Hyperthermic Antiblastic Perfusion Research Articles

The application of hyperthermia in regional chemotherapy

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. Semin. Surg. Oncol. 14:215–223, 1998. © 1998 Wiley-Liss, Inc.

Hyperthermic antiblastic perfusion with TNF-Alpha and L.Pam in patients with stage II, IIIA and IIIAB limb melanoma

Hyperthermic antiblastic perfusion with TNF-Alpha and L.Pam in patients with stage II, IIIA and IIIAB limb melanoma

TNF-alpha and doxorubicin in hyperthermic perfusion for limb sarcomas

Eighteen patients, subdivided into groups of three, were perfused for 90 min with escalating doses of TNF-alpha (0.5-3.3 mg) and standard doses of doxorubicin (bolus 0.7-1.4 mg/kg) at a tumor temperature of at least 41 degrees C, with the aim to ascertain the maximum tolerable dose (MTD) and the activity of TNF-alpha combined with doxorubicin in hyperthermic antiblastic perfusion (HAP) for patients with limb sarcomas, candidates for amputation. Tumor response was assessed both pathologically and radiologically. Severe systemic toxicity (WHO) was observed in only 2 patients. Locoregional toxicity (Wieberdink's) was grade I in 3 patients, grade II or III in 10 and grade IV in 5. A strict correlation between the TNF dosage and the grade of limb reaction was found, grade IV being retrieved only with TNF dose >1 mg and/or muscular temperature >41.5 degrees C. Tumor necrosis was evaluated in 16 patients: in 11 (68.8%) it scored more than 75% while in 5 it was 25 to 75%. Four cases (25%) had 100% tumor histological necrosis. Limb sparing surgery was feasible in 13 (81%). Our findings suggest that this is a well-tolerated and highly active regimen in HAP.

Limb-sparing treatment for soft tissue sarcomas: influence of prognostic factors.

At present, limb-sparing surgery is the most appropriate and acceptable treatment available for sarcomas of the extremities, although the right balance between conservative therapy and maximum efficacy has yet to be found. A better knowledge of prognostic factors may help in planning the appropriate strategy for each case. Eighty patients underwent limb-sparing surgery for limb sarcomas (17 had surgery alone; 19 had neoadjuvant hyperthermic antiblastic perfusion combined or not with postoperative radiotherapy, and 44 had adjuvant radiotherapy). Univariate and multivariate analyses were made to detect statistically significant differences between subgroups and identify the more significant subset of prognostic factors. Only microscopically positive surgical margins were related to a greater risk of local recurrence, whereas overall survival was compromised by high grade and large tumor size.

Hyperthermic antiblastic perfusion in the treatment of stage IIIA-IIIAB melanoma patients. Comparison of two experiences

Hyperthermic antiblastic perfusion in the treatment of stage IIIA-IIIAB melanoma patients. Comparison of two experiences

Influence of thermal parameters on tumor response in recurrent limb melanoma patients treated with hyperthermic antiblastic perfusion

Influence of thermal parameters on tumor response in recurrent limb melanoma patients treated with hyperthermic antiblastic perfusion

Adriamycin (ADR) in hyperthermic antiblastic perfusion (HAP) for high grade (HG) limb sarcomas

Adriamycin (ADR) in hyperthermic antiblastic perfusion (HAP) for high grade (HG) limb sarcomas

Hyperthermic antiblastic perfusion in the treatment of local recurrence or "in-transit" metastases of limb melanoma.

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.

Prognostic variables in recurrent limb melanoma treated with hyperthermic antiblastic perfusion

Between October 1969 and December 1986, 136 patients with recurrent limb melanoma were treated with hyperthermic antiblastic perfusion (HAP). This retrospective analysis is aimed at identifying tumor-related and treatment-related variables likely to influence tumor response, locoregional control, disease-free survival, and overall survival. Independent factors predicting a complete response (CR) were the number of lesions (P less than 0.0001) and the minimum tumor temperature (minT) (P = 0.03). Only a positive trend was observed for the drug dose (P = 0.08). However, the proportion of CR was significantly higher (57.7%; P = 0.02) in patients who had a minT of 41.5 degrees C or greater and who were given a dose equal to or greater than the standard dose than in patients treated with lower temperatures and/or lower drug doses. The occurrence of a CR significantly increased the rates of locoregional control (77%; P = 0.007), disease-free survival (55.6%; P = 0.006), and overall survival (68.6%; P = 0.03). Treatment optimization may provide further therapeutic improvements by increasing the incidence of CR. However, the overall survival rates also were influenced by the number of lesions (P = 0.0014), sex (P = 0.04), and the number of previous relapses (P = 0.01). Therefore, tumor aggressiveness also is crucial in determining the outcome of the disease, and only early treatment with HAP can reduce the risk of distant metastases.

The role of hyperthermic perfusion as a first step in the treatment of soft tissue sarcoma of the extremities.

