A Prospective Real-World Multi-Center Study to Evaluate Progression-Free and Overall Survival of Radiotherapy with Cetuximab and Platinum-Based Chemotherapy with Cetuximab in Locally Recurrent Head and Neck Cancer

Hecht, Markus; Hahn, D; Wolber, Philipp; Hautmann, Matthias G.; Reichert, Dietmar; Weniger, Steffi; Belka, C.; Bergmann, Tobias B.; Göhler, Thomas; Welslau, Manfred; Große-Thie, Christina; Guntinas‐Lichius, Orlando; Grün, Jens von der; Balermpas, Panagiotis; Orlowski, Katrin; Messinger, Diethelm; Stenzel, Karsten G.; Fietkau, Rainer

doi:10.3390/cancers13143413

Cited by 6 publications

(5 citation statements)

References 21 publications

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“…Other two studies have reported that the 1-year OS of Cmab + RT were 44 and 47.5%, respectively (10,11). The overall response rate (ORR) in these reports was 16-58%, which was different from previous study (9)(10)(11). In contrast, the 1-year OS of salvage surgery was approximately 50% (5,6) and 1-year OS of chemotherapy with Cmab (EXTREME regimen and Cmab plus paclitaxel) was approximately 40% in recurrent or metastatic (R/M) OSCC (12,13).…”

Section: Discussionmentioning

confidence: 64%

“…We experienced three cases of favorable locoregional control against locoregional recurrence of OSCC with Cmab + RT. In a prospective study of locoregional recurrence of HNSCC, Hecht et al reported that Cmab + RT had superior progression-free survival and overall survival (OS) compared to Cmab alone, with a 1-year OS of 53% (9). Other two studies have reported that the 1-year OS of Cmab + RT were 44 and 47.5%, respectively (10,11).…”

Section: Discussionmentioning

confidence: 99%

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Complete response of recurrent oral squamous cell carcinoma treated with cetuximab in combination with radiotherapy: A case series

et al. 2022

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Salvage surgery for recurrent oral squamous cell carcinoma (OSCC) often leads to a poor quality of life (QOL). The present study described three cases that resulted in favorable locoregional control with cetuximab in combination with radiotherapy (Cmab + RT). Case 1 had regional recurrence of OSCC at the lower right mastoid area 4 months after primary surgery. Case 2 had regional recurrence of OSCC at the parotid area 7 months after primary surgery. Case 3 had local recurrence of OSCC at the masticatory muscle and Rouviere's lymph nodes 1 year and 3 months after primary surgery. In all cases, Cmab + RT was performed, and disease-free survival was confirmed 4 months, 2 years and 6 months, and 10 months after Cmab + RT, respectively. Immunohistochemically, all resected tumors had no expression of 110-kDa catalytic subunit of class IA phosphatidylinositol 3-kinase (PI3Kp110α). In conclusion, if salvage surgery for recurrent OSCC results in a significantly low QOL, then shifting to chemoradiotherapy may be appropriate as a treatment strategy. In addition, strong evidence indicated that PI3Kp110α expression is associated with Cmab therapy efficacy.

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Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Complete response of recurrent oral squamous cell carcinoma treated with cetuximab in combination with radiotherapy: A case series

et al. 2022

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“…Two (patient 1 and 2 in Table 3 ) patients received additional target therapy with cetuximab after ICT failure and showed longer survival than those without therapy. Several studies ( 34 , 35 ) have shown that cetuximab can improve survival outcomes in advanced HNC. Taken together, these findings indicate that the early identification of potential poor responders to ICT and an early shift in treatment regimens to target therapy or immune therapy may improve survival outcomes in HNC.…”

Section: Discussionmentioning

confidence: 99%

Interval changes of histogram-derived diffusion indices predict treatment response to induction chemotherapy in head and neck cancer: a feasibility study

