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1.
Front Oncol ; 11: 772789, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34796118

RESUMO

Brain metastases (BMs) represent the most frequent event during the course of Non-Small Cell Lung Cancer (NSCLC) disease. Recent advancements in the diagnostic and therapeutic procedures result in increased incidence and earlier diagnosis of BMs, with an emerging need to optimize the prognosis of these patients through the adoption of tailored treatment solutions. Nowadays a personalized and multidisciplinary approach should rely on several clinical and molecular factors like patient's performance status, extent and location of brain involvement, extracranial disease control and the presence of any "druggable" molecular target. Radiation therapy (RT), in all its focal (radiosurgery and fractionated stereotactic radiotherapy) or extended (whole brain radiotherapy) declinations, is a cornerstone of BMs management, either alone or combined with surgery and systemic therapies. Our review aims to provide an overview of the many modern RT solutions available for the treatment of BMs from NSCLC in the different clinical scenarios (single lesion, oligo and poly-metastasis, leptomeningeal carcinomatosis). This includes a detailed review of the current standard of care in each setting, with a presentation of the literature data and of the possible technical solutions to offer a "state-of-art" treatment to these patients. In addition to the validated treatment options, we will also discuss the future perspectives on emerging RT technical strategies (e.g., hippocampal avoidance whole brain RT, simultaneous integrated boost, radiosurgery for multiple lesions), and present the innovative and promising findings regarding the combination of novel targeted agents such as tyrosine kinase inhibitors and immune checkpoint inhibitors with brain irradiation.

2.
Blood Adv ; 5(21): 4504-4514, 2021 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-34597375

RESUMO

The role of consolidation radiotherapy (RT) for bulky lesions is controversial in patients with advanced-stage Hodgkin lymphoma who achieve complete metabolic response (CMR) after doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD)-based chemotherapy. We present the final results of the Fondazione Italiana Linfomi HD0801 trial, which investigated the potential benefit of RT in that setting. In this phase 3 randomized study, patients with a bulky lesion at baseline (a mass with largest diameter ≥5 cm) who have CMR after 2 and 6 ABVD cycles were randomly assigned 1:1 to RT vs observation (OBS) with a primary endpoint of event-free survival (EFS) at 2 years. The sample size was calculated estimating an EFS improvement for RT of 20% (from 60% to 80%). The secondary end point was progression-free survival (PFS). One hundred sixteen patients met the inclusion criteria and were randomly assigned to RT or OBS. Intention-to-treat (ITT) analysis showed a 2-year EFS of 87.8% vs 85.8% for RT vs OBS (hazard ratio [HR], 1.5; 95% confidence interval [CI], 0.6-3.5; P = .34). At 2 years, ITT-PFS was 91.3% vs 85.8% (HR, 1.2; 95% CI, 0.5-3; P = .7). Patients in CMR randomly assigned to OBS had a good outcome, and the primary end point of a 20% benefit in EFS for RT was not met. However, the sample size was underpowered to detect a benefit of 10% or less, keeping open the question of a potential, more limited role of RT in this setting. This trial was registered at www.clinicaltrials.gov as #NCT00784537.


Assuntos
Doença de Hodgkin , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina , Dacarbazina/uso terapêutico , Doxorrubicina/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/radioterapia , Humanos , Estadiamento de Neoplasias , Vimblastina/uso terapêutico
3.
Br J Radiol ; 94(1127): 20210618, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34677090

RESUMO

In the last decades, the substantial technical progress in radiation oncology offered the opportunity for more accurate planning and delivery of treatment. At the same time, the evolution of systemic treatment and the advent of modern diagnostic tools allowed for more accurate staging and consequently a safe reduction of radiotherapy (RT) target volumes and RT doses in the treatment of lymphomas. As a result, incidental irradiation of organs at risk was reduced, with a consequent reduction of severe late toxicity in long-term lymphoma survivors. Nevertheless, these innovations warrant that professionals pay attention to concurrently ensure precise planning and dose delivery to the target volume and safe sparing of the organs at risk. In particular, target and organ motion should be carefully managed in order to prevent any compromise of treatment efficacy. Several aspects should be taken into account during the treatment pathway to minimise uncertainties and to apply a valuable motion management strategy, when needed. These include: reliable image registration between diagnostic and planning radiologic exams to facilitate the contouring process, image guidance to limit positioning uncertainties and to ensure the accuracy of dose delivery and management of lung motion through procedures of respiratory gating and breath control. In this review, we will cover the current clinical approaches to minimise these uncertainties in patients treated with modern RT techniques, with a particular focus on mediastinal lymphoma. In addition, since uncertainties have a different impact on the dose deposition of protons compared to conventional x-rays, the role of motion management and position verification in proton beam therapy (PBT) will be discussed in a separate section.


