NASOPHARYNGEAL CANCER OF CHILDHOOD AND ADOLESCENCE: A Single Institution Experience

Nasopharyngeal cancer is rare in childhood and results with radiotherapy are far from encouraging. A total of 52 patients with stage I to IVB nasopharygeal cancer and age <18, received radiotherapy to 60–66 Gy in 2-Gy fractions to the nasopharynx and cervical nodes, while 22 of these patients also received chemotherapy with cisplatin and 5 FU. Three-year disease-free survival with concurrent chemotherapy was 82% compared to 40% for patients who had radiotherapy alone (p =. 001; HR 0.33; 95% CI 0.25–0.74). The 3-year overall survival in the patients who received radiotherapy was 72% and that in the patients who received concurrent chemotherapy was 77% (p =. 38). A statistically significant improvement in disease-free survival was observed with concurrent chemoradiation in nonmetastatic nasopharyngeal cancer in young patients.     

Outcome after relapse in an unselected cohort of children and adolescents with Ewing sarcoma

BACKGROUND: Survival after relapse in patients with Ewing sarcoma is very poor and this retrospective study attempts to identify of prognostic factors predicting survival after relapse. PROCEDURE: A total of 191 patients with localised Ewing sarcoma were registered in the ET-2 trial of the United Kingdom Children's Cancer Study Group (UKCCSG). All patients received standardised primary treatment with chemotherapy and surgery and or radiotherapy as local modality treatment. Sixty-four patients who relapsed are included in this report. Treatment at relapse was variable and included chemotherapy, surgery, radiotherapy and high dose therapy (HDT) or megatherapy with peripheral stem cell transplantation (PBSCT) or autologous bone marrow transplantation (ABMT) in various combinations. A subgroup of patients had only non-specific symptomatic treatment at relapse. Both univariate and multivariate methods were used to investigate variables affecting survival after relapse. RESULTS: The overall actuarial median survival from relapse for all patients was 14 months (95% CI 11-16 months). Univariate analysis showed that males had a longer survival (median, 16 months vs. 11 months); patients who relapsed while on treatment did worse (median, 3 months vs. 16 months) and patients who had a longer disease-free interval (DFI) prior to relapse had a better outcome (DFI <1 year, median survival = 3 months; DFI 1-2 years, survival = 8 months; DFI > 2 years, median survival = 24 months, P < 0.001). Multivariate analysis confirmed that duration of first remission was the only factor associated with longer survival after relapse. CONCLUSIONS: These data suggest that although aggressive therapy may delay disease progression after relapse for some children, the course of the disease after relapse is usually fatal. International co-operative studies are needed to evaluate new strategies.     

Nasopharyngeal carcinoma in Turkish children: review of 33 cases.

A retrospective and prospective analysis is reported of epidemiological, clinical, and therapeutic aspects of 33 children with nasopharyngeal carcinoma who were treated in a single institution over a period of 10 years. Twenty-three male and 10 female children ranging from 9 to 17 years were referred to our center. Histopathology was WHO type 3 carcinoma in 21, WHO type 2 in 8, WHO type 1 in 1, and unclassified in 3 patients. Disease extent was T2a (n = 15), T2b (n = 2), T3 (n = 11), and T4 (n = 5); N1 (n = 5), N2 (n = 12), and N3a (n = 16). Five patients had base of skull invasion. Four patients had M1 disease on admission. Four patients were treated with irradiation only. Three patients received neoadjuvant, 4 patients received adjuvant, and 22 patients received neoadjuvant + adjuvant chemotherapy in addition to radiotherapy. Patients received 50-72 Gy to the primary tumor and involved nodes and 45-50 Gy to uninvolved regions. Chemotherapy consisted of combinations of cisplatin, fluorouracil or Adriamycin, vincristine, and cyclophosphamide. Twenty-nine patients (88%) attained locoregional control. Overall, 10 patients died with progressive disease or infectious complications, and 2 patients are still receiving therapy. Three patients are still living with multiple metastases and stable disease. Eight patients were lost to follow-up. Twelve patients are alive without relapse 3 and 63 months from diagnosis. Seven patients had 6 relapses at distant and 1 relapse at local site. The median time for first relapse was 8 months. Overall, the 5-year survival rate was 63% and disease-free survival rate was 53%. Although the locoregional control rate is high, long-term survival rates will be the real test of the impact of chemotherapy. Further studies are needed to confirm the optimal combination of effective chemotherapeutic agents and radiotherapy.     

