up of intensive chemotherapy followed by reduced-dose and reduced-field irradiation for intracranial germ cell tumor.

OBJECTIVE The authors analyzed the efficacy of intensive chemotherapy followed by reduced-dose and reduced-field irradiation for intracranial germ cell tumors (GCTs) and evaluated the long-term late effects caused by chemoradiotherapy (CRT). METHODS The authors performed a retrospective study. The subjects were 24 patients who received CRT between April 1994 and April 2015. After surgery, intensive chemotherapy followed by reduced-dose and reduced-field irradiation was administered. For those with pure germinoma, who comprised the "good prognosis" group, five courses of conventional-dose chemotherapy (CDC) were administered, and radiotherapy (24 Gy) was applied to the whole ventricle. For all others, defined as the "intermediate and poor prognosis" group, two or three courses of CDC and high-dose chemotherapy were administered with peripheral blood stem cell transplantation and radiotherapy (24­30 Gy) applied to the whole ventricle or a larger field with or without local boost irradiation (20 Gy), which was applied as needed. RESULTS The median period of follow-up was 112.5 months (range 28­261 months), and the 5-/10-year overall and progression-free survival rates were 100%/83.5% and 91.3%/86.5%, respectively. The 5-/10-year overall survival rates determined based on the histological subtypes were 100%/100% for pure germinoma and 93.8%/78.7% for others, respectively. The late toxicities were as follows: endocrine disorder (33% in pure germinoma, 56% in others), involuntary movements (17% in pure germinoma, 39% in others), ear and labyrinth disorders (17% in pure germinoma, 33% in others), and psychiatric disorders (0% in pure germinoma, 33% in others). Nineteen of 24 patients underwent MRI (T2*- or susceptibility-weighted imaging) after radiotherapy, and 16 (84%) of those 19 patients had microbleeds detected, while 2 (10.5%) had radiation-induced cavernous vascular malformations detected. CONCLUSIONS Intensive chemotherapy followed by reduced-dose and reduced-field irradiation for intracranial GCTs had the same outcome as that reported in the literature, but late adverse effects after treatment were observed. Almost all of the complications were relatively mild but had the potential to lead to psychiatric disorders and intracranial hemorrhaging. ABBREVIATIONS AFP = alpha-fetoprotein; CDC = conventional-dose chemotherapy; CMB = cerebral microbleed; CRT = chemoradiotherapy; CSI = craniospinal irradiation; EP = etoposide and cisplatin; GCT = germ cell tumor; HCG = human chorionic gonadotropin; HDC = high-dose chemotherapy; ICE = ifosfamide, cisplatin, and etoposide; NGGCT = nongerminomatous GCT; OS = overall survival; PBSCT = peripheral blood stem cell transplantation; PFS = progression-free survival; RICM = radiation-induced cavernous malformation; STGC = syncytiotrophoblastic giant cell; SWI = susceptibility-weighted imaging.

A comparison of two types of microcatheters used for a novel external carotid arterial sheath system for intra-arterial chemotherapy of head and neck cancer.

PURPOSE: We developed an external carotid arterial sheath (ECAS) for performing intra-arterial chemotherapy (IACT) via the superficial temporal artery for head and neck cancer. This study aimed to assess the potential of a novel microcatheter with a steerable tip inserted through the ECAS in comparison to an existing hook-type microcatheter. MATERIALS AND METHODS: The same operator used two types of microcatheters alternately for each weekly IACT session with the same patient, and the fluoroscopy time required for catheterization and the arterial selectivity of each microcatheter were compared. RESULTS: Ten patients with advanced head and neck cancer were enrolled. The steerable microcatheter significantly shortened the fluoroscopy time required for catheterization in comparison to the hook-type microcatheter (45.9 ± 4.8 vs 70.2 ± 9.8 s, p < 0.02). The arterial selectivity was equivalent [97.1%, (34/35) vs 88.6%, (31/35), p = 0.36]. No serious adverse events were observed in association with the procedure. CONCLUSION: In combination with an ECAS, the steerable microcatheter might be more useful than the hook-type microcatheter.

