Carbon-ion radiotherapy for hepatocellular carcinoma with major vascular invasion: a retrospective cohort study.

BACKGROUND: Macroscopic vascular invasion (MVI) significantly impacts survival in patients with hepatocellular carcinoma (HCC), warranting systemic therapy over locoregional therapy. Despite novel approaches, HCC with MVI has a poor prognosis compared to early-to intermediate-stage HCC. This study aimed to evaluate the safety and efficacy of carbon-ion radiotherapy (C-ion RT) for HCC characterized by MVI. METHODS: This retrospective cohort study evaluated HCC patients with MVI treated using C-ion RT with a dose of 45.0-48.0 Gy/2 fractions or 52.8-60.0 Gy/4 fractions between 1995 and 2020 at our institution in Japan. We analyzed the prognostic factors and rates of local recurrence, survival, and adverse events. The local recurrence rate was determined using the cumulative incidence function, with death as a competing event. Survival rates were determined using the Kaplan-Meier method. The log-rank test for univariate analysis and the Cox proportional hazards model for multivariate analysis were used to compare subgroups. RESULTS: In total, 76 patients with a median age of 71 years (range, 45-86 years) were evaluated. Among them, 68 had Child-Pugh grade A while eight had grade B disease. In 17 patients, the vascular tumor thrombus reached the inferior vena cava or main trunk of the portal vein. Over a median follow-up period of 27.9 months (range, 1.5-180.4 months), the 2-year overall survival, progression-free survival, and local recurrence rates were 70.0% (95% confidence interval [CI]: 57.7-79.4%), 32.7% (95% CI: 22.0-43.8%), and 8.9% (95% CI: 1.7-23.5%), respectively. A naïve tumor and a single lesion were significant prognostic factors for overall survival in the univariate analysis. Albumin-bilirubin grade 1 and a single lesion were independent prognostic factors in the multivariate analysis. Overall, four patients (5%) experienced grade 3 late adverse events, with no observed grade 4 or 5 acute or late adverse events. CONCLUSIONS: C-ion RT for HCC with MVI showed favorable local control and survival benefits with minimal toxicity.

Analysis of the cost-effectiveness of proton beam therapy for unresectable pancreatic cancer in Japan.

BACKGROUND: Proton beam therapy (PBT) has recently been included in Japan's social health insurance benefits package. This study aimed to determine the cost-effectiveness of PBT for unresectable, locally advanced pancreatic cancer (LAPC) as a replacement for conventional photon radiotherapy (RT). METHODS: We estimated the incremental cost-effectiveness ratio (ICER) of PBT as a replacement for three-dimensional conformal RT (3DCRT), a conventional photon RT, using clinical evidence in the literature and expense complemented by expert opinions. We used a decision tree and an economic and Markov model to illustrate the disease courses followed by LAPC patients. Effectiveness was estimated as quality-adjusted life years (QALY) using utility weights for the health state. Social insurance fees were calculated as the costs. The stability of the ICER against the assumptions made was appraised using sensitivity analyses. RESULTS: The effectiveness of PBT and 3DCRT was 1.67610615 and 0.97181271 QALY, respectively. The ICER was estimated to be ¥5,376,915 (US$46,756) per QALY. According to the suggested threshold for anti-cancer therapy from the Japanese authority of ¥7,500,000 (US$65,217) per QALY gain, such a replacement would be considered cost-effective. The one-way and probabilistic sensitivity analyses demonstrated stability of the base-case ICER. CONCLUSION: PBT, as a replacement for conventional photon radiotherapy, is cost-effective and justifiable as an efficient use of finite healthcare resources. Making it a standard treatment option and available to every patient in Japan is socially acceptable from the perspective of health economics.

