Radiation Oncology Unit San Giuseppe Moscati Hospital Via per Martina Franca Taranto - Italy
gisilva@tin.it
Dr Giovanni Silvano was born on April 28th, 1952 in Lucca, Italy. Graduated in Medicine with maximum grades from the University of Pisa in 1978 completed his residency in Radiology at the University of Pisa in 1982 with maximum grades and honours. Completed residency in Oncology at the University of Modena in 1989. National pass certificate qualifying him for the position of department chief in 1992 with maximum grades.
Registrar at the Radiotherapy Department, S. Chiara Hospital, in Pisa from March 1982 to December 1993 when he assumed the position of Senior Registrar, responsible for the Oncology Informatic Section. He moved to “Azienda Ospedaliera SS. Annunziata” in Taranto on November 2000 as chief of the Radiation Therapy Unit where he still works.
Lecturer at the University of Pisa: School of Specialisation in Radiology since 1988 and School of Specialisation in Industrial Medicine since 1982 till 1997. He has been teaching “Thoracic Radiotherapy” in the Clinical Oncology course at the University of Pisa from 1992 to 2000. Lecturer at the University of Bari, School of Specialisation in Radiation Oncology since 2001 till now.
In 1985 he was registered in the National Board of Authorised Physicians for medical surveillance of workers exposed to radiation and since 1986 to the end of 2000 he has been active in that role for the workers in Pisa Hospital.
He was the local head of a FONICAP (Italian Operative Force Against Lung Cancer) multicenter national study on radiotherapy of lung tumours. He was the national head of the Radiation Therapy Commitee for the ALPI (Adjuvant Lung Project Italy) multicenter study. He was in the scientific board of two randomised multicenter national studies on NSCLC. The first one on surgery plus adjuvant chemotherapy and radiotherapy (ALPI); the second on neoadjuvant chemotherapy plus radiotherapy alone or with concomitant chemotherapy (PITCAP). He was the scientific co-ordinator of SIROIS (An Integrated System of Radiation Oncology in the Ionico-Salentina Area).
He is author of more than 200 articles and abstracts published on Italian and international papers. He participated as speaker to more than 100 national and international conferences and courses. His interests lie prevalently in the fields of lung and rectum radiation therapy and radio-chemotherapy, brain, breast, and prostate tumours radiotherapy, organisation and management of oncological data bases; radiosensitizers, radiopathology and radiation protection.
He is member of ASTRO, ESTRO, IASLC, AIRO (Italian Society of Radiation Therapy), FONICAP (Italian National Force against Lung Cancer), AINO (Italian Association for neuro-Oncology. He is in the Directive Board of FONICAP and has been the coordinator of AIRO Working Group on Lung and Mediastinic cancers .
Abstract: The present study aims to assess the feasibility and the effectiveness of a second-line Fotemustine chemotherapy in patients with recurrent Glioblastoma after standard primary treatment. Between 2005 and 2007, 50 patients with relapsed malignant glioma (median age=56.8 years; median KPS=90) underwent a second-line chemotherapy with Fotemustine. Selected patients were previously treated with a standard 60 Gy Radiotherapy course and Temozolomide Chemotherapy. Patients were stratified into classes according to the prognostic Recursive Partition Analysis. Endpoints of the study were Progression Free Survival at 6 months, duration of Objective Response and Stabilization, Overall Survival and toxicity. At analysis, 36 patients were dead and 14 were alive. Median follow-up from primary diagnosis was 26.6 months. The Efficacy control of the disease was 62%. PFS was 6.1 months; PFS-6 was 52% and median overall survival from primary diagnosis was 24.5 months, with few manageable haematological toxicities. Fotemustine was safe and effective as second-line chemotherapy in recurrent glioblastoma.
