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The effect of surgery, radiation therapy, and combined radiation therapy and chemotherapy on immunocompetence in patients with lung carcinoma
280
£esponders, and those patients with a bron~ choscopically confirmed complete response survived significantly longer. There was no significant difference between the patients with strictly limited stage disease and those in the broader category. Eight patients are tumor free and alive one year or more after the end of treatment. The median followup is 17 months. Twenty-four patients were delayed 1-2 weeks during treatment because of chemotherapy induced toxicity. Six patients died probably of infection associated with leucopaenia. The majority of the patients' Karnofsky performance improved with the treatment as did their breathlessness assessed on a respiratory score. The short intensive chemotherapy regimen of 3 months produced similar results to those following more prolonged treatment regimens. A Randomized Comparison of the Effects of Adjuvant Therapy on Resected Stages II and III Non-Small Cell Carcinoma of the Lung. Holmes, E.C., Hill, L.D., Gail, M. UCLA, Los Angeles, CA, U.S.A. The Lung Cancer Study Group has evaluated postoperative chemotherapy and immunotherapy in patients with Stages II and III adenocarcinoma and large cell undifferentiated carcinoma. Patients were randomized following surgery and careful intraoperative staging to receive either chemotherapy or immunotherapy. Chemotherapy consisted of Cis Platinum (Reg. trademark), Adriamycin (Reg. trademark), and Cytoxan (Reg. trademark) and immunotherapy consisted of Levamisole (Reg. trademark) and Intrapleural BCG (Reg. trademark). Sixty-eight patients were randomized to the immunotherapy arm and 62 to the chemotherapy arm. There were 49 recurrences in the immunotherapy group and 35 in the chemotherapy group (p = 0.003). These studies indicate that surgical adjuvant chemotherapy is effective in prolonging the disease-free survival in patients with Stages II and III adenocarcinoma and large cell undifferentiated carcinoma. Patients with Stages II and III resected squamous cell carcinoma were randomized to receive postoperative radiation therapy or no further treatment. There was no significant difference in terms of survival between the two treatment groups. However, those who received radiation therapy had a significantly lower incidence of local recurrence (p = 0.001). These studies indicate that postoperative radiation therapy is effective in controlling the local disease but that effective systemic therapy is necessary for improved survival in patients with Stages II and III squamous cell carcinoma of the lung. Chemotherapy P o l l o w e d b y Lung Resection in Inoperable Non-Small Cell Lung Carcinomas Due to Locally Far-Advanced Disease.
Takita, H., Regal, A.-M., Antkowiak, J.G. et al. Department of Thoracic Surgery and Oncology, Roswell Park Memorial Institute, Buffalo, NY 14263, U.S.A. Cancer 57: 630635, 1986. From 1977, 29 patients with inoperable non-small cell lung carcinoma due to locally far-advanced disease underwent lung resection after receiving two to eight courses of chemotherapy. After the surgery was performed, three additional courses of chemotherapy were given. The overall median survival from onset of the chemotherapy was 30.5 months; postoperatively, it was 24.5 months (five patients survived > 5 years). Postoperative mortality was 10.3%. The overall survival results compare favorably with those obtained with radiation therapy. ~0nsurgical Combined Modality Therapies in Non-Small Cell Lung Cancer. Klastersky, J., Sculier, J.P. Service de Medecine, Institut Jules Bordet, Centre des Tumeurs de l'Universite Libre de Bruxelles, Brussels, U.S.A. Chest 89: 289S-294S, 1986. Nonsurgical combined approaches of nonsmall cell lung cancer represent a concept that has only been investigated so far with chemotherapy and radiation therapy. Thoracic irradiation of locoregional disease is associated with a high rate of local control and a 5-10% long-term (5-year) survival; however, distant metastases remain the main cause of failure. This observation suggests that the tumor is' often microscopically disseminated at the time of diagnosis. Systemic