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.
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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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.
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GEOZS, IJS, NUK, OILJ, UL, UM, UPUK
Background: Health care system in Slovenia has not fully defined all liabilities to cancer patients at the primary, secondary and tertiary levels. No official documents describing precisely the ...mission of oncology and its tasks to be performed at each individual level have been so far available. Given that we are lacking an adequate national cancer control program and that the management of a cancer patient in Slovenia is included in the compulsory health insurance system. Our health care as well as health insurance policy should have long ago accepted the challenge of taking more decisive steps. The quality of management of cancer patients is as much dependent on medical proficiency (knowledge) as on organization of work at the primary and secondary levels. The major critique addresses particularly undergraduate and postgraduate education, i. e. the fields that have not been touched by the changes in the epidemiologic view of morbidity for several decades.Conclusions: The prerequisites in oncology, such as multidisciplinarity and multiprofessionality, are considered as new added values which should have a direct effect on the quality and multiplicity of individuals and institutions that are likely to be included in diagnostic and therapeutic networks. In oncology in Slovenia, the views on multidisciplinarity are not consistent, multiprofessionality has not yet entered our conscious awareness, quality assurance is often out of control, whereas multiplicity is history-based. It is high time that health care policy steps in and takes adequate measures in the management of cancer patients. The first prerequisite is to set up a national cancer control program and, of course, to appoint supervisors who will be in charge of (as the term indicates itself) supervising the implementation of the program. Its smooth implementation can only be ensured by applying a uniform information system, thereby also assuring a uniform evaluation of costs.
Background: The aim of our study was to determine whether local application of electric pulses to tumours, which induce transient
reduction of tumour perfusion, could potentiate the antitumour ...effectiveness of hyperthermia. Materials and Methods: The antitumour
effectiveness of local application of electric pulses (1300 V/cm, 100 μs, 1 Hz) and 910 MHz local hyperthermia at 43.5°C,
alone or in combination, was determined on LPB tumours in C57Bl/6 mice by measurement of tumour growth delay, changes in tumour
perfusion using the Patent blue technique and extent of tumour necrosis. Results: When hyperthermia was performed immediately
after application of electric pulses, at a time of maximally reduced tumour perfusion, greater than additive antitumour effectiveness
was observed, resulting in 14.5±3.1 days growth delay of tumours that regrew and 43% complete responses. Single treatment,
application of electric pulses or hyperthermia had minor or no effect on tumour growth. When hyperthermia was performed 24
hours after application of electric pulses, at a point when tumour perfusion was restored, the effect of both treatments was
additive, resulting in 4.1±1.1 days growth delay and no cures. Conclusion: The probable mechanisms for the observed, more
than additive, interaction when hyperthermia was performed immediately after application of electric pulses are the potentiation
of thermic cytotoxicity, due to the reduced tumour perfusion induced by application of electric pulses and prolonged tumour
perfusion reduction after combined treatment leading to additional cell kill, due to the protracted ischemia.
Purpose: To compare the efficacy of concomitant irradiation with mitomycin C and bleomycin in patients with inoperable head and neck carcinoma with radiotherapy alone.
Methods and materials: Between ...March 1991 and December 1993, 64 patients with inoperable head and neck carcinoma (41 with oropharyngeal site) were randomized to radiotherapy alone (group A) or radiotherapy combined with simultaneous application of mitomycin C and bleomycin (group B). In both groups patients were irradiated five times weekly with 2 Gy to a total dose of 66–70 Gy. The planned concomitant treatment in group B was: bleomycin 5 units twice a week IM, total dose 70 units, mitomycin C 15 mg/m
2 IV after delivery of 10 Gy, and 10 mg/m
2 IV on the last day of radiotherapy. To enhance the effect of these two drugs, patients received also nicotinamide, chlorpromazine, and dicoumarol.
Because significantly better results were achieved in arm B for patients with inoperable oropharyngeal carcinoma, the study was closed and such patients were after December 1993 routinely treated with the combined therapy (as in arm B). Until October 1996, we treated and followed up 48 such consecutive patients.
Results: Median follow-up of our study patients is 42 months. Complete remission (CR) rate in group A was 31% and in group B 59% (p = 0.04); disease-free survival (DFS) in group A was 8% and in group B 37% (P = 0.01); and overall survival (OS) was 7% in group A and 26% in group B (p = 0.08). CR rate for patients with oropharyngeal carcinoma was 29% in group A (N = 21) and 75% in group B (N = 20) (p = 0.007); DFS in group A was 10% and in group B 48% (p = 0.001); and the OS was 10% in group A and 38% in group B (p = 0.019). In patients with inoperable oropharyngeal carcinoma treated after December 1993, complete remission was achieved in 32/48 (67%, 95% CI: 52%–80%). DFS at the median follow-up of 14 months was 60% (95% CI 43–77%) and OS 58% (95% CI 42–74%).
Conclusion: From the results of our study it seems that the concomitant treatment significantly improves CR rate, DFS, and OS in patients with inoperable oropharyngeal carcinoma in comparison with radiotherapy alone.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Purpose: Retrospective analysis was performed to assess the influence fo primary surgical or irradiation treatment on local control, survival, and final preservation of larynx in comparable groups of ...patients with T1N0 and T2N0 glottic cancer.
Methods and Materials: Two hundred sixty-three previously untreated patients with invasive squamous cell carcinoma of the glottis (187T1 and 76T2) were treated with primary radiotherapy (159T1 and 60T2) or primary surgery (28T1 and 16T2) between January 1976 and December 1990, at the University of Ljubljana, Slovenia. Conventional one daily fraction of 2 Gy to doses of 60–74 Gy (median: 65 Gy) were used in 98% of primarily irradiated patients through out the observed period. To enable better comparison between the two treatment groups, primarily irradiated patients were retrospectively stratified by the criteria of suitability for primary voice-sparing operation. Several host, tumor, and treatment parameters were analyzed.
Results: Only the stage of the disease significantly influenced both 10-year recurrence-free and disease-specific survival regardless primary treatment modality (p = 0.0002). In all primary irradiated patients local control was significantly better for those with overall treatment time of less than 48 days (p = 0.007). In patients suitable for voice-sparing operation, local control of primarily operated patients was similar to that of patients primarily irradiated with shorter overall treatment time, which was 93 and 88% for T1 and 67 and 64% for T2 tumors, respectively. Ultimate local control in primary surgery and radiotherapy group was 96 and 96% for T1 and 89 and 88% for T2 tumors, respectively. Equal larynx preservation of 100% in T1 and 90% in T2 patients was achieved in finally cured primarily operated patients and those patients primarily irradiated with a shorter overall treatment time. If treatment time was longer than 48 days, significantly worse final larynx preservation of 84% in T1 and 75% in T2 patients was observed (p = 0.003). In patients unsuitable for voice sparing operation, 87% of T1 and 50% of T2 patients in primary radiotherapy group finally had their larynx preserved.
Conclusions: Stratification based on criteria of possibility for initial voice-sparing operation is important when comparing primary surgery with primary radiotherapy treatment in ealry glottic cancer. The detrimental effect of prolonged treatment time of irradiation resulted not only in inferior local control rate but also in worse final larynx preservation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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