RESUMO
PURPOSE: Secondary breast cancer is a frequent late adverse event of mediastinal Hodgkin lymphoma radiotherapy. Secondary breast cancers overwhelmingly correspond to ductal carcinoma and develop from the glandular mammary tissue. In addition, during childhood, radiation overexposure of the glandular tissue may lead to a late breast hypotrophy at adult age. The aim of this study was to evaluate the radiation exposure to the glandular tissue in patients treated for mediastinal Hodgkin lymphoma with intensity-modulated proton therapy, in order to evaluate the potential dosimetric usefulness of its delineation for breast sparing. MATERIALS AND METHODS: Sixteen consecutive intermediate-risk mediastinal female patients with Hodgkin lymphoma treated with consolidation radiation with deep inspiration breath hold intensity-modulated proton therapy to the total dose of 30Gy were included. Breasts were delineated according to the European Society for Radiotherapy and Oncology guidelines for treatment optimization (âÅclinical organ at riskâ?). The glandular tissue (âÅglandular organ at riskâ?) was retrospectively contoured on the initial simulation CT scans based on Hounsfield unit (HU) values, using a range between âÌ'80HU and 500HU. RESULTS: The mean and maximum doses delivered to the glandular organ at risk were significantly lower than the mean and maximum doses delivered to the clinical organ at risk, but were statistically correlated. Glandular organ at risk volumes were significantly smaller. CONCLUSION: Optimizing the treatment plans on the clinical breast contours will systematically lead to overestimation of the dose received to the glandular tissue and, consequently, to an indistinct and involuntary improved glandular tissue sparing. As such, our findings do not support the consideration of the glandular tissue as an additional organ at risk when planning intensity-modulated proton therapy for mediastinal Hodgkin lymphoma in female patients.
RESUMO
Because of the physical properties of proton beam radiation therapy (PT), which allows energy to be deposited at a specific depth with a rapid energy fall-off beyond that depth, PT has several theoretical advantages over photon radiation therapy for esophageal cancer (EC). Protons have the potential to reduce the dose to healthy tissue and to more safely allow treatment of tumors near critical organs, dose escalation, trimodal treatment, and re-irradiation. In recent years, larger multicenter retrospective studies have been published showing excellent survival rates, lower than expected toxicities and even better outcomes with PT than with photon radiotherapy even using IMRT or VMAT techniques. Although PT was associated with reduced toxicities, postoperative complications, and hospital stays compared to photon radiation therapy, these studies all had inherent biases in relation with patient selection for PT. These observations were recently confirmed by a randomized phase II study in locally advanced EC that showed significantly reduced toxicities with protons compared with IMRT. Currently, two randomized phase III trials (NRG-GI006 in the US and PROTECT in Europe) are being conducted to confirm whether protons could become the standard of care in locally advanced and resectable esophageal cancers.
Assuntos
Neoplasias Esofágicas , Terapia com Prótons , Radioterapia de Intensidade Modulada , Reirradiação , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/radioterapia , Humanos , Terapia com Prótons/efeitos adversos , Prótons , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Estudos RetrospectivosRESUMO
PURPOSE: Protontherapy for mediastinal Hodgkin lymphoma reduces cardiac, lung and breast exposure, which may limit radiation-induced adverse events. While this technique is already widely implemented in the United-States, clinical experience is still limited in France. This study analyses the practice of mediastinal Hodgkin lymphoma protontherapy at the Institut Curie to implement this technique at a larger scale. MATERIALS AND METHODS: Data from all mediastinal Hodgkin lymphoma patients from the hematology department of the Institut Curie who were subsequently evaluated at the Protontherapy Center of Orsay (CPO) of Institut Curie for adjuvant protontherapy were retrieved. We analyzed why these patients were ultimately treated with protontherapy or not. RESULTS: Between January 2018 and January 2021, twenty mediastinal Hodgkin lymphoma patients from the hematology department of the Institut Curie have been screened for protontherapy at the CPO. Four of them (20%) were ultimately treated with proton beams. Treatment was well tolerated without grade 3-4 adverse events. With a median follow-up of two years, none of these patients relapsed. The others sixteen patients were not treated with protontherapy due to multiple reasons including: lack of treatment room disponibility, accessibility difficulties, psychiatric disorder, and anatomic or dosimetric considerations. CONCLUSION: Despite notable dosimetric superiority over photon radiotherapy and excellent clinical tolerance, lack of availability of protontherapy facilities limit implementation of mediastinal Hodgkin lymphoma protontherapy. Additionally, strict selection criteria must be defined.
