Nadia Puma

Anthracycline-related cardiotoxicity: risk factors and therapeutic options in childhood cancers

Anthracyclines play an important role in chemotherapeutic regimens for a wide spectrum of childhood tumors, but they can cause cytotoxic damage to cardiac cells, especially in combination with radiotherapy. Furthermore, cardiotoxicity increases with the cumulative dose and may lead to congestive heart failure and cardiomyopathy. Other factors, including age, pre-existing cardiac disease, length of follow-up, gender, route of administration, concomitant exposure to some chemotherapeutic drugs, trisomy 21 and black race, play a role in increasing the risk of cardiac dysfunction. The prevention of anthracycline-induced cardiotoxicity is mandatory as children are expected to survive for decades after being cured of their cancer. The purpose of this work is to point out the major risk factors of cardiotoxicity in children and to summarize some strategies to limit or prevent this complication and to treat the development of acute heart failure.

Anthracycline cardiotoxicity in childhood

Over the last 40 years, a significant advance has been made in the treatment of childhood and adult cancers. However, the increase of the survival rate points out medium-and long-term adverse effects that constitute a serious limitation for the quality of life in adults survived from a childhood cancer. Cardiovascular disease is an important cause of morbidity and mortality in adults treated with chemo-and radiotherapy for childhood cancers. Although some antitumor treatments are potentially cardiotoxic, anthracycline therapy and radiotherapy are mostly responsable for long-term cardiac damage. Anthracycline toxicity is generally limited to the myocardium, while radiation can cause injury to all components of the heart. The purpose of this review is to discuss the mechanisms of action of anthracyclines, their cardiotoxicity, the feasibility of screening, and the prevention of cardiac damage after treatment in childhood.

Surgical approach to primary tumors of the chest wall in children and adolescents: 30 years of mono-institutional experience.

Aims and background Chest wall reconstruction after surgical resection for malignancies in children is a challenge for surgeons because of growth-related complications. The aim of this study is to analyze the surgical treatment and outcomes of 30 pediatric and adolescent patients treated at Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, over a 30-year period. Methods Pediatric patients undergoing chest wall resection were retrospectively reviewed and selected for malignant primary tumor. Endpoints were survival, recurrences, and long-term results. We also reported the use of the innovative rib-like technique in 2 young patients. Results Twenty-one patients were male. Median age was 13.7 years. Eleven patients (37%) presented with a chest wall mass. Twenty-six (87%) had Ewing sarcoma family tumors. Twenty-eight (94%) received neoadjuvant chemotherapy after histologic diagnosis. One rib was resected in 13 cases; 2 or 3 contiguous ribs in 8 cases. No postoperative mortality was observed and the complication rate was 40%. Overall survival was 85.2% (95% confidence interval [CI] 65.2%-94.2%) at 5 and 10 years. Relapse occurred in 7 patients. The 5-year disease-free survival rate was 82% (95% CI 62%-92%). Conclusions Long-term survival is achievable for chest wall tumors in a high-volume referral center where a multimodal treatment should be set to reach the best result. As advances in medical treatment have increased survival, surgical techniques must ensure a lasting functional result. When refining the reconstruction techniques, such as the rib-like approach, it is necessary to expand the options of curative surgery for young patients.

Extragonadal yolk sac tumor outside of the midline of the body: a case report of a child with a yolk sac tumor of the pontocerebellar angle

Yolk sac tumor is a rare germ cell neoplasm occurring mainly in the gonads. Extragonadal yolk sac tumor is a very rare malignancy; its main distribution is along the midline of the body at three principal sites: mediastinum, central nervous system and retroperitoneum. Most yolk sac tumors are diagnosed between seven months and three years of age. We report a case of primary yolk sac tumor in a 13-month-old child. The tumor was located in the pontocerebellar angle, an atypical location that may not have suggested a yolk sac tumor as first diagnosis. We want to highlight the importance of performing tumor marker measurements during the first year of life, also for tumors located away from the midline.

Front-line window therapy with cisplatin in patients with primary disseminated Ewing sarcoma: A study by the Associazione Italiana di Ematologia ed Oncologia Pediatrica and Italian Sarcoma Group

The aim was to assess the activity of cisplatin (CDDP) in Ewing sarcoma (ES). The study consisted of front‐line window therapy with CDDP 120 mg/sqm every 3 weeks for two courses in children and young adults with primary disseminated ES. Response was assessed using the Response Evaluation Criteria in Solid Tumours criteria, and Simons two‐stage design was applied. Twelve consecutive patients were enrolled in stage 1. Only one objective response was observed. Since the target response rate was not achieved, accrual was stopped and CDDP as a single agent in ES was judged unworthy of further assessment.

Oral etoposide in relapsed or refractory Ewing sarcoma: A monoinstitutional experience in children and adolescents

