Radiotherapy

Rationale
- 80% of limited stage patients ill

Controversies

  • Total radiation dose
  • Dose fractionation
  • Timing of RT
  • Treatment fields
  • Agents/doses of chemotherapy
  • Potential applicability of novel targeted therapies

Effect of RT (Limited stage)

  • Warde et al (1992;10:890 in JCO) - Meta-analysisImproved 2 year survival by 5.4%; tumour control improved by 25%; minimal toxicity
  • Pignon NEJM 1992 327:1618 - Metaanalysis, Improved 3 year survival by 5.4%. No effect if early/late or sequential/concurrent. Slightly increased toxicity; most benefit in under 55yo.

Dose

Dose escalation is of benefit:

  • Coy et al (1998) IJROBP - 25 Gy vs 37.5 Gy, local progression 70% versus 80 Gy
  • Choi et al IJROBP 1989 -

Max dose 50-56 Gy:

  • Papac et al IJROBP 1987; 13:993 - retrospective study; 60 Gy associated with 96% local control; consider this dose in patients who can not receive chemotherapy.

Two ongoing RCTs examining dose escalation, not yet published.

Volumes

Contour pre- or post-chemotherapy volumes - see Kies et al JCO 1989; 5:592

  • No differences in outcomes
  • Increased severe myelosuppressive toxicity in larger fields
  • Therefore use post-chemotherapy volumes

Also note Liengswangwong et al (JCO 1994; 12:496) which showed that all intrathoracic recurrences were in-field (about 30%).
Add 1.5-2 cm on to CTV for PTV.

Newer evidence: Selective Nodal Irradiation on Basis of 18FDG-PET (IJROBP 2010 77,2,329-336). Attempted to limit RT dose to post-chemotherapy, PET-positive nodes. Out-of-field nodal recurrences were 12%. This is significantly lower than the 20-30% out of field recurrences when CT alone was used. Non-randomised study.

Fractionation

Accelerated hyperfractionation has been employed since the Turrisi trial (NEJM 1999 340:265). 45 Gy / 30# over 3 weeks was compared to 45 Gy/25# over 5 weeks 2 year survival improved from 41 to 47%. Oesophagitis is a common side effect (25% vs 10%).
45/30 is the ideal treatment currently. This may become controversial if dose escalation is proven to be effective.

Sequencing

Options:

  • Separate
  • Concurrent
  • Alternating

Daily cisplatin has been shown to have no benefit over conventional RT.