Endobronchial brachytherapy with curative intent: the impact of reference points setting according to the bronchial diameter.

Endobronchial brachytherapy (EBB) is an effective treatment for endobronchial tumors. However, bronchial toxicity caused by over-irradiation remains problematic. To decrease bronchial toxicity, we developed a source-centralizing applicator for EBB. The purpose of the present study was to assess the efficacy and safety of EBB with varying reference dose points according to the bronchial diameter, using a source-centralizing applicator. We reviewed 15 patients with endobronchial carcinoma who were treated with curative intent using a combination of external beam radiotherapy (EBRT) and high-dose-rate EBB between 2005 and 2014. During each EBB session, we used a source-centralizing applicator that maintained the source-delivering catheter in the center of the bronchial lumen. Reference dose points were 5-7 mm from the source axis, depending on the bronchial diameter. The median radiation doses of EBRT and EBB were 40 Gy in 20 fractions and 18 Gy in 3 fractions, respectively. The median observation period was 36 months. The 3-year overall survival, progression-free survival and local control rates were 79%, 77% and 100%, respectively. Grade 2 radiation pneumonitis was observed in two cases. Bronchial toxicities, such as hemoptysis or the symptoms of chronic bronchitis, were not observed. EBB with varying reference dose points according to bronchial diameter, using a source-centralizing applicator, is a promising procedure that may be effective for tumor elimination and reducing toxicity to the bronchial wall.

A Novel External Carotid Arterial Sheath System for Intra-arterial Infusion Chemotherapy of Head and Neck Cancer.

PURPOSE: The purpose of this study was to describe a novel system for treating advanced head and neck cancer consisting of an external carotid arterial sheath (ECAS) and a microcatheter to inject drugs retrogradely into multiple feeding arteries through the superficial temporal artery (STA). MATERIALS AND METHODS: Four consecutive patients with head and neck cancer that had more than one feeding artery were enrolled in this study. The ECAS was made of polyurethane and surface-coated with heparin resin to prevent thrombus formation, allowing it to remain in place for a prolonged period of time. The ECAS was inserted through the STA, and its tip was placed between the maxillary artery and facial artery. The tumor-feeding arteries were selected using a hooked-shaped microcatheter through the ECAS. RESULTS: A total of 13 target arteries were selected in the four patients. The microcatheter inserted via the ECAS was used to catheterize ten arteries (five lingual arteries and five facial arteries). The remaining three lingual arteries were directly selected by the catheter without ECAS. All of the target arteries were able to be catheterized superselectively. The technical success rate was 100%. Vascular occlusion, which might have been caused by the ECAS, was observed in one patient. No neurologic toxicities occurred. CONCLUSION: This ECAS system is a new approach for retrograde superselective intra-arterial chemotherapy that covers the entire tumor with anticancer drugs. It has the potential to increase the effectiveness of therapy for advanced head and neck cancer. LEVEL OF EVIDENCE: Level 4, Case Series.

The impact of epidermal growth factor receptor mutations on patterns of disease recurrence after chemoradiotherapy for locally advanced non-small cell lung cancer: a literature review and pooled analysis.

