Clinical outcomes and factors involved in the local control of proton beam therapy for oligometastatic liver tumors in patients with colorectal cancer.

BACKGROUND AND PURPOSE: There are no existing reports on proton beam therapy (PBT) for local control (LC) of liver metastasis of colorectal cancer (LMCRC). We calculated the LC rate of PBT for LMCRC and explored the influence of each factor on the LC rate. MATERIALS AND METHODS: Cases in which PBT was performed at our center between 2009 and 2018 were retrospectively selected from the database. Patients with LMCRC without extrahepatic lesions and no more than three liver metastases were included. Effectiveness was assessed based on LC, overall survival (OS), and progression-free survival (PFS) rates. Adverse events (AEs) are described. Factors that may be related to LC were also investigated. RESULTS: This study included 23 men and 18 women, with a median age of 66 (range 24-87) years. A total of 63 lesions were included in the study. The most frequent dose was 72.6 Gy (relative biological effectiveness)/22 fractions. The median follow-up period was 27.6 months. The 3­year LC, OS, and PFS rates were 54.9%, 61.6%, and 16.7%, respectively. Our multivariate analysis identified the distance between the tumor and the gastrointestinal (GI) tract as a factor associated with LC (P = 0.02). No grade ≥ 3 AEs were observed. None of the patients experienced liver failure during the acute or late phase. CONCLUSION: Care must be taken with tumors that have reduced planning target volume coverage owing to organs at risk restrictions, especially in tumors near the GI tract.

Safety of hydrogel spacers for rectal wall protection in patients with prostate cancer: A retrospective analysis of 200 consecutive cases.

OBJECTIVE: To evaluate the safety and complications of hydrogel spacer implantation. METHODS: This single-center historical cohort study retrospectively analyzed cases of hydrogel spacer implantation between October 2018 and March 2022. The survey items were the rates of possible hydrogel injection implementation, the success rate of hydrogel implantation including asymmetry, higher position, rectal wall infiltration, subcapsular injection, and other adverse events, and width created by the spacer. To investigate the learning curve, 1, 2, and 3 points were assigned to adverse event grades G1, G2, and G3, respectively. Spacer effectiveness obstruction, such as asymmetry was assigned 3 points. A Mann-Whitney U test was performed to assess statistically significant differences. RESULTS: The study included a total of 200 patients with a median (range) age of 70 (44-85) years. In 10 (5%) patients, hydrogel injection implementation was not possible. Of 190 patients who underwent hydrogel spacer placement, 168 (88%) received a satisfactory placement. The median (range) width of hydrogel spacers was 13.1 (4.4-18.7) mm. Spacer asymmetry, higher position, rectal wall infiltration, and prostate subcapsular infiltration occurred in 7 (3.7%), 5 (2.6%), 12 (6.3%), and 1 (0.5%) patients, respectively. G1 and G3 adverse events occurred in 13 (7%) and 4 (2%) patients, respectively. Practitioner #1 who performed the highest number of procedures had significantly (p = 0.04) lower total scores in group B. CONCLUSION: Spacer implantation yielded favorable outcomes with a high percentage of appropriate spacer implantation, and few major complications.

The effectiveness of proton beam therapy for liver metastatic recurrence in gastric cancer patients.

OBJECTIVE: The purpose of this cross-sectional study was to evaluate the efficacy and safety of proton beam therapy for liver metastatic recurrence in gastric cancer patients. METHODS: Consecutive patients who underwent proton beam therapy from 2010 to 2015 were isolated from our institutional database. Patients with extrahepatic metastatic lesions were excluded. Seven patients were enrolled. The median diameter of target lesions was 31 mm (13-68 mm). The most frequent dosage was 72.6 Gy equivalent in 22 fractions. The effectiveness was assessed based on the local control, overall survival and progression-free survival rates. The local control, overall survival and progression-free survival rates were calculated using the Kaplan-Meier method. Adverse events were described according to the patients' medical records. RESULTS: The median follow-up period was 41.7 months (20.7-66.3 months). The 3-year local control, overall survival and progression-free survival rates were 85.7, 68.6 and 43%, respectively. All patients completed proton beam therapy without interruption. No grade ≥3 adverse events were observed. CONCLUSIONS: Proton beam therapy might be a treatment option for patients with liver metastasis of gastric cancer.