放疗及二次根治手术对儿童横纹肌肉瘤的疗效影响分析

目的探讨儿童横纹肌肉瘤(RMS)的治疗手段与疗效、预后的关系。方法回顾性分析中山大学孙逸仙纪念医院儿科2013年1月—2017年12月收治的24例儿童RMS的临床资料,总结儿童RMS的治疗策略、疗效,分析放疗及二次根治手术对儿童RMS预后的影响。结果初治儿童RMS共24例,男18例,女6例,发病中位年龄3.6岁(11个月~11岁),其中原发于颌面部14例,颈部1例,腹盆腔2例,肢体4例,生殖系统2例,肝脏1例;病理类型包括胚胎型22例,腺泡型2例;低危组3例,中危组18例,高危组3例。所有患儿均按横纹肌肉瘤全国协作组重庆方案(RMS-CQ-2009)进行化疗,并依据实际病情及疗效反应选择性采取根治手术及放疗。截止2020年6月1日共9例患儿死亡,3年总体生存率(OS)为65.7%。化疗+放疗组的3年OS(80.0%)高于化疗+二次根治术组(50.0%)(χ²=3.896,P=0.048)。对于颌面部RMS,行二次根治术的患儿3年0S(25.0%)低于未行二次根治术的患儿(80.0%)(χ²=6.521,P=0.011);行放疗的患儿3年OS(80.0%)高于未行放疗的患儿(25.0%)(χ²=4.168,P=0.041)。对于非颌面部RMS,行二次根治术和未行二次根治术的患儿3年OS分别是68.6%和66.7%(χ²=0.035,P=0.852),行放疗和未行放疗的患儿3年OS分别为53.3%和80.0%(χ²=0.076,P=0.783)。结论放疗有助于提高儿童RMS生存率,二次根治术并不能显著改善颌面部RMS的预后。     

NASOPHARYNGEAL CARCINOMA IN TURKISH CHILDREN: Review of 33 Cases

A retrospective and prospective analysis is reported of epidemiological, clinical, and therapeutic aspects of 33 children with nasopharyngeal carcinoma who were treated in a single institution over a period of 10 years. Twenty-three male and 10 female children ranging from 9 to 17 years were referred to our center. Histopathology was WHO type 3 carcinoma in 21, WHO type 2 in 8, WHO type 1 in 1, and unclassified in 3 patients. Disease extent was T2a (n = 15), T2b (n = 2), T3 (n = 11), and T4 (n = 5); N1 (n = 5), N2 (n = 12), and N3a (n = 16). Five patients had base of skull invasion. Four patients had M1 disease on admission. Four patients were treated with irradiation only. Three patients received neoadjuvant, 4 patients received adjuvant, and 22 patients received neoadjuvant + adjuvant chemotherapy in addition to radiotherapy. Patients received 50-72 Gy to the primary tumor and involved nodes and 45-50 Gy to uninvolved regions. Chemotherapy consisted of combinations of cisplatin, fluorouracil or Adriamycin, vincristine, and cyclophosphamide. Twenty-nine patients (88%) attained locoregional control. Overall, 10 patients died with progressive disease or infectious complications, and 2 patients are still receiving therapy. Three patients are still living with multiple metastases and stable disease. Eight patients were lost to follow-up. Twelve patients are alive without relapse 3 and 63 months from diagnosis. Seven patients had 6 relapses at distant and 1 relapse at local site. The median time for first relapse was 8 months. Overall, the 5-year survival rate was 63% and disease-free survival rate was 53%. Although the locoregional control rate is high, long-term survival rates will be the real test of the impact of chemotherapy. Further studies are needed to confirm the optimal combination of effective chemotherapeutic agents and radiotherapy.     

