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Biomedical subjects

F Pozza

Publications and source records attributed to F Pozza.

At least 37 records · Page 2Linked to original sources

PC-10 antibody to proliferating cell nuclear antigen (PCNA) is not related to prognosis in human breast carcinoma.

The PC-10 monoclonal antibody to PCNA was employed to analyze proliferative grade in conventionally-formalin fixed, paraffin-embedded tumour samples of 162 patients with primary breast carcinoma. To perform the immunocytochemical method, sections were not heated, were de-waxed using alcohol, and then immersed in a phosphate-buffered saline solution and in methanol with 0.5% hydrogen peroxide to block endogenous peroxidase activity. Immunostaining was performed by a streptavidin-biotin peroxidase substrate. A semiquantitative scoring system was used to evaluate the fraction of nuclei that were PCNA-positive. The score ranged from 0% to 75% with a median value of 25%, mean of 27.8 +/- 1.5. PCNA staining was significantly associated with oestrogen receptor-negativity (p = 0.011) and correlated, but not at a statistically significant level, with tumour size (p = 0.08). No significant association was observed between PCNA and node status, grading, DNA ploidy, progesterone receptor or menopausal status. Prognostic indices such as number of positive lymph nodes and DNA ploidy were significantly associated with relapse-free survival (RFS) and overall survival (OS). No significant correlation between PCNA nuclear immunostaining and RFS or OS was observed after a median follow-up of 4 years. Our results indicate that analysis of PCNA alone does not seem to be a useful marker in identifying patients at different prognosis in human breast cancer.

Breast Neoplasms↗

Development of a second generation stereotactic apparatus for linear accelerator radiosurgery.

Linear accelerator radiosurgery technique is based on a multiple intersecting arc irradiations procedure. The coincidence of the axis of two rotation movements (of gantry and treatment couch) into the isocenter is critical for focusing irradiation. In October 1989, our linear accelerator was changed and the stereotactic apparatus had to be adapted to the new machine. After multiple mechanical tests of the new machine, the stereotactic head frame was fixed to the roller bearing allowing rotation of the couch. The new apparatus is described.

Humans↗

Phase I study of escalating dose mitoxantrone in combination with alpha-2-interferon in patients with advanced solid tumors.

In vitro and preclinical in vivo data have shown a synergistic antitumor activity between alpha-interferon and some antiproliferative agents. A phase I study of the concurrent administration of interferon-alpha 2 and mitoxantrone was initiated, to determine the maximum tolerated dose of mitoxantrone given i.v. every 3 weeks in escalating doses combined with a fixed dose of s.c. interferon alpha 2 (6 x 10(6) IU three times per week 3), in patients with advanced solid tumors resistant to conventional chemotherapy. At least three evaluable patients were entered in each dose level of mitoxantrone starting at 4 mg/m2, with no escalations allowed in the same patient. Twenty-seven patients received a total of 101 cycles and five dose-levels were explored (4-6-8-10-12 mg/m2 of mitoxantrone). The dose-limiting toxicities were leukopenia and granulocytopenia at 12 mg/m2 of mitoxantrone, at which dose hematological toxicity occurred in greater than 50% of cases, with one patient presenting grade 4 leuko-granulocytopenia. No severe thrombocytopenia occurred. In the majority of patients transient hepatic enzyme elevations and a flu-like syndrome due to interferon alpha 2 were observed in all dose-levels explored. These observations suggest that the hepatotoxic effects of interferon alpha 2 do not emphasize mitoxantrone side-effects if given simultaneously. When mitoxantrone is administered with 6 x 10(6) IU of interferon alpha 2, the recommended dose for future phase II studies is 10 mg/m2/weeks 3 with escalation up to 12 mg/m2 in selected patients if such a combination is well tolerated in terms of myelosuppression. Regarding therapeutic activity, four out of 25 (16%) cases evaluable for response achieved a partial response.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Weekly epirubicin versus doxorubicin as second line therapy in advanced breast cancer. A randomized clinical trial.