Abstract: BACKGROUND AND PURPOSE: In a previous randomized trial we showed that the short-course radiotherapy (RT) regimen of 8 Gy x 2 was feasible in patients with metastatic spinal cord compression (MSCC) and short life expectancy. This phase III trial was planned to determine whether in the same category of patients 8 Gy single-dose is as effective as 8 Gy x 2. MATERIALS AND METHODS: Three hundred and twenty-seven patients with MSCC and short life expectancy were randomly assigned to a short-course of 8 Gy x 2 or to 8 Gy single-dose RT. Median follow-up was 31 months (range, 4-58). RESULTS: A total of 303 (93%) patients are assessable, 150 treated with the short-course and 153 with the single-dose RT. No difference in response was found between the two RT schedules adopted. Median duration of response was 5 and 4.5 months for short-course and single-dose RT (p=0.4), respectively. The median overall survival was 4 months for all cases. Light acute toxicity was registered in a minority of cases. Late toxicity was never recorded. CONCLUSIONS: Both RT schedules adopted were effective. As already shown in several trials evaluating RT regimens in uncomplicated painful bone metastases, also MSCC patients may achieve palliation with minimal toxicity and inconvenience with a single-dose of 8 Gy.
Abstract: The management of advanced non-small cell lung cancer (NSCLC) has progressed over the last 3 decades due to advances in chemotherapeutic drugs and targeted agents improving survival and quality of life. In particular erlotinib, an orally available human epidermal growth factor receptor (HER1/EGFR) tyrosine kinase inhibitor advancing through clinical trials for the treatment of various human malignancies in a large placebo-controlled phase III study, has shown a significantly better OS vs. placebo suggesting its potential benefits in third line and possibly in second line treatments. The association of erlotinib with ionizing radiation has been recently published showing an enhancing antitumor activity and good tolerance. No information are available on side effects when erlotinib is associated with abdominal hypofractionated radiotherapy although diarrhoea is the most known side effect dose-limiting toxicity when the abdomen is treated. Here we report a fatal acute diarrhoea in a metastatic NSCLC patient taking erlotinib during abdominal hypofractionated radiotherapy for metastatic spinal cord compression (MSCC).
Abstract: Approximately 20-25% of patients with limited small cell lung cancer (SCLC) can be cured with an aggressive approach (chest radiation concomitant with chemotherapy) followed by prophylactic cranial irradiation (PCI) to a total dose of 30-36Gy with 3-2Gy per fraction, five fractions per week. Steroid prophylactic therapy with dexamethasone is usually prescribed during PCI to minimize acute radiation induced brain oedema. This approach may induce an immunosuppressive condition leading to a reactivation of an endogenous latent Herpes simplex virus and severe or fatal acute encephalitis may occur as our report will show. A 55-year-old man affected by locally advanced SCLC was referred to our institution after four cycles of chemotherapy with a good partial remission. Chest radiation started concomitantly with two cycles of chemotherapy followed by PCI 36Gy total dose and dexamethasone 8mg i.m. daily. Fifteen days after PCI completion the patient developed acute neurological symptoms of confusion, cognitive impairment, fever with shaking requiring severe sedation therapy. Twenty-five days later MRI T1 weighted images showed haemorrhagic streaked lines on cortical convolutions of the right cerebral hemisphere and diffuse oedema suggestive of herpetic encephalitis. The DNA consensus test on cerebrospinal fluid (CSF) was positive for Herpes simplex virus 1 infection (HSV-1). A diagnosis of herpetic encephalitis HSV-1 was made. Antiviral therapy with high doses of acyclovir was prescribed but symptoms did not ameliorate leading to a comatose state. The patient died 55 days after the end of PCI. In eligible SCLC patients, PCI is an important part of an aggressive therapeutic approach that improves overall and disease free survival decreasing the risk of relapse in the brain. A primary infection or a reactivation of an endogenous latent HSV in brain parenchyma under steroid therapy concomitant to brain irradiation may compromise these benefits.
Abstract: 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.
