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Biomedical subjects

G Silvano

Publications and source records attributed to G Silvano.

At least 19 recordsLinked to original sources
PubMed2006

New radiation techniques for treatment of locally advanced non-small cell lung cancer (NSCLC).

Local control is a main step to cure NSCLC because at least 30-40% of patients die for local or regional progression of their disease. Surgery is still the more efficient approach to increase survival but radiation therapy is the only treatment that can cure patients with T1-T2 lesions if they are not suitable for surgery or refuse it. However, doses higher than 60-66 Gy must be given to improve tumor control but doses to the organs at risk (OAR) are the main limit to deliver more than 70 Gy to the planning treatment volume (PTV). The optimal solution would be to 'paint' the dose to the PTV avoiding as possible OARs, but this ballistic precision was not possible till some years ago because of both technology and respiratory movement control. In last ten years many new techniques have been made available for treating NSCLC with radiation more accurately. Some techniques like Intensity Modulated Radiotherapy (IMRT), Image Guided Radiotherapy (IGRT), Stereotactic Radiotherapy can be carried out also with a traditional linear accelerator (LINAC) updated with the new software and hardware, using or not radiopaque markers inside the tumor. On the other hand, a new generation of machines like Cyberknife or Tomotherapy have been especially projected to optimize stereotactic technique and IMRT, respectively, and respiratory gating systems are now disposable from several manufactures.

Carcinoma, Non-Small-Cell Lung↗
PubMed2000

Combined Nd-YAG laser/HDR brachytherapy versus Nd-YAG laser only in malignant central airway involvement: a prospective randomized study.

BACKGROUND: Laser debulking and prosthetic stents are useful modalities in the palliative treatment of initial inoperable or recurrent lung cancer. Recently, endobrochial brachytherapy was introduced to extend the duration of palliation and reduce the number of endoscopic treatments. This trial compares Nd-YAG laser alone and associated to high dose rated (HDR)-brachytherapy. PATIENTS AND METHODS: From 1995 to 1998, 29 consecutive patients, with non-small cell lung cancer (NSCLC) and central airway involvement, were randomized in two groups: group 1 (15 patients) received Nd-YAG laser only; group 2 (14 patients) underwent a combined Nd-YAG laser/ HDR brachytherapy treatment. RESULTS: There was no mortality or morbidity related to the treatment. The period free from symptoms was 2.8 months for group 1 and increased to 8.5 months in group 2 (P<0.05). The disease's progression free period grew from 2.2 months of group 1 to 7.5 months of group 2 (P<0.05) and the number of further endoscopic treatment reduced from 15 to 3 (P<0.05). CONCLUSION: The results confirm the potential of brachytherapy to prolong relief from symptoms, lessen disease progression and reduce costs of treatment. A detailed analysis is presented of both groups.

Aged↗
PubMed2000

Erk-dependent cytosolic phospholipase A2 activity is induced by CD95 ligand cross-linking in the mouse derived Sertoli cell line TM4 and is required to trigger apoptosis in CD95 bearing cells.

In the present study we demonstrated that CD95L cross-linking generated reverse signalling in the mouse derived Sertoli cell line TM4. Treatment of TM4 cells with mAb anti-CD95L induced activation of the cytosolic phospholipase A2 (cPLA2). Cytosolic PLA2 activation was controlled by the MAPK pathway as indicated by the ability of the specific MEK inhibitor, PD098059, to abolish cPLA2 activation. In addition, Western blot experiments showed a rapid increase in phosphorylated Erk1/2 following CD95L cross-linking, while no effect on the phosphorylation of other MAPK, p38 or JNK, was observed. CD95L cross-linking by mAb increased the levels of soluble CD95L and apoptotic activity of TM4 cell supernatants, which was blocked by co-incubation with the PLA2 inhibitor, AACOCF3 or PD098059. Finally, pre-treatment of TM4 cells with AACOCF3 or PD098059 completely abolished TM4-induced apoptosis of Jurkat T cells, thus indicating that the Erk/cPLA2 pathway is required for CD95L-induced apoptosis.

