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C Nervi

Publications and source records attributed to C Nervi.

At least 73 records · Page 4Linked to original sources

Tumor control and therapeutic gain with different schedules of combined radiotherapy and local external hyperthermia in human cancer.

Tumor control and therapeutic gain have been evaluated in a series of studies on patients with multiple lesions employing different protocols of combined radiotherapy (RT) and local external hyperthermia (HT). Tumor response has been evaluated during a follow-up ranging 6 to 18 months. Therapeutic enhancement factor (TEF) was defined as the ratio of thermal enhancement (TE) of tumors to TE of skin, where TE was clinically evaluated as the ratio of percent response (i.e., complete tumor clearance and moist desquamation, respectively) after combined modality to percent response after RT alone. Local tumor control was constantly better in lesions treated with any combined modalities in comparison with RT alone. The use of high RT dose per fraction appeared to increase tumor control only in the combined modalities groups, the immediate (so called "simultaneous") schedule (HT at 42.5 degrees C/45 min, applied immediately after each RT fraction, twice a week) being more effective than the delayed (so called "sequential") treatment (HT at 42.5 degrees C/45 min, delivered 4 h after each RT fraction, twice a week). The combination of high RT dose per fraction with high temperature HT (45 degrees C for 30 min) achieved the best tumor control. No increased radiation skin reaction was observed when a conventional fraction size of RT was used (3 daily fractions of 1.5-2 Gy, 4 h interval between fractions) in association with HT (42.5 degrees C/45 min, every other day, immediately after the second daily RT fraction). A remarkable enhancement of skin reaction was observed, however, when using high RT doses per fraction in association with 42.5 degrees C HT, especially with the immediate treatment schedule. No enhancement of skin reaction was obtained after high RT doses per fractions and 45 degrees C HT because an active skin cooling by means of circulating cold water was used in these cases. Consequently, a good TEF (1.58) was obtained when conventional RT doses per fraction were used in association with 42.5 degrees C HT. TEF values of 1.40 and 1.15 were observed when high RT doses per fraction were employed in association with the delayed and immediate 42.5 degrees C HT, respectively. HT at 45 degrees C can be safely employed only when tumors can be heated selectively or at least preferentially in comparison with normal tissue; in the lesions treated with such a schedule a TEF of 2.10 was obtained.

Diathermy↗

Combined radiation and drugs: the effect of intra-arterial chemotherapy followed by radiotherapy in head and neck cancer.

This study was designed to ascertain whether a prior reduction of tumor size by drugs could affect the final outcome of tumors treated with radiation. 142 patients with head and neck cancer (oropharynx, maxillary antrum and intra-oral) were randomized for the study. In 72 cases, irradiation was preceded by a continuous intra-arterial infusion of 3-5 mg/day methotrexate to a total dose of 90-120 mg; the other 70 patients were treated with radiotherapy alone. Chemotherapy, given prior to radiotherapy, caused a shift in the tumor stage (i.e. a reduction in tumor size) in more than one third of the cases. The overall 5-year survival was 43% in the combined treatment group and 25% in the group treated with radiation alone (statistical difference: p less than .05). However, when analysed separately the difference was statistically significant only in oral cavity tumors (5-year survival of 54% in the combined modality group vs. 27% in the control group), although local control rates after both single and combined modalities were not statistically different from those of oropharynx and maxillary antrum tumors. In these last lesions, however, the dissemination of disease was more frequent; therefore, the lack of improvement of cure rate with the combined modality in these cases seems to be related to both the higher tendency of these tumors to disseminate and the low effectiveness of intra-arterial chemotherapy in controlling distant metastases. Mild and transient local and systemic toxicities were observed during chemotherapy infusion, but no radiosensitising effect on normal skin and mucosa was seen during radiotherapy in patients who had received pre-irradiation chemotherapy.

Combined Modality Therapy↗

Clinical results after different protocols of combined local heat and radiation.

