Radiotherapy in congenital vulvar lymphangioma circumscriptum.

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.

Vaginal high dose rate brachytherapy alone in patients with intermediate- to high-risk stage I endometrial carcinoma after radical surgery.

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.

Use of plasma Epstein-Barr virus DNA monitoring as a tumor marker in follow-up of patients with nasopharyngeal carcinoma: preliminary results and report of two cases.

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.

Importance of timing of antiaggregant treatment in the prevention of radiation induced enteropathy.

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.

1,25-Dihydroxy vitamin D3: can it be an effective therapeutic option for aggressive fibromatosis.

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.

Acute phase response during radiotherapy.

PURPOSE: The acute phase response is characterized by changes in the plasma concentrations of a number of liver-synthesized proteins, one of which is C-reactive protein (CRP). The existence of these changes in the plasma profile underlies the change in erythrocyte sedimentation rate (ESR). Acute phase response itself is an illness and may result from immunologic reactions and inflammatory processes. This study is designed to determine whether the CRP level and ESR increase during radiotherapy and whether their rise correlates with acute and late radiation morbidity. METHODS AND MATERIALS: Between April 1997 and October 1998, 51 patients with the diagnosis of endometrium and cervical cancer were treated with surgery and postoperative radiotherapy. Median age at the time of radiotherapy was 52 (range, 26-73) years. Thirty patients received pelvic radiotherapy, and 21 patients were treated by pelvic-paraaortic irradiation. A total dose of 50.4 Gy to the pelvis and 45 Gy to the paraaortic field were delivered in conventional fraction. Erythrocyte sedimentation rates and CRP levels were studied before, during, and at the end of radiotherapy. RESULTS: The mean ESR measurements before and after radiotherapy were 40 (8-100) and 52 (10-120), and mean CRP levels were 1.4 (0.12-9.8) and 2.7 (0.12-32.2), respectively. The statistical analysis yielded significant rise in ESR and CRP levels at the end of radiotherapy (p < 0.001). The increase was more prominent in patients who were irradiated through pelvic-paraaortic field than in patients with pelvic radiation (p = 0.005 and 0.028 respectively). CONCLUSION: Acute phase response was present during radiotherapy. Radiotherapy should be considered as a cause of increase in CRP level and ESR especially in clinical conditions where acute phase response is important.

Comparison of AJCC 1988 and 1997 classifications for nasopharyngeal carcinoma. American Joint Committee on Cancer.

PURPOSE: A comparison of American Joint Committee on Cancer (AJCC) 1988 and 1997 nasopharyngeal carcinoma (NPC) classifications was made in terms of patient distribution and efficacy in predicting prognosis. METHODS AND MATERIALS: Between 1993-1997, 90 patients (64 M, 26 F) with non-metastatic NPC were treated. The mean age was 42.02 (range: 9-82) years old. Histopathological diagnosis was WHO 2 and 3 in 83 (92.2%) patients. All patients were prospectively staged using AJCC 1988 and modified Ho's classifications (1989) and these data were stored in a computer database. Retrieval of this information enabled us to restage patients according to the AJCC 1997. Median follow-up was 38 months. RESULTS: According to the AJCC 1988 there were 2 (2.2%), 6 (6.7%), 13 (14.4%), and 69 (76.7%) patients in Stage I, II, III and IV, respectively. Same figures were 8 (8.8%), 21 (23.3%), 26 (28.9%), and 35 (38.8%), according to AJCC 1997. Three year overall survival (OS) rates were 100%, 100%, 67%, and 62% for patients Stage I, II, III, and IV according to the AJCC 1988 and 100%, 72%, 65%, and 55%, (I vs. IV; p = 0.03, I vs. III; p = 0.05) respectively, according to the AJCC 1997. Three year loco-regional relapse free survival (LRRFS) rates were 50%, 100%, 100%, and 83% (I vs. III; p = 0.03) for patients in Stage I, II, III, and IV according to the AJCC 1988. Same figures were 88%, 90%, 89%, and 85% according to the AJCC 1997. Three year distant metastasis free survival (DMFS) rates were 100%, 100%, 82%, and 67% for patients in Stage I, II, III, and IV according to the AJCC 1988. Same figures were 100%, 74%, 80%, and 57% (I vs. IV; p = 0.03) according to the AJCC 1997. We did not observe any significant difference in LRRFS among T stages for both staging system and the N stage was the primary determinant for DMFS in both systems. CONCLUSIONS: We observed a better patient distribution with AJCC 1997 comparing to AJCC 1988. The new classification also attained better statistical significances among stages in the OS and DMFS rates.