The purpose of this review was to evaluate the impact of epidermal growth factor receptor (EGFR) mutation status on disease recurrence in patients treated with chemoradiotherapy (CRT) for locally advanced non-small cell lung cancer (NSCLC). A literature search was conducted and a total of three studies were analyzed. There was no significant difference in the objective response rate between the EGFR mutation group and the EGFR wild-type group (odds ratios [OR] 1.46, 95% CI, 0.79-2.70, P = 0.228), and there was no significant difference in the incidence of disease recurrence (OR 1.37, 95% CI, 0.68-2.75, P = 0.379) between the two groups. There were significant difference in the incidence of local/locoregional progression (LP) (OR 0.35, 95% CI, 0.18-0.71, P = 0.003) and distant progression (DP) (OR 2.97, 95% CI, 1.59-5.54, P < 0.001). Brain metastasis (BM) was one of the main recurrence patterns of DP, and the incidence was significantly higher in the EGFR mutant group (OR 2.75, 95% CI, 1.43-5.31, P = 0.003). There were no statistically significant heterogeneities in these pooled analyses. The patterns of recurrence after CRT for locally advanced NSCLC were different according to EGFR mutation status. LP after CRT in patients with EGFR mutation was less frequent, but the high incidence of DP, especially BM, continued to be the major problem. On the other hand, LP continued to be the major problem in EGFR wild-type patients. In multimodality treatment for inoperable locally advanced NSCLC, we may need to consider different treatment strategies according to EGFR mutation status.

Minimally invasive surgery using intraoperative electron-beam radiotherapy for the treatment of soft tissue sarcoma of the extremities with tendon involvement.

BACKGROUND: When a soft tissue sarcoma (STS) is located at the distal part of an extremity and involves the tendon, a wide excision usually causes severe functional disability. We therefore developed a minimally invasive surgical technique using intraoperative electron-beam radiotherapy (IOERT) to reduce the incidence of post-operative functional disability in patients with peri-/intra-tendinous STS. We assessed the clinical outcomes of the novel minimally invasive surgery. METHODS: The study population included five patients who received treatment for distal extremity STSs. After elevating the tumor mass, including the tendon and nerve from the tumor bed with a wide margin, a lead board was inserted beneath the tumor mass to shield the normal tissue. IOERT (25-50 Gy) was then applied, and the tumor excised with care taken to maintain the continuity of the tendon. RESULTS: In a desmoid patient, local recurrence was observed outside the irradiated field. No cases of neuropathy or bone necrosis were observed. The mean limb function score was excellent in all patients. None of the high-grade sarcoma patients had local recurrence or distant metastasis. CONCLUSIONS: Although the current study is only a pilot study with a small number of patients, it shows that this minimally invasive procedure has the potential to become a standard treatment option for selected patients. TRIAL REGISTRATION: H17-250 (registered 2 November 2005) and H25-250 (modified from H17-250, registered 5 December 2013).

The impact of emphysema on dosimetric parameters for stereotactic body radiotherapy of the lung.

The purpose of this study was to evaluate the impact of emphysematous changes in lung on dosimetric parameters in stereotactic body radiation therapy (SBRT) for lung tumor. A total of 72 treatment plans were reviewed, and dosimetric factors [including homogeneity index (HI) and conformity index (CI)] were evaluated. Emphysematous changes in lung were observed in 43 patients (60%). Patients were divided into three groups according to the severity of emphysema: no emphysema (n = 29), mild emphysema (n = 22) and moderate to severe emphysema groups (n = 21). The HI (P < 0.001) and the CI (P = 0.029) were significantly different in accordance with the severity of emphysema in one-way analysis of variance (ANOVA). The HI value was significantly higher in the moderate to severe emphysema group compared with in the no emphysema (Tukey, P < 0.001) and mild emphysema groups (P = 0.002). The CI value was significantly higher in the moderate to severe emphysema group compared with in the no emphysema group (P = 0.044). In multiple linear regression analysis, the severity of emphysema (P < 0.001) and the mean material density of the lung within the PTV (P < 0.001) were significant factors for HI, and the mean density of the lung within the PTV (P = 0.005) was the only significant factor for CI. The mean density of the lung within the PTV was significantly different in accordance with the severity of emphysema (one-way ANOVA, P = 0.008) and the severity of emphysema (P < 0.001) was one of the significant factors for the density of the lung within the PTV in multiple linear regression analysis. Our results suggest that emphysematous changes in the lung significantly impact on several dosimetric parameters in SBRT, and they should be carefully evaluated before treatment planning.

