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 < or =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.

Zoledronic acid concurrent with either high- or reduced-dose palliative radiotherapy in the management of the breast cancer patients with bone metastases: a phase IV randomized clinical study.

INTRODUCTION: In this prospective study, the efficacy and safety of radiotherapy combined with zoledronic acid was evaluated. MATERIALS AND METHODS: Breast cancer patients with painful bone metastases were randomized to either high- or reduced-dose radiotherapy. All patients received zoledronic acid (4 mg) every 28 days from the beginning of radiotherapy. Analgesic and pain scores in addition to visual analog score (VAS) for treatment satisfaction and whole-body bone scintigraphy were evaluated. RESULTS AND CONCLUSION: No significant differences could be found in analgesic or pain scores and bone scintigraphy results between the groups. Our results suggest that reduced-dose radiotherapy produces similar response rates and response durations when used concomitantly with zoledronic acid.

The treatment of childhood Hodgkin lymphoma: improved survival in a developing country.

BACKGROUND: To evaluate the clinical characteristics, treatment regimens, and outcome of children with Hodgkin lymphoma in a developing country over a period of 34 years. METHODS: This paper retrospectively evaluates the treatment and prognosis of 614 children with Hodgkin lymphoma disease between 1971 and 2005. All patients were treated with chemotherapy, and also received radiotherapy. RESULTS: There were 452 males and 162 females with a median age of 8 years (2 to 21); 183 patients had B symptoms. There were 165, 185, 145, and 119 patients in stage I, II, III, and IV, respectively. Histopathologic subtypes were mixed cellularity (344 patients), nodular sclerosis (90), lymphocytic predominance (62), lymphocytic depletion (46), unclassified types (69), and nodular lymphocyte predominant Hodgkin lymphoma (3). Overall (OS) and event-free survival (EFS) rates were 83 and 60%, though OS rates varied according to chemotherapy protocol; age; presence of B symptoms, leukocytosis, anemia, and extranodal involvement; and stage at diagnosis. Over the years, the median age of patients increased, as did the frequency of the nodular sclerosing type of disease. CONCLUSIONS: This is one of the largest series in a single center. The increase in the median age and in the frequency of the nodular-sclerosing type are thought to be related to the development status of Turkey. The ABVD protocol yielded the best survival rates and should be used for treatment of patients with Hodgkin lymphoma.

Late recurrence in children with Wilms' tumor.

We aimed in this study to evaluate the clinical and radiological features of the late recurrence of Wilms' tumor in children. Among 553 children diagnosed with Wilms' tumor between 1972 and 2004, four cases were determined to be late recurrences. Clinical, histopathological parameters, treatment details, and outcomes of the patients were evaluated retrospectively. The ages of the patients at the time of diagnosis were 2, 5, 5, and 9 years and the male/female ratio was 1/3. Two patients had stage II disease and two had stage IV characteristics. Histopathological examination showed favorable histology in all of the patients. Initial treatment was surgery and chemotherapy, which included vincristine and actinomycin-D. Abdominal radiotherapy was performed in two patients. Recurrence times were 36, 41, 51, and 96 months. Local recurrence and lung metastasis were detected in two patients, local recurrence in one, and lung nodules in the fourth patient. At the time of relapse, the chemotherapy protocols were as follows: vincristine, actinomycin-D, adriamycin, and cyclophosphamide in two patients; vincristine, actinomycin-D, and epirubicin in one patient; and vincristine, actinomycin-D, and adriamycin in the last patient. In the cases with late local recurrence, one patient had a local spillage and one patient had regional lymph node involvement. Although the other patient had local spillage, regional lymph node involvement, and renal artery invasion, isolated lung recurrence was observed. Only one patient had progressive disease and is still under treatment, whereas the other patients died with disease. Major recurrence sites were both local and the lungs. All of the patients had regional features including spillage, regional lymph node involvement, and vascular or capsular involvement. Late recurrence in patients with Wilms' tumor is a poor prognostic factor and should be treated with an intensified regimen.

Astrocytic tumors in children: treatment results from a single institution.

