Secondary malignancy after radiotherapy for Hodgkin Lymphoma

Hodgkin lymphoma (HL), formerly called Hodgkin disease, has attained high survival rates (≥75% at ten years for all grades and stages combined, age-standardised), with continued improvements in treatment modalities since the 1940s, when radiotherapy was first used to combat the disease. Today, sequential chemotherapy and radiation are used in many cases, but certain groups of patients, dependent on stage and prognostic factors, will have either chemotherapy or, in limited stage nodular lymphocyte predominant HL, radiotherapy alone to minimise exposure to potentially toxic treatment which carries the risk of long-term sequelae, such as the recognised increased risk of secondary cancers in HL survivors. The original radiotherapy approach for limited (stage I or II) disease above the diaphragm is known as wide-field (WFRT) or mantle radiotherapy, a mantle being a cloak worn draped over the shoulders, and the distribution of radiotherapy fields resembles this appearance. This approach treats the major lymph node groups above the diaphragm, including mediastinal, hilar, axillary, supraclavicular and cervical chains. The standard dose would be considered as 30-35Gy in 20 fractions over three weeks. Although this article focuses mainly on the after-effects of WFRT to the upper body, a similar approach for disease below the diaphragm is termed inverted-Y radiotherapy, treating the para-aortic, iliac and pelvic nodal groups. A combination of wide-field upper body and para-aortic nodal radiotherapy is referred to as extended-field radiotherapy (EFRT). Immediate toxicities of WFRT include reddening of the skin, hair loss in the treated area, oesophagitis, nausea, fatigue and bone marrow suppression. These would be generally managed with supportive medications and blood products as required. Radiation pneumonitis (RP) can develop in those treated with mediastinal radiotherapy, which causes cough and pronounced breathlessness in up to 15% of treated patients and is managed with steroids. Radiologic studies showing signs of inflammation in the affected lung tissue indicate the numbers affected by subclinical RP is much higher – around 65% in some series. Long-term side effects of WFRT, among others, include soft tissue fibrosis and skin thickening, telangiectasia, hypothyroidism, cardiac perfusion defects and reduction in ejection fraction and the development of a second solid tumour. Lung fibrosis can develop in the months and years following RP. The affected areas often demonstrate straight edges on imaging and sharp opposition to unaffected tissue, corresponding to the applied radiation fields at treatment. Certain groups of patients are at greater risk of developing fibrosis: Older age at treatment, those with co-morbidities and sequential chemotherapy delivery.