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2.
Haematologica ; 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34758610

RESUMO

Standard of care (SOC) chimeric antigen receptor (CAR) T-cell therapies such as axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are associated with multisystem toxicities. There is limited information available about cardiovascular (CV) events associated with SOC axi-cel or tisa-cel. Patients with CV comorbidities, organ dysfunction, or lower performance status were often excluded in the clinical trials leading to their FDA approval. An improved understanding of CV toxicities in the real-world setting will better inform therapy selection and management of patients receiving these cellular therapies. Here, we retrospectively reviewed the characteristics and outcomes of adult patients with relapsed/refractory large B-cell lymphoma treated with SOC axi-cel or tisa-cel. Among the 165 patients evaluated, 27 (16%) developed at least one 30-day Major adverse CV event (MACE). Cumulatively, these patients experienced 21 arrhythmias, 4 exacerbations of heart failure/cardiomyopathy, 4 cerebrovascular accidents, 3 myocardial infarctions (MI), and one patient died due to MI. Factors significantly associated with an increased risk of 30-d MACE included age ≥60 years, an earlier start of cytokine release syndrome (CRS), CRS ≥ grade 3, long duration of CRS, and use of tocilizumab. After a median follow-up time of 16.2 months (range 14.3-19.1), the occurrence of 30-d MACE was not significantly associated with progression-free survival (PFS) or with overall survival (OS). Our results suggest that the occurrence of 30-d MACE is more frequent among patients who are elderly, with early, severe, and prolonged CRS. However, with limited followup, larger prospective studies are needed, and multidisciplinary management of these patients is recommended.

3.
J Cancer Educ ; 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34601699

RESUMO

The role of radiation therapy (RT) varies across hematologic malignancies (HM). Radiation oncology (RO) resident comfort with specific aspects of HM patient management is unknown. The International Lymphoma RO Group (ILROG) assessed resident HM training opportunities and interest in an HM away elective. RO residents (PGY2-5) in the Association of Residents in RO (ARRO) database (n = 572) were emailed an anonymous, web-based survey in January 2019 including binary, Likert-type scale (1 = not at all, 5 = extremely, reported as median [interquartile range]), and multiple-choice questions. Of 134 resident respondents (23%), 86 (64%) were PGY4/5 residents and 36 (27%) were in larger programs (≥ 13 residents). Residents reported having specialized HM faculty (112, 84%) and a dedicated HM rotation (95, 71%). Residents reported "moderate" preparedness to advocate for RT in multidisciplinary conferences (3 [2-3]); make HM-related clinical decisions (3 [2-4]); and critique treatment planning (3 [2-4]). They reported feeling "moderately" to "quite" prepared to contour HM cases (3.5 [3-4]) and "quite" prepared to utilize the PET-CT five-point scale (4 [3-5]). Overall, residents reported feeling "moderately" prepared to treat HM patients (3 [2-3]); 24 residents (23%) felt "quite" or "extremely" prepared. Sixty-six residents (49%) were potentially interested in an HM away elective, commonly to increase comfort with treating HM patients (65%). Therefore, HM training is an important component of RO residency, yet a minority of surveyed trainees felt quite or extremely well prepared to treat HM patients. Programs should explore alternative and additional educational opportunities to increase resident comfort with treating HM patients.

4.
Br J Radiol ; 94(1127): 20210360, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34378402

RESUMO

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, accounting for 30-40% of all non-Hodgkin lymphoma cases and presenting later in life, most often in the sixth decade. Although DLBCL is curable, long-term remission rates are only 60-80%. The most recent major advance in upfront therapy for DLBCL was the monoclonal anti-CD20 antibody rituximab, which was approved in the late 1990s; now, 25 years later, up to 40% of patients will experience primary refractory or relapsed disease, thereby underscoring the importance of salvage therapy. Radiation therapy can be highly effective in DLBCL, both initially as consolidation therapy and later as salvage therapy and is currently being explored in the context of immune and cellular therapies. The aim of this review is to examine the therapeutic approaches for relapsed or refractory DLBCL, with a focus on whether using radiation therapy as salvage therapy can improve the likelihood of cure.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Linfoma Difuso de Grandes Células B/radioterapia , Recidiva Local de Neoplasia/radioterapia , Terapia de Salvação/métodos , Humanos , Recidiva
5.
Radiother Oncol ; 163: 199-208, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34454975