Assuntos
Linfoma/radioterapia , Órgãos em Risco/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Suspensão da Respiração , Humanos , Linfoma/diagnóstico por imagem , Movimento (Física)
4.
Hematol Rep ; 13(2): 9080, 2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34221295

RESUMO

The rate of complete remission (CR) with the anti-PD1 immune checkpoint inhibitors (ICI) nivolumab (N) and pembrolizumab (P) in patients with relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL) is low (20-30%), and the majority of patients eventually relapse. One strategy to improve their outcome is to combine ICI with radiotherapy (ICI-RT), taking advantage of a supposed synergistic effect. We retrospectively collected data of 12 adult patients with R/R cHL treated with ICI-RT delivered during or within 8 weeks from the start or after the end of ICI. Median age at ICI-RT was 37 years, 50% had previously received an autologous stem cell transplantation (SCT) and 92% brentuximab vedotin. RT was given concurrently, before or after ICI in 4, 1 and 7 patients. Median RT dose was 30Gy, for a median duration of 22 days. Median number of ICI administrations was 15. Overall response and CR rate were 100% and 58%. Nine patients received subsequent SCT consolidation (7 allogeneic and 2 autologous). After a median follow-up of 18 months, 92% of patients were in CR. No major concerns about safety were reported. ICI-RT combination appears to be a feasible and highly active bridge treatment to transplant consolidation.

5.
Br J Radiol ; 94(1123): 20210012, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34111959

RESUMO

OBJECTIVES: To investigate the efficacy of a schedule of low-dose radiotherapy (LDRT) with 4 Gy (2 Gy x 2) in a cohort of unselected MALT or MZL patients. METHODS: We retrospectively collected all patients receiving LDRT, either for cure or palliation, for a stage I-IV histologically proven MALT or MZL between 2016 and 2020. Response to LDRT was evaluated with the Lugano criteria. Local control (LC), distant relapse-free survival (DRFS), progression-free survival (PFS) and overall survival (OS) were stratified for treatment intent (curative vs palliative) and estimated by the Kaplan-Meier product-limit. RESULTS: Among 45 consecutively enrolled patients with a median age of 68 years (range 22-86), 26 (58%) were female. Thirty-one patients (69%) with a stage I-II disease received LDRT as first line therapy and with a curative intent. Overall response rate was 93%, with no significant difference among curative and palliative intent. With a median follow-up of 18 months, LC, DRFS, PFS and OS at 2 years were 93, 92, 76 and 91%, respectively, in the overall population. Patients receiving curative LDRT had a better PFS at 2 years (85% vs 54%, p < 0.01) compared to patients receiving palliative treatment. LDRT was well tolerated in all patients, without any significant acute or chronic side-effect. CONCLUSIONS: LDRT is effective and well tolerated in patients affected with MALT or nodal MZL, achieving high response rates and durable remission at 2 years. ADVANCES IN KNOWLEDGE: This study shows the efficacy of LDRT in the treatment of MALT and MZL.


Assuntos
Linfoma de Zona Marginal Tipo Células B/radioterapia , Dosagem Radioterapêutica , Adulto , Feminino , Humanos , Linfoma de Zona Marginal Tipo Células B/mortalidade , Linfoma de Zona Marginal Tipo Células B/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Cuidados Paliativos , Estudos Retrospectivos , Taxa de Sobrevida
6.
Front Horm Res ; 54: 115-129, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33556955

RESUMO

Long-term cancer survivors are at high risk of developing cardiac complications from the treatments, both systemic agents and thoracic irradiation, received to cure the primary tumor. Modern advances, particularly in the field of radiotherapy, aim to reduce the risk of cardiovascular disease. Also, new diagnostic tools increasingly improve their efficacy in early detection of the preclinical treatment-induced cardiac damage. In this review, we summarize the mechanisms of radiotherapy- and chemotherapy-induced cardiac injury, the available clinical data, the strategies to mitigate cardiac exposure with modern radiotherapy and the current diagnostic tools for an early detection and prompt management of these complications in long-term cancer survivors.