Medulloblastoma—A retrospective analysis

A retrospective review of 45 patients was undertaken at the All India Institute of Medical Sciences to assess the outcome and prognostic factors for these patients who received post operative radiotherapy with or without chemotherapy for medulloblastoma. The median age at diagnosis was 11 years, with 34 males and 11 female patients. Thirty four tumours were confined to midline structures, and 11 were localised to one cerebellar hemisphere or involved midllne and lateral structures. Complete macroscopic removal was achieved in 24 patients and subtotal removal in 21 patients. Forty one patients underwent craniospinal irradiation and 27 patients received adjuvant chemotherapy. Median overall and disease free survival was 57 and 31 months respectively and 3 year overall, survival was 76%. The addition of adjuvant chemotherapy was a significant factor for disease free survival (p = 0.01) whereas extent of surgery (total vs subtotal, p = 0.01) was a significant factor for overall survival only. Eleven patients developed recurrent disease, with ten relapsing first in the posterior fossa.     

Selective use of whole-lung irradiation for patients with Ewing sarcoma family tumors and pulmonary metastases at the time of diagnosis

PURPOSE: The benefit of whole-lung irradiation (WLI) for patients who have pulmonary metastases (PM) of Ewing sarcoma family tumors (ESFT) is unclear. At our institution, WLI is reserved for patients with PM that do not respond completely to induction chemotherapy. We reviewed our experience to assess the impact of WLI on clinical outcome. PATIENTS AND METHODS: Twenty-eight patients with ESFT and PM were treated in three consecutive institutional trials (1979-1996). Extent of pulmonary involvement at diagnosis, response of PM after induction chemotherapy, local treatment of PM thereafter, and clinical outcome were recorded. Treatment included primary tumor surgery and/or radiotherapy and 42 to 58 weeks of multiagent chemotherapy. RESULTS: Only eight patients (29%) received WLI. For the entire study group, the estimated 5-year event-free survival was 22.9% +/- 9.0%; the 5-year survival was 37.3% +/- 9.8%. Complete resolution of PM after induction chemotherapy was not correlated with survival (P = 0.53), nor was treatment with WLI (P = 0.87). CONCLUSIONS: The comparable survival of patients with poor and good response of PM to induction chemotherapy suggests that WLI may benefit poor responders. The use of WLI in good responders may provide similar benefit and merits further study.     

Second malignant neoplasms in patients treated for childhood leukemia. A population-based cohort study from the Nordic countries. The Nordic Society of Pediatric Oncology and Hematology (NOPHO).

Among a cohort of 981 children who were followed up 4.3-26.5 years after cessation of antileukemic therapy, eight patients in remission of acute lymphoblastic leukemia (ALL) developed a distinctively new malignant disease. The second malignant neoplasms (SMN) included brain tumors, basal cell carcinomas, thyroid cancer, leiomyosarcoma and finally rhabdomyosarcoma in a patient who also had suffered from Hodgkin's disease while still on antileukemic treatment. Cranial radiation had been given to 58.4% of the patients in the study group, which consisted of 895 ALL patients who had completed various chemotherapy protocols. With one exception, the SMN appeared after 7.5-16.5 years at a location previously exposed to radiotherapy (RT). The estimated cumulative risk of SMN appearing within 20 years after diagnosis was 2.9%, and the corresponding risk for cases with RT was 8.1% compared to 0.3% for those without (p = 0.05). In a Cox regression analysis, the incidence rate ratio of SMN between patients with and without RT was 6.7 (95% CI = 0.8, 57.7). Based on age-, year- and sex-specific cancer incidence figures for Norway, the overall standardized incidence rate ratio (SIR) of SMN after treatment for ALL was 5.9 (95% CI = 2.2, 12.9). The number of brain tumors among patients who had received cranial radiation was nearly 27 times greater than expected, whereas no such tumors were seen after chemotherapy. Individuals treated for childhood ALL are at increased risk of a new malignancy, and this seems mainly to be associated with previous irradiation.     

