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BACKGROUND: Locally advanced pancreatic ductal adenocarcinoma (PDAC), accounting for about 30% of PDAC patients, is difficult to cure by radical resection or systemic chemotherapy alone. A multidisciplinary strategy is required and our TT-LAP trial aims to evaluate whether triple-modal treatment with proton beam therapy (PBT), hyperthermia, and gemcitabine plus nab-paclitaxel is a safe and synergistically effective treatment for patients with locally advanced PDAC. METHODS: This trial is an interventional, open-label, non-randomized, single-center, single-arm phase I/II clinical trial organized and sponsored by the University of Tsukuba. Eligible patients who are diagnosed with locally advanced pancreatic cancer, including both borderline resectable (BR) and unresectable locally advanced (UR-LA) patients, and selected according to the inclusion and exclusion criteria will receive triple-modal treatment consisting of chemotherapy, hyperthermia, and proton beam radiation. Treatment induction will include 2 cycles of chemotherapy (gemcitabine plus nab-paclitaxel), proton beam therapy, and 6 total sessions of hyperthermia therapy. The initial 5 patients will move to phase II after adverse events are verified by a monitoring committee and safety is ensured. The primary endpoint is 2-year survival rate while secondary endpoints include adverse event rate, treatment completion rate, response rate, progression-free survival, overall survival, resection rate, pathologic response rate, and R0 (no pathologic cancer remnants) rate. The target sample size is set at 30 cases. DISCUSSION: The TT-LAP trial is the first to evaluate the safety and effectiveness (phases1/2) of triple-modal treatment comprised of proton beam therapy, hyperthermia, and gemcitabine/nab-paclitaxel for locally advanced pancreatic cancer. ETHICS AND DISSEMINATION: This protocol was approved by the Tsukuba University Clinical Research Review Board (reference number TCRB22-007). Results will be analyzed after study recruitment and follow-up are completed. Results will be presented at international meetings of interest in pancreatic cancer plus gastrointestinal, hepatobiliary, and pancreatic surgeries and published in peer-reviewed journals. TRIAL REGISTRATION: Japan Registry of Clinical Trials, jRCTs031220160. Registered 24 th June 2022, https://jrct.niph.go.jp/en-latest-detail/jRCTs031220160 .
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Carcinoma Ductal Pancreático , Hipertermia Induzida , Neoplasias Pancreáticas , Humanos , Albuminas , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Ductal Pancreático/tratamento farmacológico , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Gencitabina , Paclitaxel/uso terapêutico , Neoplasias Pancreáticas/patologia , Prótons , Neoplasias PancreáticasRESUMO
AIM: Hepatocellular carcinoma (HCC) with bile duct invasion (BDI) (BDIHCC) has a poor prognosis. Moreover, due to the paucity of reports, there is no consensus regarding optimal management of this clinical condition yet. The aim of this study was to clarify the efficacy and safety of proton beam therapy (PBT) for BDIHCC. METHODS: Between 2009 and 2018, 15 patients with BDIHCC underwent PBT at our institution. The overall survival (OS), local control (LC), and progression-free survival (PFS) curves were constructed using the Kaplan-Meier method. Toxicities were assessed using the Common Terminology Criteria of Adverse Events version 4.0. RESULTS: The median follow-up time was 23.4 months (range, 7.9-54.3). The median age was 71 years (range, 58-90 years). Many patients were Child A (n = 8, 53.3%) and most had solitary tumors (n = 11, 73.3%). Additionally, most patients had central type BDI (n = 11, 73%). The median tumor size was 4.0 cm (range, 1.5-8.0 cm). The 1-, 2-, and 3-year OS rates were 80.0%, 58.7% and 40.2%, respectively, and the corresponding LC and PFS rates were 93.3%, 93.3%, and 74.7% and 72.7%, 9.7%, and 0.0%, respectively. Acute grade 1/2 dermatitis (n = 7, 46.7%), and grades 2 (n = 1, 6.7%) and 3 (n = 1, 6.7%) cholangitis were observed. Late toxicities such as grade 3 gastric hemorrhage and pleural effusion were observed. No toxicities of grade 4 or higher were observed. CONCLUSIONS: PBT was feasible with