Animals↗
PubMed2000

Fas and Fas ligand expression in fetal and adult human testis with normal or deranged spermatogenesis.

In mice, the Fas/Fas ligand (FasL) system has been shown to be involved in germ cell apoptosis. In the present study we evaluated the expression of Fas and Fas ligand (FasL) in fetal and adult human testis. Semiquantitative RT-PCR demonstrated the expression of Fas and FasL messenger ribonucleic acids in adult testis, but not in fetal testis (20-22 weeks gestation). In situ RT-PCR and immunohistochemistry experiments on adult human testis demonstrated the expression of FasL messenger ribonucleic acid and protein in Sertoli and Leydig cells, whereas the expression of Fas was confined to the Leydig cells and sporadic degenerating spermatocytes. The number of Fas-positive germ cells per 100 Sertoli cell nuclei was increased in 10 biopsies with postmeiotic germ cell arrest compared to 10 normal testis biopsies (mean, 3.82 +/- 0.45 vs. 2.02 +/- 0.29; P = 0.0001), but not in 10 biopsies with meiotic germ cell arrest (mean, 1.56 +/- 1.07). Fas and FasL proteins were not expressed in cases of idiopathic hypogonadotropic hypogonadism. Together, these findings may suggest that Fas/FasL expression in the human testis is developmentally regulated and under gonadotropin control. The increased germ cell expression of Fas in patients with postmeiotic germ cell arrest suggests that the Fas/FasL system may be involved in the quality control mechanism of the produced gametes.

Abortion, Therapeutic↗
PubMed2000

Sequential chemoradiation therapy with vinorelbine, ifosfamide, and cisplatin in stage IIIB non-small cell lung cancer: a phase II study.

Meta-analysis has demonstrated survival benefit for patients with stage IIIB non-small cell lung cancer treated with sequential chemoradiotherapy versus radiotherapy alone. The introduction of chemotherapy as part of a multimodality approach has improved the outcome in this poor prognostic subset of cancer patients. In the present phase II study we evaluated the safety and activity of a new cisplatin-based three-drug regimen consisting of vinorelbine/ifosfamide/cisplatin (VIP) followed by curative thoracic irradiation in 28 patients with stage IIIB non-small cell lung cancer. Patients received vinorelbine 25 mg/m2 on days 1 and 8, ifosfamide 3 g/m2 on day 1 (with mesna), and cisplatin 80 mg/m2 on day 1 every 3 weeks. After three courses of induction chemotherapy, patients with objective response or stable disease were eligible for thoracic radiotherapy. Twenty-six of the 28 patients received at least three courses of chemotherapy and were evaluable for response. The response rate to induction VIP was 58% (15 of 26 patients; one complete response and 14 partial responses). Seven patients had disease stabilization and four progressed during chemotherapy. Radiation treatment started from 4 to 6 weeks after the end of chemotherapy with standard fractionation (200 cGy/day, 5 fractions/wk/6 wk). Eighteen of 22 patients started thoracic irradiation; 14 completed the treatment plan, reaching the total dose of 60 Gy. The most relevant acute and late toxicities of radiotherapy were grade 3 dysphagia and pneumonitis in two patients and grade 3 lung fibrosis in six patients. By comparing the tumor volumes before and after radiation treatment we observed six clinical remissions, three stable diseases, and five local progressions. The first site of recurrence was local in 10 of 18 patients (56%), distant in seven patients (38.8%), and both local and distant in one patient. Median progression-free survival and overall survival for the patients treated with radiotherapy (18 patients) were 14 months (range, 4 to 36 months) and 26 months (range, 7 to 54+ months), respectively; the 1- and 2-year survival rates were 61% and 52%. Curative thoracic radiotherapy was well tolerated after VIP induction chemotherapy; it reduced residual tumor volume in six patients.

Adult↗
PubMed1998

In vivo neutron dosimetry during high-energy Bremsstrahlung radiotherapy.

