The objective of this study was to analyze the efficacy and morbidity of vaginal cuff brachytherapy alone in intermediate- to high-risk stage I endometrial cancer patients after complete surgical staging. Between October 1994 and November 2005, 128 patients with intermediate- to high-risk stage I endometrial adenocarcinoma were treated with high dose rate (HDR) brachytherapy alone after complete surgical staging. The intermediate- to high-risk group was defined as any stage I with grade 3 histology or stage IB grade 2 or any stage IC disease. The comprehensive surgery was in the form of total abdominal hysterectomy, bilateral salpingo-oophorectomy in addition to infracolic omentectomy, and routine pelvic and para-aortic lymphadenectomy. The median number of the lymph nodes dissected was 33. The median age at the time of diagnosis was 60 years. Forty patients were staged as IB (grade 2: 25 and grade 3: 15), and 88 patients were staged as IC (grade 1: 31, grade 2: 41, and grade 3: 16). A total dose of 27.5 Gy with HDR brachytherapy, prescribed at 0.5 cm, was delivered in five fractions in 5 consecutive days. Median follow-up was 48 months. Six (4.7%) patients developed either local recurrence (n = 2) or distant metastases (n = 4). Five-year overall survival and disease-free survival (DFS) rates are 96% and 93%, respectively. Only age was found to be significant prognostic factor for DFS. Patients younger than 60 years have significantly higher DFS (P = 0.006). None of the patients experienced grade 3/4 complications due to the vaginal HDR brachytherapy. Vaginal cuff brachytherapy alone is an adequate treatment modality in stage I endometrial adenocarcinoma patients with intermediate- to high-risk features after complete surgical staging with low complication rates.

This study evaluates treatment outcomes and possible prognostic factors of inoperable cervical cancer patients treated with external beam radiotherapy (EBRT) and high–dose rate brachytherapy (HDR BRT). Between 1993 and 2000, 183 patients with cervical cancer were treated at our institute. Radiotherapy was the sole treatment modality until January 1997; after the announcement of National Cancer Institute in 1999, 40 mg/m2of cisplatin (49%) was routinely applied every week. Median age was 54 years (32–92 years). Most patients (88%) had advanced-stage disease (IIB–IIIB). With a median follow-up time of 45 months (6–121 months), the 5-year overall survival (OS), local recurrence–free survival, disease-free survival (DFS), and distant metastasis–free survival (DMFS) rates were 55%, 71%, 51%, and 77%, respectively. Univariate analysis revealed that age, tumor size, lymph node status, and concomitant cisplatin were prognostic factors for OS. The DFS rates were lower in young age group. Patients with tumor greater than 4 cm and age greater than 40 were at greater risk for local recurrence. Distant metastases were more frequent in patients with adenocarcinoma. Concurrent cisplatin use increases DMFS rates (91% vs 78%;P= 0.05). In multivariate analysis, extensive stage, parametrial infiltration, young age, adenocarcinoma histopathology, and lymph node metastasis were negative prognostic factors for OS while concomitant cisplatin increases OS. Likewise, patients with extensive stage, adenocarcinoma, and without concurrent cisplatin administration had more risk for distant metastasis. There was no treatment-related mortality. Grade 3–4 morbidity rates were seen only in eight patients (4%). The combination of EBRT and HDR BRT together with concomitant chemotherapy in the treatment of locally advanced carcinoma of cervix is safe and well tolerated with acceptable morbidity.

Recent studies suggest that plasma Epstein-Barr virus (EBV) DNA may reflect tumor burden in patients with nasopharyngeal cancer. A prospective study was initiated to investigate this correlation in 125 patients (34 pretreatment [Group A], 78 in remission [Group B] and 13 relapsed [Group C]) and 19 healthy controls. In group A, EBV DNA was detected in plasma samples of 24 (70%) patients. In Group B, EBV DNA was detected in 7 patients (range 77-13,731 copies/mL) and further imaging in all but one of these patients revealed active disease confirmed by ultrasound-guided fine-needle biopsy. There was only one false-positive case; this patient is currently under follow-up. Here we describe 2 of the 7 patients with detectable plasma EBV DNA in whom recurrence was documented by PET scan during follow-up. Our results showed that in group B the positive predictive value of quantitative analysis of plasma EBV DNA was 85%. Quantitative analysis of EBV DNA in plasma seems to become an integral part of screening, staging, monitoring, and prediction of relapse in patients with nasopharyngeal carcinoma. However, previous studies cannot be considered definitive and more reports on the use of this technique are urgently needed from both endemic and non-endemic regions.

