Updated statistics with estimated new cases and deaths for 2019 (cited American Cancer Society as reference 1).
Added text to state that the best predictor of treatment failure is a positron emission tomography–computed tomography (PET-CT) scan obtained after two cycles (PET-2 scan) of chemotherapy (cited Agostinelli et al. as reference 6 and Gallamini et al. as reference 7). For limited-stage disease, there are frequent false-positive tests because the relapse risk is low. For advanced-stage disease, up to 15% of patients relapse despite a negative PET-2 scan. Also added that combining biomarkers with PET-CT scanning responses or calculating metabolic tumor volume with PET-CT scanning are methods under evaluation to improve prognostic predictions (cited Spina et al., Cottereau et al., Akhtari et al., and Moskowitz et al. as references 8, 9, 10, and 11, respectively).
Added text to state that a retrospective survey of over 6,000 HL patients treated on trials between 1964 and 2004 found that cardiac exposure to radiation and utilization of doxorubicin were significant predictors of ischemic heart disease, congestive heart failure, arrhythmias, and vascular disease.
Revised text to state that other therapies have been proposed for elderly patients too frail to withstand conventional regimens, but no randomized trials have been conducted with these regimens. Also added that brentuximab has been combined with dacarbazine (cited Friedberg et al. as reference 6) or sequentially with AVD (doxorubicin, vinblastine, dacarbazine) (cited Evens et al. as reference 7), reporting acceptable toxicities in an elderly population.
Revised Table 4 to include additional chemotherapy regimens used to treat HL.
Added text to state that when mediastinal radiation will encompass the left side of the heart or will increase breast cancer risk in young female patients, proton therapy may be considered to reduce the radiation dose to organs at risk (cited Dabaja et al. as reference 12). Revised text to state that when used as a single modality, radiation therapy is delivered to the neck, chest, and axilla and then to an abdominal field to treat para-aortic nodes and the spleen. In some patients, pelvic nodes are treated with a third field.
Added text to state that a retrospective review found that infradiaphragmatic early-stage disease appears to have an inferior outcome compared with the more frequent supradiaphragmatic disease, with a decrement in overall survival (OS) of 6% (cited Sasse et al. as reference 1 and level of evidence: 3iiiD).
Added text to state that in the German Hodgkin Study Group HD18 trial, PET scan negativity after two cycles of escalated BEACOPP allowed reduction to four cycles of therapy instead of six or eight cycles because of the equivalent 5-year progression-free survival (cited Borchmann et al. as reference 16 and level of evidence 1iiDiii). Also added that the HD18 trial established a Deauville score of 4 or 5 as PET-2 positive based on a 3-year OS (cited Kobe et al. as reference 17).
Revised text to state that other trials have investigated the role of PET scans or new combinations for patients with advanced classic HL.
Added Shah et al. as reference 16 and Martínez et al. as reference 17.
Added text to state that in a phase 1/2 study of 62 relapsed or refractory HL patients, the combination of nivolumab and brentuximab was well tolerated and resulted in an 82% objective response rate and a 61% complete response rate, allowing patients to proceed to an autologous stem cell transplantation (cited Herrera et al. as reference 43 and level of evidence 3iiiDiv).
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