Nõu E

The effect of metastasectomy: fact or fiction?

Metastasectomy in the treatment of solitary metastases has been recommended almost unanimously. The basis for this recommendation has been that 5-year survival after metastasectomy is around 30%, which is just as good as after operation for bronchial carcinoma. It has been assumed, implied, or claimed that the 5-year survival without operation is nil. Control material is, however, lacking. Seventy surgically treated patients were compared with a small, historical control group of 12 patients. There was no difference in 5-year survival. Because of these findings and after a study of the literature, we postulate that patients with lung metastases fulfilling the criteria for operation constitute a selected group with a favorable natural history. Five-year survival, therefore, is an insufficient way of describing the effect of metastasectomy. However, patients with 10-year survival are rare in the literature. In some patients with a favorable tumor-host relationship or with possibilities for effective chemotherapy, cure or prolongation of life has been achieved. Such patients should undergo operation. Randomized studies are needed in all groups for which we do not have sufficiently strong evidence that metastasectomy contributes to the longevity of the patient.

Neurone specific enolase: a useful diagnostic serum marker for small cell carcinoma of the lung.

Among lung cancers small cell carcinoma is the most sensitive to chemotherapy and radiation. This has emphasised the importance of an accurate diagnosis of this cell type, and the present study examined the use of serum neurone specific enolase (NSE) as a diagnostic marker for small cell carcinoma. NSE was measured in pretreatment sera from 103 patients with small cell carcinoma and in sera from relevant controls, including patients with other lung cancers, non-malignant lung diseases, and healthy adults. Serum NSE concentration was raised (greater than 25 ng/ml) in 72% of patients with small cell carcinoma. Ninety one per cent of patients with extensive disease and 50% of patients with limited disease were serum NSE positive. Patients with extensive disease in general had higher serum NSE concentrations than patients with limited disease. No definite difference in serum NSE positivity could be shown between oat cell and intermediate cell subtypes. Out of 51 patients with other lung cancers, four (8%) had a raised serum concentration, whereas all patients with non-malignant diseases and healthy individuals had normal serum NSE concentrations. Serum NSE determination seems to be a valuable tool for the diagnosis of small cell carcinoma.

A randomized study of radiation treatment in small cell bronchial carcinoma treated with two types of four-drug chemotherapy regimens.

Of an unselected series of 133 patients with small cell bronchial carcinoma, 110 patients (54 with extensive disease and 56 with limited disease) were randomly allocated to receive either chemotherapy with cyclop hosphamide, doxorubicin, vincristine, and methotrexate, alternating after four cycles with cyclophosphamide, lomustine, vincristine, and methotrexate, or the same chemotherapy combinations together with irradiation at 40 Gy to the primary tumor area and the adjacent mediastinum. In patients with extensive disease the total response rates were 70% and 86% and the median survival 7.6 and 9.2 months, respectively. There were no long‐term survivors, and no advantage was gained from radiation combination treatment. The results confirm previously reported findings. In limited disease the complete remission rates were 68% and 64%, the partial remission rates 26% and 28%, and the median survival was 14.8 and 15.4 months, respectively. There were no statistically significant differences favoring either treatment regimen. The disease‐free survival exceeding 2 years in the two respective groups was 6.5% and 25%; this difference was not statistically significant. A slight advantage of combined radiation and chemotherapy in the direction of better long‐term survival was confirmed by the 4‐year disease‐free survival rate of 12% as compared with 0% in the nonirradiation group. This difference was statistically significant. There was considerable toxicity with both treatment regimens. The addition of radiation treatment to the chemotherapy most likely benefits patients with limited disease. The overall median survival of all the unselected 133 patients (nonrandomized included) was 10.3 months, and the cure rate was 3%.

Full chemotherapy in elderly patients with small cell bronchial carcinoma.

