Comparison of Techniques for Involved-Site Radiation Therapy in Patients With Lower Mediastinal Lymphoma

PurposePatients with lower mediastinal lymphoma (LML) benefit dosimetrically from proton therapy (PT) compared with intensity modulated radiation therapy (IMRT). The added dosimetric benefit of deep-inspiration breath-hold (DIBH) is unknown; therefore, we evaluated IMRT versus PT and free-breathing (FB) versus DIBH among patients with LML.Methods and MaterialsTwenty-one patients with LML underwent 4-dimensional computed tomography and 3 sequential DIBH scans at simulation. Involved-site radiation therapy target volumes and organ-at-risk contours were developed for both DIBH and FB scans. FB-IMRT, DIBH-IMRT, FB-PT, and DIBH-PT plans were generated for each patient for comparison.ResultsThe median difference in lung volume between the DIBH and FB scans was 1275 mL; the average difference in clinical target volume was 5.7 mL. DIBH-IMRT produced a lower mean lung dose (10.8 vs 11.9 Gy; P < .001) than FB-IMRT, with no difference in mean heart dose (MHD; 16.1 vs 15.0 Gy; P = .992). Both PT plans produced a significantly lower mean dose to the lung, heart, left ventricle, esophagus, and nontarget body than DIBH-IMRT. DIBH-PT reduced the median MHD by 4.2 Gy (P < .0001); left ventricle dose by 5.1 Gy (P < .0001); and lung V5 by 26% (P < .0001) versus DIBH-IMRT. The 2 PT plans were comparable, with DIBH-PT reducing mean lung dose (7.0 vs 7.7 Gy; P = .063) and with no difference in MHD (10.3 vs 9.5 Gy; P = .992).ConclusionsAmong patients with LML, DIBH (IMRT or PT) improved lung dosimetry over FB but had little influence on MHD. PT (DIBH and FB) significantly reduced lung, heart, esophagus, and nontarget body dose compared with DIBH IMRT, potentially reducing the risk of late complications.     

Radiation Dose Reduction in Early-Stage Hodgkin Lymphoma

IntroductionTreatment for early-stage Hodgkin lymphoma (HL) involves radiotherapy (RT), chemotherapy, or combined modality therapy (CMT). We analyzed reduction of RT dose in CMT, particularly in the context of German Hodgkin Study Group (GHSG) HD10 randomized trial results of 2010.Patients and MethodsThe National Cancer Data Base was queried for patients with stage I-II HL receiving CMT. RT dose and associated characteristics were analyzed. Stage I and absence of B symptoms were used as a surrogate for early-stage favorable disease.ResultsOf 31,301 patients with stage I-II HL, 11,457 received CMT between 2004 and 2015. Using the surrogate defined above, 1955 patients (17.1%) were classified as having favorable disease. The majority (61.6%) received 30-36 Gy, while 7.0% received 20 Gy. The provision of 20 Gy was more common in stage I patients (12.3% vs. 5.4% in stage II) and at academic facilities (10.8% vs. 6.3%-8.9% at other facilities). Use of 20 Gy (vs. 30-36 Gy) was less likely with thorax site (odds ratio [OR] 0.43 vs. head and neck), stage II disease (OR 0.41), and B symptoms (OR 0.33). Notably, the use of 20 Gy increased dramatically after 2010 (the year of publication of GHSG HD10 trial results), with rates of 12.3% in 2010-2015 versus 0.1% in 2004-2009 (OR 6.3, P < .001). This was even more pronounced in cases of favorable early-stage disease, with 25.5% after 2010 versus 2.8% before 2010 (OR 13.2, P < .001). The use of doses > 36 Gy decreased over a corresponding time period (OR 0.44, P < .001).ConclusionAnalysis of CMT for patients with early-stage HL demonstrates variability in RT dose, including increasing use of 20 Gy and decreasing use of high doses > 36 Gy.     

