Employment among Childhood Cancer Survivors: A Systematic Review and Meta-Analysis.

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.

Work Placement and Job Satisfaction in Long-Term Childhood Cancer Survivors: The Impact of Late Effects.

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.

Advanced glycation end products and their related signaling cascades in adult survivors of childhood Hodgkin lymphoma: A possible role in the onset of late complications.

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)-1ß 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.

Cardiometabolic Risk, Part 2: Indirect Cardiotoxicity in Cancer Survivors - The Emerging Role of Metabolic Syndrome.

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.

Cancer Treatment-Induced Bone Loss in Hormone-Sensitive Cancer: The Paradigm of Cancer Survivor Bone Health Management.

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.

Impact of Allogeneic Stem Cell Transplantation on Testicular and Sexual Function.

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.

Biomarkers for acute and chronic graft versus host disease: state of the art.

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.

Effects of treatments on gonadal function in long-term survivors of pediatric hematologic malignancies: A cohort study.

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/m2 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.

Optimal Delivery of Follow-Up Care After Allogeneic Hematopoietic Stem-Cell Transplant: Improving Patient Outcomes with a Multidisciplinary Approach.

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.

Advanced glycation end products and chronic inflammation in adult survivors of childhood leukemia treated with hematopoietic stem cell transplantation.

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-1ß (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.

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.

The biopsychosocial condition of childhood cancer survivors in the transition towards adult care: a national survey from the joint pediatric and adult transition care group.

BACKGROUND: To provide successful transfer from childhood to adult-oriented healthcare is one of the priorities of survivorship care plans. PURPOSE: This study describes adolescent and young adult childhood cancer survivors' conditions at the moment of the transition to adult care deepening their biological, psychological, social and assistant state and their associations with socio-demographic and clinical characteristics. METHODS: A biopsychosocial check-list in four health domains (biological, psychological, social and assistant) was filled in by healthcare professionals (oncologists, psychologists, social workers and nurses) through qualitative interviews and clinical observations of 79 survivors (58% boys; Mage = 20 years old) at the moment of the transition from the Pediatric Oncology Unit to the Transition Unit of the Childhood Cancer Survivors. RESULTS: At the moment of transition, 38% of survivors showed a positive condition in all the four health domains without any kind of impairment. Biological (37%) and psychological areas (44%) were found to be those with major incidence of impairments. Association phenomena were found between psychological and social condition (p < 0.05) and between social and assistant condition (p < 0.05). Biological condition was also significantly associated with the type of cancer (χ = 6,2414, p < 0.05). CONCLUSION: Although many survivors entered in adult care system without any impairment, the biopsychosocial approach highlighted that there is a presence of impairments in at least one of the main health domains.

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 patient's clinical history and of the potential side effects, in agreement with the patients.

Valproic Acid, a Histone Deacetylase Inhibitor, in Combination with Paclitaxel for Anaplastic Thyroid Cancer: Results of a Multicenter Randomized Controlled Phase II/III Trial.

Anaplastic thyroid cancer (ATC) has a median survival less than 5 months and, to date, no effective therapy exists. Taxanes have recently been stated as the main drug treatment for ATC, and the histone deacetylase inhibitor valproic acid efficiently potentiates the effects of paclitaxel in vitro. Based on these data, this trial assessed the efficacy and safety of the combination of paclitaxel and valproic acid for the treatment of ATC. This was a randomized, controlled phase II/III trial, performed on 25 ATC patients across 5 centers in northwest Italy. The experimental arm received the combination of paclitaxel (80 mg/m2/weekly) and valproic acid (1,000 mg/day); the control arm received paclitaxel alone. Overall survival and disease progression, evaluated in terms of progression-free survival, were the primary outcomes. The secondary outcome was the pharmacokinetics of paclitaxel. The coadministration of valproic acid did not influence the pharmacokinetics of paclitaxel. Neither median survival nor median time to progression was statistically different in the two arms. Median survival of operated-on patients was significantly better than that of patients who were not operated on. The present trial demonstrates that the addition of valproic acid to paclitaxel has no effect on overall survival and disease progression of ATC patients. This trial is registered with EudraCT 2008-005221-11.

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.

Pituitary lesions in breast cancer patients: A report of three cases.

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.

Meningiomas after cranial radiotherapy for childhood cancer: a single institution experience.

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.

Prevalence of cardiovascular risk factors in long-term survivors of childhood cancer: 16 years follow up from a prospective registry.

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.

Early surgery and survival of patients with anaplastic thyroid carcinoma: analysis of a case series referred to a single institution between 1999 and 2012.

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.