Clinical results of proton beam therapy for hepatocellular carcinoma over 5 cm.

AIM: This study aimed to evaluate the safety and efficacy of proton beam therapy for large hepatocellular carcinoma (HCC). METHODS: Twenty-four patients with a HCC larger than 5.0 cm were treated with proton beam therapy at our institution between 2008 and 2015. RESULTS: The clinical stage was I in 2 patients, II in 9 patients, and IIIB in 13 patients. Ten of the 24 patients were not surgical candidates because of advanced HCC or old age. Median tumor size was 90 mm (range, 50-180 mm). Median total dose delivered was 72.6 Gray-equivalents (GyE) in 22 fractions (range, 60.8-85.8 GyE). Median follow-up period was 17.5 months (range, 3-70 months). Local control rate at 2 years was 87.0%. The 2-year overall survival rate was 52.4%. The predominant tumor progression pattern was new hepatic tumor development outside the irradiated field. No acute or late treatment-related toxicity of grade 3 or higher, other than dermatitis, was observed. CONCLUSIONS: These results show that proton beam therapy offers an effective and safe method for treating patients with large HCC. Proton beam therapy represents a promising method for treatment of large-volume HCC.

Preliminary results of proton beam therapy combined with weekly cisplatin intra-arterial infusion via a superficial temporal artery for treatment of maxillary sinus carcinoma.

OBJECTIVE: This study aimed to evaluate the efficacy and toxicity of proton beam therapy combined with cisplatin intra-arterial infusion via a superficial temporal artery as treatment for maxillary sinus carcinoma. METHODS: Twenty-six patients with confirmed maxillary sinus carcinoma were enrolled in this study from May 2009 to April 2011. Patients underwent proton beam therapy and intra-arterial infusion chemotherapy with cisplatin. RESULTS: The median total dose was 70.4 GyE per 32 fractions, and the median dose of cisplatin was 300 mg/body for six cycles of intra-arterial infusion. The 3-year overall survival rate was 58% for all patients (n = 26), 58% for patients with stage T4 disease (n = 12), 57% for patients with

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

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.

Clinical Outcomes of Proton Beam Therapy for Unresectable Locally Advanced Pancreatic Cancer: A Single-Center Retrospective Study.

Purpose: We retrospectively researched the treatment outcome of proton beam therapy (PBT) and assessed its efficacy for inoperable locally advanced pancreatic cancer (LAPC) at our institution. Methods and Materials: Fifty-four patients (28 men and 26 women, median age 67 years ranging from 40-88 years) were diagnosed with unresectable stage III LAPC and administered PBT from April 2009 to March 2020. Patients who could not complete PBT, had new distant metastases during the treatment, or did not have enough follow-up time were excluded from this study. All patients were clinically staged based on the International Union of Cancer TNM staging system (eighth edition) using computed tomography, magnetic resonance imaging, and positron emission tomography and were diagnosed as stage III (histologic type: 18 patients with adenocarcinoma and 36 clinically diagnosed patients). PBT was performed using the passive method, with a median total dose of 67.5 GyE (range, 50-77 GyE/25-35 fractions).Chemotherapy was used in combination during PBT in 46 patients (85.2%). Overall survival (OS), local progression-free survival (LPFS), progression-free survival, and median OS time were analyzed by Kaplan-Meier and log-rank tests. Univariate and multivariate analyses were performed for the following factors: maximum standardized uptake value (SUVmax), Eastern Cooperative Group performance status (PS), tumor site, total irradiation dose, concurrent chemotherapy, and primary tumor site. Cutoff values for SUVmax and tumor diameter were estimated using receiver operating characteristic curves and the area under the curve based on OS. Multivariate analysis was evaluated using the Cox proportional hazards models. Adverse events were evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Results: The median observation period was 17.4 months, ranging from 4.0 to 89.7 months. The median tumor diameter was 36.5 mm, ranging from 15 to 90 mm, the median SUVmax was 5.85 (range, 2.1-27.6), and their cutoff values were estimated to be 37 mm and 4.8 mm, respectively. The 1- and 2-year OS was 77.8% and 35.2%, respectively, with a median OS time of 18.2 months, and only one patient survived >5 years. Twelve patients (22.2%) developed local recurrence, and 1- and 2-year LPFS rates were 89.7% and 74.5%, respectively; progression-free survival at 1 year was 58.8%. The PS score, tumor site, and irradiation dose were the prognostic factors related to OS that showed a significant difference. On the other hand, there was a significant difference in factors involved in LPFS, at 96.7%/77.9% in the first year and 86.6%/54.4% in the second year in the groups with tumor dose ≥67.5 GyE and <67.5 GyE, respectively (P = .015). Treatment-related acute toxicities were neutropenia (grade 1/2/3 at 3.7%/11.1%/31.5%, respectively), leukopenia (grade 1/2/3 at 1.8%/7.4%/20.4%, respectively), and thrombocytopenia (grade 1/2 at 1.8%/7.4%, respectively), whereas the late effects including peptic ulcer were captured only grade 2+. The late adverse events of grade 3 or higher were not observed. Conclusions: PBT achieving 67.5 Gy combined with standard chemotherapy showed excellent local control for unresectable LAPC. Total irradiation dose, tumor site, and PS score at an initial diagnosis could be important prognostic factors. In this study, the dose-effect relationship was found, so an increase in dose should be considered to improve prognosis.