The effect of verapamil in the prevention of radiation-induced cataract.

PURPOSE: Cataract is an unavoidable complication when radiation therapy includes the lens, even in small doses. Alterations in the ion content of the lens were considered to play an essential role in cataract formation. In this experimental study, the effect of verapamil on ion concentrations within the irradiated lenses was investigated in rats. METHODS AND MATERIALS: Forty female Wistar albino rats, each weighing 180-250 g, were divided into three groups: (a) radiation treated (n = 10); (b) no treatment (n = 10); (c) or a combination of radiation and verapamil (n = 20). Both the radiation group and verapamil-treated group received 5 Gy radiation to the cranium in a single fraction, including the eyes, within the irradiation volume. All animals were sacrificed by bleeding, 7.5 weeks posttreatment. Calcium, sodium, and potassium levels were measured in blood and in lens homogenates. However, for technical reasons, magnesium levels could only be studied in lens homogenates. RESULTS: Potassium and sodium concentrations in lens homogenates did not differ in the control and radiation groups, but both were significantly lower in the verapamil-treated group (p = 0.001, p = 0.009, respectively). Calcium levels were higher in the radiation group and lower in the verapamil-treated group compared to the controls (p < 0.0001); magnesium levels did not differ (p = 0.37). CONCLUSION: Verapamil effectively decreased the lens calcium concentration, which is accepted as the key element in radiation cataractogenesis. It is therefore concluded that verapamil may reduce the risk of radiation-induced cataract formation.

Accelerated hyperfractionated radiotherapy in supratentorial malignant astrocytomas.

PURPOSE: To determine the safety and effectiveness of accelerated hyperfractionated radiotherapy in the treatment of supratentorial malignant astrocytomas. MATERIALS AND METHODS: Between June 1995-July 1997, 75 patients were enrolled to a prospective phase II study. A total dose of 60 Gy was delivered in 2 Gy b.i.d. fractions with an interval of 6-8 h, 5 days per week, in an overall time of 3 weeks. The treatment protocol was planned to give 40 Gy to a treatment volume covering the contrast-enhancing lesion and oedema (+ 3-cm margin) and additional 20 Gy to the volume encompassing the contrast-enhancing lesion alone with a 1-cm margin based on preoperative magnetic resonance imaging and/or CT findings. The patients had a median age of 46 years and a median Karnofsky performance status score of 80. Histology consisted of anaplastic astrocytoma (AA) in 16 (21%) and glioblastoma multiforme (GBM) in 59 (79%) patients. RESULTS: Median survival was 11 months for all patients; 10 months for GBM patients and 40 months for AA patients. Survival rates at 1 and 3 years were 41%, 11% for all patients; 62, 37% for AA patients and 35, 6% for GBM patients, respectively. Multivariate analysis revealed significant impact of age, histology and neurological functional class on survival. The incidence of grade 3 or worse late neurological toxicity was 5.3%. CONCLUSIONS: Although accelerated hyperfractionated radiotherapy showed no significant advantage on survival, it shortened the treatment period from 6 to 3 weeks. Radiotherapy was well tolerated and the incidence of late toxicity is acceptable.

Results of post-operative or exclusive radiotherapy in grade I and grade II cerebellar astrocytoma patients.

43 Patients with the diagnosis of cerebellar astrocytoma were post-operatively treated, between 1 January 1976 and 31 December 1985. Their age ranged between 2 and 51 years with a median of 13. There were 22 males and 21 females. The tumours were reported as grade I in 18, and grade II in 25 patients. The primary surgical intervention was in the form of biopsy in 3, subtotal excision in 24 and macroscopic total excision in 16. All patients were treated with cobalt-60 teletherapy unit, to a total tumour dose of 4500-5500 cGy in 6-7 weeks. The obtained 5 and 10 year actuarial survival rates are 78% and 78%. Our study gives the impression that, age, sex and tumour grade are not determining factors in survival and post-operative radiotherapy improves prognosis in cases treated by subtotal excision while it remains unnecessary in those who had undergone total surgical removal.

Factors influencing the distribution of metastases and survival in metastatic breast carcinoma.

