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Novelty in total body irradiation (TBI) as part of pre-transplant conditioning regimens lacked until recently, despite the developments in the field of allogeneic stem cell transplants. Long-term toxicities have been one of the major concerns associated with TBI in this setting, although the impact of TBI is not so easy to discriminate from that of chemotherapy, especially in the adult population. More recently, lower-intensity TBI and different approaches to irradiation (namely, total marrow irradiation, TMI, and total marrow and lymphoid irradiation, TMLI) were implemented to keep the benefits of irradiation and limit potential harm. TMI/TMLI is an alternative to TBI that delivers more selective irradiation, with healthy tissues being better spared and the control of the radiation dose delivery. In this review, we discussed the potential radiation-associated long-term toxicities and their management, summarized the evidence regarding the current indications of traditional TBI, and focused on the technological advances in radiotherapy that have resulted in the development of TMLI. Finally, considering the most recent published trials, we postulate how the role of radiotherapy in the setting of allografting might change in the future.

The transition from pediatric to adult care poses several emotional and personal challenges to adolescents and young adult (AYA) childhood cancer survivors (CCSs), which need attention to avoid the risk of nonadherence and medical dropout. This brief report describes the condition of AYA-CCSs at the moment of transition in terms of emotional state, personal autonomy, and expectations regarding future care. The results provide insights for clinicians dealing with survivorship care, to enhance AYA-CCSs emotional resilience and to support them in being in charge of their health, thus facilitating their transition to adulthood.

To date, there are heterogeneous studies related to childhood cancer survivors' (CCS) employment rates. Given the importance of this topic, we aimed to perform a systematic review and meta-analysis to investigate the prevalence of employment among CCS and to examine its association with socio-demographic and clinical factors. We followed the PRISMA guidelines to search for pertinent articles in relevant electronic databases. Eighty-nine articles comprising 93 cohorts were included. The overall prevalence of employment was 66% (CI: 95% 0.63-0.69). Subgroup meta-analyses showed that lower rates were found for central nervous system tumor survivors (51%, CI: 95% 0.43-0.59), and for CCS treated with cranial-radiotherapy (53%, CI: 95% 0.42-0.64) or haematopoietic stem-cell transplantation (56%, CI: 95% 0.46-0.65). The studies conducted in Asia highlighted employment rates of 47% (CI: 95%, 0.34-0.60). Univariate meta-regressions identified the following socio-demographic factors associated with higher rates of employment: a female gender ( p = 0.046), a higher mean age at the time of investigation ( p = 0.00), a longer time since diagnosis ( p = 0.00), a higher educational level ( p = 0.03), and a married status ( p = 0.00). In conclusion, this systematic review and meta-analysis provides evidence that two-thirds of CCS are employed worldwide. Identifying vulnerable groups of CCS may allow for the design of multidisciplinary support strategies and interventions to promote employment in this population.

Late effects of cancer and its treatments during childhood or adolescence can impact work placement and increase the risk of unemployment. The aim of this study is to describe the work placement and the perceived job and economic satisfaction of long-term childhood cancer survivors (CCS). Jobs have been categorized according to the International Standard Classification of Occupations version 08 (ISCO-08), and satisfaction has been evaluated through the Satisfaction Profile (SAT-P). Out of 240 CCS (female = 98) included: 53 were students, 46 were unemployed and 141 were employed. Within unemployed survivors, 89.13% were affected by late effects (n = 41). The presence of at least one severe late effect was significantly associated with the probability of unemployment (OR 3.21; 95% CI 1.13−9.12, p < 0.050), and having any late effect was inversely related to the level of satisfaction of the financial situation of unemployed CCS (b −35.47; 95% CI −59.19, −11.74, p = 0.004). Our results showed that being a survivor with severe comorbidities has a significantly negative impact on occupation and worsens the perception of satisfaction of economic situations. Routinary follow-up care of CCS should include the surveillance of socioeconomic development and provide interventions, helping them to reach jobs suitable for their health.