Proton beam reirradiation for locally recurrent rectal cancer patients with prior pelvic irradiation.

The aim of the present study was to report the feasibility of proton beam reirradiation for patients with locally recurrent rectal cancer (LRRC) with prior pelvic irradiation. The study population included patients who were treated with proton beam therapy (PBT) for LRRC between 2008 and December 2019 in our institution. Those who had a history of distant metastases of LRRC, with or without treatment, before reirradiation, were excluded. Overall survival (OS), progression-free survival (PFS) and local control (LC) were estimated using the Kaplan-Meier method. Ten patients were included in the present study. The median follow-up period was 28.7 months, and the median total dose of prior radiotherapy (RT) was 50 Gy (range, 30 Gy-74.8 Gy). The median time from prior RT to reirradiation was 31.5 months (range, 8.1-96.6 months), and the median reirradiation dose was 72 Gy (relative biological effectiveness) (range, 56-77 Gy). The 1-year/2-year OS, PFS and LC rates were 100%/60.0%, 20.0%/10.0% and 70.0%/58.3%, respectively, with a median survival time of 26.0 months. Seven patients developed a Grade 1 acute radiation dermatitis, and no Grade ≥ 2 acute toxicity was recorded. Grade ≥ 3 late toxicity was recorded in only one patient, who had developed a colostomy due to radiation-related intestinal bleeding. Reirradiation using PBT for LRRC patients who had previously undergone pelvic irradiation was feasible. However, the indications for PBT reirradiation for LRRC patients need to be considered carefully due to the risk of severe late GI toxicity.

Identification of Induced Radionuclides Produced from Dental Metals in Proton Beam Therapy for Head and Neck Cancer.

Purpose: To identify the induced radionuclides produced from dental metals in proton beam therapy and investigate the accuracy of the Monte Carlo (MC) simulation by comparing the measured radioactivity. Methods and Materials: Two dental metals of pure titanium and gold-silver-palladium alloy, commonly used in Japan, were used in this study. The dental metal placed at the center of Spread-out Bragg Peak was irradiated by 150-MeV passive scattering proton beam. The gamma rays emitted from the activated dental metals were measured using a high purity germanium (HPGe) detector. The induced radionuclides were identified from the measured gamma-ray energies. Furthermore, the Particle and Heavy Ion Transport code System v.3.24 and DCHAIN were used for the MC simulation. The measured radionuclides and their radioactivity were compared with the simulation results. Results: In the MC simulation for the activated titanium, vanadium-47, with a half-life of 32.6 minutes had the strongest radioactivity among the induced radionuclides. The energy peaks of gamma rays emitted from titanium-51, scandium-43, scandium-44, and annihilation gamma rays were observed for the activated titanium in the HPGe detector. In the MC simulation for the activated gold-silver-palladium alloy, silver-108, with a half-life of 2.4 minutes had the strongest radioactivity. The energy peaks of gamma rays emitted from silver-104, silver-104 m, silver-108, and annihilation gamma rays were observed for the activated gold-silver-palladium alloy in the HPGe detector. Furthermore, the induced radionuclides and their radioactivity in the MC simulation were consistent with the measurement results for both dental metals, except for a few radionuclides. Conclusions: We identify the induced radionuclides produced from 2 dental metals and compared their radioactivity between the measurements and the MC simulation. Although the identification of the induced radionuclides using the MC simulation remains uncertain, the MC simulation can be clinically effective for pre-estimating the induced radionuclides in proton beam therapy.