Abstract: BACKGROUND: Surgery is the primary treatment for patients with stage I, II, or IIIA non-small-cell lung cancer (NSCLC). However, long-term survival of NSCLC patients after surgery alone is largely unsatisfactory, and the role of adjuvant chemotherapy in patient survival has not yet been established. METHODS: Between January 1994 and January 1999, 1209 patients with stage I, II, or IIIA NSCLC were randomly assigned to receive mitomycin C (8 mg/m2 on day 1), vindesine (3 mg/m2 on days 1 and 8), and cisplatin (100 mg/m2 on day 1) every 3 weeks for three cycles (MVP group; n = 606) or no treatment (control group; n = 603) after complete resection. Randomization was stratified by investigational center, tumor size, lymph-node involvement, and the intention to perform radiotherapy. The primary endpoint was overall survival and secondary endpoints were progression-free survival and toxicity associated with adjuvant treatment. Survival curves were analyzed using the log-rank test. All statistical tests were two-sided. RESULTS: After a median follow-up time of 64.5 months, there was no statistically significant difference between the two patient groups in overall survival (hazard ratio = 0.96, 95% confidence interval = 0.81 to 1.13; P =.589) or progression-free survival (hazard ratio = 0.89, 95% confidence interval = 0.76 to 1.03; P =.128). Only 69% of patients received the three planned cycles of MVP. Grades 3 and 4 neutropenia occurred in 16% and 12%, respectively, of patients in the MVP arm. Radiotherapy was completed by 65% of patients in the MVP arm and by 82% of patients in the control group. In the multivariable analysis, only disease stage and sex were associated with survival. CONCLUSION: This randomized trial failed to prospectively confirm a statistically significant role for adjuvant chemotherapy in completely resected NSCLC. Given the poor compliance with the MVP regimen used in this study, future studies should explore more effective treatments.
Abstract: PURPOSE: Chemotherapy and concurrent irradiation, intended to cure, are presently standard treatments for non metastatic, unresectable oesophageal cancer. The results of the combined therapy are superior to those of radiotherapy alone, attaining 25-35% 2-year survival rates. However these results mainly refer to stage I and II tumours as most of the available literature has focussed on these groups. The aim of our report is to present our experience with Stage III and IV patients. MATERIAL AND METHODS: Sixty-four Stage III and IV oesophageal cancer patients were referred to our Departments from January 1, 1990 to December 31, 1996. Diagnosis was obtained through oesophagoscopy and biopsy, stage was assessed by physical examination, chest CT scan, bronchoscopy, barium X-ray examination, upper abdomen ultrasonography and bone nuclide scan. Thirty-four patients, with no signs of blood-born metastases and in satisfactory medical conditions (i.e. age not exceeding 70 years, weight loss not exceeding 10% of body weight, normal serum values of BUN and creatinine, no other severe disease), were submitted to concurrent chemo-radiotherapy. The case features were as follows: histology of squamous cell carcinoma in 32 cases, of adenocarcinoma in 2; tumour in the upper third of the oesophagus in 11 (32.5%), in the middle third in 18 (53%), in the lower third in 5 (14.5%); male/female ratio 29/5, age 48-68 years (mean 56), Karnofsky performance status of 60% or higher. On referral, 18 out of 34 (53%) had a weight loss more than 5% of body weight and 22 (64.5%) had dysphagia. Twenty-one had Stage III (61.75%) and 13 stage IV (38.25%) cancer, with metastasis limited to the supraclavicular or coeliac nodes, which could be included in the radiation volume. In all cases chemotherapy consisted of 5-Fluoruracil (administered in a continuous i.v. infusion, from day 1 to 5, with a 750-1.000 mg/n.sq daily dose) and Cisplatin (75-100 mg/n.sq on the first day, or 20 mg/n.sq for 5 consecutive daily doses, administered by i.v. bolus). Three to 5 cycles were administered, one every 21 days. Irradiation started with the first cycle of chemotherapy in 5 patients, with the second or third cycle in 29. At least two cycles of chemotherapy were administered during the course of radiation. Radiotherapy was performed with 4 to 18 MeV linear accelerator X-rays, or telecobalt, through opposite anterior and posterior treatment portals or more complex field arrangements. The doses were in the range of 44-66 Gy, with fractionation