Characterization of Underrepresented Populations in Modern Era Clinical Trials Involving Radiation Therapy

PurposeThe demographic composition of modern radiation therapy (RT) clinical trials is incompletely studied. Understanding and minimizing disparities in clinical trials is critical to ensure health equity and the generalizability of research findings.Methods and MaterialsClinicaltrials.gov was searched to identify RT clinical trials that occurred from 1996 to 2019. A total of 1242 trials were reviewed for patient characteristics. The demographic composition of the studies was summarized by the frequency and percentage of patients by race, gender, and ethnicity. The racial composition of the study population was compared with the 2018 US Census using a 1-sample χ² test. Subgroup racial composition was compared using χ² tests of independence. Analyses used a complete case approach.ResultsA total of 122 trials met the inclusion criteria, and 121 of these (99.1%) reported race. Trial subgroups included 63 trials in the United States (51.6%), 9 proton therapy trials (7.4%), 34 RT toxicity mitigation or prevention trials (27.9%), 24 trials for female cancer (19.7%), and 17 trials for male cancer (13.9%). US clinical trials overall, US RT toxicity mitigation or prevention trials, US trials for female cancer, and US trials for male cancer had significantly different racial compositions compared with the 2018 US Census data (P < .001 for all). Compared with all clinical trials, those for proton therapy had the largest magnitude of significantly lower enrollment of participants who identified their race as Black, Asian, or other (P < .001).ConclusionsThis study characterized the racial composition of prospective RT clinical trials in a modern cohort. The racial population represented across multiple categories in the United States differed significantly from US census data and was most pronounced in trials evaluating proton therapy. This is a benchmark study for future efforts to characterize and balance the participation of underrepresented populations in RT clinical trials.     

Rituximab Combined With MACOP-B or VACOP-B and Radiation Therapy in Primary Mediastinal Large B-Cell Lymphoma: A Retrospective Study

BackgroundThird-generation regimens (MACOP-B [methotrexate/leucovorin (LV)/doxorubicin/cyclophosphamide/vincristine/prednisone/bleomycin] or VACOP-B [etoposide/LV/doxorubicin/cyclophosphamide/vincristine/prednisone/bleomycin]) in combination with local radiation therapy seem to improve lymphoma-free survival of primary mediastinal large B-cell lymphoma (PMLBCL). Recently, the superiority of R-CHOP (rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone) over CHOP-like regimens has been demonstrated in elderly and younger patients with low-risk diffuse large B-cell lymphoma.Patients and MethodsRetrospectively, between February 2002 and July 2006, 45 previously untreated patients with PMLBCL were treated with a combination of a third-generation chemotherapy regimen (MACOP-B or VACOP-B), concurrent rituximab, and mediastinal radiation therapy.ResultsTwenty-six (62%) patients achieved a complete response (CR), and 15 (36%) obtained a partial response after MACOP-B/VACOP-B plus rituximab. After radiation therapy, the CR rate was 80%. At a median follow-up of 28 months, among the 34 patients who obtained a CR, 3 relapsed after 16, 19, and 22 months, respectively. Projected overall survival was 80% at 5 years; the relapse-free survival (RFS) curve of the 34 patients who achieved CR was 88% at 5 years.ConclusionIn this retrospective study, in patients with PMLBCL, combined-modality treatment using the MACOP-B/VACOP-B regimen plus rituximab induces a high remission rate, with patients having a > 80% chance of surviving relapse free at 5 years. In comparison with historical data on MACOP-B/VACOP-B without rituximab, there are no statistically significant differences in terms of CR and RFS rates.     

