Francesco Felicetti

Endocrine health conditions in adult survivors of childhood cancer: the need for specialized adult-focused follow-up clinics

BACKGROUND Survival rates among childhood cancer survivors (CCS) have enormously increased in the last 40 years. However, this improvement has been achieved at the expense of serious late effects that frequently involve the endocrine system. AIM To evaluate the cumulative incidence of endocrine diseases in a cohort of long-term CCS. MATERIALS AND METHODS We analyzed the clinical data of 310 adults, followed for a median time of 16.0 years after the first cancer diagnosis. The monitoring protocols applied to each patient were personalized on the basis of cancer diagnosis and previous treatments, according to the Childrens Oncology Group guidelines. RESULTS The cumulative incidence of endocrine late effects steadily increased over time. At the last follow-up visit available, 48.46% of females and 62.78% of males were affected by at least one endocrine disease. The most common disorders were gonadal dysfunction, primary hypothyroidism, and GH deficiency (GHD). The main risk factors for endocrine disease were male sex (hazard ratio (HR)=1.45, 95% confidence interval (95% CI) 1.05-1.99), radiotherapy (HR=1.91, 95% CI 1.28-2.84), hematopoietic stem cells transplantation (HR=3.11, 95% CI 2.23-4.34), and older age at cancer diagnosis (HR=1.89, 95% CI 1.25-2.85). Male sex was associated with a higher risk of gonadal disorders, whereas radiotherapy specifically increased the risk of GHD and thyroid dysfunction. CONCLUSIONS Endocrine disorders among CCS have a high prevalence and increase over time. Thus, endocrinologists need to cope with an increasing demand for health care in a field that is still little developed and that, in perspective, could also be extended to some selected types of adult cancer survivors.

Ultrasound surveillance for radiation-induced thyroid carcinoma in adult survivors of childhood cancer

INTRODUCTION The optimal surveillance strategy to screen for thyroid carcinoma childhood cancer survivors (CCS) at increased risk is still debated. In our clinical practice, beside neck palpation we routinely perform thyroid ultrasound (US). Here we describe the results obtained using this approach. METHODS We considered all CCS referred to our long term clinic from November 2001 to September 2014. One hundred and ninety-seven patients who had received radiation therapy involving the thyroid gland underwent US surveillance. Thyroid US started 5 years after radiotherapy and repeated every 3 years, if negative. RESULTS Among 197 CCS previously irradiated to the thyroid gland, 74 patients (37.5%) developed thyroid nodules, and fine-needle aspiration was performed in 35. In 11 patients the cytological examination was suspicious or diagnostic for malignancy (TIR 4/5), whereas a follicular lesion was diagnosed in nine. Patients with TIR 4/5 cytology were operated and in all cases thyroid cancer diagnosis was confirmed. The nine patients with TIR 3 cytology also underwent surgery and a carcinoma was diagnosed in three of them. Prevalence of thyroid cancer was 7.1%. Tumour size ranged between 4 and 25 mm, but six (43%) were classified T3 because of extra-thyroidal extension. Six patients had nodal metastases; in eight patients the tumour was multifocal. At the time of the study all patients are disease free, without evidence of surgery complications. CONCLUSION Applying our US surveillance protocol, the prevalence of radiation-induced thyroid cancer is high. Histological features of the thyroid cancers diagnosed in our cohort suggest that most of them were clinically relevant tumours.

GH deficiency in adult survivors of childhood cancer

Childhood cancer survivors (CCS) are a fast growing population, but late adverse effects of cancer therapies are not rare. In CCS treated with cranial radiotherapy, growth hormone deficiency (GHD) is a well-known occurrence and the potential impact of GH replacement therapy on the global outcome of CCS is under continuous evaluation. In the present review, we discuss advantages and disadvantages of GH replacement therapy in survivors of pediatric malignancies, taking into consideration the different reasons for treating GHD during childhood or adult life. It is doubtless that GH treatment is advisable to obtain a normal growth in pediatric patients. As far as the beginning/continuation of the replacement therapy in adult age is concerned, contrasting results have been reported in literature. The suggestion is that the decision to treat adult CCS should be taken after careful evaluation of each patients clinical history and of the potential side effects, in agreement with the patients.

