Platinum compound-related ototoxicity in children: long-term follow-up reveals continuous worsening of hearing loss

OBJECTIVES: The purpose of this study was to evaluate the severity of hearing loss after cisplatin and/or carboplatin treatment in young children and to analyze its evolution and its relation to different therapy schedules. METHODS: One hundred twenty patients treated in the Pediatrics Department at the Institut Gustave-Roussy from 1987 to 1997 for neuroblastoma, osteosarcoma, hepatoblastoma, or germ cell tumors were analyzed. Median age at diagnosis was 2.6 (range 0-17) years. Median follow-up was 7 (1-13) years. Chemotherapy regimens contained cisplatin and/or carboplatin. Three patients also received high-dose carboplatin. Cisplatin was administered at a dose of 200 mg/m/course in 72% of cases. The median cumulative dose was 400 mg/m for cisplatin and 1,600 mg/m for carboplatin. Hearing loss of grade 2 or above, according to Brock's grading scale, was revealed with pure tone audiometry and behavioral techniques. RESULTS: Carboplatin alone was not ototoxic. Deterioration of hearing of grade 2 or above was observed in 37% of patients treated with cisplatin and 43% of patients treated with cisplatin plus carboplatin (P = NS). Fifteen percent of patients experienced grade 3 or 4 ototoxicity. Ototoxicity was most often observed after a total cisplatin dose of at least 400 mg/m. No improvement was observed with time; on the contrary, worsening or progression of hearing loss at lower frequencies was detected during follow-up. Only 5% of audiograms showed toxicity of at least grade 2 before the end of therapy; in contrast, this level was observed in 11% of early post-therapy evaluations and in 44% after more than 2 years of follow-up. CONCLUSIONS: Children treated with cisplatin at cumulative doses approaching 400 mg/m require long-term surveillance to avoid overlooking hearing deficits. Carboplatin, at a standard dose, does not appear to be a significant risk factor for ototoxicity even in patients who have already been treated with cisplatin.     

Hearing loss in pediatric oncology patients receiving carboplatin-containing regimens

Carboplatin is a well-established chemotherapeutic agent used to treat a variety of pediatric malignancies. Platinum analogues such as cisplatin are known to be ototoxic, but little is known regarding the ototoxicity of carboplatin. We performed a single institution retrospective chart review of pediatric oncology patients who received platinum-containing regimens from 1993 to 2002. Ninety-nine patients with sufficient medical and audiologic data were identified. Significant hearing loss was defined as a Brock grade 1 or higher. The incidence was compared among 3 treatment groups (carboplatin only, carboplatin and cisplatin, and cisplatin only). Significant hearing loss in patients receiving carboplatin only was rare, observed in only 1/25 (4%) of patients. In contrast, 19/27 (70%) of patients receiving carboplatin and cisplatin possessed significant hearing loss, as did 27/47 (57%) of those patients receiving cisplatin only P<0.001. The difference in hearing loss could not be explained by different cumulative exposures of the platinum agents. Carboplatin, when used without cisplatin, is rarely associated with severe hearing loss, even at high cumulative doses.     

Long-term follow-up of survivors of childhood cancer

Objective: This study was designed to improve the long-term follow-up of childhood cancer survivors by developing standard monitoring for adverse effects; Providing concise treatment summaries for each patient and identifying already existing adverse effects; Determining patient risks for long-term adverse effects; and providing individualized 10-year of plants for followup.Methods: A retrospective chart review of long-term childhood cancer survivors followed by the institution’s pediatric oncologists was performed. Criteria for review included being at least 5 years from diagnosis and 2 years off chemotherapy. Patients are followed annually by the pediatric oncologists.Results: At the time of review, there were 26 long-term survivors of childhood cancers enrolled at the clinic. Their charts have been reviewed and treatment summaries formulated. Fifty-four adverse effects have been detected. 74% of the patients have long-term adverse effects from receiving cancer therapy. The most common were growth hormone deficiency, hypothyroidism, seizures, and hearing loss. Ten year follow-up plans have been devised for each patients.Conclusion: The presence of long-term adverse effects is common in childhood cancer survivors. The pediatrician is pivotal in helping assure their patients are receiving adequate follow-up to detect these complications as well as assisting in the transition to care as an adult.     

