PREDICTORS OF INFLAMMATORY LOCAL RECURRENCE AFTER BREAST-CONSERVING THERAPY FOR BREAST CANCER: MATCHED CASE-CONTROL STUDY.

BACKGROUND: Inflammatory local recurrence (ILR) after breast-conserving surgery for noninflammatory breast cancer (BC) is associated with dismal prognosis. Risk factors for ILR are not well defined. METHODS: Between 2001 and 2010, twelve patients at our hospital developed ILR after breast-conserving surgery, adjuvant chemotherapy, and radiotherapy for BC. We compared their clinico-pathological characteristics to those of 24 patients with noninflammatory local recurrence (non-ILR), 24 patients with distant metastases, and 48 disease-free controls, matched for age and observation period. RESULTS: The median time to ILR was 10 months. In univariate analysis, extent of lymph node involvement (p < 0.05), multifocality (p < 0.05), c-erbB2 overexpression (p < 0.05), and lymphovascular invasion (LVI) (p < 0.001) affected the risk of ILR. Conditional logistic regression analysis showed a significant association between ILR and combined LVI and high histopathological grade. The odds ratio (OR) for ILR versus non-ILR was 6.14 (95% confidence interval [CI] 1.48-25.38) and for ILR versus distant metastases it was 3.05 (95% CI 0.09-97.83) when both LVI and high histopathological grade were present. Patients with family history of BC were more likely to present with ILR than non-ILR (OR 5.47; 95% CI 1.55-19.31) or distant relapse (OR 5.62; 95% CI 0.26-119.95). CONCLUSIONS: Pre- and postmenopausal women with high-grade BC and LVI are at increased risk to develop ILR, especially in the presence of family history of BC. Identification of risk factors for this lethal form of recurrent BC may lead to more effective preventive treatment strategies in properly selected patients.

Early-onset breast cancer in a Lebanese family with Lynch syndrome due to MSH2 gene mutation.

BACKGROUND: There are still controversies about the integration of breast cancer as a part of the disease spectrum in Lynch syndrome. METHODS: A regular follow-up of a Lebanese pedigree with Lynch syndrome due to a point mutation of MSH2 gene at the splice donor site of intron 3 started in 1996. RESULTS: A 26-year-old pregnant woman, mutation carrier, developed an aggressive breast cancer, refractory to standard chemotherapy regimens. The microsatellite analysis of the tumor showed an unstable pattern for markers BAT25 and BAT26. The immunohistochemical staining was negative for MSH2 and MSH6 and normal for MLH1 and PMS6 enzymes. CONCLUSION: The segregation of the mutation with the disease phenotype and these results suggest that MSH2 inactivation may be involved in the accelerated breast carcinogenesis and might be considered in the cancer screening program.

Salvage abdominal irradiation for refractory non-Hodgkin's lymphoma.

BACKGROUND: Abdominal irradiation, as a part of treatment, is often ignored in the management of refractory non-Hodgkin's lymphoma (NHL). OBJECTIVE: To evaluate the efficacy and the toxicity of this approach after failure of chemotherapy. MATERIALS AND METHODS: 27 patients with intraabdominal lymphoma underwent salvage irradiation between 1982 and 2001. All patients were treated with a Cobalt-60 machine. The total dose administered to the abdomen was 18-20 Gy at the rate of 1.5-1.8 Gy per daily fraction, followed by a boost to gross disease up to 20 Gy. All patients had previously been heavily pretreated with chemotherapy. Fourteen patients, nine with follicular and five with diffuse lymphomas, had primary refractory tumors that had never achieved remission. Thirteen patients, six with follicular and seven with aggressive tumors, had refractory relapsed tumors after achieving one or more complete remissions. RESULTS: The response rate was 77%. The median follow-up was 53 months. The 5-year and 10-year survival rates were 25 and 17%, respectively. The in-field and out-of-field recurrence rates were 22 and 33%, respectively. Survival rates were significantly better for patients with refractory relapse compared to those with primary refractory lymphoma (P < 0.01). There was no significant difference in terms of response, recurrence, or survival rates between follicular and aggressive types. Out-of-field recurrence occurred more frequently in initial stage III and IV disease. Toxic deaths occurred in three patients (11%). CONCLUSION: Salvage radiotherapy for refractory abdominal NHL is a feasible alternative for both follicular and diffuse subtypes and may provide significant palliation and prolongation of survival. It is less effective in patients with primary refractory NHL than in those with refractory relapsed NHL.

Nasopharyngeal cancer in the Middle East: experience of the American University of Beirut Medical Center.