7.
Radiother Oncol ; 156: 193-198, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33387584

RESUMO

BACKGROUND AND PURPOSE: The prevalence of patients with a cardiac implantable device (CIED) developing cancer and requiring a course of radiotherapy (RT) is increasing remarkably. Previously published reports agree that standard and conventionally fractionated RT is usually safe for CIEDs, but no "in-vivo" reports are available on the potential effects of thoracic stereotactic ablative radiotherapy (SABR) regimens to CIEDs functioning. The purpose of our study is therefore to evaluate the effects of SABR on CIEDs (pacemakers [PM] or implantable cardiac defibrillators [ICD]) in a cohort of patients affected by primary or metastatic lung lesions. MATERIALS AND METHODS: We retrospectively collected all CIED-bearing patients undergoing SABR between 2007 and 2019 at our Institution. All CIEDs were interrogated before and after the SABR course to check for any malfunction. Prescription dose, beam energy and maximum dose (Dmax) to CIEDs were retrieved for each patient. Electrical records of the CIEDs were reviewed by the medical records. RESULTS: Thirty-four consecutive patients (24 with a PM and 10 with an ICD), who underwent 38 separate SABR courses, were included in the study. Eight patients (24%) were PM-dependent. Prescription dose of SABR ranged 26-60 Gy in 1-8 fractions, with a photon energy ranging 6-to-10 MV (76.3% and 23.7%, respectively) and a median Dmax to CIEDs of 0.17 Gy (range 0.04-1.97 Gy). Electrical parameters were stable in post-treatment device programming visits and no transient or persistent alteration of the CIED function was recorded in any patient. No inappropriate interventions were recorded in the 10 ICD-bearing patients during the treatment fractions. CONCLUSIONS: Thoracic SABR proved to be safe for CIEDs when the dose is kept <2 Gy and the beam energy is ≤10 MV, irrespective of the pacing-dependency and of the CIED type.


Assuntos
Desfibriladores Implantáveis , Marca-Passo Artificial , Eletrônica , Humanos , Pulmão , Estudos Retrospectivos
8.
Clin Lymphoma Myeloma Leuk ; 21(4): e309-e316, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33257284

RESUMO

Post-transplant lymphoproliferative disorder (PTLD) is an aggressive malignancy that occurs in patients who have undergone solid organ transplantation or hematopoietic stem cell transplantation. It develops as the result of uncontrolled cell proliferations owing to reduced immunological surveillance. PTLD may occur with a various spectrum of clinical presentations, including both localized and extensive disease. Management can be significantly variable according both to the clinical presentation and to the histologic features. The most important systemic treatment strategies are reduction of immunosuppressive therapy, chemotherapy, anti B-cell antibodies, especially rituximab and cytokine-based therapies. The localized form of PTLD could be efficiently treated, and potentially cured, with surgery or radiotherapy (RT). Involved site RT may be a feasible effective option for the treatment of patients with PTLD, given the excellent radio-sensitivity of lymphoid disorders. In this report, we describe 3 adult patients with PTLD treated with moderate-dose RT (24-36 Gy) having a good local control with negligible toxicity. We also review the literature data on the role of radiation therapy in this particular setting.

9.
Pract Radiat Oncol ; 11(1): 66-73, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32565414

RESUMO

PURPOSE: Mediastinal radiation therapy (RT) in patients with lymphoma implies involuntary coronary artery (CA) exposure, resulting in an increased risk of coronary artery disease (CAD). Accurate delineation of CAs may spare them from higher RT doses. However, heart motion affects the estimation of the dose received by CAs. An expansion margin (planning organ at risk volume [PRV]), encompassing the nearby area where CAs displace, may compensate for these uncertainties, reducing CA dose and CAD risk. Our study aimed to evaluate if a planning process optimized on CA-specific PRVs, rather than just on CAs, could provide any dosimetric or clinical benefit. METHODS AND MATERIALS: Forty patients receiving RT for mediastinal lymphomas were included. We contoured left main trunk, left anterior descending, left circumflex, and right coronary arteries. An isotropic PRV was then applied to all CAs, in accordance with literature data. A comparison was then performed by optimizing treatment plans either on CAs or on PRVs, to detect any difference in CA sparing in terms of maximum (Dmax), median (Dmed), and mean (Dmean) dose. We then investigated, through risk modeling, if any dosimetric benefit obtained with the PRV-related optimization process could translate to a lower risk of ischemic complications. RESULTS: Plan optimization on PRVs demonstrated a significant dose reduction (range, 7%-9%) in Dmax, Dmed, and Dmean for the whole coronary tree, and even higher dose reductions when vessels were located 5- to 20-mm from PTV (range, 13%-15%), especially for left main trunk and left circumflex (range, 16%-21%). This translated to a mean risk reduction of developing CAD of 12% (P < .01), which increased to 17% when CAs were located 5- to 20-mm from PTV. CONCLUSIONS: Integration of CA-related PRVs in the optimization process reduces the dose received by CAs and translates to a meaningful prevention of CAD risk in patients with lymphoma treated with mediastinal RT.