Aims To assess the efficacy and toxicity of low-dose oral etoposide (VP) 16 in relapsing/refractory Ewing sarcoma. Methods The records of all patients treated at our department between 1989 and 2012 for relapsing/refractory Ewing sarcoma who received oral VP-16 were analyzed. The dose was 40 mg/m2 daily for 21 consecutive days in every 28. Response was assessed after 2/3 cycles according to Response Evaluation Criteria in Solid Tumors 1.0. Results A total of 46 of 58 patients completed at least 2 cycles; 12 suspended the treatment earlier due to rapid disease progression. The patients’ median age at diagnosis was 14 years and 25/58 had metastatic disease. All patients received intensive polychemotherapy including VP-16 IV as first- (n = 53) or second-line (n = 5) treatment; 21/58 had myeloablative regimens with peripheral blood stem cell rescue, and 1 underwent allogeneic stem cell transplantation. Oral VP-16 was prescribed as 2nd-, 3rd-, and 4th-line treatment for 19, 27, and 12 patients, respectively. The cycles administered totaled 241 (median 3, mean 4 per patient; range 1-14). A total of 46 of 58 patients were evaluable: 11 responded (9 partial remission, 1 very good partial remission, 1 complete remission) and 10 were stable, the response lasting a mean of 8 months. Hematologic toxicity G3/G4 (in 164/241 evaluable cycles) occurred in 15%, 16%, and 11% of cycles for leukocytes, hemoglobin, and platelets, respectively. There were 5 cases of pneumonia. Two patients developed secondary leukemia after receiving 12 and 14 cycles. Conclusions Low-dose oral VP-16 may be suitable in a palliative setting with an acceptable toxicity. The risk of secondary leukemia is in line with reports in the literature.

Platinum compounds and sodium metabolism in children with diencephalic glioma

In this brief report we have described eight children affected by optic pathway/hypothalamus gliomas and treated with carboplatin and/or cisplatin, which developed a derangement of sodium and water metabolism, due to diabetes insipidus (DI) or to syndrome of inappropriate antidiuretic hormone secretion (SIADH) after surgical resection. In four out of these eight patients the treatment with platinum compounds produced prolonged haematological toxicity and in five out of them it caused neurosensorial bilateral hypoacusia. In addition cisplatin worsened electrolytes disturbances. Hence children with DI or SIADH should be carefully monitored before, during and after the treatment with platinum compounds.

Paediatric Tumours of Neuroendocrine/Peripheral Neuroectodermal Origin

The neoplasms arising from the neural crest-derived cells in the adrenal medulla or extra-adrenal paraganglia include peripheral neuroblastic tumours, pheochromocytoma and paraganglioma.

When curing a pediatric tumor is not enough: The case of a psychiatric disorder in a woman surviving osteosarcoma

Aims and background We describe the case of a woman cured of osteosarcoma who took part in a mono-institutional study using different questionnaires to assess pediatric cancer survivors’ quality of life and behavioral features 12 years after completing her cancer treatment. Results The high levels of psychological distress and psychopathologic symptoms revealed by this patient prompted us to offer her specific and prolonged support at our institution, since she refused to seek the help of other psychiatric services. The woman revealed a dysfunctional social and family setting and a borderline personality disorder. She was hospitalized after attempting suicide. No psychological distress had previously come to light during her long follow-up for cancer. Conclusions Cancer survivors are at risk of psychological and behavioral problems, so they should be followed up over time. Questionnaires and standard scales are important, but not enough: the physician-patient relationship is crucial to bring out a patients psychological issues and needs. This means that dedicated resources should be made available, whenever possible.

HG-06RE-IRRADIATION (RE-RT) FOR CHILDREN WITH RELAPSING DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG): BETTER SURVIVAL AND BETTER TIME

HG-06. RE-IRRADIATION (RE-RT) FOR CHILDREN WITH RELAPSING DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG): BETTER SURVIVAL AND BETTER TIME Maura Massimino1, Emilia Pecori1, Elisabetta Schiavello1, Veronica Biassoni1, Emanuele Pignoli1, Barbara Diletto1, Filippo Spreafico1, Michela Casanova1, Roberto Luksch1, Andrea Ferrari1, Monica Terenziani1, Marta Podda1, Cristina Meazza1, Serena Catania1, Stefano Chiaravalli1, Nadia Puma1, Stefano Bergamaschi1, Loris De Cecco1, Andrea Anichini1, Manila Antonelli3, Piergiorgio Modena2, Francesca Buttarelli3, Felice Giangaspero3, and Lorenza Gandola1; Fond. IRCCS Istituto Nazionale dei Tumori, Milano, Italy; Ospedale S.Anna, Como, Italy; Universita Sapienza, Roma, Italy Since 2009 we launched a strategy for children with centrally reviewed MRI DIPG diagnosis. Vinorelbine with nimotuzumab–an anti-EGFR monoclonal antibody-were weekly administered during the delivery of 54 Gy irradiation, 1.8 Gy/fraction daily, and for a total of 12 weeks, thereafter any other week until tumor progression or for two years duration. Since 7/2011 re-RT was offered both in case of local/disseminated progression: for local it consisted of 19.8 G/11 daysfractions; if needed, craniospinal irradiation (CSI) dose was 36 Gy/20 fractions. Of 40 patients treated, 29 had local (24) or disseminated (5) progression and 19 were given local (16) or CS (3) re-irradiation a median 8 months after first radiotherapy (2.5-19 months). Reasons for not re-irradiating the other 10 children were: progression before 7/2011(4), refusal(4), too poor PS(2); progression site were not different in the two groups. Survival after re-irradiation lasted between two weeks-14 months, median 6; a statistically different median OS between the reirradiated/not-reirradiated children was found, being 16 and 12 months, respectively(P 1⁄4 0.003). Re-irradiation induced, in 17 radiologically evaluated patients: 9 tumor volume reduction, 3 stable volumes, while 5 had progression; 14 had symptom amelioration and 13 steroid suspension. 8/9 volume reductions were obtained after same response at previous irradiation while one had stable disease after first irradiation. No adverse event occurred. Re-irradiation after progression was a concrete benefit for both OS and quality of patients life with symptom amelioration in 14/19. This option is worth to be offered also in case of disseminated progression. Neuro-Oncology 18:iii48–iii77, 2016. doi:10.1093/neuonc/now073.5 #The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.