Effect of dosimetric parameters on postoperative respiratory morbidity in locally advanced esophageal cancer treated with preoperative chemoradiotherapy (CRT).
Authors: Dworczak Marie , Bogart Emilie , Adenis Antoine , Le Deley Marie-Cecile , Thenot Aurelie , Piessen Guillaume , Lacornerie Thomas , Lartigau Eric , Mirabel Xavier , Pasquier David 
Published: June 2022

e16075 Background: Postoperative pulmonary complications are common after neoadjuvant CRT of locally advanced esophageal cancers. Using data from the French multicenter randomized phase II PROTECT trial (NCT02359968), we aimed to evaluate the dosimetric parameters which could be associated with the occurrence of postoperative respiratory morbidities in patients (pts) who underwent preoperative CRT. Methods: Key eligibility criteria for the PROTECT trial were stage II or III resectable adenocarcinoma or squamous cell carcinoma of the esophagus located below the carina. Pts received FOLFOX or Carboplatin-Paclitaxel, combined with radiotherapy (RT): total dose of 41.4 Gy, 5 fractions of 1.8 Gy per week, starting at day 1 of chemotherapy. The patient's position and definition of the target volumes and organs at risk were the same as in the CROSS trial (van Hagen, 2012). Pts were treated using 3D conformal RT or IMRT. Surgery occurred 4 to 8 weeks after completion of CRT through a transthoracic or mini-invasive approach with a two field extended lymphadenectomy. Pts recruited in the PROTECT trial up to Sept. 2019 who underwent surgery after CRT were eligible for this ancillary study. The primary endpoint of our translational study was the occurrence of postoperative respiratory morbidity, of any grade (Clavien-Dindo classification for early morbidity < 31 days; NCI-CTCAE v4 for later events), up to 1 year following surgery, considering disease progression or death as competing events. Cause-specific Cox models were used to model the risk of respiratory morbidity, considering the following factors: performance status, BMI, smoking, histological subtype, tumor site, FEV1, RT technique, time interval between CRT and surgery, and dosimetric parameters derived from the Dose-Volume Histogram analysis (mean lung dose, V10Gy, V20Gy and V30Gy, as other parameters strongly correlated to these 4 ones). Results: Among the 98 pts recruited in the PROTECT trial from Feb. 2015 to Sept. 2019, 78 underwent surgery after CRT and were included in our translational study. Median age was 63.5 years (range 33 to 79). Tumor was located at the middle or lower third of the esophagus for 67% of pts. Mean lung dose was 10.2 Gy (sd = 3.2). Mean PTV volume was 566 cc (sd = 272). A total of 33 pts experienced at least one respiratory morbidity (16 pneumonia, 7 pleural effusion, 4 ARDS, 21 miscellaneous events). The cumulative incidence of respiratory morbidity was 42% one month after surgery (95% CI, 32-54), 44% at 3 months (32-54), and 46% at 6 months (35-57). None of the dosimetric parameters and other studied factors appeared associated with postoperative respiratory morbidity. Conclusions: We did not identify dosimetric factors that could predict the risk of postoperative respiratory morbidity after treatment with preoperative CRT with FOLFOX or Carboplatin-Paclitaxel. Clinical trial information: NCT02359968.