Clinical impact of carbon-ion radiotherapy on hepatocellular carcinoma with Child-Pugh B cirrhosis.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) patients with Child-Pugh (CP)-B not eligible for surgery nor other focal therapy options due to impaired liver function, have very limited treatment options. This study aims to retrospectively investigate the toxicity and efficacy of Carbon-ion radiotherapy (C-ion RT) on HCC with CP-B patients. MATERIALS AND METHODS: Patients with CP-B, no extrahepatic metastasis, and treated with C-ion RT between May 2000 and March 2020 were retrospectively extracted and included in this study. RESULTS: Sixty-nine lesions of 58 patients were included. The median follow-up duration was 20.5 (2.7-108) months. During follow-up, recurrence was observed in 43 patients, including 2 local recurrences and 39 intrahepatic recurrences beyond the irradiation field. A grade 3 acute hepatotoxicity was observed in one patient during the observation period. No acute or late adverse event of grade ≥4 was observed. Overall survival was 80.4% and 46.0% at 1 and 2 years, respectively, and the median survival time was 22.6 months. Local control rate was 96.4% at both 1 and 2 years, and progression-free survival was 38.6% and 6.9% at 1 and 2 years, respectively, with a median of 9.7 months. CONCLUSION: The C-ion RT showed low toxicity and good local effect in patients with HCC and CP-B. Therefore, C-ion RT could be an appropriate treatment for patients with HCC with poor liver function.

Analysis of particle therapy registries based on a unified treatment policy for esophageal cancer.

This study aimed to evaluate the efficacy and safety of particle therapy (proton beam therapy and carbon-ion radiotherapy) for esophageal cancer by analyzing prospective nationwide registry data from particle therapy facilities throughout Japan. Patients diagnosed with esophageal cancer who received particle therapy between May 2016 and June 2018 were recruited from the registries of 12 particle therapy centers in Japan. Eventually, we enrolled 174 patients who met the inclusion criteria. Of the 174 patients, 137 (78.7%) were male, with a median age of 69 years (range: 41-88 years). Clinical stages included I (n = 55; 31.6%), II (n = 31; 17.8%), III (n = 82; 47.1%), IV (n = 3; 1.7%) and unknown (n = 3; 1.7%) (Union for International Cancer Control, seventh edition), and the median follow-up period was 908 days (range: 76-1669 days) for all patients. The 3-year overall survival (OS) rate, the 3-year progression-free survival (PFS) rate and the 3-year local control (LC) rates were 60.5, 53.2 and 72.7%, respectively. For each clinical stage, the 3-year OS rates were I, 84.8%; II, 60.3% and III, 42.9%; the 3-year PFS rates were I, 71.9%; II, 58.3% and III, 37.0% and the 3-year LC were I, 78.4%; II, 79.8% and III, 65.2%, respectively. Notably, four patients (2.3%) with ≥Grade 3 cardiopulmonary toxicities were observed (Common Terminology Criteria for Adverse Events, version 5.0). Our study showed that particle therapy for esophageal cancer has lower rates of adverse cardiopulmonary events than X-ray radiotherapy.

Clinical Impact of Proton Beam Therapy for Postoperative Lymph Node Oligorecurrence of Esophageal Cancer.

BACKGROUND/AIM: Radiotherapy is a salvage therapy type for postoperative recurrence of esophageal cancer. Compared to conventional photon-based radiotherapy, proton beam therapy can reduce the irradiated dose to the surrounding organs, facilitating the management of patients who are unfit for radiotherapy. In this study, the outcomes and toxicity of proton beam therapy for postoperative lymph node oligorecurrence of esophageal cancer were investigated. PATIENTS AND METHODS: We retrospectively evaluated the clinical outcomes and toxicity of 13 sites in 11 patients treated with proton beam therapy for postoperative lymph node oligorecurrence of esophageal cancer. In total, eight men and three women with a median age of 68 years (range=46-83 years) were included. RESULTS: The median follow-up period was 20.2 months. During the follow-up period, four patients died of esophageal cancer. Eight of the 11 patients developed recurrence; of these, seven patients had recurrence outside the irradiated field, and one had recurrence inside and outside the irradiated field. The 2-year overall survival, progression-free survival, and local control rates were 48.0%, 27.3%, and 84.6%, respectively. The median survival time was 22.4 months. There were no severe acute or late adverse events. CONCLUSION: Proton beam therapy could be a safe and effective treatment method for postoperative lymph node oligorecurrence of esophageal cancer. It may be beneficial even in cases where conventional photon-based radiotherapy is difficult to administer in combination with increased doses or with chemotherapy.

