Emin Darendeliler

Brain metastasis in pediatric extracranial solid tumors: survey and literature review

Objectives: Brain is a rare site of metastasis in most extracranial pediatric solid tumors. The aim of this study is to investigate the incidence, treatment, prognosis of brain metastasis in extracranial pediatric malignant tumors in a single institution and to review the literature.Methods: From September 1989 to December 2002, 1100 children ≤16 years of age with extracranial solid tumors including lymphomas were diagnosed and treated in the Division of Pediatric Oncology, Oncology Institute, Istanbul University. Patients with parenchymal metastases in the brain were assessed.Results: Sixteen (10 female, 6 male) of 1100 patients (1.45%) with extracranial solid tumors developed brain metastases. The median age of the patients was 10.5 (1–16) years. The diagnosis was sarcomas in 12 patients: 5 osteosarcomas, 4 Ewing’s sarcoma family tumors, 1 rhabdomyosarcoma, 1 clear cell sarcoma of the soft tissue, 1 alveolar soft part sarcoma. Two patients had Wilms’ tumor and two had germ cell tumors. Four patients (25%) had brain metastasis at diagnosis. Twelve (75%) developed brain metastasis during therapy or relapse at a median duration of 16 (1–70) months from initial diagnosis. All patients had metastases to various sites, mostly lung, at the time the brain metastases were detected. Treatment included surgery, followed by postoperative radiotherapy (RT) and chemotherapy (CT) in 1, S and RT in 1, S in 1, RT and CT in 6, RT in 1, CT in 1 and no treatment in 5. Only one patient with alveolar soft part sarcoma is alive with disease 20 months from diagnosis of brain metastasis. All other patients died at a median time of 2 months (2 days–6 months) from the time of brain metastasis.Conclusions: Children with metastatic cancer who develop headaches or any other neurologic symptom should be investigated for possible brain metastasis. Although, the outcome for these patients is dismal in this series and in the literature; reports of long term survival in a few cases with Wilms’ tumor, osteosarcoma and alveolar soft part sarcoma who had isolated brain metastasis, suggest that a subset of patients may benefit from therapy.

Ependymal tumors in childhood

Ependymal tumors are classified as ependymoma (benign or low grade) versus anaplastic ependymoma (malignant or high grade). Ependymomas represent 5–10% of intracranial neoplasm in children. In this study, demographic data and the treatment results of pediatric patients with ependymal tumors, treated in a single institute, is reported.

The role of surgery and radiotherapy in treatment of soft tissue sarcomas of the head and neck region: Review of 30 cases

BACKGROUND Thirty adult patients with head and neck soft tissue sarcoma (HNSTS) treated between 1987 and 2000 were retrospectively analysed. PATIENTS AND METHODS The most frequent histopathological subtypes were chondrosarcomas (27%) and malignant fibrous histiocytoma (20%). The surgical resection was performed in 25 of the 30 patients (83%). Twenty-three patients in the surgical resection arm received postoperative radiotherapy. RESULTS Five-year local control rates for patients with negative surgical margins (n=9), microscopically positive disease (n=10), gross residual disease (n=6) and inoperable cases (n=5) were 64, 70, 20 and 0%, respectively. However, there was no significant difference in local control between patients with negative or microscopically positive disease who received postoperative radiotherapy (71 vs. 70%). The patients who received doses>or=60 Gy had significantly higher local control rates than the ones who received doses lower than 60 Gy (p=0.048). The local control rates were lower in patients with grade 2-3 tumours when compared with grade 1 tumours (44 vs. 83%). The median overall survival of whole group was 31 months. Median survivals of patients receiving both surgery and radiotherapy with negative and microscopically positive margins were significantly better than patients who were not treated with surgery (34.8 and 36 vs. 13.3 months). CONCLUSION Our results confirm that the optimal treatment of HNSTSs is complete surgical excision, and that postoperative adjuvant radiotherapy clearly improves local control.

Plastic surgery in irradiated areas: analysis of 200 consecutive cases

Reconstructive surgery in previously irradiated areas is more difficult than in non-irradiated cases. A retrospective analysis of the outcome of 200 previously irradiated patients who had skin graft or flap reconstruction performed by the same surgeon is presented, and the most suitable surgical technique in irradiated areas is discussed. One hundred and fifty-six patients had skin and oral cavity cancer, and were operated on after local recurrence. Twenty patients had breast cancer; 15 were operated on for local recurrence and five for breast reconstruction. Twenty-four patients had soft tissue sarcomas. Eighty-five patients had a skin graft (group 1), 35 had a skin flap (group 2), 10 had a fascia/muscle flap plus skin graft and 70 had a myocutaneous flap (group 3). Analysis of complications revealed statistically significant differences in terms of incomplete graft/flap necrosis between group 1 and 2 (P < 0.001) and groups 1 and 3 (P < 0.001), and in terms of infection between groups 1 and 3 (P < 0.01). We conclude that the method of reconstruction is determined by the characteristics of the defect such as size and localization; the quality, fractionation, total dose, and energy of radiation used; skin and subcutaneous tissue changes due to radiation; and operation time. However, it is reasonable to choose fascia/muscle or myocutaneous flaps for reconstruction in previously irradiated areas. These methods are more resistant to bacterial inoculation, more prone to clean residual infection, and provide better vascularized tissue and volume replacement for contour defects.