Assuntos
Doenças Cardiovasculares , Linfoma , Radioterapia de Intensidade Modulada , Vasos Coronários/diagnóstico por imagem , Coração , Humanos , Linfoma/radioterapia , Órgãos em Risco , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador
10.
Blood Adv ; 4(9): 2064-2072, 2020 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-32396621

RESUMO

Controversy exists regarding the definition and prognostic significance of bulk in advanced-stage (stage III/IV) Hodgkin lymphoma (ASHL), and bulk location (mediastinum vs other sites) further complicated the setting. This retrospective, multi-institutional study comprised 814 ASHL patients between 2000 and 2010 and aimed to evaluate the significance of bulk in ASHL. End points of interest included progression-free survival (PFS) and overall survival (OS). Covariates included maximum diameter and the site of bulky disease. SmoothHR and Kaplan-Meier analyses were used to assess for an association of PFS and OS with covariates. In the exploratory cohort (n = 683), maximum diameter had no association with PFS and a complex, U-shaped association with all-cause mortality on smoothHR analysis. Using 5 cm as a cutoff for bulk, Kaplan-Meier analyses confirmed the smoothHR results. The site of bulk was incorporated to divide patients into 2 groups. The mediastinal bulk (MB) type had more favorable characteristics than the nonbulky/non-MB (NB/NMB) type on age, histology, and bone marrow involvement (P < .001). The MB type was associated with better OS than the NB/NMB-type on univariable analysis (5-year OS, 92% vs 86%; HR, 0.53; 95% confidence interval, 0.34-0.84; P = .007). These findings persisted in the subgroup treated with chemotherapy alone and were confirmed in an independent validation cohort (n = 131). Our findings indicate that mediastinal bulk was associated with more favorable disease characteristics and improved OS in ASHL, and may be a surrogate of a more favorable biology.


Assuntos
Doença de Hodgkin , Protocolos de Quimioterapia Combinada Antineoplásica , Intervalo Livre de Doença , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/tratamento farmacológico , Humanos , Prognóstico , Estudos Retrospectivos
11.
Blood ; 135(26): 2365-2374, 2020 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-32211877

RESUMO

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is an uncommon histologic variant, and the optimal treatment of stage I-II NLPHL is undefined. We conducted a multicenter retrospective study including patients ≥16 years of age with stage I-II NLPHL diagnosed from 1995 through 2018 who underwent all forms of management, including radiotherapy (RT), combined modality therapy (CMT; RT+chemotherapy [CT]), CT, observation after excision, rituximab and RT, and single-agent rituximab. End points were progression-free survival (PFS), freedom from transformation, and overall survival (OS) without statistical comparison between management groups. We identified 559 patients with median age of 39 years: 72.3% were men, and 54.9% had stage I disease. Median follow-up was 5.5 years (interquartile range, 3.1-10.1). Five-year PFS and OS in the entire cohort were 87.1% and 98.3%, respectively. Primary management was RT alone (n = 257; 46.0%), CMT (n = 184; 32.9%), CT alone (n = 47; 8.4%), observation (n = 37; 6.6%), rituximab and RT (n = 19; 3.4%), and rituximab alone (n = 15; 2.7%). The 5-year PFS rates were 91.1% after RT, 90.5% after CMT, 77.8% after CT, 73.5% after observation, 80.8% after rituximab and RT, and 38.5% after rituximab alone. In the RT cohort, but not the CMT cohort, variant immunoarchitectural pattern and number of sites >2 were associated with worse PFS (P < .05). Overall, 21 patients (3.8%) developed large-cell transformation, with a significantly higher transformation rate in those with variant immunoarchitectural pattern (P = .049) and number of involved sites >2 (P = .0006). OS for patients with stage I-II NLPHL was excellent after all treatments.


