Radiotherapy and concurrent continuous infusion of cisplatin with adjuvant surgery in nonresectable Stage III lung carcinoma: short- and long-term results of a Phase II study.

PURPOSE: Cisplatin-enhanced radiotherapy plus adjuvant surgery was evaluated in nonresectable non-small cell lung carcinoma (NSCLC). METHODS AND MATERIALS: Doses of 50 Gy (administered in standard fractionation in 5 weeks) were delivered with concurrent cisplatin in continuous infusion (daily dose: 4 mg/m2), to 32 Stage IIIa and 45 Stage IIIb patients enrolled in a Phase II study. Patients without progression underwent surgery. RESULTS: Esophagitis (64%), nausea/vomiting (34%), and pulmonary toxicity (14%) were the main side effects. Grade 3 toxicity occurred in 4 instances. A clinical locoregional major response was achieved by 55 patients (there were 10 complete responses). Forty patients underwent surgery, 7 with a nonradical procedure. Seven patients died due to surgery-related complications, which were significantly impacted by right pneumonectomy (71% vs. 6% of the other procedures, p < 0.0001). Eighteen of the 40 surgical patients were assessed to be without viable tumor and 11 with microresidual carcinoma. There were 13 disease-free, 5-year survivors. CONCLUSIONS: Toxicity was low but activity high with the chemoradiotherapy. Adjuvant surgery increased the rate of complete responses, but right pneumonectomy had an unacceptable mortality. The role of surgery needs further refinement. Integration of the chemoradiotherapy schedule with cisplatin-based induction chemotherapy is advisable.

Non-resectable Stage IIIa-b lung carcinoma: a phase II study on continuous infusion of cisplatin and concurrent radiotherapy (plus adjuvant surgery).

Thirty-eight patients with non-resectable non-small-cell Stage IIIa-b lung cancer were treated in a Phase II study with radiotherapy (50 Gy in a 25-fraction split-course) plus con-current continuous infusion of cisplatin given at a daily dose of 6 mg/m2, with the aim of investigating its radiopotentiation properties. Treatments were given on an outpatient basis by means of a central venous catheter and a portable pump. Adjuvant surgery was undertaken when feasible. Toxicity was mild to moderate. The probability of a partial or complete locoregional response at 4 weeks after treatment completion was 83% (confidence limits at 95%: 13). Eighteen patients were resected. Overall 1-, 2- and 3-year progression-free survival probabilities were 42, 24 and 21%. These figures were 63, 37 and 24% in observed survival curves. Patients with squamous-cell tumors had observed survival rates of 82, 50 and 28% at 1, 2 and 3 years, compared to 42, 19 and 19% in patients with non-squamous histology. The high response and survival rates obtained at a low price according to toxicity require further investigation.

cis-Diamminedichloroplatinum(II) given in low-dose continuous infusion with concurrent radiotherapy to patients affected by inoperable lung carcinoma: a pharmacokinetic approach.

The pharmacokinetics of cis-diamminedichloro platinum(II) (cisplatin), given as a continuous infusion with concurrent radiotherapy to patients with locally advanced inoperable non-small-cell lung carcinoma, was investigated in 16 cases. The regimen, repeated for 6 consecutive weeks, consisted of weekly 10-Gy radiotherapy given in five fractions from Monday to Friday, and concurrent 100-h infusion of cisplatin delivered at a daily dose of 4 mg/m2 by a central venous catheter and a portable pump. Throughout the weeks of therapy the platinum levels were determined in plasma and in ultrafiltered plasma by respectively inductively coupled plasma atomic emission spectrometry and inductively coupled plasma mass spectrometry. Mean levels of platinum in plasma ([Pt]tot ) increased from the 1st to the 6th week of infusion, while mean levels of platinum in ultrafiltered plasma ([Pt]uf), 110 microg/l, showed no marked variation throughout the therapy. [Pt]uf ranged from 16% to 22% of the total Pt. Mean levels of Pt in ultrafiltered plasma were of the same order of magnitude as those found to be active in vitro as radiopotentiators. Pt decay levels were measured for 24 h at the end of the 1st and 5th weeks of infusion, allowing the calculation of the Pt half-life and the area under the decay curves. The mean value of the area under the decay curve, plotting [Pt]tot against time (AUC), in the range 0-24 h from the end of the 5th week of infusion, was about twice that from the end of the 1st week; by contrast, the mean AUC values did not vary for the [Pt]uf against time curves. The mean values of the alpha half-life of Pt in the ultrafiltered plasma were in accordance with those published in the literature; however, an unexpected very long beta half-life was found (more than 100 h). Thus it was suggested that Pt species other than free cisplatin were present in the ultrafiltered plasma; such species probably involve metal bound to low-molecular-mass proteins. Throughout the therapy, the toxic effects in all patients were negligible, and 75% of them had an objective locoregional reduction of disease. In only 2 cases was progression of disease observed within the irradiated area. On the basis of these data, it can be concluded that cisplatin at a level of 110 microg/l in the ultrafiltered plasma, in the reported scheme of continuous intravenous infusion, has an enhancing effect on radiation and avoids concentration peaks of platinum not bound to protein.