Advanced Nasopharyngeal Carcinoma in the Young: The Northern Israel Oncology Center Experience, 1973-1991

Between 1973 and 1991, 10 patients with locally advanced [stages III and IV] nasopharyngeal carcinoma were treated at the Northern Israel Oncology Center. All patients were treated with wide-field irradiation to the primary tumor, including the base of skull, neck, and supraclavicular region. After 1984, 6 patients also received cisplatin/5FU-based chemotherapy prior to radiotherapy and 1 patient received it after radiotherapy. All the patients who received chemotherapy are alive with no evidence of disease, for a mean disease-free survival of 96 months (range, 77 to 108 months), and no serious therapy-related late side-effects have been noted, except in one patient. We conclude that adjuvant chemotherapy may be effective in improving outcome, but only randomized prospective studies can evaluate its exact role.     

Experience and outcomes of nephroblastoma in Johannesburg, 1998 - 2003.

INTRODUCTION: Outcomes for children with cancer in the developing world are compromised by the difficulties for patients in accessing health services and by competition for resources between oncological services and the myriad other health problems of emerging nations. The purpose of this study is to document and analyse our experience and the outcomes of children with nephroblastoma over recent years. METHODS: This is a retrospective review of all patients who underwent combined oncological and surgical treatment for nephroblastoma in the Paediatric Oncology Unit between 1998 and 2003. RESULTS: Sixty-three patients were treated for Wilms' tumour; the mean age was 3 years 8 months (range 4 months to 11 years). The majority of children presented with an abdominal swelling or mass. Preoperative chemotherapy was given in forty-six cases (73 %). The tumour stage distribution was 11/63 stage I (17 %), 11/63 stage II (17 %), 21/63 stage III (33 %), 16/63 stage IV (25 %) and 4/63 stage V (6 %). Postoperative chemotherapy and radiotherapy was given according to the SIOP protocol. During the study period, thirteen patients (21 %) died (7 cancer-specific, 2 postoperative, 4 sepsis related), thirteen (21 %) were lost to follow-up and thirty-seven (59 %) are free of disease with a mean follow-up period of 3.67 years. Children with stage I and stage II had a disease-free survival at 4 years of 89 %. However, those with stage III, IV and V disease had 4-year survival of 66.75 % (p = 0.07). Overall, four-year post-nephrectomy survival was 76 %. CONCLUSION: Outcomes for children with cancer have improved dramatically over recent years; however, in the developing world, the scarcity of hospital resources and the overwhelming burden of non-cancer diseases can mean that oncological treatment is extremely challenging. In our society, children tend to present with nephroblastoma at an advanced stage; however, treatment by dedicated, multidisciplinary teams can achieve good results.     

Intraoperative electron beam treatment for pediatric malignancies: The Ohio State University experience

