Cyclin D1 and E-cadherin are important factors in the progression and metastasis of cancers. Their role in laryngeal carcinoma has been studied with conflicting results. To define the frequency of cyclin D1 and E-cadherin expression and its correlation with both the clinicopathological characteristics and prognosis of patients with laryngeal squamous cell carcinoma (LSCC). Tumor tissue samples from 75 patients with laryngeal squamous cell carcinoma were examined for cyclin D1 and E-cadherin expression by immunohistochemistry. The relationship between the expression of both molecules and the age and sex of the patient, tumor site, tumor differentiation, lymph node metastasis, tumor invasiveness, TNM stages, tumor recurrence and overall survival was analyzed. Cyclin D1 was found to be a significant independent prognostic factor of lymph node metastasis (p = 0.000). The multivariate analysis revealed that cyclin D1 and E-cadherin expression wasn't an independent prognostic factor of local recurrence free survival (LRFS) in patients with LSCC (P = 0.56 and 0.28) respectively. However, the univariate analysis revealed a significant association between them and LRFS (p = 0.003 and 0.000) respectively. Also, the group of high cyclin D1 /low E-cadherin expression had the poorest prognosis, so they might serve as potential predictors of the prognosis of the patients with LSCC. E-cadherin was found to affect the overall survival (OAS) significantly by the univariate analysis (p = 0.01). However, by the multivariate analysis the TNM stage was the only independent prognostic factor of OAS (p < 0.05). Cyclin D1 can be used as an independent prognostic marker of lymph node metastasis in patients with LSCC and can help to identify those patients with clinically negative lymph nodes but with considerable risk for occult metastasis. Detection of cyclin D1 and E-cadherin status in LSCC may contribute to the identification of patients with high risk factors of local recurrence. However, they don't appear to be better prognostic predictors than other established markers in LSCC.
The management of cervical lymph node metastases of squamous cell carcinoma from an unknown primary site is still a therapeutic challenge. We report here our experience in treating these patients with chemoradiotherapy as a curative approach. Data from 40 patients were reviewed. In total, 20 (50%) patients underwent excisional biopsy. All patients underwent radiotherapy, which was delivered to both sides of the neck and pharyngeal mucosa (extensive field), and concurrent chemotherapy consisting of weekly cisplatin at a dose of 40 mg/m2. The clinical stage of the cervical nodes at presentation was N1 in 25%, N2 in 60%, and N3 in 15%. Most patients (75%) developed at least grade 3 mucositis. Eight patients (20%) had grade 3 xerostomia and 18 patients (45%) required esophageal dilation for stricture. The 5-year overall survival (OS) rate of all patients was 67.5%. The 5-year OS rates of patients with N1, N2, and N3 lesions were 100%, 67%, and 41%, respectively (P = 0.046). The 5-year progression-free survival rate was 62.5%. In multivariate analysis, only N stage significantly affected OS (P = 0.022). Emergence of the occult primary was very limited (1 patient only). Our results suggest that extensive irradiation of both sides of the neck and pharyngeal mucosa with concurrent chemotherapy results in a lower emergence of primary tumor. Because the survival of patients with unknown primary is comparable to that of patients with known primary, an attempt at cure should always be made.
Purpose Adjuvant trastuzumab is currently an internationally standard for the treatment of localised breast cancer that over express HER2 with the most adverse effect being cardiotoxicity. We conducted this study to evaluate the cardiac safety of trastuzumab in clinical practice. Methods This study is a retrospective observational single institutional study conducted in the Oncology Center of King Abdulla Medical City (KAMC), Makkah, Saudi Arabia, from June 2011 to January 2014. We evaluated the incidence of cardio toxicity and associated risk factors during adjuvant trastuzumab treatment. Results Of 57 patients, 20 patients (35%) exhibited cardiotoxicity. About 14% of patients had drop of left ventricular ejection fraction (LVEF) below 50%, whilst 10% and 15% drop of LVEF below their baseline levels were found in 30% and 5% of patients, respectively. About 98.3% of our patients have completed treatment, of whom 21% had a provisional interruption because of a fall in LVEF. A definitive trastuzumab discontinuation has been made in 1.75% of cases because of a nonregressive reduction in LVEF. Analysis of risk factors related to trastuzumab cardio toxicity found that patients older than 40 years were more likely to develop cardio toxicity compared to those younger than 40 years. This difference was statistically significant (p = 0.042). Conclusion In our study, the cardiac safety seems comparable with the literature data. Trastuzumab-related cardiotoxicity is manifested by an asymptomatic decrease in the LVEF and less commonly by clinical heart failure. Most instances are transient, asymptomatic and reversible.
