Dose response relation in esophageal cancer after neoadjuvant therapy: multi-institutional analysis

Purpose or Objective
Curative treatment for locally advanced esophageal
cancer (EC) consists of neoadjuvant chemoradiotherapy
(nCRT) followed by surgery. Various chemotherapy and
radiotherapy regimens are currently used worldwide. The
aim of this study was to explore whether a higher total
radiation dose leads to a higher probability to obtain a
pathological major response (pMR).
Material and Methods
All consecutive patients who underwent nCRT followed by
surgery for locally advanced squamous cell carcinoma
(SCC) or adenocarcinoma (AC) of the esophagus between
2000 and 2017 at four major university medical centres
were included and stratified according to a prescribed
dose of 36Gy, 40Gy, 41.4Gy, 45Gy or 50.4Gy in fractions
of 1.8Gy or 2Gy. Clinical and treatment-related
characteristics were collected from the prospectively
obtained databases: age at diagnosis, sex, clinical tumor
and nodal stage, histology, chemotherapy regimen, use of
induction chemotherapy and the time interval from nCRT
to surgery. The primary endpoint for the analysis was a
pMR, defined as Mandard 1 (no residual tumor cells) or
Mandard 2 (fibrosis with scattered tumor cells). A
multivariable logistic regression analysis was used to
analyse the relation between neoadjuvant radiation dose
and pMR. Subgroup analysis was performed according to
histology.
Results
A total of 1102 patients were eligible for analysis, who
received either 36Gy (162; 14.7%), 40Gy (79; 7.2%),
41.4Gy (211; 19.1%), 45Gy (271; 24.6%) or 50.4Gy (379;
34.4%). A pMR was achieved in 604 patients (54.8%). In
multivariable analysis, the total radiation dose was the
only factor increasing the probability of reaching a pMR
(odds ratio (OR) 1.031), Table 1. Factors reducing this
probability were a higher cT stage (cT1: reference; cT2:
OR 1.030; cT3: OR 0.556; cT4: OR 0.448), the presence of
an AC (OR 0.362) and the use of non-platinum versus
platinum based chemotherapy (OR 0.294). The interaction
between tumor type and chemotherapy regimen indicated
that using non-platinum based chemotherapy for AC
patients increases the likelihood of achieving a pMR (OR
4.336). The interaction between tumor type and the use
of induction chemotherapy showed that the use of
induction chemotherapy is beneficial to reach a pMR in AC
patients (OR 1.731).
For AC, 417 of 819 patients (50.9%) achieved a pMR.
Factors increasing the probability to achieve a pMR were
total radiation dose (OR 1.027) and the use of induction
chemotherapy (OR 1.702), Table 1. Tumor stage was the
only factor reducing this probability (cT1: reference; cT2:
OR 0.423, cT3: OR 0.260; cT4: OR 0.241).
For SCC, 187 of 283 patients (66.1%) achieved a pMR. No
subgroup analysis with reliable adjustment of covariables
was possible for the cohort of SCC patients.
Conclusion
In this cohort of 1102 patients with EC who were treated
with nCRT followed by surgery at four high volume
institutes, it was demonstrated that the total radiation
dose has a major impact on pathological response,
especially in AC patients.