Comparison of proton-based definitive chemoradiotherapy and surgery-based therapy for esophageals cell carcinoma: a multi-center retrospective Japanese cohort study.

BACKGROUND: Proton-based, definitive chemoradiotherapy (P-CRT) for esophageal squamous cell carcinoma (ESCC) previously showed comparable survival outcomes with the surgery-based therapy, i.e., neoadjuvant chemotherapy followed by esophagectomy (NAC-S), in a single-institutional study. This study aimed to validate this message in a Japanese multicenter study. METHODS: Eleven Japanese esophageal cancer specialty hospitals have participated. A total of 518 cases with clinical Stage I-IVA ESCC between 2010 and 2019, including 168 P-CRT and 350 NAC-S patients, were enrolled and long-term outcomes were evaluated. Propensity-score weighting analyses with overlap weighting for confounding adjustment were used. RESULTS: The 3-year overall survival (OS) of the P-CRT group was equivalent to the NAC-S group (74.8% vs. 72.7%, hazard ratio [HR]: 0.87, 95% confidence interval [CI]: 0.61-1.25). Although, the 3-year P-CRT group progression-free survival (PFS) was inferior to the NAC-S group (51.4% vs. 59.6%, HR 1.39, 95% CI 1.04-1.85), the progression P-CRT group cases showed better survival than the NAC-S group (HR 0.58, 95% CI 0.38-0.88), largely because of salvage surgery or endoscopic submucosal dissection for local progression. The survival advantage of P-CRT over NAC-S was more pronounced in the cT1-2 (HR 0.61, 95% CI 0.29-1.26) and cStage I-II (HR 0.50, 95% CI 0.24-1.07) subgroups, although this trend was not evident in other populations, such as cT3-4 and cStage III-IVA. CONCLUSIONS: Proton-based CRT for ESCC showed equivalent OS to surgery-based therapy. Especially for patients with cT1-2 and cStage I-II disease, proton-based CRT has the potential to serve as a first-line treatment.

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.

No increase in translocated chromosomal aberrations, an indicator of ionizing radiation exposure, in childhood thyroid cancer in Fukushima Prefecture.

To investigate the effects of radiation exposure due to the Fukushima nuclear power plant accident, following the disaster Fukushima Prefecture launched thyroid ultrasound examinations of residents who were generally younger than 18 years at the time of the earthquake. As the rate of pediatric thyroid cancer was higher than expected, we conducted biological dose assessment based on the frequency of translocated chromosome (Tr) aberrations using peripheral blood lymphocytes. Tr formation frequency was compared among the thyroid cancer (n = 38, median age 18 years, age range 12-26 years), thyroid-related disease (n = 30, median age 21 years, age range 15-28 years), and healthy controls (n = 31, median age 22 years, age range 20-23 years) groups. Tr aberration frequency was initially significantly higher in the thyroid cancer than in the other two groups; however, differences among the groups disappeared after adjusting for history of CT scan, as 92%, 67%, and 28% of those in the thyroid cancer, thyroid-related disease, and control groups, respectively, had undergone CT previously. Therefore, the significant difference in the initial number of Tr formations is presumably due to radiation exposure from CT. Accordingly, the effects of medical exposure on the chromosomes of children and adolescents should be noted.

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.

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.

E3 Ubiquitin Ligase NEDD4 Affects Estrogen Receptor α Expression and the Prognosis of Patients with Hormone Receptor-Positive Breast Cancer.