Prognostic factors and survival in late adolescent and adult patients with small round cell tumors

The primary objective of this study is to review the clinical characteristics of 25 patients in the adult and late adolescent age group, diagnosed and treated with small round cell tumors involving soft tissues (extraosseous Ewing sarcoma, rhabdo-myosarcoma, primitive neuroectodermal tumor, and undiffer-entiated small round cell tumors). Additionally, survival and prognostic factors influencing the outcome with multimodality treatment are evaluated. There were 19 males (76%) and 6 females (24%). The median age was 26 years (range: 15-56 years). In 9 patients (36%), the tumor was located at an extremity, whereas 16 patients (64%) had central localizations. Tumor size was larger than 10 cm in 7 patients (29.2%). Six patients (24%) had metastatic disease. Twelve patients (48%) received radiation and 16 patients (64%) underwent surgery. Among the resected tumors, 2 were resected with contaminated margins (12.5%), whereas 2 were radically resected and 12 (75%) were resected with wide margins. All patients were given a median of 4 cycles of multiagent chemotherapy (1–14 cycles). With preoperative chemotherapy, complete regression (CR) of the tumor was achieved in 6 patients (24%). In 4 patients (16%), a partial response was obtained. After the completion of multimodality treatment, 12 patients (48%) had a CR. Progression-free (PFS) and overall survival (OS) for the entire group was 25.0 ± 10.8% at 1 year and 30.5 ± 15.5% at 3 years, respectively. Nonmetastatic disease, wide and radical resection, and presence of CR to multimodality treatment were associated with a significantly longer PFS and OS by univariate analysis. By multivariate analysis, CR to multimodality treat-ment was the only independent predictive factor for a longer OS (p: 0.0036, relative risk [RR]: 23.6, 95% CI: 2.8; 198.7) and metastatic presentation was the only independent factor predic-tive for a shorter PFS (p: 0.017, RR. 15, 95% CI: 1.6; 141.2). Large-scale, multicenter studies are required for a better eval-uation of the nonpediatric age group with small round cell tumors.

Hypertrophic osteoarthropathy and intrathoracic Hodgkin disease of childhood.

BACKGROUND Hypertrophic osteoarthropathy (HOA), well known in adults, is rarely encountered in children. The clinical features include clubbing of the fingers and toes, arthritis, and painful periosteal new bone formation of the tubular bones. The association of malignant disorders with HOA is more common in adults than in children. CASE In this paper, a 12-year-old boy with intrathoracic Hodgkin disease and HOA is presented and four other children with HOA and Hodgkin disease in the literature reviewed. DISCUSSION The presence of HOA has been thought to be a bad prognostic sign, but complete remission of Hodgkin disease and regression of clinical signs and symptoms of HOA were attained in our patient after chemotherapy and radiotherapy, and continue during 9 months post-therapy follow-up. CONCLUSIONS HOA accompanying a malignant tumor in children is very rare. Only 5 cases have been associated with Hodgkin disease, including the present boy. It is important that patients with symptoms of HOA and an intrathoracic mass be examined carefully to rule out a malignancy.

MICROSCOPIC LOCAL LEPTOMENINGEAL INVASION AT DIAGNOSIS OF MEDULLOBLASTOMA

PURPOSE To document the incidence and outcome of patients with microscopic local leptomeningeal invasion at presentation, children with medulloblastoma were reviewed. METHODS AND MATERIALS Nineteen patients (1-12 years of age), who had surgical resection (14 total, 5 subtotal) and were diagnosed as medulloblastoma, were evaluated for disease extent by pre- and postoperative computerized tomography/magnetic resonance imaging, histopathologic evaluation of leptomeninges adjacent to the resected tumor tissue, myelography/magnetic resonance of the entire spine, and analysis of cerebrospinal fluid cytology. Patients were also reviewed for disease outcome. RESULTS Staging revealed one T2, nine T3a, eight T3b, and one T4 disease. There were 10 M0, 2 M1, 2 M2, 2 M3, and 3 Mx patients according to Changs classification. Ten out of 19 patients (52.6%) demonstrated microscopic local leptomeningeal invasion. When only the 10 patients with M0 disease were considered, three out of five patients with microscopic local leptomeningeal invasion was found to have one or more relapses. The five other M0 patients without microscopic local invasion were in complete remission at the time of analysis. CONCLUSION The incidence of microscopic local leptomeningeal invasion in patients with medulloblastoma is high. Whereas the impact on survival remains to be determined in larger series, data suggests prognostic role for isolated microscopic local leptomeningeal invasion, thus validity for inclusion in the future staging system.