OBJECTIVE: The aims of this study are to evaluate the patients with astrocytomas and to investigate survival rates and prognosis. PATIENTS AND METHODS: Five hundred fourteen patients diagnosed with brain tumor between 1972 and 2003 were retrospectively analyzed. Three different chemotherapy regimens were used according to years. CCNU-based protocols were used in the early years; COPP (cyclophosphamide, oncovin, procarbazine, prednisolone) and CDDP+VP16 (cisplatinum + etoposide) were the other protocols used in the following years. Radiotherapy was used after 3 years of age according to protocols. RESULTS: Ninety-eight (19%) out of 514 patients have astrocytic histopathology. The histopathologic distribution was as follows: low grade, 55 patients; high grade, 43 patients. COPP regimen was given to 24 patients, CCNU-based regimen to 13, and CDDP+VP16 to 10 patients. We did not use any chemotherapy in 51 patients. Overall survival (OS) and event free-survival rates were 59.2 and 45.7% in whole group. OS rates were 93.3 and 22.4% for low-grade and high-grade histopathology, respectively (p=0.0001). OS for CCNU, CDDP+VP16, and COPP were 35.9, 22.8, and 30.4%, respectively. CONCLUSION: Low-grade astrocytomas are highly responsive to the surgery, and they do not need any further treatment unless the patient has relapse or recurrence. Still, the treatment of the high-grade tumors is a problem, and it needs new treatment approaches.

Evaluation of radiotherapy response of cervical carcinoma with gray scale and color Doppler ultrasonography: resistive index correlation with magnetic resonance findings.

PURPOSE: To investigate the role of the resistive index measured with transvaginal color Doppler ultrasonography (TVCDUS) for assessing the radiotherapy response of cervical carcinoma and to compare it with magnetic resonance findings. MATERIALS AND METHODS: A total of 13 patients with advanced stage cervical carcinoma (>IIA) underwent magnetic resonance imaging (MRI) and TVCDUS exams 6 months prior to and 6 months after radiotherapy. Pre- and post-treatment resistive indices obtained from the central and peripheral zones of the tumor were compared. These values were also compared with MRI findings and resistive indices obtained from the control group. RESULTS: Tumoral masses could be visualized in all patients with B-mode TVCDUS prior to the treatment. Resistive indices before and after treatment were 0.20-0.82 (mean: 0.52+/-0.15), and 0.70-0.99 (mean: 0.81+/-0.14), respectively. Eleven out of 13 patients responded to the treatment completely and no mass was detected in MRI and TVCDUS. Investigations were performed in areas with flow within the tumor-free cervix. A residual mass was noted in 2 patients with MRI and TVCDUS. There was a statistically significant difference between complete response to the treatment and increased resistive indices (P=0.001). In 2 patients with residual masses, no increase in resistive indices was detected. The mean resistive index of the control group was 0.65+/-13 and the difference was statistically significant compared to the resistive indices of the patients prior to the treatment. CONCLUSION: Since there was a significant correlation between the MRI findings and resistive indices, the spectral parameters obtained with TVCDUS were a good alternative to such an expensive modality as MRI in the evaluation of the response of cervical cancer to the treatment.

Improved survival of children with wilms tumor.

To analyze changes in the overall survival (OS) rate of children with Wilms tumor treated in a single institute over nearly 30 years. This study included 327 children with a newly diagnosed Wilms tumor. Their median age was 3 years, and the male:female ratio was 1.1. Survival rates were analyzed according to the stage of disease, histopathology, and different treatment regimens used between 1972 and 1999. At diagnosis, 51.1% of patients had advanced stage disease. Ten patients had anaplasia, and; 97% (317 patients) of the tumors had favorable histopathology. The 10-year OS rate was 60.6% for the entire group, but varied according to the years in which the patients were treated, the chemotherapy regimen, and stage of disease. Patients treated during the periods of 1972 to 1979, 1980 to 1989, and 1990 to 1999 had 10-year OS rates of 48.5%, 64.3%, and 72.8%, respectively. The 10-year OS rate in children treated with actinomycin only was 36.7% compared with 48% for children treated with the actinomycin-D+vincristine regimen with a 3-month interval, 67% for the actinomycin-D+vincristine regimen with a 1.5-month interval, 54.5% for the poor-risk regimen (actinomycin-D, vincristine, cyclophosphamide, and adriamycin), and 53.4% for the SIOP-9 protocol. Children with stage I to IV disease had 10-year OS rates of 75%, 77.1%, 54.4%, and 30.4%, respectively. The 10-year OS rates for children with stage III and IV disease increased from 46.4% and 13.4% for patients treated between 1972 to 1979 period to 75% and 54.5% for children treated during 1990 to 1999. The 10-year OS rate for children with Wilms tumor improved as treatment strategies evolved, illustrating that pediatric oncology in Turkey is developing parallel to the Western world.

Postoperative radiotherapy in the treatment of male breast carcinoma: a single institute experience.