Cisplatin ototoxicity in children: a practical grading system

A long-term follow-up study was carried out to assess ototoxicity in children who had been treated for a malignant tumour with "standard dose" cisplatin (60-100 mg/m2 per course), and were at least 2 years from stopping treatment. The median age at diagnosis was 2 years 2 months (range 1 month to 13.5 years). On the basis of hearing assessment by pure-tone audiometry, a practical grading system of hearing loss from 0 to 4 is proposed. Moderate to severe high-frequency hearing loss (grade 2-4) was found in half the children and 10 require appropriate hearing aids. The risk of developing ototoxicity increased significantly with the cumulative cisplatin dose (P = 0.027), although there was considerable individual susceptibility. Serial follow-up testing, to a median of 4 years after completion of cisplatin treatment, showed no recovery of hearing in any of these children. We suggest careful monitoring of young children by a consultant audiological physician throughout treatment with cisplatin, particularly when doses of 400 mg/m2 and over have been reached. Alternative chemotherapy should be discussed if grade 2 ototoxicity develops.     

Screening for psychological distress in very long-term adult survivors of childhood cancer

This study evaluated the prevalence of psychological distress (PD) in a cohort of 348 adult childhood cancer survivors with a very long-term follow-up and assessed the characteristics associated with this distress (cancer type, treatment, sex, age at diagnosis, self-reported late effects, social support, type of remembrance, time since the diagnosis, age at evaluation), assuming that with time since the diagnosis, the PD of survivors will approximate that of the general population. Before attending a long-term follow-up consultation, survivors were sent 3 questionnaires: the Brief Symptom Inventory-18, the Impact of Event Scale, and the Illness Worry Scale (IWS). During the visit, they were administered the Mini-International Neuropsychiatric Interview (MINI) by a psychologist. The mean age of the survivors was 38.5 years (18.1–65.8) at consultation, 7 years (0.0–18.0) at cancer diagnosis, and mean time since diagnosis was 31.5 years (8.8–56.1). Multiple regression analyses of the data collected from self-administered questionnaires confirmed that being female, living alone, and self-reported late effects were associated with the high scores for all scales. Negative remembrances and being accompanied to the clinic were associated with higher IWS scores. Unlike the initial hypothesis, the MINI showed that, compared with controls, survivors experienced a higher prevalence of anxiety and mood disorders even after a very long time since the diagnosis. These findings show that a substantial subset of survivors experiment a high prevalence of PD, higher than the general population, and should be screened for PD whatever the time since the diagnosis.     

Long‐term pulmonary disease among Swiss childhood cancer survivors

1 Background

Pulmonary diseases are potentially severe late complications of childhood cancer treatment that increase mortality risk among survivors. This nationwide study assesses the prevalence and incidence of pulmonary diseases in long‐term childhood cancer survivors (CCS) and their siblings, and quantifies treatment‐related risks.

2 Methods

As part of the Swiss Childhood Cancer Survivor Study, we studied CCS who were diagnosed between 1976 and 2005 and alive at least 5 years after diagnosis. We compared prevalence of self‐reported pulmonary diseases (pneumonia, chest wall abnormalities, lung fibrosis, emphysema) between CCS and their siblings, calculated cumulative incidence of pulmonary diseases using the Kaplan–Meier method, and determined risk factors using multivariable logistic regression.

3 Results

CCS reported more pneumonias (10% vs. 7%, P = 0.020) and chest wall abnormalities (2% vs. 0.4%, P = 0.003) than siblings. Treatment with busulfan was associated with prevalence of pneumonia (odds ratio [OR] 4.0, 95% confidence interval [CI] 1.1–14.9), and thoracic surgery was associated with chest wall abnormalities and lung fibrosis (OR 4.1, 95% CI 1.6–10.7 and OR 6.3, 95% CI 1.7–26.6). Cumulative incidence of any pulmonary disease after 35 years of follow‐up was 21%. For pneumonia, the highest cumulative incidence was seen in CCS treated with both pulmotoxic chemotherapy and radiotherapy to the thorax (23%).

