Experimental validation of the filtering approach for dose monitoring in proton therapy at low energy.

The higher physical selectivity of proton therapy demands higher accuracy in monitoring of the delivered dose, especially when the target volume is located next to critical organs and a fractionated therapy is applied. A method to verify a treatment plan and to ensure the high quality of the hadrontherapy is to use Positron Emission Tomography (PET), which takes advantage of the nuclear reactions between protons and nuclei in the tissue during irradiation producing beta(+)-emitting isotopes. Unfortunately, the PET image is not directly proportional to the delivered radiation dose distribution; this is the reason why, at the present time, the verification of depth dose profiles with PET techniques is limited to a comparison between the measured activity and the one predicted for the planned treatment by a Monte Carlo model. In this paper we test the feasibility of a different scheme, which permits to reconstruct the expected PET signal from the planned radiation dose distribution along beam direction in a simpler and more direct way. The considered filter model, based on the description of the PET image as a convolution of the dose distribution with a filter function, has already demonstrated its potential applicability to beam energies above 70 MeV. Our experimental investigation provides support to the possibility of extending the same approach to the lower energy range ([40, 70] MeV), in the perspective of its clinical application in eye proton therapy.

High-dose chemotherapy combined with escalating doses of cyclosporin A and an autologous bone marrow transplant for the treatment of drug-resistant solid tumors: a phase I clinical trial.

High response rates are seen in patients undergoing dose-intensive chemotherapy and autologous marrow transplantation due to the ability of the therapy to overcome inherent or acquired drug resistance. However, relapse rates are also high because this drug resistance reversal is incomplete. Because both P-glycoprotein- and platinum-induced resistance appear to be clinically important and can be reversed in vitro with a short exposure of cyclosporin A (CSA) at 2000 and 5000 ng/ml, respectively, we undertook a trial of high-dose chemotherapy with carboplatin (1500mg/m2), mitoxantrone (75 mg/m2), and cyclophosphamide (120 mg/kg) over a 5-day period combined with escalating doses of CSA. Thirty-seven patients with primarily breast cancer (61% doxorubicin resistant) and ovarian cancer (85% platinum resistant) were treated with CSA given as a bolus 18 h prior to chemotherapy, followed by a 5-day infusion at doses of 5.0-28.2 mg/kg/day and the chemotherapy. The maximum tolerated dose of CSA was a bolus of 5.5 mg/kg and an infusion of 15. 9 mg/kg/day, which gave a mean serum CSA level of 1544 ng/ml. The dose-limiting toxicity was severe mucositis and enteritis, leading to infectious complications. Nephrotoxicity was seen in 42% and, while usually mild and reversible, was fatal in two patients with pretreatment creatinine clearances h80 ml/min. Grade III-IV isolated hyperbilirubinemia was seen in 39%, but appeared to be of no clinical significance. The overall response rate for the 26 patients with measurable/evaluable disease was 73% and 63% for those with doxorubicin- or platinum-resistant disease. The median overall survival and progression-free survival for the group were 18.1 and 8. 0 months. The overall survival for the nine patients with doxorubicin-resistant breast cancer was 19.3 months. Although we did not achieve CSA levels needed to reverse platinum resistance in vivo, levels approaching those needed to reverse P-glycoprotein resistance were reached at the maximum tolerated dose. The strategy of combining dose intensity with drug resistance reversal deserves further study, especially with the advent of potentially less toxic agents available to reverse P-glycoprotein-mediated resistance.

Dysontogenetic neoplasms of the thyroid gland in infancy: two case reports.

Two rare cases of benign dysontogenetic neoplasms of the thyroid gland in pediatric age are presented, which were observed at the E.N.T. department of the Bambino Gesù Hospital of Rome, and successfully operated. The first case turned out to be a dysembryoma, classified as monodermic because of its origin from derivatives of only one germinal layer, the entoderm. The second case, a teratoma, presented a high seric concentration of AFP as the consequence of the synthetic activity of the share of embryonal epatic tissue present in the neoformation. Criteria to distinguish thyroid from cervical teratomata and to classify the different types of dysontogenetic neoplasms are discussed. The usual clinical and pathological manifestations of teratomas of the neck in infancy are mentioned. The necessity of a prompt surgical removal and of pre- and postoperative thyroid function studies is mentioned.

[The therapy of peripheral obstructive arteriopathies: rational bases]. / Terapie delle arteriopatie ostruttive periferiche: basi razionali.

The authors underline the relations among the anatomical lesion progression, the appearance of the clinical signs (claudicatio) of tissue ischaemia and the thromboembolic event in vascular districts like myocardium and brain, at high morbidity and mortality risk. They widely state the pathogenetic mechanism of the atherosclerotic arterial disease and the compensative mechanisms that may prevent the ischaemic effects of the vascular obstruction. It has been considered the importance of the hemorheologic changes and their influence on the development of the ischaemic syndrome. The therapeutic choice in relation to physiopathologic and hemorheologic events in the peripheral obstructive arterial disease is considered.

A phase II trial of high-dose mitoxantrone, carboplatin, and cyclophosphamide with autologous bone marrow rescue for recurrent epithelial ovarian carcinoma: analysis of risk factors for clinical outcome.

Despite high initial response rates to platinum-based chemotherapy, most patients with advanced ovarian carcinoma die of drug-resistant disease. Drug resistance can be overcome in the hematologic malignancies and lymphomas with high-dose therapy and bone marrow transplantation (BMT) when used early, suggesting that this therapy may also be of value in ovarian carcinoma. As a prelude to the use of high-dose chemotherapy with BMT early in the management of advanced ovarian carcinoma, we evaluated a new high-dose regimen in patients with relapsed/refractory ovarian carcinoma to define toxicities and responses. Thirty patients were treated, of whom 20 were platinum resistant and 22 had > 1 cm maximum diameter disease. They received mitoxantrone (75 mg/m2), carboplatin (1500 mg/m2), and cyclophosphamide (120 mg/kg), followed by an autologous BMT. Overall, 89% responded, with clinical complete responses seen in 88 vs 47% (P = 0.06) of platinum-sensitive vs -resistant disease. There was only one early death (3.3%) due to Aspergillus pneumonia. Median survival for all 30 patients was 29 months, and at 3 years 23% are alive without disease. There was a 10.1- vs 5.1-month progression-free survival for patients with platinum-sensitive versus -resistant disease, and at a median follow-up of 12 months, 80% of the platinum-sensitive patients are alive. This regimen is safe, and for platinum-sensitive disease appears superior to other salvage therapies. Its use should be explored earlier in the management of advanced ovarian carcinoma.