Indication for surgery in small-cell carcinoma of the lung.

While the development of chemotherapeutic agents has lead to progress in the treatment of small-cell carcinomas of the lung, the number of local recurrences still remains high. Surgery in tumors stage I and II followed by postoperative chemotherapy is the treatment of choice and has been accepted worldwide. In tumors stage IIIa, especially in T1-3 N2 we obtained good results in the projected 3-year survival using a multimodality therapeutic regime consisting of neoadjuvant chemotherapy (3 cycles preoperative) and surgery as well as postoperative chemotherapy and irradiation of the mediastinum. Projected 3-year survival was 67% in stage I tumors, 42% in stage II and with our multimodality therapeutic regime 38% in stage III a tumors.     

Cancer-associated retinopathy during treatment for small-cell lung carcinoma.

A 70-year-old woman with small-cell lung carcinoma (c-T4N2M0) was treated by six courses of combination chemotherapy (carboplatin and etoposide). After two weeks, she complained of a sense of darkness and night blindness. A Western blot analysis showed that the patient's serum bound with the recombinant 23-kDa retinal cancer-associated retinopathy (CAR) antigen at 1:1,000 dilution. Her visual acuity became so poor that she could only recognise a hand motion at 50 cm despite treatment with corticosteroids and combination chemotherapy. The patient was diagnosed as having a rare type of CAR because CAR is usually found before the diagnosis of primary cancer.     

Human lung small-cell carcinoma contains bombesin.

The presence of immunoreactive bombesin in a human lung small-cell carcinoma grown in nude mice was established by several criteria: (i) Radioimmunoassay of tissue extracts for bombesin revealed approximately 6.5 pmol/g of tissue; (ii) bombesin was found in 12-14% of the tumor cells by immunohistochemical localization; (iii) gel filtration of small-cell carcinoma extract on Sephadex G-75 and Bio-Gel P-4 gave only a single peak of immunoreactivity, which occurred at the elution volume of bombesin; and (iv) reverse-phase HPLC of acid-solubilized extracts separated the immunoreactive material into three discrete peaks, one of which eluted with a retention time identical to that of synthetic bombesin. The presence of bombesin may represent the ectopic expression of this peptide in small-cell carcinoma, because immunoreactive bombesin was found in human fetal and neonatal lung but apparently not in adult lung tissue [Wharton, J., Polak, J. M., Bloom, S. R., Ghatei, M. A., Solcia, E., Brown, M. R. & Pearse, A. G. E. (1978) Nature (London) 273, 769-770]. The immunoreactive bombesin previously found in mammalian tissues is considerably larger than amphibian bombesin; these data substantiate the presence of a mammalian form of bombesin in a human tumor that may have a structure similar to that of the amphibian peptide.     

Enteric neuronal autoantibodies in pseudoobstruction with small-cell lung carcinoma.

Severe gastrointestinal dysmotility is a newly recognized paraneoplastic syndrome that occurs with small-cell lung carcinoma. Thirty-four patients with small-cell carcinoma, of whom 5 had chronic intestinal pseudoobstruction and 29 had no digestive symptoms, were studied serologically. Four of the 5 patients with gut dysmotility had immunoglobulin G antibodies reactive with neurons of the myenteric and submucosal plexuses of jejunum and stomach in an indirect immunofluorescence assay. Antibodies of this type were not found in any of the 29 patients who had no gut dysmotility, nor were they found in patients with chronic idiopathic intestinal pseudoobstruction (n = 8), ovarian cancer (n = 20), or epilepsy (n = 4) or in normal subjects (n = 9). In 4 of the patients with paraneoplastic pseudoobstruction, antibodies in highly diluted serum (1:4000-1:8000) bound selectively to nuclei and cytoplasm of neuronal elements in the gut. This novel autoantibody activity suggests that intestinal pseudoobstruction occurring in patients with small-cell carcinoma may have an autoimmune basis. From a clinical standpoint, serological testing offers a simple means for determining which patients with gut dysmotility syndromes may have associated small-cell carcinoma, thereby enabling earlier diagnosis and treatment of the tumor.     

Is bone marrow examination in small-cell lung cancer really necessary?