Assuntos
Doença de Hodgkin/radioterapia , Neoplasias do Mediastino/radioterapia , Terapia com Prótons/métodos , Adolescente , Adulto , Mama/efeitos da radiação , Institutos de Câncer , Criança , Feminino , Seguimentos , França , Acessibilidade aos Serviços de Saúde , Coração , Humanos , Pulmão/efeitos da radiação , Masculino , Órgãos em Risco/efeitos da radiação , Terapia com Prótons/efeitos adversos , Terapia com Prótons/estatística & dados numéricos , Adulto JovemRESUMO
PURPOSE: Breast protontherapy efficiently limits cardiac, lung and contralateral breast exposure, which may clinically translate into better late tolerance profile compared with classic photon techniques. While breast protontherapy is already implemented in the United States and in some European countries, clinical experience of breast cancer protontherapy is currently limited in France. The aim of this study is to evaluate the clinical practice of breast cancer protontherapy at the Institut Curie in order to implement this technique at a larger scale. MATERIALS AND METHODS: Data from all breast cancer patients that have been addressed to the protontherapy centre of Orsay (CPO, Institut Curie) for adjuvant breast protontherapy were retrieved. We analysed why these patients were ultimately treated with protontherapy or not. RESULTS: Between November 2019 and November 2020, eleven breast cancer patients have been evaluated for adjuvant protontherapy at the CPO. Two of them were ultimately treated with proton beams; adjuvant breast protontherapy therapy was well tolerated. The nine other patients were not treated with protontherapy due to lack of availability of protontherapy treatment rooms in acceptable time limits, at the time of patient evaluation. CONCLUSION: Despite dosimetric advantages and excellent clinical tolerance, lack of availability of protontherapy machines currently limits wider implementation of breast protontherapy.
Assuntos
Neoplasias da Mama/radioterapia , Terapia com Prótons , Adulto , Fatores Etários , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/cirurgia , Cardiotoxicidade/prevenção & controle , Feminino , França , Genes BRCA1 , Humanos , Mutação , Seleção de Pacientes , Terapia com Prótons/estatística & dados numéricos , Lesões por Radiação/prevenção & controle , Radioterapia Adjuvante/estatística & dados numéricos , Radioterapia de Intensidade Modulada , Reirradiação , Estudos Retrospectivos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/radioterapia , Neoplasias de Mama Triplo Negativas/cirurgia , Neoplasias Unilaterais da Mama/tratamento farmacológico , Neoplasias Unilaterais da Mama/genética , Neoplasias Unilaterais da Mama/radioterapia , Neoplasias Unilaterais da Mama/cirurgia , Adulto JovemRESUMO
PURPOSE: The use of IMRT for the treatment of breast cancer has been growing considerably in our institution since 2009. Alternatively, helical tomotherapy (HT) using a field width of 2.5 and 5cm (HT_FW_5), volumetric-modulated arc therapy (VMAT), or proton therapy with pencil-beam scanning (PT-PBS) have also been used to reduce treatment duration or optimize organ-at-risk (OAR) sparing. The purpose of this study was to compare the 4 treatment modalities available at our site. PATIENTS AND METHODS: We studied 10 patients treated for breast cancer with lymph node involvement. The prescribed dose was 51.8Gy to the breast with a simultaneous integrated boost up to 63Gy, and 50.4Gy to lymph nodes in 28 fractions. The CTV was delineated according to ESTRO Guidelines. Dosimetric planning in routine clinical practice was performed using HT_FW_2.5. The approved clinical plan was compared to the 3 other plans. Dosimetric goals for PTV coverage were D95%≥95% and D2%≤107% of the prescribed dose. Mean and maximum doses to OAR were recorded. RESULTS: HT_FW_5 and VMAT plans ensure equivalent or even better PTV coverage compared to the initial clinically approved plan but at the cost of poorer OAR sparing. PT_PBS plans showed that an excellent PTV coverage can be maintained with significantly lower doses to OAR. CONCLUSION: HT_FW_5 and VMAT plans allow a significant reduction of treatment duration and can be a good alternative to HT_FW_2.5 for specific populations. HT_FW_2.5 could be chosen for patients at higher risk of side effects. In addition, PT_PBS should be considered in the near future as it has been shown to have a major potential benefit to lower the risk of side effects with the same level of PTV coverage.