Tapia Syndrome and Severe Pain Induced by Occipital Bone Metastasis of Prostate Cancer.

Tapia syndrome is characterized by unilateral tongue paralysis, hoarseness, and dysphagia. It is often associated with issues in the lower cranial nerves and is rarely caused by malignant tumors. A 71-year-old Japanese male with prostate cancer and bone metastases experienced severe headaches, oral discomfort, dysphagia, and hoarseness for a month. Neurological examination revealed left-sided tongue atrophy and left vocal cord paralysis, suggesting problems with cranial nerves IX and XII. CT scans showed bone metastasis in the left occipital bone. Brain MRI showed no brain or meningeal metastasis, but neck MRI revealed a mass near the left hypoglossal canal. His prostate-specific antigen (PSA) level was 53.2 ng/mL. Based on these findings, we diagnosed him with occipital bone metastasis of prostate cancer with Tapia syndrome. We treated him with palliative radiation therapy (RT), delivering 30 Gy in 10 fractions over two weeks. We did not use drug treatment or chemotherapy due to side effects and the patient's preferences. After just one day of RT, his severe headache and oral discomfort significantly improved. By the end of the two-week treatment, his hoarseness had also improved, and he was able to eat. However, tongue atrophy had not improved three months after RT. We presented a unique case of palliative RT for occipital bone metastasis of prostate cancer with Tapia syndrome. Within two weeks, the patient's headache and dysphagia had greatly improved, although tongue atrophy remained partially unresolved after palliative RT.

Outcomes and Prognostic Factors for Locally Recurrent Rectal Cancer Treated With Proton Beam Therapy.

Purpose: Our objective was to report the outcome and prognostic factors for patients with locally recurrent rectal cancer (LRRC) treated with proton beam therapy (PBT) at our institution. Methods and Materials: The study included PBT-treated patients with LRRC between December 2008 and December 2019. Treatment response was stratified using an initial imaging test after PBT. Overall survival (OS), progression-free survival (PFS), and local control (LC) were estimated using the Kaplan-Meier method. Each outcome's prognostic factors were verified using the Cox proportional hazards model. Results: Twenty-three patients were enrolled (median follow-up, 37.4 months). There were 11 patients with complete response (CR) or complete metabolic response (CMR), 8 with partial response or partial metabolic response, 2 with stable disease or stable metabolic response, and 2 with progressive disease or progressive metabolic disease. Three- and 5-year OS, PFS, and LC were 72.1% and 44.6%, 37.9% and 37.9%, and 55.0% and 47.2%, respectively, with 54.4 months' median survival time. The maximum standardized uptake value of fluorine-18-fluorodeoxyglucose-positron emission tomography-computed tomography (18F-FDG-PET/CT) before PBT (cutoff value, 10) showed significant differences in OS (P = .03), PFS (P = .027), and LC (P = .012). The patients who achieved CR or CMR after PBT had significantly better LC than those with non-CR or non-CMR (hazard ratio, 4.49; 95% confidence interval, 1.14-17.63; P = .021). Older patients (aged ≥65 years) had significantly higher LC and PFS rates. Patients with pain before PBT and larger tumors (≥30 mm) also had significantly lower PFS. Of 23 patients, 12 (52%) experienced further local recurrence after PBT. One patient developed grade 2 acute radiation dermatitis. Regarding late toxicity, grade 4 late gastrointestinal toxic effects were recorded in 3 patients, in 2 of whom reirradiation was associated with further local recurrence after PBT. Conclusions: The results showed that PBT may have potential to be a good treatment option for LRRC. 18F-FDG-PET/CT before and after PBT may be useful for assessing tumor response and predicting outcomes.

Effectiveness of proton beam therapy for liver oligometastatic recurrence in patients with postoperative esophagus cancer.