Neural precursor cell-expressed developmentally downregulated 4-1 (NEDD4) is an E3 ligase that leads to the degradation of proteins, including estrogen receptor α. We evaluated whether the expression level of NEDD4 affected the outcome of breast cancer patients. We performed a retrospective cohort study enrolling 143 patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer. Of the 66 patients with high NEDD4 mRNA levels (high NEDD4 group) and 77 patients with low NEDD4 mRNA levels (low NEDD4 group), 98.4% and 96.1%, respectively, of the patients had received neoadjuvant/adjuvant hormone therapy. Disease-free survival and overall survival were significantly longer in the low NEDD4 group than in the high NEDD4 group (p = 0.048 and p = 0.022, respectively). Western blotting revealed a high expression of estrogen receptor α in the NEDD4-knockdown culture cells. The proliferation of NEDD4-knockdown cells treated with tamoxifen or estradiol deprivation was suppressed, compared with that of NEDD4-expressing cells. Knockdown of NEDD4 in breast cancer cells induced the accumulation of estrogen receptor α and increased sensitivity to hormone therapy. In summary, this mechanism may lead to a better prognosis in hormone receptor-positive breast cancer patients with a low expression of NEDD4.

[A Case of Emergency Radiotherapy for Intramedullary Spinal Cord Metastasis from Breast Cancer].

Intramedullary spinal cord metastasis(ISCM)is rare. However, with advances in diagnostic imaging, the incidence of ISCM is increasing. We herein present a case of breast cancer metastasis in the lower thoracic spinal intramedullary area in a patient who was then successfully treated with emergency radiotherapy. A 56‒year‒old woman with breast cancer was admitted to our hospital due to rapidly progressing weakness in both legs and bladder and rectal disturbance. Spinal MRI revealed a gadolinium‒enhancing intramedullary lesion. The patient was treated with emergency radiotherapy and oral steroids. Although the prognosis of ISCM is extremely poor, emergency radiotherapy could be an effective treatment for ISCM to improve the patient's quality of life(QOL).

Chromosomal translocation t(11;14) and p53 deletion induced by the CRISPR/Cas9 system in normal B cell-derived iPS cells.

Multiple myeloma (MM) cells are derived from mature B cells based on immunoglobulin heavy chain (IgH) gene analysis. The onset of MM is often caused by a reciprocal chromosomal translocation (cTr) between chr 14 with IgH and chr 11 with CCND1. We propose that mature B cells gain potential to transform by reprograming, and then chromosomal aberrations cause the development of abnormal B cells as a myeloma-initiating cell during B cell redifferentiation. To study myeloma-initiating cells, we have already established normal B cell-derived induced pluripotent stem cells (BiPSCs). Here we established two BiPSCs with reciprocal cTr t(11;14) using the CRISPR/Cas9 system; the cleavage site were located in the IgH Eµ region of either the VDJ rearranged allele or non-rearranged allele of IgH and the 5'-upsteam region of the CCND1 (two types of BiPSC13 with t(11;14) and MIB2-6 with t(11;14)). Furthermore, p53 was deleted using the CRISPR/Cas9 system in BiPSC13 with t(11;14). These BiPSCs differentiated into hematopoietic progenitor cells (HPCs). However, unlike cord blood, those HPCs did not differentiated into B lymphocytes by co-culture with BM stromal cell. Therefore, further ingenuity is required to differentiate those BiPSCs-derived HPCs into B lymphocytes.

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.

Risk of immunotherapy-related narcolepsy in genetically predisposed patients: a case report of narcolepsy after administration of pembrolizumab.

BACKGROUND: Immune-related adverse events associated with immune checkpoint therapy cause autoimmune disease-like symptoms. People who carry specific genotypes or haplotypes of human leucocyte antigen (HLA) are known to be predisposed to develop autoimmune diseases including narcolepsy. Immunotherapy could be a trigger to develop narcolepsy in predisposing HLA positive patients. CASE PRESENTATION: A 66-year-old woman with stage IVB endometrial carcinosarcoma experienced daytime sleepiness and temporary muscle weakness 14 days after the administration of an immune checkpoint inhibitor, pembrolizumab. These were consistent with the main symptoms of narcolepsy with cataplexy. This patient carried a highly predisposing HLA haplotype for narcolepsy; HLA-DQB1*06:02, DRB1*15:01, DQA1*01:02 and DRB5*01:01:01. A hypocretin-1/orexin-A concentration in the patient's cerebrospinal fluid was low at 9.6 pg/mL in ELISA, and 155.5 pg/mL in radioimmunoassay that was below the normal level of 200 pg/mL. Therefore, she was diagnosed with narcolepsy tentatively according to the International Classification of Sleep Disorders, third edition diagnostic criteria for narcolepsy. The onset of narcolepsy in the 60s is very rare, and narcoleptic symptoms in our patient were likely to be caused by pembrolizumab. CONCLUSIONS: This case suggests that treatment with immune checkpoint inhibitors potentially causes narcolepsy in genetically predisposed patients.