Prognostic significance of marker half-life during chemotherapy in non-seminomatous germ cell testicular tumors.

Decrease in serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) levels is considered as a response during chemotherapy of non-seminomatous germ cell testicular tumors, but data on the prognostic significance of marker half-life remains inconclusive. Serum marker half-life was evaluated in 34 patients with elevated markers, receiving chemotherapy (CT). Marker half-life was calculated from the natural logarithm of the sequential AFP or HCG concentrations. The correlation between event-free (EFS) and overall survival (OS) with unfavorable half-lives of AFP and HCG was evaluated. Median actual half-life (AHL) AFP was 3.9 days (range, 1.4-21.5) and median AHL HCG was 4.4 days (range, 1.4-21.0); 82% of the patients had a satisfactory initial decline in AFP, and 71% had a satisfactory initial decline in HCG. There was a significant difference in EFS and OS between the two groups of patients with an AFP half-life < 7 days and > 7 days. HCG half-life did not adversely affect EFS and OS. The correlation of better EFS and OS with appropriate AFP marker half-life during chemotherapy could provide a dynamic method, which could complement the standard baseline prognostic factors, for the prediction of prognosis.

Response Rates and Adverse Effects of Continuous Once-daily Sunitinib in Patients with Advanced Renal Cell Carcinoma: A Single-center Study in Turkey

OBJECTIVE Therapy targeted against the vascular endothelial growth factor pathway is a standard of care for patients with metastatic renal cell carcinoma. This study assessed the response rates and toxicity profiles of sunitinib on a continuous once-daily dosing regimen in Turkish patients with metastatic renal cell carcinoma. METHODS Between April 2006 and August 2010, 74 patients with metastatic renal cell carcinoma who received sunitinib on a continuous, once-daily dosing regimen were included. Sunitinib was administered daily at a dose of either 37.5 mg (94% of the patients) or 25 mg (6% of the patients), without interruption, either as a second-line treatment after interferon-α or as a first-line treatment. Response, toxicity, progression-free survival and overall survival were evaluated. RESULTS Of the 74 patients, 65 (88%) were diagnosed with clear cell renal cell carcinoma. The median treatment duration was 10 months (range, 2-42 months). The most common treatment-related adverse events were fatigue (75%), stomatitis (51%) and hypertension (50%). The most common Grade 3 or 4 adverse events were anemia (10%) and hand-foot syndrome (7%). Dose reductions were required in 50% of the patients, and early treatment discontinuation was necessary in 16% of the patients. Cardiovascular events were the most common adverse events that resulted in drug discontinuation. The objective response rate and the disease control rate were 30 and 78%, respectively. The median progression-free survival and overall survival were 13 and 25 months, respectively. CONCLUSIONS Continuous, once-daily administration of sunitinib was generally well tolerated in Turkish patients with advanced renal cell carcinoma in a daily practice setting. This studys response rates were comparable to those in previous randomized trials.

TREATMENT OF WILMS TUMOR: A Report from the Turkish Pediatric Oncology Group (TPOG)

Aim: To standardize diagnosis and treatment of childhood Wilms tumor (WT) in Turkey. Methods and patients: Between 1998 and 2006, WT patients were registered from 19 centers. Patients <16 years with unilateral WT whose treatment started in first postoperative 3 weeks were included. Treatments were stage I favorable (FH) and unfavorable histology (UH) patients, VCR + Act-D; stage IIA FH, VCR + Act-D; stage IIB FH, VCR + Act-D + radiotherapy (RT); stage III–IV FH, VCR + Act-D + adriamycin (ADR) + RT; stages II–IV UH tumors, VCR + Act-D + ADR + etoposide + RT. Results: 165/254 registered cases were eligible (bilateral, 5.9%) [median age 3.0 years; M/F: 0.99; 50/165 cases ≤2 years]. 9.7% cases had UH tumors. Disease stages were stage I 23.6%; IIA 36.4%; IIB 5.5%; III 22.4%; IV 12.1%. Cases >2 years had significantly more advanced disease. 1/11 cases with recurrent disease died; 2/165 had progressive disease, 2/165 had secondary cancers, and all 4 died. In all cases 4-year OS and EFS were 92.8 and 86.5%, respectively. Both OS and EFS were significantly worse in stage IV. Conclusions: Despite problems in patient management and follow-up, treatment results were encouraging in this first national experience with a multicentric study in pediatric oncology. Revisions and modifications are planned to further improve results and minimize short- and long-term side effects.