tolerable toxicities for the treatment of BDIHCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Terapia com Prótons , Idoso , Humanos , Ductos Biliares , Intervalo Livre de Progressão , Terapia com Prótons/efeitos adversos , Terapia com Prótons/métodos , Pessoa de Meia-Idade , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: The details of gastrointestinal bleeding/ulcer in paediatric cancer patients treated with proton beam therapy have not been reported previously. METHODS: Patients aged 15 years or younger at the time of proton beam therapy and whose gastrointestinal tract was included in the irradiated field participated. RESULTS: A total of 124 patients participated in the study; their median age at irradiation was 5.4 years. Concurrent chemotherapies were vincristine-cyclophosphamide (16 patients), irinotecan-based treatment (16 patients), vincristine-cyclophosphamide-ifosfamide-etoposide (14 patients), other chemotherapy (27 patients) and no chemotherapy (51 patients). Gastrointestinal bleeding/ulcer occurred in four patients (3.2%), with no death due to the bleeding/ulcer. The sites of the gastrointestinal bleeding/ulcer were the stomach (two patients) and the duodenum (two patients). The ages of the four patients at PBT were 5.3, 13.8, 14.2 and 14.8 years, which were significantly older than those of patients without GI bleeding/ulcer (p = 0.017). The maximum irradiated doses to the GI tract in the four patients were 43.2, 45, 50.4 and 50.4 gray equivalent, respectively. The concomitant chemotherapy was vincristine-cyclophosphamide-ifosfamide-etoposide 3 and vincristine-cyclophosphamide 1. Weeks from proton beam therapy to bleeding/ulcer were 15, 20, 22 and 264. DISCUSSION AND CONCLUSIONS: Patients who developed gastrointestinal bleeding/ulcer were treated concurrently with vincristine-cyclophosphamide-ifosfamide-etoposide or vincristine-cyclophosphamide, and their ages were older than those of patients without gastrointestinal bleeding/ulcer. Bleeding occurred in the upper gastrointestinal tract in all the cases, and most cases occurred early and during chemotherapy. Upper gastrointestinal irradiation in older children undergoing intensive chemotherapy may increase the risk of developing gastrointestinal complications.
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Neoplasias , Terapia com Prótons , Criança , Humanos , Pré-Escolar , Ifosfamida/efeitos adversos , Etoposídeo , Vincristina/efeitos adversos , Úlcera , Terapia com Prótons/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doxorrubicina , Ciclofosfamida/efeitos adversos , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Hemorragia Gastrointestinal/induzido quimicamenteRESUMO
PURPOSE: Whilst proton beam therapy (PBT) for children with cancer is expected to reduce their comorbidities, to date only a limited number of studies have been published. To analyze the long-term comorbidity and health-related quality of life (HRQoL) of childhood cancer survivors (CCSs) after PBT, we conducted a questionnaire-based study. METHODS: Questionnaires were sent to CCSs who underwent PBT at the University of Tsukuba Hospital during the period from 1984 to 2020. Scores from 41 CCSs who did not undergo PBT (noPBT-CCSs) and from the general population were used for comparison. RESULTS: In total, 110 individuals who underwent PBT participated in the study. Among them, 40 individuals were longitudinally analyzed. The range of change in the scores was significantly greater in the CCSs whose initial scores were low. Although the comorbidity levels were more severe, HRQoL tended to be better in the PBT-CCSs than in the noPBT-CCSs with central nervous system (CNS) or solid tumors, respectively. When compared with the general population, the psychosocial health summary scores and its components were not different in the noPBT-CNS-CCSs. On the other hand, the psychosocial health summary scores and/or at least one of the scores of emotional, social, and school functioning were significantly higher in the other CCSs groups. CONCLUSIONS: The HRQoL scores of CCSs with low initial scores can be greatly changed over time. Appropriate psychosocial support for this population is warranted. PBT may avoid reduction in HRQoL in terms of the psychosocial functioning of CCSs with CNS tumors.
