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Peer-reviewedCC BY 4.0International Journal of Molecular Sciences

Prediction of Tumor Complete Response Using Genomic and Clinical Data in Solid Cancer Undergoing Definitive Radiation Therapy

  • Jun Young Chang1
  • Seung-Hyun Jung1,2,3
  • Dong Soo Lee4
4 affiliations
  1. 1Department of Medical Sciences, Graduate School, The Catholic University of Korea, Seoul 06591, Republic of Korea
  2. 2Catholic Research Institute for Human Genome Polymorphism, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
  3. 3Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
  4. 4Department of Radiation Oncology, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
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Abstract

In this retrospective, single-center observational study, targeted next-generation sequencing (NGS) was performed on pre-radiation therapy (RT) tumor specimens to identify genomic features associated with RT response and clinical outcomes. This study included 77 eligible patients with esophageal squamous cell carcinoma (ESCC, n = 23), non-human papilloma virus-related head and neck squamous cell carcinoma (HNSCC, n = 24), and rectal adenocarcinoma (RAC, n = 30) treated between 2014 and 2020. Treatment was employed for definitive aim (chemoradiotherapy or pre-operative chemoradiotherapy followed by radical surgery). Treatment response was assessed using clinical and pathological criteria and was dichotomized as complete response (CR) versus non-CR. Targeted NGS was performed using a customized panel composing 161 genes. A total of 1263 nonsynonymous somatic variants were identified across 153 genes. The most commonly altered genes were TP53 (70.1%), APC (41.6%), NOTCH1 (41.6%), KMT2C (39.0%), NOTCH3 (36.4%), and NOTCH2 (35.1%). Overall, 25 (32.5%) and 52 patients (67.5%) were classified as CR and non-CR, respectively. APC (P = 0.008), KMT2C (P = 0.018), and KRAS (P = 0.012) alterations were associated with non-CR, whereas CD274 (P = 0.003), MSH3 (P = 0.011), and NOTCH3 (P = 0.048) alterations were associated with CR. KRAS alterations occurred exclusively in RAC, and most concurrent APC–KMT2C alterations in non-CR tumors were also observed in RAC, suggesting that these associations may partly reflect tumor type-specific genomic backgrounds. An exploratory pooled model incorporating age and six candidate genomic variables achieved a cross-validated area under the curve of 0.867 for CR prediction. In survival analysis, alterations in CCND1, CXCL9, ERCC6, LIF, and RAD51B were independently associated with poor recurrence-free survival. Pre-RT tumor genomic profiling identified candidate features associated with RT response and recurrence-free survival in this heterogeneous cohort. The pooled genomic associations and prediction model should not be interpreted as pan-cancer biomarkers or predictors and require validation in larger, independent, cancer-specific cohort.

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Cite

BibTeXRIS
BibTeX
@article{chang2026prediction,
  title = {{Prediction of Tumor Complete Response Using Genomic and Clinical Data in Solid Cancer Undergoing Definitive Radiation Therapy}},
  author = {Jun Young Chang and Seung-Hyun Jung and Dong Soo Lee},
  journal = {International Journal of Molecular Sciences},
  year = {2026},
  month = oct,
  doi = {10.3390/ijms27208991},
  url = {https://www.mdpi.com/1422-0067/27/20/8991},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Prediction of Tumor Complete Response Using Genomic and Clinical Data in Solid Cancer Undergoing Definitive Radiation Therapy
AU  - Jun Young Chang
AU  - Seung-Hyun Jung
AU  - Dong Soo Lee
PY  - 2026
DA  - 2026/10/01
JO  - International Journal of Molecular Sciences
DO  - 10.3390/ijms27208991
UR  - https://www.mdpi.com/1422-0067/27/20/8991
AB  - In this retrospective, single-center observational study, targeted next-generation sequencing (NGS) was performed on pre-radiation therapy (RT) tumor specimens to identify genomic features associated with RT response and clinical outcomes. This study included 77 eligible patients with esophageal squamous cell carcinoma (ESCC, n = 23), non-human papilloma virus-related head and neck squamous cell carcinoma (HNSCC, n = 24), and rectal adenocarcinoma (RAC, n = 30) treated between 2014 and 2020. Treatment was employed for definitive aim (chemoradiotherapy or pre-operative chemoradiotherapy followed by radical surgery). Treatment response was assessed using clinical and pathological criteria and was dichotomized as complete response (CR) versus non-CR. Targeted NGS was performed using a customized panel composing 161 genes. A total of 1263 nonsynonymous somatic variants were identified across 153 genes. The most commonly altered genes were TP53 (70.1%), APC (41.6%), NOTCH1 (41.6%), KMT2C (39.0%), NOTCH3 (36.4%), and NOTCH2 (35.1%). Overall, 25 (32.5%) and 52 patients (67.5%) were classified as CR and non-CR, respectively. APC (P = 0.008), KMT2C (P = 0.018), and KRAS (P = 0.012) alterations were associated with non-CR, whereas CD274 (P = 0.003), MSH3 (P = 0.011), and NOTCH3 (P = 0.048) alterations were associated with CR. KRAS alterations occurred exclusively in RAC, and most concurrent APC–KMT2C alterations in non-CR tumors were also observed in RAC, suggesting that these associations may partly reflect tumor type-specific genomic backgrounds. An exploratory pooled model incorporating age and six candidate genomic variables achieved a cross-validated area under the curve of 0.867 for CR prediction. In survival analysis, alterations in CCND1, CXCL9, ERCC6, LIF, and RAD51B were independently associated with poor recurrence-free survival. Pre-RT tumor genomic profiling identified candidate features associated with RT response and recurrence-free survival in this heterogeneous cohort. The pooled genomic associations and prediction model should not be interpreted as pan-cancer biomarkers or predictors and require validation in larger, independent, cancer-specific cohort.
SN  - 1422-0067
ER  -