Hodgkin lymphoma (HL) is today one of the most curable pediatric cancers. Despite survival rates now exceeding 90%, survivors of pediatric HL are still at higher risk to develop late effects of cancer therapy. Premature aging has been proposed as a paradigm to explain the onset of long-term complications in these subjects. High levels of advanced glycation end products (AGEs), together with chronic inflammation and oxidative unbalance, have been shown to be among the main factors contributing to aging. The present study aims to evaluate glycoxydation, inflammatory status, and oxidative stress in plasma and peripheral blood mononuclear cells (PBMC) obtained from 20 adult survivors of pediatric HL and 40 age- and sex-matched healthy controls. After the isolation of PBMC and the collection of plasma, we performed the analyses of gene expression by qRT-PCR and measured inflammatory and oxidative-stress markers. AGEs plasma levels, expressed as Nϵ-carboxymethyl-lysine and methylglyoxal hydroimidazolone, were markedly higher in HL survivors than in healthy subjects. HL survivors also showed a condition of higher oxidative stress, as demonstrated by an increased expression of NADPH oxidase on PBMC. Antioxidant defenses, evaluated in terms of alpha-tocopherol, GSSG/GSH ratio and catalase plasma levels, were strongly impaired in survivors. This pro-oxidative condition led to the over-expression of both NLRP3 and NFkB genes in PBMC and, consequently, to increased plasma levels of interleukin(IL)-1β and IL-6. Finally, the expression of the receptors for AGEs in PBMC confirmed the dysregulated AGE pathways. Data show AGEs accumulation in survivors of pediatric HL. The consequent activation of the receptor for AGEs leads to the persistent activation of intracellular signaling toward inflammation. These results suggest that the co-existence of AGEs accumulation, unbalanced oxidative status, and inflammation could play a role in the onset of late complications in HL survivors., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Despite a good prognosis, thyroid cancer (TC) survivors often report psychological distress and decreased quality of life. This longitudinal study aims to evaluate TC survivors' levels of distress, anxiety, depression and unmet needs, checking potential life events., Methods: Distress Thermometer, Hospital Anxiety Depression Scale, Supportive Care Need Survey (short form) and Interview for Recent Life Events were administered to 73 TC survivors (T0) and 44 of them were re-tested one year later (T1). Participants were at 0-5, 5-10 or >10 years from the end of their cancer-related treatments., Results: At T0, distress, anxiety and depression mean scores were 6.4, 6.8 and 5.3, while at T1 they were 5.5, 4.8 and 5.1. Only anxiety scores decreased significantly between T0 and T1. 50.7% of patients had unmet psychological needs at T0 and 50.0% at T1. Most participants were satisfied in the communicative/ informative (T0:79.5%; T1: 77.3%) and social/health care areas (T0:74.0%; T1:75.0%). The most experienced stressful events detected concerned their working areas., Conclusions: Results confirmed that patients reported distress, anxiety and depression concerns even many years after the end of treatments. Both medical and psychological surveillance are relevant to improving TC survivors' wellbeing., (© 2021. The Author(s).)

High-dose chemotherapy and radiotherapy, administered as a conditioning regimen before stem cell transplantation, are known to negatively impact testicular function and sexuality. However, to date, only a few studies have simultaneously analyzed the real prevalence of these complications in this clinical setting. Therefore, this study aimed to assess the prevalence of testicular dysfunction and sexual impairment in a cohort of males who underwent allogeneic stem cell transplantation in adulthood. This observational, cross-sectional, single-center study consecutively enrolled 105 subjects on outpatient follow-up. Testicular function and sexuality were evaluated through a hormonal profile (testosterone, follicle-stimulating hormone, luteinizing hormone, and inhibin B) and the IIEF-15 questionnaire, respectively. We found a higher prevalence of hypogonadism (21%), impaired spermatogenesis (87%), and erectile dysfunction (72%) compared with the general population. Chronic graft-versus-host disease, especially of moderate/severe grade, was associated with an increased risk of developing erectile dysfunction (odds ratio, 6.338). Moreover, a high proportion of patients presented with alterations in all domains of sexual function, even after complete clinical remission of hematologic disease. Our data confirm both testicular function and sexuality alterations as frequent complications after allogeneic stem cell transplantation. A multidisciplinary approach is advisable for early diagnosis and adequate treatment., (Copyright © 2020 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Cancer therapy-induced bone loss (CTIBL), occurring especially in hormone-treated breast and prostate cancer patients, is a noteworthy long-term consequence of cancer treatments. Because of its negative impact on the quality life of cancer survivors, it deserves much attention. We here summarize the pathophysiology of CTIBL in breast and prostate cancer, its clinical presentation, management, and treatment., (© 2021 S. Karger AG, Basel.)

