Lung SCLC

Pathology

  • WHO subdivides SCLC into
    • pure
    • variant cell
    • mixed (SCLC & NSCLC)
  • Mixed type should be treated like NSCLC as it chemo- and radiosenitivity is like that of NSCLC.

Limited Stage (L-SCLC)

Definition

  • confined to the hemithorax of origin, the mediastinum, and the supraclavicular nodes, which can be encompassed within a “tolerable” radiation therapy port.
  • There is no universally accepted definition of this term, and patients with pleural effusion, massive pulmonary tumor, and contralateral supraclavicular nodes and hialr have been both included within and excluded from limited stage by various groups. (NCI 2003)
  • Median survival 12 weeks with supportive care alone.

Evaluation

  • FEV1 ≥ 1.0

Radiation Treatment

  • 45 Gy in 1.5 Gy BID concurrent with Cisplatinum and etoposide
  • In weeks 2 and 3 PM treatment is off cord (total cord dose 30 Gy)
  • Include ipsilateral hilum, bilatera mediastinum with 1.0 to 1.5 cm margin
  • It was forbidden to include non-involved supraclavicular fossa

QD Dose-Escalation[1]

  • Between 1974 and 1986, 576 patients (284 limited and 292 extensive stages) were treated at this Mass Gen. (CRT w/ > 3 cycles)
  • Loco-regional failure rates at 2.5 years were
    • 37%, 39%, 49%, 79%, and 84%
    • 50 Gy, 45 Gy, 4 0Gy, 35 Gy, and 3 0Gy, respectively.
  • NCCN Recommends 60-70 Gy QD in 1.8 to 2.0 Gy per fraction.

Chemotherapy

  • cisplatinum 60 mg/kg-m2 day 1 and etoposide 120 mg/kg-m2 days 1-3
  • Start with RT and for 4 cycles.

Timing of Chemotherapy and radiation

  • Metaanalysis of randomized trials of chemotherapy an thoracic irradiation did not identify the optimal timing for thoracic irradiation. In contrast, most trials showing an advantage of thoracic irradiation gave it early in the course or concurrently.

Complications

  • 27% Grade 3 esophagitis risk

Outcome

  • 26% Overall survival at 5-years

PCI (Prophylatic Cranial Irradiation)

  • 25 Gy in 10 fractions (RTOG)
  • 36 in 2 Gy fractions (Gregor et al. 1997- UKO2)
    • No overall survival advantage over 24 Gy but did have fewer brain failures.
  • Meta-analysis of 987 patients and 7 prospective trials by Aupérin showed 5.4% 3-OS advantage. (Auperin NEJM 341:476-484,1999)
  • Typically PCI given within 6 months of completion of thoracic radiation or as soon as possible after completion of chemotherapy in complete responders.

Extensive Stage (E-SCLC)

With CR at distant sites

  • initially give 3 cycles of carboplatin plus etoposide
  • Partial or CR in the chest
  • 54 Gy in 36 fractions with cisplatin and etoposide
  • followed by 2-4 cycles of cisplatin and etoposide
  • 9.1% vs 3.7% 5-yr overall survival [2]

Brain metastasis in E-SCLC [3]

  • E-SCLC with brain and chest disease only may benefit from WBRT and thoracic RT
  • 14 month median survival.

Prophylactic Brain Metastasis in E-SCLC [4]

  • (Amsterdam)
  • Take ALL E-SCLC response to chemotherapy with PS 0-2 ( No brain metastasis on imaging )
  • PCI 4-6 weeks after chemotherapy
    • 20 in 5 to 8 fractions; 24 Gy in 12 fractions; 25 Gy in 10 fractions or 30 Gy in 10-12 fractions.
  • Results
    • 14.6% vs 40.4% brain metastases at 1 year (RT vs No RT groups)
    • DFS 14.7 mo. vs 12.0 mo (RT vs No)
    • OS 6.7 mo. to 5.4 mo. (RT vs No)
    • 27.1% vs 13.3% 1 year overall survival (RT vs No)
  • prophylactic cranial irradiation reduces the incidence of symptomatic brain metastases and prolongs disease-free and overall survival.

Neoplastic Syndromes

  • ACTH (Cushing): hypokalemia, hyperglycemia, myopathy, and edema
  • SIADH: severe hyponatremia due to retention of water
  • Eaton-lambert: proximal muscle weakness
Bibliography
1. Choi NC, Carey RW. Int J Radiat Oncol Biol Phys 1989 Aug;17(2):307-10
2. Jeremic B, Shibamoto Y, Nikolic N, Milicic B, Milisavljevic S, Dagovic A, Aleksandrovic J, Radosavljevic-Asic G. Role of radiation therapy in the combined-modality treatment of patients with extensive disease small-cell lung cancer: A randomized study. J Clin Oncol. 1999 Jul;17(7):2092-9.
3. Kochhar R, Frytak S, Shaw EG. Survival of patients with extensive small-cell lung cancer who have only brain metastases at initial diagnosis. Am J Clin Oncol. 1997 Apr;20(2):125-7.
4. Slotman B, Faivre-Finn C, Kramer G, Rankin E, Snee M, Hatton M, Postmus P, Collette L, Musat E, Senan S; EORTC Radiation Oncology Group and Lung Cancer Group. Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med. 2007 Aug 16;357(7):664-72.
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