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Peer-reviewedCC BY 4.0Cancers

Baseline Host Biomarkers and Six-Month Sustained Drug-Free Status After Atezolizumab–Bevacizumab for Hepatocellular Carcinoma: Exploratory Clinical Stratification Using PAN-DF Score

  • Chikara Iino1
  • Tamami Abe2
  • Kei Endo2
  • Yudai Fujiwara2
  • Kenta Yoshida1
  • Satoshi Sato1
  • Hiroshi Numao3
  • Go Igarashi3
  • Takayoshi Oikawa4
  • Masashi Ninomiya5
  • Mio Tsuruoka5
  • Wataru Sato6
15 more authors
  • Shinichiro Minami6
  • Kazumichi Abe7
  • Masashi Fujita7
  • Nobukazu Tanabe8
  • Tomohiro Katsumi9
  • Keita Maki9
  • Goki Suda10
  • Takuya Sho10
  • Yoshiya Yamamoto11
  • Masaru Baba12
  • Takashi Meguro13
  • Hirotake Sakuraba1
  • Naoya Sakamoto10
  • Yoshiyuki Ueno9
  • Hidekatsu Kuroda2
13 affiliations
  1. 1Department of Gastroenterology, Hematology and Clinical Immunology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Aomori, Japan
  2. 2Department of Gastroenterology and Hepatology, Division of Internal Medicine, Iwate Medical University, Yahaba 028-3694, Iwate, Japan
  3. 3Department of Gastroenterology, Aomori Prefectural Central Hospital, Aomori 030-8553, Aomori, Japan
  4. 4Department of Gastroenterology, Japanese Red Cross Morioka Hospital, Morioka 020-8560, Iwate, Japan
  5. 5Division of Gastroenterology, Tohoku University Hospital, Sendai 980-8574, Miyagi, Japan
  6. 6Department of Gastroenterology, Akita University Graduate School of Medicine, Akita 010-8543, Akita, Japan
  7. 7Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima 960-1295, Fukushima, Japan
  8. 8Department of Gastroenterology, National Hospital Organization Sendai Medical Center, Sendai 983-8520, Miyagi, Japan
  9. 9Department of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata 990-9585, Yamagata, Japan
  10. 10Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Hokkaido, Japan
  11. 11Department of Gastroenterology, Hakodate City Hospital, Hakodate 041-8680, Hokkaido, Japan
  12. 12Department of Gastroenterology and Hepatology, Japan Community Health Care Organization (JCHO) Hokkaido Hospital, Sapporo 062-8618, Hokkaido, Japan
  13. 13Department of Gastroenterology, Hokkaido Gastroenterology Hospital, Sapporo 065-0041, Hokkaido, Japan
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Abstract

Background/Objectives: Sustained drug-free status is an emerging milestone after atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma. We examined baseline host biomarkers associated with achievement of 6-month sustained drug-free status and evaluated a composite stratification score. Methods: This multicentre retrospective study included patients treated with atezolizumab plus bevacizumab. The endpoint required systemic therapy discontinuation after complete response or no viable disease, followed by at least 6 months without viable or recurrent hepatocellular carcinoma and sustained normalization of initially elevated tumour markers. The PAN-DF score (preserved hepatic reserve, altered immune-inflammatory status, and nutritional-immune reserve for achieving drug-free status) combined modified albumin–bilirubin grade, neutrophil-to-lymphocyte ratio, and prognostic nutritional index. Results: Among 655 patients, 25 achieved the endpoint; median post-discontinuation follow-up was 533 days. In the complete-case cohort (n = 473; 17 events), achievement rates were 0.0%, 2.9%, 3.7%, and 13.6% for scores 0–3. Each one-point increase was associated with higher odds of achievement (odds ratio 2.90, 95% confidence interval 1.51–5.55; p = 0.001), and the area under the curve was 0.719. The examined baseline tumour-related factors were not significantly associated with the primary endpoint, and the examined host-related factors were not associated with objective response. Conclusions: Selected baseline host biomarkers were associated with achievement of 6-month sustained drug-free status. PAN-DF stratified the observed probability of this outcome and may help identify patient groups with a relatively higher likelihood of a sustained drug-free state, supporting early multidisciplinary planning.