Assuntos
Doença de Hodgkin/patologia , Adulto , Idoso , Terapia Combinada/efeitos adversos , Feminino , Seguimentos , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/terapia , Humanos , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/epidemiologia , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Induzidas por Radiação/epidemiologia , Neoplasias Induzidas por Radiação/etiologia , Segunda Neoplasia Primária/epidemiologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Recidiva , Estudos Retrospectivos , Terapia de Salvação , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
12.
Radiat Oncol ; 15(1): 62, 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32164700

RESUMO

AIM: Advances in therapy have resulted in improved cure rates and an increasing number of long-term Hodgkin's lymphoma (HL) survivors. However, radiotherapy (RT)-related late effects are still a significant issue, particularly for younger patients with mediastinal disease (secondary cancers, heart diseases). In many Centers, technological evolution has substantially changed RT planning and delivery. This consensus document aims to analyze the current knowledge of Intensity-Modulated Radiation Therapy (IMRT) and Image-Guided Radiation Therapy (IGRT) for mediastinal HL and formulate practical recommendations based on scientific evidence and expert opinions. METHODS: A dedicated working group was set up within the Fondazione Italiana Linfomi (FIL) Radiotherapy Committee in May 2018. After a first meeting, the group adopted a dedicated platform to share retrieved articles and other material. Two group coordinators redacted a first document draft, that was further discussed and finalized in two subsequent meetings. Topics of interest were: 1) Published data comparing 3D-conformal radiotherapy (3D-CRT) and IMRT 2) dose objectives for the organs at risk 3) IGRT protocols and motion management. RESULTS: Data review showed that IMRT might allow for an essential reduction in the high-dose regions for all different thoracic OAR. As very few studies included specific dose constraints for lungs and breasts, the low-dose component for these OAR resulted slightly higher with IMRT vs. 3D-CRT, depending on the technique used. We propose a set of dose objectives for the heart, breasts, lungs, and thyroid. The use of IGRT is advised for margin reduction without specific indications, such as the use of breath-holding techniques. An individual approach, including comparative planning and considering different risk factors for late morbidity, is recommended for each patient. CONCLUSIONS: As HL therapy continues to evolve, with an emphasis on treatment reduction, radiation oncologists should use at best all the available tools to minimize the dose to organs at risk and optimize treatment plans. This document provides indications on the use of IMRT/IGRT based on expert consensus, providing a basis for clinical implementation and future development.


Assuntos
Consenso , Doença de Hodgkin/radioterapia , Neoplasias do Mediastino/radioterapia , Guias de Prática Clínica como Assunto/normas , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Guiada por Imagem/métodos , Radioterapia de Intensidade Modulada/métodos , Doença de Hodgkin/patologia , Humanos , Neoplasias do Mediastino/patologia , Prognóstico , Dosagem Radioterapêutica
13.
Int J Cardiol ; 300: 73-79, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31619362

RESUMO

BACKGROUND: Cystatin C (CyC) role in the detection of contrast induced acute kidney injury (CIAKI) is controversial. This study assessed whether a single CyC determination before coronary angiography (CA)could predict CIAKI and long-term adverse events. METHODS: CyC was assessed before CA in 713 consecutive patients. CIAKI was the primary endpoint, defined as ≥0.3 mg/dl creatinine (sCR) increase at 48 h or ≥50% in 7-days. All-cause death, cardiovascular (CV)death and MACE (acute coronary syndrome, acute pulmonary edema,CV death) were secondary endpoints. Re-hospitalization, in-hospital death and worsening renal function were tertiary endpoints. RESULTS: CIAKI occurred in 47 (6.7%) patients. ROC analysis showed a good accuracy of CyC in the prediction of CIAKI (AUC 0.82,p < 0.01), compared with baseline sCR and sCR-eGFR (AUC 0.70 and 0.75 respectively, both p < 0.01). CyC was associated with 10-year CV-death, all-cause death and MACEs (AUC 0.76,0.74 and 0.64 respectively,all p < 0.01). A CyC cut-off value of 1.4 mg/L was not only accurate in predicting or ruling-out CIAKI following CA (97% negative predictive value, 84% specificity), but also useful as a prognostic marker for 10-year adverse events (50% vs.16% all cause mortality, 29% vs.3% CV death, 39% vs.13% MACE,all p < 0.01), re-hospitalizations (54% vs.35%,p < 0.01) and worsening renal function (34% vs.19%,p < 0.01). The strongest and independent risk factor for 10-year CV death was baseline CyC>1.4 mg/L (HR 17.3, 95% CI 1.94-155.1). CONCLUSIONS: A baseline determination of CyC before CA can accurately rule out CIAKI and predict adverse events in the long term. CIAKI can be ruled out before CA in 97% patients with a CyC value < 1.4 mg/L.