Assuntos
Radioterapia de Intensidade Modulada/métodos , Neoplasias Unilaterais da Mama/radioterapia , Adulto , Mama/efeitos da radiação , Fracionamento da Dose de Radiação , Feminino , Coração/efeitos da radiação , Humanos , Pulmão/efeitos da radiação , Linfonodos/patologia , Irradiação Linfática , Órgãos em Risco/efeitos da radiação , Planejamento da Radioterapia Assistida por Computador/métodos , Neoplasias Unilaterais da Mama/diagnóstico por imagem , Neoplasias Unilaterais da Mama/patologiaRESUMO
The aim of this work is to perform Monte Carlo simulations of a proton pencil beam scanning machine, characterise the low-dose envelope of scanned proton beams and assess the differences between various approximations for nozzle geometry. Measurements and Monte Carlo simulations were carried out in order to describe the dose distribution of a proton pencil beam in water for energies between 100 and 220â¯MeV. Dose distributions were simulated by using a Geant4 Monte Carlo platform (TOPAS), and were measured in water using a two-dimensional ion chamber array detector. The beam source in air was adjusted for each configuration. Double Gaussian parameterisation was proposed for definition of the beam source model in order to improve simulations starting at the nozzle exit. Absolute dose distributions and field size factors were measured and compared with simulations. The influence of the high-density components present in the treatment nozzle was also investigated by analysis of proton phase spaces at the nozzle exit. An excellent agreement was observed between experimental dose distributions and simulations for energies higher than 160â¯MeV. However, minor differences were observed between 100 and 160â¯MeV, suggesting poorer modelling of the beam when the full treatment head was not taken into account. We found that the first ionisation chamber was the main cause of the tail component observed for low proton beam energies. In this work, various parameterisations of proton sources were proposed, thereby allowing reproduction of the low-dose envelope of proton beams and excellent agreement with measured data.
Assuntos
Método de Monte Carlo , Terapia com Prótons/métodos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por ComputadorRESUMO
Intensity-modulated radiation therapy (IMRT) is presently the recommended technique for the treatment of locally advanced head and neck carcinomas. Proton therapy would allow to reduce the volume of irradiated normal tissue and, thus, to decrease the risk of late dysphagia, xerostomia, dysgeusia and hypothyroidism. An exhaustive research was performed with the search engine PubMed by focusing on the papers about the physical difficulties that slow down use of proton therapy for head and neck carcinomas. Range uncertainties in proton therapy (±3 %) paradoxically limit the use of the steep dose gradient in distality. Calibration uncertainties can be important in the treatment of head and neck cancer in the presence of materials of uncertain stoichiometric composition (such as with metal implants, dental filling, etc.) and complex heterogeneities. Dental management for example may be different with IMRT or proton therapy. Some uncertainties can be somewhat minimized at the time of optimization. Inter- and intrafractional variations and uncertainties in Hounsfield units/stopping power can be integrated in a robust optimization process. Additional changes in patient's anatomy (tumour shrinkage, changes in skin folds in the beam patch, large weight loss or gain) require rescanning. Dosimetric and small clinical studies comparing photon and proton therapy have well shown the interest of proton therapy for head and neck cancers. Intensity-modulated proton therapy is a promising treatment as it can reduce the substantial toxicity burden of patients with head and neck squamous cell carcinoma compared to IMRT. Robust optimization will allow to perform an optimal treatment and to use proton therapy in current clinical practice.
Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Física Médica , Terapia com Prótons , Lesões por Radiação/prevenção & controle , Radioterapia (Especialidade) , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Pesquisa Translacional Biomédica , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/prevenção & controle , Disgeusia/etiologia , Disgeusia/prevenção & controle , Humanos , Hipotireoidismo/etiologia , Hipotireoidismo/prevenção & controle , Modelos Teóricos , Órgãos em Risco , Lesões por Radiação/etiologia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Radioterapia Guiada por Imagem , Radioterapia de Intensidade Modulada/efeitos adversos , Incerteza , Xerostomia/etiologia , Xerostomia/prevenção & controleRESUMO
The purpose of this work was reducing treatment-related toxicity for Hodgkin lymphomas using practical procedure inspired by the ILROG guidelines. Reporting the first case of localized Hodgkin lymphoma treated with protontherapy in France. A 24-year-old female with mediastinal, bulky, localized, mixed-cellularity, classic Hodgkin lymphoma required an involved-site radiation therapy after complete response following polychemotherapy. Three-dimensional conformal radiation therapy was not acceptable due to high doses to breasts, heart and lungs. We realized a four-dimensional computed tomography (CT) to evaluate target movements and another CT with gating and breath-hold technique. Delineation was performed on both CT using the initial fluorodeoxyglucose positron-emission tomography/CT. One dosimetric plan with rotational intensity-modulated radiation therapy with a helical Tomotherapy© was realized and compared to another one with conformational protontherapy. Ninety-five percent of the planning target volume was covered by 98 and 99% of the prescribed dose with protontherapy and helical Tomotherapy©. Protontherapy provided the best organ at risk protection. Lung and heart protections were better with protontherapy: lung mean dose (3.7Gy vs. 8.4Gy) and median dose (0.002Gy vs. 6.9Gy), heart mean dose (2.6Gy vs. 3.7Gy). Breast sparing was better for both breasts using protontherapy: right breast mean dose (2.4Gy vs. 4.4Gy) and left (1.9Gy vs. 4.6Gy). The biggest difference was seen with low doses, which were better with protontherapy: volume of lung receiving 5Gy was 17.5% vs. 54.2% with Helical Tomotherapy©. In view of these results, we decided to treat our patient with protontherapy using respiratory assessment. We delivered 30Gy (15 fractions) using protontherapy with one direct anterior field using pencil beam scanning and deep inspiration breath-hold technique. We observed only grade 1 skin erythema during treatment and no toxicity during early follow-up.
Assuntos
Doença de Hodgkin/radioterapia , Neoplasias do Mediastino/radioterapia , Fótons/uso terapêutico , Terapia com Prótons/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bleomicina/administração & dosagem , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Coração/diagnóstico por imagem , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/tratamento farmacológico , Humanos , Pulmão/diagnóstico por imagem , Neoplasias do Mediastino/diagnóstico por imagem , Neoplasias do Mediastino/tratamento farmacológico , Tratamentos com Preservação do Órgão/métodos , Órgãos em Risco/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Guias de Prática Clínica como Assunto , Prednisona/administração & dosagem , Procarbazina/administração & dosagem , Lesões por Radiação/prevenção & controle , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada , Vincristina/administração & dosagem , Adulto JovemRESUMO
PURPOSE: The aim of this study was to assess the treatment outcome and toxicity for patients with locally advanced nasopharyngeal carcinoma treated with a complementary dose with proton. PATIENTS AND METHODS: Between November 1999 and September 2016, 17 patients have been treated for a stage III-IVa nasopharyngeal carcinoma in the proton therapy centre of Curie Institute. Bilateral lymph node in the neck (I-V levels) received from 40 to 54Gy with photon beam. The primary tumor volume including microscopically extensions received a complementary dose with proton in order to reach the dose of 70 to 78Gy. All the patients received a concomitant chemotherapy. The end-points of the study were loco-regional control, survival, and treatment-related toxicity. RESULTS: Patients characteristics were: median age 49, 71 % male, 88% stage IVa, with a majority (82%) of T4N0M0. The median follow-up was 99 months. The 2-, 5- and 10-year actuarial locoregional free survival and overall survival were 94% and 88%, 86% and 74%, and 86% and 66%, respectively. The grade≥3 late adverse events were sphenoid bone radionecrosis (5.9%) and hearing loss (23.5%). CONCLUSION: This study showed that a complementary dose with proton seems to be a good option for the treatment of locally advanced nasopharyngeal carcinoma, particularly for T4N0M0.
