TY - JOUR
T1 - A systematic review and proportional meta-analysis of image-based pattern of loco-regional failure analyses outcomes in head and neck squamous cell carcinoma
AU - Kristensen, Morten Horsholt
AU - Nielsen, Signe Bergliot
AU - Alsner, Jan
AU - Holm, Anne Ivalu Sander
AU - Hansen, Christian Rønn
AU - Overgaard, Jens
AU - Eriksen, Jesper Grau
N1 - Publisher Copyright:
© 2025 The Authors
PY - 2025/6
Y1 - 2025/6
N2 - Background and purpose: The prognosis following loco-regional failure after primary radiotherapy (RT) for head and neck squamous cell carcinoma (HNSCC) is poor. The hypothesis that most failures occur as a consequence of tumor radioresistance, can be evaluated by proxy as the proportion of failures that occur in the high-dose region. Several studies have investigated possible reasons for treatment failure by an image-based pattern of failure analyses (POF), comparing the initial planning CT scan with a scan conducted upon failure. The aim of the present systematic review and meta-analysis was to evaluate the proportion of failures that occurred in the high-dose region of all analyzed failures. Materials and Methods: A systematic database search from 2000 to 2023, was performed for studies including results from image-based loco-regional POF, regardless of the method, after primary RT for HNSCC. Proportions of volumetrically in-field (opposed to marginal or outfield) failures, point of origin-based inside high-dose targets, or covered by curative doses for both the number of patients and the number of failure sites were analyzed in proportional meta-analyses. The review was registered at Prospero (CRD42023412545). Results: Out of 56 included studies, accumulated image-based POF results were available from 1,161 patients and 658 individual failure sites. The majority of patients had in-field failures in volumetric-based studies (84 % (95 % CI: 77;90)), inside failures in point of origin-based studies (82 % (95% CI:61;85)) or failures covered by 95 % of dose prescribed to CTV1 (84 % (95% CI:69;95)). A trend toward increasing proportions of non-high-dose failures in more recently treated patients was observed. Conclusion: Most loco-regional failures for patients treated with primary RT for HNSCC are related to the high-dose volume. Therefore, a focus on biomarkers predicting individual tumor radiosensitivity is warranted to enable individualized treatment intensification to increase loco-regional control.
AB - Background and purpose: The prognosis following loco-regional failure after primary radiotherapy (RT) for head and neck squamous cell carcinoma (HNSCC) is poor. The hypothesis that most failures occur as a consequence of tumor radioresistance, can be evaluated by proxy as the proportion of failures that occur in the high-dose region. Several studies have investigated possible reasons for treatment failure by an image-based pattern of failure analyses (POF), comparing the initial planning CT scan with a scan conducted upon failure. The aim of the present systematic review and meta-analysis was to evaluate the proportion of failures that occurred in the high-dose region of all analyzed failures. Materials and Methods: A systematic database search from 2000 to 2023, was performed for studies including results from image-based loco-regional POF, regardless of the method, after primary RT for HNSCC. Proportions of volumetrically in-field (opposed to marginal or outfield) failures, point of origin-based inside high-dose targets, or covered by curative doses for both the number of patients and the number of failure sites were analyzed in proportional meta-analyses. The review was registered at Prospero (CRD42023412545). Results: Out of 56 included studies, accumulated image-based POF results were available from 1,161 patients and 658 individual failure sites. The majority of patients had in-field failures in volumetric-based studies (84 % (95 % CI: 77;90)), inside failures in point of origin-based studies (82 % (95% CI:61;85)) or failures covered by 95 % of dose prescribed to CTV1 (84 % (95% CI:69;95)). A trend toward increasing proportions of non-high-dose failures in more recently treated patients was observed. Conclusion: Most loco-regional failures for patients treated with primary RT for HNSCC are related to the high-dose volume. Therefore, a focus on biomarkers predicting individual tumor radiosensitivity is warranted to enable individualized treatment intensification to increase loco-regional control.
KW - Geographical miss
KW - High-dose failure
KW - HNSCC
KW - Image co-registration
KW - Image-based pattern of failure
KW - In-field failure
KW - Meta-analysis
KW - Pattern of failure
KW - Radioresistance
KW - Recurrence
KW - Systematic review
UR - http://www.scopus.com/inward/record.url?scp=105000619964&partnerID=8YFLogxK
U2 - 10.1016/j.radonc.2025.110838
DO - 10.1016/j.radonc.2025.110838
M3 - Review
C2 - 40089161
AN - SCOPUS:105000619964
SN - 0167-8140
VL - 207
JO - Radiotherapy and Oncology
JF - Radiotherapy and Oncology
M1 - 110838
ER -