Cardiovascular diseases represent one of the most common and serious late complications of anticancer treatments. In the general population, metabolic syndrome is closely related to the risk of cardiovascular events and mortality. In recent years, metabolic syndrome has gained attention as a crucial determinant of long-term cardiovascular risk in cancer survivors. Several risk factors have been associated with metabolic syndrome after cancer treatments, even if the pathophysiological mechanisms of this association are not fully understood. This chapter reviews the clinical features of metabolic syndrome in cancer survivors, analyzing in more detail patients treated with hormonal therapy and survivors of hematopoietic stem cell transplantation, who are burdened with a greater cardiovascular risk. Moreover, the role of lifestyle factors in the development of metabolic syndrome is discussed as well as the screening strategy for the early detection of metabolic alterations in cancer survivors. Finally, we discuss the available recommendations for cardiovascular risk assessment in cancer survivors and treatments for metabolic syndrome in this specific context., (© 2021 S. Karger AG, Basel.)

Introduction: Despite significant advances in treatment and prevention, graft-versus-host disease (GVHD) still represents the main cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Thus, considerable research efforts have been made to find and validate reliable biomarkers for diagnosis, prognosis, and risk stratification of GVHD., Areas Covered: In this review the most recent evidences on different types of biomarkers studied for GVHD, such as genetic, plasmatic, cellular markers, and those associated with microbiome, were summarized. A comprehensive search of peer-review literature was performed in PubMed including meta-analysis, preclinical and clinical trials, using the terms: cellular and plasma biomarkers, graft-versus-host disease, cytokines, and allogeneic hematopoietic stem cell transplantation., Expert Opinion: In the near future, several validated biomarkers will be available to help clinicians in the diagnosis of GVHD, the identification of patients at high risk of GVHD development and in patients' stratification according to its severity. Then, immunosuppressive treatment could be tailored to each patient's real needs. However, more efforts are needed to achieve this goal. Although most of the proposed biomarkers currently lack validation with large-scale clinical data, their study led to improved knowledge of the biological basis of GVHD, and ultimately to implementation of GHVD treatment.

Background: Potentially gonadotoxic protocols are currently used for the treatment of childhood hematologic malignancies. This study aims to evaluate the prevalence of gonadal dysfunction and the most important associated risk factors in a cohort of hematologic malignancy survivors., Procedure: We considered all patients referred to our long-term follow-up clinic for childhood cancer survivors, between November 2001 and December 2017. Inclusion criteria were: (a) previous diagnosis of hematologic malignancy; (b) age at hematologic malignancy diagnosis < 18 years; (c) at least five years after the end of anticancer treatments; (d) at least one evaluation of gonadal function after the 18th birthday. Patients diagnosed before January 1, 1990, were excluded., Results: Three hundred twenty-seven survivors (males = 196) were included. Isolated spermatogenesis damage was found in 58/196 (29.6%) of males, whereas 18/196 (9.2%) had Leydig cell failure. In females, 35/131 (26.7%) experienced premature ovarian insufficiency. In both sexes, abdominopelvic irradiation and hematopoietic stem cell transplantation were strongly associated with the risk of gonadal dysfunction. For every 1000 mg/m 2 increase in cyclophosphamide-equivalent dose exposure, the risk of spermatogenesis damage increased 1.52-fold and that of Leydig cell failure increased 1.34-fold, whereas the risk of premature ovarian insufficiency increased 1.80-fold. About 30% of those males who developed Leydig cell failure did so more than five years after the end of treatments., Conclusions: Gonadal dysfunction is still a significant late effect of therapies for pediatric hematologic malignancies. In males, the reevaluation of Leydig cell function may be useful even several years after the exposure to gonadotoxic treatments., (© 2020 Wiley Periodicals LLC.)

