Peter Coy

The role of curative radiotherapy in the treatment of lung cancer

From 1963–1974, 141 patients with lung cancer were treated with curative intent in the A. Maxwell Evans Clinic in Vancouver. The clinical presentation, age and sex distribution, histology, and reasons for surgery not being carried out are examined. The results of this treatment are presented. An attempt has been made to isolate a group of patients who have a better prognosis so that treatment selection can be improved. Hemoptysis, cough, dyspnea, and incidental finding on routine chest x‐ray were the most common manner of presentation. Thirty‐four percent of the patients were over 70 years of age and 13% were women. The crude overall three‐ and five‐year survival rates were 18 and 10% (19 and 9% in the men, 17 and 14% in the women). Patients presenting with dyspnea had a better survival than those presenting with cough and hemoptysis. Patients with lesions less than 3 cm in diameter had a 28% three‐year survival, compared with 14% for lesions greater than 5 cm in diameter. The three‐ and five‐year survival rates in patients over 70 years of age were 23 and 17% respectively. The response to treatment and the survival was better in the patients with squamous cell carcinoma. Twenty‐two percent were alive at three years and 12% at five years as compared with 9 and 5% for other histologies. Fifty‐four percent of the 35 patients with a complete response and with squamous cell carcinoma were alive at three years, compared with only 8% of the 12 patients with other histologies who showed a complete response. Cancer 45:698‐702, 1980.

Macrophage-tumor cell associations: a factor in metastasis of breast cancer?

In human breast carcinomas tumor cells and macrophages are often proximal. We previously reported on the relationship between tumor cell growth and macrophage concentration and report here on the possible involvement of macrophages in the metastatic process. We hypothesize that during the initial stages of metastasis, tumor cells are likely to encounter macrophages and form aggregates. Using a cell culture method that encourages cellular interactions, we found aggregates involving macrophages. Macrophages partly or completely surround other cell types without any apparent ill effect. Units involving macrophages and tumor cells would possess many properties necessary for invasion, which is a normal process for macrophages. Properties such as motility and production of specific enzymes necessary to traverse the extracellular matrix, basement membrane, and endothelial cell barriers may provide an advantage for tumor cells. Physical support and protection from immune recognition during transport of the tumor cell through the vascular system may also be enhanced, and paracrine growth stimulation and angiogenic activity may be provided at the new metastatic site. Verification of these observations in vivo could lead to new directions for limiting breast cancer metastasis.

Heterogeneous estrogen receptor levels detected via multiple microsamples from individual breast cancers

Twenty‐six surgical breast cancer specimens were subjected to multiple estrogen receptor (ER) assays with a microsample technique. In most tumors there were large variations in ER levels in samples taken from different regions of the same tumor. After correction of individual samples for differences in carcinoma content, such variations were not abolished. Nine of the 26 breast cancers, although positive overall, were devoid of ER in some regions. For ER‐positive tumors the average coefficient of variation (CV) for intratumor ER levels was 86%, with a range from 25% to 200%. This is well above the CV obtained with repeat samples of homogeneous tissue (14%). These results suggest that many ER‐positive cancers may be composed of cells with a variety of ER levels. An assessment of individual intratumor ER variability may have biologic and clinical significance. Cancer 56: 2019‐2024, 1985.

Estrogen Receptor Distribution in the Peripheral, Intermediate and Central Regions of Breast Cancers

The central, intermediate and peripheral regions of 25 breast tumors were analyzed for estrogen receptors (ER) using a combined biochemical (BC)/immunohistochemical (IHC) micromethod. To optimize the regional comparison, the percentage carcinoma per sample (PCS) was evaluated and incorporated into the quantification of the ER. Correction of the measured ER for the PCS eliminated differences in receptor levels between the central and peripheral regions but not the intermediate region. Although the corrected BC-ER level in this region was found to be about 20% higher, the IHC method did not detect such a difference. Determination of the ER status at the actual growth front of a tumor, rather than in the intermediate region where ER levels appear to be highest, may be of greater clinical relevance. Intra-regional ER heterogeneity appears, however, to be particularly pronounced in this area of a tumor.

