Katelyn Knoepke
DOS741
Protocol Summary
NRG-GI006: Phase III Randomized Trial of Proton Beam Therapy (PBT) Versus Intensity
Modulated Photon Radiotherapy (IMRT) for the Treatment of Esophageal Cancer
This clinical trial belongs to the NRG Oncology Group and is a Phase III randomized
trial comparing IMRT and PBT for the treatment of esophageal cancer. The current standard of
care for the treatment of esophageal cancer is radiation with concurrent chemotherapy. This
treatment regimen involves significant toxicities related to radiation exposure to the intrathoracic
organs that impact overall survival. PBT offers the benefit of heart sparing, reduction in
postoperative complications, improved grade 4 lymphopenia, and increased overall survival and
disease specific outcomes.1-4 However, the current knowledge has been acquired in an
uncontrolled, non-randomized manner. This study aims to provide valid and reliable outcome
measurements to compare IMRT and PBT. The primary objective of this trial is to evaluate
overall survival and grade 3+ cardiopulmonary toxicity between IMRT and PBT. Secondary
objectives include patient reported outcomes, locoregional failure, distant metastatic free
survival, progression-free survival, and early and late cardiovascular and pulmonary events.
This trial will accrue 300 patients who will be randomized to two different arms.
Participants must have histologically confirmed adenocarcinoma or squamous cell carcinoma
involving the thoracic esophagus or gastroesophageal junction. AJCC staging eligible for this
trial includes Stage I-IVA, excluding participants with T4b disease. Participants with cervical
esophageal cancers are ineligible. Participants randomized to arm 1 will receive PBT (50.4 Gy
in 28 fractions) with concurrent chemotherapy. Participants randomized to arm 2 will receive
IMRT (50.4 Gy in 28 factions) with concurrent chemotherapy. Participants in either arm may
undergo an esophagectomy within 4-8 weeks after treatment per physician discretion.
Standard terminology is provided for the target volumes included in treatment planning.
The IGTV includes the primary tumor plus the grossly involved regional lymph nodes. The CTV
includes an expansion proximally and distally along the length of the esophagus and proximal
stomach. The PTV includes an additional margin for set-up error and movement. Prescription
coverage should encompass 95% of PTV, 95-99% of the CTV, and greater than 99% of the
IGTV. Organs at risk in the treatment area include the lungs, heart, kidneys, spinal canal, liver,
small and large bowel, stomach, and spleen.
This study provides treatment planning guidelines to be followed. 4D Motion assessment
is required and motion management techniques such as breath hold, gating, and active breathing
control may be used for tumor motion greater than 1.0 cm. An appropriate imaging data set
corresponding with the motion management technique chosen should be utilized for planning
purposes. Immobilization devices that consider both reproducibility and beam range variations
should be utilized. IMRT planning can be accomplished utilizing multiple fields with DMLC,
helical arc therapy, or volumetric arc therapy (VMAT). PBT planning can be accomplished
utilizing 3DCPT or IMPT, with spot scanning beams being preferred. Coplanar or non-coplanar,
non-overlapping, non-opposed proton beams should be utilized to improve conformity, OAR
sparing, and plan robustness. Careful consideration of the beam path is required during treatment
planning. Daily IGRT is required as well as once weekly 4DCT verification scans for the first 3
weeks of treatment.
References
1. Lin SH, Zhang N, Godby J, et al. Radiation Modality Utilization and Cardiopulmonary
Mortality Risk in the Elderly with Esophageal Cancer. Cancer. 2016; 122(6):917-28.
2. Lin SH, Merrell KW, Shen J, et al. Multi-institutional Analysis of Radiation Modality Use and
Postoperative Outcomes of Neoadjuvant Chemoradiation for Esophageal Cancer. Radiother
Oncol. 2017; 123(3):376-381.
3. Davuluri R, Jiang W, Fang P, et al. Lymphocyte Nadir and Esophageal Cancer Survival
Outcomes Following Chemoradiotherapy. Int J Radiat Oncol Biol Phys. 2017; 99(1):128-135.
4. Xi M, Xu C, Liao Z, et al. Comparative Outcomes after Definitive Chemoradiotherapy using
Proton Beam Therapy versus Intensity-Modulated Radiation Therapy for Esophageal Cancer:
A Retrospective Single-Institutional Analysis. Int J Radiat Oncol Biol Phys. 2017; 99(3):667-
676.