Diagnosis Of SCLC Research Articles

The Use of Immunohistochemistry Improves the Diagnosis of Small Cell Lung Cancer and Its Differential Diagnosis. An International Reproducibility Study in a Demanding Set of Cases

IntroductionThe current WHO classification of lung cancer states that a diagnosis of SCLC can be reliably made on routine histological and cytological grounds but immunohistochemistry (IHC) may be required, particularly (1) in cases in which histologic features are equivocal and (2) in cases in which the pathologist wants to increase confidence in diagnosis. However, reproducibility studies based on hematoxylin and eosin–stained slides alone for SCLC versus large cell neuroendocrine carcinoma (LCNEC) have shown pairwise κ scores ranging from 0.35 to 0.81. This study examines whether judicious use of IHC improves diagnostic reproducibility for SCLC. MethodsNineteen lung pathologists studied interactive digital images of 79 tumors, predominantly neuroendocrine lung tumors. Images of resection and biopsy specimens were used to make diagnoses solely on the basis of morphologic features (level 1), morphologic features along with requested IHC staining results (level 2), and all available IHC staining results (level 3). ResultsFor the 19 pathologists reading all 79 cases, the rate of agreement for level 1 was 64.7%, and it increased to 73.2% and 77.5% in levels 2 and 3, respectively. With IHC, κ scores for four tumor categories (SCLC, LCNEC, carcinoid tumors, and other) increased in resection samples from 0.43 to 0.60 and in biopsy specimens from 0.43 to 0.64. ConclusionsDiagnosis using hematoxylin and eosin staining alone showeds moderate agreement among pathologists in tumors with neuroendocrine morphology, but agreement improved to good in most cases with the judicious use of IHC, especially in the diagnosis of SCLC. An approach for IHC in the differential diagnosis of SCLC is provided.

Protocol for the CONVERT trial—Concurrent ONce-daily VErsus twice-daily RadioTherapy: an international 2-arm randomised controlled trial of concurrent chemoradiotherapy comparing twice-daily and once-daily radiotherapy schedules in patients with limited stage small cell lung cancer (LS-SCLC) and good performance status

IntroductionConcurrent ONce-daily VErsus twice-daily RadioTherapy (CONVERT) is the only multicentre, international, randomised, phase III trial open in Europe and Canada looking at optimisation of chemoradiotherapy (RT) in limited stage small...

Screening with Low-Dose Computed Tomography Does Not Improve Survival of Small Cell Lung Cancer

IntroductionSmall cell lung cancer (SCLC) constitutes a distinct component of symptomatic or advanced-stage lung cancers in clinical practice and in lung cancer screening trials. The purpose of this study was to describe the outcome of SCLC in lung cancer screening trials and compare the frequency of SCLC in our cohort with that in the major lung cancer screening trials. MethodsSubjects with a diagnosis of SCLC were selected from two lung cancer screening trials by low-dose computed tomography (LDCT), and their demographic characteristics, clinical parameters, tumor stage at diagnosis, therapy, and survival times were recorded. Survival curves were estimated using the Kaplan-Meier method. ResultsTen cases of SCLC were reported in 45,141 person-years (22 in 100,000 person-years), representing the 6% of all lung cancer cases. Cumulative tobacco consumption was 82 pack-years compared with 39 and 46 pack-years for the overall study population and subjects with non-SCLC, respectively. Most of the neoplasms were in an advanced stage (seven in stage IV and one each in stages IIIb, IIIa, and Ia). Two subjects were treated with lobectomy for curative purposes and died of diffuse metastasis within 2 years of diagnosis. The median overall survival time in the LDCT arms was 20.6 months, with no survivors remaining at 3 years. ConclusionsSubjects in whom SCLC develops are a subgroup of smokers with extremely high cumulative tobacco consumption. Consequently, the frequency of SCLC in our population was lower than in other screening populations, with higher cumulative tobacco consumption. Screening for lung cancer by LDCT does not improve survival of SCLC, with no survivors remaining at 3 years after diagnosis.

Diagnostic difficulties with the diagnosis of small cell carcinoma of the lung.

Small cell carcinoma of the lung (SCLC) is a well characterized form of lung cancer that is frequently already metastatic at diagnosis. Thus, patients with SCLC are usually treated with chemotherapy, and therefore emphasis has been placed on distinguishing that tumor from squamous cell carcinomas, large cell carcinomas and other pulmonary neoplasms that can more often be managed surgically. SCLC can be readily and accurately diagnosed in biopsy specimens or cytological preparations, but in selected cases, it can pose difficult diagnostic dilemmas. This review discusses selected problems encountered during the pathologic diagnosis of SCLC, including its distinction from other neuroendocrine lesions such as large cell neuroendocrine carcinoma and "carcinoid" tumors." The role of immunohistology is also considered in this context.