4 Conclusion

This nationwide study in CCS found an increased risk for pulmonary diseases, especially pneumonia, while still young, which indicates that CCS need long‐term pulmonary follow‐up.     

Early‐onset colorectal cancer in young adult survivors of childhood cancer

We describe the cases of two childhood cancer survivors (CCS) who developed colorectal cancer at 21 and 30 years of age. They had been treated with 30 Gy abdominal irradiation and chemotherapy including platinum and high‐dose alkylating agents at age 1 year, and 12 Gy total body irradiation and high‐dose cyclophosphamide at age 15 years, respectively. Both had not been screened for colorectal cancer. One patient with advanced cancer died, whereas the other with early cancer was still alive at the time of writing. Two guidelines for long‐term follow‐up of CCS recommend that CCS who had >30 Gy irradiation receive periodic check‐ups at age ≥ 35 years. The present cases suggest that CCS, even with irradiation <30 Gy, should receive earlier check‐ups for colorectal cancer. © 2016 Japan Pediatric Society     

Educational Paper: Decreasing the burden of cardiovascular disease in childhood cancer survivors: An update for the pediatrician

The cardiovascular impact of cancer therapies on the heart is one of the major concerns in the long-term follow-up of childhood cancer survivors (CCSs). Long-term cardiovascular effects include the development of left ventricular dysfunction resulting in congestive heart failure and ischemic heart disease, as well as valvular and pericardial disease. This is mainly ascribed to the cardiotoxic side effects of chemotherapeutic agents (especially anthracyclines) and radiotherapy, but other factors such as radiation and inflammation play a role in the effect of childhood cancer on the cardiovascular health. The most concerning effect is the high incidence of symptomatic heart failure in CCS patients treated with anthracyclines. More than 50 % of CCSs treated with anthracyclines develop asymptomatic left ventricular dysfunction after cancer therapy, with approximately 5 % developing clinical signs of heart failure during long-term follow-up. Once CCS patients develop congestive heart failure, prognosis is poor and is not influenced by current medical treatment strategies. To reduce the long-term burden of cardiovascular disease in pediatric cancer patients, a diversified approach will be necessary. In the acute phase, prevention of cardiac damage through the use of cardioprotective agents (e.g., dexrazoxane) or by administering less cardiotoxic chemotherapeutic agents is to be considered. A recent randomized trial suggested that the use of dexrazoxane reduced cardiac toxicity without affecting cancer outcomes. Especially patients requiring high doses of chemotherapeutic agents could benefit from this approach. Recent data suggest that genetic testing might identify patients at higher risk for cardiotoxicity. This seems mainly related to genes involved in drug metabolism. This would allow personalized approach adjusting chemotherapy based on cardiovascular risk profiling. This could be combined with newer monitoring strategies in the acute phase using newer echocardiographic techniques and biomarker screening to identify patients with early damage to the myocardium. For the long-term CCS cohort, early detection and treatment of early dysfunction prior to the development of congestive heart failure could potentially improve long-term outcomes. Promoting healthy lifestyles and controlling additional cardiovascular risk factors (e.g., obesity, diabetes, arterial hypertension) is an important task for every physician involved in the care of this growing cohort.     

Prospective evaluation of late effects after childhood cancer therapy with a follow-up over 9 years

