Management Of Nsclca

MANAGEMENT

Early Stage

  • Surgical resection is the mainstay of the treatment
    • Lobectomy preferred over Pneumonectomy
      • Less morbidity
        • 3% vs 8%
    • Lobectomy preferred over wedge resection
      • Less locoregional failure:
        • 8% vs 16%
      • OS the same(5yr)
        • 80%
  • 5yr survival —> 80%
  • Treatment failure is mostly systemic
  • Survival following resection for NSCLC is associated with the number of lymph nodes evaluated during surgery
    • 11-16 LN

Defenitive RT for medically non-operable patients

  • Conventional fractionation results worse than surgery
  • Higher dose —> better results ( 70Gy vs 55Gy )

Stereotactic Body RT

  • Rational is based on that lung is a parallel organ
  • After certain dose to certain volume; the toxicity does not increase
    • Heterogeneity within the target
  • Results for T1 ~ 90% local control ( all institutional results )
  • No randomized trial result yet but ongoing
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Pattern of failure after surgery

  • Local —> 20%
  • Distant —> 70%
  • Local and distant concurrent —> 10%

Post-OP Radiation

  • Not recommended for use following complete resection of stage II
  • for stage IIIA:
    • No definitive recommendation
      • No OS benefit
      • Local control data is conflicting
  • Detrimental after node negative disease
    • Increase in risk of death —> 18%
    • Absolute detriment of 6% at 2 years
      • Reducing OS from 58% to 52%
  • Consider in N2 disease

Evidence on PORT

  • Port Meta-analysis
  • LCSG
    • locoregional failure rate (as first site of failure): reduced from 41% to 3% with RT for all node-positive patients.
    • No survival benefit for stage II patients from PORT
    • more than two thirds of first failures were distant

Post-OP Chemo

  • Evidence showing benefit in T2 and higher stages(II and III)
  • Cisplatinum based
  • 5% benefit in 5yr OS

Potentially Resectable Disease: IIIA and IIIB

Pre-OP Radiation

  • Several trials from 60s:
    • RT does NOT improve survival
    • Rt increase surgical complication
      • bronchopleural fistulae
  • CALGB and LCSG
    • Randomized Unresectable stage IIIA and IIIB
      • Pre-OP RT vs Pre-OP Chemo
      • No difference
  • A prospective randomized multi-institution trial
    • 478 patients with lung cancer
    • Pre-OP RT (20 Gy / 5) —> surgery vs Surgery alone
    • No difference in the 5-year survival in stage I and II
    • Stage III patients
      • Combined : 49.4% at 3 yr & 29.2% at 5yr
      • Surgery alone : 28.1% at 3yr & 15.8% at 5yr

Preoperative Chemotherapy

  • Role of pre-op chemo:
    • Benefits:
      • Reduction in tumor size that may facilitate surgical resection
      • Early eradication of micrometastases
      • Better tolerability
    • Disadvantage:
      • Delay potentially curative surgery
  • Not for stage I
  • Stage II and III could benefit from neoadjuvant therapy
  • Absolute benefit —> 5%
  • Stage II (T1N1 and T2N1)
    • lower survival rates (25% to 50%) after surgery w/o chemo
  • Stage III disease(very low survival )
  • Depierre (French) (1991-97) –
      • Induction chemo —> surgery vs surgery alone
      • 2 cycles mitomycin, ifosfamide, and cisplatin. 2 additional cycles were given postoperatively for pts who responded
      • 355 pts. Stage IB - IIIA..
      • Pts in both arms received post-op RT for pathologic T3 or N2 disease.
      • Median survival 37 m (PCT) vs 26 m (S), N.S.
      • Survival difference 8.6% at 4 yrs (S.S.).
      • Survival difference was S.S. only for pts with N0-N1 disease.
  • Two randomized trials have been reported for patients with stage III
    • Roth and Russel
    • Improved Survival
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Role of surgery in stage III Lung ca

  • RTOG/ECOG
    • Induction chemo then randomized between
      • RT
      • Surgery
    • No difference in survival
    • Inadequately powered
  • North Americal intergroup trial ( INT 0139 )
    • Pathologic N2 disease
    • Randomized between
      • defenitice Chemo-RT ( Cis-Etoposide + 61Gy )
      • Pre-OP Chemo-RT ( Cis-Etoposide + 45Gy ) —> Surgery ==> Better disease free survival / no OS difference

Unresectable Stage IIIA and IIIB

Data on dose of radiation

  • RTOG 73-01
  • Randomized bwteen 40Gy(split 20-20) vs 50Gy vs 60Gy
  • Higher dose —> Better LC and modest better OS

Local Control after RT or chemo RT : ~ 17-20% in 1 year and ONLY 10% in 4 years

CHEMO-RADIATION