PURPOSE: A new technique is presented for in vivo measurements of the dose equivalent from photoneutrons produced by high-energy radiotherapy accelerators. METHODS AND MATERIALS: The dosimeters used for this purpose are vials of superheated halocarbon droplets suspended in a tissue-equivalent gel. Neutron interactions nucleate the formation of bubbles, which can be recorded through the volume of gel they displace from the detector vials into graduated pipettes. These detectors offer inherent photon discrimination, dose-equivalent response to neutrons, passive operation, and small sensitive size. An in vivo vaginal probe was fabricated containing one of these neutron detector vials and a photon-sensitive diode. Measurements were carried out in patients undergoing high-energy x-ray radiotherapy and were also repeated in-phantom, under similar irradiation geometries. RESULTS AND CONCLUSION: Neutron doses of 0.02 Sv were measured in correspondence to the cervix, 50 cm from the photon beam axis, following a complete treatment course of 46.5 Gy with an upper mantle field of 18-MV x-rays. This fraction of dose from neutrons is measured reliably within an intense photon background, making the technique a valid solution to challenging dosimetry problems such as the determination of fetal exposure in radiotherapy. These measurements can be easily carried out with tissue-equivalent phantoms, as our results indicate an excellent correlation between in vivo and in-phantom dosimetry.

Aged↗
PubMed1996

Phase II study of vinorelbine/ifosfamide/cisplatin for the treatment of advanced non-small-cell lung cancer.

PURPOSE: To evaluate the combination of vinorelbine, ifosfamide and cisplatin (VIP) in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Seventy-six untreated patients with stages IIIB-IV NSCLC; the chemotherapy regimen consisted of vinorelbine (25 mg/sqm on days 1 and 8), ifosfamide (3 g/sqm on day 1 with uroprotective mesna), and cisplatin (80 mg/sqm on day 1). The cycles were administered on an outpatient basis every 3 weeks. RESULTS: Leukopenia was the most frequent toxicity: grades 3-4 neutropenia was observed in 26% of the cycles and 19 episodes of febrile neutropenia were reported in 289 evaluable courses. Filgrastim 5 micrograms/kg was administered in 27% of the courses. Sixty-seven of 76 patients were evaluable for response: the overall response rate was 51% (95% confidence interval 35%-77%) with 2 complete responses (3%) and 32 (48%) partial responses. No significant differences in response rate were observed according to histology or stage of disease. The median time to progression was 6 months (range 1 to 29+) and the median overall survival 10 months (range 1-33+). CONCLUSION: The combination of vinorelbine, ifosfamide and cisplatin in the dose and schedule employed in this trial shows an interesting response rate with acceptable toxicities. This regimen should be tested in the multimodality therapy of stage IIIA/B NSCLC.

Adult↗
PubMed1995

Pre-operative chemotherapy for stage IIIa (N2) non-small cell lung cancer.

From June 1990 to December 1993, 36 patients were enrolled in a phase II study, aimed at determining the feasibility of surgery, patterns of disease recurrence and survival after neoajuvant chemotherapy in non-small cell lung cancer (NSCLC) stage IIIA-N2. Twenty-seven patients underwent invasive staging procedures (i.e. mediastinoscopy or needle biopsy). Two CHT schedules were used. Cisplatin (P) 90 mg/mq, day 1, mitomycin (M) 6 mg/mq, day 1, and vindesine (V) 5 mg/mq, days 1, 8, 15, were administered every 3 weeks for 3 cycles in the first 20 patients. The last 16 patients were treated with cisplatin (P) 90 mg/mq, day 1, mitomycin (M) 6 mg/mq, day 1, and vinorelbina 20 mg/mq, days 1, 8, 15. Thoracotomy was performed 15-20 days after haematological recovery in the objective-responders. Thirty-two patients were evaluable for response to CHT. The overall objective response (OR) rate was 78.1%. There were three complete (CR) (9.4%) and 22 partial responses (PR) (68.7%). The 25 patients with OR underwent radical surgery (16 pneumonectomies, one bilobectomy, seven lobectomies and one wedge resection). The only morbidity reported was a late broncho-pleural fistula (on post-operative day 37). There were three post-operative deaths in patients who underwent pneumonectomy: two due to an empyema following a broncho-pleural in fistula and one by pulmonary embolism. Histology was negative for the three CRs. Six patients with residual nodal involvement at surgery underwent radiotherapy. Relapse occurred in seven resected patients. Presently 14 patients are alive, all but one being disease-free, with a median follow-up of 30.5 months (15-47). Median survival was 31 months (5-47). Actuarial 3-year survival rate is 49%. Our results confirm the high response rate of CHT, as well as the feasibility and the overall low complication rate of both treatments (CHT and surgery).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Risk of thyroid nodules in subjects occupationally exposed to radiation: a cross sectional study.

