The aim of the study was to investigate how the expression of tumor markers p21, p27, p53, cyclin D1, EGFR, Ki-67, and CD31 influenced the outcome of advanced inoperable oropharyngeal carcinoma ...patients, treated with concomitant radiochemotherapy.
The pretreatment biopsy specimens of 74 consecutive patients with inoperable stage IV oropharyngeal squamous cell carcinoma treated with concomitant radiochemotherapy were in retrospective study processed by immunochemistry for p21, p27, p53, cyclin D1, EGFR, Ki-67, and CD31. Disease-free survival (DFS) was assessed according to the expression of tumor markers.
Patients with a high expression of p21 (≥10%), p27 (>50%), Ki-67 (>50%), CD31 (>130 vessels/mm2) and low expression of p53 (<10%), cyclin D1 (<10%) and EGFR (<10%) (favorable levels - FL) had better DFS than patients with a low expression of p21 (<10%), p27 (≤50%), Ki-67 (≤50%), CD31 (<130 vessels/mm2) and high expression of p53 (≥10%), cyclin D1 (≥10%) and EGFR (≥10%) (unfavorable levels - UL). However, statistical significance in survival between FL and UL was achieved only for p27 and cyclin D1. DFS significantly decreased with an increasing number of markers with an unfavorable level per tumor (1–4 vs. 5–7) (78% vs. 32%, respectively; p = 0.004). The number of markers per tumor with UL of expression retained prognostic significance also in multivariate analysis.
Statistical significance in survival between FL and UL emerged only for p27 and cyclin D1. The number of markers per tumor with UL of expression was an independent prognostic factor for an adverse outcome.
Choroidal melanoma is the most common primary malignancy of the eye, which frequently metastasizes. The Cancer Registry of Slovenia reported the incidence of choroid melanoma from 1983 to 2009 as ...stable, at 7.8 cases/million for men and 7.4/million for women. The aim of the retrospective study was to determinate the prognostic factors of survival for choroidal melanoma patients in Slovenia.
From January 1986 to December 2008 we treated 288 patients with malignant choroidal melanoma; 127 patients were treated by brachytherapy with beta rays emitting ruthenium-106 applicators; 161 patients were treated by enucleation.
Patients with tumours thickness < 7.2 mm and base diameter < 16 mm were treated by brachytherapy and had 5- and 10-year overall mortality 13% and 32%, respectively. In enucleated patients, 5- and 10-year mortality was higher, 46% and 69%, respectively, because their tumours were larger. Thirty patients treated by brachytherapy developed local recurrence. Twenty five of 127 patients treated by brachytherapy and 86 of 161 enucleated patients developed distant metastases. Patients of age ≥ 60 years had significantly lower survival in both treatment modalities. For patients treated by brachytherapy the diameter of the tumour base and treatment time were independent prognostic factors for overall survival, for patients treated by enucleation age and histological type of tumour were independent prognosticators. In first few years after either of treatments, the melanoma specific annual mortality rate increased, especially in older patients, and then slowly decreased.
It seems that particularly younger patients with early tumours can be cured, whereby preference should be given to eyesight preserving brachytherapy over enucleation.
The long term results and patterns of failure in patients with squamous cell head and neck carcinoma (SCHNC) treated in a prospective randomized trial in which concomitant postoperative ...radiochemotherapy with Mitomycin C and Bleomycin (CRT) was compared with radiotherapy only (RT), were analyzed.
Between March 1997 and December 2001, 114 eligible patients with Stage III or IV SCHNC were randomized. Primary surgical treatment was performed with curative intent in all patients. Patients in both groups were postoperatively irradiated to the total dose of 56-70 Gy. Chemotherapy included Mitomycin C 15 mg/m2 after 10 Gy and 5 mg of Bleomycin twice weekly during irradiation. Median follow-up was 76 months (48-103 months).