of 5x180-200 cGy weekly sessions. After treatment, periodic follow-up controls were carried out in all cases. Thorough restaging was performed only in selected cases, thus a systematic evaluation of objective responses was not possible. Data on improvement of swallowing were always available, however, and the early therapeutic results were analysed accordingly. Toxicity was recorded according to the WHO parameters. Two-year survival after conclusion of the treatment was calculated according to Kaplan and Maier. Survival was analysed (log-rank test) according to stage, Performance Status, oesophagectomy and body weight loss. RESULTS: After treatment, subjective symptomatic relief occurred in 17 of the 22 patients presenting dysphagia (77.5%). Acute toxicity (Grade III or IV WHO) of the treatment accounted for 47% of hematologic adverse effects, 40% of mucositis, 20.5% of vomiting or diarrhoea not responding to drug treatment. Treatment delays of more than one week, due to toxicity, occurred in 23.5%. Moreover, we observed 20.5% of mild cardiotoxicity and 6% of mild nephrotoxicity. No symptomatic lung fibrosis was observed. No death could be related to toxicity. Overall 2 year survival was 13%, with a median value of 10 months. Survival analysis, according to stage, showed 2 year values of 24% in Stage III and 0% in Stage IV (p=0.09). No significant difference was related to Performance Status and weight loss. Six patients showed a remarkable improvement in symptoms and general conditions after treatment, and were restaged with oesophagoscopy, thoracic CT scan and bronchoscopy, which evidenced resectable residual tumors, and they were then operated. Although histologic examination showed tumour in all the resected specimens, 2 patients survived more than two years (33.5% survival, median 14 months). Due to the small number of operated patients, no attempt was made to assess the significance of this result, in comparison with the other cases. DISCUSSION AND CONCLUSIONS: Many Stage III and IV patients, selected for an aggressive chemo-radiation approach on the grounds of satisfactory medical conditions, can obtain relief of dysphagia. Toxicity can be severe, but is rarely life-threatening. Some cases, without extrathoracic spread of the tumor can achieve long term survival (in our experience 24% 2-year survival in Stage III, in our experience which favourably compares with the results obtained by other authors). Whether surgery may improve the therapeutic results of chemo-radiotherapy in patients whose tumour has become resectable, is an issue that cannot be satisfactorily addressed on the basis of our experience, nor are the results from the available literature exhaustive to this regard.
Abstract: 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.
Abstract: 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.
Abstract: 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.
Abstract: The prevalence of thyroid nodules was studied with ultrasonography in a group of male hospital workers (n = 44) who had been exposed occupationally to x-rays. This group was compared with a group of nonexposed workers (n = 88) who were age- and sex-matched with the exposed workers. Thyroid nodules were detected in 18 (41%) of the exposed workers, compared with 11 (13%) of the nonexposed controls. Both groups were subdivided with respect to age (i.e., 30-39 y, 40-49 y, 50-59 y), and there was a higher and significant relative risk for thyroid nodule formation in the exposed group. We also divided the groups into subgroups according to levels of exposure (i.e., nonexposed, exposed for < 20 y, and exposed for > 20 y), and a significant result was obtained with the linear-trend chi-square test. The preliminary results of our study suggest that occupationally induced exposure to radiation may be a risk factor for thyroid nodule formation.
Abstract: 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.
Abstract: 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.
Abstract: 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).
Abstract: 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.
Abstract: 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.
Abstract: 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.
Abstract: 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.
Abstract: During avoidance conditioning heart rate levels tend to increase or to decrease according to their initial values and these changes are not related to learning or performance of the task.
