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.     

Central nervous system relapse of rhabdomyosarcoma

1 Purpose

The optimal management of central nervous system (CNS) relapse of rhabdomyosarcoma (RMS) is unclear. We examined diagnosis, management, and outcomes of patients with RMS developing CNS relapse.

2 Methods

Records of 23 patients diagnosed with CNS relapse between 1999 and 2016 were reviewed. Median age at presentation of CNS relapse was 15 years (range, 1–34 years). High‐risk features at initial presentation were as follows: 16 alveolar patients, 13 Stage IV, and 13 with primary tumor in parameningeal locations.

3 Results

CNS relapse occurred at a median 12 months (range, 1–23 months) from diagnosis and most common presenting symptoms were headache (n = 9), nausea/vomiting (n = 8), visual difficulty (n = 5), and none (n = 5). Leptomeningeal metastases were detected in 21 patients while only 2 developed parenchymal metastases without leptomeningeal involvement. Fifteen patients received CNS‐directed radiation therapy (RT), including craniospinal irradiation to a median 36 Gy (range, 18–36 Gy) and/or whole brain radiotherapy to a median 30 Gy (range, 6–41.4 Gy). Three patients received concurrent chemotherapy. Follow‐up magnetic resonance imaging was conducted in 13 patients after RT initiation with 8 demonstrating improvement, 2 with stable disease, and 3 with progression. Twelve patients were tested for reactivity to I‐131‐labeled monoclonal antibody 8H9, and three tested positive and received at least one intra‐Ommaya dose; all three lived >12 months post‐CNS relapse. Twenty‐one patients died of CNS disease and two of metastatic disease at other sites. Median survival post‐CNS relapse was 5 months (range, 0.1–49 months).

4 Conclusions

The prognosis for patients with RMS developing CNS relapse remains poor. Treatment including CNS‐directed RT should be considered and investigation into preventative therapies is warranted.     

An approach for cure: PEI-chemotherapy and regional deep hyperthermia in children and adolescents with unresectable malignant tumors

BACKGROUND: Elevated temperatures of 40 - 44 degrees C increase the actions of various anticancer drugs including N-lost derivatives, cytotoxic antibiotics and platinum analoga. In clinical usage thermochemotherapy (TCH) should facilitate surgical resection and ameliorate local tumor control. PATIENTS AND METHODS: From 07/1993 to 12/2002 a total of 39 patients have been enrolled onto a phase-II study (female = 24, male = 15, age 1 - 37.5 years, median 5.2). Among these, 24 patients had extracranial non-testicular germ cell tumors and 15 patients soft tissue or chondrosarcomas. Indication: locoregional relapse (n = 29) or unresectable tumor after neoadjuvant chemotherapy (n = 10). Among these two groups, there were ten patients with poor response or progressive disease under primary or relapse chemotherapy. Ten out of the 29 relapse patients had more than one relapse. Tumor site: pelvis (30), abdomen (4), head and neck (2), proximal leg (2) and lumbar spine (1). Thermochemotherapy (TCH): 1800 - 2000 mg ifosfamide/m (2) and 100 mg etoposide/m (2) on days 1 - 4 and 40 mg cisplatin/m (2) on days 1 + 4 combined with regional deep hyperthermia (42 - 44 degrees C, 1 h) on days 1 + 4. RESULTS: In 39 protocol patients a total of 166 TCH courses (332 heat sessions) were applied. 20 patients achieved complete response, and 10 patients achieved partial response. TCH was followed by surgical tumor resection in 28/39 patients and/or radiotherapy in 13/39 patients. At a median follow-up of 27 months, outcome in this high-risk patient population was 22 NED, 3 AWD, 12 DOD, 2 DOC. Five year event free (EFS) and overall survival (OS) for the whole study cohort was 0.39 +/- 0.11 (20/39 patients) and 0.52 +/- 0.11 (25/39 patients), respectively. CONCLUSION: TCH shows substantial therapeutic efficacy and facilitates complete tumor resection in 14 out of 28 operated patients. Multimodal treatment including TCH, surgical resection and/or radiotherapy leads to sustained remission in the majority of patients with locoregional tumor recurrence. The therapeutic effect is most pronounced, if TCH is administered at first relapse. Due to the clinical and histologic heterogeneity the number of patients eligible for TCH is limited. Therefore, a more valid assessment of treatment efficacy can only be made by a matched-pair comparison in cooperation with the clinical registers.     