RESUMO

BACKGROUND AND PURPOSE: We previously evaluated late cardiac disease in long-term survivors in the Childhood Cancer Survivor Study (CCSS) based on heart radiation therapy (RT) doses estimated from an age-scaled phantom with a simple atlas-based heart model (HAtlas). We enhanced our phantom with a high-resolution CT-based anatomically realistic and validated age-scalable cardiac model (HHybrid). We aimed to evaluate how this update would impact our prior estimates of RT-related late cardiac disease risk in the CCSS cohort. METHODS: We evaluated 24,214 survivors from the CCSS diagnosed from 1970 to 1999. RT fields were reconstructed on an age-scaled phantom with HHybrid and mean heart dose (Dm), percent volume receiving ≥ 20 Gy (V20) and ≥ 5 Gy with V20 = 0 ( [Formula: see text] ) were calculated. We reevaluated cumulative incidences and adjusted relative rates of grade 3-5 Common Terminology Criteria for Adverse Events outcomes for any cardiac disease, coronary artery disease (CAD), and heart failure (HF) in association with Dm, V20, and [Formula: see text] (as categorical variables). Dose-response relationships were evaluated using piecewise-exponential models, adjusting for attained age, sex, cancer diagnosis age, race/ethnicity, time-dependent smoking history, diagnosis year, and chemotherapy exposure and doses. For relative rates, Dm was also considered as a continuous variable. RESULTS: Consistent with previous findings with HAtlas, reevaluation using HHybrid dosimetry found that, Dm ≥ 10 Gy, V20 ≥ 0.1%, and [Formula: see text]  ≥ 50% were all associated with increased cumulative incidences and relative rates for any cardiac disease, CAD, and HF. While updated risk estimates were consistent with previous estimates overall without statistically significant changes, there were some important and significant (P < 0.05) increases in risk with updated dosimetry for Dm in the category of 20 to 29.9 Gy and V20 in the category of 30% to 79.9%. When changes in the linear dose-response relationship for Dm were assessed, the slopes of the dose response were steeper (P < 0.001) with updated dosimetry. Changes were primarily observed among individuals with chest-directed RT with prescribed doses ≥ 20 Gy. CONCLUSION: These findings present a methodological advancement in heart RT dosimetry with improved estimates of RT-related late cardiac disease risk. While results are broadly consistent with our prior study, we report that, with updated cardiac dosimetry, risks of cardiac disease are significantly higher in two dose and volume categories and slopes of the Dm-specific RT-response relationships are steeper. These data support the use of contemporary RT to achieve lower heart doses for pediatric patients, particularly those requiring chest-directed RT.

6.
Blood Adv ; 5(14): 2799-2806, 2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34264268

RESUMO

The Endothelial Activation and Stress Index (EASIX) score, defined as [(creatinine × lactate dehydrogenase [LDH])/platelets], is a marker of endothelial activation that has been validated in the allogeneic hematopoietic stem cell transplant setting. Endothelial activation is one of the mechanisms driving immune-mediated toxicities in patients treated with chimeric antigen receptor-T (CAR-T)-cell therapy. This study's objective was to evaluate the association between EASIX and other laboratory parameters collected before lymphodepletion and the subsequent onset of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) those patients. Toxicity data were collected prospectively on 171 patients treated with axicabtagene ciloleucel (axi-cel) for large B-cell lymphoma (LBCL). CRS grades 2 to 4 were diagnosed in 81 (47%) patients and ICANS grades 2 to 4 in 84 (49%). EASIX combined with ferritin (EASIX-F) identified 3 risk groups with CRS grades 2 to 4 cumulative incidence of 74% (hazards ratio [HR], 4.8; 95% confidence interval [CI], 2.1-11; P < .001), 49% (HR, 2.3; 95% CI, 1.02-5; P = .04), and 23% (reference), respectively. EASIX combined with CRP and ferritin (EASIX-FC) identified 3 risk groups with an ICANS grade 2 to 4 cumulative incidence of 74% (HR, 3.6; 95% CI, 1.9-6.9; P < .001), 51% (HR, 2.1; 95% CI, 1.1-3.9; P = .025), and 29% (reference). Our results indicate that common laboratory parameters before lymphodepletion correlate with CAR-T-related toxicities and can help support clinical decisions, such as preemptive toxicity management, hospitalization length, and proper setting for CAR-T administration.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma Difuso de Grandes Células B , Receptores de Antígenos Quiméricos , Síndrome da Liberação de Citocina , Ferritinas , Humanos
7.
Leuk Lymphoma ; 62(10): 2400-2407, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33942701