Role of Radiation Therapy in the Treatment of Hodgkin Lymphoma

Radiation therapy has historically been the pillar of curative treatment for Hodgkin lymphoma (HL). With improved efficacy of systemic therapy and the ever-increasing recognition of treatment-related morbidity in long-term survivors, the role of radiotherapy has evolved significantly. Modern combined modality therapy (CMT) with multi-agent chemotherapy followed by involved site radiation therapy (ISRT) to initially involved sites of disease remains the gold standard for the majority of patients with HL. Reduction of long-term treatment-related toxicity has become the major driver in clinical trial design for early-stage HL while improved disease-specific survival remains the goal in patients with more advanced and unfavorable disease. This review will address the data supporting the use of radiotherapy in HL as well as specific methods for reducing late toxicity from radiotherapy.     

Radiation Therapy of Primary Malignant Lymphoma of the Brain

Primary malignant lymphoma of the brain (PMLB) is uncommon. Between 1975 and 1982, the authors observed 11 patients with histologically confirmed PMLB. Mean survival after radiation therapy was 7 months with 5 patients surviving for more than 2 years. Multifocal lesions were seen in 9 patients and spontaneous regression was seen at computed tomography in 2 patients. Radiation doses in excess of 30 Gy controlled the primary tumor, but intracranial recurrences occurred even after whole brain irradiation to 40 Gy. Only one patient had a relapse outside the central nervous system, and none had clinical evidence of seeding to the spinal canal. The authors postulate that PMLB usually is a multifocal intracranial disease, and that whole brain irradiation of at least 30 to 40 Gy should be given to all patients with this disease.     

A Review of Modern Radiation Therapy Dose Escalation in Locally Advanced Head and Neck Cancer

The management of head and neck cancer is complex and often involves multimodality treatment. Certain groups of patients, such as those with inoperable or advanced disease, are at higher risk of treatment failure and may therefore benefit from radiation therapy dose escalation. This can be difficult to achieve without increasing toxicity. However, the combination of modern treatment techniques and increased research into the use of functional imaging modalities that assist with target delineation allows researchers to push this boundary further. This review aims to summarise modern dose escalation trials to identify the impact on disease outcomes and explore the growing role of functional imaging modalities. Studies experimenting with dose escalation above standard fractionated regimens as outlined in National Comprehensive Cancer Network guidelines using photon therapy were chosen for review. Seventeen papers were considered suitable for inclusion in the review. Eight studies investigated nasopharyngeal cancer, with the remainder treating a range of subsites. Six studies utilised functional imaging modalities for target delineation. Doses as high as 85.9 Gy in 2.6 Gy fractions (EQD2 90.2 Gy₁₀) were reportedly delivered with the aid of functional imaging modalities. Dose escalation in nasopharyngeal cancer resulted in 3-year locoregional control rates of 86.6–100% and overall survival of 82–95.2%. For other mucosal primary tumour sites, 3-year locoregional control reached 68.2–85.9% and 48.4–54% for overall survival. There were no clear trends in acute or late toxicity across studies, regardless of dose or addition of chemotherapy. However, small cohort sizes and short follow-up times may have resulted in under-reporting. This review highlights the future possibilities of radiation therapy dose escalation in head and neck cancer and the potential for improved target delineation with careful patient selection and the assistance of functional imaging modalities.     

Dose Selection for Multiple Myeloma in Modern Era

PurposeThe management of multiple myeloma (MM) has evolved over the past 20 years, secondary to novel biologic therapeutics. Radiation therapy remains an important intervention in the management of painful lytic bone lesions. However, the currently used radiation therapy regimens were developed in the pre-biologic therapy era. The goal of this study is to assess the effects of dose and fractionation in pain control for patients with MM in the modern era.Methods and materialsWe conducted a retrospective study based on data collected from patients who received radiation therapy at our institute between 2007 and 2017. A total of 130 patients (266 treatment sites) were included in this study. Univariate Cox proportional hazards models were used to analyze the association of risk of pain recurrence with treatment characteristics and compute the hazard ratios (HRs).ResultsThe median follow-up time was 14 months. Patients who received a total dose of 20 to <30 Gy (including 20 Gy) had a significantly lower probability of pain recurrence when compared with those who received <20 Gy (HR, 0.36; 95% confidence interval, 0.14-0.94; P = .0365). There was no statistically significant difference in treatment response or pain recurrence between the different fraction numbers and sizes. However, we noted a trend indicating lower pain recurrence in the group that received 6 to 10 fractions of radiation therapy (P = .06). Among the most commonly used regimens, 8 Gy in a single fraction resulted in a statistically significant increased chance of pain recurrence compared with 20 Gy in 10 fractions and a borderline statistically significant increased chance of pain recurrence when compared with 30 Gy in 10 fractions.ConclusionsRadiation therapy remains highly effective at managing lytic bone lesions in patients with MM, and 6- to 10-fraction treatment courses are equally as effective as longer courses at treating these lesions. Treatment with 20 Gy in 10 fractions resulted in a significantly lower probability of pain recurrence when compared with 8 Gy in 1 fraction.     