Since 1977, 69 patients with 138 multiple lesions have been treated with combined radiotherapy and hyperthermia, according to 3 protocols. Firstly, radiotherapy was given following a thrice-a-day fractionation scheme of 1.5 to 2 Gy/fraction, up to 60 Gy. Hyperthermia (42.5 degrees C/45 min) was applied each other day, immediately after the 2nd radiation fraction. Immediate response resulted significantly higher in the combined group (76% clearances in comparison with 46% after radiotherapy alone). Secondly, tumors received 40 Gy/8 fractions, twice a week, and hyperthermia (42.5 degrees C/45 min) was applied with each radiotherapy fraction, either immediately after irradiation (simultaneously) or 4 h later (sequentially). A remarkable improvement of radiation response was obtained, especially with the simultaneous treatment. Thirdly, tumors received 30 Gy/6 fractions, twice a week. Hyperthermia (45 degrees C/30 min) was applied simultaneously with each radiotherapy fraction and the surrounding skin was cooled. Complete tumor clearance was achieved in 88% lesions in comparison with 31% after radiotherapy alone. As expected, the incidence of thermal damage on uncooled skin was also increased. In conclusion, the best therapeutic ratio was obtained with low fractional radiotherapy doses and low temperature hyperthermia.

Hot Temperature↗

[Elective radiotherapy in breast carcinoma].

From March 1972 to November 1979 a total of 157 patients with stage I to III primary breast cancers have been irradiated after segmental resection (12 cases), tilectomy (89 cases) or biopsy (56 cases). Complete local control was achieved in all Stage I lesions, in 97% of Stage II lesions and in 68% of Stage III lesions. Non recurrence has been observed in patients previously operated by segmental resections, while local failures occurred in 6/89 and in 16/56 patients operated by tilectomy or biopsy, respectively. Of the 28 Stage I patients, 24 (86%) are alive, one with distant metastases. Four patients of this group are dead, 2 of intercurrent disease and 2 of breast cancer. Of the 61 (Stage II) patients, 38 (62%) are alive, 5 of these with distant metastases. Twenty-three patients are dead, 15 with active disease, and 8 suffered intercurrent death. Of the 68 Stage III patients, 21 (31%) are alive, 6 of these with distant metastases. Fourty-seven patients are dead, 43 of breast cancer and 4 of intercurrent disease. The high probability of initial subclinical deposits is evidenced by the fact that 49 of the 68 patients in this group developed distant metastases. The patients with T1 lesions appear to comprise the most favourable group with a relapse free survival at five years of 76%. The 5 years relapse free survival was 62% for T2 lesions and 25% for T3 and T4 lesions. N0 status does not confer the same favourable prognosis as T1 status. N+ status, however, resulted in a definitely negative prognostic factor. Cosmetic results after our treatment approach appear to be extremely good. A marked difference between the irradiated and controlateral breast occurred only in 10 of the 125 patients after a minimum of 2 years observation.

Breast Neoplasms↗

Cytometric evidence of cytogenetic and proliferative heterogeneity of human solid tumors.

Flow cytometry is a widely recognized method of rapidly assessing the ploidy and proliferation status of experimental and solid tumors. In the present work, a variety of human cancers from various sites (lung, head and neck, etc.), of traditional interest in our laboratory, have been analyzed. In agreement with a number of recent reports, a general heterogeneity of human solid tumors can be evidenced. In particular: (a) solid tumors are characterized by a variable degree of aneuploidy; (b) the internal structure of solid tumors is highly heterogeneous especially with respect to the fraction of aneuploid malignant cells and their distribution through the cycle phases; and (c) some solid tumors are also characterized by the presence, to a variable extent, in the tumor of mass of multiple cell clones. Static fluorimetry of Feulgen-stained (mitotic) single cells offers a way to confirm this kind of observations.

Aneuploidy↗

Multiple daily fractionation (MDF) radiotherapy in association with hyperthermia and/or misonidazole: experimental and clinical results.