Nasopharyngeal carcinoma in the pediatric age group: the northern Israel (Rambam) medical center experience, 1989-2004

Nasopharyngeal carcinoma (NPC) is rare in children, accounting for less than 1% of all malignancies. Radiation therapy has been the mainstay of treatment of many years, but to improve survival, the use of chemotherapy has been advocated. This is a retrospective analysis of 13 patients less than 20 years of age treated for NPC the Rambam Medical Center during 1989 to 2004. Eight boys and five girls with a median age of 14.5 years (range 10-19) were included. Median follow up (including patients who died) was 6.15 years (range 1-15 years). Duration of symptoms was 1 to 24 months (median 5 months). Of the 13 patients, one patient had stage I, 6 had stage III, 5 had stage IV-A, and 1 had stage IV-B disease. Ten patients (77%) had undifferentiated carcinoma (WHO type III) and three patients (23%) had nonkeratinizing carcinoma (WHO type II). Most of the children received two or three courses of neoadjuvant multiagent chemotherapy consisting of cisplatin and 5-FU, followed by radiotherapy with doses in excess of 60 Gy. One child received concomitant chemoradiation. Ten of the 13 patients (77%) are alive without disease 6 years after diagnosis (range 1-15 years). One patient developed local and distant metastases 1 year after diagnosis and is currently receiving combined radiochemotherapy. Two patients died. Overall survival was 84%; event-free survival was 77%. Nine patients (69%) developed moderate to severe long-term complications. Pediatric NPC is curable by combined radiation and chemotherapy, with doses of radiation in excess of 60 Gy. Long-term follow-up is important for early detection of second malignancies as well as for radiation-induced endocrinologic deficiencies and other normal tissue complications.     

Grossly-resected synovial sarcoma treated by the German and Italian Pediatric Soft Tissue Sarcoma Cooperative Groups: discussion on the role of adjuvant therapies

Differently from adult oncologists that considered synovial sarcoma (SS) a tumor with uncertain chemosensitiveness, since two decades pediatric oncologists in Europe assumed that chemotherapy played an important role in SS treatment, so most pediatric patients were included in rhabdomyosarcoma protocols, receiving adjuvant chemotherapy regardless of risk factors. The German and Italian groups reviewed the data of grossly resected SS patients in order to define a risk-adapted treatment program for the next European protocol. A total of 150 patients < 21 years with localized SS who underwent initial gross resection between 1975 and 2002 were the object of this study. All but four cases received adjuvant chemotherapy. Post-operative radiotherapy was administered to 50% Group I and to 92% Group II patients. Five-year event-free survival (EFS) and overall survival (OS) were 77% and 89%, respectively. Survival rates were influenced by tumor size (EFS 92% and 56% for size < or = and > 5 cm, respectively) and local invasiveness, not by surgical margins. No metastatic relapses occurred in Group I < or = 5 cm patients, while the outcome was poor for T2B patients (EFS 41%) due to a high rate of metastatic relapse. Our study was unable to assess the role of adjuvant treatments in grossly-resected SS, but identified a subset of low-risk patients (IRS Group I, size < or = 5 cm), for which the omission of adjuvant chemotherapy could be suggested, and a subset of high-risk patients (T2B), who need treatment intensification.     