The increasing indications for allogeneic stem-cell transplant in patients with hematologic malignancies and non-malignant diseases combined with improved clinical outcomes have contributed to increase the number of long-term survivors. However, survivors are at increased risk of developing a unique set of complications and late effects, besides graft-versus-host disease and disease relapse. In this setting, the management capacity of a single health-care provider can easily be overwhelmed. Thus, to provide appropriate survivorship care, a multidisciplinary approach for the long-term follow-up is essential. This review aims at summarizing the most relevant information that a health-care provider should know to establish a follow-up care plan, in the light of individual exposures and risk factors, that includes all organ systems and considers the psychological burden of these patients., Competing Interests: The authors declare no potential conflicts of interest relevant to the article., (© 2020 Giaccone et al.)

Background: Among survivors of pediatric acute lymphoblastic leukemia (ALL), those who received hematopoietic stem cell transplantation (HSCT) conditioned with total-body irradiation (TBI) show the highest risk of late complications, including cardiovascular (CV) disease. Advanced glycation end products (AGEs) have been associated with CV disease in diabetes mellitus and other clinical conditions. This study explores AGEs plasma levels, inflammatory status, and lipid profile in survivors of pediatric ALL who received HSCT conditioned with TBI., Procedure: Inclusion criteria were (a) previous diagnosis of ALL at age < 18 years, treated with HSCT conditioned with TBI; (b) age > 18 at the time of the study enrollment; (c) off-therapy for at least five years. Radiotherapy other than TBI, preexisting heart disease, glucose metabolism impairment, body mass index > 25, active graft versus host disease (GvHD), smoking, or treatment with cholesterol lowering medications were exclusion criteria. Eighteen survivors and 30 age-matched healthy controls were enrolled., Results: AGEs plasma levels were markedly higher in ALL survivors than in healthy subjects (2.15 ± 2.21 vs 0.29 ± 0.15 pg/mL, P < 0.01). Survivors also showed higher levels of high-sensitivity C-reactive protein (2.32 ± 1.70 vs 0.88 ± 1.09 mg/dL, P < 0.05), IL-1β (7.04 ± 1.52 vs 4.64 ± 2.02 pg/mL, P < 0.001), IL17 (37.44 ± 3.51 vs 25.19 ± 6.34 pg/mL, P < 0.001), an increased glutathione/reduced glutathione ratio (0.085 ± 0.07 vs 0.041 ± 0.036, P < 0.05) and slight alterations in their lipid profile., Conclusions: Our data show AGEs accumulation and chronic inflammation in ALL survivors who received HSCT conditioned with TBI. These alterations may contribute to the increased risk of CV disease reported in these subjects., (© 2019 Wiley Periodicals, Inc.)