therapy therefore must be associated to radiation therapy to try to control both the undetectable metastases and the local disease. However, the results reported so far have been disappointing, probably because of the modest activity of the available chemotherapy. Further progress with the combined approach requires new developments in the chemotherapy of non-small cell lung cancer, particularly the introduction of new active drugs. The effect of Surgery, Radiation Therapy, and Combined Radiation Therapy and Chemotherapy on Immunocompetence in Patients with Lung Carcinoma. Jakobsson, M., Taskinen, P.J., Ryhanen, P. et al. Department of Radiation Therapy, Oulu University Central Hospital, Oulu, Finland. Acta. Radiol., Ser. Oncol. 24: 481486, 1985. The immunologic status of 59 patients with lung carcinoma was determined by analysis of peripheral venous blood samples. The following tests were performed: total leucocyte and lymphocyte counts, the number of acid alpha-naphthyl acetate esterase (ANAE) positive cells (T-cells), and phytohaemagglutinin (PHA) and tuberculin (PPD) transformation tests. The patients were di-
281
vided into three treatment groups; a surgery group (S), a radiation therapy group (R), and a combined cytostatic and radiation therapy group (C). A follow-up was carried out 4 to 6 months after treatment. The therapeutic measures} resection, irradiation, and chemotherapy, produced a decrease in the total leucocyte and lymphocyte counts, in the number of T-cells, and in the leucocyte transformation response to PPD. In the surgically treated group the decrease was transient. In the groups treated with radiation therapy and combined cytostatic and radiation therapy the values remained low throughout the follow-up. The lymphocyte response to PHA was not altered in any of the groups during initial treatment or follow-up. The results did not suggest a correlation between the immunologic parameters used and the stage and histologic type of lung cancer. The tests were of no clinical value in the determination of the individual prognosis.
10,
OTHERTREATMENTMODALITIES
Controlled Trial of RSV, Herbs or Placebo as Adjuvants to Complete Resection of Squamous Cell Lung Cancer. Osterlind, K., Hansen, M., Hansen, H.H., Dombernowsky, P. Department of Oncology I I , Finsen Institute, DK-2100 Copenhagen, Denmark. Eur. J. Surg. Oncol. ii: 349-351, 1985. 152 completely resected patients with high or intermediate differentiated squamous cell lung cancer were randomized to receive 6 months adjuvant therapy with RSV (1,2diphenyl-abeta-diketone) herbs or placebo. No significant differences were observed in duration of survival or relapse rates between the three groups.
Treated with Neodymi~u-YAG-Laser, Initially Misinterpreted as Small Cell Lung Cancer. Berendsen, H.H., Postmus, P.E., Edens, E.T., Slutter, H.J. Department of Pulmonary Diseases, State University Hospital, 9713 EZ Groningen, Netherlands. Eur. J. Respir. Dis. 68: 151-154, 1986. Two patients are described with bronchial carcinoid. In both, the initial diagnosis was small cell lung carcinoma (SCLC). This diagnosis was discordant with the clinical course; a second evaluation yielded the diagnosis of carcinoid. Good palliation was achieved with YAG-laser therapy.
11,
REVIEWS
Recent Advances in the Biology of Small Cell
Lung Cancer. Carney, D.N. The Mater Hospital, Dublin, Ireland. Chest 89: 253S-257S, 1986. Advances in the techniques for culturing human tumors in vitro, especially lung cancer cells, have greatly facilitated studies of the biologic properties of both small cell and nonsmall cell lung cancer cells. Detailed analysis has been done of wellcharacterized cell lines of both groups with respect to growth properties, biomarker and antigen expression, cytogenetics, and oncogene amplification and expression. Two major conclusions have emerged from these studies: (i) considerable heterogeneity exists within a given tumor type (eg, SCLC) in the expression of a given biomarker, and (2) overlap in the expression of biomarkers exists between cells of SCLC and non-SCLC, suggesting a common stem cell for all types lung cancer. In the future, clinical trials on the impact of the biological properties of cells on responses to therapy and survival will need assessment.
