Enis Özyar

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.

Comparison of AJCC 1988 and 1997 classifications for nasopharyngeal carcinoma

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 Hos 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.

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.

Treatment results of 84 patients with nasopharyngeal carcinoma in childhood

To evaluate the clinical characteristics, treatment regimens, survival, and late complications in patients with nasopharyngeal carcinoma.

Reduced incidence of the somnolence syndrome after prophylactic cranial irradiation in children with acute lymphoblastic leukemia

A prospective double blind randomized trial comparing two different dose schedules of continuous steroid coverage during prophylactic cranial radiotherapy (CRT) in leukemic children was conducted to find out the optimum dose to be prescribed to reduce the incidence of Somnolence Syndrome (SS). Between April 1994 and February 1996, 32 patients with acute lymphoblastic leukemia received CRT of 18 Gy in 10 fractions. Patients were randomized to receive oral dexamethasone of 2 or 4 mg/m2 during radiotherapy. The diagnosis of SS was made clinically based on symptoms of somnolence. All patients were followed for a minimum of 8 months. The overall incidence of SS was 40%. The development of SS was steroid dose dependent. In low dose steroid arm the incidence of SS was 64.3% (9/14), compared to 17.6% (3/17) in high dose arm with statistically significant difference (P = 0.008). The median time to development of SS was 4 weeks. The most common symptom of SS was drowsiness followed by anorexia, headache, nausea, vomiting, decreased activity, irritability, fever and ataxia, respectively. The duration of symptoms ranged from 2 to 14 days. The development of SS was not related to the presence of acute reactions, age at the time of CRT and sex. In all cases the symptoms subsided completely and spontaneously. Our results suggest that steroid coverage at a dose of 4 mg/m2 during CRT reduces the incidence of SS. However, a multicentric prospective randomized trial is needed to determine the role and the optimal dose of steroid.

Induction chemotherapy with cisplatin and 5-fluorouracil followed by chemoradiotherapy or radiotherapy alone in the treatment of locoregionally advanced resectable cancers of the larynx and hypopharynx: Results of single-center study of 45 patients

Induction chemotherapy with cisplatin and fluorouracil and radiotherapy is an effective alternative to surgery in patients with carcinoma of the larynx and hypopharynx who are treated for organ preservation.

Adjuvant high-dose-rate brachytherapy after external beam radiotherapy in nasopharyngeal carcinoma

PURPOSE To compare the local control and survival rates obtained with either external beam radiation therapy (ERT) and adjuvant high-dose-rate (HDR) brachytherapy (BRT) or ERT alone in patients with nasopharyngeal cancer. METHODS AND MATERIALS Between December 1993 and December 1999, 144 patients (106 male, 38 female) with the diagnosis of nasopharyngeal cancer were treated with either ERT and adjuvant HDR BRT (Group A) or ERT alone (Group B) at our department. BRT was not applied in 38 patients for the following reasons: (1) Unit was unavailable (n = 13), (2) Patient was younger than 18 years (n = 17), (3) Patient received accelerated hyperfractionated ERT (n = 6), and (4) Patient refused BRT (n = 2). The median age for whole group was 43 (range: 9-82 years). According to the AJCC-1997 staging system, there were 11 (7.6%), 35 (24.3%), 38 (26.4%), and 60 (41.7%) patients in Stage I, II, III, and IV, respectively. There were 57 (39.6%) patients with T1, 41 (28.5%) with T2, 20 (13.9%) with T3, and 26 (18.1%) with T4 tumors. Histopathologic diagnosis was WHO 2-3 in 137 (95.2%) patients. ERT doses ranged between 58.8 and 74 Gy (median: 66 Gy). There were significantly more patients with young age, N2 status, and Stage III disease in Group B and with Stage II disease in Group A. Significantly more patients received chemotherapy in Group B. BRT with an HDR 192Ir microSelectron afterloading unit was delivered in 106 patients at the conclusion of ERT using a single-channel nasal applicator. Dose was prescribed at 1 cm from the source, and total dose of 12 Gy in 3 fractions on 3 consecutive days was given immediately after ERT. Besides radiotherapy, 82 (56.9%) patients received cisplatin-based chemotherapy, as well. Follow-up time ranged between 12 and 80 months (median: 32 months). RESULTS The two groups were comparable in terms of local recurrence, locoregional failure, regional failure, and rate of distant metastasis. Local failure was observed in 11 (10.3%) out of 106 patients in Group A and in 2 (5.2%) out of 38 patients in Group B (p > 0.05). Three-year disease-free survival rate was 67% and 80% (p = 0.07), respectively, and 3-year local recurrence-free survival rate was 86% and 94% (p = 0.23) for Group A and B, respectively. Multivariate analysis showed that advanced nodal status and male gender were significantly unfavorable factors for disease-free survival, and Stage II disease was unfavorable for local recurrence-free survival. The administration of adjuvant HDR BRT was not an independent prognostic factor in multivariate analysis. Out of 106 patients, 42 (39.7%) experienced nasal congestion, transient nasal obstruction, and/or fibrinous exudate in response to antihistaminic treatment. Only three (2.8%) patients experienced nasal synechy related, most probably, to the BRT. Five patients developed severe neural complications; only one out of five was observed in Group A. No severe complication attributed directly to BRT was detected. CONCLUSION The acute and late morbidity of adjuvant HDR BRT is acceptable with our treatment scheme, but we did not find any local control difference between our patients treated with adjuvant BRT after ERT and ERT alone. We believe that the exact role of adjuvant HDR BRT can be elucidated only by prospective randomized studies.

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.

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.