Francesco Ducci

Neoadjuvant chemotherapy, surgery, and postoperative radiation therapy for invasive thymoma

Between January 1988 and June 1990, seven previously untreated patients with histologically confirmed and clinically staged IIIa invasive thymoma (IT) were enrolled in a prospective, single treatment arm study of neoadjuvant chemotherapy (NC) followed by surgery and postoperative radiation therapy (4600 to 6000 cGy). The NC included three cycles of cisplatin (75 mg/m2 on day 1), epirubicin (100 mg/ m2 on day 1), and etoposide (120 mg/m2 on days 1, 3, and 5), every 3 weeks. All patients showed a partial response (>50%) and underwent complete (n = 4) or incomplete (gross [n = 1] or microscopic [n = 2] residual tumor) surgical resection. Histologic examination was negative for two completely resected patients. Projected 2‐year survival was 80%; all patients but one currently are alive and disease‐free. This approach appeared to be feasible and may be a new therapeutic choice in the management of IT, but its use on a regular basis should be reserved until a larger number of patients and longer follow‐up are available.

Maxillary sinus augmentation with platelet-rich plasma and fibrinogen cryoprecipitate: a tomographic pilot study.

The purpose of this study was to evaluate the clinical efficacy of platelet-rich plasma, autologous bone, and autologous fibrinogen as cryoprecipitate in maxillary sinus augmentation procedures. Six patients (age range, 29–58) undergoing sinus augmentation procedures were included in the study. Platelet-rich plasma and autologous fibrinogen in the form of cryoprecipitate were prepared from 300 ml of blood. Sinus augmentation was performed with intraoral bone grafts, platelet-rich plasma, and cryoprecipitate. The amount of regeneration was then evaluated quantitatively and qualitatively with Spiral TC (Dentascan) pre- and postoperatively 6 months after the intervention. Orthopantomography was performed preoperatively 3 and 6 monthsafter the surgery. A mean platelet concentration of 320.5% was obtained from the baseline platelet blood count. The tomographic analysis indicated an average bone augmentation of 6.27 mm (range, 3.5–10 mm). Radiologically, a satisfactory morphological recovery of the maxillary jaw was obtained. No graft resorption was noticed. Orthopantomography indicated mineralization as early as 3 months postoperatively in the entire study population. This technique appeared to be safe and effective. Our preliminary results encourage the clinical use of platelet-rich plasma associated with cryoprecipitate.

Carbogen and nicotinamide combined with unconventional radiotherapy in glioblastoma multiforme: a new modality treatment.

PURPOSE A new radiotherapy schedule to treat glioblastoma multiforme after surgery, combining nicotinamide and carbogen. METHODS AND MATERIALS We analyzed 36 patients with glioblastoma multiforme treated after surgery with radiotherapy, Nicotinamide and Carbogen as follows: 7 patients were treated with accelerated fractionation: two fractions/day, 1.5 cGy/fraction, 6 h interval, 5 days/week, total dose 60 Gy in 4 weeks; 8 patients were treated with the same irradiation scheduling plus Nicotinamide at the dose of 4 g and 2 g in capsules, respectively, 1 h before the first and the second irradiation fraction; 21 patients were treated with accelerated radiotherapy, Nicotinamide, and Carbogen (inhaled 10 min before radiotherapy and during the whole course of irradiation). On the basis of surgical removal our patients were subdivided in three groups: totally resected, with residual tumor <50%, or >50%. Radiotherapy with accelerated fractionation was completed in the scheduled time without side effects on the whole group of patients and Carbogen inhalation did not cause significant change of cardiopulmonar parameters. The toxicity observed was predominant in the gastrointestinal tract and was related to Nicotinamide. RESULTS The median survival time (M.S.T.) was 10 months, as reported by others authors with conventional treatment, but in patients without surgical residual tumor and submitted to the complete treatment schedule, the survival at 35 months was around 25%. CONCLUSIONS We conclude that this method is feasible with acceptable toxicity; analyzing the survival curves appears to be a trend towards an improvement in survival in the subgroup of patients with gross total removal treated with the combination of Carbogen, Nicotinamide, and accelerated fractionation.

Carbogen Breathing in Patients with Glioblastoma Multiforme Submitted to Radiotherapy Assessment of gas Exchange Parameters

It has been reported that carbogen breathing yields a remarkable increase of radiosensitivity in murine tumour models. Hence, application of carbogen might be promising in radiotherapy of human tumours. We describe a method to increase arterial oxygenation and to ensure stability of O2 and CO2 during carbogen breathing in patients with malignant disease. We measured in 6 patients with histologically proven intracranial glioblastoma multiforme arterial blood gases, inspired and expired gas concentrations and vital signs either baseline and during carbogen breathing. The highest values of arterial oxygenation were achieved after 10 min of carbogen breathing and they remained stable up to 15 min. In none of our patients was N2 wash-out from the lungs completed in 15 min of carbogen breathing. In conclusion, carbogen breathing increased arterial oxygenation in patients with intracranial malignant diseases. The system used is reliable and of practical use. Monitoring of expired gas concentrations is highly recommended.