At 5 years in the RT and CRT arms, the locoregional control was 65% and 88% (p = 0.026), disease-free survival 33% and 53% (p = 0.035), and overall survival 37% and 55% (p = 0.091) respectively. Patients who benefited from chemotherapy were those with high-risk factors. The probability of distant metastases was 22% in RT and 20% in CRT arm (p = 0.913), of grade III or higher late toxicity 19% in RT and 26% in CRT arm (p = 0.52) and of thyroid dysfunction 36% in RT and 56% in CRT arm (p = 0.24). The probability to develop a second primary malignancy (SPM) was 34% in the RT and 8% in the CRT arm (p = 0.023). One third of deaths were due to infection, but there was no difference between the 2 groups.
With concomitant radiochemotherapy, locoregional control and disease free survival were significantly improved. Second primary malignancies in the CRT arm compared to RT arm were significantly less frequent. The high probability of post treatment hypothyroidism in both arms warrants regular laboratory evaluation.
To evaluate the toxicity and efficacy of concomitant chemoradiotherapy with mitomycin C and cisplatin in the treatment of advanced unresectable squamous cell carcinoma of the head and neck.
Treatment ...consisted of conventional radiotherapy (70 Gy in 35 fractions), mitomycin C 15 mg/m(2) IV, applied after the delivery of 10 Gy, and cisplatin at an initial dose of 10 mg/m(2)/d IV, applied during the last 10 fractions of irradiation ("chemoboost"). The cisplatin dose was escalated with respect to the toxic side effects by 2 mg/m(2)/d up to the maximum tolerated dose (MTD) or at the most 14 mg/m(2)/d (Phase I study), which was tested in the subsequent Phase II study.
All 36 patients had Stage T4 and/or N3 disease, and the majority had oropharyngeal (50%) or hypopharyngeal (39%) primary tumors. Six patients were treated at each of the three cisplatin dose levels tested (Phase I study). Dose-limiting toxicity was not reached even at 14 mg/m(2)/d of cisplatin, which was determined as the MTD and tested in an additional 18 patients (Phase II study). After a median follow-up time of 48 months, 4-year locoregional control, failure-free, and overall survival rates were 30%, 14%, and 20%, respectively. In 24 patients treated at the cisplatin dose level of 14 mg/m(2)/d, the corresponding rates were 40%, 20%, and 22%, respectively.
Concomitant chemoradiotherapy with mitomycin C and cisplatin "chemoboost" at 14 mg/m(2)/d is feasible, with encouraging survival results if the extremely poor disease profile of the treated patients is considered.
Cysteine proteinases cathepsins (Cats) B and L and their endogenous inhibitors stefins (Stefs) A and B are implicated in the processes of local and metastatic tumor spread. They were identified as ...potential prognosticators in various malignant diseases, particularly in breast cancer. The aim of the present study was to determine the concentrations of Cats B and L and Stefs A and B in the tumor and adjacent normal tissue samples collected from 49 patients (the present group) with squamous cell carcinoma of the head and neck (SCCHN), using quantitative immunosorbent assays (ELISA; KRKA d.d., Novo mesto, Slovenia). Their clinical significance was compared with that from a previous study (the reference group, 45 patients; Budihna et al., Biol. Chem. Hoppe-Seyler, 377: 385-390, 1996). The follow-up of patients from the latter report was updated for this purpose. In the present group, significantly higher concentrations of Cat B (P < 0.0001), Cat L (P < 0.0001) and Stef A (P = 0.006) were found in tumors compared with concentrations in their normal tissue counterparts. Cat concentrations in normal laryngeal tissue were significantly/marginally elevated compared with nonlaryngeal tissue (Cat B, P = 0.02; Cat L, P = 0.06). The tumor concentration of Cat L was found to correlate with pT classification (P = 0.005) and tumor-node-metastasis stage (P = 0.05), whereas the concentrations of Stefs A and B correlated with pN classification (P = 0.007 and P = 0.03, respectively) and tumor-node-metastasis stage of the disease (P = 0.02 and P = 0.03, respectively). There was no statistically significant difference between low and high Cat B or Cat L groups, regarding either disease-free survival or disease-specific survival, using a minimum P approach to determine cutoff concentrations. The risk of disease recurrence and SCCHN-related death was significantly higher in patients with low Stef A (P = 0.0006 and P = 0.0005, respectively) and Stef B (P = 0.0009 and P = 0.0007, respectively) tumors, compared with those with high-Stef A and Stef B tumors. These results remained significant even after Ps were adjusted for a possible bias in the estimated effect on survival. The survival analysis in the reference group also confirmed these findings (Stef A: P = 0.0009 and P = 0.002, respectively; Stef B: P = 0.03 and P = 0.009, respectively). To avoid any possible bias arising from the differences between the laboratories that performed the biochemical analysis, the concentrations of both Stefs in the present group and in the reference group were standardized and coupled together to form a uniform group. In univariate survival analysis, standardized values of Stef A and Stef B correlated inversely with the rate of relapse (P = 0.0000) and mortality rate (P = 0.0000). Multivariate regression analysis showed that the standardized value of Stef A is the strongest independent prognostic factor for both disease-free survival and disease-specific survival. These findings show the specific role of Cats B and L and Stefs A and B in the invasive behavior of SCCHN. Furthermore, Stef A proved to be a reliable prognosticator of the risk of relapse and death in patients with this type of cancer.