Particle beam therapy for pelvic recurrence of colorectal cancer: a registry data analysis in Japan and a systematic review.

The aim of this study was to investigate the efficacy and safety of particle beam therapy (PBT) with proton or carbon ion beam for pelvic recurrence of colorectal cancer (PRCC) by comparing the clinical outcomes of a dataset of prospectively enrolled patients for PBT with those from the literature, which were collected by a systematic review of external X-ray radiotherapy (XRT) and PBT. Patients with PRCC treated at 14 domestic facilities between May 2016 and June 2019 and entered the database for prospective observational follow-up were analyzed. The registry data analyzed included 159 PRCC patients treated with PBT of whom 126 (79%) were treated with carbon ion radiation therapy (CIRT). The 3-year overall survival and local control rate were 81.8 and 76.4%, respectively. Among these PRCC patients, 5.7% had Grade 3 or higher toxicity. Systematic search of PubMed and Cochrane databases published from January 2000 to September 2020 resulted in 409 abstracts for the primary selection. Twelve studies fulfilled the inclusion criteria. With one additional publication, 13 studies were selected for qualitative analysis, including 9 on XRT and 4 on PBT. There were nine XRT studies, which included six on 3D conformal radiotherapy and three on stereotactic body radiation therapy, and four PBT studies included three on CIRT and one on proton therapy. A pilot meta-analysis using literatures with median survival time extractable over a 20-month observation period suggested that PBT, especially CIRT, may be a promising treatment option for PRCC not amenable to curative resection.

Long-term Outcomes After Moderate Hypofractionated Proton Therapy for Centrally Located Non-small Cell Lung Cancer.

BACKGROUND/AIM: To investigate the outcomes of patients with centrally located non-small-cell lung cancer (NSCLC) treated with proton beam therapy (PBT) using moderate hypofractionation. PATIENTS AND METHODS: Between 2006 and 2019, 34 patients with centrally located T1-T4N0M0 NSCLC who received moderate hypofractionated PBT were retrospectively reviewed. RESULTS: The median follow-up was 50.8 months (range=5.8-100.4 months). The 3-year overall survival, progression-free survival (PFS), and local control rates were 70.4%, 55.5% and 80.5%, respectively. Grade 2 or 3 lung adverse events (AEs) after PBT were observed in five (14.7%) patients; however, grade 3 radiation pneumonitis was observed in one (2.9%) patient. Notably, no grade 4 or higher AEs were observed. Regarding the correlation between the lung dose and proximal bronchial tree maximum dose and grade 2 or higher lung AEs, a weak correlation was observed between the mean lung dose and AEs (p=0.035). Although the clinical target volume (CTV) was a risk factor for poor PFS, no significant correlation was found between the CTV and lung AEs after PBT. CONCLUSION: Moderate hypofractionated PBT may be a useful radiotherapy method for centrally located cT1-T4N0M0 NSCLC.

Safety and Efficacy of Carbon-Ion Radiotherapy for Elderly Patients with High-Risk Prostate Cancer.

Carbon-ion radiotherapy (CIRT) is a high-dose intensive treatment, whose safety and efficacy have been proven for prostate cancer. This study aims to evaluate the outcomes of CIRT in elderly patients with prostate cancer. Patients aged 75 years or above at the initiation of CIRT were designated as the elderly group, and younger than 75 years as the young group. The overall survival (OS), disease-specific survival (DSS), biochemical control rate (BCR), biochemical relapse-free survival (BRFS), and adverse events were compared between the elderly and young patients with high-risk prostate cancer treated with CIRT. The elderly group comprised 173 of 927 patients treated for high-risk prostate cancer between April 2000 and May 2018. The overall median age was 69 (range: 45−92) years. The median follow-up period was 91.9 (range: 12.6−232.3) months. The 10-year OS, DSS, BCR, and BRFS rates in the young and elderly groups were 86.9%/71.5%, 96.6%/96.8%, 76.8%/88.1%, and 68.6%/64.3%, respectively. The OS (p < 0.001) was longer in the younger group and the BCR was better in the elderly group (p = 0.008). The DSS and BRFS did not differ significantly between the two groups. The rates of adverse events between the two groups did not differ significantly and no patient had an adverse event of Grade 4 or higher during the study period. CIRT may be as effective and safe in elderly patients as the treatment for high-risk prostate cancer.