Cheng¹,

Lu²,

Lin³

et al. 2022

Quant Imaging Med Surg

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Background: This retrospective study investigated whether the interval change of apparent diffusion coefficient (∆ADC) [baseline and after the first cycle of induction chemotherapy (ICT)] can be used as a valid predictive imaging biomarker of the treatment response to ICT in head and neck cancer (HNC). Methods: A total of 19 consecutive patients with HNC who underwent diffusion-weighted magnetic resonance imaging (DWI) at baseline and after the first cycle of ICT were included. Whole-tumor ADC histogram parameters (mean, median, kurtosis, skewness, entropy, minimal, maximum, 25th percentile, and 75th percentile) were obtained. The correlations of ∆ADC histogram parameters, volume, T-stage, N-stage, and age with the treatment response were examined using the Mann-Whitney U test. The predictive value of histogram parameters was examined using receiver operating characteristic (ROC) curves.Results: Responders showed significantly higher values of ∆ADC 25 (0.19±0.23) and ∆ADC min (1.78±2.98) than non-responders (−0.09±0.15 and −0.73±0.36; P=0.035 and 0.009, respectively). When ∆ADC 25 and ∆ADC min were used for predicting the treatment response, the area under the ROC curve was 0.850/0.933 with a sensitivity of 73.3%/80.0% and specificity of 100%/100% (P=0.036 and 0.009, respectively).Conclusions: ∆ADC 25 and ∆ADC min derived from whole-tumor histogram analysis are valuable imaging biomarkers for the early prediction of the ICT response in HNC.

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“…Another FDA-approved example for treatment in recurrent or metastatic HNSCC is the immune checkpoint inhibitor Pembrolizumab, which binds to tumor cells expressing high levels of PD-L1 and achieved a response rate of ~20% in clinical trials; however, it led to hyperprogressive tumor disease in some patients [21,22]. Despite advancements in the knowledge on HNSCC epidemiology and pathogenesis, the prognosis of HNSCC remains poor, showing no significant improvement in survival rates and a high incidence of locoregional recurrence or distant metastases in more than half of HNSCC patients [2,23,24]. The critical demand for an improved understanding of therapy response and the development of new treatment options is particularly crucial for advanced-stage, HPV − cases of HNSCC [25][26][27][28].…”

Section: Introductionmentioning

confidence: 99%

Different Impacts of DNA-PK and mTOR Kinase Inhibitors in Combination with Ionizing Radiation on HNSCC and Normal Tissue Cells

Klieber,

Hildebrand,

Faulhaber

et al. 2024

Cells

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Despite substantial advancements in understanding the pathomechanisms of head and neck squamous cell carcinoma (HNSCC), effective therapy remains challenging. The application of kinase inhibitors (KIs) in HNSCC, specifically mTOR and DNA-PK inhibitors, can increase radiosensitivity and therefore presents a promising strategy when used simultaneously with ionizing radiation (IR) in cancer treatment. Our study focused on the selective DNA-PK-inhibitor AZD7648; the selective mTOR-inhibitor Sapanisertib; and CC-115, a dual inhibitor targeting both mTOR and DNA-PK. The impact of these KIs on HNSCC and normal tissue cells was assessed using various analytical methods including cell death studies, cell cycle analysis, real-time microscopy, colony-forming assays and immunohistochemical staining for γH2AX and downstream mTOR protein p-S6. We detected a strong inhibition of IR-induced DNA double-strand break (DSB) repair, particularly in AZD7648-treated HNSCC, whereas normal tissue cells repaired DNA DSB more efficiently. Additionally, AZD7648 + IR treatment showed a synergistic decline in cell proliferation and clonogenicity, along with an elevated G2/M arrest and cell death in the majority of HNSCC cell lines. CC-115 + IR treatment led to an elevation in G2/M arrest, increased cell death, and a synergistic reduction in cell proliferation, though the effect was notably lower compared to the AZD7648 + IR- treated group. Sapanisertib led to a high cellular toxicity in both HNSCC and normal tissue cells, even in non-irradiated cells. Regarding cell proliferation and the induction of apoptosis and necrosis, Sapanisertib + IR was beneficial only in HPV+ HNSCC. Overall, this study highlights the potential of AZD7648 as a radiosensitizing agent in advanced-stage HPV-positive and negative HNSCC, offering a promising therapeutic strategy. However, the dual mTOR/DNA-PK-I CC-115 did not provide a distinct advantage over the use of selective KIs in our investigations, suggesting limited benefits for its application in KI + IR therapy. Notably, the selective mTOR-inhibitor Sapanisertib was only beneficial in HPV+ HNSCC and should not be applied in HPV− cases.

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A Prospective Real-World Multi-Center Study to Evaluate Progression-Free and Overall Survival of Radiotherapy with Cetuximab and Platinum-Based Chemotherapy with Cetuximab in Locally Recurrent Head and Neck Cancer

Cited by 6 publications

References 21 publications

Complete response of recurrent oral squamous cell carcinoma treated with cetuximab in combination with radiotherapy: A case series

Complete response of recurrent oral squamous cell carcinoma treated with cetuximab in combination with radiotherapy: A case series

Interval changes of histogram-derived diffusion indices predict treatment response to induction chemotherapy in head and neck cancer: a feasibility study

Different Impacts of DNA-PK and mTOR Kinase Inhibitors in Combination with Ionizing Radiation on HNSCC and Normal Tissue Cells

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