PURPOSE: To report the result of intraoperative electron beam radiation therapy (IOERT) in patients with extensive pediatric tumors. METHOD: From October 1989 through June 2000, 13 children were treated with chemotherapy, maximal surgery, and 10-15 Gy IOERT at a total of 18 sites. IOERT was used for palliative purposes in 5 children with metastatic disease and in 3 others who were previously treated with external beam radiation (EBRT). The remaining five patients received definitive IOERT. Postoperative EBRT of 35.4-45 Gy was given in 5 patients. RESULTS: After a median follow-up of 42 months (range = 18-63 months), 4 patients were alive and without evidence of disease. Overall and 3 year actuarial survival rates were 31% (4/13) and 26%, respectively. Local control was achieved at 13/18 sites (72%). Poor prognostic factors included metastatic disease, recurrent disease, and the absence of adjuvant EBRT. Two children with Wilms tumors had 100% local control, disease-free survival, and overall survival without the addition of EBRT. CONCLUSION: A boost dose of IOERT allows for reduction in the dose of EBRT, thereby limiting growth-related morbidity without compromising local control or disease-free survival. Except for Wilms tumors, which achieved 100% local control and disease-free survival, adjuvant EBRT is necessary for successful local control and survival in children with soft tissue sarcomas. Based on this study and others, intraoperative irradiation should be considered for inclusion in prospective, multi-institutional trials designed to treat localized malignancies in young children.     

Sparing strategy does not compromise prognosis in pediatric localized synovial sarcoma: experience of the International Society of Pediatric Oncology, Malignant Mesenchymal Tumors (SIOP-MMT) Working Group

Background

The aim of this analysis was to identify if the modified indications of radiotherapy (RT) or radical surgery compromised survival in pediatric synovial sarcoma (SS).

Procedure

Children with non‐metastatic SS, prospectively enrolled in three trials, were analyzed. After primary surgery or biopsy, they received chemotherapy. RT was planned after chemotherapy in patients who had not achieved a complete response (CR). The considered outcome was 5‐year overall survival (OS) and event‐free survival (EFS).

Results

Eighty‐eight patients were identified. Primary tumors were mainly located in limbs (66%). The first‐line therapy for 65 patients was primary resection. Of the 49 patients who had gross tumor resection, 43 received adjuvant chemotherapy, and 8 had RT. All of the 39 patients with macroscopic residual disease received chemotherapy, then only surgery (n = 12) ± RT (n = 22). The 5‐year EFS and OS rates were 68% and 85%, respectively. The TNM stage was a prognostic factor for relapse, whereas primary site of the tumor and TNM stage were prognostic factors for death.

Conclusions

Only 32% of survivors received RT. OS was similar to published data. Omission of RT may be considered in younger children, to limit the potential sequelae in patients with tumors less than 5 cm in size initially submitted to marginal resection. This strategy may also be considered in initially unresected cases, when the tumor is resected at delayed surgery with microscopically free margins, and in patients in complete remission after primary chemotherapy. Pediatr Blood Cancer 2011; 57: 1130–1136. © 2011 Wiley Periodicals, Inc.     

Primary chemotherapy followed by radiotherapy for localized non-Hodgkin's lymphomas: a preliminary report

Twenty-eight evaluable patients with clinical stage I-II of non-Hodgkin's lymphoma were treated with primary chemotherapy followed by involved field radiotherapy. The frequency of the follicular versus diffuse histological pattern was 14.3 versus 85.7%, and 24/28 (86%) of patients were in stage II. No lymphoma examined was identified as T-cell in origin. A complete response was obtained in 21 (78%) of 27 patients with measurable disorder. [Gastrectomy rendered one patient disease-free survival, and one partially responded showing a complete response after radiotherapy.] Sixteen (76%) of the 21 employed for complete response. After 36 months, elapsed disease-free survival was rated at 100% together with actuarial survival of all patients at 81%. Chemotherapy contributed to reduce the radiation dosage to 3000 rads and to control the areas infiltrated with preexisting tumors. These findings, although the median follow-up time in our study remains short (28 months), provide a strong rationale for further clinical trials of primary chemotherapy, followed by regional radiotherapy for localized stages of non-Hodgkin's lymphomas.     

