ESTRO 2023

Session Item

Saturday

May 13

10:30 - 11:30

Plenary Hall

Upper GI

Chair: Marianne Nordsmark, Denmark;

Co-Chair: , The Netherlands

Session Code: 1215

Session Type: Proffered Papers

Track: Clinical

10:50 - 11:00

First randomized evidence of the lymphocyte-sparing effect of proton beam therapy (NCT01512589)

, The Netherlands

Presentation Number: OC-0101

Abstract

Abstract Title:

First randomized evidence of the lymphocyte-sparing effect of proton beam therapy (NCT01512589)

Authors:

Xin Wang^1,2, Peter van Rossum², Yan Chu³, Brian Hobbs⁴, Clemens Grassberger⁵, Theodore Hong⁶, Zhongxing Liao², Radhe Mohan⁷, Steven Lin²

¹Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Radiation Oncology, Tianjin, China; ²The University of Texas MD Anderson Cancer Center, Radiation Oncology, Houston (TX), USA; ³The University of Texas at Houston, UTHealth, Houston (TX), USA; ⁴The University of Texas at Austin, Population Health, Dell Medical School, Austin (TX), USA; ⁵Massachusetts General Hospital, Radiation-Drug Treatment Design Lab, Boston (MA), USA; ⁶Massachusetts General Hospital, Radiation Oncology, Boston (MA), USA; ⁷The University of Texas MD Anderson Cancer Center, Radiation Physics, Houston (TX), USA

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Purpose or Objective

While lymphocytes play an important role in anti-tumor immunity, they are also especially vulnerable to depletion during chemoradiotherapy (CRT). Since the extent of radiation dose scatter within the irradiated region has been implicated in the degree of radiation-induced lymphopenia (RIL), the primary purpose of this study was to compare the incidence of grade 4 lymphopenia (G4L) between proton beam therapy (PBT) and intensity-modulated photon RT (IMRT) in esophageal cancer patients treated with CRT in a completed randomized trial. A second purpose was to ascertain patient heterogeneity to G4L risk based on treatment factors and established prognostic factors.

Material and Methods

Between April 2012 and March 2019, a single-institutional, open-label, nonblinded, phase II randomized trial was conducted at The University of Texas MD Anderson Cancer Center. Patients with locally advanced esophageal cancer were randomly assigned to IMRT or PBT, either definitively or pre-operatively. The primary endpoint of this post-hoc analysis was grade 4 lymphopenia (G4L) during concurrent CRT according to CTCAE version 5.0.

Results

In total, 105 patients were evaluable for analysis with a median follow-up of 46 months. Among them, 44 patients (42%) experienced G4L at a median of 28 days after the start date of concurrent CRT. Figure 1 illustrates the absolute lymphocyte counts for the patients over the 5-week monitoring period during CRT stratified by treatment arm. The incidence of G4L for PBT versus IMRT was 27.3% versus 52.5%, respectively (relative risk 0.52, p=0.010). Induction chemotherapy (hazard ratio [HR] = 3.78, 95% confidence interval [CI] 1.59-8.97, p=0.003), baseline absolute lymphocyte count (ALC in K/μL; HR = 0.19, 95%CI 0.09-0.38, p<0.001), radiotherapy modality (IMRT vs. PBT; HR = 3.00, 95%CI 1.48-6.07, p=0.002), and planning treatment volume (PTV) (per 100 mL; HR = 1.13, 95%CI 1.01-1.27, p=0.033) were found to be significantly associated with G4L. Multivariable classification analysis partitioned patients into five subgroups for whom the incidence of G4L was observed in 0%, 14%, 35%, 70%, and 100% of patients (Figure 2). The benefit of PBT over IMRT was most pronounced in patients with an intermediate baseline ALC and large PTV (G4L in 35% versus 70%, respectively, p=0.011).

Figure 1. Distribution of absolute lymphocyte counts during concurrent CRT for patients stratified by treatment arm. G4L: grade 4 lymphopenia. *: p<0.05. **: p<0.01.

Figure 2. Decision risk tree model based on predictive factors for grade 4 lymphopenia (G4L).

Conclusion

This is the first prospective and randomized evidence demonstrating that limiting dose scatter through using PBT instead of IMRT can significantly reduce the incidence of severe lymphopenia, especially in the intermediate-risk patients. The implication of this immune-sparing effect of PBT, especially in the recently adopted context of standard adjuvant immunotherapy, needs further examination in the currently ongoing phase III randomized trials.