Abstract
Purpose
Although three dimensional-conformal radiotherapy (3D-CRT) remains a standard treatment approach for esophageal cancers (EC), intensity modulated radiation therapy (IMRT) is increasingly used given its improved sparing of thoracic organs-at-risk. Our goal was to compare the long-term outcomes and toxicities in EC patients treated with either definitive concurrent chemoradiation (dCRT) or trimodality therapy with neoadjuvant CRT and surgery (nCRT) at MD Anderson, using IMRT with two approaches: either step-and-shoot (SS) or Volumetric Modulated Arc Therapy (VMAT).
Methodology
All consecutively treated, American Joint Committee on Cancer 7th edition clinical stage I-IV EC patients from 2001 to 2022 were retrospectively analyzed. Standard RT dose for most patients was 50.4 Gy/28 fractions. Kaplan-Meier method was used to compare overall survival (OS), locoregional recurrence-free survival (LRRFS) and distant metastatic-free survival (DMFS) after propensity score matching (PSM). Cox proportional hazards model was used to determine associations. Common Terminology Criteria for Adverse Events, version 4.0 was used to grade toxicities, and differences were estimated using Chi-Square after PSM.
Results
There were 1,002 EC IMRT patients: 557 (55.6%) had dCRT and 445 (44.4%) had nCRT. Median follow-up was 53 months. Median, 5- and 10-year OS were 43 months, 42.9% and 27.4%, respectively. Median LRRFS was not reached and median DMFS was 42 months. VMAT yielded better OS than SS and was driven by nCRT (Table 1). Esophagitis, fatigue, nausea, and stricture were significantly more common with SS than with VMAT (Table 2), and all G4+ toxicities were seen only in SS patients.
Table 1:
Part a:
Outcome | Step-and-shoot (N%) | VMAT (N%) | p-value
Overall | 640 (63.9) | 362 (36.1)
3-yr OS | 48.6% | 59.6%
5-yr OS | 38.1% | 46.6%
Median OS | 33 mos | 58 mos | 0.034
Med. LRRFS | NR | NR | 0.465
Med. DMFS | 40 mos | 37 mos | 0.218
dCRT | 338 (60.7) | 219 (39.3)
3-yr OS | 41.6% | 48.9% | 0.261
5-yr OS | 29.5% | 34.7%
nCRT | 302 (67.9) | 143 (32.1)
3-yr OS | 57.4% | 75.5% | 0.013
5-yr OS | 48.9% | 66.4%
Part b:
Step-and-shoot (N%)
Outcome | dCRT (months) | nCRT (months) | HR (95% CI) | p-value
Median OS | 20 | 73 | 0.45 (0.37-0.55) | <0.001
Med. LRRFS | 38 | NR | 0.28 (0.21-0.38) | <0.001
Med. DMFS | 22 | NR | 0.59 (0.47-0.74) | <0.001
VMAT (N%)
Outcome | dCRT (months) | nCRT (months) | HR (95% CI) | p-value
Median OS | 32 | NR | 0.36 (0.23-0.57) | <0.001
Med. LRRFS | 17 | NR | 0.22 (0.13-0.37) | <0.001
Med. DMFS | 14 | NR | 0.45 (0.31-0.64) | <0.001
NR, not reached
Table 2:
Toxicities | Step-and-shoot, any grade, N (%) | VMAT, any grade, N (%) | p-value
Esophagitis | 271 (53.8) | 233 (46.2) | 0.003
Fatigue | 263 (69.2) | 117 (30.8) | 0.000
Nausea | 202 (64.1) | 113 (35.9) | <0.001
Stricture | 51 (81.0) | 12 (19.0) | <0.001
Conclusions
To our knowledge, this is the largest single-institutional study on EC long-term outcomes and toxicity using CRT. Our cohort demonstrates better outcomes with VMAT and trimodality therapy, and fewer toxicities using VMAT. IMRT should be considered a standard treatment approach for EC patients.