Carbon-ion radiotherapy for urological cancers.

Carbon-ions are charged particles with a high linear energy transfer, and therefore, they make a better dose distribution with greater biological effects on the tumors compared with photons and protons. Since prostate cancer, renal cell carcinoma, and retroperitoneal sarcomas such as liposarcoma and leiomyosarcoma are known to be radioresistant tumors, carbon-ion radiotherapy, which provides the advantageous radiobiological properties such as an increasing relative biological effectiveness toward the Bragg peak, a reduced oxygen enhancement ratio, and a reduced dependence on fractionation and cell-cycle stage, has been tested for these urological tumors at the National Institute for Radiological Sciences since 1994. To promote carbon-ion radiotherapy as a standard cancer therapy, the Japan Carbon-ion Radiation Oncology Study Group was established in 2015 to create a registry of all treated patients and conduct multi-institutional prospective studies in cooperation with all the Japanese institutes. Based on accumulating evidence of the efficacy and feasibility of carbon-ion therapy for prostate cancer and retroperitoneal sarcoma, it is now covered by the Japanese health insurance system. On the other hand, carbon-ion radiotherapy for renal cell cancer is not still covered by the insurance system, although the two previous studies showed the efficacy. In this review, we introduce the characteristics, clinical outcomes, and perspectives of carbon-ion radiotherapy and our efforts to disseminate the use of this new technology worldwide.

Proton Beam Therapy in Elderly Patients With cT1-3N0M0 Non-small Cell Lung Cancer.

BACKGROUND/AIM: To investigate the outcomes of elderly patients with cT1-3N0M0 non-small cell lung cancer (NSCLC) undergoing proton beam therapy (PBT). PATIENTS AND METHODS: Between 2009 and 2019, 110 patients receiving hypofractionated PBT for cT1-3N0M0 NSCLC were retrospectively reviewed. RESULTS: The median follow-up was 36.5 months (range=4.9-131.0 months). In the elderly group (80 years or older), the 3-year overall survival and progression-free survival rates were 79.8% and 73.9%, respectively, and the corresponding rates in the younger group were 80.5% and 61.2%, respectively. Grade 3 radiation pneumonitis (RP) was observed in 4.4% patients in the young group, whereas no grade 3 RP was observed in the elderly group. Age was not a risk factor for symptomatic RP. There were no significant differences in the survival and adverse events between the elderly and younger groups. CONCLUSION: PBT may be a reasonable approach for treating lung cancer in elderly patients with T1-3N0M0 NSCLC.

Stereotactic Body Radiotherapy for Stage I Lung Cancer With a New Real-time Tumor Tracking System.

BACKGROUND/AIM: Suppression of respiratory movement is crucial for safe and effective stereotactic body radiotherapy (SBRT). SyncTraX FX4 is a novel device for synchronous respiratory irradiation. The purpose of this study was to evaluate the efficacy and toxicity of SBRT using SyncTraX FX4 for patients with lung cancer. PATIENTS AND METHODS: Patients treated with SBRT using SyncTraX FX4 between November 2017 and August 2020 were included. In all cases, fiducial markers were inserted into the lung, and the total dose administered was 55 or 60 Gy, depending on the distance from the central region of the lung. Acute and late toxicities were reported, and local control, progression-free survival, cancer-specific survival, and overall survival were analyzed. RESULTS: We evaluated 16 patients and 17 sites. The median follow-up period was 14.4 months. In both the acute and late phases, one patient experienced grade 3 radiation pneumonitis; however, grade 4 or higher toxicities were not observed. There was no local recurrence during the observation period, and the overall survival, cancer-specific survival, and progression-free survival at 2 years were 54.6%, 85.1%, and 33.7%, respectively. CONCLUSION: SBRT with SyncTraX FX4 can provide safe and effective treatment for lung cancer patients in poor condition.

External validation of the Candiolo nomogram for high-risk prostate cancer patients treated with carbon ion radiotherapy plus androgen deprivation therapy: a retrospective cohort study.

