Small Cell Lung Cancer and Bronchial Neuroendocrine Tumor
Background
Small cell lung cancer (SCLC) accounts for what % of new lung cancer Dx in the U.S.? What % of lung cancer deaths?
~15% (~33,000 cases/yr) of new lung cancer is SCLC, accounting for 25% of lung cancer deaths annually.
What % of SCLC is linked to smoking?
>90% of SCLC cases are linked to smoking.
What is the median age of Dx of SCLC? What % of pts are >70 yrs old at Dx?
The median age of SCLC Dx is 64 yrs, with 25% of pts presenting at age >70 yrs.
What % of pts with SCLC presents with metastatic Dz?
67% of SCLC pts present with mets, most commonly to the contralat lung, contralat or bilat malignant pleural effusion, liver, renal, adrenals, bone, BM, and brain.
What are the pathologic characteristics of SCLC?
Small round blue cells of epithelial origin with neuroendocrine differentiation, ↑ mitotic count, and ↑ N/C ratio
What are the markers that characterize SCLC?
Markers that characterize SCLC include S100, synaptophysin+, chromagranin+, and neurotensin + EGFR−.
What are some common neurologic and endocrine paraneoplastic syndromes associated with SCLC?
Neurologic: Lambert-Eaton syndrome (antibody to presynaptic voltage-gated calcium channels), encephalomyelitis, sensory neuropathy (anti-Hu antibody)
Endocrine: Cushing Dz (↑ ↑ ACTH), syndrome of inappropriate secretion of antidiuretic hormone (SIADH) (↑ ↑ADH)
What is the most common chromosomal abnormality associated with SCLC but not seen with extrapulmonary small cell carcinomas?
Deletion of 3p (95% of cases, particularly 3p14-25 region, with inactivation of at least 3 tumor suppressor genes, including FHIT and RASSF1A)
What is the most common genetic alteration seen in SCLC?
Amplification of the bcl-2/C-myc family of oncogenes is most common but likely is not the initiating event. Other common abnormalities include loss of p16, loss of Rb, and mutation in p53.
Workup/Staging
How do pts with SCLC usually present?
Large hilar mass with bulky mediastinal LAD that causes cough, shortness of breath, weight loss, postobstructive pneumonia, and debility. Other common presentations include paraneoplastic syndromes such as Lambert-Eaton, SIADH, or ectopic ACTH production.
Classically, does SCLC present centrally or peripherally in the lung?
Classically, SCLC presents centrally in the lung.
What histology is most commonly associated with superior vena cava obstruction (SVCO) syndrome?
SCLC is most commonly associated with SVCO syndrome.
Do SCLC pts present with solitary peripheral nodules without mediastinal LAD?
This is very uncommon (<3%).
How should pts be managed whose FNA results cannot clearly differentiate between small cell and atypical carcinoid histology?
Surgical staging, with mediastinoscopy → surgical resection if the mediastinum (MN) is negative (per the NCCN)
Once SCLC has been diagnosed in a pt who presents with a large hilar mass, what further workup is necessary besides the basic H&P and labs?
LDH levels, CT C/A/P +/− PET, MRI brain, bone scan if PET is not done, BM Bx (for pts with elevated LDH), thoracentesis with cytopathologic exam for pts with pleural effusion, and smoking cessation counseling
What % of pts with SCLC at the time of Dx present with brain mets, BM involvement, and bone mets?
Brain mets: 10%–15% (30% are asymptomatic)
BM involvement: 5%–10%
Bone mets: 30%
What is the latest AJCC system for staging SCLC?
The same as for non-SCLC, but this system is not commonly used.
How is SCLC most commonly staged?
SCLC is staged using the International Association of Lung Cancer system, which is a modification of the Veterans Administration Lung Cancer Study Group (VALCSG) system. There are 2 stages: limited and extensive. Tumors are staged according to whether the Dz can be encompassed within an RT port. Limited stage Dz is typically confined to the ipsi hemithorax, without malignant pleural effusion, contralat Dz, or mets; other presentations are usually extensive stage.
What % of pts present with limited-stage SCLC?
~33% of pts present with limited-stage SCLC.
What are some adverse prognostic factors in SCLC?
Poor performance status (PS); weight loss (>5% in prior 6 mos); ↑LDH; male gender; endocrine paraneoplastic syndromes (controversial), variant, or of mixed cell type; metastatic Dz
What is the MS of untreated limited-stage and extensive-stage SCLC?
~12 wks for limited stage and ~6 wks for extensive stage, based on a VALCSG trial comparing cyclophosphamide to placebo.
What is the MS for pts with limited- vs. extensive-stage SCLC?
Limited stage: 19–23 mos (Turrisi AT et al., NEJM 1999)
Extensive stage: 5–7 mos (Slotman B et al., NEJM 2007)
What is the long-term survival rate in limited-stage SCLC treated with a combined modality?
~20%–30% long-term survival (5-yr OS)
What additional workup should be considered for pts with carcinoid tumors of the lung?
Consider octreotide scan.
Treatment/Prognosis
What is the Tx paradigm for pts with extensive-stage SCLC?
Extensive-stage SCLC Tx paradigm: multiagent chemo regimen including etoposide/cisplatin (EP) or Cytoxan/Adriamycin/vincristine (CAV). Consider consolidation RT to the thorax for pts who achieve a CR to distant Dz after initial chemo. (Jeremic B et al., JCO 1999)
What are some important poor prognostic factors for limited stage SCLC?
Karnofsky PS <70, weight loss, ↑LDH
What is the Tx paradigm for pts with limited-stage SCLC?
Limited-stage SCLC Tx paradigm: 4 cycles of EP chemo (etoposide [120 mg/m2, days 1–3] + cisplatin [60 mg/m2, day 1, q3wks]) + concurrent RT (only 1 cycle is concurrent). Current standard RT regimen is based on INT-0096: 45 Gy in 1.5 Gy bid × 30 fx.
How should a tumor characterized as a high-grade neuroendocrine carcinoma, or as large cell neuroendocrine carcinoma, be managed?
Treat per non-SCLC guidelines. (NCCN 2010)
How should a pt with a carcinoid tumor of the lung be managed?
Surgery is 1st line if it is resectable.
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