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Sobreviventes de Câncer , Neoplasias do Sistema Nervoso Central , Neoplasias , Terapia com Prótons , Humanos , Criança , Sobreviventes de Câncer/psicologia , Neoplasias/radioterapia , Qualidade de Vida/psicologia , SobreviventesRESUMO
Glioblastoma (GBM) is a refractory disease with a poor prognosis and various methods, including maximum resection and immunotherapy, have been tested to improve outcomes. In this retrospective study we analyzed the prognostic factors of 277 newly diagnosed GBM patients over 11 years of consecutive cases at our institution to evaluate the effect of these methods on prognosis. Various data, including the extent of removal (EOR) and type of adjuvant therapy, were examined and prognostic relationships were analyzed. The median overall survival (OS) of the entire 277-case cohort, 200 non-biopsy cases, and 77 biopsy cases was 16.6 months, 19.7 months, and 9.7 months, respectively. Gross total removal (GTR; 100% of EOR) was achieved in 32.9% of the cases. Univariate analysis revealed younger age, right side, higher Karnofsky performance status, GTR, intraoperative magnetic resonance imaging (MRI) use for removal, proton therapy, combination immunotherapy, and discharge to home as good prognostic factors. Intraoperative MRI use and EOR were closely related. In the multivariate analysis, GTR, proton therapy, and a combination of immunotherapies, including autologous formalin-fixed tumor vaccine, were the significant prognostic factors. A multivariate analysis of 91 GTR cases showed that immunotherapy contributed to prognostic improvements. The median OS and 5-year OS % values were 36.9 months and 43.3% in GTR cases receiving immunotherapy. In conclusion, GTR, proton therapy, and immunotherapy were good prognostic factors in single-center GBM cases. Tumor vaccine therapy for GTR cases achieved a notably high median survival time and long-term survival ratio, indicating its usefulness in GTR cases.
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Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/terapia , Glioblastoma/mortalidade , Glioblastoma/terapia , Idoso , Antineoplásicos Imunológicos , Vacinas Anticâncer , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Terapia com Prótons , Estudos RetrospectivosRESUMO
Pediatric brain tumor survivors who received proton beam therapy at the University of Tsukuba Hospital from 2004 to 2011 were retrospectively evaluated for cognitive function. Five patients were included. The median age of diagnosis was 5.4 years (range: 1.5 to 12.5 y) and the median follow-up time was 5.8 years (range: 3.1 to 8.1 y). IQ scores at follow-up were decreased in 2 of 5 patients; 1 underwent whole-brain irradiation and the other was examined just after surgical removal of recurrent tumors. Local proton beam therapy may preserve cognitive function in survivors of pediatric brain tumors.
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Neoplasias Encefálicas/radioterapia , Sobreviventes de Câncer/estatística & dados numéricos , Cognição/fisiologia , Terapia com Prótons/métodos , Adolescente , Neoplasias Encefálicas/patologia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: The optimal treatment for rhabdomyosarcoma (RMS) requires multidisciplinary treatment with chemotherapy, surgery, and radiotherapy. Surgery and radiotherapy are integral to the local control (LC) of RMS. However, postsurgical and radiotherapy-related complications could develop according to the local therapy and tumor location. In this study, we conducted a single-center analysis of the outcomes and toxicity of multidisciplinary treatment using proton beam therapy (PBT) for pediatric RMS. MATERIALS AND METHODS: RMS patients aged younger than 20 years whose RMS was newly diagnosed and who underwent PBT at University of Tsukuba Hospital (UTH) during the period from 2009 to 2019 were enrolled in this study. The patients' clinical information was collected by retrospective medical record review. RESULTS: Forty-eight patients were included. The 3-year progression-free survival (PFS) and overall survival (OS) rates of all the patients were 68.8% and 94.2%, respectively. The 3-year PFS rates achieved with radical resection, conservative resection, and biopsy only were 65.3%, 83.3%, and 67.6%, respectively (p = 0.721). The 3-year LC rates achieved with radical resection, conservative resection, and biopsy only were 90.9%, 83.3%, and 72.9%, respectively (p = 0.548). Grade 3 or higher mucositis/dermatitis occurred in 14 patients. Although the days of opioid use due to mucositis/dermatitis during the chemotherapy with PBT were longer than those during the chemotherapy without PBT [6.1 and 1.6 (mean), respectively, p = 0.001], the frequencies of fever and elevation of C-reactive protein were equivalent. CONCLUSIONS: Multidisciplinary therapy containing PBT was feasible and provided a relatively fair 3-year PFS, even in children with newly diagnosed RMS without severe toxicity.