AbstractEighty‐six patients with locally advanced, high‐grade soft tissue sarcomas of the extremities were studied prospectively in order to determine the efficacy of hyperthermic perfusion (HP) or hyperthermic antiblastic perfusion (HAP) as the first step of a combined multimodality therapy.The immediate response was evaluated in terms of tumor regression, and results confirmed the in vivo sensitivity of human sarcomas to the selective antineoplastic action of heat alone or combined with drugs (melphalan, actinomycin D, and cis‐platinum). HAP has been shown to be simpler and safer than HP, and it is now currently routinely employed.As far as the long‐term cure is concerned, all the patients have been evaluated for functional results, locoregional control, and survival, according to the different treatment schedules.The first clinical trials employed HP or HAP followed by delayed surgery alone. In 11 of 17 evaluable patients treated with HP, and in 17 of 29 treated with HAP, conservative surgery could be performed. A high incidence of locoregional relapse (24%) occurred, with low overall survival rates: 50.1% and 31.7% at 5 and 10 years after HP plus surgery, and 47.9% after HAP plus surgery at both 5 and 10 years.The protocol was, therefore, modified to include continuous intraarterial infusion of Adriamycin® (ADR) (17 patients) or radiotherapy (9 patients) before surgery.The results obtained thus far may be summarized as follows: (a) conservative surgery with functional limb‐salvage was possible in all patients; (b) the percentage of locoregional failure decreased to approximately 12% after HAP + ADR infusion + excision, the 5‐ and 10‐year overall survival rates both being 77.6 %, and the 5‐ and 10‐year disease‐free rates both being 57.8%; (c) no local recurrences occurred in the group treated with HAP + radiotherapy + excision with a 5‐year overall survival rate of 71.5% and a 5‐year disease‐free rate of 50.4%.In conclusion, the combined multimodality approaches employed appear to have improved both functional results and long‐term cure, even though these must be further confirmed on a larger series of patients.

Isolation perfusion of the lower limb with platinum.

AbstractFrom August, 1983 to February, 1986, a total of 14 patients affected by osteogenic sarcoma of the limbs have been treated at the National Cancer Institute, Milan, Italy. For all patients, due to the size of tumor and the extracompartmental invasion, the only possible treatment was an amputation or disarticulation and, for this reason, it was decided to submit the patients to combined treatments according to this schedule: 2 subsequent intraarterial infusions of cis‐platinum (CDDP) + systemic high‐dose methotrexate (MTX), followed by hyperthermic antiblastic perfusion in extracorporeal circulation and 2 more cycles of systemic high‐dose MTX + CDDP.This schedule of treatment is reasonably well tolerated by the patients, despite the side effects and the length of the entire presurgical period. No significant complications have been observed, either local or systemic.

Limb Salvage in Osteogenic Sarcoma of Extremities: A New Therapeutic Approach Associating Infusion and Hyperthermic Antiblastic Perfusion

(J. Extra-Corpor. Technol. 19[3] p. 338-347 Fall 1987, 49 ref.) From August 1983 to September 1986, 17 patients affected by osteogenic sarcoma of extremities were admitted to our Division with only surgical alternatives of amputation or disarticulation due to the impressive local extension of disease. Trying to avoid this procedure we started a program of limb salvage as follows: two cycles of intraarterial cis-platinum (CCDP) plus systemic high dose of methotrexate (HDMTX) followed by hyperthermic antiblastic perfusion (HAP) with high dose COOP and for the majority of patients 2 more cycles of systemic HDMTX + COOP with or without radiotherapy on the primary. Immediate response, evaluated both in terms of necrosis and of clinical and radiologic reduction of the tumor mass, was so impressive that in 10 patients it was possible to perform a conservative surgery, en bloc resection of the primary tumor plus endoprosthesis, with a satisfactory functional and cosmetic result. None ofthe patients relapsed locally; 8 developed lung metastases that, whenever possible, were resected.

Hyperthermic Antiblastic Perfusion in Extracorporeal Circulation: Surgical Technique and Results in the Treatment of Extemities’ Tumor

Regional perfusion in extracorporeal circulation is finding more and more applications in the treatment of extremities’ tumors. In order to avoid any influence from surgical variables rises the necessity of a standardization of the technique. In this paper we propose a new surgical technique with subsequent results based on the experience at the National Cancer Institute of Milan on 89 consecutive patients treated by regional hyperthermic antiblastic perfusion without significant complications.

Hyperthermic antiblastic perfusion in the treatment of cancer of the extremities.

From February 1982 to December 1983, 42 patients affected by neoplasms of the limbs were treated at the Istituto Nazionale Tumori of Milan by hyperthermic antiblastic perfusion in extracorporeal circulation at the temperature of 40-41 degrees C for 1 h. Thirty-two were affected by melanoma, 4 by osteogenic sarcoma, 2 by squamous-cell carcinoma, 1 by liposarcoma, 1 by hemangiopericytoma, 1 by clear-cell sarcoma and 1 by Kaposis's sarcoma. As regards the immediate response, a complete plus partial remission rate of 88% without any major complication was obtained. The follow-up period is too short for any considerations about overall survival. However, because of these good clinical results we consider this method able to locally control the evolution of neoplasms of the extremities, allowing in many cases a limb salvage.