Does enamel matrix derivative application provide additional clinical benefits in residual periodontal pockets associated with suprabony defects? A systematic review and meta‐analysis of randomized clinical trials

OBJECTIVE To review the effectiveness of enamel matrix derivative (EMD) in the treatment of periodontal pockets of suprabony defects. METHODS Randomized Clinical Trials comparing open flap debridement (OFD) versus EMD in periodontal suprabony defects were identified through electronic and manual search. Screening, data extraction and quality assessment were conducted. The primary outcome measures were tooth survival (TS) and clinical attachment level (CAL) gain. Pocket probing depth (PPD) reduction and recession (REC) increase were secondary outcome measures. Information concerning clinical and radiological bone gain was also collected. RESULTS The search identified 1170 studies, three articles reporting on (99 subjects/358 teeth) met the inclusion criteria and were included. No tooth was lost during follow-up (8-12 months). The adjunctive mean benefit of EMD was: 1.2 mm for CAL gain [confidence interval (CI): (0.9, 1.4), p < 0.00001, I(2) = 66%], 1.2 mm for the PPD reduction (CI: [0.8, 1.5], p < 0.0001, I(2) = 0%), -0.5 mm for the REC increase (CI: [-0.8, -0.2], p = 0.003, I(2) = 0%). Potential risk of bias was identified. CONCLUSIONS No differences were noted in TS but EMD application resulted in clinical and radiographic additional benefits compared to OFD alone. Nevertheless, the paucity of data, the risk of methodological and potential publication bias suggests caution in interpreting these results while supporting multicenter studies for this specific application.

Pharmacokinetics and Tolerance of Nicotinamide Combined with Radiation Therapy in Patients with Glioblastoma Multiforme

The pharmacokinetic properties of nicotinamide and its tolerance were studied in seven patients affected by glioblastoma multiforme and treated with two fractions per day of radiation therapy. Nicotinamide was given orally at two daily doses of 4 g and then 2 g separated by a 6-h-interval. The treatment was well tolerated in almost all patients and had no effect on blood pressure, cardiac rhythm or body temperature. Pharmacokinetic analysis showed peak plasma levels (Cmax) above 100 mg/l 45 minutes after the administration of both doses. This was followed by a biexponential decay of plasma concentrations with a thermal half life of 9.4h. Tumours were irradiated 1 hour after each drug dose to match with drug Cmax in plasma, and although it is too early to evaluate the tumour response, the drug levels achieved should be sufficient to improve radiation therapy.

Postoperative adjuvant chemoradiotherapy for rectal cancer: analysis of acute and chronic toxicity.

Aims and background The aim of the study was to evaluate acute and chronic toxicity of combined postoperative standard radiation therapy to the pelvis and 5-fluorouracil plus levamisole in resectable rectal cancer. Methods Between July 1990 and September 1993, 58 patients with histologically confirmed adenocarcinoma of the rectum entered the prospective study. The schedule consisted of 5-fluorouracil, 450 mg/m2 i.v. for 5 days, and from day 28 5-fluorouracil, 450 mg/m2 i.v. weekly for 24 weeks, plus levamisole given orally at the dose of 150 mg every day for 3 days every 2 weeks for 6 months; radiotherapy (180 cGy/day) 5 days a week for a total dose of 45 Gy was administered from day 28. Results After the first cycle of chemotherapy (before radiotherapy), overall toxicity was mild. During chemoradiotherapy, dose-limiting toxicity was grade 3 diarrhea and proctitis, for which the combined treatment was interrupted for more than 7 cumulative days in 28 patients. During the 24 weeks of weekly 5-fluorouracil (after radiotherapy), no severe toxicity was reported. Three-year survival and progression-free survival were 65% and 50–55%, respectively. Conclusions Although adjuvant chemoradiotherapy is usually feasible, in our study toxicity was severe in a substantial proportion of patients, probably due to the schedule applied. We are evaluating the feasibility and toxicity of a combined treatment which includes 5-fluorouracil in continuous chronomodulated infusion during radiotherapy.

Neo-Adjuvant chemotherapy for invasive thymoma: an interim analysis

The therapeutic indexes of surgery and/or radiotherapy for invasive thymoma (IT) are often limited by either local involvement of unresectable structure (s) or tumor dissemination outside the radiation fields. An important step forward has been systemic chemotherapy, the efficacy of which has been demonstratedeither as first-line or as adjuvant therapy [1, 2].