A total of 370 patients with metastatic breast, carcinoma who had been followed at Hacettepe Oncology Department between 1980 and 1991 were retrospectively analyzed for the factors influencing the distribution of metastases and survival. Median age was 47 years. Radical or modified radical mastectomies were performed in 199 (53.8%). Infiltrative ductal carcinoma was the most common pathologic subtype (69.4%). In 191 patients who were evaluated for estrogen receptor (ER) status, 101 (52.9%) were positive and 90 (47.1%) were negative. The distribution of first metastases did not differ between the soft tissue, bone, and visceral sites. The second, third, and fourth metastases were more common in visceral sites (p < 0.05). ER and menopausal status did not affect distribution. Mortality rate was significantly lower in the group having the first metastasis to the bone (p < 0.05). Of interest, first metastases were predominantly found in visceral sites in patients having radical or modified radical mastectomies (p < 0.05). Response to therapy, presence of initial metastases, axillary status, and age were the important factors influencing the overall survival in univariate analysis, whereas response to therapy, ER status, age, and presence of initial metastases were the important factors according to the multivariate analysis.

Malignancy in Behçet's disease: a report of 13 cases and a review of the literature.

Behçet's disease (BD) has rarely been reported in association with malignant diseases. In most cases the autoimmune nature of the disease itself or immunosuppressive drug use has been blamed for malignant transformation. We report 13 cases of BD concurrent with neoplastic disease as well as treatment-related morbidities in this particular patient group. Between 1986 and 1999, 400 patients were diagnosed as having BD in Hacettepe University Hospitals. Of these 13 patients, 3.25% developed malignant diseases within a median follow-up time of 9.8 years. Solid tumors were diagnosed in 10 patients and haematological or lymphoid malignancies in three. Surgery was performed in seven patients, whereas radiotherapy was applied in six and chemotherapy in eight. A literature review revealed 27 cases of BD associated with malignancies, mostly lymphoid or haematological. Ten of our cases were solid tumors, and to our knowledge most of these are the first reported cases of specific malignancies concurrent with BD. Treatment-related morbidities were wound infection as surgical morbidity in one patient (1/7) and radiotherapy-related morbidity in three (3/6) patients in a median follow-up time of 2 years. Solid tumors in addition to lymphoid and haematological malignancies are also seen during the course of BD. Radiation therapy may cause severe late toxicities in the presence of BD. Chemotherapy and surgery are fairly safe for the treatment of malignancies in BD patients.

Neoadjuvant chemotherapy in locally advanced breast cancer: a preliminary report. Turkish Oncology Study Group.

AIMS AND BACKGROUND: A pilot study of neoadjuvant chemotherapy with cyclophosphamide-epirubicin-5-fluorouracil (FEC) was performed on 85 patients with locally advanced breast cancer. METHODS AND STUDY DESIGN: Patients received four cycles of neoadjuvant chemotherapy followed by surgery, radiotherapy and a treatment with cyclophosphamide-methotrexate-5-fluorouracil for three cycles. RESULTS: Major clinical response was obtained in 76 (89%) patients. Complete response was documented in 14 (17%) patients at pathologic examination of surgical specimen. Grade 1-2 nausea and vomiting was the most common (77%) side effect. Grade 2-3 alopecia was 66%. Grade 2-3 neutropenia occurred in 16% of patients. None of the patients developed febrile neutropenia. Sinus tachycardia was observed only in one patient. Three patients had a more than 10% decrease in the left ventricular ejection fraction without any clinical signs. Nine patients had progressive or stable disease and 4 did not undergo surgery or receive radiation therapy; thus 13 were excluded from survival analysis. After a median followup of 31 months (range, 15-41), disease-free survival and overall survival were 20 (range, 13-32) and 23 months (range, 17-32). CONCLUSIONS: The FEC combination is safe and effective for a neoadjuvant setting in locally advanced breast cancer. A longer follow-up is necessary for the end point results.

Non-Hodgkin's lymphomas of the tonsil: a retrospective analysis of twenty-eight patients with primary tonsillary lymphoma.