Assuntos
Injúria Renal Aguda/sangue , Injúria Renal Aguda/diagnóstico por imagem , Meios de Contraste/efeitos adversos , Angiografia Coronária/tendências , Cistatina C/sangue , Injúria Renal Aguda/induzido quimicamente , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Coortes , Angiografia Coronária/métodos , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Taxa de Filtração Glomerular/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Tempo
14.
Phys Imaging Radiat Oncol ; 16: 50-53, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33458343

RESUMO

While proton therapy offers an excellent dose conformity and sparing of organs at risk, this can be compromised by uncertainties, e.g. organ motion. This study aimed to investigate the influence of cardiac motion on the contoured oesophagus using electrocardiogram-triggered imaging and to assess the impact of this motion on the robustness of proton therapy plans in oesophageal cancer patients. Limited cardiac-induced motion of the oesophagus was observed with a negligible impact on the robustness of proton therapy plans. Therefore, our data suggest that cardiac motion may be safely ignored in the robust optimisation strategy for proton planning in oesophageal cancer.

15.
Onco Targets Ther ; 12: 8033-8046, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632057

RESUMO

The combination of brief chemo-radiotherapy provides high cure rates and represents the first line of treatment for many lymphoma patients. As a result, a high proportion of long-term survivors may experience treatment-related toxic events many years later. Excess and unintended radiation dose to organs at risk (particularly heart, lungs and breasts) may translate in an increased risk of cardiovascular events and second cancers after a few decades. Minimizing dose to organs at risk is thus pivotal to restrain the risk of long-term complications. Proton therapy, with its peculiar physic properties, may help to better spare organs at risk and consequently to reduce toxicities especially in patients receiving mediastinal radiotherapy. Herein, we review the physical basis of proton therapy and the rationale for its implementation in lymphoma patients, with a detailed description of the clinical data. We also discuss the potential disadvantages and uncertainties of protons that may limit their application and critically review the dosimetric studies comparing the risk of late complications between proton and photon radiotherapy.

16.
Radiother Oncol ; 138: 52-58, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31146071

RESUMO

BACKGROUND AND PURPOSE: Radiotherapy is an effective treatment for Hodgkin's lymphoma (HL), but increases the risk of long term complications as cardiac events and second cancers. This study aimed to reduce the risk of cardiovascular events through an optimization of the dose distribution on heart substructures in mediastinal HL patients with the adoption of different volumetric modulated arc therapy (VMAT) techniques, while maintaining the same risk of second cancer induction on lungs and breasts. MATERIALS AND METHODS: Thirty patients (15 males and 15 females, 15 bulky lesions) treated between 2012 and 2017 at our institution were selected. Disease extent was mediastinum plus neck (n = 10), mediastinum plus unilateral axilla (n = 10) and mediastinum alone (n = 10). Lungs, breasts, whole heart and sub-structures (coronary arteries, valves and chambers) were contoured as organs at risk and included in the optimization process. A "first-generation" multi-arc butterfly VMAT (B-VMAT) planning solution was compared to a full-arc butterfly VMAT (FaB-VMAT) approach, consisting of a full arc plus a non-coplanar arc. Lifetime attributable risk (LAR) of second breast and lung cancer and relative risk (RR) of coronary artery disease (CAD) and chronic heart failure (CHF) were estimated. RESULTS: FaB-VMAT resulted in lower mean dose to whole heart (7.6 vs 6.9 Gy, p = 0.003), all coronary arteries (16.1 vs 13.5 Gy, p < 0.001), left ventricle (4.2 vs 3.4 Gy, p = 0.007) and in lower V20Gy to the lungs (15% vs 14%, p = 0.008). A significant lower RR for CAD and CHF was observed for FaB-VMAT. The risk of second breast and lung cancer was comparable between the two solutions, with the exception of female patients with mediastinal bulky involvement, where B-VMAT resulted in lower mean dose (2.8 vs 3.5 Gy, p = 0.03) and V4Gy (22% vs 16%, 0.04) to breasts, with a significant reduction in LAR (p = 0.03). CONCLUSIONS: FaB-VMAT significantly decreased the RR for CAD and CHF compared to B-VMAT, with almost the same overall risk of lung and breast cancer induction. These results are influenced by the different anatomical presentations, supporting the need for an individualized approach.