OBJECTIVES: To examine, by ultrasonography the prevalence of thyroid nodules in a cross sectional study of male medical workers occupationally exposed to chi radiation at the Pisa hospital, in comparison with controls matched for age and sex. METHODS: 50 male medical workers exposed to radiation were randomly matched for age (+/- 2 years) with 100 male workers not occupationally exposed to ionising radiation who lived in a slightly iodine deficient area of Tuscany (Lunigiana) (control group 1), and with 100 male workers not exposed to radiation who lived in the same area (Pisa) (control group 2). RESULTS: Of the occupationally exposed subjects, thyroid nodules were detected in 19/50 (38.0%). Among controls, thyroid nodules were detected in 19/100 subjects of control group 1 and in 13/100 of control group 2. Comparison of exposed and control groups, stratified into 30-39, 40-49, and 50-59 year old age subgroups, showed a higher significant relative risk for thyroid nodules in the exposed subjects. CONCLUSION: The results suggest that occupational exposure to radiation may be a risk factor for thyroid nodules.

Adult↗
PubMed1995

[The role of adjuvant therapy in the management of pN2 non-small-cell carcinoma of the lung].

Over a period of eleven years (1983-1993), the role of adjuvant chemo and/or radiotherapy was evaluated on 222 resected patients (pts) with NSCLC at atage IIIA(N2). All the patients underwent an attentive mediastinal limphoadenectomy. Fifty-five patients had a clinical mediastinal node involvement. 174 pts had a single mediastinal node station involved while 48 had two or more stations involved. One hundred and seventy-one pts (77%) underwent adjuvant therapies, consisting of citotoxic chemotherapy in 40 pts, radioterhapy in 97 pts and chemoradioterhapy in 34 pts. Follow-up lasted until September 1994. Overall 5-yr survival was 17.5%, the median being 17 months. Forty-two pts were, at that moment, still living (median 43.5 months, min 11-max 120) with 37 disease free. We verified a significant difference concerning survival among the three histologic types (p = 0.03), with the squamous achieving the best result (21.3% at 5-yrs). Surgical N2 had a better survival (20/5% at 5-yrs) than the clinical one (9%), (p = 0.01). In particular, if only one nodal station was involved, survival was 21.3% compared to 4.5% when metastases were present at two or more nodal station (p = 0.0001). Considering the level of mediastinal node involvement, the worst prognosis was linked to the carina node metastases (p = 0.02). Survival benefits were obtained by means of adjuvant therapies (20/2% vs 8.1%), (p = 0.0002). Analyzing all the pts, the best survival was achieved in those treated by surgery plus chemo-radiotherapy (32.4%), (p = 0.0001). As regards the squamous cell tumors, pts who underwent surgery plus radiotherapy had the best prognosis (24.2%), (p = 0.0026). Further, in non-squamous cell tumor, chemo-radiotherapy increased survival (45%), (p = 0.0001). At multivariate analysis, only the level of nodal involvement and the adjuvant therapy maintained their statistical significance. Our results prompt us to conclude that: 1) Squamous cell tumors and single nodal station involvement are linked to the best prognosis; 2) Squamous cell carcinoma should be treated by adjuvant radiotherapy; 3) Non-squamous tumors should undergo to chemo-radiotherapy; 4) Clinical N2 (according to our recent experience) may benefit from neoadjuvant chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Combination chemotherapy with vinorelbine, ifosfamide, and cisplatin: a phase II study in stage IIIB-IV non-small cell lung cancer.

