Proton therapy for adults with mediastinal lymphomas: the International Lymphoma Radiation Oncology Group guidelines.
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ABSTRACT:
SUBMITTER: Dabaja BS
PROVIDER: S-EPMC6212652 | biostudies-literature | 2018 Oct
REPOSITORIES: biostudies-literature
Publications
Proton therapy for adults with mediastinal lymphomas: the International Lymphoma Radiation Oncology Group guidelines.
Dabaja Bouthaina Shbib BS Hoppe Bradford S BS Plastaras John P JP Newhauser Wayne W Rosolova Katerina K Flampouri Stella S Mohan Radhe R Mikhaeel N George NG Kirova Youlia Y Specht Lena L Yahalom Joachim J
Blood 20180814 16
Among adult lymphoma survivors, radiation treatment techniques that increase the excess radiation dose to organs at risk (OARs) put patients at risk for increased side effects, especially late toxicities. Minimizing radiation to OARs in adults patients with Hodgkin and non-Hodgkin lymphomas involving the mediastinum is the deciding factor for the choice of treatment modality. Proton therapy may help to reduce the radiation dose to the OARs and reduce toxicities, especially the risks for cardiac ...[more]
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Project description:PurposeCombined modality therapy with multiagent chemotherapy and radiation therapy is a standard treatment option for aggressive mediastinal non-Hodgkin lymphomas (AMNHLs); however, concerns regarding acute and late radiation toxicities have fueled an effort to use systemic therapy alone. The use of proton therapy (PT) is a promising treatment option, but there are still limited data regarding clinical outcomes with this treatment modality. In this Particle Therapy Cooperative Group lymphoma subcommittee collaboration, we report outcomes of patients with AMNHL treated with pencil-beam scanning PT or double-scatter PT after chemotherapy.Methods and materialsThis was a multi-institutional retrospective observational cohort study of patients with AMNHL treated with PT following chemotherapy between 2011 and 2021. Progression-free survival (PFS), local recurrence-free survival (LRFS), and overall survival (OS) rates were estimated with the Kaplan-Meier method. PT toxicity was graded by the Common Terminology Criteria for Adverse Events version 5.0. A 2-tailed paired t test was used for dosimetric comparisons.ResultsTwenty-nine patients were identified. With a median follow-up time of 4.2 years (range, 0.2-8.9 years), the estimated 5-year PFS for all patients was 93%, 5-year LRFS was 96%, and estimated 5-year OS was 87%. Maximum acute grade 1 (G1) toxicities occurred in 18 patients, and 7 patients had maximum G2 toxicities. No G3+ radiation-related toxicities were observed. Average mean lung dose and lung V20 Gy were lower for patients treated with pencil-beam scanning PT compared with double-scatter PT (P = .016 and .006, respectively), while patients with lower mediastinal disease had higher doses for all evaluated dosimetric heart parameters.ConclusionsPT after chemotherapy for patients with AMNHL resulted in excellent outcomes with respect to 5-year PFS, LRFS, and OS without high-grade toxicities. Future work with larger sample sizes is warranted to further elucidate the role of PT in the treatment of AMNHL.
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Project description:Safety concerns may arise from a lack of standardization and ambiguity during the treatment planning and delivery process in radiation therapy. A standardized target and organ-at-risk naming convention in radiation therapy was developed by a task force comprised of several Radiation Oncology Societies. We present a nested-survey approach in a community setting to determine the methodology for radiation oncology departments to standardize their practice. Our Institution's continuous quality improvement (CQI) committee recognized that, due to growth from one to three centers, significant variability existed within plan parameters specific to patients' treatment. A multidiscipline, multiclinical site consortium was established to create a guideline for standard naming. Input was gathered using anonymous, electronic surveys from physicians, physicists, dosimetrists, chief therapists, and nurse managers. Surveys consisted of several primary areas of interest: anatomical sites, course naming, treatment plan naming, and treatment field naming. Additional concepts included capitalization, specification of laterality, course naming in the event of multiple sites being treated within the same course of treatment, primary versus boost planning, the use of bolus, revisions for plans, image-guidance field naming, forbidden characters, and standard units for commonly used physical quantities in radiation oncology practice. Guidelines for standard treatment naming were developed that could be readily adopted. This multidisciplinary study provides a clear, straightforward, and easily implemented protocol for the radiotherapy treatment process. Standard nomenclature facilitates the safe means of communication between team members in radiation oncology. The guidelines presented in this work serve as a model for radiation oncology clinics to standardize their practices.