Data on small cell lung cancer (SCLC) in elderly patients with full chemotherapy are sparse. We present material of 345 patients treated with chemotherapy (CT) with no age limits. CT was given with 2 different types of 4-drug combinations, including cyclophosphamide, doxorubicin, vincristine, methotrexate, lomustine and etoposide. Radiotherapy 40 Gy was given to 85% of the limited disease (LD) and 15% of the extensive disease (ED) patients. In 345 consecutive SCLC patients (50% LD and 50% ED) with a median survival time (MST) of 10 months and a disease-free 5-year survival 3.8%. Multivariate analysis showed clear correlation between stage of disease and survival as well as between age and survival though less pronounced. One hundred and ten patients were > 70 years of age with a median survival time of 7.4 months (LD 12.3 and ED 4.6) and 235 patients < 70 years of age had a median survival time of 10.9 months (LD 14.4 and ED 7.5) and a disease-free 5-year survival of 5.1%. The survival differences were statistically significant. Treatment toxicity was higher in patients > 70 years of age. Seventy-seven patients 70-75 years of age had an MST of 9.5 months (LD 13.2 and ED 6.2) and a disease-free 5-year survival of 1.3%. The survival differences between patients 70-75 years old and those < 70 years of age were small but statistically significant in LD at 5% level but not in ED. There were more septicemias per courses CT given in all patients 70-75 years of age and also more lethal septicemias in ED patients. Patients with LD SCLC 70-75 years of age might benefit from full treatment in terms of median and long-term survival.

Comparison of Induction Chemotherapy Before Radiotherapy with Radiotherapy Only in Patients with Locally Advanced Squamous Cell Carcinoma of the Lung

The aim of this randomised trial was to investigate the effect of induction chemotherapy before radiotherapy on survival in 302 patients with non-resectable squamous cell carcinoma of the lung. Radiotherapy, 56 Gy to the chest, was given to 154 patients and combined treatment, with chemotherapy preceding the radiotherapy, to 148 patients. Chemotherapy consisted of three courses of cisplatin (120 mg/m2) and etoposide (100 mg/m2 i.v. for 3 days) administered every fourth week. Median survival was 10.5 months in the radiotherapy arm and 11 months in the combined treatment arm. The 2-year survival rate was 17% in the radiotherapy arm and 21% in the combined treatment arm. Addition of chemotherapy seemed to significantly improve survival, according to the Cox multivariate analysis (P = 0.04), but as only a trend according to life-table analysis (P = 0.11). Chemotherapy also accomplished a trend towards improved local control (P = 0.08) and towards decreased metastatic disease (P = 0.10). 2 patients in the combined treatment arm, but none in the radiotherapy arm, died from toxicity. The conclusion was that the value of the chemotherapy used in this study was very modest, but the results strongly support further research for more efficient drugs and combinations.

Neuron-specific enolase as a follow-up marker in small cell bronchial carcinoma: a prospective study in an unselected series

The value of measurement of serum neuron‐specific enolase (NSE) as a follow‐up marker was investigated in 88 patients with small cell bronchial carcinoma. Of these, 42 had extensive disease and 46 had limited disease. The mean NSE levels before treatment, at response, and at recurrence in extensive disease were 107, 10, and 52 ng/ml, respectively, and the corresponding levels in limited disease were 35, 10, and 19 ng/ml, respectively. All differences were statistically clearly significant. However, the sensitivity of NSE in serum at response was 66% and at recurrence, 38%. The predictive value of an NSE decrease at response was 88%, and at recurrence, 72%. It is concluded that NSE changes during follow‐up support the evaluation of the outcome but cannot be used as a monitoring agent in an individual patient.

The Choice of Operation for Bronchial Carcinoids

In a review of the literature, 1,392 patients with bronchial carcinoids were found. Of these, there were 313 patients for whom individual data with regard to type of operation, follow-up period, and outcome were given. Actuarial curves for proportions of patients who had not died of the disease or who had not undergone reoperation for residual disease were constructed for each type of operation. The prognosis up to 20 years after surgical treatment for bronchial carcinoids is excellent. For 15 to 20 years postoperatively, the prognosis after a lobectomy is excellent and after a pneumonectomy, slightly worse. The prognosis after a lung parenchyma-saving operation (wedge or segmental resection and bronchoplastic procedures) is similar to that after a lobectomy up to 7 years postoperatively. After that, the proportion of disease-free patients declines precipitously. At 20 years the difference in comparison with a lobectomy is statistically significant for both wedge or segmental resections and bronchoplastic procedures. Parenchyma-saving operations cannot therefore be said to be radical. A policy for decision-making at the operating table is formulated.