Endobronchial Management of Lung Cancer. Cortese, D.A. Division of Thoracic Diseases and Internal Medicine, Mayo Clinic and Mayo Foundation, Rochester, MD 55905, U.S.A. Chest 89: 234S-236S, 1986. Bronchoscopic phototherapy is available now for 2 distinct categories of tracheobronchial cancer: roentgenographically occult superficial squamous cell carcinoma and advanced malignancy causing significant airway obstruction. Laboratory and clinical experience show that the photodynamic effect of hematoporphyrin derivative phototherapy (HpD~PT) may be useful for treating superficial cancers that penetrate less than 5 mm into bronchial mucosa. The larger, obstructing cancers are better managed by high~ power laser sources, such as the YAG laser, which are effective by hyperthermal photocoagulation, thermal necrosis, and tissue vaporization. Irresectable Bronchial Carcinoid with a 32Year Natural History. A Report of Two Cases
Bronchioloalveolar Carcinomas. Cell Types, Patterns of Growth, and Prognostic Correlates. Calyton, F., Department of Pathology, University of Utah Hospital, Salt Lake City, UT, U.S.A. Cancer 57: 1555-1564, 1986. Forty-five bronchioloalveolar carcinomas were studied, including 27 cases by electron microscopy. Bronchioloalveolar carcinomas can be classified by routine sections or by diastase-digested periodic acid-Schiff (PAS) stains, but electron microscopy is useful in confirming Clara cell or type II pneumocyte (noum~clnous) differentiation and excluding metastases. Mucinous bronchioloalveolar carcinoma can mimic metastatic adenocarcinoma histologically and ultrastructurally. Of the nine tumors with mucinous differentiation, eight had aerogenous dissemination (multifocal or with pneumonic spread), and seven of those eight were fatal. Twenty-four of 36 nonmucinous bronchioloalveolar tumors had aerogenous spread; all
£esponders, and those patients with a bron~ choscopically confirmed complete response survived significantly longer. There was no significant difference between the patients with strictly limited stage disease and those in the broader category. Eight patients are tumor free and alive one year or more after the end of treatment. The median followup is 17 months. Twenty-four patients were delayed 1-2 weeks during treatment because of chemotherapy induced toxicity. Six patients died probably of infection associated with leucopaenia. The majority of the patients' Karnofsky performance improved with the treatment as did their breathlessness assessed on a respiratory score. The short intensive chemotherapy regimen of 3 months produced similar results to those following more prolonged treatment regimens. A Randomized Comparison of the Effects of Adjuvant Therapy on Resected Stages II and III Non-Small Cell Carcinoma of the Lung. Holmes, E.C., Hill, L.D., Gail, M. UCLA, Los Angeles, CA, U.S.A. The Lung Cancer Study Group has evaluated postoperative chemotherapy and immunotherapy in patients with Stages II and III adenocarcinoma and large cell undifferentiated carcinoma. Patients were randomized following surgery and careful intraoperative staging to receive either chemotherapy or immunotherapy. Chemotherapy consisted of Cis Platinum (Reg. trademark), Adriamycin (Reg. trademark), and Cytoxan (Reg. trademark) and immunotherapy consisted of Levamisole (Reg. trademark) and Intrapleural BCG (Reg. trademark). Sixty-eight patients were randomized to the immunotherapy arm and 62 to the chemotherapy arm. There were 49 recurrences in the immunotherapy group and 35 in the chemotherapy group (p = 0.003). These studies indicate that surgical adjuvant chemotherapy is effective in prolonging the disease-free survival in patients with Stages II and III adenocarcinoma and large cell undifferentiated carcinoma. Patients with Stages II and III resected squamous cell carcinoma were randomized to receive postoperative radiation therapy or no further treatment. There was no significant difference in terms of survival between the two treatment groups. However, those who received radiation therapy had a significantly lower incidence of local recurrence (p = 0.001). These studies indicate that postoperative radiation therapy is effective in controlling the local disease but that effective systemic therapy is necessary for improved survival in patients with Stages II and III squamous cell carcinoma of the lung. Chemotherapy P o l l o w e d b y Lung Resection in Inoperable Non-Small Cell Lung Carcinomas Due to Locally Far-Advanced Disease.