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., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: We retrospectively analyzed the efficacy and safety of lenvatinib in 12 patients with advanced radioiodine-refractory thyroid cancer in the setting of daily clinical practice., Patients and Methods: The starting daily dose of lenvatinib was 24 mg, tapered in the case of adverse events. Disease status was periodically evaluated by a single radiologist and safety assessment was regularly performed., Results: After a median follow-up of 13.3 months, 6- and 12-month progression-free survival rates were 63.6% and 54.6%, respectively. Overall survival at 6 and 12 months was 83.3% and 75.0%. Partial response was observed in five patients, while two showed stable disease as their best response. Conversely, progressive disease at first radiological assessment was detected in four patients. All patients experienced at least one adverse event, including systemic and gastrointestinal toxicity, high blood pressure and hand-foot syndrome. In order to manage toxicity, transient drug interruption and dose reduction were required in 10 and 9 cases, respectively., Conclusion: Our data confirm lenvatinib efficacy in patients with advanced thyroid cancer, despite an important toxic profile., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Diabetes and cancer are common, chronic, and potentially fatal diseases that frequently co-exist. Observational studies have reported an increased risk of cancer in patients with diabetes. Furthermore, many patients with cancer already have diabetes, or develop hyperglycaemia as a consequence of the tumor or of cancer therapies, and coexisting diabetes confers a greater risk of mortality for many malignancies. Managing oncologic patients with diabetes is often complicated, since the co-existence of diabetes and cancer poses several complex clinical questions: what level of glycaemic control to achieve, which therapy to use, how to deal with glucocorticoid therapies and artificial nutrition, how diabetes complications can affect cancer management, which drug-drug interactions should be taken into account, or even how to manage diabetes at the end of life. In the clinical setting, both at hospital and at home, there are little agreed, evidence-based guidelines on the best management and criteria upon which clinical decisions should be based. A practical solution lies in the implementation of care networks based on communication and ongoing collaboration between Oncologists, Endocrinologists, and the nursing staff, with the patient at the centre of the care process. This manuscript aims to review the current evidence on the effect of cancer therapies on glucose metabolism and to address some of the more common challenges of diabetes treatment in patients with cancer., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: The goal of evidence-based practice guidelines is to optimize the management of emerging diseases, such as differentiated thyroid cancer (DTC). The aim of this study was to assess therapeutic approaches for DTC in Italy and to see how closely these practices conformed to those recommended in the 2009 American Thyroid Association (ATA) guidelines., Methods: The Italian Thyroid Cancer Observatory was established to collect data prospectively on thyroid cancers consecutively diagnosed in participating centers (uniformly distributed across the nation). Data on the initial treatment of all pathologically confirmed DTC cases present in the database from January 1, 2013 (database creation) to January 31, 2016, were analyzed., Results: A total of 1748 patients (77.2% females; median age 48.1 years [range 10-85 years]) were enrolled in the study. Most (n = 1640; 93.8%) were papillary carcinomas (including 84 poorly differentiated/aggressive variants); 6.2% (n = 108) were follicular and Hürthle cell carcinomas. The median tumor diameter was 11 mm (range 1-93 mm). Tumors were multifocal in 613 (35%) and presented extrathyroidal extension in 492 (28%) cases. Initial treatments included total thyroidectomy (involving one or two procedures; n = 726; 98.8%) and lobectomy (n = 22; 1.2%). A quarter of the patients who underwent total thyroidectomy had unifocal, intrathyroidal tumors ≤1 cm (n = 408; 23.6%). Neck dissection was performed in 40.4% of the patients (29.5% had central compartment dissection). Radioiodine remnant ablation (RRA) was performed in 1057 (61.2%) of the 1726 patients who underwent total thyroidectomy: 460 (41.2%) of the 983 classified by 2009 ATA guideline criteria as low-risk, 570 (87.1%) of the 655 as intermediate-risk, and 82 (93.1%) of the 88 as high-risk patients (p < 0.001). RRA was performed in 44% of the cases involving multifocal DTCs measuring ≤1 cm., Conclusions: The treatment approaches for DTCs used in Italy display areas of inconsistency with those recommended by the 2009 ATA guidelines. Italian practices were characterized by underuse of thyroid lobectomy in intrathyroidal, unifocal DTCs ≤1 cm. The use of RRA was generally consistent with risk-stratified recommendations. However, its frequent use in small DTCs (≤1 cm) that are multifocal persists, despite the lack of evidence of benefit. These data provide a baseline for future assessments of the impact of international guidelines on DTC management in Italy. These findings also illustrate that the dissemination and implementation of guideline recommendations, and the change in practice patterns, require ongoing education and time.