Early diagnosis of carcinoma of the lung. Simultaneous screening with chest X-ray and sputum cytology.

Two thousand one hundred and twelve male cigarette smokers over the age of 40, who either suffered from chronic bronchitis, showed long standing radiologic abnormalities, or recently recovered from pneumonia—or who showed another factor making them particularly prone to development of cancer of the lung—were screened with sputum cytology and chest x‐ray. Incidence of lung cancer was high: 17 cases (1 in 125 persons screened) were discovered. Eight of these cases were detected by x‐ray alone, 7 by cytology alone, and only 2 by both of these methods. This suggests that these screening techniques are deficient when used alone. Further confirmation of this is derived from investigation of 228 patients who were screened with negative results in 1965—9 of them developed and then succumbed to lung cancer, and at least 5 of them presumably had it at the time of initial screening. In screening programs an effort should be made not to give the participants a false sense of security concerning absence of lung cancer when results of screening tests are negative. Of the 17 cases, 13 died from cancer of the lung and one from another cause. Three are alive and well. The poor survival in this group was due, to an appreciable extent, to the fact that the same selective factors, such as chronic bronchitis, which rendered these patients liable to lung cancer precluded the possibility of surgical treatment.Two thousand one hundred and twelve male cigarette smokers over the age of 40, who either suffered from chronic bronchitis, showed long standing radiologic abnormalities, or recently recovered from pneumonia—or who showed another factor making them particularly prone to development of cancer of the lung—were screened with sputum cytology and chest x-ray. Incidence of lung cancer was high: 17 cases (1 in 125 persons screened) were discovered. Eight of these cases were detected by x-ray alone, 7 by cytology alone, and only 2 by both of these methods. This suggests that these screening techniques are deficient when used alone. Further confirmation of this is derived from investigation of 228 patients who were screened with negative results in 1965—9 of them developed and then succumbed to lung cancer, and at least 5 of them presumably had it at the time of initial screening. In screening programs an effort should be made not to give the participants a false sense of security concerning absence of lung cancer when results of screening tests are negative. Of the 17 cases, 13 died from cancer of the lung and one from another cause. Three are alive and well. The poor survival in this group was due, to an appreciable extent, to the fact that the same selective factors, such as chronic bronchitis, which rendered these patients liable to lung cancer precluded the possibility of surgical treatment.

A randomized study of irradiation and vinblastine in lung cancer

A study was made to investigate the possibility that cobalt irradiation would be more effective with the addition of concurrent chemotherapy with intravenous vinblastine. Patients under 70 years of age with histologically or cytologically verified bronchogenic carcinoma not amenable to surgical treatment or with residual disease after surgery were allocated randomly to 2 treatment regimens. Half the patients were treated with cobalt irradiation alone, the others with cobalt irradiation and intravenous vinblastine. Survival up to 2 years gave no evidence of an improvement and neither did measurement of such factors as tumor size and symptoms. It is recognized that the parameters used in this study and, particularly, in patients with lung cancer leave much to be desired if any difference in response to treatment of differing kinds is to be shown in a statistically significant manner with relatively small numbers of patients. This is because the parameters chosen are difficult to measure and because the prognosis in lung cancer is often determined by disease beyond the treated area.

Estrogen receptor assay on breast cancer microsamples: Implications of percent carcinoma estimation

Forty‐milligram strips of malignant breast tissue were divided longitudinally into 20‐mg microsamples. Soluble protein concentration was determined for one‐half, and histologic evaluation for viable carcinoma content was made on its sister half. The correlation coefficient for 88 such comparisons was 0.330. This suggests that estrogen receptor (ER) assays that do not take into account the actual amount of carcinoma present in the sample may not permit reliable stratification of ER data. Using this technique, ER values obtained for 129 breast tumor microsamples were adjusted to reflect carcinoma content. A comparison of ER values before and after such adjustment revealed that the relative status of 73% was not significantly changed. The ER status of 27%, however, was changed sufficiently to be of potential clinical significance.