The Use of Computed Tomography Numbers in Dose Calculations for Radiation Therapy

Although corrections for 'beam hardening' and 'scattering' have been implemented in currently available CT scanners, systematic differences exist between a real CT image and an ideal, artefact-free and monochromatic image. The appearance and magnitude of these differences are discussed. Conversion to the ideal image, i.e. conversion from CT number to X-ray attenuation coefficient at diagnostic photon energies, turns out to be possible with an accuracy of 5 per cent. In order to use the CT 'density' information from patients, in clinical photon and electron beam dose calculations, conversions must be made from the X-ray attenuation coefficient at diagnostic energies to relevant high energy radiation interaction properties. These conversions turn out to be possible within an accuracy also of 5 per cent. These limited accuracies cause errors in the photon beam dose calculation of less than 1 per cent of the dose maximum and errors in electron beam dose calculations of less than 2 per cent of the dose maximum.     

A Systematic Overview of Radiation Therapy Effects in Hodgkin's Lymphoma

A systematic review of radiation therapy trials in several tumour types was carried out by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on radiation therapy for Hodgkin's lymphoma (HL) is based on data from 12 randomized trials and 2 meta-analyses. Data from 3 prospective studies, 29 retrospective studies and 58 other articles were also used. In total, 58 scientific articles are included, involving 27 280 patients. The results were compared with those of a similar overview from 1996 including 38 362 patients. The conclusions reached can be summarized thus: Solid scientific documentation shows that in patients with HL more than 80% in the early stages and 60-70% of younger patients in advanced stages of disease are now cured by the development of radiotherapy and combination chemotherapy.Long-term follow-up shows that after 15 to 20 years the mortality from HL in early and intermediate stages is exceeded by other causes of death, mostly secondary malignancies and cardiac deaths, especially myocardial infarction.Convincing data show that radiotherapy plays a major role in the development of solid cancers and cardiovascular disease, but no randomized trials have been performed.During the past decade increasing awareness of fatal long-term sequelae has fundamentally changed treatment strategies in early and intermediate stages. A thorough long-term follow-up is essential to evaluate the effects of the modifications of the therapy.In early stages of disease extended field irradiation is now replaced by short periods of chemotherapy followed by limited radiotherapy to decrease late sequelae. This approach is strongly supported by early reports from randomized trials. Final results cannot be fully evaluated for many years.The optimal radiation dose and volume after chemotherapy are not defined or if irradiation is needed at all. Several studies are under way.In intermediate stages two recently reported randomized trials indicate that combined modality therapy is preferable and that involved field could replace extended field irradiation. It is still too early to draw any firm conclusions.In advanced stages, there is no evidence of any survival benefit from additional radiotherapy.The role of radiotherapy in the case of residual tumour and bulky disease still remains controversial.There is no scientific support for improved survival with radiotherapy in conjunction with high-dose chemotherapy with stem-cell support.Radiotherapy as salvage treatment might be an alternative in late limited nodal recurrence after initial chemotherapy. However, the body of knowledge is small.The role of radiotherapy in the treatment of HL is decreasing.