# Radiation Oncology/SCLC/Review

* Front Page: Radiation Oncology | RTOG Trials | Randomized Trials
Small Cell Lung Cancer Review

## Epidemiology

* US Incidence: ~35 thousand
* Primary risk factor: tobacco
* Limited stage: 20-30% at diagnosis

## Clinical Presentation & Workup

* Clinical presentation: Cough and dyspnea
* Paraneoplastic syndromes:
** Lambert-Eaton: progressive muscular weakness similar to myasthenia gravis, but starting with proximal leg muscles, caused by autoantibody to voltage-gated calcium channels. 50% of LEMS are found to have underlying SCLC
** Paraneoplastic encephalomyelitis: multiple neurologic deficits, caused by anti-Hu antibody that cross-reacts with SCLC antigens and neuronal RNA-binding proteins
** Cushing's syndrome: central obesity (including moon face and buffalo hump), thin skin, hirsutism, striated skin, caused by inappropriate ACTH release
** SIADH: hyponatremia and fluid overload, caused by inappropriate ADH release. Found in ~16% SCLC vs 2% NSCLC
* CXR presentation: Large hilar mass with bulky mediastinal lymphadenopathy; solitary nodule ~5%
* Pathology
** Malignant epithelial tumor, small cells, scant cytoplasm, high mitotic count
** In up to 30% of autopsies, areas of NSCLC differentiation, suggesting pluripotent stem cell origin
** Immunoreactive for keratin, epithelial membrane antigen, TTF-1 and neuroendocrine markers (chromogranin A, NSE, NCAM, synaptophysin) though these alone not sufficient since they are present in ~10% of NSCLC
** p53 positive in 90% SCLC vs. 50% NSCLC; RB LOH in 90% SCLC vs 10% NSCLC;
* Workup
** Chest/liver/adrenal CT
** Head MRI (positive in 10-15%)
** PET (optional) or bone scan (positive in 30% with no bone pain or LDH elevation)
* Staging:
** Limited stage: can be safely enclosed in RT portal (corresponds to Stage I-IIIB)
** Extensive stage: metastatic disease (corresponds to Stage IV)

## Limited Stage Therapy

* Median OS 14-20 months; 2-year OS 40%; 5-year OS 15-25%
* Chemotherapy primary therapy
** Cisplatin/etoposide is NCCN recommended combination; cisplatin/irinotecan not superior
* Addition of thoracic RT: improves local control and survival (meta-analysis)
** RT used in most of the trials was 45 Gy QD
** Chemotherapy alone intrathoracic failure: 50-90%
** Intrathoracic control benefit: chemo-RT improved by 25% (SS)
** Survival benefit: 3-year chemo-RT 14% vs. chemo alone 9% (SS); 5% absolute benefit
** Excess treatment-related deaths: chemo-RT worse by 1.2% (SS)
* Timing/duration of RT (meta-analysis)
** Benefit for early RT in cisplatin-based concurrent trials (HR 0.6), 5-year OS 10-15% to 20-30%
** If RT started with 30 days of chemo: 2-year OS benefit HR 0.7 (SS)
** If duration <30 days: even more benefit
* RT dose/fractionation
** INT 0096 (Turisi): 45 QD vs 45 BID with concurrent cisplatin 60 mg/m2 and etoposide 120 mg/m2 Q3W
*** Survival benefit: 2-years QD 41% vs BID 47%, 5-years 16% vs 26% (SS)
*** Local failure: QD 52% vs. BID 36% (p=0.06)
*** Grade 3 esophagitis: QD 11% vs 27% (SS), no differen

## Extensive Stage Therapy

* Median OS 9-11 months; 2-year OS <5%
* Chemotherapy primary therapy
** No benefit to dose intensification
** If symptomatic brain mets, whole brain RT first
** If asymptomatic brain mets or no brain involvement, start with chemotherapy
** If no progression on chemo, prophylactic cranial irradiation
* RT may benefit patients in CR after chemotherapy (Yugoslavian Trial - Jeremic)
** Cisplatin/etoposide x3 cycles. If distant CR and local CR/PR, RT 54/35
** Median OS 11 months vs 17 months (SS)

## Prophylactic Cranial Irradiation

* Incidence: 15-20% at diagnosis, 60-80% at autopsy
* Limited stage, in CR after induction (meta-analysis), WBRT improves local control and overall survival
** Brain mets without PCI: 3-years ~60%
** Brain mets with PCI: 3-years 33%, reduction of 50% (SS)
** Survival benefit: 3-year 21% vs 15% (SS); 5% absolute benefit
** RT dose: 25/10 noninferior to "high dose" (36/18 or 36/24), with survival benefit
* Extensive stage, with response after induction (EORTC 08993/22993), WBRT improves local control and overall survival
** Symptomatic brain mets without PCI: 40%
** Symptomatic brain mets with PCI: 15%
** Survival benefit: 1-year 27% vs 13% (SS)
** RT dose: 20/5 used in 60%, considered reasonable given short survival