There are several reports of hepatic resection for postoperative hepatic metastatic recurrence of esophageal cancer. However, it is unclear whether surgery is the best local treatment for liver metastases. Thus, this study aimed to retrospectively analyze proton beam therapy (PBT) for postoperative liver metastatic recurrence of esophageal cancer without extrahepatic lesions and examine outcomes and adverse events. This single-center historical cohort study selected patients who underwent PBT at our proton therapy center between 2012 and 2018. The patients were selected based on the following criteria: primary esophagus carcinoma was resection and metachronous liver oligometastasis recurrence without extrahepatic tumors and no more than three liver metastases. This study included seven males with a median age of 66 (range, 58-78) years, and 15 lesions were included in the study. The median tumor size was 22.6 (7-55.3) mm. The most frequent dose was 72.6 Gy relative biological effect (RBE)/22 fractions (fr) for four lesions and 64 Gy (RBE)/8 fr for four lesions. The median survival time was 35.5 (13.2-119.4) months. The 1-, 2- and 3-year overall survival (OS) rates were 100%, 57.1% and 42.9%, respectively. The median progression-free survival (PFS) time was 8.7 (1.2-44.1) months. The 1-, 2- and 3-year PFS rates were 28.6%. The 1-, 2- and 3-year local control (LC) rates were 100%. No grade ≥4 radiation-induced adverse events (AEs) were observed. We conclude that PBT can be considered an alternative to hepatic resection for recurrent liver metastases postoperative esophageal cancer.

Profile analysis of adverse events after boron neutron capture therapy for head and neck cancer: a sub-analysis of the JHN002 study.

The purpose of this study was to outline the course and profile of adverse events specific to boron neutron capture therapy (BNCT) for head and neck cancer. This was a sub-analysis of the phase II JHN002 trial. Patients received 400 mg/kg borofalan(10B), followed by neutron irradiation. The course of adverse events after BNCT was documented in the JHN002 Look Up study. Patients were grouped into face/front (FF), face/lateral (FL) and neck (N) beam groups according to the point of skin incidence of the epithermal neutron beam axis, and the profile of adverse events dependent on beam incidence position was examined. The courses of adverse events in eight recurrent squamous cell carcinoma (R-SCC) and 13 recurrent or locally advanced non-SCC cases were analyzed. Median interval to complete recovery was 23 days (interquartile range (IQR), 14-48 days) for oral mucositis, 40 days (IQR, 24-56 days) for dermatitis, 58 days (IQR, 53-80 days) for dysgeusia and 156 days (IQR, 82-163 days) for alopecia. In the FF beam group, parotitis (P = 0.007) was less frequent, while oral mucositis (P = 0.032), fatigue (P = 0.002), conjunctivitis (P = 0.001), epistaxis (P = 0.001) and abdominal discomfort (P = 0.029) tended to be more frequent than in the FL and N beam groups. Courses and irradiation site-specific profiles of adverse events in BNCT for head and neck cancer were identified. This profile may be useful for considering interventions to prevent exacerbation of treatment-related adverse events on BNCT.

Proton Beam Therapy With Space-Making Surgery (Omental Plombage) for Oligorecurrent Liver Metastasis of Esophageal Adenocarcinoma.

Proton beam therapy (PBT) with space-making surgery has been used recently; however, its effectiveness for recurrent esophageal cancer (EC) is unclear. We herein report an unusual case of successful PBT with space-making surgery (omental plombage) for recurrent liver metastasis after EC surgery. A 58-year-old Japanese man underwent proximal gastrectomy for esophagogastric (EG) junction cancer seven months before presentation to our hospital. Microscopic findings after the surgery showed that the tumor was adenocarcinoma of the EG junction (pT1N0M0, stage I). Seven months after the proximal gastrectomy, liver metastases in S6 and S8 were revealed by positron emission tomography-computed tomography. Initial PBT was performed for those two liver metastases, and complete response (CR) was obtained for both liver metastases. Recurrence of liver metastasis in S2 was found eight months after the first PBT, and CR was achieved by chemotherapy. However, new liver metastasis recurred in S2. Considering the effects of radiation exposure on the surrounding gastrointestinal organs, we performed space-making surgery to place the omentum around the liver metastasis. We were able to complete the second PBT for the liver metastasis with 72.6 Gy relative biological effectiveness in 22 fractions. After the second PBT, the patient survived for seven years without recurrence. PBT with space-making surgery (omental plombage) for recurrent liver metastasis after EC surgery is considered to be a therapeutic option.

Boron neutron capture therapy using cyclotron-based epithermal neutron source and borofalan (10B) for recurrent or locally advanced head and neck cancer (JHN002): An open-label phase II trial.