Takita, H., Regal, A.-M., Antkowiak, J.G. et al. Department of Thoracic Surgery and Oncology, Roswell Park Memorial Institute, Buffalo, NY 14263, U.S.A. Cancer 57: 630635, 1986. From 1977, 29 patients with inoperable non-small cell lung carcinoma due to locally far-advanced disease underwent lung resection after receiving two to eight courses of chemotherapy. After the surgery was performed, three additional courses of chemotherapy were given. The overall median survival from onset of the chemotherapy was 30.5 months; postoperatively, it was 24.5 months (five patients survived > 5 years). Postoperative mortality was 10.3%. The overall survival results compare favorably with those obtained with radiation therapy. ~0nsurgical Combined Modality Therapies in Non-Small Cell Lung Cancer. Klastersky, J., Sculier, J.P. Service de Medecine, Institut Jules Bordet, Centre des Tumeurs de l'Universite Libre de Bruxelles, Brussels, U.S.A. Chest 89: 289S-294S, 1986. Nonsurgical combined approaches of nonsmall cell lung cancer represent a concept that has only been investigated so far with chemotherapy and radiation therapy. Thoracic irradiation of locoregional disease is associated with a high rate of local control and a 5-10% long-term (5-year) survival; however, distant metastases remain the main cause of failure. This observation suggests that the tumor is' often microscopically disseminated at the time of diagnosis. Systemic therapy therefore must be associated to radiation therapy to try to control both the undetectable metastases and the local disease. However, the results reported so far have been disappointing, probably because of the modest activity of the available chemotherapy. Further progress with the combined approach requires new developments in the chemotherapy of non-small cell lung cancer, particularly the introduction of new active drugs. The effect of Surgery, Radiation Therapy, and Combined Radiation Therapy and Chemotherapy on Immunocompetence in Patients with Lung Carcinoma. Jakobsson, M., Taskinen, P.J., Ryhanen, P. et al. Department of Radiation Therapy, Oulu University Central Hospital, Oulu, Finland. Acta. Radiol., Ser. Oncol. 24: 481486, 1985. The immunologic status of 59 patients with lung carcinoma was determined by analysis of peripheral venous blood samples. The following tests were performed: total leucocyte and lymphocyte counts, the number of acid alpha-naphthyl acetate esterase (ANAE) positive cells (T-cells), and phytohaemagglutinin (PHA) and tuberculin (PPD) transformation tests. The patients were di-
281
vided into three treatment groups; a surgery group (S), a radiation therapy group (R), and a combined cytostatic and radiation therapy group (C). A follow-up was carried out 4 to 6 months after treatment. The therapeutic measures} resection, irradiation, and chemotherapy, produced a decrease in the total leucocyte and lymphocyte counts, in the number of T-cells, and in the leucocyte transformation response to PPD. In the surgically treated group the decrease was transient. In the groups treated with radiation therapy and combined cytostatic and radiation therapy the values remained low throughout the follow-up. The lymphocyte response to PHA was not altered in any of the groups during initial treatment or follow-up. The results did not suggest a correlation between the immunologic parameters used and the stage and histologic type of lung cancer. The tests were of no clinical value in the determination of the individual prognosis.
