Local stage of advanced cervical cancer changes in 27% comparing MRI and clinical examination.• For treatment allocation important clinical stages IB1-IIA2 changed to IIB on MRI in 31%.• Pelvic wall/bladder infiltration vary considerably, likely due to different definitions for clinical and imaging findings. • 50% of this cohort are allocated to stage IIIC with FIGO 2018, obscuring local tumour extent.• TNM offers the most differentiated stage allocation with 26 subgroups in this cohort.
Objective To identify prognostic factors for penile cancer (OR=1.88) and age (OR=1.04) as independent prognostic variables for survival. Penile amputation and to evaluate the treatment strategy for early-stage disease, proposed recently by the European Board of in tumours <4 cm in diameter improved local control but not survival. Regional control and survival Urology (EBU). Patient and methods The records of 82 patients consecu-were not significantly improved by prophylactic adenectomy. tively referred to the uro-oncological centre at Aarhus University Hospital between 1965 and 1993 wereConclusion Differentiation, T-stage and age were prognostic factors for survival. The results support the EBU reviewed. The importance of tumour stage, differentiation, patient age, local control and regional lymph treatment strategy involving penis-conserving therapy and watchful waiting for early-stage disease. node control were assessed using univariate and multivariate analyses.
A few minute's exposure to a high temperature (sensitizing treatment, ST) may substantially increase the cytotoxic and the radiosensitizing effect of a subsequent heating at a lower temperature (test treatment, TT). This phenomenon, which is known as step-down heating (SDH) or thermosensitization, has been observed both in cultured cells in vitro and in tumours and normal tissues in vivo. The effect of SDH increases with a lowering of TT temperature, but it is rapidly lost at temperatures very close to 37 degrees C. SDH-induced thermosensitization decays within a few hours, when an interval is inserted between ST and TT. In vitro results suggest an exponential decay of the SDH effect with half times ranging from 1.5- to 3.1 h. The effect of SDH increases with increasing ST time or temperature. For single heating, the Arrhenius plot is biphasic with activation energies of 500-800 and 1200-1700 kJ/mol above and below a break point temperature in the region 42.5-43.0 degrees C, respectively. For SDH, the Arrhenius plot gradually becomes monophasic with increasing severity of ST and it approaches asymptotically to an activation energy of about 400 kJ/mol. The reduction of the activation energy depends on cell survival after the priming ST and not on the specific ST heating time or temperature. SDH strongly enhances hyperthermic radiosensitization with a 5-6-fold reduction of the radiation dose required to achieve tumour control. The thermosensitizing and the radiosensitizing effects of SDH have several features in common. Both effects become more prominent when the TT temperature is decreased and when the ST heating time or temperature increases. In addition, the decay kinetics for both effects are comparable. For heat alone, the effect of SDH in tumour and normal tissue seems to be quantitatively similar. However, the therapeutic ratio may be increased by combining SDH with radiation. Biologically, the critical subcellular targets involved in the SDH effect have not been revealed. However, the ability of SDH to inhibit the clearance of heat-induced aggregation of proteins in the nucleus is interesting. Blockage of the nuclear function by proteins is a central theory in the present molecular biological models for both cell kill by heat and heat radiosensitization. Clinically, SDH may be an advantage since even a short exposure to high temperature increases the effect of an otherwise inadequate heat treatment. The disadvantages are that SDH complicates thermal dose calculations, and may cause unacceptable damage to normal tissue.
technique. Chemotherapy consisted of paclitaxel 135 mg/m2 d1 and cisplatin 25mg/m2 d1-3 intravenously every 4 weeks with radiation. Results: The hazard ratios (HR) for disease-free survival (DFS) and overall survival (OS) in the CRT arm versus the RT alone arm were 0.84 (95% CI Z 0.36e1.93, P Z 0.67) and 0.61 (95% CI Z 0.20e1.86, P Z 0.38), respectively. The 5-year DFS and OS for CRT and RT alone groups were 85.9% versus 83.5%, and 92.6% versus 88.4%, respectively. For subgroup analysis, CRT significantly increased the 5-year DFS and OS for patients tumor sizes !3 cc (HR Z 0.23; 95% CI Z 0.05e1.0 and HR Z 0.21; 95% CI Z 0.04e0.99, for DFS and OS, respectively). For patients with negative lymphovascular invasion, CRT increased 5-year DFS (HR Z 0.21; 95% CI Z 0.04e0.99). Multivariate analysis indicated that tumor size was a significant prognostic factor associated with both DFS and OS, and age was significantly associated with OS. Grade 2 to 4 gastrointestinal disorders, radiation enteritis, radiation cystitis, and myelosuppression were more frequent side effects observed in the CRT arm. Grade 3 and 4 toxicities were rare and manageable overall. Conclusion: Chemoradiation therapy with cisplatin and paclitaxel achieved better DFS and OS in early-stage cervical cancer patients after radical hysterectomy with negative lymph nodes compared with RT alone, along with higher rates of acute grade 2e4 complications. Concurrent chemotherapy might enhance radiosensitizing effect to improve survival outcome for patients with large tumor size. Grade 3 and 4 toxicities were infrequent and tolerable overall.
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