Assuntos
Cardiopatias/prevenção & controle , Coração/efeitos da radiação , Doença de Hodgkin/radioterapia , Radioterapia de Intensidade Modulada/métodos , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/efeitos adversos , Adulto Jovem
17.
Radiol Med ; 124(8): 777-782, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31104276

RESUMO

Radiotherapy is one of the primary treatment options in cancer management. Modern radiotherapy includes complex processes requiring many different kinds of expertise. Among them, knowledge and skills are needed in clinical oncology, radiobiology, radiotherapy planning and simulation, dose measurement and calculation, radiation safety and medical physics. Radiation oncologists should assume the full and final responsibility for treatment, follow-up and supportive care of the patient. For all these activities, radiation oncologist should coordinate and collaborate with a team including different professionals: nurses, radiographers (RTT), clinical engineers, information system experts, taking advantage in particular of the dosimetry expertise of the medical physicist. Radiation therapy is widely recognized to be one of the safest areas of modern medicine, and errors are very rare. However, radiation protection recommendations developed at national level should comply with the EURATOM Directive 2013/59. This paper describes several contemporary and emerging concerns related to radioprotection in radiation therapy including quality and safety in external beam radiotherapy and brachytherapy, foetal dose, secondary malignancies, and the safety issues related to the new techniques and treatment strategies.


Assuntos
Neoplasias/radioterapia , Exposição Ocupacional/prevenção & controle , Segurança do Paciente/normas , Exposição à Radiação/prevenção & controle , Proteção Radiológica/normas , Prevenção de Acidentes , Braquiterapia/efeitos adversos , Braquiterapia/métodos , Braquiterapia/normas , Criança , Competência Clínica , Feminino , Humanos , Oncologia/normas , Neoplasias Induzidas por Radiação/prevenção & controle , Gravidez , Proteção Radiológica/métodos , Radioterapia/efeitos adversos , Radioterapia/métodos , Radioterapia/normas , Risco , Gestão da Segurança
18.
Int J Radiat Oncol Biol Phys ; 104(3): 522-529, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30858143

RESUMO

PURPOSE: We previously reported that ∼30% of patients with localized follicular lymphoma (FL) staged by 18F-fluorodeoxyglucose positron emission tomography-computed tomography receiving primary radiation therapy (RT) will relapse within 5 years. We sought to report outcomes for those who relapsed. METHODS AND MATERIALS: We conducted a multicenter, retrospective study of patients aged ≥18 years who received RT ≥ 24 Gy for stage I to II, grade 1 to 3A FL, staged with 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography. Observation was defined as >6 months without treatment from relapse. Overall survival (OS) and freedom from progression (FFP) were estimated with Kaplan-Meier analysis and univariable and multivariable analyses with Cox regression. RESULTS: Of 512 patients with median follow-up of 52 months, 149 (29.1%) developed recurrent lymphoma at a median of 23 months (range, 1-143) after primary RT. Median follow-up was 33 months after relapse. Three-year OS was 91.4% after recurrence. OS was significantly worse for those with relapse ≤12 months from date of diagnosis versus all others-88.7% versus 97.6%, respectively (P = .01)-and remained significantly worse on multivariable analyses (follicular lymphoma international prognostic index-adjusted hazard ratio, 3.61; P = .009). Histology at relapse included 93 indolent (grade 1-3A), 3 FL grade 3B/not otherwise specified, and 18 diffuse large B-cell lymphoma; 35 patients did not undergo biopsy. Of those with follow-up ≥3 months who underwent biopsy (n = 74) or had presumed (n = 23) indolent recurrence, 58 patients (59.8%) were observed, 19 (19.6%) had systemic therapy, 16 (16.5%) had RT, and 4 (4.1%) had systemic therapy + RT. For patients with indolent recurrences that were observed, 3-year FFP or freedom from treatment was 56.6% (median, 48 months). For all patients with biopsied/presumed indolent recurrence receiving salvage treatment (n = 59, including 20 initially observed) 3-year FFP was 73.9%. CONCLUSIONS: Prognosis for patients with relapsed FL after primary radiation therapy is excellent, supporting the role of primary radiation in the management of early stage disease. Patients with localized FL treated with primary RT who experience early relapse (<12 months) have inferior survival compared with those with longer disease-free interval.