Forty-nine patients with advanced breast cancer who had failed from first-line cyclophosphamide, methotrexate, and 5-fluorouracil (CMF regimen) chemotherapy, were randomized to treatment with either epirubicin (Epi) or doxorubicin (Dox) at a dose of 20 mg/m2 given intravenously (i.v.) weekly to compare the efficacy and toxicity of these two anthracyclines given in such a schedule. Of 43 evaluable patients 36% (eight of 22) treated with Epi and 38% (eight of 21) treated with Dox achieved a complete plus partial response rate (95% confidence limits 16-56% +/- 20% and 18-58% +/- 20%, respectively). Patients who obtained a major therapeutic response to previous CMF exhibited a significantly higher response rate with both the drugs: seven of eight (87.5%) compared with one of 13 (8%); p less than 0.05 for Epi and six of seven (86%) compared with two of 15 (13%); p less than 0.05 for Dox. The median duration of response was 4.5 months with Epi compared with 7 months with Dox, and the median survival of the two groups of patients were superimposable (12 months with Epi versus 11 months with Dox). The median cumulative dose was 220 mg/m2 (range 160-620) and 240 mg/m2 (range 160-860) for Epi and Dox, respectively. Gastrointestinal and hematological toxicities were moderate for both the drugs, with fewer episodes of nausea and vomiting, stomatitis, and leukopenia following Epi administration. A very low incidence of alopecia was recorded for both the drugs. Regarding cardiac evaluation, no significant differences were evident; however, the only case that developed symptomatic congestive heart failure was in the Dox arm, after a cumulative dose of 820 mg/m2 at 11.5 months. Epi given weekly at low doses preserves efficacy in the treatment of patients with advanced breast cancer, and given at equimolar doses, has a slightly better therapeutic index than the parent compound.

Adult↗

Simultaneous cis-platinum and radiotherapy in inoperable or locally advanced squamous cell carcinoma of the head and neck.

A synergism between cis-platinum (CDDP) and radiotherapy (RT) has been demonstrated both in culture systems and in clinical studies. On the above basis, we planned, in patients with locally advanced or unresectable squamous cell carcinoma of the head and neck, a concomitant treatment with CDDP 80 mg/m2 i.v. every 3 weeks for three doses (days 1, 21 and 42) and RT in the primary and in the neck nodes bilaterally, for a total dose of 60-70 Gy. Thirty-five untreated patients with poor prognosis unresectable stage II and stages III-IV disease were entered in the study and 32 were evaluable. Complete response (CR) rate was 75% (24/32) with 95% confidence limits from 60 to 90% (+/- 15%): 8 cases (25%) achieved a partial response, for an overall response rate of 100%. A significantly higher CR rate and a longer survival rate was observed in patients with good performance status (PS = 90-100) and stages II-III. The overall estimated 2-year survival is 46%; 59% for patients who obtained a CR versus 0% for those who achieved only a partial response. Overall the treatment was well tolerated and gastrointestinal and hematologic toxicities were the most common side effects. In conclusion, the combination of CDDP plus RT is a very effective and safe treatment and we recommend such an approach in head and neck squamous cell carcinoma, particularly in those patients with good PS and with unresectable stage II or stage III disease.

Carcinoma, Squamous Cell↗

Radiotherapeutic treatment for breast cancer choroidal metastases.

A series of 14 eyes (11 patients) with choroidal metastases from breast cancer were reported. The lesions were classified into three grades according to the severity and extent of involvement. Eleven eyes (9 patients) were treated by radiotherapy with two opposed lateral fields using a 4 MeV linear accelerator. The contralateral eye received a prophylactic irradiation. An average dose of 42 Gy was delivered (range, 30-50). Results of radiotherapy were the following: 5 CR and 2 PR in grade II (9 eyes) and 2 PR in grade III (2 eyes). We conclude that radiotherapy is useful to control choroidal metastases of breast cancer. No contralateral metachronous involvement was found. Quality of life of responders showed a marked improvement. Radiation-induced injury was not seen.

Breast Neoplasms↗

Combined radiosurgery and external radiotherapy of intracranial germinomas.

Germinomas are successfully treated with radiation therapy; we have observed six cases that have been stereotactically irradiated by means of a linear accelerator (radiosurgery). In most cases a single dose of stereotactic irradiation effects the reduction of the tumor volume in a few days. External whole brain and, in two cases, spinal irradiation completed the treatment to avoid seeding of tumor cells. The technique and the advantages of this original therapeutical approach to intracranial germinomas are described and discussed.