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Cite

BibTeXRIS
BibTeX
@article{iino2026baseline,
  title = {{Baseline Host Biomarkers and Six-Month Sustained Drug-Free Status After Atezolizumab–Bevacizumab for Hepatocellular Carcinoma: Exploratory Clinical Stratification Using PAN-DF Score}},
  author = {Chikara Iino and Tamami Abe and Kei Endo and Yudai Fujiwara and Kenta Yoshida and Satoshi Sato and Hiroshi Numao and Go Igarashi and Takayoshi Oikawa and Masashi Ninomiya and Mio Tsuruoka and Wataru Sato and Shinichiro Minami and Kazumichi Abe and Masashi Fujita and Nobukazu Tanabe and Tomohiro Katsumi and Keita Maki and Goki Suda and Takuya Sho and Yoshiya Yamamoto and Masaru Baba and Takashi Meguro and Hirotake Sakuraba and Naoya Sakamoto and Yoshiyuki Ueno and Hidekatsu Kuroda},
  journal = {Cancers},
  year = {2026},
  month = oct,
  doi = {10.3390/cancers18203366},
  url = {https://www.mdpi.com/2072-6694/18/20/3366},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Baseline Host Biomarkers and Six-Month Sustained Drug-Free Status After Atezolizumab–Bevacizumab for Hepatocellular Carcinoma: Exploratory Clinical Stratification Using PAN-DF Score
AU  - Chikara Iino
AU  - Tamami Abe
AU  - Kei Endo
AU  - Yudai Fujiwara
AU  - Kenta Yoshida
AU  - Satoshi Sato
AU  - Hiroshi Numao
AU  - Go Igarashi
AU  - Takayoshi Oikawa
AU  - Masashi Ninomiya
AU  - Mio Tsuruoka
AU  - Wataru Sato
AU  - Shinichiro Minami
AU  - Kazumichi Abe
AU  - Masashi Fujita
AU  - Nobukazu Tanabe
AU  - Tomohiro Katsumi
AU  - Keita Maki
AU  - Goki Suda
AU  - Takuya Sho
AU  - Yoshiya Yamamoto
AU  - Masaru Baba
AU  - Takashi Meguro
AU  - Hirotake Sakuraba
AU  - Naoya Sakamoto
AU  - Yoshiyuki Ueno
AU  - Hidekatsu Kuroda
PY  - 2026
DA  - 2026/10/01
JO  - Cancers
DO  - 10.3390/cancers18203366
UR  - https://www.mdpi.com/2072-6694/18/20/3366
AB  - Background/Objectives: Sustained drug-free status is an emerging milestone after atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma. We examined baseline host biomarkers associated with achievement of 6-month sustained drug-free status and evaluated a composite stratification score. Methods: This multicentre retrospective study included patients treated with atezolizumab plus bevacizumab. The endpoint required systemic therapy discontinuation after complete response or no viable disease, followed by at least 6 months without viable or recurrent hepatocellular carcinoma and sustained normalization of initially elevated tumour markers. The PAN-DF score (preserved hepatic reserve, altered immune-inflammatory status, and nutritional-immune reserve for achieving drug-free status) combined modified albumin–bilirubin grade, neutrophil-to-lymphocyte ratio, and prognostic nutritional index. Results: Among 655 patients, 25 achieved the endpoint; median post-discontinuation follow-up was 533 days. In the complete-case cohort (n = 473; 17 events), achievement rates were 0.0%, 2.9%, 3.7%, and 13.6% for scores 0–3. Each one-point increase was associated with higher odds of achievement (odds ratio 2.90, 95% confidence interval 1.51–5.55; p = 0.001), and the area under the curve was 0.719. The examined baseline tumour-related factors were not significantly associated with the primary endpoint, and the examined host-related factors were not associated with objective response. Conclusions: Selected baseline host biomarkers were associated with achievement of 6-month sustained drug-free status. PAN-DF stratified the observed probability of this outcome and may help identify patient groups with a relatively higher likelihood of a sustained drug-free state, supporting early multidisciplinary planning.
SN  - 2072-6694
ER  -