Hyperthermic treatment of tumours: experimental and clinical applications.
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Biomedical subjects
Publications and source records attributed to R Cavaliere.
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To evaluate the role of hyperthermia combined with chemotherapy in the loco-regional treatment of tumors, a retrospective analysis was done with 228 limb melanoma patients treated with hyperthermic antiblastic perfusion (HAP). A series of treatment- and tumor-related prognostic factors was analyzed to establish their influence on tumor response, loco-regional control, and survival. Concerning tumor response, the logistic model showed that the number of lesions and the minimal tumor temperature (min T) maintained their individual predictive values (P < 0.000001 and P = 0.04, respectively). For loco-regional control, only the number of lesions had a significant predictive value. No direct correlation was found between the treatment-related variables and loco-regional control. However, the 5-year survival rate was significantly higher for patients who achieved a complete response (CR) (51.5%, P = 0.0033) as compared to those who did not (33.3%), providing indirect evidence of the role of the treatment. Multivariate analysis showed that both disease-free and overall survival are strongly influenced by numerous clinical variables and the min T always maintained its significance. When analyzing the subgroup of 119 patients evaluable for tumor response, the Cox model selected the tumor response as the dominant factor for both disease-free and overall survival. These data seem to demonstrate that the optimization of treatment parameters is crucial in determining the CR rate, which, in turn, positively affects the disease outcome. HAP is the treatment of choice for recurrent limb melanoma, and hyperthermia plays an important role in exploiting the efficacy of this technique.
On the basis of personal experience and a review of the literature, the authors have evaluated the results obtained with hyperthermic antiblastic perfusion (HAP) for the treatment of stage II, III and IIIAB limb melanoma. The evaluation showed that today HAP may be considered a safe and effective treatment, with a major complication rate ranging between 1% and 4%. In terms of tumor response, locoregional control and survival, this treatment has provided better results than other regional chemotherapeutic modalities and undoubtedly better results than those obtained with conventional, even radical, surgery. The multiparametric analysis showed that, of the treatment-related prognostic factors, the minimum tumor temperature influenced the percentage of complete response (CR) to the greatest extent (P < 0.03), with a positive trend also with regard to the dosage of the antiblastic drug employed (P < 0.08). In turn, the complete response rate was a determinant as far as locoregional control (75.3%; P < 0.0009) and disease-free (51.4%; P < 0.009) and overall survival (63.2%; P < 0.009) rates were concerned. Of the tumor-related prognostic factors, the number of lesions (P < 0.0014), sex (P < 0.04), and the number of disease recurrences (P < 0.01) appear to influence overall survival.
Thirty-two patients with recurrent (skin) or metastatic (skin, node, or both) melanoma have been treated with a hyperthermia-cisplatin regimen. The hyperthermic treatment was carried out for 60 minutes at 43 degrees C with the MHS-SMA and the Sapic SVO3 ALENIA devices once a week. When the tumor temperature reached 42 degrees C, cisplatin was administered at a dosage of 50 mg/m2 given by intravenous bolus infusion. The treatment was repeated four times and the tumor response evaluated 4 weeks after the last treatment. Significant systemic or local toxicity was not seen. In terms of results, there were 9 patients with complete responses (28.1%), 13 with partial responses (40.6%), 8 with no change (25.0%), and two with disease progression (6.3%). The objective response rate was 68.7%. The response duration for those with complete responses ranged from 4 to 49 months (median 20 months). The median time to progression for patients with partial responses and those with no change was 6 and 5 months, respectively, with ranges of 1-7 and 1-10 months, respectively. The 4-year actuarial survival rates were 47.6% and 20.3% for the complete and incomplete responders, respectively. These results can be considered satisfactory, taking into account that most patients were pretreated with radiotherapy, chemotherapy or both, confirming the therapeutic potential of the hyperthermia and cisplatin regimen.
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The aim of the present report was to establish the effectiveness of different prophylactic antibiotic regimens and administration times in colorectal cancer surgery. Six thousand and sixty nine patients from 36 selected randomized clinical trials, published between 1980 and 1989, were reviewed. The occurrence of septic events, isolated bacterial strains, fever and postoperative hospitalization times were also analyzed. The therapeutic schedules that included the perioperative administration of antibiotics provided better results that those that did not (p. less than .0001 for infections both specifically related and unrelated to colorectal surgery). The number of postoperative administrations did not affect the clinical results, even if the predominant choice was to give more than one administration of antibiotics. A factorial design demonstrated that prolonging the perioperative administrations up to the postoperative period provided statistically significant benefits (p less than .0001) only with regard to the risk of infections that were not specifically related to colorectal surgery.
DNA ploidy and cell proliferation were studied by means of flow cytometry in 98 patients with primary colorectal adenocarcinoma. Multiple samples of tumour burden were pooled and freshly dissociated immediately after surgery for FACS analysis. The relationships between ploidy, proliferative activity, evaluated in terms of S-phase percentages (%S), and some clinico-pathological variables were analyzed. 87 of the 98 tumors yielded evaluable DNA histograms: 32 were diploid (37%) and 55 were aneuploid (63%; median DNA index = 1.6). Multiple aneuploid cell populations were found in 15 tumors (17%). The % S was estimated by means of a mathematical model. Aneuploid tumors showed % S values significantly higher than diploid ones (p < 0.0001). Differences in the distribution of DNA aneuploidy were observed in relation to Dukes' stage and tumor site, left colon, rectum and stage D tumors being more frequently aneuploid. No significant differences in proliferative activity were observed in relation to most of the clinical variables, except for higher % S values observed in tumors of right colon compared to those of left colon and rectum.