Second-Line Therapy of Small-Cell Lung Cancer: Topotecan Compared to a Combination Treatment with Adriamycin, Cyclophosphamide And Vincristine (ACO) - a Single Center Experience.

Background: Randomized trials established topotecan and the combination of adriamycin, cyclophosphamide and vincristine (ACO) as second-line therapy options for small-cell lung cancer. We retrospectively evaluated the outcome of SCLC patients undergoing second-line chemotherapy.Patients and Methods: 92 consecutive patients with a diagnosis of SCLC between 2000 and 2010 were analyzed.Results: 86 patients (93.5%) were evaluable for outcome analysis. All patients diagnosed with limited disease (LD) SCLC received platinum-based chemotherapy as first-line treatment. 69 patients (98.6%) diagnosed with extensive disease (ED) SCLC received first-line palliative chemotherapy. In the total cohort, the median overall survival (OS) was 10.3 months (19.2 months and 9.2 months for LD-SCLC and ED-SCLC, respectively). 42 patients received second-line therapy (ACO in 47.6% and topotecan in 31.0% of patients, respectively). Eight patients (19.0%) were re-challenged with platinum/etoposide. Neither the overall response rate (52.9% vs. 22.2%; p=0.128) nor progression-free survival (2.4 vs. 2.4 months; p=0.794) or OS (5.5 vs. 5.0 months; p=0.997) were significantly different between ACO and topotecan. ACO-treated patients showed a trend towards a longer duration of inpatient care.Conclusion: We showed similar outcomes as reported in clinical trials. Second-line combination chemotherapy with ACO did not show superiority to intravenous topotecan, but was associated with a clinically relevant longer hospitalization time.

Clinicopathological Features in Young Patients Treated for Small-Cell Lung Cancer: Significance of Immunohistological and Molecular Analyses

BackgroundSmall-cell lung cancer in young patients is very rare and has not been adequately described. In addition, malignancies associated with genetic rearrangements of nuclear protein of the testis (NUT) have been reported in young patients. Patients and MethodsWe reviewed the clinical records of patients younger than 40 years of age who had been diagnosed as having SCLC and had been treated for this condition. We also examined NUT rearrangements using immunohistochemistry (IHC) staining and fluorescence in situ hybridization (FISH) analysis. ResultsWe evaluated the diagnoses and treatment outcomes of 8 young patients among 747 SCLC patients. Based on further analyses using IHC staining and FISH, NUT rearrangements were found in 2 of these cases. The range of the overall survival period was 3.6 to 49.7 months. The 2 patients with NUT rearrangements survived for less than 12 months. ConclusionNUT rearrangements were identified in 2 patients who had been previously diagnosed as having SCLC. Further attention regarding the diagnosis of SCLC in young patients is needed.

Pathways impact on chemotherapy administration before death.

86 Background: Continuing IV chemotherapy (chemo) in patients (pts) with advanced cancer near death does not extend survival or improve quality, but does increase costs. Pathways (PW) programs have compared treatment (tx) costs but have not evaluated the impact on chemo given near death. The primary goal is to evaluate IV chemo administered in the last 14 and 30 days of life in pts treated On vs. Off-PW. Methods: Eligibility: in US Oncology’s (USO) iKnowMed (iKM) EHR 7/1/09-6/30/12; diagnosis (dx) of breast, colon, NSCLC, SCLC or pancreas cancer; >/=3 visits to a USO clinic; assessed for Level I PW compliance in the last 12 mths of life; and a date of death. IV chemo received in the last year of life was assessed. Pts were defined On-PW if all tx was On-PW or if pts did not receive IV chemo 12 mths before death (best supportive care). Pts were Off-PW if any tx received was Off-PW. PW-status, age, sex, dx, and last line of therapy (LOT) received were assessed. Multivariate logistic regression analysis was used to assess if PW status predicted likelihood of chemo within 14 and 30 days of death. Results: 12,551 pts met inclusion criteria. PW status was independently associated with chemo 14 and 30 days before death. Pts treated Off-PW had 2-fold higher odds of receiving IV chemo within 14, 30 days of death vs. pts treated On-PW (OR: 2; 95% CI: 1.8-2.3, OR: 2.2, 95% CI: 2-2.4), see Table. Findings were similar for each dx. Tx for pts On-PW vs Off-PW showed lower mean last LOT overall (1 vs. 2) and by dx. Conclusions: Pts On-PW were less likely to receive IV chemo within 14 and 30 days of death and had fewer LOT. This suggests adherence to Level I PWs is associated with improved quality metrics. [Table: see text]

Impact of pathways on chemotherapy administration before death.