Several modalities involving a Multiple Daily Fractionation (MDF) course in combination with hyperthermia and/or the hypoxic sensitizer misonidazole have been tested on a mouse tumor system and then applied, with the proper sequencing, to a group of patients with multiple (N2-N3) neck node metastases from H&N cancers. Different lesions of the same patients underwent different modalities. The clinical results indicate the effectiveness, in respect to a historical series of patients treated with conventional fractionation (200 rads/day, five days/week), of either MDF alone (200 + 150 + 150 rads/day, five days/week) or MDF + hyperthermia (500 MHz, 42-43 C, 45 min., after 2nd daily fraction, on day 1, 3, and 5 of each week) or MDF + misonidazole (1.2 g/m2 daily, 2 hours before 1st fraction, up to a maximum dose of 12 g/m2), or MDF + hyperthermia + misonidazole. The latter modality appears to be possibly the most effective at inducing a complete local tumor response lasting longer in time (follow-up to a minimum of four months). The pharmacology of misonidazole has been monitored in the patients to avoid undesired excessive drug plasma level. No neurological symptoms have been observed. Oropharyngeal mucositis has been observed only in patients treated with misonidazole and radiation through two cross-firing portals. The problem of selecting individual patients for a particular modality is discussed.

Animals↗

Cytokinetic evaluation in human head and neck cancer by autoradiography and DNA cytofluorometry.

As part of a comprehensive research program on cell proliferation characteristics of squamous cell carcinoma in humans and the relation of these characteristics to treatment, 4 untreated cases of head and neck cancer and 2 recurrences were studied. Previously, cell kinetics following the percent labelled mitoses method were done and the same carcinomas now studied by measuring microfluorometrically the time distribution of the nuclear DNA content. Two cases were characterized by a homogeneous cell population, whereas in 2 other cases, two cycling subpopulations distinguished by their DNA content were encountered. The clinical response was not related to the occurrence of single- or multiple-cell populations. In all cases, a great variability in the mitotic index (MI) and in the proportion of cells in the different cycle phases was found. The heterogencity in the proliferative structure of these tumors stresses the need for a greater accuracy in performing cell kinetics studies in vivo and could account for the difficulties in devising a therapeutic regimen based on cycle or phase-specific agents.

Autoradiography↗

A critical appraisal of the usefulness of some biological parameters in predicting tumour radiation response of human head and neck cancer.

Tumour stage is considered to be a valuable prognostic parameter. However, in our experience with head and neck tumours, previous reduction of the tumour stage and/or size by chemotherapy does not affect the response to radiotherapy. Furthermore, we have found no clear correlation between response to treatment and kinetic parameters such as growth rate, generation time, growth fraction and cell loss. Recently, using cytometric analysis of biopsies, we concluded that the presence in the tumour of a single dividing "diploid" population vs subpopulations with more than one "ploidy" and different growth characteristics has little predictive value. At present, the possibility of selecting radioresistant tumours for a particular modality of treatment can only rely on empirical grounds. Holstsi et al. (1978) have proposed the use of (an) initial large fractional radiation dose(s) in tan attempt to exploit the possible increase in cell killing and/or reoxygenation. Following this approach, 34 patients with advanced or recurrent tumours have been irradiated with an initial single dose of 8-10 Gy. After 10 days of rest, the tumour shrinkage was estimated and the tumours classified as responders or nonresponders. When the patients underwent the remaining part of treatment according to a conventional fractionation, 2/3 to 3/4 of the responders exhibited a complete tumour shrinkage while none of the nonresponders exhibited a complete response. We feel that this approach could be an interim method of empirically identifying radioresistant tumours.

Breast Neoplasms↗

Enhanced effectiveness of adriamycin and bleomycin combined with local hyperthermia in neck node metastases from head and neck cancers.

The results of this study concern the comparison of the clinical effects of adriamycin (ADM) or bleomycin (BLM) alone and combined with local hyperthermia on 15 patients with multiple (29) neck node metastases from head and neck cancers. With repeated low fractional daily doses of drug a significant though transient tumor regression was obtained in 2/8 and in 3/6 of the lesions treated with ADM or BLM alone, respectively. When the drugs were combined with 42-43 degrees C hyperthermia, an overall response, either complete or partial, was seen in all the lesions. Complete regression was observed in 38% (3/8) and 43% (3/7) of the lesions treated with ADM or BLM, respectively, combined with heat. At a 4-month follow-up, 33% (2/6) and 40% (2/5) of the same groups of lesions remained still undetectable. These results suggest that the combined treatment of drugs and local hyperthermia can be advantageously employed in clinical practice for treating local tumors, especially recurrences in previously irradiated areas.

Bleomycin↗