Treatment response lowers tumor symptom burden in recurrent and/or metastatic head and neck cancer

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

Abstract

Background: Head and neck squamous cell cancer (HNSCC) frequently causes severe symptoms that may be reduced, when the tumor is successfully treated. The SOCCER trial studied the association of treatment response with patient reported tumor symptom burden in first line treatment of recurrent and/or metastatic HNSCC.

Methods: In this prospective, multi-center, non-interventional trial patients were treated either with platinum-based chemotherapy and cetuximab or radiotherapy and cetuximab. Tumor symptom burden was assessed every four weeks with a questionnaire containing ten visual analogue scales (VAS, range 0-100), which were summarized to the overall VAS score.

Results: Fourhundred seventy patients were registered in 97 German centers. A total of 315 patients with at least the baseline and one subsequent questionnaire were available for analysis. Changes in the VAS score were rated as absolute differences from baseline. Negative values indicate improvement of symptoms. The overall VAS score improved significantly at the first post-baseline assessment in responders (- 2.13 vs. non-responders + 1.15, p = 0.048), and even more for the best post-baseline assessment (- 7.82 vs. non-responders - 1.97, p = 0.0005). The VAS for pain (- 16.37 vs. non-responders - 8.89, p = 0.001) and swallowing of solid food (- 16.67 vs. non-responders - 5.06, p = 0.002) improved significantly more in responders (best post-baseline assessment). In the multivariable Cox regression analysis, worse overall VAS scores were associated with worse overall survival (hazard ratio for death 1.12 per 10 points increment on the overall VAS scale, 95% CI 1.05-1.20, p = 0.0009).

Conclusion: In unselected patients beyond randomized controlled trials, treatment response lowers tumor symptom burden in recurrent and/or metastatic HNSCC.

Trial registration: ClinicalTrials.gov, NCT00122460 . Registered 22 Juli 2005.

Keywords: Cetuximab; Chemotherapy; HNSCC; Response; Symptom.

Conflict of interest statement

M.H. conflict of interest with Merck Serono (advisory boards, honoraria for lectures, travel grants, research funding); MSD (advisory boards, travel grants, research funding); AstraZeneca (research funding); Novartis (research funding); BMS (advisory boards, honoraria for lectures); Teva (travel grants). M.G.H. conflict of interest with MerckSerono (honoraria as speaker and author) as well as honoraria, travel grant from AstraZeneca, MSD, BMS, Celgene. M.W. no conflict of interest with Merck Serono; conflict of interest with other companies (AMGEN, Astellas, AstraZeneca, Celgene, Gilead, Hexal, Janssen, Lilly, Novartis, Roche, SANOFI). C.G.T. conflict of interest with Merck Serono (speaker fee); conflict of interest with other companies (speaker fee: Amgen, Celgene, Novartis, BMS; travel grants: Daiichi Sankyo, Alexion, BMS, Novartis). O.G.L received lecture fees and travel grants from Merck Serono. K.O. employee of Merck Serono. D.M. employee of Prometris GmbH which provides statistical services for Merck Serono. K.G.S. employee of Merck Serono. R.F. conflict of interest with Merck Serono (AdBoard, Honoraria, Research funding); AstraZeneca (AdBoard, Honoraria, Research funding); MSD (AdBoard, Honoraria, Research funding); Novocure (AdBoard, Honoraria, Research funding); Brainlab (AdBoard, Honoraria, Research funding); Fresenius Kabi (AdBoard, Honoraria, Research funding); BMS (AdBoard, Honoraria, Research funding); Sennewald (Honoraria). The other authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
Consort diagram. TAS: Target Analysis Set; mTAS: modified TAS; CT: Chemotherapy; RT: Radiotherapy; VAS: Visual Analogue Scale. *Some patients violated more than one criterion
Fig. 2
Fig. 2
Baseline symptom burden. Baseline symptom burden of the 315 mTAS patients. Values range from 0 to 100, higher values represent heavier symptoms. The point ♦ in the box indicates the mean and the horizontal lines the median
Fig. 3
Fig. 3
Changes in overall symptom burden in responders and non-responders (ANCOVA analysis). Changes from baseline were analyzed at the three time points “first post-baseline assessment”, “best post-baseline assessment” and “assessment at treatment end” in responders and non-responders. Negative values indicate improved symptoms and positive values deteriorated symptoms. n indicates the number of analyzed questionnaires. Results show the overall VAS score calculated from the ten single symptom VAS scores
Fig. 4
Fig. 4
Changes in single tumour symptoms in responders and non-responders (ANCOVA analysis). Changes from baseline were analyzed at the three time points “first post-baseline assessment”, “best post-baseline assessment” and “assessment at treatment end” in responders and non-responders. Negative values indicate improved symptoms and positive values deteriorated symptoms. n indicates the number of analyzed questionnaires. The ten single symptom VAS assessed swallowing of solid food (a), swallowing of mashed food (b), swallowing of liquids (c), pain (d), restriction of sense of taste (e) and smell (f), speech problems (g), breathing problems (h), restriction of physical activity (i) and the self-reported current health state (j)

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Source: PubMed

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