Small cell lung cancer

Epidemiology
40,000 cases/year (about 20-25% of all lung cancer cases)
25% of patients have limited stage disease at diagnosis
Smoking is the major risk factor

Pathology
Classic: small round blue cell tumor; chemo/radiation sensitive
Variant: < 5% of cases
Mixed: treat like NSCLC

Prognostic factors
Stage* (extensive vs. limited)
Pleural effusion; patients with + pleural fluid cytology in turn do worse than negative
Performance status
Sex - women do better
Increased LDH - worse
Paraneoplastic syndrome - worse

Paraneoplastic syndromes - SCLC is famous for these
1) SIADH: hyponatremia, hypervolemia, excessive thirst despite hyponatremia, concentrated urine
2) Cushing's syndrome: ectopic ACTH secretion; usual symptoms of corticosteroid excess; if you don't know what these are you have not been seeing many radiation oncology patients
3) Lambert-Eaton syndrome: antibodies against the pre-synaptic calcium channel; weakness improves with exertion (c/w myasthenia gravis, where symptoms get worse)
4) Limbic encephalopathy, paraneoplastic cerebellar degeneration: Anti-Hu, anti-Yo Ab's in CSF
5) Subacute sensory neuropathy

Staging
PET-CT
Always obtain brain MRI
Bone marrow bx if advanced stage/cytopenic/LDH

Therapy
Fractionation
Phase III trial compared 45Gy at 1.8Gy/day to 45Gy at 1.5Gy b.i.d. (PMID 9920950)
Both arms got concurrent cisplatin/etoposide q3wks x 4 cycles
Twice daily fractionation was associated with increased overall survival (15 vs 24% at 5 years) and improved local control
Major toxicity was esophagitis

Timing
NCI Canada and Japanese Cooperative Oncology Group both performed early (concurrent) vs. late (sequential) thoracic RT RCT's; both showed increased OS for early RT. Meta-analysis showed a benefit for concurrent early RT assuming platinum based chemotherapy regimen is used (PMID 17513057)

PCI in limited stage SCLC
Meta-analysis showed decreased risk of death (HR 0.84), decreased risk of brain mets (HR 0.46) among patients with limited stage SCLC given PCI (PMID 10441063)

RTOG trial 0212 compared 25Gy in 10fx vs 36Gy in 18fx vs. 36Gy/24fx (1.5Gy b.i.d.) (PMID 19386548)
This showed no difference in the incidence of brain metastasis among the arms
Higher mortality was seen in the high dose arms (due to disease progression not neurotoxicity)

PCI in extensive stage SCLC
EORTC randomized trial demonstrated PFS and OS benefit (1-yr OS 27 vs 13%) as well as a decreased incidence of brain mets in patients with complete or partial response of extensive stage SCLC to induction chemo who received PCI (PMID 17699816)