Latissimus dorsi reverse flap to substitute the diaphragm after extrapleural pneumonectomy.

BACKGROUND: The standard procedure for diaphragm reconstruction after extrapleural pneumonectomy for a malignancy consists of the use of prosthetic patches. Our original technique utilizing the reverse flap of the latissimus dorsi is evaluated. METHODS: Once the extrapleural pneumonectomy is performed, the distal portion of the latissimus dorsi, which has been divided with a standard posterolateral thoracotomy at the level of the fifth to sixth rib, is elevated into the chest through the passage obtained by resection of the tenth rib and sutured to the lower pericardium and to the chest wall. Nine patients were evaluated. RESULTS: No operative death occurred. No flap-related complication nor infection was postoperatively assessed. Six patients received adjuvant radiotherapy. No late complication was observed. CONCLUSIONS: The distal latissimus dorsi can be used for total reconstruction of one hemidiaphragm, ensuring a watertight separation between the pleural and peritoneal cavities and avoiding paradoxical respiratory motion. In our opinion, the technique was easier, faster, and more reliable than the standard procedure employing prosthetic materials. We recommend that the procedure be integrated with the standard technique of extrapleural pneumonectomy.

Determination of platinum in plasma of patients affected by inoperable lung carcinoma treated with radiotherapy and concurrent low-dose continuous infusion of cis-dichlorodiammine platinum(II).

Platinum microquantities were determined in plasma of patients affected by lung carcinoma during treatment with radiotherapy (RT) and concurrent low-dose continuous infusion of cis-dichlorodiammineplatinum(II) (CDDP). RT was given at 50 Gy in continuous course; CDDP was continuously infused at 4 mg/m2 daily for 100 h/week for 5 weeks, and the infusions were separated by 68 h of rest. The percentage of free drug versus total drug in plasma was about 3%. It did not vary with therapy duration and was not significantly different from that found in 5-day continuous infusions at much higher daily doses. Nevertheless, maximal values of free Pt in plasma were very low and agreed with the low level of CDDP toxicity encountered on the present administration schedule.

Resectable breast cancer: axillary dissection sparing pectoralis muscles and nerves.

In breast cancer surgery, axillary dissection is currently considered an essential step. Nevertheless, procedures commonly used include the resection of the pectoralis minor muscle and/or pectoralis nerves. Since 1984 we have performed axillary dissection by sparing both the pectoralis muscles and their nerves. In this paper we present the surgical technique. The comparison of the two groups with clinical N0 N1a assessment, the former of 103 patients submitted to this kind of surgical procedure, the latter (108 women) treated by resection of the pectoralis minor muscle, showed that the mean number of dissected lymph nodes in both procedures was superimposable.

Extrapericardial solitary fibrous tumour of the pericardium.

Solitary fibrous tumour (SFT) occurs most commonly in the pleura and is extremely rare in the pericardium. The authors report a case of a 60-year-old man in whom a large mediastinal mass was accidentally discovered. Computed tomography showed involvement of the left anterosuperior mediastinum with displacement of the trachea, large vessels and oesophagus; histopathological findings after complete resection of the neoplasia demonstrated an SFT of the pericardium, the first reported case with extrapericardial pattern of growth. A review of the literature on SFTs of the pericardium is provided.