10,
OTHERTREATMENTMODALITIES
Controlled Trial of RSV, Herbs or Placebo as Adjuvants to Complete Resection of Squamous Cell Lung Cancer. Osterlind, K., Hansen, M., Hansen, H.H., Dombernowsky, P. Department of Oncology I I , Finsen Institute, DK-2100 Copenhagen, Denmark. Eur. J. Surg. Oncol. ii: 349-351, 1985. 152 completely resected patients with high or intermediate differentiated squamous cell lung cancer were randomized to receive 6 months adjuvant therapy with RSV (1,2diphenyl-abeta-diketone) herbs or placebo. No significant differences were observed in duration of survival or relapse rates between the three groups.
Treated with Neodymi~u-YAG-Laser, Initially Misinterpreted as Small Cell Lung Cancer. Berendsen, H.H., Postmus, P.E., Edens, E.T., Slutter, H.J. Department of Pulmonary Diseases, State University Hospital, 9713 EZ Groningen, Netherlands. Eur. J. Respir. Dis. 68: 151-154, 1986. Two patients are described with bronchial carcinoid. In both, the initial diagnosis was small cell lung carcinoma (SCLC). This diagnosis was discordant with the clinical course; a second evaluation yielded the diagnosis of carcinoid. Good palliation was achieved with YAG-laser therapy.
11,
REVIEWS
Recent Advances in the Biology of Small Cell
Lung Cancer. Carney, D.N. The Mater Hospital, Dublin, Ireland. Chest 89: 253S-257S, 1986. Advances in the techniques for culturing human tumors in vitro, especially lung cancer cells, have greatly facilitated studies of the biologic properties of both small cell and nonsmall cell lung cancer cells. Detailed analysis has been done of wellcharacterized cell lines of both groups with respect to growth properties, biomarker and antigen expression, cytogenetics, and oncogene amplification and expression. Two major conclusions have emerged from these studies: (i) considerable heterogeneity exists within a given tumor type (eg, SCLC) in the expression of a given biomarker, and (2) overlap in the expression of biomarkers exists between cells of SCLC and non-SCLC, suggesting a common stem cell for all types lung cancer. In the future, clinical trials on the impact of the biological properties of cells on responses to therapy and survival will need assessment.
Endobronchial Management of Lung Cancer. Cortese, D.A. Division of Thoracic Diseases and Internal Medicine, Mayo Clinic and Mayo Foundation, Rochester, MD 55905, U.S.A. Chest 89: 234S-236S, 1986. Bronchoscopic phototherapy is available now for 2 distinct categories of tracheobronchial cancer: roentgenographically occult superficial squamous cell carcinoma and advanced malignancy causing significant airway obstruction. Laboratory and clinical experience show that the photodynamic effect of hematoporphyrin derivative phototherapy (HpD~PT) may be useful for treating superficial cancers that penetrate less than 5 mm into bronchial mucosa. The larger, obstructing cancers are better managed by high~ power laser sources, such as the YAG laser, which are effective by hyperthermal photocoagulation, thermal necrosis, and tissue vaporization. Irresectable Bronchial Carcinoid with a 32Year Natural History. A Report of Two Cases
Bronchioloalveolar Carcinomas. Cell Types, Patterns of Growth, and Prognostic Correlates. Calyton, F., Department of Pathology, University of Utah Hospital, Salt Lake City, UT, U.S.A. Cancer 57: 1555-1564, 1986. Forty-five bronchioloalveolar carcinomas were studied, including 27 cases by electron microscopy. Bronchioloalveolar carcinomas can be classified by routine sections or by diastase-digested periodic acid-Schiff (PAS) stains, but electron microscopy is useful in confirming Clara cell or type II pneumocyte (noum~clnous) differentiation and excluding metastases. Mucinous bronchioloalveolar carcinoma can mimic metastatic adenocarcinoma histologically and ultrastructurally. Of the nine tumors with mucinous differentiation, eight had aerogenous dissemination (multifocal or with pneumonic spread), and seven of those eight were fatal. Twenty-four of 36 nonmucinous bronchioloalveolar tumors had aerogenous spread; all