Franco Pozza

External Stereotactic Irradiation by Linear Accelerator

Stereotactic radiotherapy has two advantages: (a) the possibility of giving high radiation doses to small but spatially well-defined target volumes and (b) the presence of a stepped dose gradient between the target volume and the surrounding healthy tissues. To utilize these advantages, the authors built a new stereotactic head frame by which the intracranial target is fixed to the rotational isocenter of a 4-MV linear accelerator. The collimator openings are selected according to the volume and the three-dimensional configuration of the target, and the radiation dose is based on the radiosensitivity of the lesion. After the patient is fixed to the frame, the radiation source and the patient are rotated so that the target is irradiated through infinite portals distributed over the convexity of the skull. It is thereby possible to obtain very high radiation doses centered into the target with a stepped dose gradient. The preliminary radiodosimetric tests and the operative technique are described. The advantages of this technique compared to interstitial radiotherapy and Leksells radiosurgery are emphasized. This noninvasive procedure has been used to treat a series of intracranial tumors.

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.

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 anthracy-clines 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 < 0.05 for Epi and six of seven (86%) compared with two of 15 (13%); p < 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.

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.

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.

A multiparametric study on the prognostic value of epidermal growth factor receptor in operable breast carcinoma

SummaryEpidermal growth factor receptor (EGFR) is a potentially useful new biological prognostic and predictive indicator in human breast cancer. Additional research on EGFR is warranted to enhance our information on: i) the method of choice for its detection and quality control issues; ii) its association with novel pathobiological markers of prognosis; iii) its prognostic value in multivariate analysis; and iv) its capability to predict response to hormone therapy and, in the future, to biological treatments using antibodies against the specific receptor or its ligands.In the present study we update previous data on EGFR status, determined immunocytochemically, by prolonging the period of observation up to 5 years and by including, in the multivariate analysis, several new biological indicators. The main results obtained are: i) EGFR is weakly associated with Ki-67 score (p=0.073) and with p53 expression (p=0.06); ii) EGFR is a significant indicator for recurrence (p<0.01 and odds ratio of 2.82) but not for death (p=0.27 and odds ratio of 1.49); iii) the prognostic power of EGFR is enhanced when combined with the knowledge of S-phase fraction; and iv) in multivariate analysis on relapse-free survival, EGFR and S-phase fraction (likelihood ratio test=26.40; p<0.01), c-erbB-2 protein and p53 mutant protein expression (likelihood ratio test= 5.94; p=0.05), cathepsin D (likelihood ratio test= 9.78; p<0.01), and nodal status (likelihood ratio test= 7.32; p<0.01) are significant and independent prognostic factors in early-stage breast carcinoma.This new information could be of help for a more rational approach in the use of EGFR as a marker in future clinical research.

Linear Accelerator Radiosurgery of Cerebral Arteriovenous Malformations: Current Status

228 patients affected by cerebral arteriovenous malformations (AVMs) underwent linear accelerator radiosurgery. Follow-up ranges from 1 to 100 months (mean 42 months). Complete angiographic obliteration was achieved in 47% of treated patients at one year and 80% at 2 years. 17 haemorrhages were observed after treatment and 6 patients died from them. No bleeding took place after complete angiographic obliteration. 11 patients suffered for radionecrosis. In 6 patients complete recovery was obtained with corticoid medication. The aim of this study is to present our results and to evaluate the effect of irradiation on the risk of bleeding after radiosurgery. Patients were considered at risk in the time lapse after irradiation and before angiographic obliteration or other definitive treatment or death. Patients were followed from the date of radiosurgery and the number of haemorrhages were recorded every six months. In our series the bleeding risk in patients harbouring incompletely obliterated AVMs decreases from 8% in the first year after radiosurgery to 0% starting from the 24th month of the follow-up.

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.

Osteogenic Osteosarcoma of the Calvaria following Radiotherapy for Cerebellar Astrocytoma: Report of a Case in Childhood

Sarcoma as a second malignant neoplasm following radiotherapy is a rare occurrence in childhood. A case of osteogenic osteosarcoma of temporoparietal bone that developed 56 months after irradiation for a cerebellar astrocytoma in a 10-year-old child is reported and the pertinent literature is briefly reviewed. The possibility of an association (in the same patient) between these two rather uncommon lesions is extremely unlikely. Therefore, it is possible that radiotherapy played a role in the induction of the sarcoma. The indolent course of the latter is stressed.

Peritumoral lymphatic vessel invasion compared with DNA ploidy, proliferative activity, and other pathologic features as prognostic indicators in operable breast cancer

SummaryIn 164 breast carcinomas the presence of peritumoral lymphatic vessel invasion (PLVI) was evaluated and correlated with other known indicators of prognosis and with the clinical outcome of the patients. Overall 22% of tumors were PLVI-positive. The presence of PLVI was significantly associated with axillary node involvement (p<0.0001) and tumor size (p=0.005), and tended toward an association with grading (p=0.065). No significant association was found between PLVI and steroid hormone receptors, DNA ploidy, or proliferative activity. Univariate analysis shows that peritumoral vessel invasion was significantly associated with a higher risk of recurrence (p=0.012) and with a trend toward shorter survival (p=0.074). Besides the presence of PLVI, prognosis was significantly worse also for patients with high proliferative aneuploid tumors and with axillary node metastases. Moreover, within the subsets of patients generally considered to have good prognosis, the presence of PLVI identified patients with a trend for higher risk such as those with PLVI-positive diploid tumors, PLVI-positive low-proliferative tumors, and PLVI-positive node-negative tumors. Adopting multivariate analysis, PLVI failed to retain prognostic importance when adjusted for node status, DNA ploidy, and proliferative activity.In conclusion, we found that the presence of PLVI has prognostic significance when singly evaluated. Multivariate analysis shows that PLVI is not an independent prognostic factor in stage I–II breast cancer.