Of 403 patients with small-cell lung cancer, we identified by aspiration, biopsy, or both 67 with bone marrow involvement and found the two procedures to be complementary in detecting marrow involvement. The mean surface area of the positive biopsy specimens was significantly greater than that of a randomly selected group of negative biopsy specimens, suggesting that the larger the specimen, the greater the chance of detecting tumour. Patients with marrow involvement had only a slightly worse prognosis compared with other patients who had extensive disease. Only 7 of the 403 patients (1.7%) had extensive disease based on marrow involvement alone. Because bone marrow examination rarely changes the stage of cancer in noninvasively assessed patients, and has no impact on the tolerance of chemotherapy and only a small effect on length of survival, we do not recommend this procedure in the routine staging of small-cell lung cancer.     

Peptide hormone immunoreactivity and prognosis in small-cell carcinoma of the lung

Paraffin-embedded specimens from a total of 94 small-cell carcinomas of the lung (SCCL) were screened for immunoreactivity to nine different peptide hormones (ACTH, calcitonin, gastrin, glucagon, growth hormone, human chorion gonadotropin, insulin, somatostatin and vasoactive intestinal peptide, VIP) using an indirect immunoperoxidase technique with commercially available kits. Special attention was focused on the prognostic significance of the peptide immunoreactivity. A total of 32 carcinomas (34%) showed immunoreactivity to one or more peptide hormones, the cases with ACTH reactivity (24.5%) far outnumbering those with reactivity to calcitonin (1.1%), somatostatin (1.1%), VIP (3.3%) or multiple peptides (4.3%). The mean survival of the patients was 8.4 months, being shorter (7.3 months) for the SCCLs with peptide reactivity than for the nonreactive carcinomas (9.2 months). The most favorable survival was found in VIP-reactive tumors (20.5 months), and the worst (2.0 months) in cases reactive to multiple peptides. The results suggest that immunohistochemical screening of the SCCL biopsies for the peptide hormones might be of benefit in predicting the clinical outcome of the disease.     

Dose intensity of chemotherapy in small-cell lung carcinoma. Review of comparative studies

Chemotherapy improves survival and achieves an impressive response rate, and, eventually, a percentage of long-term survivors in small-cell lung cancer. A possible way to a further improvement of these therapeutic outcomes is increasing chemotherapy dose-intensity. However, randomised comparative trials only show a slight improvement of results, with small clinical relevance. Prophylactic use of colony-stimulating factors decrease the incidence of neutropenia and neutropenic fever in comparative studies when an exceedingly myelotoxic chemotherapy regimen is used. And they also permit a little increase in chemotherapy dose-intensity without significant antineoplastic effect and almost no impact in overall survival. Nowadays, the administration of higher doses of chemotherapy in small-cell lung cancer still remains investigational in oncology.     

Expression of neurophysin-related precursor in cell membranes of a small-cell lung carcinoma.

A monoclonal antibody (mAb L6) to a small-cell lung carcinoma surface antigen recognizes a common epitope of vasopressin-neurophysin and oxytocin-neurophysin in hypothalamic nuclei. We now report on the identification of a neurophysin-like precursor in human lung carcinoma (LX-1) cell membrane. mAb L6 immunoaffinity chromatography of solubilized membranes resulted in a single band of approximately 45 kDa. Western blot analysis demonstrated immunoreactivity of this band with mAb L6, anti-vasopressin, and an antibody to the vasopressin precursor, pro-pressophysin. N-terminal sequencing of this band demonstrated a 21-amino acid homology with the N terminus of human pro-pressophysin, and substitution of a Cys33 residue in the tumor antigen with Arg33. Absence of immunoreactivity with the antibodies described above in cytosolic extracts and culture medium suggests nonsecretion of processed or intact pro-pressophysin-like peptide. Northern analysis of LX-1 mRNA with a 30-mer to the C terminus of rat pro-pressophysin resulted in a band of approximately 1000 base pairs, 250 base pairs larger than hypothalamic message. In situ hybridization of LX-1 tumor-bearing nude rat brain with the same probe demonstrated specific hybridization in rat hypothalamus and xenografted tumor. These findings suggest expression of a pro-pressophysin-like protein in this tumor cell line that is preferentially targeted to the cell membrane.     