AIMS: To analyze the clinical and therapeutic aspects of patients with primary tonsillary non-Hodgkin's lymphoma. METHODS: Twenty-eight patients with primary tonsillary non-Hodgkin's lymphoma who had been followed in the Hacettepe Oncology Institute between 1974 and 1992 were retrospectively analyzed. Fifteen patients were male, 13 were female. Median age was 55 years. RESULTS: Constitutional symptoms were present in 10 patients (35.7%). Stages according to the Ann Arbor classification were I and II in 12 and 16 patients, respectively. According to the Rappaport classification, poorly differentiated lymphocytic was the most common pathologic subgroup (42.9%). Grades according to the Working Formulation were low, intermediate and high in 3, 22 and 3 patients, respectively. Twenty-two patients had received chemotherapy. Cyclophosphamide, vincristine and prednisone (CVP), and cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) were the regimens most commonly employed. Eighteen patients received radiotherapy to Waldeyer's ring and neck. Eight patients achieved remission with chemotherapy plus radio-therapy, 7 patients with chemotherapy alone, and 5 patients with radiotherapy alone. In addition to the 20 patients who achieved complete remission, 3 patients achieved partial remission; the overall response rate was 82.1%. The response rates and survival attained with the combined modality, chemotherapy, or radiotherapy alone were not statistically different (P > 0.05). The median follow-up was 14 months. Overall and disease-free survival at 5 years were 62.6% and 77.6%, respectively. Pathologic grade was the most important prognostic factor influencing overall survival in the Cox multivariate model. CONCLUSIONS: Poorly differentiated lymphocytic lymphomas were the most common pathologic subtype, and pathologic grade was the most important prognostic factor to influence survival in the present study. Although combined modality treatment did not appear to be superior to chemotherapy or radiotherapy alone, a larger number of patients is needed to draw definite conclusions.

Thyroid dysfunction in children receiving neck irradiation for Hodgkin's disease.

Thyroid function was studied in 46 long-term survivors of pediatric Hodgkin's disease with a median follow-up time of 10.5 years. The mean age of the patients at the time of treatment was 8 years. Treatment consisted of radiotherapy alone in seven patients and combined radiation and chemotherapy in 39 patients. The radiotherapy dose to the thyroid gland was less than 2000 cGy in one, 2000-2500 cGy in 15, 2500-3000 cGy in 17, and greater than 3000 cGy in 13 patients. Evaluation consisted of clinical examination and thyroid function tests of total and free triiodothyronine, thyroxin, arid thyroid stimulating hormone levels. Twenty-one of 46 patients (45.6%) showed thyroid function abnormalities, however only nine of them had diffuse or nodular hyperplasia on physical examination. Risk factors of age, chemotherapy schema, total radiation dose, and dose per fraction did not significantly influence the incidence of thyroid dysfunction.

Cranial nerve involvement in nasopharyngeal carcinoma: its prognostic role and response to radiotherapy.

Between 1975 and 1989, 23 nasopharyngeal carcinoma patients presenting with cranial nerve involvement (CNI) of one or more nerves at the time of diagnosis were treated and followed-up in our department. All patients were irradiated with curative intent, and total doses of 50 to 70 Gy (median 65 Gy) were delivered to the nasopharynx. Cranial nerves VI, III, V, IV, IX, and XII were the most commonly involved nerves. The total response rate of cranial nerves was 74% in a median follow-up time of 2 years, with the highest rate observed in the third and sixth cranial nerves. All complete responses except two were observed in the first month after radiotherapy.

Intracranial ependymomas: treatment results and prognostic factors.

Forty-nine intracranial ependymoma patients were postoperatively irradiated with craniospinal, cranial, or wide local fields. Thirty-two patients received an adjuvant chemotherapy regimen of vincristine and CCNU with or without procarbazine. The 10-year actuarial overall and progression-free survival rates were 57% and 57%, respectively. Age was the only significant prognostic factor in favor of adults (p = 0.01).

Familial glioma in two siblings.

We report two siblings who had intracranial gliomas, one with glioblastoma multiforme and the other with mixed oligo-astrocytoma. The genetic influences in the development of glioma are discussed.

Choroid metastasis of undifferentiated nasopharyngeal carcinoma.

Choroid metastasis of primary nasopharyngeal carcinoma is an infrequent event. Here, we report a case of nasopharyngeal carcinoma with metastases to the choroid successfully treated by external beam radiotherapy.

Plaque radiotherapy in the management of retinoblastoma.

Retinoblastoma is the most common intraocular malignant tumor in childhood and is radiosensitive. We treated five patients with solitary intraocular retinoblastoma using iodine-125 plaque radiotherapy as a primary procedure. Tumor basal diameters ranged from six to 16 mm and thickness ranged from three to 11 mm. The radiation dose delivered to tumor apex ranged from 3500 to 5000 centigrays. All tumors regressed considerably within a follow-up ranging between seven to 12 months. There was no tumor recurrence or any complications related to plaque brachytherapy within this early period. We concluded that plaque radiotherapy is an effective method in local tumor control and allows eye preservation in patients with retinoblastoma.