title: Prediction of acute toxicity grade ≥ 3 in patients with locally advanced non-small-cell lung cancer receiving intensity modulated radiotherapy and concurrent low-dose Cisplatin.
abstract: BACKGROUND
  Intensity modulated radiotherapy (IMRT) is increasingly used with concurrent chemotherapy but toxicity data are not well investigated. We correlated clinical and dosimetric parameters with acute toxicity grade ≥ 3 in patients with locally advanced NSCLC treated with IMRT and concurrent low-dose cisplatin.
  
  
  METHODS
  We analyzed age, PS, comorbidities, gross tumor volume, and the volume of the esophagus irradiated with 50 Gy (V50oes) in relation with acute toxicity. The mean lung dose (MLD) and pulmonary toxicity was described. Treatment consisted of 24 × 2, 75 Gy, and daily cisplatin 6 mg/m². Patients with an MLD ≥ 20 Gy or a PS > 2 were excluded from CCRT. Toxicity was prospectively scored using the Common Toxicity Criteria for adverse events version 3.0. The Charlson Comorbidity Index (CCI) was applied for scoring comorbidities. Multivariable logistic regressions for toxicity and survival estimates (Kaplan-Meier) were used for evaluation.
  
  
  RESULTS
  From 2008 to 2011, 188 patients received standard CCRT. In 35% of the patients, acute toxicity grade ≥ 3 was reported. Grade 5 toxicity was scored in 1% of the patients. V50oes (odds ratio [OR], 1.33 per 10% increase; P = .01) and PS ≥ 2 (OR, 3.45; P = .07) were significantly correlated with acute toxicity ≥ grade 3. No differences in toxicity were observed between age groups (< 70 and ≥ 70; P = .26), and those with a CCI score < 5 and ≥ 5, and acute severe toxicity (P = .36). Grade ≥ 3 pulmonary toxicity was seen in 7%. The 1- and 2-year overall survival in stage III disease were 78% and 52%, respectively. Patients with a poor PS or a high CCI score had similar survival outcomes.
  
  
  CONCLUSIONS
  Concurrent low-dose cisplatin using IMRT is effective in a large cohort of consecutive patients with NSCLC and life threatening toxicity is rare (1%). PS ≥ 2 and V50oes are correlated with acute toxicity grade ≥ 3.
authors.affiliation: Department of Thoracic Oncology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. w.uyterlinde@nki.nl
authors.forename: Wilma
authors.initials: W
authors.lastname: Uyterlinde
authors.forename: José
authors.initials: J
authors.lastname: Belderbos
authors.forename: Claudia
authors.initials: C
authors.lastname: Baas
authors.forename: Erik
authors.initials: E
authors.lastname: van Werkhoven
authors.forename: Joost
authors.initials: J
authors.lastname: Knegjens
authors.forename: Paul
authors.initials: P
authors.lastname: Baas
authors.forename: Arthur
authors.initials: A
authors.lastname: Smit
authors.forename: Chris
authors.initials: C
authors.lastname: Rikers
authors.forename: Michel
authors.initials: M
authors.lastname: van den Heuvel
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy / Q000009:adverse effects*; D002945:Cisplatin / Q000009:adverse effects*; D015897:Comorbidity; D004305:Dose-Response Relationship, Drug; D004947:Esophagus / Q000187:drug effects / Q000528:radiation effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects*; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin
keywords: Chemoradiation; Comorbidity; IMRT; Toxicity; non–small-cell lung cancer