Intensive multimodality treatment has led to a remarkable improvement of prognosis in paediatric cancer patients, however, a great number of long-term survivors suffer from considerable tumour- or treatment-related late effects. Between January 1990 and December 1998, 223 consecutive survivors of childhood malignancies entered a prospective follow-up study designed to evaluate the frequency and severity of tumour- and/or therapy-related long-term sequelae. After cessation of therapy and subsequently once a year, all patients underwent a detailed examination programme including physical examination, laboratory tests, abdominal sonography, echocardiography, electrocardiography, electroencephalography, spirometry, audiometry, ophthalmological examination and endocrine stimulation tests. Median follow-up was 5 years (range 0.4 to 9.6 years). A total of 167 patients (75%) had at least one chronic medical problem of whom 80 needed permanent medical support. The organ systems most frequently affected were the nervous system in 39%, the endocrine system in 32%, the ears/eyes in 22%, the kidneys in 17%, and the liver in 12% of the patients. Some late effects (endocrine deficits, hearing loss, tubulopathy) were primarily diagnosed only several years after the end of oncological therapy. Conclusion The results of this study indicate that a considerable number of former paediatric cancer patients suffer from remarkable long-term side-effects. Since life quality is an important parameter of cancer survival, careful follow-up of long-term survivors is mandatory with the aim to reduce or even abrogate possible side-effects at the earliest time. Received: 8 December 1999 and in revised form: 1 March 2000 / Accepted: 31 March 2000     

Renal late effects in patients treated for cancer in childhood: a report from the Children's Oncology Group

Improvements in childhood cancer therapy have led to increasing numbers of long-term survivors. These survivors are at risk for a variety of late effects due to the disease itself, treatment exposures (surgery, chemotherapy, and radiotherapy), underlying medical problems, and health behaviors. The COG LTFU Guidelines are risk-based, exposure-related recommendations for the identification and management of late effects due to therapies utilized in the treatment of childhood cancer, and are designed for asymptomatic survivors presenting for routine medical follow-up 2 or more years after completion of cancer therapy. The COG Guidelines Task Force on Urinary Tract Complications conducted an extensive review of the medical literature via MEDLINE. Specific treatment exposures which were reviewed include nephrectomy, chemotherapy regimens known to be nephrotoxic (cisplatin, carboplatin, ifosfamide, and methotrexate), and renal irradiation. Literature sources were ranked according to the strength of evidence and are cited in the review. This review summarizes the literature that supported the recommendations for cancer survivors at risk for nephrotoxicity previously outlined in the Children's Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent and Young Adult Cancers (COG LTFU Guidelines).     

Hearing loss in children with brain tumors treated with cisplatin and carboplatin-based high-dose chemotherapy with autologous bone marrow rescue

Carboplatin is less ototoxic than cisplatin, but ototoxicity may occur with carboplatin at higher doses. We evaluated hearing in children with brain tumors treated with conventional dose cisplatin followed by high-dose carboplatin. Children under 6 years of age, newly diagnosed with brain tumors, were treated after surgery with cisplatin, Etoposide, cyclophosphamide, and vincristine, followed by consolidation with carboplatin, ThioTEPA, Etoposide, and autologous bone marrow rescue. Hearing was assessed before and after consolidation, utilizing standard audiometric techniques. Seven of the 11 evaluable patients developed high-frequency sensorineural hearing loss after induction therapy. Hearing deteriorated after consolidation in five patients, with pure tone threshold shifts of up to 65 dB between 2,000 and 8,000 Hz. Of these five patients, audiological abnormalities were documented in four prior to consolidation, one received cranial irradiation after consolidation, and all five received aminoglycoside antibiotics for at least 2 weeks, with toxic drug levels in four. Three patients have subsequently required hearing aids. Significant ototoxicity is common in these patients. Ototoxicity related to consolidation therapy is likely due to the high dose of carboplatin used, prior cisplatin therapy, aminoglycosides, and, in one patient, cranial irradiation. Audiological assessment is essential in children treated with dose-intensive chemotherapy regimens containing cisplatin and carboplatin for identification and rehabilitation of ototoxicity. © 1996 Wiley-Liss, Inc.     