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Project description:BACKGROUND:Interpretation of mediastinal biopsy is often challenging even for experienced pathologists especially when a hematolymphoid neoplasm is suspected. Primary mediastinal large B-cell lymphoma (PMLBCL) and classic Hodgkin lymphoma (CHL) represent two major types of mature B-cell lymphomas of the mediastinum. Although PMLBCL and mediastinal CHL share many clinicopathologic characteristics, their treatment strategies and responses are remarkably different. We therefore aimed to find distinctive histologic or protein markers to better differentiate these two lesions. METHODS:Search for primary mediastinal B-cell lymphomas found 52 consecutive cases from 3 university hospitals of Korea during 2005 to 2012. Among them, 32 cases that were available for additional immunohistochemistry (IHC) assessment were enrolled in this study. These cases consisted of the following: CHL (N = 13), PMLBCL (N = 16), and B-cell lymphoma unclassifiable, with features intermediate between diffuse large B-cell lymphoma and CHL (gray zone lymphoma, N = 3). Along with the clinicopathologic findings, the expression of p63, GATA3 and cyclin E was investigated by IHC in the three categorized lesions mentioned above. RESULTS:Most clinical features overlapped between PMLBCL and CHL except for the increased disease progression and mortality found in PMLBCL. In the pathologic review, the presence of epithelioid granuloma favored a diagnosis of CHL, whereas reticulated or alveolar patterns of fibrosis were characteristic of PMLBCL. For protein markers, p63 was predominantly positive in PMLBCL (15/16) compared with CHL (2/13), which indicates that p63 is a marker of the highest diagnostic accuracy when calculated by the area under the ROC curve. GATA3 was expressed in the majority of CHL cases (10/13) compared with PMLBCL (0/16), while the expression of cyclin E was only rarely present in a minor population of PMLBCL. CONCLUSIONS:P63 expression in tumor cells, even focal expression, and no GATA3 is the most helpful feature in distinguishing PMLBCL from mediastinal CHL.
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Project description:BACKGROUND:Technological advances in Hodgkin lymphoma (HL) radiation therapy (RT) by high conformal treatments potentially increase control over organs-at-risk (OARs) dose distribution. However, plan optimization remains a time-consuming task with great operator dependent variability. Purpose of the present study was to devise a fully automated pipeline based on the Pinnacle3 Auto-Planning (AP) algorithm for treating female supradiaphragmatic HL (SHL) patients. METHODS:CT-scans of 10 female patients with SHL were considered. A "butterfly" (BF) volumetric modulated arc therapy was optimized using SmartArc module integrated in Pinnacle3 v. 9.10 using Collapsed Cone Convolution Superposition algorithm (30 Gy in 20 fractions). Human-driven (Manual-BF) and AP-BF optimization plans were generated. For AP, an optimization objective list of Planning Target Volume (PTV)/OAR clinical goals was first implemented, starting from a subset of 5 patients used for algorithm training. This list was then tested on the remaining 5 patients (validation set). In addition to the BF technique, the AP engine was applied to a 2 coplanar disjointed arc (AP-ARC) technique using the same objective list. For plan evaluation, dose-volume-histograms of PTVs and OARs were extracted; homogeneity and conformity indices (HI and CI), OARs dose-volume metrics and odds for different toxicity endpoints were computed. Non-parametric Friedman and Dunn tests were used to identify significant differences between groups. RESULTS:A single AP objective list for SHL was obtained. Compared to the manual plan, both AP-plans offer comparable CIs while AP-ARC also achieved comparable HIs. All plans fulfilled the clinical dose criteria set for OARs: both AP solutions performed at least as good as Manual-BF plan. In particular, AP-ARC outperformed AP-BF in terms of heart sparing involving a lower risk of coronary events and radiation-induced lung fibrosis. Hands-on planning time decreased by a factor of 10 using AP on average. CONCLUSIONS:Despite the high interpatient PTV (size and position) variability, it was possible to set a standard SHL AP optimization list with a high level of generalizability. Using the implemented list, the AP module was able to limit OAR doses, producing clinically acceptable plans with stable quality without additional user input. Overall, the AP engine associated to the arc technique represents the best option for SHL.