Multimodality Treatment for Patients with Node-Positive Prostate Cancer: the Role of Radiation Therapy.

Prostate cancer is the secondary most frequently diagnosed cancer in the world. Although numerous prospective randomized trial have been conducted to guide the management of patients with localized or locally advanced prostate cancer, few clinical trials targeting node-positive prostate cancer have been reported. Therefore, there are still controversies in the optimal management of node-positive prostate cancer. Recently, efficacy of multimodality treatment, including radiation therapy (RT), for such patients has been reported in several articles. The results indicate potential benefit of RT both in adjuvant therapy after prostatectomy and in definitive therapy for node-positive prostate cancer. The aim in this article was to summarize the current evidence for RT and evaluate the role in multimodality treatment for patients with node-positive prostate cancer.

Roles of Valproic Acid in Improving Radiation Therapy for Glioblastoma: a Review of Literature Focusing on Clinical Evidence.

Glioblastoma (GBM) is the most common and aggressive type of primary brain neoplasm. The current standard therapy for GBM consists of maximal surgical resection within safe limits, followed by radiation therapy (RT) and chemotherapy with temozolomide. Despite advances in treatment, the prognosis of GBM remains poor. Epileptic seizure is one of the most common symptoms in patients with GBM. Valproic acid (VPA), a histone deacetylase inhibitor, is often used as an anti-epileptic drug in patients with brain neoplasms due to its effectiveness and low toxicity profile. Several in vivo and in vitro studies have indicated that VPA has radiosensitizing effects for gliomas and radioprotective influence on normal brain tissue or hippocampal neurons. The results of several retrospective studies have also indicated potential benefit to improve survival of patients with GBM. Moreover, the promising treatment results of a phase 2 trial of concurrent radiation therapy, temozolomide, and VPA for patients with GBM have been recently reported. The use of VPA in patients with GBM has thus recently receiving more attention. In this article, we review the role of VPA in radiation therapy for GBM, focusing on the clinical evidence.

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.

Treatment results of alternating chemoradiotherapy followed by proton beam therapy boost combined with intra-arterial infusion chemotherapy for stage III-IVB tongue cancer.

PURPOSE: Proton beam therapy (PBT), compared with conventional radiotherapy, can deliver high-dose radiation to a tumor, while minimizing doses delivered to surrounding normal tissues. The better dose distribution of PBT may contribute to the improvement in local control rate and reduction in late adverse events. We evaluated therapeutic results and toxicities of PBT combined with selective intra-arterial infusion chemotherapy (PBT-IACT) in patients with stage III-IVB squamous cell carcinoma of the tongue. MATERIALS AND METHODS: After 2 systemic chemotherapy courses and whole-neck irradiation (36 Gy in 20 fractions), we administered concurrent chemoradiotherapy comprising PBT for the primary tumor [28.6-33 Gy(RBE) in 13-15 fractions] and for the metastatic neck lymph node [33-39.6 Gy(RBE) in 15-18 fractions] with weekly retrograde intra-arterial chemotherapy by continuous infusion of cisplatin with sodium thiosulfate. RESULTS: Between February 2009 and September 2012, 33 patients were enrolled. The median follow-up duration was 43 months. The 3-year overall survival, progression-free survival, local control rate, and regional control rate for the neck were 87.0, 74.1, 86.6, and 83.9 %, respectively. Major acute toxicities >grade 3 included mucositis in 26 cases (79 %), neutropenia in 17 cases (51 %), and dermatitis in 11 cases (33 %). Late grade 2 osteoradionecrosis was observed in 1 case (3 %). CONCLUSIONS: PBT-IACT for stage III-IVB tongue cancer has an acceptable toxicity profile and showed good treatment results. This protocol should be considered as a treatment option for locally advanced tongue cancer.