Assuntos
Carcinoma de Células Escamosas/terapia , Neoplasias Nasofaríngeas/terapia , Terapia com Prótons , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , França , Perda Auditiva/etiologia , Humanos , Linfonodos/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Dosagem Radioterapêutica , Xerostomia/etiologia , Adulto JovemRESUMO
PURPOSE: We report the patient outcomes of a treatment combining proton therapy and Tomotherapy in sinonasal adenoid cystic carcinoma involving skull base. MATERIALS AND METHODS: We included patients treated at Curie Institute, Paris, France, between March 2010 and February 2014 for an advanced adenoid cystic carcinoma involving skull base. Patients received Tomotherapy, proton therapy or both. We evaluated treatment toxicity (according to CTCAE V4), local control, distant metastasis-free survival and overall survival. RESULTS: Thirteen patients were included, with a median follow-up of 34 months. Radiation therapy followed surgery for 77% of the patients and margins were positive in all those cases. Median dose was 73.8Gy. Local control, distant metastasis-free survival and overall survival at 3 years were respectively 60%, 48% and 60%. One-sided grade 3 hearing impairment occurred in 46% of the patients. CONCLUSION: Combining high-dose proton therapy and Tomotherapy is effective and has moderate toxicity in the treatment of T4 sinonasal adenoid cystic carcinoma involving skull base.
Assuntos
Carcinoma Adenoide Cístico/radioterapia , Neoplasias dos Seios Paranasais/radioterapia , Terapia com Prótons , Radioterapia Conformacional , Radioterapia de Intensidade Modulada , Neoplasias da Base do Crânio/radioterapia , Carcinoma Adenoide Cístico/diagnóstico por imagem , Carcinoma Adenoide Cístico/mortalidade , Feminino , Seguimentos , França/epidemiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Órgãos em Risco/diagnóstico por imagem , Neoplasias dos Seios Paranasais/diagnóstico por imagem , Neoplasias dos Seios Paranasais/mortalidade , Dosagem Radioterapêutica , Radioterapia Adjuvante , Radioterapia Guiada por Imagem , Estudos Retrospectivos , Neoplasias da Base do Crânio/diagnóstico por imagem , Neoplasias da Base do Crânio/mortalidadeRESUMO
PURPOSE: The aim of this study was to assess efficacy and safety of proton beam therapy of paragangliomas of the head and neck, rare benign tumours developed close to crucial structures such as cranial nerves and vascular tissues. PATIENTS AND METHODS: Ten patients with a paraganglioma of the head and neck were treated from 2001 to 2014 with image-guided proton therapy. Neurological and ear nose throat symptoms were collected in addition to audiometric testing, before and after the treatment. Acute and late toxicities were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v4. RESULTS: Median age at diagnosis was 52.6years (range: 18.2-65.8years). Proton therapy was the exclusive treatment in six patients and four patients had a postoperative radiotherapy. Median dose was 50.4Gy relative biological effectiveness (RBE; range: 45.0-67.0Gy). With a median follow-up of 24.6months (range: 6.7-46.2 months), local tumour control rate was 100% (stable, n=10). No upper grade 2 acute toxicity was reported. To the latest news, seven patients had controlled symptoms (improved, n=1, stabilized, n=6). One patient out of seven with initial tinnitus had a decrease in his symptoms, while the six other patients had a sustained stabilization. CONCLUSION: Proton beam therapy is an effective and well-tolerated treatment modality of skull base paragangliomas, with documented functional benefit. A longer follow-up is planned in order to assess local control and long-term toxicities.
Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Paraganglioma/radioterapia , Terapia com Prótons , Radioterapia Guiada por Imagem , Adolescente , Adulto , Idoso , Seguimentos , Humanos , Pessoa de Meia-Idade , Qualidade de Vida , Estudos Retrospectivos , Zumbido/etiologia , Zumbido/terapia , Adulto JovemRESUMO
Congenital toxoplasmosis is a potentially serious fetal infection associated with maternal seroconversion or a reactivation of toxoplasmosis during pregnancy. We report the case of congenital toxoplasmosis with severe neurological injury with normal prenatal obstetric ultrasounds in a mother infected with HIV at the AIDS stage and previously immunized against toxoplasmosis.