6580 Background: Continuing IV chemotherapy (chemo) in patients (pts) with advanced cancer near death neither extends survival nor improves quality, but does increase costs. Pathways (PW) programs have focused on comparing treatment (tx) costs but have not evaluated the impact on chemo given near death. The primary goal is to evaluate IV chemo administered in the last 14 days of life for pts treated On-PW vs. Off-PW. Methods: Eligible pts: in US Oncology’s (USO) iKnowMed (iKM) EHR; diagnosis (dx) of breast, colon, NSCLC, SCLC or pancreas cancer; >/=3 visits to a USO clinic; assessed for Level I PW compliance in the last 12 mths of life; and a documented date of death. IV chemo received in the last year of life was assessed. Pts were defined On-PW if all tx was On-PW or if pts did not receive IV chemo 12 mths before death (best supportive care). Pts were defined Off-PW if any tx received was Off-PW. PW-status, age, sex, dx, and last line of therapy (LOT) received were assessed. Multivariate logistic regression analysis was used to assess if PW status predicted likelihood of chemo within 14-days of death. Results: From 7/1/09-6/30/12, 12,551 pts met inclusion criteria. PW status was independently associated with chemo 14 days before death. Pts treated Off-PW had a two-fold higher odds of receiving IV chemo within 14 days of death compared to pts treated On-PW (OR: 1.99; 95% CI: 1.77-2.26), see the Table. Findings were similar for each dx. Tx for pts On-PW vs Off-PW showed lower mean last LOT overall (1 vs. 2) and by dx. Conclusions: Pts On-PW were less likely to receive IV chemo within 14 days of death and had fewer LOT. This suggests adherence to Level I PWs is associated with improved quality metrics. [Table: see text]

A randomized double-blind phase II study of the Seneca Valley virus (NTX-010) versus placebo for patients with extensive stage SCLC (ES-SCLC) who were stable or responding after at least four cycles of platinum-based chemotherapy: Alliance (NCCTG) N0923 study.

7509 Background: NTX-010 is a naturally occurring replication-competent picornavirus with potent and selective tropism for SCLC tumor cells expressing neuroendocrine markers. A phase I study of NTX-010 showed evidence of antitumor activity in patients with SCLC. Methods: ES-SCLC patients (pts) with SD, PR or CR after at least 4 cycles of platinum-based chemotherapy were pre-registered to confirm diagnosis of SCLC with > 1 neuroendocrine marker by a central pathology review. Eligible pts were.randomized 1:1 to placebo (B) or NTX-010 (A). NTX-010 or placebo was administered intravenously as a 1-hour infusion in 100 mL normal saline as a single dose of 1 x1011vp/kg. Viral studies to determine distribution, clearance of the virus and the presence of neutralizing antibodies were done. The primary goal of this trial was to compare the progression-free survival (PFS) of arm A to B based on a sample size of 45 patients per arm to detect an improvement in median PFS from 3 to 5 months (m). A pre-planned interim futility analysis was done after 40 PFS events, and reported here. Results: The trial is permanently closed to accrual. One-hundred and twenty pts were pre-registered, of whom 58 were randomized. Baseline age, gender, ECOG performance status, and histology were balanced between arms. Median age was 63 (range: 44 - 82). 31% of pts had a PS of 0 and 69% of 1. Grade 4 adverse events were seen in 3 (12.5%) patients in arm A and none in arm B. Based on the interim futility analysis, PFS was 1.7 m (95% CI: 1.3-3.1) for arm A and 1.7 m (95% CI: 1.4-4.3) for arm B. Pts with viral RNA at 7 (7 pts) and 14 (6 pts) days had worse PFS compared to those with no detectable levels within arm A (1.0 vs 1.6 m, p=0.02; 0.9 vs. 1.2 m, p=0.06). Median follow-up in pts is 6.1 m. The 3-month OS estimates are 83% (95% CI: 69%-100%) and 85% (70%-100%) for arms A and B respectively. Conclusions: This phase II study showed no benefit in PFS for ES-SCLC patients receiving NTX-010. Pts with detectable virus at 7 and 14 days had worse PFS. Clinical trial information: NCT01017601.