This trial compared 6 cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC) with a sequential regimen of 3 cycles of FEC followed by 3 cycles of docetaxel (FEC-D) as adjuvant treatment for women with node-positive or/and T3 or T4 breast cancer. Between January 2006 and January 2010, 657 patients with operable breast cancer were randomly assigned to either FEC every 21 days for 6 cycles, or 3 cycles of FEC followed by 3 cycles of docetaxel, both given every 21 days. Radiotherapy was mandatory for all patients who had undergone breast conserving surgery. Radiation to the chest wall, supraclavicular area, was recommended following mastectomy. Hormone-receptor-positive patients received tamoxifen for 5 years after chemotherapy. The primary end point was 5-year disease-free survival (DFS). Median follow-up was 61 months. Five-year DFS rates were 74 % with FEC and 78 % with FEC-D (P = 0.013). Multivariate analysis adjusted for prognostic factors showed a 17 % reduction in the relative risk of relapse with FEC-D. Five-year overall survival rates were 85 % with FEC and 89.4 % with FEC-D, demonstrating a 27 % reduction in the relative risk of death (P = 0.014). The incidence of grade 3-4 neutropenia, the need for hematopoietic growth factor, and incidence of nausea/vomiting were higher with FEC. Docetaxel was associated with more febrile neutropenia, stomatitis, edema, and nail disorders. Though rare overall, there were fewer cardiac events after FEC-D, attributable mainly to the lower anthracycline cumulative dose. Sequential adjuvant chemotherapy with FEC followed by docetaxel significantly improves disease-free and overall survival in node-positive or/and T3 or T4 breast cancer patients. Although the magnitude of the benefit observed with FEC-D, differences in the toxicity profiles of FEC and FEC-D may influence the choice of treatment for patients.
The purpose of this prospective phase III study was to compare the role of concomitant chemoradiation using paclitaxel versus cisplatin in locally advanced head and neck cancers. Patients and methods: 52 patients were randomly assigned to one of the two concomitant chemoradiation arms: arm I (n=26) and arm II (n= 26) who received injection of paclitaxel 20 mg/m 2 I/V 1 hour infusion before radiation, repeated weekly for 6 cycles, and cisplatin 30 mg/m 2 I/V 1 hour infusion before radiation, repeated weekly for 6 cycles, respectively. The planned radiotherapy dose was 66-70 Gy, 1.8-2 Gy/day, 5#/Week in 6-7 weeks. Results: Response rates were 76 and 69.2% in arm I and arm II, respectively (P = 0.53). The hematological toxicity was generally mild. On the contrary, non-hematologic toxicities were severe. Grade III mucositis occurred in 32% in arm I and in 23.1% in arm II (P = 0.04). Moreover, grade III dermatitis were encountered in 28% in arm I and 11.5% in arm II (P = 0.03). The 2-year local-regional control figures were 60 and 57.1% in arm I and arm II, respectively(P=0.52) ; however the 2-year progression-free survival figures were 36.8 and 33.3% in arm I and arm II, respectively(P=0.43), while the 2-year overall survival figures were 56 and 50% in arm I and arm II, respectively (P = 0.68). Conclusion: Both concomitant chemoradiotherapy regimens were easily given in the outpatient clinic. The regimen based on paclitaxel was more effective; however, the difference was insignificant.
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