In a prospective randomized clinical study, simultaneous postoperative application of irradiation (RT), mitomycin C, and bleomycin was tested in a group of patients with operable advanced ...head-and-neck carcinoma. It was expected that the planned combined postoperative therapy would reduce the number of locoregional recurrences and prolong survival.
A total of 114 eligible patients with Stage III or IV squamous cell head-and-neck carcinoma were randomized to receive postoperative RT alone (Group 1) or RT combined with simultaneous mitomycin C and bleomycin (Group 2). Patients were stratified according to the stage and site of the primary tumor and the presence or absence of high-risk prognostic factors. Primary surgical treatment was performed with curative intent in all patients. Patients in both groups were postoperatively irradiated to the total dose of 56–70 Gy. Chemotherapy included mitomycin C 15 mg/m
2 after 10 Gy and 5 mg of bleomycin twice a week during RT to the planned total dose of 70 mg.
At 2 years, patients in the radiochemotherapy group had better locoregional control (86%) than those in the RT alone group (69%;
p = 0.037). Disease-free survival and overall survival was also better in the radiochemotherapy group compared with the RT-alone group (76% vs. 60%,
p = 0.099; and 74% vs. 64%,
p = 0.036, respectively). Patients who benefited from chemotherapy were those with high-risk factors.
The results of the present study indicate that concomitant postoperative radiochemotherapy with mitomycin C and bleomycin improves locoregional control and survival in patients with advanced head-and-neck carcinoma. The patients who benefited from chemotherapy were those with high-risk factors.
Summary Aim To evaluate the treatment results of squamous cell carcinoma of the oral cavity treated with radical or postoperative radiotherapy at the Institute of Oncology Ljubljana, in the period ...1990–1995. Materials/Methods The medical records of patients were used to collect the data according to the predefined Data Acquisition Protocol. The impact of individual clinical and histopathological factors on the treatment outcome was evaluated by uni- and multivariate analysis. Results Combined therapy was performed in 142 patients, and 93 patients had radiotherapy only. In each of the two subgroups, the performance status of patients was assessed as “poor” in 7% and 30%; the proportion of T1–2 tumours was 53.6% and 16.1%, and the proportion of cN0-stage tumours was 38% and 29%. The 5-year survival without local failure in surgically treated and irradiated only patients was 89% and 30%, without neck failure 85.7% and 50.3%, without any failure 79.1% and 27.5%, and overall survival 43.9% and 11.5%, respectively (all P<0.0001). In multivariate analysis, the performance status and cT-stage emerged as independent prognostic factors for all four types of survival analyzed. The type of therapy retained its independent prognostic value only in the case of survival without local failure. Conclusions The only independent predictors of survival were performance status and cT stage, whereas the type of therapy impacted only local cure rate. The difference in survival results between the two treatments reflects primarily selection bias which occurred when patients were directed to one of the two treatment options.
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