Elevated serum chromogranin A concentrations in small-cell lung carcinoma

Serum chromogranin A concentrations measured by radioimmunoassay in patients with small-cell lung carcinoma were compared with values from healthy adults and patients with non-small-cell lung carcinoma or chronic obstructive pulmonary disease. The mean (+/- SE) level was significantly higher (p less than or equal to 0.02) in patients with small-cell lung carcinoma (815 +/- 290 ng/mL, n = 46) than in normal controls (123 +/- 6 ng/mL, n = 20) or patients with chronic obstructive pulmonary disease (169 +/- 18 ng/mL, n = 39), lung adenocarcinoma (180 +/- 22, ng/mL, n = 62), large-cell lung carcinoma (183 +/- 23 ng/mL, n = 18), or lung epidermoid carcinoma (203 +/- 37 ng/mL, n = 78). The mean concentration in extensive-stage small-cell lung carcinoma (1155 +/- 449 ng/mL, n = 29) was significantly greater (p = 0.026) than in limited disease (234 +/- 56 ng/mL, n = 17). Elevated serum chromogranin A values were seen in 53% of patients with limited and 72% with extensive disease. Four patients originally classified as having non-small-cell lung carcinomas with raised chromogranin A levels were subsequently found to have mixed small-cell and non-small-cell tumors. Serum chromogranin A concentrations may be a useful marker of small-cell lung carcinoma disease activity.     

Vincristine (NSC-67574) in the treatment of small-cell anaplastic carcinoma of the lung.

In a phase II trial the effect of vincristine as a single agent was evaluated in patients with small-cell anaplastic carcinoma of the lung. The dosage of vincristine was 1.5 mg/m2/week given iv for 4 weeks, followed by 1.5 mg/m2 given every other week with dose modifications according to neurologic tolerance. Nineteen of 27 patients included in the study were evaluable. Objective response was observed in eight patients (42%) including three who were not previously treated and five who were previously treated. The median duration of response was 60 days (range, 21-182 days) with the response always occurring within 4 weeks. This study demonstrates that vincristine is an active agent for small-cell anaplastic carcinoma without cross resistance to CCNU, cyclophosphamide, or methotrexate.     

Management of small-cell lung cancer in the elderly.

More than 50% of lung cancer patients are diagnosed over the age of 65 and about 30% over 70. Small-cell lung cancer (SCLC) accounts for 20-25% of lung carcinomas. Chemotherapy is the cornerstone of treatment for SCLC. Usually in the elderly it is difficult to administer the same chemotherapy administered to younger patients because elderly patients tolerate chemotherapy poorly. The empirical reduction of drug doses may be criticized. The best approach is to design specific trials in order to develop active and well-tolerated chemotherapy regimens for SCLC elderly patients. The standard therapy in limited disease is combined chemo-radiotherapy followed by prophylactic brain irradiation for patients achieving a complete response. In the elderly, the addition of radiotherapy to chemotherapy must be accurately evaluated, considering the slight survival improvement and the potential relevant toxicity.     

Conditional survival among patients with carcinoma of the lung.

OBJECTIVE: One- and 5-year probabilities of survival or death change once a patient has already survived > or = 1 year after diagnosis. The current paper reports these probabilities for lung cancer patients according to histologic subtype, stage, and age at diagnosis. METHODS: Cumulative observed survival rates were calculated and compared among 95,283 patients with histologically confirmed lung cancer (diagnosed from 1983 to 1992 and followed through 1995) by the life-table method using population-based tumor registries participating in the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute. On the basis of the cumulative survival estimates, we derived the probability of death in the next year, conditioned on having already survived to the start of the year (annual hazards), and the probability of survival conditioned on having already survived > or = 1 year (conditional survival). These rates were reported according to histologic subtype, stage, and age groups. RESULTS: At the time of diagnosis, annual hazard rates differ greatly among histologic subtypes. However, by 5 years after diagnosis, the rates become similar. Bronchioloalveolar carcinoma displays the lowest annual hazards and small-cell carcinoma displays the highest annual hazards. Stage-age subcategories within histologic subtypes continue to show large differences in annual hazard rates. Five-year conditional survival probabilities are also reported, providing survival information that is consistent to that obtained from the annual hazards. CONCLUSIONS: One- and 5-year prognosis for lung cancer patients is influenced by years already survived and histology, stage, and age at diagnosis. Annual hazards and conditional survival provides useful and more relevant information than conventional survival estimates for patients and their physicians. These statistics can be directly obtained from cumulative survival estimates and should be more widely reported.