Evaluation of residual tissues after adjuvant therapy in germ cell tumors

OBJECTIVE: Germ cell tumors are the tumors sensitive for adjuvant therapy such as radiotherapy and chemotherapy. We evaluated the pathological findings of these heterogeneous tumors to determine the persistence of residual viable tumor cells after adjuvant therapy. PATIENTS AND METHODS: Between 1988 and 2005, we treated 31 patients with germinoma or germinoma with syncytiotrophoblastic giant cells (STGC) and 15 patients with non-germinomatous malignant germ cell tumors (NGMGCTs). All 46 patients received a combination of chemo- and radiotherapy. A second-look operation was performed in 3 of 31 patients with germinomas or germinomas with STGC and 12 of 15 patients with NGMGCTs. The follow-up period was 2-139 months (median 95) in patients with germinomas or germinomas with STGC (group 1) and 10-202 months (median 65) in NGMGCT patients (group 2). RESULTS: Post-treatment, 3 group 1 and 12 group 2 patients manifested residual tumors. The pathological diagnosis in group 1 patients was mature teratoma, pineal cyst, and fibrous tissue with calcification; in group 2 it was yolk sac tumor (n = 1), immature teratoma (n = 3), mature teratoma (n = 4), and necrosis or fibrous tissue (n = 4). While no group 1 patients manifested tumor cells, MIB-1-positive viable tumor cells were present in resected tissues from one-third of the group 2 patients (3 immature teratomas and 1 yolk sac tumor). CONCLUSION: The absence of viable tumor cells in residual tissue indicates that the combination of cisplatin-based chemo- and radiotherapy was effective in our germinoma patients. On the other hand, in patients with NGMGCTs, these cells persisted despite this combination therapy.     

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.     

Total body irradiation and melphalan as a conditioning regimen for children with hematological malignancies undergoing transplantation with stem cells from HLA‐identical related donors

Watanabe N, Takahashi Y, Matsumoto K, Horikoshi Y, Hama A, Muramatsu H, Yoshida N, Yagasaki H, Kudo K, Horibe K, Kato K, Kojima S. Total body irradiation and melphalan as a conditioning regimen for children with hematological malignancies undergoing transplantation with stem cells from HLA‐identical related donors.
Pediatr Transplantation 2011: 15: 642–649. © 2011 John Wiley & Sons A/S. Abstract: Although some studies have reported that TBI and MEL offer an effective conditioning regimen for autologous SCT in acute leukemia, little has been reported regarding outcomes of allogeneic SCT. We retrospectively evaluated outcomes for 50 pediatric patients who underwent allo‐SCT conditioned with intravenous MEL (180–210 mg/m²) and fractionated TBI (12–13.2 Gy) from HLA‐identical related donors. Nineteen patients were in CR1, 18 were in CR2, and 13 showed advanced‐stage disease (≥CR3). Patients had received allo‐SCT from HLA‐identical siblings (n = 45) or phenotypically HLA‐identical family donors (n = 5). Median duration of follow‐up for all disease‐free patients was 61 months (range, 8.8–177 months). At the time of analysis, 12 patients had died. Eleven of those died of relapse, and one died of TRM. DFS rates for all patients, patients with AML (n = 12), and patients with lymphoid malignancy (n = 38) were 61.4% and 82.1%, respectively. DFS rates for CR1, CR2, and ≥CR3 cases were 89.2%, 88.1%, and 23.1%, respectively (p < 0.05). MEL/TBI for pediatric patients with hematological malignancies was associated with lower relapse rates and no increase in toxicity, resulting in better survival.     

The role of radiotherapy in the treatment of childhood intracranial germinoma: long-term survival and late effects

BACKGROUND: The aim of the present report was to evaluate the role of radiotherapy in the treatment of childhood intracranial germinoma in view of long-term survival and functional outcome. PROCEDURE: Nine children with histologically verified intracranial germinomas treated in Slovenia between 1983 and 1995 were reviewed. The four boys and five girls were 8.8-16.9 years old (median, 11.3 years). Five tumors were suprasellar, three were in the pineal region, and one patient had bifocal disease. Two patients had disseminated tumor. All patients received radiotherapy: six to the tumor bed, one to the whole brain, and two to the whole central nervous axis (CNA). The doses to the tumor bed ranged from 30 to 46 Gy (median, 44 Gy) and to the CNA were 24 and 34.5 Gy. Five patients received neoadjuvant cyclophosphamide and three patients, all with beta-human chorionic gonadotropin secreting tumors, received neoadjuvant cisplatin-based chemotherapy. RESULTS: Six patients are alive 12.8-21.8 years (median, 19 years) from diagnosis. The causes of death in three patients were disseminated disease, toxicity of salvage chemotherapy, and secondary etoposide-induced leukemia. All patients with suprasellar tumors presented with overt endocrinopathy. Results of psychological evaluation were subnormal in one out of five patients tested. Estimate of mental deterioration due to therapy ranged from 0% to 30% (median, 15%). Emotional disorder was registered in four patients and psycho-organic syndrome in three. CONCLUSIONS: Our results on long-term survival and functional outcome confirm the efficacy and relative safety of limited-field and reduced-dose radiotherapy for childhood intracranial germinoma when supplemented with chemotherapy.     

