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Feasibility of image-guided radiotherapy and concurrent chemotherapy for locally advanced nonsmall cell lung cancer

Significance Statement

Two-third  of patients  with non-small  cell  lung  cancer (NSCLC)  presented  with  locally  advanced  stages  (IIIA  and  IIIB)  at  diagnosis.  The  prognosis  is  very  poor.  High  rates  of  loco-regional  and  distant  recurrences  were  observed  following  treatment  with  concurrent  chemoradiation.  Conventional  radiotherapy  technique  such  as  3-dimensional  conformal  radiotherapy  (3-D  CRT)  does  not  allow  radiation  dose  escalation  because  of  treatment  toxicity.  A  recent  randomized  study  reported  a  2-year  survival  of  21%  and  29%  for  patients  with  locally  advanced  NSCLC  treated  to  74  Gy  (high  dose)  and  60  Gy  (low  dose)  respectively  with  3-D  CRT  (Bradley  et  al).  The  inferior  survival  observed  with  a  higher  radiation  dose  may  be  related  to  excessive  cardiac  irradiation.  Image-guided  radiotherapy  (IGRT)  by  virtue  of  the  combination  of  a  steep  radiation  dose  gradient  associated  with  daily  imaging  allows  reduction  of  radiation  dose  to  the  heart  and  lungs  and  tumor  dose  escalation.  The  3-year  survival  of  45%  for  patients  with  locally  advanced  lung  NSCLC  treated  with  chemotherapy  and image-guided radiotherapy  to  70-75  Gy  is  encouraging.   Minimal  long-term  toxicity   was  also  observed   despite  a  higher  radiation  dose.  Future  prospective  studies  should  be  performed  to  confirm  this  hypothesis.

References

Bradley  J,  Paulus  R,  Komaki  R,  et  al.  Standard  dose  versus  high  dose  conformal  radiotherapy  with  concurrent  and  consolidation  carboplatin  plus  paclitaxel  with  or  without  cetuximab  for  patients  with  stage  IIIA  and  IIIB  non-small  cell  lung  cancer  (RTOG  0617):  a  randomized,  two-by  two  factorial  phase  3   study.  Lancet  Oncol  2015;16:187-189.

Journal Reference for the featured paper: 

Nguyen NP, Kratz S, Chi A, Vock J, Vos P, Shen W, Vincent VH, Ewell L, Jang S, Altdorfer G, Karlsson U, Godinez J, Woods W, Dutta S, Ampil F; International Geriatric Radiotherapy Group.

Cancer Invest. 2015 Mar;33(3):53-60.

Abstract

A retrospective review of 32 patients with stage III nonsmall cell lung cancer who underwent chemoradiation with image-guided radiotherapy (IGRT) was recorded. Acute grade 3-4 hematologic and esophageal toxicities developed in 6 and 13 patients respectively. At a median follow-up of 14.5 months, only one patient developed grade 3 pneumonitis. The median survival was estimated to be 17 months. Five patients (15%) developed loco-regional recurrences, and 17 patients (53%) distant metastases. Grade 3-4 toxicities remained significant during chemoradiation with image-guided radiotherapy. However, the reduced rate of severe pneumonitis despite a high tumor dose is encouraging and needs to be investigated in future prospective studies.

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