Adolescent↗

Linear accelerator radiosurgery of three-dimensional irregular targets.

Current radiosurgical techniques allow concentration of radiation from external sources into spherical targets. Nonspherical target volumes require a modification of the irradiation technique. Moreover, isodose shaping is sometimes necessary to spare nearby important radiosensitive structures. To meet these prerequisites we have introduced some technical refinements: (1) computer-controlled rectilinear translations of the target in combination with different angular positions of the source and (2) computer-controlled rotations of the target around a vertical axis in combination with different angular positions of the source. The first solution has proven efficient for treating irregular targets, while the second one was employed for focusing the radiation dose inside volumes obtained by rotation of ellipses.

Brain Neoplasms↗

Correlation of growth fraction by Ki-67 immunohistochemistry with histologic factors and hormone receptors in operable breast carcinoma.

Breast cancer tissue samples obtained from 147 Stage I and II patients were tested with the monoclonal antibody Ki-67 and avidin-biotin-peroxidase complex in frozen sections. The percentage of cells with nuclear staining ranged from 5% to 65%. The frequency of Ki-67 positivity was classified in five groups: 0% (45/147 = 31%); 5-9% (38/147 = 26%); 10-19% (15/147 = 10%); 20-39% (24/147 = 16%) and greater than or equal to 40% (25/147 = 17%). The mean value was 20%, median 18% with standard deviation of 14.5%. A significant positive correlation was observed between the presence of high Ki-67 nuclear staining rate with pathological tumor size (p = 0.003), histologic grading (p = 0.04), and axillary lymph node metastases (p = 0.009). An inverse significant correlation was found between Ki-67 and estrogen receptor expression (p less than 0.001). No correlation was observed with progesterone receptor expression or menopausal status. The overall picture is of an inverse relationship between high growth fraction determined with Ki-67 antibody and tumor differentiation parameters. These correlations confirm those already reported by thymidine labeling index and flow cytometry methods. The proliferative rate determined with Ki-67 antibody may provide information regarding cell kinetics of breast carcinoma, potentially useful in identifying patients with a different clinical course in order to improve the therapeutic approach, by a rapid, practical and easily performed immunohistochemical method.

Antibodies, Neoplasm↗

Low-grade astrocytomas: treatment with unconventionally fractionated external beam stereotactic radiation therapy.

Fourteen patients with nonoperable low-grade astrocytomas were treated with unconventionally fractionated stereotactic radiation therapy. The target volume was defined with computed tomography (CT) performed under stereotactic conditions. The treatment was carried out with a technique producing multiple noncoplanar arc irradiation, with the center of the target volume placed at the isocenter of the linear accelerator. A total dose of 16-50 Gy was administered in either one fraction or two fractions 8 days apart. The concentration of dose within the target volume allowed reduction of dose absorbed by adjacent critical structures of the intact brain. Patients were followed up for 11-48 months. Twelve of 14 patients had a partial or complete response to treatment, as demonstrated by CT. Stereotactic radiation therapy appears to be effective in the control of small radioresistant cerebral neoplasms, without damaging surrounding healthy tissues.

Adolescent↗

Linear accelerator radiosurgery of cerebral arteriovenous malformations.

A technique for linear accelerator radiosurgery has been used in clinical practice since 1982. The technique is based on multiple intersecting arc irradiations focused on a stereotactic target. From November 1984 to October 1988, 97 patients with cerebral arteriovenous malformations have been treated. Seventy-nine patients suffered one or more than one hemorrhage. Four patients had progressive neurological symptoms. In 14 patients, epilepsy was the principal complaint. Stereotactic localization was performed by stereotactic angiography. Lesion dimensions varied from 4 to 40 mm in diameter. Doses from 18.7 to 40 Gy were delivered in one or two sessions. Mean follow-up is 17.1 months (from 1 to 49). Four instances of minor rebleeding were observed after treatment; 3 patients complained of transient neurological deterioration. Of 56 patients who were followed longer than 1 year, 50 underwent 12-month follow-up angiography. In 26 patients complete obliteration of the malformation was demonstrated (52%), in 12 patients subtotal obliteration was obtained (24%), in 11 patients the obliteration was evident but not significant (22%), and in 1 patient the AVM was unchanged. Other angiographic features in incompletely obliterated cases were a significant reduction of flow velocity through the malformation together with a reduction in diameter of both feeding arteries and draining veins.