RESUMO

This study aimed to assess the prognostic value of baseline disease distribution for patients with the secondary central nervous system (CNS) diffuse large B-cell lymphoma (DLBCL) treated with chemotherapy and radiation (RT). 44 patients with secondary CNS DLBCL were reviewed. Twenty patients had leptomeningeal disease (LMD), and 24 had localized/targetable disease (LTD). Of 8 patients who received stem cell transplantation (SCT) after RT, 6 had LTD with a complete or partial response after RT. Median time to CNS relapse after RT was 10.1 months; 3/24 patients with LTD and 5/15 with LMD had CNS relapse. The median overall survival (OS) was 8 and 20 months for patients with LMD and LTD, respectively (p = 0.20). On multivariable analysis, LTD, receipt of SCT, and response after RT were associated with better OS and CNS-disease-free survival. Patients with localized secondary CNS DLBCL may benefit from RT serving as a bridge to SCT.


Assuntos
Neoplasias do Sistema Nervoso Central , Linfoma Difuso de Grandes Células B , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Sistema Nervoso Central , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/terapia , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/terapia , Recidiva Local de Neoplasia , Prognóstico , Estudos Retrospectivos
8.
Front Oncol ; 11: 648655, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33842363

RESUMO

CAR T-cell therapy has revolutionized the treatment approach to patients with relapsed/refractory hematologic malignancies; however, there continues to be opportunity for improvement in treatment toxicity as well as response durability. Radiation therapy can play an important role in combined modality treatments for some patients undergoing CAR T-cell therapy in various clinical settings. In this review, we discuss the current evidence for RT in the setting of CAR T-cell therapy for patients with hematologic malignancies and propose potential opportunities for future investigation of RT and CAR T-cell treatment synergy. Future research frontiers include investigation of hypotheses including radiation priming of CAR T-cell mediated death, pre-CAR T-cell tumor debulking with radiation therapy, and selection of high risk patients for early radiation salvage after CAR T cell therapy.

9.
Int J Radiat Oncol Biol Phys ; 111(1): 36-44, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-33774076

RESUMO

PURPOSE: Primary mediastinal B cell lymphoma (PMBCL) is a highly curable subtype of non-Hodgkin lymphoma that is diagnosed predominantly in adolescents and young adults. Consequently, long-term treatment-related morbidity is critical to consider when devising treatment strategies that include different chemoimmunotherapy strategies with or without radiation therapy. Furthermore, adaptive approaches using the end-of-chemotherapy (EOC) positron emission tomography (PET)/computed tomography (CT) scanning may help to determine which patients may benefit from additional therapies. We aimed to develop evidence-based guidelines for treating these patients. METHODS AND MATERIALS: We conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline using the PubMed database. The ARS expert committee, composed of radiation oncologists, hematologists, and pediatric oncologists, developed consensus guidelines using the modified Delphi framework. RESULTS: Nine studies met the full criteria for inclusion based on reporting outcomes on patients with primary mediastinal B cell lymphoma with EOC PET/CT response scored with the 5-point Deauville scale. These studies formed the evidence for these guidelines in managing patients with PMBCL according to the EOC PET response, including after a 5-point Deauville scale of 1 to 3, 4, or 5, and for patients with relapsed and refractory disease. The expert group also developed guidance on radiation simulation, treatment planning, and plan evaluation based on expert opinion. CONCLUSIONS: Various treatment approaches exist in the management of PMBCL, including different chemoimmunotherapy regimens, the use of consolidative radiation therapy, and adaptive approaches based on EOC PET/CT response. These guidelines can be used by practitioners to provide appropriate treatment according to different disease scenarios.


Assuntos
Linfoma de Células B/terapia , Neoplasias do Mediastino/terapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Humanos , Linfoma de Células B/diagnóstico por imagem , Neoplasias do Mediastino/diagnóstico por imagem , Planejamento da Radioterapia Assistida por Computador
12.
Blood ; 137(23): 3272-3276, 2021 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-33534891