Serum sialyltransferase and fucosyltransferase activities in patients with bronchial carcinoma

Serum sialyltransferases and fucosyltransferases measured by an affinity adsorbent technique were studied in 27 exactly defined patients with malignant pulmonary diseases. Fourteen patients with benign pulmonary diseases and 56 with benign surgical diseases were used as controls. Enzyme activities were expressed as amounts of labeled precursor molecules incorporated into endogenous acceptors in counts per minute (cpm). The mean sialyltransferase activity was 583 cpm in bronchial carcinoma, 485 cpm in benign pulmonary disease and 428 cpm in benign surgical disease. The only statistically significant difference was between bronchial carcinoma and benign surgical disease. The mean fucosyltransferase activity was 813 cpm in bronchial carcinoma, 436 cpm in benign pulmonary disease and 255 cpm in benign surgical disease. All the differences were statistically significant. There were no statistically significant differences between the WHO histologic bronchial carcinoma groups. The correlation between sialyltransferase and fucosyltransferase activity in bronchial carcinoma was statistically significant (r = 0.59). In squamous cell carcinoma (N = 6), it was strongly significant (r = 0.96) and there was a significant correlation also in small cell carcinoma (N = 10; r = 0.79) but not in adenocarcinoma (N = 9; r = 0.30) and benign pulmonary disease (N = 14; r = 0.44). It is suggested that serum sialyltransferases and fucosyl transferases would not be decisive for diagnosis when used alone in bronchial carcinoma, but could be included in a screening test battery.

Serum β2‐microglobulin in patients with bronchial carcinoma and controls

We measured serum levels of β2‐microglobulin in 467 patients mainly with suspected pulmonary malignancy. By applying serum concentrations of 3.0 mg/liter as the normal upper limit, we found elevated levels in 21% of the patients with verified bronchial carcinoma (n = 230) and in 11% of the patients with lung diseases of infectious, inflammatory, or other origins but without proven malignancy. A rise in serum β2‐microglobulin levels with advancing age was demonstrated in cancer patients and controls. No significant differences in serum concentrations were seen between cancer patients subgrouped according to the WHO classification. Serial measurements on cancer patients generally revealed increasing serum‐β2‐microglobulin with time. The most striking elevations during tumor growth were observed in patients with small cell anaplastic or epidermoid carcinoma. After surgical removal of the lung tumor, no decrease of β2‐microglobulin was found. Patients who at admission had low circulating levels of β2‐microglobulin (<1.5 mg/liter) had a better prognosis than those with serum β2‐microglobulin > 3.0 mg/liter. The mechanism behind elevated β2‐microglobulin in bronchial carcinoma and the variation of this protein during progression of the cancer disease is unknown. One possible interpretation is that levels increase as a consequence of an increased cell turnover in tumor tissue in combination with an enhanced immune response secondary to the malignant process. Cancer 45:780‐785, 1980.

Local Failure in Patients Treated with Radiotherapy and Multidrug Chemotherapy for Small Cell Lung Cancer

Fifty-three patients with small cell carcinoma of the lung were treated with chemotherapy and radiotherapy, 40 Gy in the chest tumour. Intrathoracic failure occurred in 89% of the cases with extensive disease and in 60% of those with limited disease. Since 86% of all failures were localized within the target volume, one can conclude that in most cases the radiation dose was too low for eradication of the tumour. The treatment technique resulted in dose inhomogeneities of more than +/- 5% in 45% of the cases. The high local failure rate might indicate the need of improved radiotherapy, in the first place higher radiation dose. However, 82% of the patients with limited disease and local failure and 50% of those without local failure also developed distant metastases. This might indicate that the curative potential of improved thoracic radiotherapy probably is limited. Besides, lethal treatment toxicity affected particularly patients in whom local cure had been achieved, indicating the difficulty of increasing the treatment intensity without increasing the lethal toxicity in potentially curable cases.