I.L. Atahan

Sucralfate in the prevention of radiation-induced oral mucositis.

Radiotherapy-induced mucositis decreases the quality of life by impairing eating, swallowing, and talking and by disturbing sleep. Mucositis may also predispose to local and systemic infections and may cause interruption of radiotherapy course. We studied the efficacy of sucralfate suspension in the prevention and management of oral mucositis and pain during radiotherapy in a double-blind, placebo-controlled, randomized, prospective trial. Twenty-eight patients with head and neck cancer were included in the study. The patients were randomized to use either sucralfate mouth washing (n = 18) or placebo washing (n = 10) during irradiation. Oral mucositis and symptoms were assessed by the same physician using Radiation Therapy Oncology Group Acute Radiation Morbidity Scoring criteria. All patients developed varying degrees of radiation-induced mucositis. Grade 4 mucositis was not encountered in any patient. One patient had grade 1, seven patients grade 2, and two patients grade 3 mucositis in placebo group. In sucralfate group, nine patients each had grade 1 and grade 2 with no grade 3 mucositis. Patients in the sucralfate group experienced significantly lower degree of mucositis than placebo group (p < 0.05). Sucralfate mouth washing is beneficial in decreasing the intensity of radiation-induced mucositis and oral discomfort. It is cheap, easy to administer with no serious side effect, and may be routinely used in patients receiving head and neck radiotherapy.

Malignancy in Behçet’s Disease: A Report of 13 Cases and a Review of the Literature

Abstract 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.

Serum lactate dehydrogenase level is a prognostic factor in patients with locoregionally advanced nasopharyngeal carcinoma treated with chemoradiotherapy.

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/m2) 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.

Percent positive axillary lymph node metastasis predicts survival in patients with non-metastatic breast cancer

Purpose. We retrospectively evaluated the impact of percent positive axillary nodal involvement on the therapeutic outcomes in patients with non-metastatic breast cancer receiving postmastectomy radiotherapy and chemotherapy. Materials and methods. Between January 1994 and December 2002, the medical records of 939 eligible non metastatic breast carcinoma patients were analyzed. Chest wall radiotherapy was indicated in case of positive surgical margin, tumor size equal or more than 4 cm, skin-fascia invasion. Lymphatic irradiation was applied for more than three metastatic axillary lymph nodes, incomplete axillary dissection (<10 lymph nodes), extracapsular extension or perinodal fat tissue invasion. A total dose of 50 Gy was given to chest wall and lymph node regions with 2 Gy daily fractions. Statistical analyses were performed by Kaplan-Meier method, Log-rank test and Coxs regression analysis. Results. The median follow-up for all patients alive was 62 months. The 5-year overall survival (OS) and disease-free survival (DFS) for entire cohort were 81%, and 65%, respectively. Univariate analysis for OS revealed significance for tumour size (≤5 cm vs. >5cm, p<0.001), metastatic nodal involvement (0 vs. 1–3 vs. >4 LN, p<0.001), percent positive nodal involvement ([metastatic nodes/total nodes removed]×100; 0 vs.≤25% vs. 26–50% vs. >50%, p<0.001), surgical margin status (negative vs. positive, p=0.05), and hormonal treatment (present vs. absent, p=0.03). DFS had similarly significance for age (≤40 years vs. >40 years, p=0.006), tumour size (0.02), metastatic nodal involvement (p<0.001), percent positive nodal involvement (p<0.001), and perinodal invasion (present vs. absent, p=0.01). Multivariate analysis revealed significance for tumour size, percent positive nodal involvement, hormonal treatment, and surgical margin status for OS. Age and percent positive nodal involvement were found to be significant for DFS. Conclusion. Percent positive nodal involvement was found to be a significant prognostic factor for survival in all end-points.

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.

Waldeyer's ring lymphomas: Treatment results and Prognostic factors

Optimal management of patients with localized Waldeyer’s ring (WR) lymphoma remains controversial due to the lack of randomized studies and heterogenous grouping of most reported series. In this retrospective study, we have evaluated the possible prognostic factors and treatment outcome of WR non-Hodgkin’s lymphoma. Between December 1993 and February 2000, 32 patients with WR lymphoma, stage I (11 patients) and stage II (21 patients) were treated. There were 17 male patients and 15 female patients with a median age of 47 years. The distribution among different anatomical sites were as follows: tonsils in 16 (50%), nasopharynx in 10 (31%), base of tongue in 6 (19%). According to Working Formulation, 10 had high-grade, 17 intermediate grade, 3 low-grade, and 2 had unclassified lymphomas. Combined chemotherapy and radiotherapy was the primary modality of therapy for intermediate or high-grade lymphoma. Radiotherapy alone was employed only in low-grade WR lymphomas. Chemotherapy was median 6 courses of CHOP (cyclophosphamide, doxorubicin (Adriamycin), vincristine, and prednisolone) in 26 patients and CEOP (cyclophosphamide, doxorubicin, etoposide, and prednisone). Radiotherapy volume was involved field and the median dose was 40 Gy. Median follow-up is 40 months (ranged from 6–82 months). Overall survival and disease-free survival (DFS) rates at 3 years are 100% and 92%, respectively. Two patients developed recurrence, both salvaged with further chemotherapy. Only one patient died because of other reasons. International Prognostic Index score (≤2 vs. >2) is found to be an important prognostic factor for DFS. The other significant prognostic factors for DFS are performance status and serum levels of alkaline phosphatase and lactate dehydrogenase. Our results suggest that combined chemotherapy and involved field radiotherapy is appropriate treatment for stage I-II WR lymphoma. International Prognostic Index is the strongest predictor for DFS.

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.

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

Percent Positive Axillary Involvement Predicts for the Development of Brain Metastasis in High‐Risk Patients with Nonmetastatic Breast Cancer Receiving Post‐Mastectomy Radiotherapy

Abstract:  We retrospectively assessed the predictive factors for brain metastasis in high‐risk breast cancer patients receiving radiotherapy after mastectomy. Between January 1994 and 2002, the medical charts of nonmetastatic breast cancer patients receiving post‐mastectomy radiotherapy were evaluated. The clinical and pathologic features of patients who developed brain metastasis as the first site metastatic disease were compared with nonmetastatic patients treated at the same time period. All eligible patients in this study were treated with postoperative radiotherapy ± chemotherapy. Age, stage, percent positive lymph node involvement, number of lymph node metastasis, primary tumor size, grade, surgical margin status, estrogen receptor status, and perinodal fat tissue invasion were analyzed as predictive factors for brain metastasis. Statistical analyses were performed by using Log‐rank test and Cox’s regression analysis. Median follow‐up‐time was 61 months. In this period, 32 out of 957 patients (3.3%) developed brain metastasis. In univariate analysis percent positive axillary lymph node involvement (p < 0.001), primary tumor size (p < 0.001), number of lymph node metastasis (p = 0.01), and American Joint Committee on Cancer 2002 stage (p < 0.001) were found to be predictive for brain metastasis. Multivariate analysis revealed that only the primary tumor size and percent positive lymph node involvement were significant predictive factors for the development of brain metastasis. The primary tumor size and percent positive lymph node involvement increases the risk of brain metastasis in patients with nonmetastatic breast cancer receiving postoperative radiotherapy and chemotherapy.

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.