Treatment of pediatric average-risk medulloblastoma using craniospinal irradiation less than 2500 cGy and chemotherapy: single center experience in Korea

Background:Although craniospinal irradiation (CSI) of 2340 cGy plus tumor booster with chemotherapy have been established as a standard treatment of childhood average-risk (AvR) medulloblastoma (MBL) in Western counties,there are a few recent reports in outcomes ofAvR MBL using this strategy in Korean and other Asian children.We investigated the outcome of the Korean children with AvR MBL who were treated with CSI ＜2500 cGy and chemotherapy.Methods:Between January 2001 and December 2010,clinical characteristics and outcomes of 42 patients who were diagnosed with AvR MBL postoperatively and treated with radiation including CSI ＜2500 cGy and chemotherapy in Seoul National University Children's Hospital were analyzed.Results:Their median age was 9 years (range:3-18.8),and 29 were male.Histological subtypes were classic type in 28 patients,nodular/desmoplastic in 7,and large cell/anaplastic (LCA) in 7.All the patients received adjuvant radiotherapy (CSI with median 2340 cGy and booster) and multiagent chemotherapy as the first-fine treatment.With a median follow-up of 54 months,12 patients experienced relapse or progression of the tumor.The 3-and 5-year disease-free survival (DFS) rates were 78.0％±6.5％ and 75.0％±6.9％,respectively,and overall survival (OS) rates were 85.3％±5.6％ and 76.8％±6.9％,respectively.The LCA subtype was associated with poorer DFS (P=0.023) and OS (P=0.008),compared with non-LCA subtypes.Conclusion:The outcomes of children and adolescents with AvR MBL treated with radiation including CSI ＜2500 cGy and chemotherapy,are compatible to those in Western countries;however,the LCA subtype has a poor outcome with this strategy.     

Pediatric low-grade and ependymal spinal cord tumors

Our institutional experience with pediatric spinal cord tumors includes 25 patients with the diagnosis of ependymoma (EP; n = 4), myxopapillary ependymoma (MPEP; n = 4), juvenile pilocytic astrocytoma (JPA; n = 5), nonpilocytic astrocytoma (WHO grade I or II, n = 6), and other nonastrocytic spinal cord tumors (n = 6) treated during the period 1974-1999. Nineteen patients required radiation therapy (RT). The median progression-free survival following RT was 65 months (range 1-206 months). Seven patients recurred at an average of 22 months. The EP patients recurred at an average of 8.5 months, while the patients with low-grade astrocytoma recurred at an average of 42 months. Including the 6 nonsurviving patients, the median overall survival was 96 months. Two EP patients died with a progression-free survival of 9 months. One patient with MPEP died of other causes at 7 months. The treatment of pediatric spinal cord tumors should be individualized based on the histologic type. Radical surgery is indicated for nonmyxopapillary EP and low-grade astrocytic tumors. The need for adjuvant therapy most often depends on the extent of resection as well as the tumor type. Patients with disseminated EP, MPEP, JPA and nonpilocytic astrocytoma may achieve long-term progression-free survival with craniospinal irradiation.     