Introduction: In the last decade tyrosine kinase inhibitors (TKIs) have been employed for a wide range of hematological and solid tumors and today they represent a valid therapeutic option for different neoplasms. Among them, both sorafenib and lenvatinib were approved for the treatment of radioactive iodine (RAI) refractory differentiated thyroid carcinoma (DTC). Unfortunately, in some cases the efficacy of TKIs is limited by the onset of drug resistance after the initial response. Areas covered: We report the case of a patient with a RAI refractory advanced DTC, treated with lenvatinib after surgery, multiple RAI administrations, traditional chemotherapy, and sorafenib. During treatment with lenvatinib, a noticeable response was detected by sequential computed tomography scans but, after 27 months, tumor progression became evident and led to lenvatinib interruption. In absence of any active treatment, a further disease progression was documented, and lenvatinib was re-administered obtaining a new objective response. Starting from this case report, we review available reports about the rechallenge with TKIs in solid tumors, discussing the possible mechanisms underlying the efficacy of this approach. Expert commentary: Rechallenge with TKIs in solid tumors could be a therapeutic option in subjects with advanced and metastatic DTC who experience a progressive disease after initial response to lenvatinib.

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., (© 2017 S. Karger AG, Basel.)

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 patient's clinical history and of the potential side effects, in agreement with the patients., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Purpose: Medullary thyroid carcinoma (MTC) is a relatively uncommon malignant tumor of the parafollicular C cells of the thyroid, which distinguishing feature is the production of calcitonin (CT). CT is a well-recognized tool in the diagnosis and the postsurgical follow-up of patients with MTC with a high sensitivity and specificity, and represents a powerful prognostic indicator. Usually, there is a direct correlation between tumor size and basal CT levels. However, few cases of CT-negative MTCs have been reported in literature and criteria for diagnosis and follow-up are still controversial., Methods: We performed a brief review on CT-negative MTC and reported our experience on this rare condition, focusing on the clinical characteristics at presentation, the histological and immunostaining features, and the management., Results: Fifteen cases of large, palpable, CT-negative MTCs have been reported in the literature so far; moreover, we reported four cases followed at our center., Conclusions: Although CT-negative MTC is rare, normal/low serum levels of CT and CEA cannot completely exclude the possibility of the diagnosis, when suspected. It is well accepted that early diagnosis is crucial, but there is still no consensus on the optimal postoperative surveillance strategy. The ultrasound evaluation of the cervical region, together with abdominal computerized tomography scan, chest X-ray, and fluorine18-fluorodeoxyglucose ((18)F-FDG) PET/computed tomography (FDG-PET/CT), would be recommended in the follow-up of such cases.

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., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Treatment options for recurrent or metastatic differentiated thyroid cancer (DTC) refractory to radioactive iodine (RAI) are inadequate. Multitargeted kinase inhibitors have recently shown promising results in phase 2-3 studies. This retrospective study aimed to document our clinical experience on the effects of sorafenib in the setting of daily clinical practice. Retrospective study evaluating the efficacy and safety of sorafenib in a cohort of patients consecutively treated with sorafenib at a single center. Twenty patients with advanced RAI-refractory thyroid carcinoma were enrolled (March 2011-March 2014). Patients generally started with 400 mg of sorafenib twice daily, tapering the dose in case of side effects. Radiological response and toxicity were measured during follow-up, together with safety parameters. CT scans were performed by a single experienced radiologist every 3-4 months. Five patients stopped sorafenib within 90 days due to severe toxicities. Median progression-free survival was 248 days. Five patients had a partial response (PR), achieved in all cases within 3 months, whereas 5 had stable disease (SD) at 12 months. Durable response rate (PR plus SD) for at least 6 months was 50 %, among those who received sorafenib for at least 3 months. Commonest adverse events included skin toxicity, gastrointestinal and constitutional symptoms. In our cohort of patients with advanced RAI-refractory thyroid carcinoma, sorafenib confirmed antitumor activity leading to SD or PR in the majority of cases, at the expense of clinically relevant side effects. More effective and tolerable agents are still needed in the treatment of RAI-refractory DTC.