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Project description:BRAF kinase gene V600 point mutations drive approximately 40% to 50% of all melanomas, and BRAF inhibitors (BRAFi) have been found to significantly improve survival outcomes. Although radiation therapy (RT) provides effective symptom palliation, there is a lack of toxicity and efficacy data when RT is combined with BRAFi, including vemurafenib and dabrafenib. This literature review provides a detailed analysis of potential increased dermatologic, pulmonary, neurologic, hepatic, esophageal, and bowel toxicity from the combination of BRAFi and RT for melanoma patients described in 27 publications. Despite 7 publications noting potential intracranial neurotoxicity, the rates of radionecrosis and hemorrhage from whole brain RT (WBRT), stereotactic radiosurgery (SRS), or both do not appear increased with concurrent or sequential administration of BRAFis. Almost all grade 3 dermatitis reactions occurred when RT and BRAFi were administered concurrently. Painful, disfiguring nondermatitis cutaneous reactions have been described from concurrent or sequential RT and BRAFi administration, which improved with topical steroids and time. Visceral toxicity has been reported with RT and BRAFi, with deaths possibly related to bowel perforation and liver hemorrhage. Increased severity of radiation pneumonitis with BRAFi is rare, but more concerning was a potentially related fatal pulmonary hemorrhage. Conversely, encouraging reports have described patients with leptomeningeal spread and unresectable lymphadenopathy rendered disease free from combined RT and BRAFi. Based on our review, the authors recommend holding BRAFi and/or MEK inhibitors ≥3 days before and after fractionated RT and ≥1 day before and after SRS. No fatal reactions have been described with a dose <4 Gy per fraction, and time off systemic treatment should be minimized. Future prospective data will serve to refine these recommendations.
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Project description:Purpose/backgroundThe aim of this study was to evaluate pencil beam scanning (PBS) proton therapy (PT) in deep inspiration breath-hold (DIBH) for mediastinal lymphoma patients, by retrospectively evaluating plan robustness to the clinical target volume (CTV) and organs at risk (OARs) on repeated CT images acquired throughout treatment. Methods: Sixteen mediastinal lymphoma patients treated with PBS-PT in DIBH were included. Treatment plans (TPs) were robustly optimized on the CTV (7 mm/4.5%). Repeated verification CTs (vCT) were acquired during the treatment course, resulting in 52 images for the entire patient cohort. The CTV and OARs were transferred from the planning CT to the vCTs with deformable image registration and the TPs were recalculated on the vCTs. Target coverage and OAR doses at the vCTs were compared to the nominal plan. Deviation in lung volume was also calculated.ResultsThe TPs demonstrated high robust target coverage throughout treatment with D98%,CTV deviations within 2% for 14 patients and above the desired requirement of 95% for 49/52 vCTs. However, two patients did not achieve a robust dose to CTV due to poor DIBH reproducibility, with D98%,CTV at 78 and 93% respectively, and replanning was performed for one patient. Adequate OAR sparing was achieved for all patients. Total lung volume variation was below 10% for 39/52 vCTs.ConclusionPBS PT in DIBH is generally a robust technique for treatment of mediastinal lymphomas. However, closely monitoring the DIBH-reproducibility during treatment is important to avoid underdosing CTV and achieve sufficient dose-sparing of the OARs.
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Project description:PurposeRecent advances in imaging, use of prognostic indices, and molecular profiling techniques have the potential to improve disease characterization and outcomes in lymphoma. International trials are under way to test image-based response–adapted treatment guided by early interim positron emission tomography (PET)–computed tomography (CT). Progress in imaging is influencing trial design and affecting clinical practice. In particular, a five-point scale to grade response using PET-CT, which can be adapted to suit requirements for early- and late-response assessment with good interobserver agreement, is becoming widely used both in practice- and response-adapted trials. A workshop held at the 11th International Conference on Malignant Lymphomas (ICML) in 2011 concluded that revision to current staging and response criteria was timely.MethodsAn imaging working group composed of representatives from major international cooperative groups was asked to review the literature, share knowledge about research in progress, and identify key areas for research pertaining to imaging and lymphoma.ResultsA working paper was circulated for comment and presented at the Fourth International Workshop on PET in Lymphoma in Menton, France, and the 12th ICML in Lugano, Switzerland, to update the International Harmonisation Project guidance regarding PET. Recommendations were made to optimize the use of PET-CT in staging and response assessment of lymphoma, including qualitative and quantitative methods.ConclusionThis article comprises the consensus reached to update guidance on the use of PET-CT for staging and response assessment for [18F]fluorodeoxyglucose-avid lymphomas in clinical practice and late-phase trials.
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