Original article Nomogram for predicting pathologically complete response after neoadjuvant chemoradiotherapy for oesophageal cancer Eelke Lucie Anne Toxopeus a,⇑ , Daan Nieboer b , Joel Shapiro a , Katharina Biermann c , Ate van der Gaast d , Carolien M. van Rij e , Ewout Willem Steyerberg b , Joseph Jan Baptiste van Lanschot a , Bas Peter Louis Wijnhoven a a Department of Surgery ; b Centre for Medical Decision Making ; c Department of Pathology ; d Department of Medical Oncology ; e Department of Radiation Oncology, Erasmus MC, University Medical Centre Rotterdam, The Netherlands article info Article history: Received 10 February 2015 Received in revised form 27 March 2015 Accepted 6 April 2015 Available online xxxx Keywords: Oesophageal cancer Neoadjuvant chemoradiotherapy Surgery Prediction of response abstract Background: A pathologically complete response (pCR) to neoadjuvant chemoradiotherapy (nCRT) is seen in 30% of the patients with oesophageal cancer. The aim is to identify patient and tumour characteristics associated with a pCR and to develop a nomogram for the prediction of pCR. Patients and methods: Patients who underwent nCRT followed by surgery were identified and response to nCRT was assessed according to a modified Mandard classification in the resection specimen. A model was developed with age, gender, histology and location of the tumour, differentiation grade, alcohol use, smoking, percentage weight loss, Charlson Comorbidity Index (CCI), cT-stage and cN-stage as poten- tial predictors for pCR. Probability of pCR was studied via logistic regression. Performance of the predic- tion nomogram was quantified using the concordance statistic (c-statistic) and corrected for optimism. Results: A total of 381 patients were included. After surgery, 27.6% of the tumours showed a pCR. Female sex, squamous cell histology, poor differentiation grade, and low cT-stage were predictive for a pCR with a c-statistic of 0.64 (corrected for optimism). Conclusion: A nomogram for the prediction of pathologically complete response after neoadjuvant chemoradiotherapy was developed, with a reasonable predictive power. This nomogram needs external validation before it can be used for individualised clinical decision-making. Ó 2015 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology xxx (2015) xxx–xxx Oesophageal cancer is an aggressive disease, with rising inci- dences in the United States and Western Europe [1,2]. It is often diagnosed at an advanced stage; hence less than half of the patients are eligible for potentially curative treatment. Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is considered standard treatment for locoregional disease (cT1N1 and cT2-T4a, N0-N3, M0). The purpose of this multimodality approach is to downstage the primary tumour and regional lymph nodes in order to facilitate a radical resection and to eradicate micrometastases. Recently, the Dutch CROSS trial showed that patients who underwent nCRT followed by surgery had a better survival with reduced locoregional and distant recurrences as compared to surgery alone [3–6]. The extent of tumour regression in the resection specimen, as assessed by the pathologist, in the primary lesion and removed lymph nodes is associated with survival after oesophagectomy [7,8]. Approximately 30% of patients receiving nCRT followed by surgery have a pathologically complete response (pCR; i.e. no vital tumour cells in the resection specimen) [6]. Patients with pCR have a better overall survival compared to patients with residual disease in the resection specimen [4,9–11]. Patients without substantial pathological response to nCRT do not seem to benefit from nCRT but are exposed to toxicity of nCRT. Furthermore, curative surgery is delayed [12]. Identification of patients who will benefit most from nCRT has been the subject of several studies. If we were able to accurately predict pCR in individual patients, these patients might be candi- dates to postpone or even omit surgical resection. Biomarker and tumour genetic profiles have been investigated, but they are com- plex to use and none have been properly validated. Functional imaging, including positron emission tomography is moderately able to identify responders early during neoadjuvant chemother- apy, but is less accurate for the early assessment of tumour response to nCRT [13,14]. The aim of this retrospective cohort study was to identify patient and tumour characteristics that are associated with http://dx.doi.org/10.1016/j.radonc.2015.04.028 0167-8140/Ó 2015 Elsevier Ireland Ltd. All rights reserved. ⇑ Corresponding author at: Department of Surgery, Suite Na-0621, Erasmus MC – University Medical Centre Rotterdam, Rotterdam, The Netherlands. E-mail address: e.toxopeus@erasmusmc.nl (E.L.A. Toxopeus). Radiotherapy and Oncology xxx (2015) xxx–xxx Contents lists available at ScienceDirect Radiotherapy and Oncology journal homepage: www.thegreenjournal.com Please cite this article in press as: Toxopeus ELA et al. Nomogram for predicting pathologically complete response after neoadjuvant chemoradiotherapy for oesophageal cancer. Radiother Oncol (2015), http://dx.doi.org/10.1016/j.radonc.2015.04.028