BACKGROUND: To evaluate the outcomes of radiation therapy treatment of male patients with breast cancer in our single institutional cohort and discover possible adverse prognostic factors. METHODS: We retrospectively evaluated 42 male patients (median age 55; range 33-77 years) with breast cancer. Patients were irradiated postoperatively in 2 Gy/fraction/day to chest wall +/- lymphatics. RESULTS: Median follow-up was 29 months. Eleven patients had neoadjuvant and 36 patients had adjuvant Adriamycin-based chemotherapy. Nine patients (21%) had local or regional, two (5%) had distant, and one (2.5%) had both local and distant disease at the time of analysis. The actuarial five-year Overall Survival (OS) was 77%, whereas the actuarial five-year Disease-Free (DFS), Locoregional Recurrence-free (LRRFS), and Distant Metastases-Free (DMFS) survival rates were 45%, 69% and 66%, respectively. Univariate analysis of variables, including patient characteristics, treatment modalities and factors, and tumor characteristics, failed to show an association with LRRFS and DFS except percent positive nodal involvement > or = 30% and 50%. CONCLUSION: Though radiotherapy seems quite effective in reducing local recurrence, we have revealed that male breast cancer patients in our cohort with extensive nodal involvement (PPNI >30% and 50%) appeared not to have had a significant benefit from postmastectomy irradiation and adjuvant CMF-based chemotherapy.

Cavoatrial tumor extension in children with wilms tumor: a retrospective review of 17 children in a single center.

The aim of this study was to evaluate the clinical characteristics and treatment results of 17 children with cavoatrial tumor extension of Wilms tumor. Of the 360 Wilms tumors diagnosed between 1980 and 2000, 17 patients with intracaval thrombus were identified from the medical records at the pediatric oncology department of Hacettepe University. The following data were collected and reviewed: age, sex, presenting symptoms, tumor site, presence of anaplasia, stage, associated congenital anomalies, localization of tumor thrombus, radiologic findings, type and duration of preoperative chemotherapy, response to preoperative chemotherapy, recurrences, and survival. The frequency of cavoatrial extension in this group was 4.7% (15 in the inferior vena cava and 2 in the right atrium). Fourteen patients received preoperative chemotherapy consisting of two-drug regimen (vincristine and actinomycin D) ranging from 1 to 12 weeks (median 4 weeks). Since intravascular invasion is often asymptomatic, a careful radiologic examination to detect tumor thrombus before surgery is essential. There is no need for aggressive surgery in the presence of tumor thrombus. It may be resolved by preoperative chemotherapy. Surgical removal of the thrombus should be considered in the presence of life-threatening tumor thrombosis at diagnosis and in patients who had residual thrombus after chemotherapy.

Neoadjuvant chemotherapy with cyclophosphamide, mitoxantrone, and 5-fluorouracil in locally advanced breast cancer.

OBJECTIVES: Our primary objective was to determine the response rate; secondary objectives were to assess the toxicity rate, and disease-free and overall survival rates in patients with locally advanced breast cancer (LABC) receiving a cyclophosphamide (500 mg/m2), mitoxantrone (12 mg/m2) and 5-fluorouracil (500 mg/m2) (CMF) chemotherapy regimen. PATIENTS AND METHODS: The data from 74 patients with LABC with neoadjuvant CMF chemotherapy were analyzed retrospectively. Preoperatively, all patients received 3 cycles of CMF on day 1, repeated every 21 days. In 3 (4.1%) patients, breast-conserving surgery was given and in 71 (95.9%) modified radical mastectomy. All patients received radiotherapy and 3 additional cycles of CMF chemotherapy after surgery. RESULTS: Median age of the patients was 47 years (range: 17-74). 43 patients were premenopausal, whereas 31 were postmenopausal. 54 patients were in stage IIIA, and 20 were in stage IIIB. The overall clinical response rate was 88%; 11 (14.9%) had a complete response, 54 (73%) had a partial response, and 2 (2.8%) had progression. 14 (18.9%) had a pathological complete response. The median follow-up was 62 months. The median disease-free survival was 64.9 months, and the median overall survival was 97.5 months. The 5-year disease-free and overall survival rates were 52% and 79.9%, respectively. Most frequent side-effects were nausea/vomiting, mucositis, alopecia and leukopenia. CONCLUSION: The CMF regimen has a high overall response rate and an acceptable side effect profile in the treatment of locally advanced breast cancer. Further studies are needed to evaluate its effectiveness in breast-conserving strategies.

Acute blindness as a presenting sign in childhood non-Hodgkin lymphoma.

