Prognostic value of some tumor markers in unresectable stage IV oropharyngeal carcinoma patients treated with concomitant radiochemotherapy.

BACKGROUND: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

concomitant chemoradiotherapy with mitomycin C and cisplatin in advanced unresectable carcinoma of the head and neck: phase I-II clinical study.

PURPOSE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Patterns of failure in patients with locally advanced head and neck cancer treated postoperatively with irradiation or concomitant irradiation with Mitomycin C and Bleomycin.

PURPOSE: 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. PATIENTS AND METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Verrucous carcinoma of the temporal bone and maxillary antrum: two unusual presentations of a rare tumor.

BACKGROUND: Verrucous carcinoma (VC) is a low-grade variant of squamous cell carcinoma. The involvement of the temporal bone and maxillary antrum is very rare. PATIENTS AND METHODS: The clinicopathologic features of 2 such tumors are reported, and the pertinent literature is reviewed. RESULTS: In the 2 patients, the diagnostic procedure was complicated due to initial inconclusive histology. Both were treated with concomitant radiochemotherapy. They were free of disease for 5.8 and 11 years after diagnosis. An additional 15 cases of VC of the temporal bone and 10 cases of maxillary antrum tumors have been reported in the literature. In 10 patients, multiple biopsies were required, and in 7 patients, a definitive histological diagnosis was not obtained before surgery. The disease reappeared in 8 out of 15 patients treated solely with surgery. Only 2 of them were salvaged by reoperation. Radiochemotherapy only (without any surgery) was successfully used in 4 patients. CONCLUSIONS: VC of the temporal bone or maxillary antrum is an extremely rare tumor. For reliable histological diagnosis, multiple biopsies of deep and ample tissue samples are mandatory. Surgery is a mainstay of therapy; however, radiochemotherapy also represents a viable treatment option with curative potential.

Radiochemotherapy with Vinblastine, Methotrexate, and Bleomycin in the treatment of verrucous carcinoma of the head and neck.

OBJECTIVE: To explore whether the combined radiochemotherapy with Vinblastine, Methotrexate, and Bleomycin could be an effective alternative treatment to surgery in verrucous carcinoma (VC) of the head and neck. METHODS: Combined radiochemotherapy was used in 12 patients with previously untreated VC. They were irradiated to equivalent tumor dose of 44-70 Gy (median, 56 Gy) and had > or = 2 courses of concomitant chemotherapy. Chemotherapy regimen consisted of prolonged intravenous infusions of Vinblastine 2 mg (day 1); Methotrexate 50 mg (day 2); Bleomycin 15 mg (days 2 and 3), and repetition at 2-3 week intervals. RESULTS: Eleven of 12 patients were cured of VC, and one died of purulent meningitis associated with intracranial extension of VC from the oral cavity. Of 11 patients cured of VC, eight had advanced tumors. The median follow-up of cured patients was 3.6 years (range, 1.4-13.6 years). All the patients developed mucositis of grade > or = 3, whereas no serious late side-effects were recorded. CONCLUSIONS: Combined radiochemotherapy with Vinblastine, Methotrexate, and Bleomycine is highly effective in the treatment of VC of the head and neck. It could be successfully used in the patients with inoperable VC or as an alternative to surgery.

Postoperative concomitant irradiation and chemotherapy with mitomycin C and bleomycin for advanced head-and-neck carcinoma.

PURPOSE: 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. METHODS AND MATERIALS: 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. RESULTS: 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. CONCLUSION: 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.

Extramedullary plasmacytoma: clinical and histopathologic study.

PURPOSE: To review the histories of extramedullary plasmacytoma patients diagnosed in Slovenia between 1969 and 1999, to determine the relationship between radiotherapy (XRT) dose and local tumor control, and to clarify the role of elective nodal XRT and the prognostic value of Bartl's histologic grading criteria (originally devised for multiple myeloma [MM]). METHODS AND MATERIALS: The database of the Cancer Registry of Slovenia was used for the identification of patients. The inclusion criteria were as follows: bone marrow biopsy showing less than 10% plasma cells, normal skeletal survey, and immunohistochemically determined tumor monoclonality. Simulation/portal films were reviewed to assess the extent of elective nodal XRT. RESULTS: Twenty-six patients with 31 tumors fulfilled the inclusion criteria. In 4 patients, nine metachronously appearing solitary tumors were diagnosed. The head-and-neck region and other body sites were the sites of origin of primary tumors in 84% and 16% of patients, respectively, whereas in the two regions, regional disease was seen in 15% and 60% of patients, respectively. Therapy was as follows: XRT, 12 patients; surgery and postoperative XRT, 15 patients; and surgery, 4 patients. Ultimate local and regional control rates were 90% and 97%, respectively, and MM developed in 2 (8%) patients. The 10-year disease-specific and overall survival rates were 87% and 61%, respectively. The analysis of the dose-effect relationship showed that more conservative treatment is justified: for macroscopic disease, 40-50 Gy (2 Gy/day), adjusted to the bulk of disease; for microscopic disease, 36-40 Gy; after R0 surgery, no XRT is required, but close observation is needed. No attempts should be made to treat uninvolved nodal regions. Using Bartl's histologic grading criteria, trends were detected in patients with higher tumor grades: regional lymph node involvement (p = 0.04) and shorter disease-specific survival (p = 0.08). CONCLUSIONS: Extramedullary plasmacytoma is a highly curable disease when XRT is used with or without previous surgery. The rate of conversion to MM is low. Moderate-dose XRT using limited fields is recommended. The prognostic value of Bartl's grading system needs further evaluation.