Pilot study with cisplatin, ifosfamide, and etoposide in advanced non-small-cell lung carcinoma.

Twenty-five patients with advanced non-small-cell lung carcinoma (NSCLC) were treated with a multidrug regimen (CIV) consisting of ifosfamide (IFX), cisplatin (CDDP), and etoposide (VP-16). Twenty-four patients were evaluable for response. An objective response was detected in eight cases (33%), including one case with complete tumor response. Median duration of response was 31 weeks, and median overall survival 46 weeks, with no significant difference between responders and nonresponders. Myelosuppression and gastrointestinal side effects represented the main toxic manifestations; a toxic death and an ischemic cardiac episode were also observed. CIV seems a moderately effective regimen in NSCLC, but unlikely to provide an advantage over the widely employed two-drug combination of CDDP and VP-16.

Extrapleural pneumonectomy for sarcomas report of two cases.

AIMS AND BACKGROUND: Extrapleural pneumonectomy (EPP), which is a very uncommon surgical procedure, is electively indicated only in patients with early stages of malignant pleural mesothelioma, a rare condition. Two adults suffering from sarcomas and treated with EPP are described here. METHODS: A 29-year-old male with four left-sided lung metastases and ipsilateral pleural effusion from a chondrosarcoma of the mandibula and a 64-year old woman with a megamass in the left chest due to a local recurrence of a hemangiopericytoma underwent EPP. RESULTS: Extra-EPP-field multiorgan progression was diagnosed 14 months following surgery in the first patient who died at the 24th postoperative month but remained free of disease at the site of surgery. The second patient had a chest wall relapse at the forty-third month following EPP, which was treated by partial resection of the second and third ribs. She is alive and disease-free at the twelfth postoperative month. DISCUSSION: EPP may be considered for salvage treatment in selected patients with intrathoracic sarcomas not amenable to other effective therapies to achieve mid- to long-term disease control, even in the case of advanced spread.

Five-year recurrence probabilities in 330 patients curatively resected for stage Ia bronchogenic carcinoma.

Three hundred and thirty consecutive cases of resected Stage Ia (TNM UICC classification) lung carcinomas were retrospectively reviewed with the aim of evaluating actuarial probabilities of recurrence within the 5th year from operation, according to the extent of resection, the cell type, and the T number. The probabilities of recurrence according to the pattern of failure were also assessed. Five-year overall probability of recurrence was 46.3%. Pneumonectomies showed a lower rate of relapse (37.4%) than lobectomies (49.2%), even though non significant. However, patients submitted to a lobectomy had a higher rate of 5-year survivors. Cell type had no significant impact on the probability of recurrence. 35.5% of patients with T1 carcinomas had evidence of relapse compared with 51.1% of patients with T2 tumors. This datum is explained by the presence in T1 group of a high share of squamous cell cases. Patients with T1 squamous cell carcinomas had, in fact, the best prognosis (26.5% recurred) among the subgroups obtained by stratification of T number and cell type together; loco-regional failure as exclusive modality of relapse had a 5-year rate of 19.7% and metastatic failure of 30.0%. Adenocarcinomas had a significantly higher impact on the occurrence of brain metastases.

Young age is not an ominous prognostic factor in breast cancer patients.

Analysis of a series of 137 women 20-30 years of age, operated for breast carcinoma, excluding patients pregnant, lactating or with inflammatory cancer, showed that disease-free survival rates were similar and not lower than those reported for a large series of 716 breast cancer patients of all ages, treated and followed at the same Institute. Ten-year disease-free survival rates for the two series of 137 young women and 716 patients of all ages were 43.7% and 47.1% respectively. Even when considering the subgroups of patients with and without nodal axillary involvement, the corresponding figures for the two series considered were 72.6% vs. 72.1% (N-) and 25.1% vs. 24.5% (N+). It can be concluded that young age cannot be considered as an unfavorable prognostic factor.

Impact on survival of the extent of resection in unrelapsed lung cancer.

