Second Cancers in Classical Hodgkin Lymphoma and Diffuse Large B-Cell Lymphoma: A Systematic Review by the Fondazione Italiana Linfomi

Abstract

Background: The increase of lymphoma patient survival led to a modification of the incidence of long-term sequelae, including second malignancies (SM). Several groups have dealt with the incidence of SM, according to the primary treatment; however, a standardized approach for the early detection and screening of SM in the population of lymphoma survivors should be implemented. Methods: A systematic review was conducted by Fondazione Italiana Linfomi (FIL), in order to define the incidence of SM, the impact of modern radiotherapy on SM risk, and the usefulness of tailored follow-up and screening strategies for early diagnosis of SM. Classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL) survivors were investigated. The MEDLINE, Embase, and Cochrane Library databases were checked for relevant reports published up to January 2020. The selection process was reported according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Results: A total of 27 full-text manuscripts resulted as eligible for the analysis. The incidence of SM in cHL patients treated with ABVD was higher compared to the general population and was even higher in patients treated with intensified regimens. The risk increased over time, as well as after 10–15 years from therapy, and was augmented by radiotherapy exposure. In DLBCL, more intensive regimens (i.e., R-CHOEP or R-MegaCHOEP) vs. R-CHOP were associated with a higher SM incidence. Salvage chemotherapy and autologous stem cell transplants increased the risk of SM in both cHL and DLBCL cohorts. A lower incidence of SM, particularly of breast cancer (BC), was shown in cohorts of cHL survivors treated with reduced radiation volumes and doses (involved fields vs. extended fields), but robust trials are still lacking. Considering the advantage of a structured screening for early detection of SM, all the included studies regarded cHL survivors and screening strategy for early BC detection. Moreover, the authors discuss additional papers, to guide the early diagnosis of lung, colorectal, skin, and thyroid cancer in patients at risk due to family history, drug or RT exposure, or unhealthy lifestyles. These screening strategies all passed through patient awareness. Conclusion: A modern approach to chemotherapy and radiotherapy led to a lower risk of SM, which should be confirmed over time. Early detection of secondary cancers could be achieved through a tailored screening program, according to the individual risk profile.

Provision and delivery of survivorship care for adult patients with haematological malignancies: A scoping review protocol

“…A recent group of systematic reviews has been undertaken by researchers from the Fondazione Italiana Linfomi covering a variety of late effects and elements of survivorship. However, their patient population, inclusion criteria, and search strategies are narrower than the prospective review intends [ 31 – 36 ]. Other reviews that have specifically investigated models of SC have only included a small number of patients diagnosed with a HM alongside other tumour sites [ 37 , 38 ], used less rigorous methodologies [ 8 , 39 ], or need apprising with more recent research [ 18 , 19 ].…”

Clinical Management of Long-Term Survivors after Classical Hodgkin Lymphoma and Diffuse Large B-Cell Lymphoma

“…This issue has gained further attention with a new treatment approach which guarantees a higher probability of curing the disease and, as a consequence, a higher number of patients at risk of SC. In a systematic review, the incidence of SC was found to be higher in cHL and DLBCL patients treated with standard first-line treatment than in the general population, and increased over time [ 6 ]. As expected, the use of intensified regimens and autologous stem cell transplants increased the risk of SC in both patient populations, and was augmented by RT exposure.…”