RESUMO

Corticosteroids are commonly used for the management of severe toxicities associated with chimeric antigen receptor (CAR) T-cell therapy. However, it remains unclear whether their dose, duration, and timing may affect clinical efficacy. Here, we determined the impact of corticosteroids on clinical outcomes in patients with relapsed or refractory large B-cell lymphoma treated with standard of care anti-CD19 CAR T-cell therapy. Among 100 patients evaluated, 60 (60%) received corticosteroids for management of CAR T-cell therapy-associated toxicities. The median cumulative dexamethasone-equivalent dose was 186 mg (range, 8-1803) and the median duration of corticosteroid treatment was 9 days (range, 1-30). Corticosteroid treatment was started between days 0 and 7 in 45 (75%) patients and beyond day 7 in 15 (25%). After a median follow-up of 10 months (95% confidence interval, 8-12 months), use of higher cumulative dose of corticosteroids was associated with significantly shorter progression-free survival. More importantly, higher cumulative dose of corticosteroids, and prolonged and early use after CAR T-cell infusion were associated with significantly shorter overall survival. These results suggest that corticosteroids should be used at the lowest dose and for the shortest duration and their initiation should be delayed whenever clinically feasible while managing CAR T-cell therapy-associated toxicities.

13.
Br J Haematol ; 192(3): 560-567, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33517581

RESUMO

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare entity, with limited data on the outcome in the relapsed/refractory setting. We evaluated the outcome of all patients diagnosed between 04/1979 and 01/2019 with relapsed or progressive NLPHL after initial active therapy at two institutions, refractory disease being defined as lack of response to treatment and/or relapse within three months of treatment. NLPHL patients with histological evidence of transformation at time of first relapse or progression were excluded. In total, 69 patients with recurrent NLPHL were included in the study. After a median follow-up after initial diagnosis of 14 years (range, 0·5-46 years), median progression-free survival after front-line treatment (PFS-1) was four years. Second-line therapy included chemotherapy in 28 (41%) patients, biological therapy (rituximab, lenalidomide or brentuximab vedotin) in 14 (20%), high-dose chemotherapy followed by autologous stem cell transplant in 14 (20%) and radiation therapy (RT) alone in 10 (15%). The five-year PFS after second-line therapy (PFS-2) was 68% [95% confidence interval (CI), 54-79%] but the five-year overall survival (OS) after second-line therapy (OS-2) remained excellent, at 94% (95% CI, 85-99%). Due to excellent outcome in case of recurrence, studies aimed at characterizing its biology to guide therapy de-escalation are needed.


Assuntos
Doença de Hodgkin/terapia , Recidiva Local de Neoplasia/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Colúmbia Britânica/epidemiologia , Criança , Feminino , Doença de Hodgkin/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Intervalo Livre de Progressão , Transplante de Células-Tronco , Transplante Autólogo , Resultado do Tratamento , Adulto Jovem
14.
Leuk Lymphoma ; 62(6): 1361-1369, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33480830

RESUMO

We addressed the prognostic impact of cell-of-origin (COO), MYC and Bcl-2 overexpression as well as isolated MYC rearrangement among 111 patients with limited stage diffuse large B-cell lymphoma (DLBCL) treated with consolidative radiation therapy (RT) after a metabolic complete response to immunochemotherapy. With a median follow-up of 31.1 months (95% CI 27.4 - 34.8), 4 relapses occurred. The 3-year progression free survival (PFS), overall survival (OS), and loco-regional relapse free survival (LRFS) for the cohort were 95%, 96%, and 100%, respectively. There were no differences in OS, PFS, or LRFS based on COO or MYC/Bcl-2 dual expression (DE). Similarly, patients with MYC translocations without BCL2 or BCL6 rearrangements did not have worse outcomes. Consolidative RT produced excellent local control, regardless of DLBCL biology, with one late in-field failure.


Assuntos
Linfoma Difuso de Grandes Células B , Proteínas Proto-Oncogênicas c-myc , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/terapia , Recidiva Local de Neoplasia/genética , Prognóstico , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-6/genética , Proteínas Proto-Oncogênicas c-myc/genética
15.
Leuk Lymphoma ; 62(5): 1057-1065, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33274673

RESUMO

This guideline for nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) by the American Radium Society was developed by a multidisciplinary expert panel of medical, pediatric, and radiation oncologists convened to formulate guidelines for evaluation and treatment. The guideline development was based on an in-depth literature review and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of the recommendations by the panel. Given the scarcity of compelling data for strong recommendations for a rare lymphoma that has been shown to be more indolent than classical Hodgkin lymphoma, in instances where evidence is not available or equivocal, expert opinion guided the recommendations. Four clinical variants exemplify common scenarios and represent the consensus recommendations for patients with nodular lymphocyte Hodgkin lymphoma. A summary of the available published literature is also presented.