Clinical Outcomes of Extensive Stage Small Cell Lung Carcinoma Patients Treated With Consolidative Thoracic Radiotherapy

ObjectivesTo determine the rates of loco-regional (LR) failure and toxicity in extensive-stage small cell lung carcinoma (ES-SCLC) patients treated with consolidative thoracic radiotherapy (TRT). MethodsA retrospective review was conducted on SCLC patients treated from January 2005 to July 2009. Patients with ES-SCLC who received consolidative TRT ≥30Gy were identified. Sites of disease failure, toxicity Common Terminology Criteria for Adverse Events version 3.0, incidence, and cause of treatment delays and vital status were determined. The cumulative LR and distant failure rates were calculated. Progression-free and overall survivals (OS) were determined by the Kaplan-Meier method. ResultsThree hundred thirty-six patients were identified with a diagnosis of SCLC and 215 patients had ES-SCLC. Nineteen (9%) patients were identified as receiving ≥30Gy consolidative TRT. Of this subgroup, the median age was 60 years (range 47 years to 82 years) and the median follow-up was 13 months (range 8 months to 32 months). Consolidative TRT was 40Gy/15 fractions (n = 16), 45Gy/30 fractions delivered twice daily (n = 2) and 36Gy/12 fractions (n = 1). Chemotherapy was sequential (n = 11) or concurrent (n = 8) with consolidative TRT. The incidence of LR failure was 26% and 39% at 1 and 2 years, respectively. The incidence of distant failure was 58% and 74% at 1 and 2 years, respectively. The median OS was 14 months. The 1-year and 2-year OS was 58% and 14%, respectively. No patients experienced clinical pneumonitis requiring treatment. ConclusionsConsolidative TRT controlled LR disease in most patients with minimal acute toxicity, though distant failure remained a significant problem.

Clinical responses of large cell neuroendocrine carcinoma of the lung to cisplatin-based chemotherapy

The efficacy of chemotherapy in patients with large cell neuroendocrine carcinoma of the lung (LCNEC) remains unclear. Patients with LCNEC who received cisplatin-based chemotherapy were identified by reviewing 567 autopsied and 2790 surgically resected lung cancer patients. The clinical characteristics and objective responses to chemotherapy in these patients were analyzed. Overall, 20 cases of LCNEC were identified, including stage IIIA (n=3), stage IIIB (n=6), stage IV (n=6) and postoperative recurrence (n=5) cases. Six patients had received prior chemotherapy, and 14 were chemo-naive patients. The patients had received a combination of cisplatin and etoposide (n=9), cisplatin, vindesine and mitomycin (n=6), cisplatin and vindesine (n=4), or cisplatin alone (n=1). One patient showed complete response and nine showed partial response, yielding an objective response rate of 50%. The response rate did not differ between patients with the initial diagnosis of SCLC and those with the initial diagnosis of NSCLC, however, the response rate in chemo-naive patients (64%) was significantly different from that in previously treated patients (17%). Our results suggest that the response rate of LCNEC to cisplatin-based chemotherapy was comparable to that of SCLC.

Le syndrome d’hyperperméabilité capillaire idiopathique : à propos de deux cas

We report on two cases of severe hypovolemic shock related to the diagnosis of idiopathic capillary leak syndrome (SCLS). Two patients – a 34-year old man and a 47-year old woman – were admitted in an intensive care unit with circulatory failure. One patient had abdominal pain. The association of elevated hematocrit, decreased albumin serum concentration and the presence of monoclonal IgG kappa immunoglobulins confirmed the diagnosis of SCLC. SCLC is a rare disease with a poor prognosis, the pathophysiology of which remains unexplained. It is characterized by acute periods of hypotension subsequent to a shift of fluid and proteins from the intravascular to the interstitial space. During an attack, a paradoxical hypoproteinaemia in the context of major haemoconcentration suggests the diagnosis. Between attacks, a benign monoclonal gammapathy is often present and appears to be a cornerstone of the diagnosis. Currently, betamimetics and phosphodiesterase inhibitors are proposed as a prophylactic therapy.