Non-Hodgkin lymphoma is the third most common malignancy in childhood. Occasionally, a patient with lymphoma may present with neuroophthalmologic symptoms and signs. It is usually associated with 3rd, 4th, and 6th cranial nerve palsies. Here, we report three children presenting with loss of vision. Two of them were cured with modified LMB-89 (lymphoma malignant B) chemotherapy regimen and radiotherapy. In one patient, loss of vision returned to normal in the left eye but persisted in the right eye. The second patient suffered from permanent visual loss, although the primary disease responded well to treatment. Unfortunately, the third patient died at an early phase of treatment. Acute blindness as a presenting symptom is rare in lymphoma. Early diagnosis and treatment is critical to increase the survival rate and to improve the quality of the vision.

Is there a survival benefit to adjuvant radiotherapy in high-risk surgical stage I endometrial cancer?

OBJECTIVE: The aim of this study was to examine the effects of therapeutic modalities on survival of stage I endometrial cancer and also to evaluate the surgical morbidity and the prognostic importance of surgicopathological variables. METHODS: A hundred and ninety-six stage I endometrial cancer patients treated at Hacettepe University Hospital between 1982 and 1997 were included. After initial diagnosis all patients underwent surgical procedures including peritoneal cytology, infracolic omentectomy, total abdominal hysterectomy, bilateral salphingoopherectomy, and complete pelvic-paraaortic lymphadenectomy. The mean age at initial diagnosis was 56 years (SD = 9.9 years) and the patients were followed 3-18 years (median, 8 years). All patients had endometrioid carcinoma. Stage IC and/or grade 3 tumors were considered high-risk factors and by this definition 147 (75%) patients were low risk and 49 (25%) patients were high risk. Forty-nine percent of high-risk patients received adjuvant radiotherapy compared with 3.5% of patients in the low-risk group. RESULTS: The 10-year disease-free and overall survival rates of the entire group were 97 and 98%, respectively. Ten-year overall survival rate for the low-risk group was 100% compared with 94% for patients with high-risk features (P = 0.002). The 10-year disease-free survival rate in the high-risk group was 96% for 24 patients who received adjuvant radiotherapy versus 92% for 25 patients who did not receive adjuvant therapy (P = 0.53). Only high grade was a significant predictor of poor survival (P = 0.0004). Overall surgical morbidity rate was 8.1% without mortality related to surgery. CONCLUSIONS: Surgical staging achieved excellent survival for stage I endometrial cancer patients without incurring untoward morbidity and mortality. No survival advantage of adjuvant radiotherapy was detected even for high-risk patients, so we suggest the use of radiotherapy may be reserved for relapse.

Neoadjuvant chemotherapy with taxotere-epirubicin-5-fluorouracil (TEF) in local-regionally advanced breast cancer: a preliminary report.

AIMS AND BACKGROUND: Sixty-three patients with local-regionally advanced breast cancer were treated with neoadjuvant chemotherapy consisting of docetaxel (Taxotere), epirubicin, and 5-fluorouracil (TEF). METHODS AND STUDY DESIGN: Preoperatively, patients received four cycles of Taxotere (80 mg/m2), epirubicin (60 mg/m2), and 5-fluorouracil (500 mg/m2), repeated every 21 days. Following completion of four cycles of chemotherapy, appropriate surgery was performed. After the surgery, patients received one cycle of the TEF chemotherapy regimen; following chemotherapy, radiotherapy was applied, and at the end two more cycles of TEF chemotherapy regimen were given. RESULTS: Sixty-three patients with locally advanced breast cancer were treated. Three patients were excluded from the study before the evaluation of response. Median age of the patients was 50 years (range, 25-77). Twenty-seven and 33 patients were premenopausal and postmenopausal, respectively. Thirty-nine patients were in stage IIIA and 21 in stage IIIB. Complete and partial responses were observed in 15 (25%) and 42 (70%) of the patients following four cycles of preoperative TEF chemotherapy regimen, respectively. Overall response was 95%, and primary lesion progressed only in 3 (5%) patients. The mean disease-free survival was 15.9 +/- 6.8 (range, 3.5-28) months and the mean overall survival was 18.6 +/- 7.2 (range, 5-30) months. The most frequent side effects were nausea-vomiting, mucositis, alopecia and leukopenia. CONCLUSIONS: TEF therapy is a treatment with a high overall response rate and toxicities similar to other taxotere combinations. A longer follow-up of patients is necessary for the determination of disease-free survival and overall survival.