Oxaliplatin and Doxorubicin for Relapsed or Refractory High-Risk Neuroblastoma

Patients with relapsed or refractory neuroblastoma have poor long-term survival. New therapeutic regimens are needed. Doxorubicin and cisplatin are commonly used in the treatment of high-risk neuroblastoma. Oxaliplatin, a platinum compound with a 1,2-diaminocyclohexan carrier ligand, is more potent than cisplatin with less nephrotoxicity and ototoxicity. We treated seven relapsed/refractory neuroblastoma patients using oxaliplatin (105–130 mg/m²) and doxorubicin (60–75 mg/m²) together with dexrazoxane (10 mg/mg of doxorubicin) administered intravenously every three weeks. Prolonged thrombocytopenia causing treatment delay was observed when oxaliplatin was administered at 130 mg/m². A reduced dose of oxaliplatin 105 mg/m² on day 1 with doxorubicin at 20 mg/m²/dose on days 1–3 was well tolerated. Sensory neuropathies were mild and transient. No cardiotoxicity was noted despite all patients having a history of prior anthracycline exposure. Best responses included 1 complete response, 1 partial response, 1 mixed response, 3 stable diseases. In our cohort of heavily pretreated relapsed and refractory neuroblastoma patients, the combination of oxaliplatin and doxorubicin demonstrated anti-tumor activity and merits further investigation.     

Prevalence of hypertension determined by ambulatory blood pressure monitoring (ABPM) and body composition in long-term survivors of childhood cancer

Aim: In recent years, survival rates of childhood cancers have significantly increased, and occurrence of long-term adverse late effects (eg, insulin resistance, diabetes mellitus, metabolic syndrome, hypertension) has become increasingly important. Early diagnosis of obesity/hypertension in childhood is essential to avoid morbidity in the adulthood. Therefore, this study was aimed to determine the blood pressure (BP) profile by ambulatory BP monitoring (ABPM) method, and prevalence of hypertension, obesity, abdominal obesity among childhood cancer survivors. Material and method: The study was carried out with 52 cancer survivors. The ABPM measurement was performed during 24 hours. The anthropometric measurements of patients were performed using standardized protocols. The body composition analysis was performed with bioelectrical impedance analysis (BIA) method. Statistical significance was considered at p < 0.05. Results: The mean age of patients was 12.84 ± 3.88 years. Time off therapy ranged 24–125 month. The prevalence of prehypertension and hypertension were 57.7% and 9.6%, respectively. There was no statistically significant relationship between diagnosis and BP status (p = 0.59). The prevalence of obesity, and abdominal obesity were 1.9% and 30.4%, respectively. There was a positive correlation between waist circumference (WC) and time off therapy (p = 0.046). The WC was found to be higher in patients who received cranial irradiation (p = 0.048). Weight/WC were higher in patients who used corticosteroids in the treatment (p = 0.019). Conclusion: Careful follow up of BP, weight and WC is necessary for long-term cancer survivors to prevent complications. Especially patients who receive cranial radiotherapy and use corticosteroid are at increased risk of abdominal obesity.     

Pediatric Survivors of Retinoblastoma Are at Risk for Altered Bone Metabolism After Chemotherapy Treatment Early in Life

Survivors of childhood cancer frequently suffer from endocrine late effects, which are, at least partly, attributed to toxic effects of chemotherapy. Treatment of retinoblastoma typically involves chemotherapy at a very young age. The authors conducted a cross-sectional study to assess bone health in a pediatric cohort of 33 survivors of retinoblastoma (mean age: 4.4 years) who had undergone chemotherapy treatment at an especially young age (mean age: 0.76 years). Of these patients, 14 had unilateral and 19 bilateral retinoblastoma. Polychemotherapy consisted of treatment with cyclophosphamide, etoposide, vincristine, and carboplatin. Ten patients had undergone external beam radiotherapy. Clinical and biochemical parameters of growth, pubertal development, and bone health were obtained. A vitamin D deficiency was found in 51.7% of the patients, and 13.7% of patients displayed severe vitamin D deficiency. Secondary hyperparathyroidism and altered readings for bone formation or resorption markers were present in 15%. Nine percent reported bone pain or experienced fractures of the long bones after primary diagnosis. No difference between children with bilateral and unilateral disease or irradiated versus nonirradiated children was observed. The parameters of thyroid function, growth, and pubertal development were within age-appropriate norms in almost all children. In conclusion, altered parameters of bone health can be present in survivors of retinoblastoma at a young age and warrant regular follow-up in these children. The endocrine hypothalamic-pituitary axes, however, were not impaired at this early age in this group of survivors of retinoblastoma.     

