title: The impact of induction chemotherapy on the dosimetric parameters of subsequent radiotherapy: an investigation of 30 consecutive patients with locally-advanced non-small cell lung cancer and modern radiation planning techniques.
abstract: OBJECTIVE
  To investigate the influence of induction chemotherapy (ICT) on dosimetric outcomes in patients with inoperable non-small cell lung cancer (NSCLC) treated with definitive chemoradiation (CRT).
  
  
  METHODS
  30 patients with inoperable stage II-III NSCLC treated with 2-4 cycles of ICT followed by definitive CRT to ≥ 60 Gy were selected. Tumor response to chemotherapy was scored by RECIST criteria. Treatment plans based on tumor extent prior to chemotherapy were generated based on equivalent planning constraints and techniques as the original post-chemotherapy plans. Dosimetric parameters predictive of toxicity for lung, esophagus, heart, and spinal cord were compared amongst the pre- and post-ICT plans.
  
  
  RESULTS
  The majority of patients (70%) experienced an overall reduction in GTV size between the pre-ICT imaging and the time of simulation. Comparing pre-and post-ICT diagnostic imaging, 5 patients met the RECIST criteria for response, 23 were classified as stable, and 2 experienced disease progression on diagnostic imaging. Despite a significantly reduced GTV size in the post-ICT group, no systematic improvements in normal tissue doses were seen amongst the entire cohort. This result persisted amongst the subgroup of patients with larger pre-ICT GTV tumor volumes (>100 cc(3)). Among patients with RECIST-defined response, a significant reduction in lung mean dose (1.9 Gy absolute, median 18.2 Gy to 16.4 Gy, p = 0.04) and V20, the percentage of lung receiving 20 Gy (3.1% absolute, median 29.3% to 26.3%, p = 0.04) was observed. In the non-responding group of patients, an increased esophageal V50 was found post-chemotherapy (median 28.9% vs 30.1%, p = 0.02).
  
  
  CONCLUSIONS
  For patients classified as having a response by RECIST to ICT, modest improvements in V20 and mean lung dose were found. However, these benefits were not realized for the cohort as a whole or for patients with larger tumors upfront. Given the variability of tumor response to ICT, the a priori impact of induction chemotherapy to reduce RT dose to normal tissue in these patients is minimal in the setting of modern treatment planning.
authors: Department of Radiation Oncology, MD Anderson Cancer Center, 1515 Holcombe Blvd Unit 097, Houston, TX, 77030, USA. jdgrant@mdanderson.org.
authors: Jonathan D
authors: JD
authors: Grant
authors: Department of Radiation Oncology, MD Anderson Cancer Center, 1515 Holcombe Blvd Unit 097, Houston, TX, 77030, USA. asobremonte@mdanderson.org.
authors: Angela
authors: A
authors: Sobremonte
authors: Department of Radiation Oncology, MD Anderson Cancer Center, 1515 Holcombe Blvd Unit 097, Houston, TX, 77030, USA. ehillebr@mdanderson.org.
authors: Evangeline
authors: E
authors: Hillebrandt
authors: Department of Radiation Oncology, MD Anderson Cancer Center, 1515 Holcombe Blvd Unit 097, Houston, TX, 77030, USA. pallen@mdanderson.org.
authors: Pamela K
authors: PK
authors: Allen
authors: Department of Radiation Oncology, MD Anderson Cancer Center, 1515 Holcombe Blvd Unit 097, Houston, TX, 77030, USA. dgomez@mdanderson.org.
authors: Daniel R
authors: DR
authors: Gomez
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D059248:Chemoradiotherapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D060828:Induction Chemotherapy; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011874:Radiometry / Q000379:methods; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods*; D050397:Radiotherapy, Intensity-Modulated; D047368:Tumor Burden
references: J Natl Cancer Inst. 2000 Feb 2;92(3):205-16
references: 10655437
references: Int J Radiat Oncol Biol Phys. 2002 Jul 1;53(3):566-73
references: 12062598
references: Lung Cancer. 2002 Dec;38(3):297-301
references: 12445752
references: J Clin Oncol. 2007 May 1;25(13):1698-704
references: 17404369
references: Int J Radiat Oncol Biol Phys. 2007 Nov 15;69(4):985-92
references: 17689035
references: Int J Radiat Oncol Biol Phys. 2007 Nov 15;69(4):993-1000
references: 17869016
references: J Clin Oncol. 2010 May 1;28(13):2181-90
references: 20351327
references: Radiat Oncol. 2013;8:216
references: 24040865