Purpose: Childhood cancer survivors (CCS) treated with cranial radiation therapy (CRT) are at risk of developing meningiomas. The aim of this study was to evaluate the cumulative incidence of meningiomas in a cohort of CCS who previously underwent CRT., Methods: We considered all CCS who received CRT and were followed up at the "Transition Unit for Childhood Cancer Survivors" in Turin. Even though asymptomatic, they had at least one brain computed tomography or magnetic resonance imaging performed at a minimum interval of 10 years after treatment for pediatric cancer., Results: We identified 90 patients (median follow-up 24.6 years). Fifteen patients developed meningioma (median time from pediatric cancer, 22.5 years). In four patients, it was suspected on the basis of neurological symptoms (i.e., headache or seizures), whereas all other cases, including five giant meningiomas, were discovered in otherwise asymptomatic patients. Multiple meningiomas were discovered in four CCS. Ten patients underwent surgical resection. An atypical meningioma (grade II WHO) was reported in four patients. One patient with multiple meningiomas died for a rapid growth of the intracranial lesions. A second neoplasm (SN) other than meningioma was diagnosed in five out of the 15 patients with meningioma and in ten out of the 75 CCS without meningioma. Cox multivariate analysis showed that the occurrence of meningioma was associated with the development of other SNs, whereas age, sex, or CRT dose had no influence., Conclusions: CCS at risk of the development of meningioma deserve close clinical follow-up, especially those affected by other SNs.

Background: Childhood cancer survivors (CCSs) have an increased risk of overweight and dyslipidaemia, but the distribution and the potential relationships between anticancer therapies and cardiovascular risk factors have been heterogeneously and not prospectively described., Methods: All consecutive CCSs with primary cancer diagnosed between 1973-2007 and subsequently referred to our outpatient clinic were enrolled. Hypercholesterolaemia (total cholesterol >200 and/or low density lipoprotein (LDL)>160 mg/dl) was the primary end point, hypertriglyceridaemia (triglycerides >200 mg/dl) and body mass index >30 kg/m(2) the secondary end points. Cox multivariate adjustments were performed to account for differences in cancer and treatments., Results: A total of 340 patients were included (197 male, 143 female; mean age at last follow-up 24.1 ± 3.2). The most common diagnosis were haematological malignancies (n = 227) and brain tumours (n = 51). After a median follow-up of 16.1 years, hypercholesterolaemia was diagnosed in 67 CCSs (20%), hypertriglyceridaemia in 20 CCSs (6%) and obesity in 28 CCSs (8%). Total body irradiation and growth hormone deficiency increased the risk of both hypercholesterolaemia (hazard ratio (HR) = 2.7; confidence interval (CI) 1.2-4.4 and HR = 2.3; CI 1.1-4.9; all p < 0.05) and hypertriglyceridaemia (HR = 6.5; CI 1.4-31 and HR = 7.2; CI 1.1-43; all p < 0.05). The risk of hypercholesterolaemia was also higher in CCSs who underwent autologous haematopoietic stem cell transplantation (HR = 3.2; CI 1.7-5.9; p < 0.001) or platinum-based chemotherapy (HR = 2.7; CI 1.5-4.9; p < 0.001), whereas a previous diagnosis of brain tumour (HR = 10; CI 1.2-45; p < 0.05) and anthracyclines exposure (HR = 1.3; CI 1.2-26; p < 0.05) significantly predicted obesity., Conclusion: CCSs show a high and variable risk for developing dyslipidaemia and obesity, depending on cancer diagnosis and treatments. Therefore, they need accurate and tailored control of their cardiovascular risk profile., (© The European Society of Cardiology 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Pituitary metastases occur in 6-8% of breast cancer cases, but are seldom diagnosed and rarely reported. Therefore, it can be challenging to establish a clinical differential diagnosis, and at present, a definitive criteria is not available. The present study discusses the pituitary lesions identified in three patients with breast cancer, and describes their management within the collaborative framework of the Breast Unit at the Città della Salute Hospital, which also included assessment by endocrinologists. The patients were evaluated for anterior and posterior pituitary function, the appearance of the pituitary upon magnetic resonance imaging (MRI), and the oncology status and treatment. In addition, successive analysis of prolactin levels and the MRI was performed. The patients, aged 75, 83 and 76 years old, differed in their clinical presentation and successive evolution. One patient demonstrated an abrupt onset of diabetes insipidus, the second exhibited overt hypopituitarism and the final patient had a pituitary mass discovered by chance. Cases one and three exhibited systemic spread of the breast cancer, with bone and/or parenchymal metastasis, but not brain metastasis. Case two presented with a secondary pituitary tumour alone. In case three, a secondary nature to the pituitary lesion was unlikely, since there was no lesion evolution evident following MRI and as stable prolactin levels were observed over the course of the study period. By contrast, case one presented with a rapid increase of sellar lesions on MRI, together with a progressive rise in prolactin levels. Taking into account the frailty of breast cancer patients who are monitored for disease progression, management in a collaborative framework, such as at the Breast Unit, makes it possible to establish a diagnosis of sellar lesions, which is adequate for the comprehensive management of the patient with successive pituitary MRIs and prolactin evaluations, and avoids unnecessary invasive neurosurgery.