Assuntos
Doença de Hodgkin , Linfoma Folicular , Rádio (Elemento) , Criança , Consenso , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/terapia , Humanos , Linfócitos , Estados Unidos/epidemiologia
16.
Int J Radiat Oncol Biol Phys ; 109(5): 1414-1420, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33309978

RESUMO

PURPOSE: We report the long-term results of a prospective trial conducted to determine the efficacy and safety of radiation therapy (RT) alone in treating localized mucosa-associated lymphoid tissue (MALT) lymphoma. METHODS AND MATERIALS: Patients with localized MALT lymphoma were eligible and treated with involved field RT to doses of 24 to 39.6 Gy. Relapse-free survival (RFS) was the primary endpoint. Kaplan-Meier analysis was used to estimate RFS, progression-free survival (PFS), and overall survival (OS) defined from time of study entry. Preplanned subgroup analyses were performed based on site of involvement. RESULTS: From 2000 to 2012, 75 patients were accrued; 73 received protocol-specified RT. Median follow-up was 9.8 years. Thirty-four patients had gastric MALT, 17 orbital, 13 head and neck nonorbit, 4 skin, and 5 disease of other sites. Thirteen of 34 patients with gastric MALT were Helicobacter pylori positive at the time of initial diagnosis and underwent 1 to 3 courses of triple antibiotic therapy. All gastric MALT patients had documented persistent MALT without H. pylori on endoscopy before enrollment in the study. All patients achieved a complete response with a median time of 3 months. Eleven patients (15%) had disease relapse, 9 of which were at sites outside the RT field with median time to progression of 38.3 months. Median PFS was 17.5 years, and median RFS and OS were not reached. The 10-year relapse-free rate was 83% (95% confidence interval [CI], 74%-93%). The 10-year PFS rate was 71% (95% CI, 60%-84%). The 10-year OS rate was 86% (95% CI, 77%-96%). RFS, PFS, and OS did not differ by disease site (P = .17, .43, and .50, respectively). All relapses were successfully salvaged. One patient developed metastatic gastric adenocarcinoma and was found to also have recurrent MALT on biopsy. Otherwise, all relapsed patients were alive without evidence of disease at last follow-up, and no patient died of MALT lymphoma. Sixty-seven patients (92%) experienced acute toxicity during radiation, all of which were grade 1 and 2, with only 1 grade 3 toxicity. Twenty-two patients (30%) experienced late toxicity, with only 1 grade 3 toxicity. CONCLUSIONS: This prospective study confirms that RT for MALT lymphoma provides excellent long-term RFS with acceptable rates of toxicity. Current efforts are focused on RT de-escalation in an effort to further avoid treatment-related morbidity. CLINICALTRIALS.GOV: NCT04465162.


Assuntos
Linfoma de Zona Marginal Tipo Células B/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/radioterapia , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Humanos , Estimativa de Kaplan-Meier , Linfoma de Zona Marginal Tipo Células B/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Orbitárias/patologia , Neoplasias Orbitárias/radioterapia , Intervalo Livre de Progressão , Estudos Prospectivos , Lesões por Radiação/patologia , Dosagem Radioterapêutica , Recidiva , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/radioterapia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/radioterapia , Fatores de Tempo , Resultado do Tratamento
17.
Adv Radiat Oncol ; 5(6): 1255-1266, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33305086

RESUMO

Purpose: Intensity modulated radiation therapy delivered with deep-inspiration breath hold (IMRT-BH) provides favorable normal tissue dosimetric profiles when treating patients with mediastinal lymphoma. However, it is unclear if IMRT-BH plans are comparable to free breathing (FB) proton plans. We performed a retrospective, comparative dosimetric study between IMRT-BH and FB passive scatter proton therapy (P-FB) or intensity modulated proton therapy (IMPT-FB). Hypothesizing that BH would provide superior normal tissue sparing when added to proton therapy, we also compared plans to passive scatter BH (P-BH). Methods and Materials: For 15 patients who received involved-site RT with "butterfly" IMRT-BH, 3 additional proton plans (P-FB, IMPT-FB, P-BH) were optimized to deliver 30.6 Gy/Gy relative biological effectiveness. Dosimetric variables (mean dose, V30, V25, V15, and V5) for organs at risk (OARs) were calculated and compared using nonparametric Wilcoxon signed-rank tests. Results: Of 57 studied OAR parameters, IMRT-BH plans were comparable in 37 (65%) parameters with P-FB plans, 32 (56%) of IMPT-FB parameters, and 30 (53%) of P-BH parameters. Doses to breasts were generally equivalent among plans while esophageal dosing was worse with IMRT-BH. Mean doses and V5 of the total lung and heart were the highest with IMRT-BH; however, IMRT-BH resulted in comparable coronary and superior lung V30 relative to proton plans. The addition of BH with proton therapy resulted in the greatest lung sparing, with mean lung dose reductions of 11% to 38%. Conclusions: The use of BH with IMRT reduces the disparity in OAR doses with equivalence achieved in nearly two-thirds of OAR metrics compared with P-FB and 50% compared with IMPT-BH. Because each modality exhibited unique benefits, personalization of modality selection is recommended. Proton therapy via BH provides additional benefits in heart and lung sparing.