Thyroid Cancer in Cancer Survivors: The Role of Ultrasound and the Need for Committed Specialists

In their interesting review, Rose et al focus on the appropriate use of clinical imaging for diagnosing treatmentrelated complications, recurrent tumor, or emergence of second primaries in cancer survivors, which may result from mutagenic effects of radiation. We completely agree with the authors’ conclusion, which suggests that survivors need to be considered for their higher risk of long-term sequelae, including second malignancies, and that general practitioners can rely on imaging in conjunction with physical examination and laboratory values. In this setting, ultrasound represents a noninvasive, lowcost, and widely available imaging method to screen for thyroid cancer those survivors who had previously been treated by radiotherapy involving the head, neck, or upper thorax. While ultrasound screening for thyroid cancer in the general population is not cost-effective and may lead to unnecessary surgery, guidelines for diagnosis and management of thyroid nodules suggest screening by ultrasound patients at high risk for the development of thyroid malignancies. In our long-term follow-up Unit for Childhood Cancer Survivors (CCSs), we routinely perform thyroid ultrasound in all the patients who had been exposed to ionizing radiation to the neck. By doing so, we diagnosed a much higher number of thyroid carcinomas than expected. We think that it is worthy, because radiation-induced thyroid carcinoma has been suspected to be more aggressive, and early detection likely improves the outcome of these patients. Moreover, typical ultrasound findings, in conjunction with hormonal tests and physical examination, may help

Cancer survivors: An expanding population with an increased cardiometabolic risk

In the last decades the survival rate of patients diagnosed with cancer - both in childhood and adulthood - significantly improved, leading to a growing number of cancer survivors (CS) within general population. Despite the better survival rate related to the cancer diagnosis, CS show increased mortality and morbidity if compared to non-cancer population, due to the occurrence of health conditions categorized as late effects of previous anticancer treatments. Cardiovascular (CV) diseases are one of the main responsible for this increased morbidity of CS. Besides the direct injury that both chemotherapy and radiotherapy can produce to CV system, in recent years the role of metabolic syndrome in the pathogenesis of CV diseases in CS is emerging. The relationship between anticancer treatments and the development of metabolic alterations is crucial to understand and manage the cardiometabolic risk in CS. The aim of this manuscript is to review the pathophysiological and clinical features of CV risk factors in CS, exploring in more detail certain subgroups of CS (breast cancer, transplanted patients as well as lymphoma survivors) that show peculiar clinical aspects and are burdened by a greater CV risk.

Thyroid Autoimmunity and Cancer

Cancer and autoimmune diseases are often associated in the same individual. The functional link between the immune system and cancer development is only partially known. Even though the immune system can control the development of cancer through immune surveillance, cancer cell can escape it. It is debated whether autoimmune diseases have to be regarded as a cancer cause or its consequence. In particular, the association between autoimmune thyroiditis and thyroid cancer (TC; especially papillary carcinoma) is a fascinating model of this complex relationship. In this review, we present data reported in literature about autoimmune thyroiditis and papillary TC, and on the basis of available data, we try to clarify the present knowledge.

Come preservare la fertilità nel paziente oncologico

SommarioGrazie ai progressi compiuti dall’oncologia negli ultimi decenni, oggi le percentuali di guarigione dei bambini e dei giovani adulti affetti da tumore si attestano intorno all’80%. Tuttavia, anche con i moderni protocolli di terapia oltre il 50% dei giovani pazienti sviluppa nel tempo infertilità, nella maggior parte dei casi dovuta a danno gonadico diretto. La proposta di preservare la fertilità, in un momento così critico della vita, diviene quindi essenziale di fronte a trattamenti che possono ledere in modo irreversibile la capacità fecondante dell’individuo. Esistono per entrambi i sessi metodi consolidati e approcci ancora sperimentali per salvaguardare le potenzialità procreative cui si deve ricorrere nel contesto dell’inquadramento oncologico iniziale poiché, tuttora, non esistono parametri per poter prevedere con certezza l’entità dell’effetto gonadotossico dei vari trattamenti oncologici. I problemi attualmente emergenti sono relativi alla preservazione della fertilità nei prepuberi e su tale aspetto si sta soprattutto orientando la ricerca biomedica.

Complicanze endocrine a lungo temine nei cancer survivors

SommarioOggi il paziente oncologico ha probabilità di guarigione molto più elevate che in passato, soprattutto in ambito pediatrico. L’aumentata efficacia dei protocolli di terapia si paga però, non di rado, in termini di late effects, cioè di malattie causate dalle terapie antitumorali che insorgono o persistono dopo più di cinque anni dalla guarigione del tumore. Per quanto questi late effects possano interessare qualsiasi organo o apparato, le complicanze endocrinologiche sono certamente tra le più frequenti, arrivando a interessare oltre la metà dei cancer survivors. Per questo motivo, l’endocrinologo riveste un ruolo di primo piano nel monitoraggio clinico a lungo termine dei pazienti guariti da un tumore.