The aim of this study was to reclassify high-risk prostate cancer patients treated with carbon-ion radiotherapy and androgen deprivation therapy using the Candiolo nomogram and evaluate usefulness to predict the following 10-year biochemical recurrence. Six hundred seventy-two high-risk prostate cancer patients were reclassified according to the Candiolo nomogram. The cumulative incidence curves for biochemical recurrence were compared by Gray's test. Furthermore, five predictors of the Candiolo nomogram in our patients were evaluated by Fine and Gray regression hazards model. The higher the Candiolo risk, the worse the biochemical recurrence, especially in high- and very high-risk patients. Out of five predictors, age ≥70 years, cT3 stage, biopsy Gleason score ≥9 or the percentage of positive biopsy cores ≥50% had significant impacts on 10-year biochemical recurrence in our patients. The Candiolo nomogram can reclassify our high-risk prostate cancer patients treated with carbon-ion radiotherapy and androgen deprivation therapy and evaluate the biochemical recurrence preciously.

A Case Report of Radiotherapy for Skull Lesions of Langerhans Cell Histiocytosis With Dural Invasion.

Background: Langerhans cell histiocytosis (LCH) is a rare disease, especially in adults. It is often associated with non-fatal bone and skin lesions and has relatively good radiosensitivity. In contrast, brain and lymph node metastases from LCH lesions are considered to be less sensitive to radiotherapy. Case Report: At our institution, 30 Gy radiotherapy was used to treat bone lesions with dural invasion in a patient with adult-onset LCH. The patient was treated with chemotherapy and radiotherapy for 21 years since the initial diagnosis. After radiotherapy, the tumor shrank rapidly, and a complete response was achieved 1 year after treatment. The patient survived without local recurrence. Conclusion: Here, we report the details of this case, along with a review of the literature. We suggest that even with invasion of the tissues around the bone lesions in LCH, local recurrence can be prevented by middle radiation doses.

A Recurrent Solitary Fibrous Tumor With an Exceptional Response to Low-Dose Radiotherapy: A Case Report and Literature Review.

Solitary fibrous tumor (SFT) is a soft tissue tumor derived from mesenchymal cells. We report a case of a giant SFT with insulin-like growth factor 2 (IGF-2) production in the pelvis of an 85-year-old male. SFT was diagnosed in surgery for a complaint of left lower abdominal distension. Subsequent tumor recurrence and progression caused rectal passage obstruction and hypoglycemia. Low-dose radiotherapy of 15 Gy in five fractions was started five years and four months after surgery, initially for a huge tumor around the rectum to improve rectal passage obstruction. The tumor volume shrank from 1054 cc before irradiation to 449 cc at one month and 396 cc at 10 months after irradiation. He had reached 90 years old at that time. Two months after the initial irradiation, similar radiotherapy of 15 Gy in five fractions was performed for a huge tumor in the right abdominal cavity. This tumor decreased from 1874 cc before irradiation to 615 cc at two months and 556 cc at seven months after irradiation. Dexamethasone (2.5 mg) was used for paraneoplastic syndrome at the time of initial radiation but was then reduced and became unnecessary two months after the second irradiation. Acute and late adverse events were mild. The patient is alive 60 months after the first irradiation. This case suggests that low-dose radiotherapy is beneficial as palliative therapy for symptom relief in patients with SFT.

The impact of lymphopenia during chemoradiotherapy using photons or protons on the clinical outcomes of esophageal cancer patients.

We assessed the development of lymphopenia during concurrent chemoradiotherapy (CRT) using X-ray versus proton beams and the impact on survival in patients with esophageal cancer. Among patients with esophageal cancer who were administered concurrent CRT with a curative intent at our institute from 2014 to 2018, 69 (15 receiving X-ray radiotherapy (XRT) and 54 receiving proton beam therapy [PBT]) who underwent weekly blood testing during treatment were enrolled. The absolute lymphocyte counts (ALC) at 1, 5 and 6 weeks were significantly higher in the patients who received PBT than in those who received XRT (p = 0.002, p = 0.006 and p = 0.009, respectively), and a similar trend in the neutrophil-to-lymphocyte ratio (NLR) was observed (p = 0.003 at 5 weeks). The 2-year overall survival (OS) and progression-free survival (PFS) rates tended to be higher in the patients who maintained an ALC ≥200 compared with those who did not (p = 0.083 and p = 0.053, respectively), and similar trends were observed in the NLR (p = 0.061 and p = 0.038, respectively). Dose-volume analysis revealed significant correlations between volumes of the thoracic bones irradiated by 5-50 Gy and minimum ALCs and maximum NLR. These findings suggested that PBT prevented the development of lymphopenia during CRT by reducing the irradiated volume of the thoracic bone, and the maintained lymphocyte count is possibly one of the early predictors for survival in patients with esophageal cancer.

