Thermochemotherapy for soft tissue sarcoma.
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Biomedical subjects
Publications and source records attributed to F Di Filippo.
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Tissue CEA, TPA, and CA 19.9 concentrations from samples of surgical specimens were measured in 47 evaluable colorectal cancer patients (median follow-up, 20 months, 13 recurrences) and correlated with individual patient follow-up status. The quantitative method appeared to be sensitive, easily reproducible, and standardizable. The tissue marker concentration was analyzed by means of the multivariate discriminant analysis, to evaluate the risk of relapse in each patient; the tumor CEA (CEA T) showed the best discriminant capacity (P = .005). The relative Fisher function provided a reliable prognostic patient index, independently of other recognized prognostic factors (Dukes' stage and cellular differentiation grade). The Cox model showed a statistical significance analyzing the tumor (T) and healthy mucosa (M) CEA values (P = .001 and P = .006, respectively). The combination of these two variables allowed for identification of three classes of patients according to CEA T and M threshold values of 216 and 85 ng/mg of protein, respectively, and different disease-free curves were obtained for each group. The two-year disease-free rate was 81 percent for patients with low values of both CEA T and M, and 21.4 percent for the group with both values above these thresholds (P = .0008). In the third class (CEA T or M higher than the reported cut-off levels), the two-year disease-free rate was 65.9 percent.
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The role of hyperthermic perfusion (HP) for the treatment of limb osteogenic sarcoma was evaluated in 76 patients. Twelve patients were treated with HP alone, and a 5- and 10-year survival rate of 25.5% was obtained. When amputation was systematically associated to HP (12 patients), a 5- and 10-year survival rate of 50.9% was achieved. Twenty-seven patients were treated with hyperthermic antiblastic perfusion (HAP) followed by amputation 4 weeks later. With this treatment, the 5- and 10-year actuarial rates rose to 71.4 and 65%, respectively, with a 5-year disease-free survival rate of 67.4%. Fifteen patients were treated with HAP followed by an 'en bloc' resection and bone reconstruction. The 5- and 10-year actuarial survival rate obtained was 63.5% with a 5-year disease-free survival rate of 53.6%. These results seem to indicate that HAP permits carrying out conservative rather than ablative surgery for the treatment of limb osteogenic sarcoma.
Lonidamine was given to several patients affected with different types of neoplasias growing as metastases both in ascites and pleural effusion, and solid cutaneous metastases. The patients with tumor cells in ascites and pleural effusion were treated with Lonidamine per os or in loco injections. In cutaneous metastases, Lonidamine was administered by different routes: (1) per os; (2) local endoarterial; and (3) in association with hyperthermic perfusion with or without antiblastic drugs.
Lonidamine alone or in combination with hyperthermic perfusion, with or without melphalan, was investigated in 12 patients with stage II, III, and IV malignant melanoma. The authors evaluated the most effective methods and sequence of Lonidamine administration. Preliminary results suggest that the highest effectiveness is obtained with the simultaneous administration of Lonidamine and hyperthermia.
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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.
Hyperthermic isolated limb perfusion (ILP) with tumor necrosis factor-a (TNFalpha) and cytotoxic drugs is currently used for treatment of melanoma and sarcoma of the limbs. Tumor necrosis factor-alpha is involved in the systemic inflammatory response syndrome as a result of activation of inflammatory cells and production of bioactive substances. The goal of this study was to determine the circulating levels of proinflammatory cytokines and soluble adhesion molecules in 19 patients with limb melanoma or sarcoma undergoing ILP with (n = 9) or without TNFalpha (n = 10). The results obtained demonstrated that ILP with TNFalpha was responsible for a leakage of TNFalpha in the systemic circulation, followed by a rise in interleukin (IL)-6 and IL-8 levels within I h. Elevated soluble (s)P-selectin levels were found 1-3 h after ILP. Plasma sE-selectin peaked 6-9 h after ILP, and soluble vascular cell adhesion molecule (sVCAM) levels reached a maximum after 24 h. Significant correlations were observed among these variables, confirming the interdependence of all changes observed. On the other hand, ILP with cytotoxic drugs alone induced only a modest release of TNFalpha, which was not followed by an immediate rise in IL-6 and IL-8. Four of the 9 patients undergoing ILP with TNF had severe systemic toxicity. No association was found between systemic TNF levels and the clinical outcome, whereas elevated TNF perfusion levels as well as systemic IL-6 and IL-8 levels were constantly elevated in patients with severe toxicity. These results are suggestive of an important role of TNFalpha levels in the perfusion system (more than leakage of perfusate) in causing postoperative toxicity, although other ILP-related factors should not be excluded.
PURPOSE: To evaluate the opinion of patients with tumors who chose spontaneously to undergo the traditional anti-cancer treatment about Di Bella's therapy after the negative results of the experimental trial. MATERIALS AND METHODS: From November 23rd, 1998 to December 10th, 1998 a questionnaire was distributed among 50 patients with tumors. The questionnaire was anonymous, self-administered and included 9 questions. The data were compared, when possible, with those obtained in a previous study. RESULTS: Overall, 40 (70%) patients accepted favourably the conventional therapy; 27 (54%) patients did not believe in the experimental trial, as it was performed; 34 (68%) patients think the experimental trial should be repeated. CONCLUSIONS: The negative results of the experimental trial caused a distrustful feeling towards the Di Bella multi-therapy; but there is much confusion. There is a strong feeling that the conventional medicine is linked to powerful interests of the international pharmaceutical firms.
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The sentinel-node technique was first introduced by Morton in high-risk melanoma of the skin. Recently, this technique has also been used in patients with T1 breast cancer. Lymphoscintigraphy and the gamma probe are currently used in sentinel lymph-node detection. Many investigators have used this technique in clinical practice and there is no standard procedure in terms of the timing of lymphoscintigraphy, type of vital stain, radiolabelled tracer, etc. This heterogeneity might account for the broad range of false-negatives reported in the literature. The aim of our study was to carefully review and analyse the literature in order to identify the most reliable technique for use in sentinel node detection. The results of the review seem to indicate that the simultaneous use of preoperative lymphoscintigraphy, intraoperative gamma probe and vital staining is capable of ensuring the best results. These data have been confirmed in our experience of 15 patients. The sentinel node search was successful in 100% of the cases, and the percentage of false negative was 0%. The use of the best technique available might prove extremely important, particularly in randomised clinical trials, comparing sentinel node biopsy with axillary dissection. In the patient group undergoing sentinel node biopsy, the axillary pathological staging is based exclusively on this technique and therefore its reliability must be assured if it is to serve as a precise guide in the planning of adjuvant treatments.
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A multicentric prospective study has been carried on 69 patients affected by peritoneal carcinomatosis from colorectal cancer. Patients have been treated by cytoreductive surgery and intraoperative hyperthermic chemoperfusion. CC 0-1 has been achieved in 82%. Major morbidity and mortality was respectively 21.7% and 2.9%. Three years overall survival was 26.7% for all series. Difference in survival evaluating CC 0-1 vs CC 2 patients and PCI < or = 10 vs > 10 was statistically significant. Evaluating only patients CC 0-1 and PCI < or = 10 overall survival rised up to 44.7% at 4 years. A smaller subgroup of patients with a disease-free interval to peritoneal carcinomatosis > or = 2-year showed a 50% disease-free survival at 5 years. In conclusion PCI < or = 10, complete or optimal cytoreduction feasibility and disease-free interval have to be considered for the patients selection to the integrate treatment.