PURPOSE: To review the data of nasopharyngeal carcinoma (NPC) treated at the American University of Beirut Medical Center and reflect on the characteristics and treatment outcome of NPC in the Middle East compared with those of Western countries and countries in which NPC is endemic. METHODS AND MATERIALS: Between 1966 and 1998, 151 patients with the diagnosis of NPC received definitive radiotherapy at the American University of Beirut Medical Center. Of the 151 patients, 111 were males (gender ratio, 2.78); the median age was 45 years (range, 11-75 years). Most (95%) patients (n = 144) were Lebanese, 4 were Syrians, and 3 were from the Gulf countries. Most (60%) patients (n = 91) had Stage IV disease, 27% had Stage III, and 13% had Stage I or II disease; nodal disease was present in 117 patients (77%). The pathologic type was predominantly lymphoepithelioma or World Health Organization type III (95 patients, 63%). Treatment consisted of definitive radiotherapy alone for 116 patients (77%). All others received induction chemotherapy, primarily with cisplatin-containing regimens. The median radiation dose was 66 Gy (range, 47-73 Gy) to the primary and 67 Gy (range, 49-85 Gy) to involved neck nodes given at 2 Gy/fraction. The average follow-up was 3.02 years (range, 0.1-24.5 years). RESULTS: The 5-year and 10-year disease-free survival (DFS) rate was 46%. Using univariate analyses, the following factors significantly affected DFS: node size (<3 vs. 3-6 vs. >6 cm; p = 0.01), node level (upper vs. mid vs. lower neck; p = 0.004), and duration of radiotherapy (p = 0.002). However, T stage, age, gender, radiation dose, use of chemotherapy, and histologic features had no statistically significant influence on DFS. The actuarial rate of local control at 5 and 10 years was 81% and 73%. T stage, N stage, and histologic features were statistically significant variables for local control in the univariate analyses. Using a Cox regression model, N stage (N1-N2 vs. N3; relative risk 2.09, p = 0.004) was identified as an independent variable for DFS, and N stage and pathologic features were identified as independent variables for local control. The actuarial rate of distant metastases was 32% at both 5 and 10 years. Distant metastases were only affected by N stage (upper-mid vs. lower neck; p = 0.004). Six patients (4%) were reported to have Grade 4 late complications. CONCLUSION: Our results indicate that the characteristics of NPC patients in Lebanon and their parameters of outcome are comparable to those reported in Western series, particularly for the relative frequency and effect of lymphoepithelial histologic type. Because of potential confounding factors, no definite conclusions about induction chemotherapy could be drawn from this retrospective study.

Results of radiation therapy for thymoma based on a review of 27 patients.

BACKGROUND: Radiotherapy has a well recognized role as an adjuvant treatment to surgery in thymoma and remains the only available treatment, with or without chemotherapy, in unresectable tumors. OBJECTIVE: Our objective is to assess the factors predicting the outcome and the pattern of survival in patients with thymoma treated by radiotherapy in our institution. METHODS: Between February 1989 and October 2000, 27 patients underwent radiotherapy for thymoma and were reviewed retrospectively. A follow-up could be obtained on all 27 patients. The parameters assessed were: age, sex, stage, presenting Myasthenia gravis, resectability, treatment modalities and survival. The total radiation dose to the tumor area in the adjuvant setting was 40-60 Gy and in the curative setting: 50-70 Gy. RESULTS: The median follow-up time of the 18 living patients was 74 months (range: 8-144 months). According to the Masaoka classification, there were 8 stage IV, 14 stage III and 5 stage II patients (three patients had relapsed tumors). There were 15 males and 12 females with a median age of 56 years. Ten patients had Myasthenia gravis at the time of presentation, two patients had pure red cell aplasia. Eighteen patients had dyspnea or superior vena caval syndrome (six of them). And five patients had only mild chest discomfort. Sixteen patients had complete surgical resection and 11 patients had partial resection (5) or only biopsy (6). Ten of them received a mean of three courses of chemotherapy with Cisplatin, Doxorubicin, and Cyclophosphamide (CAP). The overall 5 and 10 years survival rates were 65 and 47%, respectively. The 5 years survival rate for patients with complete resection was 81% compared to 44% for patients with partial resection or biopsy (P=0.01). Patients with Myasthenia had a 5 years survival of 71% compared to 53% for non-myasthenic patients. All patients with Myasthenia had complete surgical resection. Age, sex, presence of anemia, or superior vena caval syndrome were not adverse prognostic factors. There was no difference in terms of survival between relapsed and newly diagnosed tumors or between debulking surgery and biopsy. The 2 years survival for the four patients non-responders to chemotherapy was 0% while the 5 years survival for the responders was 71% (P=0.005). CONCLUSION: Resectability and response to chemotherapy for unresectable patients seem to be factors that predict the outcome in thymoma. Myasthenia gravis appears to be important in detecting the tumor when it is still resectable.

Abdominal irradiation after chemotherapy in non-Hodgkin's lymphoma: review of 32 patients.

OBJECTIVE: Our objective is to evaluate the efficacy and toxicity of abdominal irradiation after chemotherapy in the management of Non-Hodgkin's Lymphoma. METHODS: Between 1982 and 1997, 32 patients underwent abdominal irradiation; as adjuvant treatment to chemotherapy (5 patients), as curative treatment for residual mass (9 patients) or as salvage treatment for refractory disease (18 patients). The dose administered to the total abdomen was 18-20 Gy at the rate of 1.5-1.8 Gy per daily fraction followed by a boost to gross disease up to a total dose of 40-44 Gy. All patients had received at least 6 cycles of Cyclophosphamide, Doxorubicin, Vincristin and Prednisone (CHOP). A follow-up could be obtained on all patients. RESULTS: The in-field and out of field recurrence rates were 18 and 31%, respectively, for the entire group and 22 and 44%, respectively, for the palliative group. The 5- and 10-year survival rates were 100 and 80% for the adjuvant group, 45 and 24% for the curative group and 28 and 11% for the palliative group. The local control was significantly better in patients with follicular type lymphoma than in those with the diffuse type. There was a 50% acute diarrhea, 19% grade 3/4 hematologic toxicity, 6% chronic enteritis, one late renal failure and three toxic deaths. CONCLUSION: Adjuvant whole abdominal irradiation is feasible and efficient in patients with Non-Hodgkin's Lymphoma at high risk of intra-abdominal failure. Abdominal irradiation for residual disease consolidates remission with acceptable toxicity. Salvage radiotherapy for abdominal failure after chemotherapy provides significant palliation and prolongation of survival.