Author of

• 15183

  +

  MTE 27 - Modern Approaches to Radiotherapy in Stage III Disease (Ticketed Session) (ID 79)

  • Event: WCLC 2015
  • Type: Meet the Expert (Ticketed Session)
  • Track: Treatment of Locoregional Disease – NSCLC
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/09/2015, 07:00 - 08:00, 111

  • 15184

    +

    MTE27.01 - Modern Approaches to Radiotherapy in Stage III Disease (ID 2014)

    07:00 - 08:00  |  Author(s): M. Werner-Wasik
    • Abstract
    • Slides

    Abstract:
    Thoracic radiation therapy (RT) has been historically the first definitive therapy for Stage III non-small cell lung cancer (NSCLC), achieving median survival time (MST) of 10 months (mo). Adding chemotherapy extended MST to 13.8 mo (induction chemotherapy) or 17-20 mo. (concurrent chemotherapy) in randomized trials which used two-dimensional (2D) RT. Most recently, large randomized clinical trials for PET-staged patients treated with modern thoracic RT reported MST of 28.7 mo. (1). The reasons for such impressive survival improvement over last two decades are not fully understood and are likely multifactorial, including universal FDG-PET staging on presentation (therefore removing unsuspected Stage IV patients); progress in thoracic RT (precise target definition with CT simulation; widespread 3D RT or Intensity Modulated RT[IMRT], allowing volumetric rather than point radiation dose prescribing; heterogeneity correction accounting for different density of air vs. soft tissue; increased understanding of normal tissue tolerance, such as spinal cord, allowing relative sparing of lung parenchyma; image-guided RT minimizing normal tissue margins and “missed targets” etc.); widespread use of low-dose well-tolerated outpatient chemotherapy regimens; improved supportive care; effectiveness of second- and third-line systemic therapy etc. In a population study of >5,000 SEER-Medicare patients with NSCLC, wider adoption of CT simulation for thoracic RT planning was associated with improved overall survival (2). Local control rate was 70% at 2 years in the large cooperative group Phase III randomized trial (RTOG 0617) in the 60 Gy standard arms, defined as lack of tumor progression within the irradiated field. Most patients succumb to distant metastases which continue to be the leading cause of death of patients with lung cancer. Since death from distant metastases and local failure constitute competing risks, the likely incidence of local failure may be higher if longer overall survivals are achieved. The optimal RT dose allowing improved local control has not been fully established and the current recommendation is to use 60 Gy in daily 2 Gy fractions, with concurrent chemotherapy in fit patients. RT dose escalation to 74 Gy was associated with worse MST when compared to 60 Gy in a randomized trial (20.3 vs. 28.7 mo., respectively) (RTOG 0617). While the reasons for such worse survival are not clear, the possibilities include higher RT heart doses in the 74 Gy arm, greater number of deaths in the high-dose group, extended duration of radiation therapy to 7.5 weeks, and uncertainty about true causes of death (1). Nevertheless, efforts toward RT dose intensification continue, with particular attention given to the shortening of the overall treatment time through hypofractionation (for example, in the RTOG 1106 a mid-treatment PET-adapted hypofractionated RT boost is applied to the residual tumor volumes during a total duration of 30 RT fractions )(NCT01507428). While the proportion of patients with Stage III NSCLC receiving IMRT has been increasing as compared to 3D RT (3% in 2002 vs. 26.8% in 2009)(3), the superiority of IMRT has not been convincingly demonstrated. Among patients receiving potentially curative treatment, there was no difference in overall survival (propensity adjusted HR .99, p = 0.83) or number of hospital days in the 90 days following radiation start, as demonstrated by the SEER-Medicare analysis of over 7,000 patients. The technology currently being investigated involves proton therapy, which has been shown in treatment-planning comparisons to deliver high-dose, highly conformal radiation to targets while minimizing damage to surrounding normal tissues. In particular, the subclinical cardiovascular toxicity suspected to be detrimental in the RTOG 0617 trial, which might have accounted for worse survival in the high-dose arms, may be mitigated with protons due to their physical property of a sharp distal dose edge. Long term results from a prospective single institution study of 134 patients receiving concurrent proton thoracic RT (median dose: 74 Gy) and chemotherapy (4) demonstrated the MST of 40 mo. for Stage II NSCLC patients and 30 mo. for Stage III patients, and a local + marginal failure-free rate of approximately 50% at 5 years. Grade 2 radiation pneumonitis was reported in 29 (22%) patients and Grade 3, in 2(1.5%). An ongoing study, the NRG Oncology/RTOG 1308, is a phase III trial exploiting the potential of protons compared with photons to escalate radiation dose to 70 Gy while applying strict dose volume constraints to adjacent normal tissues (NCT01993810). In summary, while numerous advances in thoracic RT for Stage III NSCLC were introduced over the last 20 years, local tumor control and overall survival need refinement and no single RT technology/RT dose and fractionation have been identified as the most optimal approach. (1) Bradley JD, Paulus R, Komaki R, Masters G, Blumenschein G, Schild S, Bogart J, Hu C, Forster K, Magliocco A, Kavadi V, Garces YI, Narayan S, Iyengar P, Robinson C, Wynn RB, Koprowski C, Meng J, Beitler J, Gaur R, Curran W Jr, Choy H. Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study. LancetOncol. 2015 Feb;16(2):187-99. PMID: 25601342 (2) Chen AB, Neville BA, Sher DJ, Chen K, Schrag D. Survival outcomes after radiation therapy for stage III non-small-cell lung cancer after adoption of computed tomography-based simulation. J Clin Oncol. 2011 Jun 10;29(17):2305-11. PMID: 21537034 (3) Chen AB, MD, Ling L, Cronin A, Schrag D. Comparative Effectiveness of Intensity-Modulated Versus 3D Conformal Radiation Therapy Among Medicare Patients with Stage III Lung Cancer. J Thorac Oncol. 2014;9:1788–1795 (4) Nguyen QN, Ly NB, Komaki R, Levy LB, Gomez DR, Chang JY, Allen PK, Mehran RJ, Lu C, Gillin M, Liao Z, Cox JD. Long-term outcomes after proton therapy, with concurrent chemotherapy, for stage II–III inoperable non-small cell lung cancer. Radiother and Oncology, e-published May 2015
    
    

    Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.