We investigated the treatment results and probable prognostic factors in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) treated with neoadjuvant chemotherapy (NCT) plus conventional radiotherapy (RT) or concomitant chemoradiotherapy (CCRT) at our hospital. We retrospectively evaluated 61 patients (48 males, 13 females) with locoregionally advanced NPC treated either with 2 cycles of NCT plus RT (Group A, 37 patients) or with three cycles of NCT plus CCRT (Group B, 24 patients) between September 1995 and October 2002. According to the AJCC 1997 classification system, 19 patients had Stage III disease and 42 had Stage IV. NCT consisted of cisplatin and 5-fluorouracil. Total RT doses were ranged between 59.4-71.6 Gy (median: 66.2 Gy). Concomitant cisplatin (75 mg/ m(2)) was given on first days of Weeks 1, 4, 7 of CCRT. Patient sex, histopathologic subtype, T status, ECOG performance status, stage, serum lactate dehydrogenase (LDH) level, and cranial nerve involvement at diagnosis were comparable in the 2 groups. There were statistically significant differences between median follow-up times and N status for the 2 groups. Fifty-five (90.2 percent) patients completed all planned NCT. Univariate analysis revealed the pretreatment LDH level as the only statistically significant prognostic factor for disease-free survival (DFS) and overall survival (OS). Four-year DFS rates were 55.9 percent and 21.3 percent for patients with normal and high serum LDH levels, respectively (P = 0.04). Four-year OS rates were 68.7 percent and 28.5 percent for patients with normal and high serum LDH levels, respectively (P = 0.01). Multivariate analysis also revealed that high serum LDH level was the only independent risk factor that predicted OS. The relative risk was 2.43 (95% CI: 1.08-5.45) for patients with high serum LDH levels (P = 0.03). No independent risk factors associated with DFS were found for other prognosticators. Our study demonstrated that high serum LDH level is the only independent unfavorable risk factor for OS in patients with locoregionally advanced NPC who were treated with NCT plus RT or CCRT.

To evaluate the efficacy of postoperative radiotherapy and to investigate prognostic factors for early-stage cervical cancer patients. From December 1993 to December 2001, 141 patients with stage I–II cervical cancer without para-aortic lymph node (LN) metastases and treated by surgery and postoperative radiotherapy (RT) were included in this study. Indications for postoperative external RT were based on pathologic findings, including LN metastasis, positive surgical margins, parametrial involvement, pT2 tumor, and presence of any two minor risk factors like lymphvascular space involvement, deep stromal invasion, and tumor diameter between 2–4 cm. Sixty-six (47%) patients received RT alone, whereas 59 (42%) were treated with RT and concomitant chemotherapy (CT), and 16 received neoadjuvant CT. Patients with positive vaginal margins also received 27.5 Gy high–dose rate vaginal cuff brachytherapy in five fractions. Median follow-up time was 55 months. The actuarial 5-year overall (OS), disease-free (DFS), locoregional recurrence-free (LRFS), and distant metastases-free (DMFS) survival rates are 70%, 68%, 77%, and 88%, respectively. Univariate and multivariate analyses revealed that level and number of metastatic LNs and concomitant CT were unique significant prognostic factors for OS, DFS, and LRFS. Endometrial involvement, on the other hand, was proven to be significant for DFS and DMFS. Patients with less than three LN metastases or having only obturator LN involvement showed similar prognosis with their counterparts having no LN metastases. On the other hand, patients with either common iliac LN or more than three LN metastases had significantly worse outcome. Our results indicate that level and number of metastatic LNs are the most important prognostic factors determining the survival rates, and patients with upper lymphatic involvement or more than three metastatic LNs seem to need more effective treatment approaches

Congenital lymphangioma circumscriptum (LC) of the vulva is a rare disorder with unknown etiology. Treatment options include ablative approaches such as laser therapy, sclerotherapy, and surgery. Radiotherapy has been shown to be effective in the management of congenital lymphangioma especially in the thoracic and abdominal lesions. In this report, we describe a patient with persistent vulvar LC despite sclerosing therapy and several surgical excisions. She was treated with a course of external radiotherapy and showed a dramatic objective response with relief of all symptoms