Background: Extensive resection of the tumor has been associated with better survival of anaplastic thyroid carcinoma (ATC) patients. However, surgery is not the rule for ATC patients with distant metastases at the time of diagnosis (stage IV-C), regardless of tumor resectability. The aim of this work was to explore the potential role of surgery in ATC patients, including those in stage IV-C., Methods: We considered all the consecutive ATC patients referred to our institution from June 1999 to July 2012. Patients with stage IV-A incidentally discovered ATC were excluded because of their better prognosis. All patients eligible for surgery at the time of diagnosis were first operated with the intent to obtain a macroscopically complete resection (R0, R1), or a R2 resection with minimal macroscopical residual tumor. These operations were defined as "maximal debulking," whereas operations that did not achieve this goal were defined as "partial debulking." After surgery, almost all patients received adjuvant chemotherapy, associated to radiotherapy in more than 50% of patients., Results: There were 55 eligible patients (34 women; median age 73.15 years). Thirty-one patients had distant metastases (stage IV-C). The median overall survival was 5.55 months [CI 4.94-6.60], with no difference according to stage. "Maximal debulking" was obtained in 70.73% of operated patients as a first modality and resulted associated with better survival than "partial debulking" (6.57 months [CI 5.52-12.09] vs. 3.25 months [CI 0.66-4.80]), without any difference between stage IV-B and IV-C patients. Furthermore, 21% of patients submitted to "maximal debulking" died secondary to local progression of the tumor, whereas this was the case for 69% of patients treated with "partial debulking" or not operated at all., Conclusions: Early "maximal debulking," followed by adjuvant therapy, can improve the survival and ameliorate the quality of residual life preventing the risk of suffocation. This effect is also observed in patients with distant metastasis at diagnosis and treated with this approach: they have an outcome similar to that observed in stage IV-B patients. We thus suggest that surgery may be considered in the management of all ATC patients, and should not be restricted a priori to stages IV-A and IV-B.

Purpose: To evaluate the effects of total body irradiation (TBI) on the endocrine system in adults treated with hematopoietic cell transplantation (HCT) during childhood., Methods: We studied 40 patients who underwent HCT between 1988 and 2004, mainly for childhood cancer. In 23 patients, the conditioning regimen consisted of high-dose chemotherapy and TBI (TBI+). In the other 17 patients, who did not receive TBI (TBI-), HCT was performed after high-dose chemotherapy alone., Results: Overall, 34% of patients in the TBI+ group showed growth hormone deficiency, compared with none of the patients in the TBI- group (P < 0.05). Leydig cell failure was found in 23% of patients in the TBI+ group and in 0% of the patients in the TBI- group. Elevated FSH levels, suggesting spermatogenesis damage, were found in all the patients receiving TBI and in 36% of the patients in the TBI- group (P < 0.001). Also, primary hypothyroidism was more common in TBI+ (34%) than in TBI- (5.8%) patients (P < 0.05)., Conclusions: Our data indicate that endocrine late effects after HCT are more frequent in patients who received TBI, an observation that should be considered, even if the choice of the conditioning regimen is determined by the underlying condition in most cases.