Proton Beam Therapy for Local Recurrence of Rectal Cancer.

BACKGROUND/AIM: Curing local recurrence of rectal cancer (LRRC) is difficult with conventional photon radiotherapy. Proton beam therapy (PBT) on the other hand, has unique physical characteristics that permit higher doses to LRRC while minimizing side effects on surrounding organs. However, the efficacy of PBT on controlling rectal cancer recurrence has not yet been reported. This study aimed to evaluate clinical outcomes and toxicities of PBT for LRRC. PATIENTS AND METHODS: Clinical outcomes were retrospectively evaluated for 12 patients with 13 total lesions that had received PBT for LRRC at our institute. RESULTS: The median follow-up period from the initiation of PBT was 35.6 months. The 3-year local control, progression-free survival and overall survival rates were 80.2%, 10.4% and 73.8%, respectively. Median survival time was 67.1 months. There were no severe acute or late adverse events. CONCLUSION: PBT could be a safe and effective treatment method for LRRC.

Retrospective analysis of neoadjuvant chemotherapy followed by surgery versus definitive chemoradiotherapy with proton beam for locally advanced esophageal squamous cell carcinoma.

BACKGROUND: This is the first study to compare the long-term outcomes between neoadjuvant chemotherapy + surgery and definitive chemoradiotherapy with proton beam therapy for locally advanced esophageal squamous cell carcinoma. METHODS: We reviewed patients with clinical stage IB-III esophageal squamous cell carcinoma (UICC 7th edition) who underwent neoadjuvant chemotherapy + surgery or definitive chemoradiotherapy with proton beam therapy (2009-2017). Overall survival, progression-free survival, and recurrence or regrowth rates were compared between the two treatment groups. Subgroup analyses of overall survival according to baseline characteristics were also performed. RESULTS: Forty-three patients received neoadjuvant chemotherapy + surgery (median follow-up 47.4 months) and 60 received definitive chemoradiotherapy with proton beam therapy (median follow-up 51.5 months). Baseline characteristics were similar between the groups except for sex, tumor location, and cT classification. The neoadjuvant chemotherapy + surgery and definitive chemoradiotherapy with proton beam therapy groups had similar 3-year overall survival rates (73.1% and 61.7%, respectively, hazard ratio: 0.88, 95% confidence interval 0.49-1.58, p = 0.66), 3-year progression-free survival rates (46.5% and 45%, respectively, hazard ratio: 1.03, 95% confidence interval 0.62-1.70, p = 0.92), and recurrence or regrowth rates (53.5% vs. 50.0%, p = 0.84). In the subgroup analysis, favorable survival was observed after definitive chemoradiotherapy with proton beam therapy for cT1-2 disease (hazard ratio 2.58, 95% confidence interval 0.84-7.99) and after neoadjuvant chemotherapy + surgery for cT3 or higher disease (hazard ratio 0.32, 95% confidence interval 0.15-0.67, p-for-interaction = 0.002). CONCLUSIONS: Long-term outcomes were comparable between the treatments. The choice of the treatment according to cT classification might affect survival.