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BACKGROUND: To evaluate long-term degenerative changes in bone and soft tissue after craniospinal irradiation (CSI). PROCEDURE: An analysis was performed for 892 vertebral bodies in 220 pediatric patients treated with CSI. To analyze vertebral growth, vertebral body height was calculated. Signal changes for vertebral bodies on MRI, scoliosis and kyphosis, degenerative changes of vertebral bones and discs, and wedging or vertebral height loss were analyzed on images, and factors that influenced these changes were investigated. RESULTS: Vertebral growth was significantly correlated with radiation dose and growth hormone (GH) deficiency. Growth rate was significantly worse at a dose >39 Gy. Fatty marrow change was found in 83% of patients, 31% had disc degenerative changes, 13% had degenerative changes of spinal bones, 17% had wedging or spinal height loss, and 27% had scoliosis. CONCLUSIONS: Vertebral bone growth was significantly reduced when high doses were administered, and adequate GH replacement was important for bone growth. Even with symmetrical irradiation, the risk of scoliosis is high after CSI. There was also frequent progression of spinal demineralization and degenerative changes after CSI. Therefore, careful attention should be paid to spinal symptoms as pediatric patients grow into adulthood.
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Neoplasias do Sistema Nervoso Central/radioterapia , Radiação Cranioespinal/efeitos adversos , Doenças da Coluna Vertebral/patologia , Coluna Vertebral/patologia , Adolescente , Neoplasias do Sistema Nervoso Central/patologia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , Estudos Retrospectivos , Doenças da Coluna Vertebral/etiologia , Coluna Vertebral/crescimento & desenvolvimento , Coluna Vertebral/efeitos da radiaçãoRESUMO
BACKGROUND: We modeled height after craniospinal irradiation (CSI) in pediatric patients with central nervous system (CNS) embryonal tumors to identify factors that impair stature. PROCEDURE: During 1996-2012, 212 pediatric patients (131 male) with CNS embryonal tumors received postoperative CSI: 23.4 Gy (n = 147) or ≥36 Gy (n = 65), similar postirradiation chemotherapy, and were followed for at least 5 years without tumor progression or other event. The group was further characterized by age at CSI and hormone-replacement therapy received. Models were developed to identify factors associated with growth impairment and estimate final height. RESULTS: With median follow up of 10.2 years (range 5.0-20.4 years), the mean final height z-scores at 18 years of age, compared to United States standards, were -1.3 for female and -1.5 for male survivors. Younger age at the time of CSI, higher CSI dose, and female sex were associated with height impairment. Factors associated with higher growth rates before 15 years of age were older age at CSI, male sex, CSI dose < 36 Gy, replacement therapy for growth hormone (GH) and central adrenal insufficiency, and white race. Growth after age 15 in male survivors was associated with treatment of gonadotropin deficiency. Linear mixed-effects models were developed using clinical factors to estimate final height, demonstrate the unique growth curve of this cohort, and interactions between clinical variable and radiation dose. CONCLUSIONS: CSI significantly impaired height at current doses used to treat standard- or high-risk CNS embryonal tumors. Measures to reduce the impact of CSI on height should be sought, with our models serving as benchmarks.
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Estatura/efeitos da radiação , Sobreviventes de Câncer/estatística & dados numéricos , Neoplasias do Sistema Nervoso Central/radioterapia , Radiação Cranioespinal/efeitos adversos , Neoplasias Embrionárias de Células Germinativas/radioterapia , Fótons/efeitos adversos , Adolescente , Adulto , Neoplasias do Sistema Nervoso Central/patologia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas/patologia , Prognóstico , Estudos Retrospectivos , Adulto JovemRESUMO
Neuroblastoma (NB) predominantly presents as high-risk disease, requiring intensive multimodal therapy. Proton beam therpy (PBT) is a promising option for many childhood cancers, but is not widely available. Patients with NB hoping to receive PBT may therefore need to be transferred between institutions during intensive multimodal therapy, risking undesirable effects. We evaluated patients with high-risk NB who received PBT at our institute as part of first-line therapy, mainly focusing on the safety and feasibility of mid-treatment patient transfer. Eighteen patients with newly diagnosed high-risk NB who received PBT between April 2010 and June 2016 were retrospectively analyzed for local control, outcomes, and toxicity. Survival (3-y overall survival 71%±11%; 3-y event-free survival 44%±12%) and local control rate (100%) were comparable with previous studies. Few acute adverse events were recorded, and all patients completed PBT without treatment delay. PBT for high-risk NB was safe and feasible for patients requiring mid-treatment interinstitutional transfer.