Neuroblastoma in adolescents and adults: the Memorial Sloan-Kettering experience

BACKGROUND: We reviewed the utility of different treatment modalities in a large series of adolescents/adults with neuroblastoma (NB). PROCEDURE: The 30 adolescents/adults (median age, 19 years) had stage 2B (n = 1), 3 (n = 2), or 4 (n = 27) NB. Treatments included conventional and myeloablative therapy; local radiotherapy (RT); immunotherapy with anti-G(D2) 3F8 monoclonal antibody +/- granulocyte-macrophage colony-stimulating factor (GM-CSF); and 3F8 alternating with low-dose oral etoposide. RESULTS: Seven patients are in first (n = 4) or second (n = 3) complete/very good partial remission (CR/VGPR) at 9+ to 181+ (median, 45+) months. Among 13 newly diagnosed or minimally prior-treated patients, no major responses were seen in 4/4 treated with N4/N5 chemotherapy, but 6/9 treated with the higher dose N6/N7 regimens and surgery had major responses, and immunotherapy produced CR in BM in three patients. Among 17 patients referred because of resistant NB, favorable responses occurred in 6/12 treated with high-dose cyclophosphamide-based salvage therapy, including one patient who is in CR 170+ months after myeloablative consolidation and five patients who achieved CR/VGPR after 3F8/GM-CSF (n = 4) or 3F8/oral etoposide (n = 1). With a median follow-up of 32+ months post-RT, no local relapses occurred in 10/10 patients who received hyperfractionated 21 Gy RT to prevent regrowth of soft tissue masses that had been resected. CONCLUSIONS: High-dose chemotherapy and surgery can achieve a minimal disease state in >50% of newly diagnosed older NB patients. In that setting, local RT, and the use of agents with recently confirmed anti-NB activity, including anti-G(D2) antibodies, and cis-retinoic acid, may improve the poor prognosis of these patients reported to date.     

Intracranial relapse in Wilms tumor patients

BACKGROUND: In children with nephroblastoma, recurrence with metastases in the central nervous system is rare. Recently, previous reports (NWTSG and UKCCSG) reported brain metastases with an incidence of respectively 0.5% and 0.6% in Wilms tumor (WT) patients (respectively n = 30/5,852 and n = 7/1,249). PROCEDURE: We retrospectively investigated the incidence and survival of patients with central nervous system relapse in WT patients, treated according to the consecutive SIOP protocols 1, 2, 5, 6, 9, and 93-01. All children with WT from 1971 until 2000 were enrolled in the study (3,040 eligible patients). Specimens at diagnosis and if possible at relapse were centrally reviewed. Patients with renal neoplasms other than WT were excluded. RESULTS: CNS relapse was documented in 14 patients (0.5%). Median time to CNS relapse was 16 months (3-69). The occurrence of relapse was not associated with specific histological subtypes. In seven patients intracranial metastases occurred at first relapse, of which two were isolated relapses. In five patients no treatment was started because of the poor condition of the patient, the other nine cases were treated with (a combination of) chemotherapy (n = 6), surgery (n = 4), and radiotherapy (n = 6). CONCLUSIONS: CNS relapse in WNT is rare. In contrast to reports of other Wilms tumor study groups, although four patients reached (local) CR, the SIOP registry showed that eventually none of the documented WT patients survived.     

Risk factors for extraocular relapse following enucleation after failure of chemoreduction in retinoblastoma

OBJECTIVE: To assess the outcome and determine risk factors for extraocular relapse in patients with retinoblastoma who had been enucleated after failure of chemoreduction. METHODS: Retrospective study (1995-2002) at three institutions. Pathological risk factors (PRF) were defined as invasion of the anterior segment, choroid, post-laminar optic nerve, subarachnoid space, or sclera according to the local pathology report. Extraocular relapse was defined as an event. RESULTS: One hundred twenty-two patients were included (17 had bilateral enucleation). Chemoreduction included vincristine, carboplatin, and etoposide (n=80, 65.6%), vincristine, and carboplatin (n=17, 13.9%), or carboplatin (n=25, 20.5%). Thirty-five also received external beam radiotherapy (28.7%). PRF included: 39 with choroidal involvement, 9 with anterior segment, 9 with scleral, and 2 with post-laminar optic nerve with subarachnoid invasion. Adjuvant chemotherapy was given to eight patients (6.5%) because of scleral invasion. Four patients had an extraocular relapse after enucleation, two of whom survive after intensive treatment including stem cell rescue. Five-year probability of event-free survival is 0.96. Only scleral invasion and bilateral enucleation were significantly associated with extraocular relapse. CONCLUSIONS: The risk of extraocular relapse is low after enucleation following failure of chemoreduction. Patients who underwent bilateral enucleation and those with scleral invasion are at higher risk of extraocular relapse.     