Long-term morbidity in children treated with fractionated high-dose-rate brachytherapy for soft tissue sarcomas

BACKGROUND: The purpose of this study was to determine the long-term local control, disease-free survival, and morbidity of fractionated high-dose-rate brachytherapy (F-HDR) in infants and children with soft tissue sarcomas. PATIENTS AND METHODS: Fifteen children (13 girls and 2 boys, ages 5-101 months) with soft tissue sarcomas were treated with chemotherapy, organ-preserving surgery, and F-HDR (36 Gy in 12 fractions) to post-chemotherapy volumes. External beam radiotherapy was not part of the primary treatment, although four patients (27%) subsequently received salvage external beam radiotherapy after treatment failure. Chemotherapy was administered to all patients based on their tumor histology and stage. RESULTS: After a median follow-up of 10 years (range 32-154 months), 12 patients (80%) were alive without evidence of disease. Ten-year overall survival and local control rates were both 80% (12/15 children). The overall survival was better (91%) for children with microscopic residual versus gross residual disease (75%). With longer follow-up, grade 3 to 4 brachytherapy-related late morbidities increased from 8% (1/12) to 20% (3/15) and included trismus/osteonecrosis, vaginal stenosis, and periurethral fibrosis. There were two late complications associated with puberty that occurred 8 to 10 years after the initial treatments. Acute toxicity occurred in five patients (38%) and consisted primarily of grade 1 to 3 skin and mucosal reactions. CONCLUSIONS: As the sole radiation modality, F-HDR achieved excellent local control and disease-free survival in properly selected children with soft tissue sarcomas while preserving normal bone and organ development. A significant percentage of patients experience adverse late sequelae as a result of this treatment.     

Second Malignant Neoplasms in Patients Treated for Childhood Leukemia: A Population-based Cohort Study from the Nordic Countries

ABSTRACT. Among a cohort of 981 children who were followed up 4.3–26.5 years after cessation of antileukemic therapy, eight patients in remission of acute lymphoblastic leukemia (ALL) developed a distinctively new malignant disease. The second malignant neoplasms (SMN) included brain tumors, basal cell carcinomas, thyroid cancer, leiomyo-sarcoma and finally rhabdomyosarcoma in a patient who also had suffered from Hodgkin's disease while still on antileukemic treatment. Cranial radiation had been given to 58.4% of the patients in the study group, which consisted of 895 ALL patients who had completed various chemotherapy protocols. With one exception, the SMN appeared after 7.5–16.5 years at a location previously exposed to radiotherapy (RT). The estimated cumulative risk of SMN appearing within 20 years after diagnosis was 2.9%, and the corresponding risk for cases with RT was 8.1% compared to 0.3% for those without ( p = 0.05). In a Cox regression analysis, the incidence rate ratio of SMN between patients with and without RT was 6.7 (95% CI = 0.8, 57.7). Based on age-, year- and sex-specific cancer incidence figures for Norway, the overall standardized incidence rate ratio (SIR) of SMN after treatment for ALL was 5.9 (95% CI = 2.2, 12.9). The number of brain tumors among patients who had received cranial radiation was nearly 27 times greater than expected, whereas no such tumors were seen after chemotherapy. Individuals treated for childhood ALL are at increased risk of a new malignancy, and this seems mainly to be associated with previous irradiation.     

Primary tumor control in patients with stage 3/4 unfavorable neuroblastoma treated with tandem double autologous stem cell transplants