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Neuroblastoma , Transferência de Pacientes , Terapia com Prótons , Criança , Pré-Escolar , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Masculino , Neuroblastoma/diagnóstico , Neuroblastoma/mortalidade , Neuroblastoma/radioterapia , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
A number of cases have been reported in recent years regarding the use of proton beam therapy to mitigate adverse events affecting important cranial organs in cases of rhabdomyosarcoma at parameningeal sites. However, few reports have described the use of proton beam therapy as urgent radiotherapy for parameningeal rhabdomyosarcoma with intracranial extension. We treated 3 patients diagnosed with parameningeal rhabdomyosarcoma extending into the cranium who were assessed at other hospitals as suitable for urgent radiotherapy and transferred to our hospital for proton beam therapy. These patients comprised 2 boys and 1 girl 6 to 12 years of age at diagnosis, and proton beam therapy was started on days 5, 11, and 23 after diagnosis, respectively. Patients with parameningeal rhabdomyosarcoma extending into the cranium can be transferred to institutions equipped to perform proton beam therapy. To minimize the interval to starting therapy, medical information should be shared with institutions capable of providing such therapy as soon as the possibility of intracranial soft-tissue sarcoma is recognized. Proton beam therapy is 1 option for radiotherapy in cases of intracranial rhabdomyosarcoma.
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Neoplasias Encefálicas/radioterapia , Terapia com Prótons , Rabdomiossarcoma/radioterapia , Criança , Feminino , Humanos , MasculinoRESUMO
INTRODUCTION: Diffuse intrinsic pontine glioma (DIPG) is a type of brain malignancy with a very poor prognosis. Although various radiation and chemotherapy protocols have been attempted, only conventional radiotherapy has yielded improvements in survival. In this study, we aimed to compare proton therapy versus conventional photon radiotherapy in terms of the outcomes of pediatric patients with DIPG. METHODS: This retrospective review included 12 pediatric patients with newly diagnosed DIPG who received a total proton therapy dose of 54 Gy (relative biological effectiveness) in 30 fractions at the University of Tsukuba Hospital between 2011 and 2017 (proton group). We additionally reviewed the medical records of 10 patients with DIPG who previously underwent conventional photon radiotherapy at our institute (historical cohort). RESULTS: The median progression-free survival (PFS) duration was 5 months (range 1-11 months), and the 6-, 12-, and 18-month PFS rates were 50%, 33%, and 25%, respectively. The median overall survival (OS) duration was 9 months (range 4-48 months), and the 6-, 12-, 18-, and 24-month OS rates were 66.8%, 50%, 41%, and 20%, respectively. There were no significant differences in survival between the proton and historical groups (PFS, p = 0.169 and OS, p = 0.16). CONCLUSIONS: Proton therapy was well tolerated by the majority of patients. No severe adverse events, including radiation necrosis, were recorded. Proton therapy did not yield superior survival outcomes vs. conventional photon radiotherapy in patients with DIPG at our institution. Further research is needed to identify the factors associated with better survival in this population.
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Neoplasias do Tronco Encefálico , Glioma Pontino Intrínseco Difuso , Glioma , Terapia com Prótons , Neoplasias do Tronco Encefálico/radioterapia , Criança , Glioma/radioterapia , Humanos , Estudos RetrospectivosRESUMO
Charged particle therapy (proton beam therapy and carbon ion therapy) is a form of radiotherapy which has the unique characteristic of superior depth dose distribution, and has been used for the treatment of hepatocellular carcinoma (HCC) in a limited number of patients, especially in Japan. We undertook a systematic review to define the clinical utility of charged particle therapy for patients with HCC. We searched the MEDLINE database from 1983 to June 2016 to identify clinical studies on charged particle therapy for HCC. Primary outcomes of interest were local control, overall survival, and late radiation morbidities. A total of 13 cohorts from 11 papers were selected from an initial dataset of 78 papers. They included a randomized controlled trial comparing proton beam therapy with transarterial chemoembolization, 9 phase I or II trials and 2 retrospective studies. The reported actuarial local control rates ranged from 71.4-95% at 3 years, and the overall survival rates ranged from 25-42.3% at 5 years. Late severe radiation morbidities were uncommon, and a total of 18 patients with grade ≥3 late adverse events were reported among the 787 patients included in this analysis. Charged particle therapy for HCC was associated with good local control with limited probability of severe morbidities. The cost-effectiveness and the distinctive clinical advantages of charged particle therapies should be clarified in order to become a socially accepted treatment modality for HCC.