Immunoradiometric Assay of Chromogranin a in the Diagnosis of Small Cell Lung Cancer: Comparative Evaluation with Neuron-Specific Enolase

The aims of our work were 1) to determine the diagnostic performance of an immunoradiometric assay of chromogranin A (CgA) in small cell lung cancer and 2) to compare its discriminatory power with that of neuron-specific enolase (NSE), the marker currently used for SCLC. We selected 166 cases of small cell (64) and non-small cell (102) lung cancer and 106 cases of non-malignant lung diseases as controls. Both CgA and NSE were assayed by immunoradiometric methods and cutoff values were established on the basis of a pre-fixed specificity of 95% in non-malignant lung diseases. The CgA assay showed better diagnostic sensitivity than NSE in SCLC (61% versus 57%), especially in limited disease, and a low positivity rate in NSCLC with respect to NSE (14% versus 22%). By contrast, NSE reflected disease extent more accurately than CgA (U test: CgA p<0.05, NSE p<0.001). Finally, we found that the CgA assay was not affected by hemolysis whereas NSE serum levels greatly increased in hemolyzed sera. In conclusion, CgA assaying by an IRMA method is a reliable procedure in the diagnosis of SCLC. NSE remains the marker of choice in staging and monitoring of the disease. Further studies are needed to evaluate the prognostic significance of the marker and its role in therapy monitoring and patient follow-up.

Effect of statins on C-reactive protein in patients with coronary artery disease

patients who had SCLC-LEMS with a matched group of patients who had SCLC only. Survival data were available for 15 SCLC-LEMS patients seen in a neuromuscular clinic since 1987. All had biopsyproven SCLC, typical clinical and electromyographic features of LEMS, and raised titres of anti-P/Q-type voltagegated calcium channel antibodies detectable by RIA. Hospital records were available for SCLC patients who had no neurological illness and who had participated in randomised SCLC treatment trials between 1988 and 1997 at the Middlesex and University College Hospitals, London, UK. We matched each of the 15 SCLC-LEMS patients with five or six SCLC-only patients (n=81) for sex, age at SCLC diagnosis, tumour extent (limited or extensive), and treatment (chemotherapy of radiotherapy). Computer matching was done by medical staff masked to the SCLCLEMS patients’ survival data. Three SCLC-LEMS patients had extensive disease at tumour diagnosis; four did not receive specific tumour treatment because they died soon after diagnosis. With one exception, symptoms of LEMS predated the diagnosis of SCLC (range 0·3–4·7 years). At the time of the study, four SCLC-LEMS patients were alive with no evidence of tumour recurrence after a median of 6 years (range 1·5–8·5) since tumour detection and treatment. Kaplan-Meier survival estimates (figure) show a significantly shorter median survival time from the diagnosis of SCLC in SCLC-only patients (10 months) than in the SCLC-LEMS patients (17·3 months, p=0·048, Log-rank test). Factors contributing to this better survival rate in SCLC-LEMS might be a slower rate of growth in tumours that provoke LEMS, or lead-time bias, in that once LEMS is diagnosed, the vigilance for associated lung cancer may be increased. In SCLC-LEMS, however, tumour macrophage infiltration is greater and MHC class I antigen expression less in patients with SCLC only, which implies more tumour-cell destruction in LEMS. Moreover, the time between onset of LEMS and clinical presentation of the tumour can be longer than would be predicted from the estimated ratio of tumour growth on the basis of radiographic analysis of non-LEMS patients. These observations and our survival data support the view that the autoimmune response in LEMS retards tumour growth. Therefore, the recognition of LEMS in any patients with SCLC could have important implications for long-term outcome after antitumour therapy.

Pro-gastrin-releasing peptide(31-98) as a tumour marker of small-cell lung cancer: comparative evaluation with neuron-specific enolase

We attempted to clarify whether serum levels of a carboxy-terminal fragment of ProGRP, ProGRP(31-98), could serve as a more accurate tumour marker in patients with SCLC than neuron-specific enolase (NSE). ProGRP(31-98) and NSE were measured retrospectively in 101 newly diagnosed untreated patients with SCLC, 111 with non-small-cell lung cancer (NSCLC) and 114 patients with non-malignant lung diseases. ProGRP(31-98) and NSE levels were determined using a sandwich enzyme-linked immunosorbent assay. Sensitivity in SCLC patients was 72.3% for ProGRP(31-98) and 62.4% for NSE. Comparing the area under curve (AUC) of 'receiver operator characteristics' of ProGRP(31-98) with that of NSE, ProGRP(31-98) was the more powerful marker in the diagnosis of SCLC (P = 0.0001). Serum levels of ProGRP(31-98) were higher in the 40 patients with extensive disease than in the 61 patients with limited disease (P = 0.0082). ProGRP(31-98) was significantly higher in patients with pure small-cell carcinoma than in patients with mixed small-cell/large-cell carcinoma (P = 0.02). In serial measurement in 16 patients responding to treatment, a high degree of correlation was noted between the decrease in serum ProGRP(31-98) levels and clinical response during the second week after treatment (P = 0.0045). These results indicate that the determination of serum ProGRP(31-98) levels plays an important role in the diagnosis and treatment of SCLC patients.