OBJECTIVE: To assess the efficacy and toxicity of local radiotherapy in achieving local control in patients with stage 4 or high-risk stage 3 neuroblastoma treated with induction chemotherapy and tandem stem cell transplants. METHODS: Fifty-two children with stage 4 or high-risk stage 3 neuroblastoma were treated on a standardized protocol that included five cycles of induction chemotherapy, surgical resection of the primary tumor when feasible, local radiotherapy, and then consolidation with tandem myeloablative cycles with autologous peripheral blood stem cell rescue. Local radiotherapy (10.5-18 Gy) was administered to patients with gross or microscopic residual disease prior to the myeloablative cycles. Thirty-seven patients received local radiotherapy to the primary tumor or primary tumor bed. Two patients with unknown primaries each received radiotherapy to single, unresectable, bulky metastatic sites. The second of the myeloablative regimens included 12 Gy of total body irradiation. RESULTS: Of the 52 consecutively treated patients analyzed, 44 underwent both transplants, 6 underwent a single transplant, and 2 progressed during induction. Local radiotherapy did not prolong recovery of hematopoiesis following transplants, did not increase peritransplant morbidity, and did not prolong the hospital stay compared with patients who had not received local radiotherapy. Local control was excellent. Of 11 patients with disease recurrence after completion of therapy, 9 failed in bony metastatic sites 3 to 21 months after the completion of therapy, 1 recurred 67 months following therapy in the previously bulky metastatic site that had been irradiated, and 1 had local recurrence concurrent with distant progression 15 months following the second transplant. The three-year event-free survival was 63%, with a median follow-up of 29.5 months. The actuarial probability of local control was 97%. CONCLUSIONS: The use of induction chemotherapy, aggressive multimodality therapy for the primary tumor, followed by tandem myeloablative cycles with stem cell transplant in patients with stage 4 or high risk stage 3 neuroblastoma has resulted in acceptable toxicity, a very low local recurrence risk, and an improvement in survival.     

Rhabdomyosarcoma treatment and outcome at a multidisciplinary pediatric cancer center in Lebanon

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. Outcome of patients treated on standard protocols, in a multidisciplinary cancer center setting outside of clinical trials, is not well reported. We reviewed characteristics and outcome of 23 pediatric patients treated at a single, multidisciplinary cancer center in Lebanon, between April 2002 and December 2010. Median follow-up was 41 months. The most commonly affected primary site was the head and neck (48%, n = 11). Nineteen tumors (82.6%) were of embryonal histology. Tumor size was ≥5 cm in eight (34.8%) patients. Sixteen patients (69.6%) had localized disease, and one (4.4%) had metastatic disease. Fifteen (65.2%) had Group III tumors. All patients received chemotherapy, for a duration ranging 21-51 weeks. Upfront surgical resection was performed in 10 patients (43.5%). Eighteen patients (78.3%) received radiation therapy. The 5-year overall and disease-free survival rates were 83% and 64%, respectively. Relapse correlated with absence of surgery. Treatment of childhood RMS in a multidisciplinary cancer center in Lebanon results in similar survival to that in developed countries when similar protocols are applied. There was a higher incidence of local relapse, but those were salvageable with further therapy and surgical local control.     

Neuroblastoma in southern Africa: epidemiological features, prognostic factors and outcome

We retrospectively analysed the epidemiological features and the importance of biochemical, histological and genetic parameters in predicting survival in 14 Namibian and 34 South African children treated for neuroblastoma (NB) from 1983 to 1997. Curative treatment consisted mainly of total (13%) or partial (44%) resection after chemotherapy (cyclophosphamide and doxorubicin x6 courses or carboplatin, etoposide, epirubicin and cyclophosphamide x6 courses). Localized radiotherapy with curative intent was given to 33% of patients. The male:female ratio was 0.9. The median age was 18 months (range 1-116) and was comparable in white, black and mixed ethnic patients. Primary disease was located in the abdomen (75%), thorax (15%), pelvis (5%) or elsewhere (5%). Evans stage distribution was: stage I, 2%; stage II, 19%; stage III, 21%; stage IV, 50%; and stage IVS, 8%. Stage III/IV disease was more common in black than in white children (p = 0.0001). Urinary vanillyl mandelic acid was elevated in 63% of those tested. Survival after 5-163 months' follow-up was 90% for stages I and II combined (median 2983, range 798-4661 days), 51% for stage III (median 367, range 61-5001 days), 6% for stage IV (median 227, range 20-4379 days) and 50% for stage IVS (median 532, range 54-1543 days). All seven children with para-spinal tumours survived. Individual factors associated with significantly poorer survival were elevated serum lactate dehydrogenase (p < 0.001), Joshi histological risk categorization adapted for age (p = 0.039), n-myc amplification (p = 0.006) and diploidy or tetraploidy (p = 0.006). All seven children with serum ferritin exceeding 149 ng/ml at the time of diagnosis died and survival was 33% in children with 1p deletion and 67% in those without, but the numbers were too small to achieve significance. These findings confirm the benefit of simple biochemical tests and histology in identifying those who are likely to respond favourably to conventional chemotherapy and surgery. Supportive genetic tests on formalin-fixed paraffin-embedded tumour tissue contributed to predicting outcome in 21 patients.     