Evaluation and Management of Hearing Loss in Survivors of Childhood and Adolescent Cancers: A Report From the Children's Oncology Group

Hearing loss (HL) is common in childhood cancer survivors exposed to platinum chemotherapy and/or cranial radiation and can severely impact quality of life. Early detection and appropriate management can mitigate academic, speech, language, social, and psychological morbidity resulting from hearing deficits. This review is targeted as a resource for providers involved in aftercare of childhood cancers. The goal is to promote early identification of survivors at‐risk for HL, appropriate evaluation and interpretation of diagnostic tests, timely referral to an audiologist when indicated, and to increase knowledge of current therapeutic options.     

Second neoplasms after treatment of childhood cancer in Slovenia

BACKGROUND: The number of long time survivors of childhood cancer treatment is constantly increasing over the last decades as a result of advances in diagnosis and treatment. The occurrence of second neoplasms is one of most serious late effects observed in cancer survivors. METHODS: The risk of secondary neoplasm was studied in a cohort of 1,577 patients treated for childhood cancer registered in the Cancer Registry of Slovenia (CRS) between 1961 and 2000. The time at risk was defined from the date of diagnosis of first malignancy to the time of death or the end of the study. RESULTS: The most frequent primary malignancies were: acute leukemia 28.5%, central nervous system (CNS) tumors 21.3%, and lymphomas 16.6%. Median observation time was 7.8 years. Forty-eight patients developed second neoplasms. CNS tumors, acute leukemias, and thyroid carcinoma were most frequent second neoplasms. The cumulative risk for second neoplasm in the entire cohort was 0.06% at 5 years, 5.1% at 15 years, and 12.6% at 25 years after diagnosis of first cancer. The overall survival after second neoplasm was 65% 10 years after the diagnosis of second neoplasm. CONCLUSIONS: Patients after treatment of childhood cancer are at special risk for subsequent neoplasms and long-term follow-up is mandatory.     

Long-term cause-specific mortality among five-year survivors of childhood cancer

BACKGROUND: The purpose of our study was to assess long-term cause-specific mortality of 5-year childhood cancer survivors. PROCEDURE: The study population consisted of 1,378 patients who had been treated for childhood cancer in The Netherlands between 1966 and 1996 and survived at least 5 years; follow-up was complete for 99% of survivors. Cause-specific mortality was compared with general population rates to assess relative and absolute excess risks of death (standardized mortality ratio (SMR) and AER). RESULTS: After a median follow-up of 16.1 years, 120 patients had died. The overall SMR was 17-fold (95% CI: 14.3-20.6) increased compared to the general population. Our cohort experienced an excess of 7 deaths per 1,000 person-years. Patients who received combined modality treatment and were treated for at least one recurrence experienced the highest risk of death (SMR = 92.3; AER = 37.0 per 1,000 person-years). The SMR appeared to stabilize at an about 4 to 5-fold increased risk of death after 20 years of follow-up. Only after more than 20 years of follow-up excess mortality due to other causes than the primary cancer exceeded mortality from the primary childhood cancer (2.3 vs. 0.3/1,000 patients/year). The SMR for all causes other than primary cancer was 5.4 in 25-year survivors. The overall risks of death strongly decreased with increasing attained age, with an SMR of 1.6 (n.s.) and an AER of 0.3 per 1,000 person-years for survivors of 30 years or older. CONCLUSIONS: The first primary cancer contributes most to the absolute excess risk of death in 5-year survivors of childhood cancer, but after 25 years childhood cancer mortality is negligible. Relative risk of death due to other causes is still significantly increased after 25 years of follow-up.     