The economics of lung cancer management in Canada.

Because lung cancer is a major health care problem in Canada, it is imperative to understand how resources are used to diagnose and treat this disease. This paper describes a method of modelling the direct patient care costs for lung cancer from the perspective of the government as payer in a universal health care system. Clinical algorithms were developed to describe the management of non-small cell (NSCLC) and small cell (SCLC) lung cancer. Patients were allocated to the treatment algorithms in the model based on a knowledge of their distribution by cell type and stage in Canadian cases. A microsimulation model developed by Statistics Canada was used to integrate the data on type of lung cancer, extent of disease, clinical management, survival and health care resource utilization. The direct care costs for diagnosis and treatment of NSCLC ranged from $Cdn 17 889 for the surgery/post-operative radiotherapy treatment of Stages I and II to $Cdn 6333 for supportive care for patients with Stage IV disease. The costs of determining relapse for NSCLC were estimated to be $Cdn 1528 and terminal care costs, made up largely of hospitalization charges and some palliative radiotherapy, were $Cdn 10 331. Direct care costs for the diagnosis and initial treatment of SCLC ranged from $Cdn 18 691 for management of limited stage disease to $Cdn 4739 for the supportive care of patients with extensive disease. The cost of determining relapse for SCLC was estimated to be $Cdn 1590 and terminal care costs averaged $Cdn 9966. For all 15 624 cases of lung cancer diagnosed in Canada in 1988, it was estimated that the total cost of providing treatment and follow-up, and managing relapse over 5 years was $Cdn 328 million. Despite the large total cost of lung cancer management, estimates of cost effectiveness of therapy showed that the cost per life year gained was approximately $Cdn 11 000 for NSCLC and $Cdn 19 560 for SCLC. These estimates of the direct health care costs assume that all patients have access to care, treatment is uncomplicated and practice is standard, and must be viewed as an idealized assessment of the cost of lung cancer management. The microsimulation model, however, does provide a useful framework for evaluating the costs of new diagnostic procedures, treatment strategies and new drugs.

Second primary malignancies following diagnosis of small-cell lung cancer.

The records of 800 patients with small-cell carcinoma of the lung (SCLC) treated between 1971 and 1985 at University of Toronto-affiliated hospitals were reviewed for the occurrence and relative risk of second primary malignancies (SPMs). Almost all patients who developed a SPM were treated previously with chemotherapy and radiation therapy. Nineteen metachronous SPMs (MSPMs) and 11 synchronous SPMs (SSPMs) were identified. SSPMs were detected between 1 and 12 months after the diagnosis of SCLC. The MSPMs were identified between 1 and 10 years after the diagnosis of SCLC. MSPMs included non-small-cell lung cancer (NSCLC) (four patients), hematologic malignancies (HM) (three patients), and 12 with other solid tumors (OST). The median survival times after the diagnosis of MSPM was 33 months, 10 months, and 1 month, respectively, for those with NSCLC, OST, and HM. Expected cancer incidence rates were used to compute a relative risk rate for developing a MSPM in a subset of 392 patients on whom accurate follow-up information was available. The calculated relative risk for all tumors was 3.73. The relative risk for the development of secondary NSCLC was 6.83. We suggest that increased predisposition to SPM may relate to secondary effects of multimodality treatment and biologic considerations.

Bombesin: a potent mitogen for small cell lung cancer.

While advances in the diagnosis and staging of SCLC have been made over the past decade, overall therapeutic results remain essentially unchanged. However, during this time period there have been major advances in understanding the biology of this tumor cell type. The recognition of considerable heterogeneity among SCLC cells may be of prognostic importance, while the demonstration of specific growth factors, including bombesin, for this tumor type may open up new means for endocrine therapy of lung carcinoma in vivo. Over the next 5-10 yr, studies of clinical trials using specific antibodies or analogs of bombesin-like growth factors in patients with SCLC will define more clearly the role of BLI and GRP in patients with this disease.