The prognosis and survival of childhood acute lymphoblastic leukemia with central nervous system relapse

Central nervous system (CNS) relapse in childhood acute lymphoblastic leukemia (ALL) has been overcome by sensitive therapeutic approachs. This study was planned to present the development of CNS relapse and survival in newly diagnosed 190 ALL patients whose cases were followed in the authors' unit between March 1991 and May 2002. St. Jude Study XI protocol was given to the patients who applied between March 1991 and March 1997 (group A) (n = 122), and St. Jude Study XIII protocol was given to the patients who applied between March 1997 and May 2002 (group B) (n = 68). The patients having isolated CNS relapse in group A received craniospinal irradiation (CSI) median 3.5 months after CNS relapse (range 2-6 months), a short time after reinduction, and 2 cures of consolidation. In group B, patients having isolated CNS relapse received IT once a month and a high-dose methotrexate treatment once every 8 weeks and 3 or 4, cures later therapy CSI median 7 months after CNS relapse (range 6-8 months) was given. When the overall survival rates of the 2 groups are compared, a statistically significant higher survival rate at 5 years was determined in group B than in group A (respectively, 82.3%, 58.4%) (p < .05). When subgroups of the patients (that is, those with no relapse, isolated CNS or BM relapse, or CNS + BM relapse) were compared in both groups, it was found that survival was much higher for the ones with no relapse and with isolated CNS relapse (respectively, 87.9%, 72.7%) compared to isolated BM or CNS + BM relapse groups (respectively, 10%, 13.3%) (p < .05). In a conclusion, for children with acute lymphoblastic leukemia and an isolated CNS relapse, with delayed definitive craniospinal irradiation allowing more intensive systemic and intrathecal chemotherapy results in better overall survival than has been previously reported.     

Challenges in the management of localized Ewing sarcoma in a developing country

Abstract

Survival in pediatric Ewing sarcoma (ES) lags in low- and middle-income countries (LMICs). This study analyzed factors contributing to a lower outcome in an LMIC center. A retrospective case review of children with localized ES treated from January 2011 till December 2017 was performed. Neoadjuvant chemotherapy with alternating cycles of vincristine, doxorubicin, cyclophosphamide; and ifosfamide, etoposide was administered 3-weekly for 48 weeks. Reassessment was planned for week 12, followed by local therapy (surgery/radiotherapy or both) tailed by adjuvant chemotherapy. Forty-eight patients with mean age 8 years (range: 0.7–14) were evaluated. Extremity and central axis tumors were seen in 25 (52%) and 23 (48%) patients. Three patients died of neutropenic sepsis and five abandoned therapy. Local therapy included primary surgery, radiotherapy and a combination of surgery and radiotherapy in 7 (16%), 20 (45%) and 17 (39%) patients. The 3-year event-free survival (EFS) and disease-free survival (DFS) for the cohort were 47.7?±?11% and 57.6?±?11.2%. Time to local therapy >16 weeks was associated with inferior DFS vs. local therapy administered within 16 weeks [46.6?±?12.4 vs. 63.9?±?19.4, p=.046]. Older age, axial site, large size and incomplete surgical resection did not predict relapse/progression. Patients who received wide local excision, as local therapy, had 100% DFS. Coordinated efforts to ensure timely therapy can improve outcome in pediatric ES. Abandonment and treatment-related mortality (TRM) are additional challenges that need to be tackled in LMICs.