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High-Grade Acute Organ Toxicity as Positive Prognostic Factor in Primary Radio(chemo)therapy for Locally Advanced, Inoperable Head and Neck Cancer

Höhergradige Akuttoxizität als positiver prognostischer Faktor bei der primären Radio(chemo)therapie lokal fortgeschrittener, inoperabler Kopf-Hals-Tumoren

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To test for a possible correlation between high-grade acute organ toxicity during primary radio(chemo)therapy and treatment outcome in patients with locally advanced head and neck squamous cell carcinoma (HNSCC).

Patients and Methods:

From 05/1994 to 01/2009, 216 HNSCC patients were treated with radio(chemo)therapy in primary approach. They received normofractionated (2 Gy/fraction) irradiation including associated nodal drainage sites to a cumulative dose of 70 Gy. 151 patients received additional concomitant chemotherapy (111 patients 5-fluorouracil/mitomycin C, 40 patients cisplatin-based). Toxicity during treatment was monitored weekly according to the Common Toxicity Criteria (CTC), and any toxicity grade CTC ≥ 3 of mucositis, dysphagia or skin reaction was assessed as high-grade acute organ toxicity for later analysis.


A statistically significant coherency between high-grade acute organ toxicity and overall survival as well as locoregional control was found: patients with CTC ≥ 3 acute organ toxicity had a 5-year overall survival rate of 44% compared to 8% in patients without (p < 0.01). Thereby, multivariate analyses revealed that the correlation was independent of other possible prognostic factors or factors that may influence treatment toxicity, especially concomitant chemotherapy and radiotherapy technique or treatment-planning procedure.


These data indicate that normal tissue and tumor tissue may behave similarly with respect to treatment response, as high-grade acute organ toxicity during radio(chemo)therapy showed to be an independent prognostic marker in the own patient population. However, the authors are aware of the fact that a multivariate analysis in a retrospective study generally has statistical limitations. Therefore, their hypothesis should be further analyzed on biomolecular and clinical levels and other tumor entities in prospective trials.


Hintergrund und Ziel:

Nach primärer Radio(chemo)therapie lokal fortgeschrittener Kopf-Hals-Tumoren kommt es bei einigen Patienten zu einer kompletten Remission, bei anderen lediglich zu einer partiellen Remission mit frühem Rezidiv. Unterschiedlich ist auch die Strahlenempfindlichkeit des Normalgewebes: Einige Patienten zeigen starke, andere hingegen weniger intensive Akutreaktionen. Im Rahmen dieser Arbeit wurde geprüft, ob Patienten, die höhergradige Akutreaktionen entwickeln, im Vergleich zu Patienten, bei denen diese nicht auftreten, eine bessere Prognose haben.

Patienten und Methodik:

Von 1994 bis 2009 wurden 216 Patienten mit lokal fortgeschrittenen Plattenepithelkarzinomen im Kopf-Hals-Bereich in der eigenen Klinik primär radiotherapiert (70 Gy). 151 Patienten erhielten begleitend eine Chemotherapie (111 Patienten 5-Fluorouracil/Mitomycin C, 40 Patienten Cisplatin-basiert). Jede Akuttoxizität ≥ Grad 3 in Form von Hautreaktion, Mukositis oder Dysphagie wurde als höhergradige akute Organtoxizität gewertet. Akuttoxizität ≥ Grad 3 wurde vor Beginn der Analyse als „cutoff value“ gewählt, da es ab dieser Toxizität zu einer signifikanten Einschränkung der Lebensqualität der Patienten kommt.


Das Gesamtüberleben sowie die lokoregionäre Kontrolle nach 5 Jahren betrugen 18% bzw. 63%. Es fand sich dabei eine statistisch signifikante Korrelation zwischen höhergradiger akuter Organtoxizität und der Prognose: In der Gruppe der Patienten mit höhergradiger akuter Organtoxizität betrugen das Gesamtüberleben und die lokale Kontrolle nach 5 Jahren 44% und 74% im Vergleich zu 8% und 56% bei den Patienten ohne akute höhergradige Nebenwirkungen (p < 0,01, p = 0,04). Diese Korrelation war in multivariater Analyse statistisch unabhängig von anderen Faktoren, die möglicherweise die Toxizität beeinflussen, wie begleitende Chemotherapie oder Strahlentherapieplanung (konventionell/dreidimensional).


Höhergradige akute Organtoxizität ist im untersuchten Kollektiv ein unabhängiger positiver prognostischer Faktor. Der Zusammenhang zwischen höhergradiger akuter Organtoxizität unter Radio(chemo)therapie und der Prognose sollte in prospektiven Studien weiter evaluiert werden.

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Correspondence to Hans Christiansen.

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Both authors share senior authorship.

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Wolff, H.A., Bosch, J., Jung, K. et al. High-Grade Acute Organ Toxicity as Positive Prognostic Factor in Primary Radio(chemo)therapy for Locally Advanced, Inoperable Head and Neck Cancer. Strahlenther Onkol 186, 262–268 (2010).

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