BACKGROUND AND PURPOSE: Boron neutron capture therapy (BNCT) can be performed without reactors due to development of cyclotron-based epithermal neutron source (C-BENS), which is optimized for treatment for deeper-seated tumors. The purpose of this study was to evaluate efficacy and safety of cyclotron-based BNCT with borofalan (10B) for recurrent or locally advanced head and neck cancer. MATERIALS AND METHODS: In this open-label, phase II JHN002 trial of BNCT using C-BENS with borofalan (10B), patients with recurrent squamous cell carcinoma (R-SCC) or with recurrent/locally advanced non-squamous cell carcinoma (R/LA-nSCC) of the head and neck were intravenously administered 400 mg/kg borofalan (10B), followed by neutron irradiation. The tumor dose was determined passively as the mucosal maximum dose of 12 Gy-Eq. The primary endpoint was the objective response rate (ORR). Post-trial observational JHN002 Look Up study was planned for evaluating locoregional progression-free survival (LRPFS). RESULTS: Eight R-SCC and 13 R/LA-nSCC patients were enrolled. All R-SCC patients had prior radiotherapy with a median dose of 65.5 Gy (range, 59.4-76.0 Gy). The ORR for all patients was 71%, and complete response/partial response were 50%/25% in R-SCC and 8%/62% in R/LA-nSCC. The 2-year overall survival for R-SCC and R/LA-nSCC were 58% and 100%, respectively. The median LRPFS was 11.5 months for R-SCC. Frequently observed adverse events included alopecia (95%), hyperamylasemia (86%), and nausea (81%). CONCLUSION: These data suggest that BNCT using C-BENS with borofalan (10B) is a promising treatment option for patients with R-SCC or R/LA-nSCC of the head and neck.

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.

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.

Proton Beam Therapy for Locally Recurrent Parotid Gland Cancer.

The aim of this study was to evaluate the efficacy and safety of proton beam therapy for patients with locally recurrent parotid cancer. Between 2009 and 2012, ten patients with locally recurrent parotid gland cancer were treated with proton beam therapy (70.2 Gy equivalents in 32 fractions) with or without intra-arterial infusion chemotherapy of cisplatin (50 mg/body/week, for a total of 5-8 weeks). The median follow-up was 24 months (range 10-49 months). The 1-year overall survival and local control rates were 80 %, and the 3-year overall survival and local control rates were 60 %. None of the patients experienced grade 3-5 toxicities in the treatment or the follow-up periods. These findings suggest that proton beam therapy could be applied effectively and safely for patients with locally recurrent parotid gland cancer.

Clinical results of proton beam therapy for elderly patients with non-small cell lung cancer.

BACKGROUND: The purpose of the present study was to evaluate retrospectively the efficacy and safety of proton beam therapy for elderly patients (≥80 years of age) with non-small cell lung cancer. METHODS: Patients diagnosed with T1-4 N0 M0 non-small cell lung cancer and treated with proton beam therapy between January 2009 and 2015 were recruited from our database retrospectively. Toxicity was evaluated using The Common Terminology Criteria for Adverse Events version 4.0. RESULTS: Thirty-five patients, including 25 (71%) with clinically inoperable lung cancer, were administered proton beam therapy. The median age was 82 years (range: 80-87 years), and the median follow-up time was 34 months (range: 10-72 months). The median dose of proton beam therapy was 80.0 Gy relative biological effectiveness (RBE) (range: 60.0-80.0 Gy [RBE]), and all patients completed the treatments. All patients were followed for at least 23 months or until their death. The 3-year overall survival rate was 67.2% (90.0% in patients with operable lung cancer, and 58.2% in those with inoperable lung cancer). The 3-year local control rate was 86.5%. Two patients presented with grade 2 pneumonitis. The occurrence rate of grade 2 pneumonitis was significantly correlated with a high lung V20 (p = 0.030), and a high mean lung dose (p = 0.030), and a low ratio of lung volume spared from 0.05 Gy (RBE) dose (total lung volume minus lung volume irradiated at least 0.05 Gy [RBE]) (p = 0.030). However, there were no cases of grade 3 or higher radiation pneumonitis. CONCLUSIONS: This study suggests that the proton beam therapy was feasible for elderly patients with non-small cell lung cancer and can be considered as one of the treatment choices for elderly patients with lung cancer.