Clinical characteristics and factors affecting growth in long-term survivors of cancer

We evaluated clinical characteristics and growth in 51 (24 males) long-term survivors of childhood cancer (median follow up 12.7 years). Patients were shorter, had a higher proportion of body fat and higher systolic blood pressure than their controls. The change in relative height during treatment was −0.83 standard deviation score (S.D.S.) in patients with cranial irradiation and −0.32 S.D.S. in patients without cranial irradiation; the figures after treatment were −0.56 and 0.20 S.D.S., respectively. Half (r² = 0.50) of the variation in growth retardation during therapy could be explained by the cumulative doses of 6-mercaptopurine (6-MP) and vincristine and relative height at diagnosis. Cranial irradiation, increased relative height at diagnosis and young age at diagnosis were significant predictors of growth failure over the total observation period, explaining 43% of the variation. We conclude that long-term survivors of childhood cancer have impaired linear growth, increased body fat mass and elevated systolic blood pressure. Young children who are tall for their age at diagnosis and treated with cranial irradiation have the highest risk of impaired growth after the diagnosis. High doses of 6-MP seem to contribute significantly to growth retardation during therapy. © 1996 Wiley-Liss, Inc.     

Long-term Effects of Chemotherapy on Dental Status of Children Cancer Survivors

Background: The aim of this study was to investigate the long-term effects of chemotherapy on the dental and gingival health and dental disturbance parameters of children cancer survivors. Procedure: Thirty-eight children (mean age 12.2 ± 0.5 years) who underwent chemotherapy at 4.29 ± 1.71 years of age formed the study group. Forty age- and gender-matched healthy children with a similar socioeconomic background served as controls. Subjects’ caries status (number of decayed, missing, or filled permanent teeth [DMF-T]) was recorded according to World Health Organization criteria. Subjects’ periodontal status was recorded according to the community periodontal index system. Radiographic dental examination was used to analyze dental malformations. Results: DMF-T, D-T (number of decayed permanent teeth), and F-T (number of filled permanent teeth) were significantly higher in the study group compared to the controls (4.61 ± 3.71, 3.97 ± 4.45, respectively, and 0.58 ± 0.14 vs. 2.21 ± 1.01, 0.84 ± 1.82, and 1.18 ±1.07, respectively. The most frequent dental disturbances were root malformation (52.6%) and agenesis (47.4%). Conclusions: According to our examination dental status of long-term survivors is worse than in controls. Hence proper oral hygiene for children cancer survivors (CCS) is critical. In order to meet the need for dental care in CCS health authorities are encouraged to revitalize the dental services Long-term follow-up of CCS is necessary to monitor their dental growth and oral health.     

Survival and long-term outcomes in children with hepatoblastoma treated with continuous infusion of cisplatin and doxorubicin

Despite high survival rates, many survivors of hepatoblastoma develop late effects including ototoxicity and cardiomyopathy. With the goal of minimizing long-term toxicities, our institution treated hepatoblastoma with continuous infusion of doxorubicin and cisplatinum (PLADO), rather than short infusion or bolus dosing as used in other treatment protocols. This retrospective cohort study includes consecutive patients diagnosed between 1985 and 2007. Patients were scheduled for treatment with 6 cycles of continuous infusion of PLADO with resection after the third or fourth cycle. Audiograms and echocardiograms were obtained at baseline, after every 2 chemotherapy cycles and yearly after the completion of therapy. Fifty-five patients were treated (34 localized; 21 metastatic). Fifty-one patients received at least 1 cycle of PLADO. Median follow-up was 7.0 years (range, 0.11 to 17.8 y). Event-free and overall survival for these 51 patients were 72.2% (standard error 6.3%) and 75.6% (standard error 6.2%) respectively. Of the 38 survivors treated with cisplatin who had an audiogram during follow-up, 4 (11%) demonstrated severe (Brock grade 3/4) and 13 (34%) mild (Brock grade 1/2) hearing loss. At a median of 10.0 years (range, 5.0 to 13.0 y) after therapy, 2 of 41 (5%) patients who were still alive had evidence of cardiac dysfunction. Overall, continuous infusion of PLADO therapy resulted in survival rates consistent with those observed in intergroup studies, but rates of chronic cardiac and ototoxicity did not differ sufficiently from those observed after shorter infusion of PLADO therapy to warrant the use of continuous infusions.