Forty-five stage IIIB-IV non-small cell lung cancer (NSCLC) patients entered a phase II study designed to evaluate the toxicity and the activity of a combination chemotherapy regimen consisting of vinorelbine (25 mg/m2 days 1 and 8), ifosfamide (3 g/m2 day 1 with uroprotective mesna), and cisplatin (80 mg/m2 day 1). The regimen, VIP, was administered on an outpatient basis every 3 weeks. White blood cell counts were checked weekly, and granulocyte colony-stimulating factor was administered in case of grade 4 neutropenia lasting for more than 48 hours. Leukopenia was the most frequent toxicity, with grades 3 and 4 neutropenia reported in 25% of cycles and 11 episodes of febrile neutropenia recorded in 175 evaluable courses. The combination of vinorelbine and cisplatin did not result in additive neurotoxicity: only five patients experienced grade 2 neurotoxicity after six courses of treatment. Thirty-five patients were evaluable for response. Twenty partial responses (57%) and one complete response (2.8%) were observed, for an overall response rate of 60% (95% confidence interval, 42% to 76%). The median time to progression, measured from the start of treatment, was 7 months (range, 1 to 18+), and median survival for the whole group was 12 months (range, 1 to 18+). VIP is a well-tolerated regimen and shows interesting activity in advanced NSCLC.

Adult↗
PubMed1991

Results of treatment and lessons learned from pathologically staged T4 non-small cell lung cancer.

Depending on the local extension of primary non-small cell lung cancer (NSCLC) and invaded T4 structure(s), 49 patients underwent complete (CR, n = 14) or palliative (PR, n = 13) resection of exploratory thoracotomy (ET, n = 22) between January 1982 and June 1988. Thoracic radiotherapy (TR) was given to all patients receiving PR (median dose, 43 Gy) and ET (median dose, 53 Gy). With a median follow-up of 44 months, overall 2- and 5-year survival was 25 and 5%, respectively. Patients undergoing ET plus TR had a significantly worse survival than those treated by CR (P = 0.041) and PR plus TR (P = 0.046). Only completely resected patients became long-term survivors (5-year survival, 29%) and significant predictors of their survival were previous weight loss, hemoglobin, and creatinine level, in univariate analysis, and previous weight loss in multivariate analysis. The site of initial treatment failure was mainly local for PR plus TR (85%) and systemic for CR (71%) and ET plus TR (86%). Presented results suggest that surgery might play a role for selected patients with T4 NSCLC, but advances in systemic and local therapy are necessary.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Phase II feasibility study of high dose epirubicin-based regimens for untreated patients with small-cell lung cancer.

17 previously untreated patients with small cell lung cancer entered a phase II study testing the feasibility of incorporating high dose epirubicin (110 mg/m2, day 1) in combination regimens, including cyclophosphamide (1 g/m2, day 1), and etoposide (120 mg/m2, day 1) (courses 1, 3, 5) or cisplatin (60 mg/m2, day 1) and etoposide (120 mg/m2, days 1-4) (courses 2, 4, 6), every 3 weeks. Complete responders with limited or extensive disease received thoracic (40 Gy) and prophylactic cranial (30 Gy) irradiation. All patients were evaluable for toxicity and response. Myelosuppression and stomatitis were the dose-limiting side-effects. Maximum myelosuppression occurred as granulocytopenia and anemia, but a recovery by day 21 was observed in the majority of courses. Neutropenic fever occurred in 47 of 99 courses. Severe stomatitis was experienced in 25 courses and lasted generally 7-12 days. Acute cardiac toxicity was uncommon and represented by mild to moderate rhythm abnormalities. No change was noted in the mean QRS voltage on electrocardiogram (ECG) and no patient had a decline of greater than or equal to 20% in the cardiac ejection fraction and/or episode of overt heart failure at any stage of treatment. The overall objective response rate was 88%, with six (35%) complete and nine (53%) partial responses. With a median follow-up of 16 months, overall median survival was 13 months (range, 2-18+). This study demonstrates that epirubicin, at the present dose and schedule, is feasible in combination regimens and that cardiotoxicity is not dose-limiting and induced or enhanced by thoracic irradiation and/or cyclophosphamide.

Adult↗