Long-term clinical outcomes of patients receiving proton beam therapy for caudate lobe hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) located in the caudate lobe (caudate HCC) is rare; however, patients with this type of tumour have poorer prognoses than those with HCC in other segments. Despite many published reports on the clinical usefulness of proton beam therapy (PBT) for HCC, data on the clinical outcomes of patients undergoing PBT for caudate HCC remain scarce. Therefore, the present study aimed to investigate the outcomes of this group of patients. Thirty patients with caudate HCC who underwent definitive PBT between February 2002 and February 2014 were retrospectively analysed. The total irradiation doses ranged from 55 to 77 (median 72.6) Gy relative biological dose. The median follow-up period was 37.5 (range, 3.0-152.0) months. The overall survival (OS) rates at one, three and five years were 86.6%, 62.8% and 46.1%, respectively. According to univariate and multivariate analyses, Child-Pugh A (P < 0.01), having a single tumour (P = 0.02) and a low serum alpha-fetoprotein level (AFP; P < 0.01) were significant factors predicting longer survival. The local control (LC) rates at one, three and five years were 100%, 85.9% and 85.9%, respectively, while the corresponding progression-free survival (PFS) rates were 65%, 27.5% and 22%, respectively. No grade 3 or worse adverse events were observed. PBT is effective and safe for the treatment of caudate HCC, and should therefore be considered a feasible option for intervention in patients with this disease.

Survival impact on triple-modal strategy comprising hyperthermia, external radiation, and chemotherapy for unresectable locally advanced (UR-LA) pancreatic ductal adenocarcinoma.

BACKGROUND: Present treatment strategy for unresectable locally advanced (UR-LA) pancreatic ductal adenocarcinoma (PDAC) patients is controversial. Hence, a triple-modal therapy, which is a multidisciplinary strategy, was designed for patients with UR-LA PDAC by adding hyperthermia to conventional chemoradiotherapy at our institution. In this study we aimed to evaluate the effectiveness of this strategy. METHODS: Data of 21 UR-LA PDAC patients who underwent the triple-modal treatment were retrospectively analyzed for evaluating the safety and oncological effect of the treatment. The treatment schedule included, five concurrent infusions of gemcitabine (800 mg/m2) followed by hyperthermia (1 h) and X-ray (2 Gy) or proton beam radiation (2.7 Gy) on days 1, 8, 15, 29, and 36. Additional radiotherapies applied a total dose of 50 Gy/25 fr for X-ray radiation or 67.5 Gy/25 fr for proton beam radiation. RESULTS: Median overall survival (OS) was 23.6 months. Conversion surgery was performed in 5 patients (23.8%), and a R0 margin could be achieved in 4 of them; however, their median OS (16.3 months) tended to be shorter than that of the patients who did not undergo resection (23.6 months, p = 0.562). Further, the median OS of patients who underwent proton beam radiation (28.0 months) was significantly longer than that of patients who underwent X-ray radiation (13.9 months, p = 0.045). Most adverse events were manageable, except for one grade 3 gastric ulcer. The median tumor size and marker reduction rates were -17% and -91%, respectively. The tumor responses were partial response, stable disease, and progressive disease in 3, 15, and 3 patients, respectively. CONCLUSION: Triple-modal strategy, especially when combined with proton beam radiation, is feasible and results in favorable survival outcomes in patients with UR-LA PDAC.

Proton beam therapy for a giant hepatic hemangioma: A case report and literature review.

BACKGROUND: Hepatic hemangiomas are benign tumors with a favorable prognosis, but giant hepatic hemangiomas can cause abdominal symptoms and are indicated for treatment. Most cases are treated with surgery, but radiotherapy has also been used. However, to date, there have been no reports of proton beam therapy for a hepatic hemangioma. CASE PRESENTATION: A 46-year-old woman had a tumor of 80 × 80 mm in the left medial lobe of the liver, which was diagnosed as a giant hemangioma based on the contrast pattern. Therapy was required for a giant hepatic hemangioma with symptoms, but the patient refused blood transfusion due to religious reasons, which made surgical resection difficult. Therefore, she was referred to our hospital for proton beam therapy. At her first visit, liver function was Child-Pugh A (5 points) and there was no elevation of tumor markers. Proton beam therapy of 28.6 Gy (RBE) given in 13 fractions was performed without interruption. The only observed acute radiation toxicity was Grade 1 dermatitis. One year after proton beam therapy, the hemangioma had significantly decreased, and a complete response has been maintained for 15 years based on ultrasound and MRI. CONCLUSION: This case is the first reported use of proton beam therapy for a hepatic hemangioma. The outcome suggests that this treatment may be effective for a giant liver hemangioma.