Hodgkin's Disease and Chemotherapy Before 40 Years

A few studies have focused on other solid cancers (colorectal, prostate). On the other hand, the study of cognitive impairment in Hodgkin's disease remains less developed, and structural and functional post-therapy MRI studies have never been carried out. The impact of cognitive impairment on Hodgkin's disease is rarely, if ever, assessed in routine clinical practice, despite the fact that it is truly disabling in 16 to 30% of patients. Cognitive impairment can persist long after diagnosis and treatment. A recent study examining cognitive functioning in patients an average of 13 years after treatment found that disorders persisted in 52% of cases, with attentional, working memory and dysexecutive (planning) difficulties. These disorders have a significant impact on the daily and professional lives of these young, often working patients. Their rapid development and persistence after treatment can therefore represent a real limiting factor, impacting both professional integration and quality of life. Finally, the current state of knowledge does not allow us to dissociate cognitive disorders from emotional disorders and fatigue, which represent a major patient complaint. A better definition of the nature, pathophysiology and specificity of these disorders would therefore enable us to take better account of their repercussions (social, professional and on quality of life) and provide better care (in terms of cognitive remediation or psychological support).

A prospective, longitudinal, multicenter, case-control interventional study in which cases are patients with Hodgkin's disease (HD) treated with CT +/- radiotherapy and controls are healthy participants will be conducted. The aim is to study the prevalence and nature of treatment-induced cognitive impairment and its correlation with emotional comorbidities, as well as structural and functional brain disorders on MRI. The patient will thus be his or her own witness, the reference state being that at the time of diagnosis, before any treatment. The fact that this state has not already been altered by the disease itself, will be verify thanks to comparison with controls.

Hodgkin's disease is a neoplasia of lymphoid tissue characterized by the characteristic presence of Reed Sternberg cells. This disease is preferentially affecting young patients under the age of 40. It is the leading cause of solid cancer in adolescents and young adults. At the time of diagnosis, positron emission tomography (PET scan) is used to determine the stage of the disease. The Ann Arbor classification differentiates between localized (I-II) and disseminated (III-IV) stages. At St Vincent de Paul Hospital (Lille, France), 60-70% of diagnoses are performed at a localized stage, versus 30-40% at a disseminated stage.

Treatment is based on chemotherapy alone (disseminated forms) or a combination of chemotherapy and radiotherapy (localized forms). The average duration of treatment is around 5 months for localized forms, and between 6 and 7 months for disseminated forms. The prognosis is favorable, with a sustained complete remission rate of up to 85% in patients of all stages. The aim of treatment for these patients is therefore to achieve complete remission while reducing medium- and long-term side-effects, which could improve their quality of life.

Recently, treatment strategies have evolved, with de-escalation of chemotherapy intensity, and strategies guided by early response to Positron emission tomography (PET) scan have become the norm, in order to significantly reduce the risk of long-term side effects.

The onset of cognitive and mood disorders in patients undergoing neoplastic treatment, particularly after chemotherapy, is a frequent and disabling complication. Numerous studies have identified the occurrence of subjective and objective attentional, memory and executive disorders. However, these studies are often limited by their small size, the variability of populations, their heterogeneous design, and the variability of neuropsychological measures and criteria for defining a cognitive deficit. Furthermore, the majority of studies have focused on patients treated with chemotherapy (CT) for breast neoplasia, through neuropsychological assessment and exploration by structural and functional medical imaging. Thus, the onset of cognitive disorders (more of a dysexecutive nature) in these patients has been clearly identified, both early at the end of treatment and over the long term.

Moreover, the social, occupational and quality-of-life repercussions of these disorders have only recently been explored. However, initial results point to a positive correlation between subjective perception of cognitive functioning and quality of life. Nevertheless, the probably multifactorial etiology of these disorders remains unclear. A recent review of the literature clarifies the factors predisposing to the development of these cognitive disorders. Factors such as age and genetic polymorphisms in apolipoprotein E, catechol-O-methyltransferase and Brain-derived neurotrophic factor (BDNF) may predispose individuals to a higher risk of cognitive disorders. In addition, changes in brain morphology (reduced grey matter volume) and changes in brain connectivity could be at the root of these disorders.

In these studies, magnetic resonance imaging (MRI) identified the presence of frontal and posterior parietal gray matter volume loss in these patients. MRI also provides information on the structural and functional functioning of brain networks. For example, changes in the integrity of substance bundles have been identified using the diffusion tensor technique. In functional MRI (fMRI (BOLD signal)), numerous disturbances have been identified: hypoactivation of the prefrontal cortex and parietal lobes during activation of the executive control network, hypoactivation of the prefrontal cortex and hippocampi during tasks involving working memory, alteration of the dorsal attentional network and the default mode network.

In addition, one study suggests the presence of pre-treatment network alterations in patients with breast neoplasia. At pathophysiological level, animal models suggest the involvement of alterations in neurogenesis, mitochondrial dysfunction or cerebral cytokine response.

Eligibility Criteria:
Inclusion criteria - case :

* Patient with newly diagnosed Hodgkin's disease
* With intention to treat with chemotherapy +/- radiotherapy
* Aged between 18 and 40 years
* Fluency in French
* Able to undergo neuropsychological evaluation (absence of major sensory disorders)
* Agreeing to take part in the study and having signed the informed consent form
* Affiliated with a social security scheme

Inclusion criteria - controls:

* Individual without Hodgkin's disease
* Aged between 18 and 40
* Proficient in French
* Agreeing to participate in the study and having signed the informed consent form
* Affiliated with a social security scheme

Cases and controls will be matched on age (± 5 years difference), and number of years of education (difference ≤ 2 years).

Non-inclusion criteria - cases + controls :

* Claustrophobia preventing MRI from being performed
* Contraindication to MRI
* Previous chemotherapy
* History of neurological or psychiatric illness, including severe depression, or cognitive impairment
* Use of medications that may cause neurological or psychiatric signs
* Alcohol or drug abuse
* Pregnant women
* Persons under guardianship or trusteeship