小儿性腺外内胚窦瘤3例诊断与治疗分析

目的总结小儿原发性腺外内胚窦瘤的诊断与治疗经验。方法回顾性分析我院2003年10月-2011年9月收治的3例性腺外内胚窦瘤患儿的病历资料。结果术前均行PEB或JEB方案新辅助化疗,根治性手术切除,术后病理均为完全缓解,术后继续化疗。随访3个月～8年,2例无病存活,1例原位复发,经术前化疗、再次手术切除及术后化疗后,现随访25个月,无病存活。结论甲胎蛋白水平对小儿性腺外内胚窦瘤诊断及术后复发监测灵敏度较高,化疗与手术结合治疗效果良好。     

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.     

Extramedullary leukemia in children with newly diagnosed acute myeloid leukemia: a report from the Children's Cancer Group

OBJECTIVES: To describe features of patients with acute myeloid leukemia presenting with extramedullary leukemic tumors (EML). METHODS: Among 1,832 patients entered on Children's Cancer Group's chemotherapy trials with acute myeloid leukemia, 199 patients had EML, defined as any leukemic collection outside the bone marrow cavity. Three patient groups were denoted: group 1 (n=109) with EML involving skin (with or without other sites of EML), group 2 (n=90) with EML in sites other than skin, and group 3 (n=1,633) without EML. RESULTS: The incidence of EML was 10.9%. Group 1 patients tended to be younger, had higher white blood cell counts, were more often CNS positive, had FAB M4 or M5 subtypes, and possessed more abnormalities of chromosome 11 than group 3 patients. Group 2 patients were younger, more often had the FAB M2 subtype, and had a higher incidence of t(8;21)(q22;q22) abnormality than group 3, but had similar white blood cell counts and incidence of CNS positivity at diagnosis. For group 1 the 5-year event-free survival was 26%, significantly worse than for group 3 at 29%. Event-free survival was better for group 2 patients (5-year estimate 46%), which remained a favorable prognostic factor by multivariate analysis. The authors retrospectively determined whether 118 (59%) of the EML patients received localized radiotherapy to the site of EML: 42 did and 76 did not. There were no differences in estimated event-free survival between patients who did and did not receive radiotherapy. CONCLUSIONS: Non-skin (group 2) EML appeared to be an independent favorable prognostic factor. Localized radiotherapy to the site of EML at the end of induction chemotherapy did not improve outcome.     

Acute lymphoblastic leukemia in children. Results of a protocol including bone marrow transplantation during the first remission in high-risk forms for relapse

Ninety-two previously untreated children with ALL were admitted to the same institution between November 1984 and November 1988. According to early prognostic factors, patients were divided into 3 groups: group 1 at "low risk" for relapse (n = 18), group 2 at "intermediate risk" (n = 62) and group 3 at "high risk" (n = 12). Every patient received an 8 week-long induction chemotherapy; after CNS prophylaxis, groups 1 and 2 children received a consolidation chemotherapy and then a classical maintenance treatment. Group 3 patients were selected to receive a bone-marrow transplantation during their first remission because of the presence, at diagnosis, of at least one of the following criteria: hyperleukocytosis greater than 100,000 (7 cases), translocation t(1;19) and t(4;11) (2 cases), adolescents (2 cases), no remission at day 30 (2 cases). Ninety-one of 92 children achieved a complete remission and none died during induction therapy. Probability of leukemia-free survival at 4 years is 73 +/- 7% for the whole patient population and 95%, 71% and 60% for patients of groups 1, 2, and 3 respectively. Persistence or disappearance of leukaemic cells in bone marrow after the initial 15 days of chemotherapy appears to influence the probability of a leukemia-free survival.     

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.