Adolescent↗

[Advanced stages of rectosigmoid cancer. The role of postoperative radiotherapy].

In patients with advanced rectosigmoid adenocarcinoma treated with radical surgery alone, loco-regional relapse rate is quite high (29%-60%). When postoperative radiotherapy is performed, loco-regional relapse rate sharply falls to 7%-15%. A series of 42 patients, stage B2, C1 and C2, is presented. All patients were treated with radical surgery and postoperative radiotherapy. Only two loco-regional relapses were found (5%). Overall actuarial survival at 5 years is 76% for B2, and 46% for C1 and C2. The authors conclude that adjuvant postoperative radiotherapy is useful in reducing loco-regional relapses, whereas survival seems to be improved only for stage B2 patients.

Adenocarcinoma↗

Dosimetric considerations on multiple arc stereotaxic radiotherapy.

The aim of this paper is to present the physical and dosimetrical features of the stereotaxic radiosurgical method already published by the authors. This method concentrates the dose into the stereotaxic target volume, placed at the isocenter of a 4 MV X-ray beam. Computer calculations showed that: 9-17 arcs provide almost spherical dose distributions; the optimal photon beam quality is about 4-6 MV. The angle between adjacent rotation planes is 20-40 degrees and the arcs are 100-160 degrees wide. In this way the dose to healthy tissue is minimized. The dose distribution was experimentally verified both by ionometric and photodensitometric methods. The procedure for dose calculation at isocenter of fields as small as required by the radiotherapist, has been investigated.

Calibration↗

[Small size breast cancer conservative surgical therapy and subsequent radiotherapy].

From february 1980 to december 1985, 115 breast carcinomas were treated with QU.A.RT. with limited surgery and following radiotherapy. Median age was 51 years (range 25 to 75). Surgical approach was quadrantectomy with axillary nodes dissection. Irradiation of residual breast was performed by an anterior high energy electron beam. 50 Gy in 25 fractions was the minimal dose to whole breast. In pN+ patients systemic adjuvant therapy was done. Local control was obtained in 111 cases. Local recurrence appeared in 4: 1 menopausal pT1 pNO and 3 premenopausal (1 pT1 pNO and 2 pT1 pN+) at respectively 31, 19, 22 months from diagnosis. Distant metastases appeared in 10 patients. 7 died for cancer and 3 are still alive. Cosmetic results were scored as good in 52, better than mastectomy in 26, unsatisfactory in 3, and not stated in 34. Our results are comparable to those of other Centers. Youth, axillary metastases and delay between surgery and radiotherapy appears to influence the risk of recurrence also in our series.

Adult↗

New technique for three-dimensional linear accelerator radiosurgery.

A new method for external stereotactic focal irradiation of three-dimensional irregular target volumes is proposed. In this method the target is irradiated by a linear accelerator set in various angular positions around the isocenter. During the irradiation the target is translated in a direction perpendicular to the beam. By controlling the velocity of the translation it is possible to modify the configuration of therapeutic isodoses so as to make them follow the borders of the target.

Brain Diseases↗

Linear accelerator radiosurgery of arteriovenous malformations.

Forty-five patients affected by cerebral arteriovenous malformations not suitable to open surgery have been treated by a radiosurgical technique employing a linear accelerator. One-year follow-up angiography is available for 10 cases. Therapeutic effect of focalized irradiation is presented.

Adolescent↗

Radiosurgery using a 4MV linear accelerator. Technique and radiobiologic implications.

In the authors' technique, the stereotactically localized target is fixed to the isocenter of a 4 MV linear accelerator. The irradiation is carried out along 9-17 non-coplanar arcs distributed on a 160 degrees cylindrical sector. High doses (10-50 Gy) are delivered in one or two sessions. From 1982, 65 patients have been treated (shortest follow-up 6 months). The dose was chosen according to the pathology and to the volume of the lesion. Good clinical results have been obtained in low-grade gliomas, acoustic neuromas, arteriovenous malformations, and other selected types of intracranial lesions. Therapeutic effects in terms of clinical condition and size of the lesions have been plotted in relation to time elapsed and dose employed.

Adolescent↗