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Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/radioterapia , Terapia com Prótons/métodos , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Ensaios Clínicos como Assunto , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/terapia , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
AIM: To assess the feasibility of transferring to the University of Tsukuba Hospital for proton beam therapy (PBT) during intensive chemotherapy in children with Ewing sarcoma family of tumors (ESFT) who had been diagnosed and started their first-line treatment at prefectural or regional centers for pediatric oncology. BACKGROUND: The treatment of ESFT relies on a multidisciplinary approach using intensive neoadjuvant and adjuvant chemotherapies with surgery and radiotherapy. Multi-agent chemotherapy comprising vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide (VDC-IE) is widely used for ESFT, and the interval between each course is very important for maintaining the intensity and effect of chemotherapy. MATERIALS AND METHODS: Clinical information of patients who received PBT and VDC-IE between April 2009 and May 2016 was collected retrospectively. The intervals between each course of VDC-IE and adverse events were assessed. RESULTS: Fifteen patients were evaluated. No delays in the intervals of chemotherapy due to transfer were observed. There were no adverse events caused during/just after transfer and no increases in adverse events. The estimated 4-year overall and event-free survival rates were 94.6% and 84.8%, respectively. DISCUSSION: Although the results of efficacy are preliminary, survival rates were comparable with past studies. More experience and follow-up are required to further assess the efficacy of PBT for patients with ESFT. CONCLUSION: Multidisciplinary therapy for children with ESFT involving transfer to our hospital for PBT during VDC-IE was feasible without treatment delay or an increase in adverse events.
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We conducted a retrospective, nationwide multicenter study to evaluate the clinical outcomes of proton beam therapy for bone sarcomas of the skull base and spine in Japan. Eligibility criteria included: (i) histologically proven bone sarcomas of the skull base or spine; (ii) no metastases; (iii) ≥20 years of age; and (iv) no prior treatment with radiotherapy. Of the 103 patients treated between January 2004 and January 2012, we retrospectively analyzed data from 96 patients who were followed-up for >6 months or had died within 6 months. Seventy-two patients (75.0%) had chordoma, 20 patients (20.8%) had chondrosarcoma, and four patients (7.2%) had osteosarcoma. The most frequent tumor locations included the skull base in 68 patients (70.8%) and the sacral spine in 13 patients (13.5%). Patients received a median total dose of 70.0 Gy (relative biological effectiveness). The median follow-up was 52.6 (range, 6.3-131.9) months. The 5-year overall survival, progression-free survival, and local control rates were 75.3%, 49.6%, and 71.1%, respectively. Performance status was a significant factor for overall survival and progression-free survival, whilst sex was a significant factor for local control. Acute Grade 3 and late toxicities of ≥Grade 3 were observed in nine patients (9.4%) each (late Grade 4 toxicities [n = 3 patients; 3.1%]). No treatment-related deaths occurred. Proton beam therapy is safe and effective for the treatment of bone sarcomas of the skull base and spine in Japan. However, larger prospective studies with a longer follow-up are warranted.
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Neoplasias Ósseas/radioterapia , Sarcoma/radioterapia , Base do Crânio/efeitos da radiação , Coluna Vertebral/efeitos da radiação , Neoplasias Ósseas/patologia , Intervalo Livre de Doença , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Terapia com Prótons/métodos , Dosagem Radioterapêutica , Estudos Retrospectivos , Sarcoma/patologia , Base do Crânio/patologia , Coluna Vertebral/patologiaRESUMO
Proton beam therapy (PBT) is a potential new alternative to treatment with photon radiotherapy that may reduce the risk of late toxicity and secondary cancer, especially for pediatric tumors. The goal of this study was to evaluate the long-term benefits of PBT in cancer survivors. A retrospective observational study of pediatric patients who received PBT was performed at four institutions in Japan. Of 343 patients, 62 were followed up for 5 or more years. These patients included 40 males and 22 females, and had a median age of 10 years (range: 0-19 years) at the time of treatment. The irradiation dose ranged from 10.8 to 81.2 GyE (median: 50.4 GyE). The median follow-up period was 8.1 years (5.0-31.2 years). The 5-, 10- and 20-year rates for grade 2 or higher late toxicities were 18%, 35% and 45%, respectively, and those for grade 3 or higher late toxicities were 6%, 17% and 17% respectively. Univariate analysis showed that the irradiated site (head and neck, brain) was significantly associated with late toxicities. No malignant secondary tumors occurred within the irradiated field. The 10- and 20-year cumulative rates for all secondary tumors, malignant secondary tumors, and malignant nonhematologic secondary tumors were 8% and 16%, 5% and 13%, and 3% and 11%, respectively. Our data indicate that PBT has the potential to reduce the risk of late mortality and secondary malignancy. Longer follow-up is needed to confirm the benefits of PBT for pediatric tumors.