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.

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 is a safe and feasible treatment for patients with second primary lung cancer after lung resection.

BACKGROUND: The purpose of the present study was to retrospectively evaluate the safety and efficacy of proton beam therapy (PBT) in patients with second primary lung cancer after lung resection. METHODS: Patients who were diagnosed with second primary lung cancer after lung resection and underwent PBT between January 2009 and February 2015 were retrospectively recruited. Toxicities were evaluated using Common Terminology Criteria for Adverse Events version 4.0. RESULTS: Nineteen patients were eligible for inclusion in this study. All of the patients completed the treatment. The median age was 75 (range: 63-82) years, and the median follow-up time of living patients was 60 months. The median dose of PBT was 76.8 Gy relative biological effectiveness (range: 66.0-80.0 Gy). The three-year overall survival rate was 63.2% and the three-year local control rate was 84.2%. No grade 4 or 5 toxicities were observed after PBT. CONCLUSIONS: Our results suggest that PBT is a safe and feasible treatment for second primary lung cancer compared to surgery or X-ray radiotherapy. PBT may become a treatment choice for patients with second primary lung cancer after lung resection.

Proton Beam Therapy in Combination with Intra-Arterial Infusion Chemotherapy for T4 Squamous Cell Carcinoma of the Maxillary Gingiva.

This study aimed to evaluate the therapeutic effect and toxicity of proton beam therapy in combination with intra-arterial infusion chemotherapy in patients with squamous cell carcinoma of the maxillary gingiva. Between December 2010 and March 2016, 30 patients with T4 squamous cell carcinoma of the maxillary gingiva were treated with radiotherapy and retrograde intra-arterial infusion chemotherapy using cisplatin (20⁻40 mg/m², 4⁻6 times). Radiotherapy was basically administered using boost proton beam therapy for primary tumor and neck lymph node tumors, following 36⁻40 Gy photon radiation therapy delivered to the prophylactic area, to a total dose of 70.4⁻74.8 Gy. The median follow-up was 33 months. The 3-year local control and overall survival rates were 69% and 59%, respectively. Major grade 3 or higher acute toxicities included mucositis, neutropenia, and dermatitis in 12 (40%), 5 (17%), and 3 (10%) patients, respectively. No grade 3 or higher late toxicities were observed. These results suggested that proton beam therapy in combination with intra-arterial infusion chemotherapy was not inferior to other treatment protocols and should be considered as a safe and effective option in patients with T4 squamous cell carcinoma of the maxillary gingiva.

Abscopal effect following radiation monotherapy in breast cancer: A case report.

Radiotherapy has been found to be valuable for the control and eradication of local foci in various malignant tumors. The abscopal effect is determined as a systemic antitumor response at a distance from the irradiation site invoked by local irradiation. We herein present an extremely rare case of breast cancer in a 64-year-old woman, in whom the abscopal effect was observed after radiotherapy induced an antitumor response in all metastatic lesions, without any combination therapy. The patient was admitted to our hospital complaining of a breast mass and pain at the left hip, and was diagnosed with breast cancer with multiple bone, lung and lymph node metastases. She received treatment with local radiotherapy delivered to the breast tumor and some of the bone metastases but did not receive chemotherapy due to her poor performance status. However, 10 months after radiotherapy, spontaneous regression was observed, not only within the irradiated field, but also in the non-irradiated areas. All signs of cancer throughout the body disappeared, and the patient's performance status drastically improved. To the best of our knowledge, there have been no reports of advanced breast cancer cases in which the abscopal effect was observed after radiation monotherapy; therefore, this case report is extremely rare and highly valuable.