BACKGROUND:To evaluate the clinical characteristics, treatment regimens, survival, and late complications in patients with nasopharyngeal carcinoma. PROCEDURE:Eighty-four patients diagnosed with nasopharyngeal carcinoma between 1972 and 2002 were retrospectively evaluated. Tumor status, lymph node involvement, metastasis, and stage were assessed according to the TNM classification. All patients were treated with radiotherapy and chemotherapy. Chemotherapeutic regimens involved cyclophosphamide from 1972 to 1982, vincristine + cyclophosphamide + epirubicine and actinomycin-D protocol from 1982 to 1999 and cisplatin + methotrexate + 5-fluorouracil with leucovorine rescue after 1999. Mean and median values were used for the demographic characteristics. Kaplan-Meier survival curves were used for survival analysis. The patient groups were compared in terms of survival duration using a log-rank test. RESULTS:There were 51 males and 33 females with a median age of 13 years (7-17) at diagnosis. At the time of diagnosis, 78.5% of the patients were at advanced stage (stages III and IV). Overall and event-free survival rates were 56.3% and 50.1%, respectively. Survival was inversely affected by advanced nodal status (P = 0.01). The survival rates (80%) were found higher with cisplatin + methotrexate + 5-fluorouracil + leucovorine rescue regimen. The most frequent late complications after therapy were hypothyroidism (9.5%), dental caries (7.1%), and trismus (7.1%). CONCLUSION:The cisplatin-based regimen was the best chemotherapeutic regimen. Less toxic regimens with better survival rates should be investigated in patients with nasopharyngeal carcinoma.

To investigate the incidence and outcome of secondary neoplasms in pediatric patients treated for childhood cancer. Between December 1971 and January 2000, a total of 5859 patients younger than age 17 were diagnosed and treated for childhood cancers in our center. Of this group, 1511 (36%) patients were followed for more than 36 months. These long-term survivors were included in this analysis. Twenty-six patients developed a secondary malignancy with an overall risk of 1.7% in this cohort. The male:female ratio was 17:10, with a median age of 7.66 at diagnosis (range, 2 to 16 y). Four patients (14.8%) with Hodgkin lymphoma; 3 each (11.1%) with retinoblastoma and rhabdomyosarcoma; 2 each (7.4%) with Wilms tumor, Ewing sarcoma, medulloblastoma, ganglioneuroblastoma, and non-Hodgkin lymphoma; and 1 each (3.7%) with ependymoma, nasopharyngeal carcinoma, osteosarcoma, astrocytoma had a secondary malignant disease during the long-term follow-up period. Secondary malignant diseases were osteosarcoma in 6 patients, acute lymphoblastic leukemia in 2, acute myelogenous leukemia in 2, and rare malignant disease in others. Four patients with osteosarcoma developed disease within the radiation field. Osteosarcoma was the most frequently occurring secondary neoplasm. Less toxic treatment modalities should be used to decrease the risk of secondary malignant diseases.

Trismus is a more common symptom in NPC patients with young age and an indicator of advanced primary tumour. Overall response rate after treatment was 88%. Trismus recovered in majority of patients at the end of treatment and patients with complete recovery of trismus may have a better survival.

Chronic radiation enteropathy (CRE) is an undesirable radiation-induced toxicity and a common health problem in patients with pelvic or abdominal malignancies. Damage to microvascular endothelial cells and connective tissue is blamed to cause this adverse effect. It is shown that platelets are the first cellular elements that initiate the homeostatic and inflammatory responses and release of several proinflammatory and fibrinogenic mediators. Antiplatelet agents such as ticlopidine and clopidogrel were shown to prevent CRE and this effect is believed to be directed by their activities against thrombocytes. However, recent studies have shown that these drugs also induce apoptosis in endothelial cells and may lead to decreased expression of endothelial prostacyclin and thrombomodulin (TM) and increased release of von Willebrand factor which are shown to be major contributors of coagulation process. Assuming that radiation induced apoptosis occur 6-10h after irradiation, we think that timing of these antiaggregant drugs with irradiation is important and a 6-10h interval between these may be beneficial to avoid this adverse interaction.

