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Biomarkers are of major interest to optimize diagnosis, prognosis and to guide treatment in head and neck cancer patients. Especially blood-based biomarkers appear promising as they can be easily collected and repeatedly analyzed during the course of radiochemotherapy.

Purpose: To retrain a model based on a previously identified prognostic imaging biomarker using apparent diffusion coefficient (ADC) values from diffusion-weighted magnetic resonance imaging (DW-MRI) in a preclinical setting and validate the model using clinical DW-MRI data of patients with locally advanced head-and-neck cancer (HNC) acquired before radiochemotherapy., Material and Methods: A total of 31 HNC patients underwent T2-weighted and DW-MRI using 3 T MRI before radiochemotherapy (35 x 2 Gy). Gross tumor volumes (GTV) were delineated based on T2-weighted and b500 images. A preclinical model previously revealed that the size of high-risk subvolumes (HRS) defined by a band of ADC-values was correlated to radiation resistance. To validate this model, different bands of ADC-values were tested using two-sided thresholds on the low-ADC histogram flank to determine HRSs inside the GTV and correlated to treatment outcome after three years. The best model was used to fit a logistic regression model. Stratification potential regarding outcome was internally validated using bootstrap, receiver-operator-characteristic (ROC)-analysis, Kaplan-Meier- and Cox-method, and compared to GTV, ADC mean and clinical factors., Results: The best model was defined by 800-6 mm 2 /s and correlated significantly to treatment outcome (p = 0.003). Optimal HRS cut-off value was found to be 5.8 cm 3 according to ROC-analysis. This HRS demonstrated highly significant stratification potential (p < 0.001, bootstrap AUC ≥ 0.84) similar to GTV size (p < 0.001, AUC ≥ 0.79), in contrast to ADC mean (p = 0.361, AUC = 0.53)., Conclusions: A preclinical prognostic model defined by an ADC-based HRS was successfully retrained and validated in HNC patients treated with radiochemotherapy. After thorough external validation, such functional HRS based on a band of ADC values may in the future allow interventional response-adaptive MRI-guided radiotherapy in online and offline approaches., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Neoadjuvant chemoradiotherapy (NCRT) is a standard treatment option for locally advanced rectal cancer. However, there is still conflicting data about the genetic landscape and potential dynamics during and after NCRT. This study evaluated oncogenic driver mutations before NCRT and investigated corresponding resection samples after treatment., Materials and Methods: In 17 patients the pre-therapeutic biopsy and in ten cases the related resection specimen were investigated by next-generation sequencing using a dedicated cancer panel (708 genes). Oncogenic driver mutations and tumor mutational burden (TMB) were compared pre- and post NCRT to evaluate stability of the genomic landscape. TMB and frequently detected driver mutations were correlated with outcome parameters., Results: In our corresponding tumor samples before and after NCRT 95.2 % of the oncogenic driver mutations could be found in both specimens whereas one ATM and one RYR1 mutation were not detectable after NCRT. TMB decreased in all patients after neoadjuvant treatment. KRAS  ±  TP53 mutations and TMB ≥ 5 were associated with impaired outcome., Conclusion: Most oncogenic driver mutations investigated persisted after neoadjuvant treatment. At the same time, we did not observe ascending TMB after treatment but decline. Thus, NCRT does not seem to induce a relevant number of new driver mutations or mutational burden. Genetic profiling implies the potential to support tumor-informed approaches and outcome estimation in future., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: KC, CG and MN report institutional collaborations including financial and non-financial support by Elekta, Philips, Siemens, Dr. Sennewald, PTW Freiburg, Kaiku and Therapanacea. CS reports institutional grants from Novartis and Illumina as well as research grants from BMS Stiftung Immunonkologie outside the submitted work., (© 2024 The Authors. Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology.)