Five-year survival of resected stage Ia non-oat cell lung cancer was evaluated in 69 consecutive patients without recurrence. The impact of the extent of resection on perioperative and long-term mortality was studied after an evaluation of confounding factors, such as age and associated cardiopulmonary diseases, which further stratified our series. Our patients were subdivided into 2 groups: the first included lobectomies and was further subdivided into 2 subsets according to whether the operation had caused the resection of less than 4 (30 cases) or more than 3 segments (18 cases). The second one included pneumonectomies (21 cases). Thirty-two patients were 60 years or older; pulmonary and/or cardiovascular diseases were assessed in 38 patients. There were 6 perioperative deaths, 3 among major lobectomies (more than 3 segments resected) and 3 among pneumonectomies. Survival rate of lobectomies was 75% (86% for minor, 55% for major lobectomies), and 57% for pneumonectomies. Major lobectomies included the highest percentage of elderly patients with cardiopulmonary diseases who had significantly poorer survival probabilities than young subjects without cardiopneumopathies. Lobectomy cases, after standardization by age, had a significantly higher probability of surviving than pneumonectomy cases. Standardization by cardiopulmonary disease showed a better chance for lobectomy cases, although it was not significant. Major lobectomy cases had poorer cumulative survival rate than minor lobectomy cases. Such a difference was revealed in patients 60 years or older and in those with pneumocardiopathies.

Intrathoracic benign metastasizing leiomyoma with extrapulmonary growth pattern. A case report.

The authors report a case of a woman in whom complete resection of an extrapulmonary differentiated leiomyomatous tumor of uterine origin was performed 39 years after hysterectomy for uterine leiomyomas.

Prognosis after nonradical resections for small cell lung carcinoma (SCLC).

Out of 52 consecutive patients resected for small cell lung carcinoma (SCLC) from 1976 to 1986, 19 were selected because they underwent nonradical surgery, 10 of them for locoregional spread and 9 for distant metastases. Of the former subset all received postoperative radiotherapy and 8 chemotherapy also. Three patients are alive and disease-free 37, 56 and 91 months after resection. Four patients had a distant recurrence, and 3 a locoregional failure. Patients of the latter subgroup received chemotherapy in 7 instances. None survived more than 16 months, distant metastases being the cause of death. In these patients N0 status was associated with 13.3 months of mean survival, N1 with 8.5 months, and N2 with 6.7 months. Surgery and adjuvant treatments seem effective in achieving local control of SCLC despite nonradical resections. Tumor burden at locoregional sites does not preclude the possibility of long term survival.

Pilot study with adriamycin and ifosfamide in small cell lung cancer.

Twenty-one patients with limited (12 cases) or extensive (9 cases) small cell lung cancer entered a pilot study with adriamycin (ADM) plus ifosfamide (IFX) as first line treatment for six planned cycles. ADM was administered at the dose of 60 mg/m2 iv push on day 1 and IFX at 3 g/m2/iv in 1-hour infusion on days 1 and 2. To prevent IFX-induced hemorrhagic cystitis, mercaptoethane sulfonate sodium (Mesna) was given after the administration of IFX at the dose of 500 mg/m2 by iv push four times (hour 0, 4, 8, 12) on days 1 and 2. In the absence of disease progression, chemotherapy was repeated every 3 weeks for 6 cycles. All patients were evaluable for analysis of response, toxicity and survival. The overall response rate clinically and radiologically assessed after four treatment cycles was 95.3% (CR 28.6%, PR 66.7%). However, by continuing the same drug treatment up to the sixth cycle, 7 of 14 partial responders showed tumor progression within the intrathoracic region. Therefore, at the end of the planned chemotherapy program the partial remission rate fell to 33.3%, for a total remission rate of 61.9% and a median total survival of 9 months (range 5 to 36+). The regimen was well tolerated with only one case presenting hemorrhagic cystitis. The results achieved with this drug combination appear comparable to those obtained with other conventional regimens. However, the high response rate achieved after four cycles and the low incidence of marrow toxicity suggest the use of this regimen for a short period with increased dose levels.

Late results after sleeve or wedge lobectomies for non-small-cell lung carcinoma.