18.
Radiother Oncol ; 153: 163-171, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33075392

RESUMO

BACKGROUND AND PURPOSE: Radiation therapy is a risk factor for late cardiac disease in childhood cancer survivors. Several pediatric cohort studies have established whole heart dose and dose-volume response models. Emerging data suggest that dose to cardiac substructures may be more predictive than whole heart metrics. In order to develop substructure dose-response models, the heart model previously used for pediatric cohort dosimetry needed enhancement and substructure delineation. METHODS: To enhance our heart model, we combined the age-scalable capability of our computational phantom with the anatomically-delineated (with substructures) heart models from an international humanoid phantom series. We examined cardiac volume similarity/overlap between registered age-scaled phantoms (1, 5, 10, and 15 years) with the enhanced heart model and the reference phantoms of the same age; dice similarity coefficient (DSC) and overlap coefficient (OC) were calculated for each matched pair. To assess the accuracy of our enhanced heart model, we compared doses from computed tomography-based planning (ground truth) with reconstructed heart doses. We also compared doses calculated with the prior and enhanced heart models for a cohort of nearly 5000 childhood cancer survivors. RESULTS: We developed a realistic cardiac model with 14-substructures, scalable across a broad age range (1-15 years); average DSC and OC were 0.84 ± 0.05 and 0.90 ± 0.05, respectively. The average percent difference between reconstructed and ground truth mean heart doses was 4.2%. In the cohort dosimetry analysis, dose and dose-volume metrics were approximately 10% lower on average when the enhanced heart model was used for dose reconstructions. CONCLUSION: We successfully developed and validated an anatomically realistic age-scalable cardiac model that can be used to establish substructure dose-response models for late cardiac disease in childhood cancer survivor cohorts.


Assuntos
Sobreviventes de Câncer , Neoplasias , Adolescente , Criança , Pré-Escolar , Coração/diagnóstico por imagem , Humanos , Lactente , Neoplasias/radioterapia , Imagens de Fantasmas , Radiometria
20.
J Cancer Educ ; 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33111188

RESUMO

We aimed to investigate whether implicit linguistic biases exist in letters of recommendation (LORs) for applicants to radiation oncology (RO) residency. LORs (n = 487) written for applicants (n = 125) invited to interview at a single RO residency program from the 2015 to 2019 application cycles were included for analysis. Linguistic Inquiry and Word Count (LIWC) software was used to evaluate LORs for length and a dictionary of predetermined themes. Language was evaluated for gender bias using a publicly available gender bias calculator. Non-parametric tests were used to compare linguistic domain scores. The median number of the LORs per applicant was 4 (range 3-5). No significant differences by applicant gender were detected in LIWC score domains or gender bias calculator (P > 0.05). However, LORs for applicants from racial/ethnic backgrounds underrepresented in medicine were less likely to include standout descriptors (P = 0.008). Male writers were less likely to describe applicant characteristics related to patient care (P < 0.0001) and agentic personality (P = 0.006). LORs written by RO were shorter (P < 0.0001) and included fewer standout descriptors (P = 0.014) but were also more likely to include statements regarding applicant desirability (P = 0.045) and research (P = 0.008). While language was globally male-biased, assistant professors were less likely than associate professors (P = 0.0064) and full professors (P = 0.023) to use male-biased language. Significant linguistic differences were observed in RO residency LORs, suggesting that implicit biases related to both applicants and letter writers may exist. Recognition, and ideally eradication, of such biases are crucial for fair and equitable evaluation of a diverse applicant pool of RO residency candidates.

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