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.

[Indication for Radiotherapy for Breast Cancer Metastasis to the Skull Base Accompanied by Cranial Nerve Palsies].

Distant metastasis to the skull base region frequently manifests various cranial nerve symptoms and reduces patients' quality of life(QOL). We report a 62-year-old woman with skull base metastasis of breast cancer, whose condition clinically improved following palliative radiotherapy. The patient presented to our hospital with hoarseness. CT screening revealed a tumor in the right breast, axial lymph node swelling, and osteoblastic change at multiple sites. A core needle biopsy of the breast tumor revealed invasive lobular carcinoma. She also had nausea, anorexia, vertigo, lower left angle of the mouth, apraxia of lid closing, and dysphagia owing to several cranial nerve palsies. MRI T1- and T2-weighted images showed a diffuse low-signal intensity of the skull base region, and the patient was diagnosed as having breast cancer with symptomatic skull base metastases. Her cranial nerve symptoms improved after 1 week of palliative irradiation to the skull base. We conclude that, even among terminal-stage patients, palliative radiotherapy to the skull base region is an effective treatment option to improve patients' QOL.

High Dose Hypofractionated Proton Beam Therapy is a Safe and Feasible Treatment for Central Lung Cancer.

BACKGROUND: There have been few reports about high total dose hypofractionated proton beam therapy for central lung cancer. The aim of this study was to examine retrospectively the safety and efficacy of high total dose hypofractionated proton beam therapy for central lung cancer. PATIENTS AND METHODS: Patients treated by proton beam therapy for central lung cancer located less than 2 cm from the trachea, mainstem bronchus, or lobe bronchus were included in this study. All patients received 80 Gy of relative biological dose effectiveness (RBE) in 25 fractions with proton beam therapy over 5 weeks between January 2009 and February 2015. The toxicities were evaluated using the Radiation Therapy Oncology Group and European Organization for Research and Treatment of Cancer criteria. RESULTS: Twenty patients, including 14 clinically inoperable patients (70%), received proton beam therapy for central lung cancer. The median patient age was 75 years (range: 63-90 years), the median follow up time was 27.5 months (range: 12-72 months), and the median tumor diameter was 39.5 mm (range: 24-81 mm). All patients were followed for at least 20 months or until death. The 2-year overall survival rate was 73.8% (100% in operable patients, and 62.5% in inoperable patients), and the 2-year local control rate was 78.5%. There was no Grade 3 or higher toxicities, including bronchial stricture, obstruction, and fistula. CONCLUSIONS: The present study suggests that a high total dose hypofractionated proton beam therapy for central lung cancer was safe and feasible.

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.

Re-irradiation using proton beam therapy combined with weekly intra-arterial chemotherapy for recurrent oral cancer.

AIM: The purpose of this study was to clarify the efficacy and toxicities of re-irradiation using proton beam therapy combined with weekly intra-arterial chemotherapy for recurrent oral cancer. METHODS: Between October 2009 and July 2014, 34 patients who had recurrent oral cancer were treated by proton beam therapy combined with intra-arterial infusion chemotherapy at the Southern Tohoku Proton Therapy Center, Japan. RESULTS: For all patients, the median follow-up was 25 months (range, 3-77 months). After treatment, 22 patients (65%) achieved a complete response, and 12 patients (35%) achieved a partial response at the primary tumor site. One-year and 2-year overall survival (OS) rates were 62% and 42%, respectively. One-year and 2-year LC rates were 77% and 60%, respectively. No treatment-related deaths were observed during the treatment and follow-up periods. CONCLUSION: Re-irradiation using proton beam therapy combined with weekly intra-arterial chemotherapy improved OS and local control rates compared with other treatment modalities and could become a new treatment modality for patients with recurrent oral cancer.