Background: In locally advanced rectal cancer, the prediction of tumor response during and after neoadjuvant treatment remains challenging. In terms of organ preservation, adaptive radiotherapy, and intensified (total) neoadjuvant therapies, biomarkers are desirable for patient stratification., Methods: In 16 patients, weekly blood samples (n = 86) to detect cell-free tumor DNA (ctDNA) during long-course neoadjuvant chemoradiotherapy were analyzed. Data were correlated with initial tumor volumes, MRI response in week 2 and 5 of radiotherapy as well as with pathologic tumor response after resection and outcome parameters., Results: Most patients showed decreasing ctDNA during the course of radiochemotherapy. However, we found heterogenous dynamics of ctDNA and could identify three groups: (1) decline (2) no clear decline and/or late shedding (3) persistence of ctDNA. In seven patients we could detect significant amounts of ctDNA in week 5 or week 6 of treatment. In our pilot cohort, we did not find significant correlations of ctDNA dynamics with pathologic response or outcome parameters. However, patients with distinct decline of ctDNA had larger tumor volumes prior to treatment, and MRI imaging in week 2 and 5 revealed bigger absolute decrease of tumor volumes. If significant levels of ctDNA were found in week 5 and / or 6, patients showed less absolute tumor volume decrease in week 2 and 5., Conclusions: Weekly measurement of ctDNA during radiochemotherapy is feasible and might represent a promising biomarker. Bigger initial primary tumors showed different ctDNA shedding profiles compared with smaller primary tumors and correlations of ctDNA dynamics with early imaging response were found., (© 2024. The Author(s).)

Background: Target volume definition for curative radiochemotherapy in head and neck cancer is crucial since the predominant recurrence pattern is local. Additional diagnostic imaging like MRI is increasingly used, yet it is usually hampered by different patient positioning compared to radiotherapy. In this study, we investigated the impact of diagnostic MRI in treatment position for target volume delineation., Methods: We prospectively analyzed patients who were suitable and agreed to undergo an MRI in treatment position with immobilization devices prior to radiotherapy planning from 2017 to 2019. Target volume delineation for the primary tumor was first performed using all available information except for the MRI and subsequently with additional consideration of the co-registered MRI. The derived volumes were compared by subjective visual judgment and by quantitative mathematical methods., Results: Sixteen patients were included and underwent the planning CT, MRI and subsequent definitive radiochemotherapy. In 69% of the patients, there were visually relevant changes to the gross tumor volume (GTV) by use of the MRI. In 44%, the GTV&#95;MRI would not have been covered completely by the planning target volume (PTV) of the CT-only contour. Yet, median Hausdorff und DSI values did not reflect these differences. The 3-year local control rate was 94%., Conclusions: Adding a diagnostic MRI in RT treatment position is feasible and results in relevant changes in target volumes in the majority of patients., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Purpose: Willingness-to-pay (WTP) analyses can support allocation processes considering the patients preferences in personalized medicine. However, genetic testing especially might imply ethical concerns that have to be considered. Methods: A WTP questionnaire was designed to compare preferences for imaging and genetic testing in cancer patients and to evaluate potential ethical concerns. Results: Comparing the options of imaging and genetics showed comparable WTP values. Ethical concerns about genetic testing seemed to be minor. Treatment success was the top priority irrespective of the diagnostic modality. In general, the majority of patients considered personalized medicine to be beneficial. Conclusion: Most patients valued personalized approaches and rated the benefits of precision medicine of overriding importance irrespective of modality or ethical concerns.

Purpose: High Mobility Group Box 1 (HMGB1) protein has been described as a consensus marker for immunogenic cell death (ICD) in cancer. To personalize treatments, there is a need for biomarkers to adapt dose prescription, concomitant chemotherapy, and follow-up in radiation oncology. Thus, we investigated the levels of HMGB1 in plasma of patients with head and neck squamous cell carcinoma (HNSCC) during the course of radiochemotherapy and follow-up in correlation with oncologic outcome and clinical confounders., Methods: In our pilot study, 11 patients with advanced HNSCC were treated with definitive radiochemotherapy. Blood samples were taken weekly during treatment and frequently at follow-up visits. HMGB1 levels as well as routine laboratory values were measured and clinical information was collected including tumor volume, infections, toxicity, and follow-up data., Results: In total, 85 samples were analyzed. In eight patients, HMGB1 levels (baseline vs. last available sample during treatment) were increasing and in three patients HMGB1 values were decreasing toward the end of treatment. All three patients with decreasing values developed tumor recurrence. By contrast, no relapse occurred in patients that showed increasing HMGB1 levels during therapy. Moreover, a positive correlation of HMGB1 levels with tumor volumes, C‑reactive protein (CRP) levels, infections, and grade three toxicity (RTOG) was observed., Conclusion: HMGB1 might be a promising marker to monitor ICD in HNSCC during the course of radiochemotherapy. However, HMGB1 seems to reflect complex and diverse immunogenic responses and potential confounders. Infections and treatment-associated toxicity should be considered when interpreting the dynamics of HMGB1., (© 2021. The Author(s).)