The authors report 3 cases of Hodgkin's disease with intracranial involvement. The patients were 4, 12, and 15 years old (male/female=1/2). Initially, they were treated with ABVD or COPP chemotherapies and low-dose involved field radiotherapy. Intracranial recurrences occurred 27, 40, and 42 months after initial diagnosis, respectively. Two patients experienced convulsions and the other complained of diplopia. The metastatic lesions were located supratentorially with CT or MRI. Despite initial response achieved following systemic chemotherapy and external irradiation to cranial lesions, all patients died with disseminated disease. In patients with intracranial involvement of Hodgkin's disease, prolonged disease-free survival may be achieved by combined modality treatment.

Aggressive fibromatosis (AF), also known as desmoid tumor is a monoclonal fibroblastic proliferation in a collagen matrix that arises in musculoaponeurotic structures. Though considered as benign, they are locally invasive and their propensity for recurrence after conservative surgery is well documented. Addition of postoperative adjuvant radiotherapy produces higher local control rates, although recurrence rates are still high in patients with positive margins. The antineoplastic activity of vitamin D has been demonstrated both in vitro and in vivo models of several cancers. The proposed mechanisms for antineoplastic activity include inhibition of proliferation associated with cell cycle arrest, induction of apoptosis and reduction in invasiveness and angiogenesis. It has also been shown that vitamin D has a negative impact on collagen homeostasis by inhibiting the formation and increasing its degradation. Since vitamin D has an antineoplastic activity and negative effect on collagen synthesis and deposition, it is proposed that 1,25-dihydroxy vitamin D3 can be a right therapeutic option for the management of desmoid tumors.

Purpose: We aimed to investigate Ebstein-Barr virus (EBV) latent membrane protein-1 (LMP-1) and Interleukine-10 (IL-10) expression in nasopharyngeal carcinoma (NPC) patients and to evaluate their prognostic significance. Material and Methods: Between 1993 and 1999, 166 patients were treated with the diagnosis of nonmetastatic NPC at our department. The expression of LMP-1 and IL-10 was investigated by using an immunohistochemical approach in 74 (53 male, 21 female) patients whose paraffin embedded tissue samples were available. A detailed histopathological analysis including degree of apoptosis and lymphocyte infiltration was made and all patients were reclassified according to the World Health Organization (WHO) classification. Univariate, multivariate, and logistic regression analyses were performed using all clinical and pathological prognostic factors. All patients were treated with radiotherapy +/-chemotherapy. Follow-up ranged between 12 and 80 months (median: 32). Results: The histopathological diagnosis was WHO-I in 1 (1.3%), WHO-II in 15 (20.2%), and WHO-III in 58 (79.5%) patients. There were 38 (51%) patients with IL-10 expression and 44 (61%) patients with LMP-1 expression. Twenty-seven (36.4%) patients were found to be both IL-10 and LMP-1 positive. There were significantly more NO disease in patients without LMP-1 expression compared to LMP-1 positive patients (65% vs. 35%, p = 0.01). The logistic regression analysis showed advanced nodal involvement to be the major parameter affecting the expression of IL-10 (p = 0.03). Three-year overall survival (OS), locoregional relapse free survival (LRRFS), and distant metastasis free survival (DMFS) rates were 67.8%, 84.4%, and 74.3%, respectively, for the whole group. On univariate analysis, LRRFS was significantly lower in WHO-III patients, DMFS was significantly lower in advanced nodal disease and IL-10 negative patients, and OS was significantly lower in WHO-III patients. Multivariate analysis showed that WHO-III and T2 patients were significantly associated with lower OS and N3 patients were significantly associated with lower DMFS. Conclusion: We observed a high rate (61%) of EBV (LMP-1 positive) and NPC association in our patients. LMP-1 positive tumors were found to be more prone to invade lymph nodes. Patients with negative IL-10 expression had more advanced N disease. We did not find a prognostic significant role of IL-10 and EBV LMP-1 on survival in multivariate analysis.