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Neoplasias Induzidas por Radiação/epidemiologia , Neoplasias/radioterapia , Terapia com Prótons/efeitos adversos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Japão/epidemiologia , Masculino , Dosagem Radioterapêutica , Estudos Retrospectivos , Inquéritos e Questionários , Adulto JovemRESUMO
Long-term efficacy of proton beam therapy (PBT) remains unclear for patients with previously untreated hepatocellular carcinoma (HCC). We aimed to study the long-term outcomes of PBT according to Barcelona Clinic Liver Cancer (BCLC) staging classifications in patients with previously untreated HCC. The major eligibility criteria of this observational study were an Eastern Cooperative Oncology Group performance status (PS) 0-2, Child-Pugh grade A or B, previously untreated HCC covered within an irradiation field, and no massive ascites. A total of 66.0-77.0 GyE was administered in 10-35 fractions. Local tumor control (LTC), defined as no progression in the irradiated field, progression-free survival (PFS), and overall survival (OS) were assessed according to BCLC staging. From 2002 to 2009 at our institution, 129 patients were eligible. The 5-year LTC, PFS, and OS rates were 94%, 28%, and 69% for patients with 0/A stage disease (n = 9/21), 87%, 23%, and 66% for patients with B stage disease (n = 34), and 75%, 9%, and 25% for patients with C stage disease (n = 65), respectively. The 5-year LTC and OS rates of 15 patients with tumor thrombi in major vessels were 90% and 34%, respectively. Multivariate analyses revealed that PS (0 versus 1-2) was a significant prognostic factor for OS. No grade 3 or higher adverse effects were observed. PBT showed favorable long-term efficacies with mild adverse effects in BCLC stage 0 to C, and can be an alternative treatment for localized HCC especially when accompanied with tumor thrombi. This study was registered with UMIN Clinical Trials Registry (UMIN000025342).
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Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/radioterapia , Terapia com Prótons/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/patologia , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Terapia com Prótons/efeitos adversos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: Understanding the irradiated area and dose correctly is important for the reirradiation of organs that deform after irradiation, such as the liver. We investigated the spatial registration error using the deformable image registration (DIR) software products MIM Maestro (MIM) and Velocity AI (Velocity). METHODS: Image registration of pretreatment computed tomography (CT) and posttreatment CT was performed in 24 patients with liver tumors. All the patients received proton beam therapy, and the follow-up period was 4-14 (median: 10) months. We performed DIR of the pretreatment CT and compared it with that of the posttreatment CT by calculating the dislocation of metallic markers (implanted close to the tumors). RESULTS: The fiducial registration error was comparable in both products: 0.4-32.9 (9.3 ± 9.9) mm for MIM and 0.5-38.6 (11.0 ± 10.0) mm for Velocity, and correlated with the tumor diameter for MIM (r = 0.69, P = 0.002) and for Velocity (r = 0.68, P = 0.0003). Regarding the enhancement effect, the fiducial registration error was 1.0-24.9 (7.4 ± 7.7) mm for MIM and 0.3-29.6 (8.9 ± 7.2) mm for Velocity, which is shorter than that of plain CT (P = 0.04, for both). CONCLUSIONS: The DIR performance of both MIM and Velocity is comparable with regard to the liver. The fiducial registration error of DIR depends on the tumor diameter. Furthermore, contrast-enhanced CT improves the accuracy of both MIM and Velocity. INSTITUTIONAL REVIEW BOARD APPROVAL: H28-102; July 14, 2016 approved.