Classic Hodgkin lymphoma (CHL) is a malignancy involving lymph nodes and the lymphatic system and is generally characterized by the presence of large binucleate cells, (Hodgkin Reed-Sternberg [HRS] cells) in a background of benign inflammatory cells. Most patients are diagnosed between 15 and 30 years of age, followed by another peak in adults aged 55 years or older.
Chemotherapy protocols for the treatment of this pathology have evolved over the years, and those used in the patients in this article are the CCG 5942 protocol used until 2015, and the Euronet protocol, after 2015.
For patients before 2015, CCG 5942 was the chosen protocol and favourable risk and intermediate risk patients received 4 and 6 monthly cycles of cyclophosphamide, vincristine, prednisone, procarbazine, doxorubicin, bleomycin, and vinblastine (COPP/ABV) respectively. High risk patients received 6 cycles of treatment: 2 cycles of COPP/ABV, 2 cycles of high-dose cytarabine with etoposide, and 2 cycles of cyclophosphamide, vincristine, doxorubicin, methylprednisolone and prednisone. Patients were evaluated at completion of chemotherapy; all patients who achieved a complete response were eligible for randomization to receive either LD-IFRT or no further therapy. Patients who did not achieve a complete response to chemotherapy were non-randomly assigned to receive LD-IFRT. A total dose of 21 Gy was given in 12 fractions to all lymph node regions containing radiologically abnormal lymph nodes at the time of diagnosis.
This meant that patients before 2015 either received 140 mg/m2 if it was a low-risk patient, 210 mg/m2 for an intermediate risk or 220 mg/m2 for an high risk.
For patients diagnosed after 2015 with stage IA, IIA, and IB CHL (with or without bulky disease) treatment was according to EuroNet-PHL-C1.
After initial cycles of chemotherapy, patients with adequate response may avoid RT and move to routine follow up. Patients with inadequate response receive ISRT (to all sites and boost to sites of inadequate response per EuroNet-PHL-C1.
For the regimen based on EuroNet-PHL-C1, after 2 initial cycles of OEPA, patients with adequate response are treated with 2 cycles of COPDAC (cyclophosphamide, vincristine sulfate, prednisone, and dacarbazine).
Patients with stage IIB, IIIA, IIIB, and IV followed EuroNet-PHL-C1 protocol.
For treatment based on EuroNet-PHL-C1, after 2 initial cycles of OEPA, patients with adequate response are treated with 4 cycles of COPDAC. Patients with inadequate response are treated with 4 cycles of COPDAC and ISRT to all sites and boost to sites of inadequate response. In both cases, based on an end of therapy PET assessment, patients were either followed up or considered for biopsy to confirm persistent active disease.
This meant that after 2015 patients were submitted to either 140 mg/m2 or 160 mg/m2 of anthracycline dose.
Cardiotoxicity is one of the possible consequences of treating Hodgkin's lymphoma. This assumes a very important role in the lives of patients since, increasingly, they have a higher survival rate, better quality of life and, inherently, longer survival. This is due to the improvement in the treatment of this pathology. (1) However, success in fighting this entity also provides a greater probability of deleterious cardiovascular alterations, such as: electrocardiographic alterations, left ventricular dysfunction subclinical or with heart failure. These changes have been increasingly reported. (two)
Additionally, these changes take on even greater dimension when we talk about individuals with pathology in pediatric age due to their greater susceptibility to this iatrogenic cardiac dysfunction. That said, the number of studies that investigated these changes in this specific population is still small and, as such, the need for research in this area is evident. (3)
Anthracycline-related cardiomyopathy is one of the most relevant patterns of cardiotoxicity regarding cancer therapy. There is evidence that left ventricular systolic dysfunction is directly related to the use of cumulative doses of anthracyclines. The cumulative total dose is the main risk factor for the occurrence of congestive heart failure related to the use of anthracyclines. However, there is no safe dose at the cardiotoxic level, which must always be balanced with its degree of anticancer efficacy.
Currently, it is estimated that more than 50% of cancer patients are treated with radiotherapy. Along with the development of new chemotherapeutic agents, radiotherapy has revolutionized the prognosis of individuals with various types of cancer. However, late cardiovascular effects are often detected after the use of this therapeutic method. Most clinical information obtained on cardiotoxicity from chest irradiation is based on studies of individuals with breast cancer or Hodgkin's lymphoma who developed symptomatic disease during treatment or monitoring.
All risk factors for cardiotoxicity resulting from Hodgkin's lymphoma therapy are closely related to early and late cardiotoxicity, and not to acute cardiotoxicity, according to the scientific literature on this topic.
The major risk factors for cardiotoxicity are younger age, female sex, high dose of anthracyclines, mediastinal radiotherapy, arterial hypertension, coronary heart disease and electrolyte disturbances.
To reduce cardiotoxicity, the dose of anthracyclines can be limited, the use of structural analogues of anthracyclines or, mainly, cardioprotective pharmacological agents can be promoted. (5)
This study aims to analyse the occurrence of these harmful effects and the impact of factors such as patient characteristics, as well as to analyse prevention measures and early diagnosis in their evolution.