9668 Background: Cancer cells utilize anaerobic glycolytic way to compensate their faster metabolism when compared to normal cells. The purpose of this study was to investigate the effect of radiation on tumor metabolism. Methods: MCF-7 breast cancer cell lines were divided into 3 groups, including 2 control groups and aerobic study group (were irradiated 600 cGy by Co-60 teletherapy unit), incubated with radiolabelled glucose for 4 hours. One control group was for aerobic, and the other was for anaerobic group after KCN addition. Radiolabelled CO2 produced by the cells was isolated and collected in specially designed sintillation vials. In supernatant the measurements of other end-products of carbohydrate catabolism including lactate, pyruvate, acetate were performed on a liquid scintillation analyzer after they were collected via anion-exchange chromatography. Finally glucose in supernatant was measured enzymatically by glucose oxidase method. Additionally, in pellets protein was determined by modified Lowry method and glycogen by Hassid and Abraham's enzymatic method (glycogen consumption per 1000 cells for each hour). Results: Radiation significantly reduced the number of cells (12.3x106), KCN group and control groups included 46.3 x106and 41.3 x106respectively. Glycogen consumption and lactate production were significantly higher in anaerobic and radiation groups. Whereas CO2 production was significantly higher in control group (Table I). Taken all results together radiation lead tumor cells more anaerobic glycolysis with high glycogen consumption, high lactate production and low CO2 production. Conclusions: Radiation itself has led tumor cells to produce energy by anaerobic glycolysis, meaning radiation exposed cells become more hypoxic. In our knowledge, this is the first experiment showing anaerobic effect of radiation on tumor cell lines. The researchers should be aware of this effect of sublethal dose of radiation. No significant financial relationships to disclose.

In human skin, keratinopoiesis is based on a functional hierarchy among keratinocytes, with rare slow-cycling stem cells responsible for the long-term maintenance of the tissue through their self-renewal potential, and more differentiated daughter progenitor cells actively cycling to permit epidermal renewal and turn-over every month. Skin is a radio-responsive tissue, developing all types of radiation damage and pathologies, including early tissue reactions such as dysplasia and denudation in epidermis, and later fibrosis in the dermis and acanthosis in epidermis, with the TGF-beta 1 pathway as a known master switch. Also there is a risk of basal cell carcinoma, which arises from epidermal keratinocytes, notably after oncogenic events in PTCH1 or TP53 genes. This review will cover the mechanisms of adverse human skin reactions and carcinogenesis after various types of exposures to ionizing radiation, with comparison with animal data when necessary, and will discuss the possible role of stem cells and their progeny in the development of these disorders. The main endpoints presented are basal cell intrinsic radiosensitivity, genomic stability, individual factors of risk, dose specific responses, major molecular pathways involved and the cellular origin of skin reactions and cancer. Although major advances have been obtained in recent years, the precise implications of epidermal stem cells and their progeny in these processes are not yet fully characterized.

Purpose: To determine the efficacy and toxicity of combined modality treatment (CMT) or radiotherapy (RT) alone in the management of clinical Stage I-IIA adult Hodgkin's disease patients.Methods and Materials: Forty-seven patients with supradiaphragmatic clinical Stage I-IIA Hodgkin's disease without bulky mediastinal lymphadenopathy were enrolled into this prospective study between September 1997 and February 2002. Patients with very favorable criteria presenting with one or two nonbulky nodal areas involved, an erythrocyte sedimentation rate of <50 mm/h, age <40 years, and either lymphocyte predominant or nodular sclerosing histologic findings were treated by RT alone. Patients missing any of these favorable criteria were classified as the other favorable group and were treated with three courses of doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy followed by involved-field RT. The median age was 36 years (range, 19-53 years). Of the 47 patients, 15 were women and 32 were men. Only 3 patients were classified as the most favorable group and treated with mantle RT alone; the remaining 44 were treated with CMT.Results: The median follow-up was 51 months (range, 20-74 months). Only 2 patients developed recurrence, both out of the irradiated field, one in the contralateral neck and the other in the abdomen. The 5-year relapse-free and overall survival rate was 95.4% and 97.8%, respectively. Although none of the prognostic factors were statistically significant for relapse-free survival, a trend was noted for the response to chemotherapy (p = 0.06). Only 2 patients developed treatment-related complications. One patient treated with mantle RT alone developed severe ischemic heart disease and one in the CMT arm developed subclinical hypothyroidism.Conclusion: Despite the short follow-up, CMT or RT alone tailored according to the clinical prognostic factors were successful in terms of disease control in clinical Stage I-IIA Hodgkin's disease. Longer follow-up is required to make definitive conclusions. (C) 2004 Elsevier Inc.