Heine H. Hansen

Prophylactic irradiation in bronchogenic small cell anaplastic carcinoma. A comparative trial of localized versus extensive radiotherapy including prophylactic brain irradiation in patients receiving combination chemotherapy

A total of 114 patients with bronchogenic small cell anaplastic carcinoma and staged as having regional disease all underwent combination chemotherapy consisting of CCNU, cyclophosphamide, and methotrexate. They were randomized to receive either radiotherapy to the primary tumor and regional lymph nodes (4000 rad) or extensive radiotherapy, which included the brain, adrenals, and upper retroperitoneal lymph nodes. Fifteen patients were free of disease after 18 months of chemotherapy and the treatment was discontinued. Only 3 patients subsequently relapsed. No difference was observed between the two groups of patients in median survival time, response rate, duration of response, or relapse pattern, including the frequency of brain metastasis.

Bone-marrow examination in the staging of small-cell anaplastic carcinoma of the lung with special reference to subtyping. An evaluation of 203 consecutive patients.

Histologic examination of bone‐marrow from the posterior iliac crest was routinely done as a pretreatment staging procedure in 203 consecutive patients with small‐cell anaplastic carcinoma of the lung. Subtyping of the patients according to the WHO classification included 27.8% with “fusiform” cell type (WHO II,1), 28.3% with “polygonal” cell type (WHO II,2), 42.8% with “lymphocyte‐like” cell type (WHO II,3), and 1.1% with mixed types (WHO II,4). Bone‐marrow involvement was found in 17.2%. No significant difference was observed among the histological subtypes with regard to bone‐marrow involvement. A comparison of bone‐marrow biopsy and aspiration in patients investigated with both procedures showed that aspiration alone was diagnostic in nine of 24 (38%) positive patients as compared with two of 24 (8%) with biopsy alone, while in the remaining 13 patients (54%) both procedures were positive. Of the 35 patients with positive bone‐marrow examination, 77% had no other evidence of distant metastatic disease if liver metastases identified by peritoneoscopy and liver biopsy are excluded as a staging procedure. With the exception of thrombocytopenia which was observed in six patients, with bone‐marrow metastases, hematological findings were of little value in detecting bone‐marrow involvement.

Hormonal polypeptides and amine metabolites in small cell carcinoma of the lung, with special reference to stage and subtypes.

To elucidate the ectopic hormonal pattern in patients with small cell carcinoma of the lung, plasma ACTH, serum calcitonin, serum gastrin, plasma glucagon, serum insulin, plasma secretin, plasma VIP, serum growth hormone, serum hCG/LH, the total of serum hCG and hCG‐β‐subunit, serum α‐subunit, serum human placental lactogen, urine ADH, urine 5‐HIAA, urine VMA, urine HVA, and urine hCG‐LH were measured prior to therapy in 75 patients. Twenty‐two patients (29%) had elevated plasma ACTH, and 18 of these had concomitant increased values of corticosteroids in a 24‐hour urine sample. Forty‐eight patients (64%) were found to have elevated serum calcitonin, and one‐third of the patients were diagnosed as having the ectopic ADH syndrome. Serum gastrin concentrations were increased in 20% of the patients, but the elevations were marginal in almost all cases. None of the remaining substances was found to be significantly elevated. Concentrations of plasma ACTH, serum calcitonin, and urine ADH were not found to be correlated with the stage of the disease, and no correlation of these substances with the histological subtypes of small cell carcinoma was disclosed.

Treatment of small cell anaplastic carcinoma of the lung with the oral solution of VP‐16‐213 (NSC 141540, 4′‐demethylepipodophyllotoxin 9‐(4,6‐0‐ethylidene‐β‐D‐glucopyranoside)

The semisynthetic podophyllotoxin derivative VP‐16‐213 (NSC 141540) has been evaluated in a phase II study in patients with small cell anaplastic carcinoma of the lung. The drug was administered as an oral solution, the drinking ampoule, in doses of 100 mg twice a day for 4 days in 30 patients previously treated with intensive combination chemotherapy and for 5 days in 10 untreated patients. The courses were repeated every third week with dose modifications according to individual tolerance. All patients had measurable disease and objective responses were obtained in 20 patients (50%), 15 previously treated (50%) and 5 untreated patients (50%). The median time for response after the start of treatment was 15 days (range 6–42) and the median duration of response was 56 days (range 16–147). Dose‐limiting toxicity was principally hematologic, consisting of leukopenia, but gastrointestinal toxicity and alopecia were also observed. The study demonstrated that VP‐16‐213 administered as an oral solution is highly effective against small cell anaplastic carcinoma of the lung without clinical cross‐resistance to CCNU, cyclophosphamide, methotrexate, or vincristine. Cancer 40:633–637, 1977.

Peritoneoscopy in the staging of 190 patients with small‐cell anaplastic carcinoma of the lung with special reference to subtyping

Peritoneoscopy with liver biopsy was routinely done as a pretreatment staging procedure in 190 patients with small‐cell anaplastic carcinoma of the lung. Subtyping of the patients according to the WHO classification included 28.3% with fusiform cell type (WHO II,1), 28.9% with polygonal cell type (WHO II, 2), 41.5% with lymphocytelike cell type (WHO II, 3) and 1.3% with mixed types (WHO II, 4). Liver metastases were found in 21% of the patients with adequate liver biopsy. In addition macroscopic signs of liver metastases were observed in 9%. No significant differences were observed among the histological subtypes. Liver function tests, such as alkaline phosphatase, LDH and GOT, were of little value in excluding liver metastases. On the other hand, 2 of 3 abnormal liver function tests were highly indicative of liver metastases. In patients with positive liver biopsy, 41% had liver metastases alone and 76% had no other evidence of distant metastatic disease if bone‐marrow involvement identified with bone marrow examination is excluded as a staging procedure.

Diagnosis of liver metastases in bronchogenic carcinoma: A comparative study of liver scans, function tests, and peritoneoscopy with liver biopsy in 111 patients

Evaluation of hepatic metastases was performed in a series of 111 patients with untreated unresectable bronchogenic carcinoma, comparing liver chemistries with liver scanning and peritoneoscopy with liver biopsy under direct vision. The latter procedure proved metastases in 10.2% of 98 patients biopsied, including 8 of 19 patients with small cell carcinoma, 1 of 41 with epidermoid carcinoma, 1 of 24 with adenocarcinoma, and 0 of 14 with large‐cell anaplastic carcinoma. Correlation of the histopathologic findings with liver scan and liver chemistries is discussed. The findings demonstrate that peritoneoscopy and liver biopsy under direct vision are indicated in order to obtain optimal staging in many cases of small cell carcinoma, and for the other cell types in those patients whose liver scans and/or liver enzymes are suggestive of malignant hepatic involvement.

Small Cell Anaplastic Carcinoma of the Lung: Staging

The presence and the type of metastases in patients with cancer are important predictable parameters for the clinical course of a malignancy, and in addition they have major indications for planning of the therapeutic strategy. Since surgery is the main curative treatment for lung cancer, much attention has been focused on the pattern of the local regional involvement. In particular, the size of the primary tumor as well as the status of regional lymph nodes as expressed in the TNM system according to the classification of the WHO and the American Joint Committee on Cancer Staging and End Results Reporting have been the subject for detailled analysis [1, 2].