Assuntos
Linfoma Folicular/mortalidade , Linfoma Folicular/radioterapia , Terapia de Salvação , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/administração & dosagem , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Fluordesoxiglucose F18 , Humanos , Estimativa de Kaplan-Meier , Linfoma Folicular/diagnóstico por imagem , Linfoma Folicular/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prednisona/administração & dosagem , Intervalo Livre de Progressão , Compostos Radiofarmacêuticos , Recidiva , Estudos Retrospectivos , Rituximab/uso terapêutico , Fatores de Tempo , Vincristina/administração & dosagem , Conduta Expectante , Adulto Jovem
19.
Blood ; 133(3): 237-245, 2019 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-30446493

RESUMO

Radiotherapy (RT) can be curative in patients with localized follicular lymphoma (FL), with historical series showing a 10-year disease-free survival of 40 to 50%. As 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography with computerized tomography (PET-CT) upstages 10 to 60% of patients compared to CT, we sought to evaluate outcomes in patients staged by PET-CT, to determine if more accurate staging leads to better patient selection and results. We conducted a multicenter retrospective study under the direction of the International Lymphoma Radiation Oncology Group (ILROG). Inclusion criteria were: RT alone for untreated stage I to II FL (grade 1-3A) with dose equivalent ≥24 Gy, staged by PET-CT, age ≥18 years, and follow-up ≥3 months. End points were freedom from progression (FFP), local control, and overall survival (OS). A total of 512 patients treated between 2000 and 2017 at 16 centers were eligible for analysis; median age was 58 years (range, 20-90); 410 patients (80.1%) had stage I disease; median RT dose was 30 Gy (24-52); and median follow-up was 52 months (3.2-174.6). Five-year FFP and OS were 68.9% and 95.7%. For stage I, FFP was 74.1% vs 49.1% for stage II (P < .0001). Eight patients relapsed in-field (1.6%). Four had marginal recurrences (0.8%) resulting in local control rate of 97.6%. On multivariable analysis, stage II (hazard ratio [HR], 2.11; 95% confidence interval [CI], 1.44-3.10) and BCL2 expression (HR, 1.62; 95% CI, 1.07-2.47) were significantly associated with less favorable FFP. Outcome after RT in PET-CT staged patients appears to be better than in earlier series, particularly in stage I disease, suggesting that the curative potential of RT for truly localized FL has been underestimated.


Assuntos
Fluordesoxiglucose F18 , Linfoma Folicular/patologia , Recidiva Local de Neoplasia/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/normas , Compostos Radiofarmacêuticos , Radioterapia/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Linfoma Folicular/diagnóstico por imagem , Linfoma Folicular/radioterapia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/radioterapia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
20.
Radiother Oncol ; 127(3): 481-486, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29729845

RESUMO

BACKGROUND AND PURPOSE: Inadvertent heart and coronary arteries (CA) irradiation may increase the risk of coronary artery disease (CAD) in patients receiving thoracic irradiation. To date, the entity of cardiac-related CA displacement and the possible margins to be used for planning organs at risk volume (PRV) have been poorly described. Aim of this study was to quantify CA displacement and to estimate PRV through the use of ECG-gated computed tomography (CT) scans. MATERIAL AND METHODS: Eight patients received an ECG-gated intravenous contrast enhanced CT for non-cancer related reasons. Nine data sets were reconstructed over the entire R-R cycle with a dedicated retrospective algorithm and the following structures were delineated: Left main trunk (LM), left anterior descending (LAD), left circumflex (CX) and right coronary artery (RCA). CA displacements across the different cardiac phases were evaluated in left-right (X), cranio-caudal (Y) and anteroposterior (Z) directions using the McKenzie-van Herk formula (1.3 * Σ + 0.5 * σ). RESULTS: The following CA displacements were found in X, Y and Z coordinates: 3.6, 2.7 and 2.7 mm for LMT, respectively; 2.6, 5.0 and 6.8 mm for LAD, respectively; 3.5, 4.5 and 3.7 mm for CX, respectively; 3.6, 4.6 and 6.9 mm for RCA, respectively. Based on the mean displacements, we created a PRV of 3 mm for LM, 4 mm for CX and 5 mm for LAD and RCA. CONCLUSION: CA showed relevant displacements over the heart cycle, suggesting the need for a specific PRV margin to accurately estimate the dose received by these structures and optimize the planning process.


Assuntos
Vasos Coronários/diagnóstico por imagem , Eletrocardiografia/métodos , Coração/diagnóstico por imagem , Neoplasias do Mediastino/diagnóstico por imagem , Neoplasias do Mediastino/radioterapia , Planejamento da Radioterapia Assistida por Computador/métodos , Algoritmos , Doença da Artéria Coronariana , Vasos Coronários/anatomia & histologia , Vasos Coronários/efeitos da radiação , Coração/anatomia & histologia , Coração/efeitos da radiação , Humanos , Mediastino/anatomia & histologia , Mediastino/diagnóstico por imagem , Mediastino/efeitos da radiação , Movimento (Física) , Órgãos em Risco/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
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