From January 1971 to June 1983, 35 lobectomies with bronchoplastic procedures for invasive non-small-cell lung carcinoma were performed. Sleeve lobectomy was carried out in 21 cases, wedge lobectomy in 11, and upper sleeve bilobectomy in 3. There were 23 stage I, 10 stage II, and 2 stage IIIa tumors. Completion pneumonectomy was required in 1 case for anastomotic fistula and in 2 for atelectasis of residual lung. One of these patients died later due to empyema. The 5-year probability of death with recurrence was 31.98%. The 5-year disease-free survival was 58.57%. Metastatic relapse was observed in 8 cases and loco-regional recurrence in 5. A new primary lung tumor occurred in 2 patients.

Long-term infusion in cancer chemotherapy with the Groshong catheter via the inferior vena cava.

AIMS AND BACKGROUND: Vascular access through a vein draining into the superior vena cava is commonly used for long-term infusion of drugs inr cancer chemotherapy; prolonged cannulation of the inferior vena cava is generally considered as having an excessively high complication rate. METHODS: Prolonged cisplatin infusion via the inferior vena cava by means of a Groshong catheter was evaluated in 20 consecutive patients with thoracic malignancies showing evidence of superior vena cava infiltration or obstruction. RESULTS: We achieved 1,291 catheter days for our survey with a mean duration of vascular access of 64.5 days per patient and a mean duration of infusion time of 40 days. There were 2 complications, a catheter obstruction after a 7-day rest period and an ileo-femoral thrombosis 6 days after catheter placement. CONCLUSIONS: Our experience compared favourably with the results obtained by long-term central venous access via the supraumbilical route, and demonstrated the reliability and safety of this approach in cases where the superior vena cava cannulation is technically difficult or impossible.

Modified Schoemacher resection for distal gastric cancer.

Between October 1979 and February 1987, 30 consecutive patients with cancer of the lower stomach underwent B1-Schoemacher resection with a tubular gastric pouch. Operative mortality was 0% and operative morbidity 10% (leak 3%, anastomotic stricture 3% and abscess 3%). After a mean follow-up of 30 months, the expected 5-year survival was 32%. The causes of death were: 7 distant relapses, 2 noncancer diseases and 1 new primary cancer. The overall incidence of postgastrectomy symptoms was 23% for the whole series and 35% for the patients harboring small tumors. Mild dyspepsia occurred in 71%. The declining concept of total gastrectomy as an essential requirement for curative resection and the recent evidence that B2 for gastric lesions is a carcinogenic operation necessitate alternative procedures. The data show that modified Schoemacher resection can be consider a valid challenge to B2.

Relationship between CaMBr1 expression and tumor progression in small cell lung carcinomas.

In order to study the possible relationship between antigenic phenotype and tumor progression, 63 small cell lung carcinomas (SCLC) biopsies derived from primary or metastatic tumors were tested by immunofluorescence and immunoperoxidase techniques with an anti-carcinoma monoclonal antibody designated MBr1. Primary tumors were found to be less reactive with MBr1 than the local and distant metastatic lesions (57% versus 75% and 89% positivity respectively). A life table analysis on the tested cases indicated an inverse association between the expression of the marker recognized by the MBr1 MAb (CaMBr1) and overall survival (p less than 0.01): patients with MBr1-positive tumors showed a shorter survival time in comparison to patients whose tumors did not express the marker. The same correlation between survival and CaMBr1 expression was found even when only the 31 cases of early stage disease patients were considered (p less than 0.05). Different tumor aggressiveness or resistance to therapy of MBr1-positive tumors could be responsible for the shorter survival time of the patients.

Surgical resection in the treatment of stages I-II of small cell lung carcinoma (SCLC).

From 1981 to 1986, 17 patients with resected small cell lung carcinoma (SCLC) staged as I or II according to the new TNM classification were recruited for a prospective study to evaluate the effectiveness of surgery and postoperative chemotherapy (plus locoregional radiotherapy only when a nonradical resection was accomplished) in the treatment of early stages of the disease. Six patients received full protocol chemotherapy (6 courses) and 8 a mean of 79.1% of the planned courses. Three patients received non adjuvant treatment. Locoregional radiotherapy for residual disease was administered in 2 cases. One patient died for myelosuppression due to chemotherapy and 10 for recurrences of cancer, all within the 20th postoperative month. Metastases accounted 80% of overall recurrences. Six patients were alive and tumor-free at 18, 22, 39, 44, 47 and 51 months from resection. Actuarial observed 3-year survival was 32%.