Ralph M.W. Roedel

High-grade acute organ toxicity as positive prognostic factor in primary radio(chemo)therapy for locally advanced, inoperable head and neck cancer.

Purpose: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.Results: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.Conclusion: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.ZusammenfassungHintergrund 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.Ergebnisse: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).Schlussfolgerung: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.

Transoral laser microsurgery for recurrence after primary radiotherapy of early glottic cancer

OBJECTIVE To analyze oncological results of transoral laser microsurgery (TLM) on recurrent early glottic cancer after primary radiotherapy. METHODS The records of 53 patients treated by TLM for early (rTis-rT2) and advanced (rT3, rT4) recurrence after curative radiotherapy were retrospectively analyzed. Data on loco-regional control, overall survival, and disease specific survival were calculated by the Kaplan-Meier method. The larynx preservation rates were given absolutely. RESULTS Mean post-therapeutic follow-up time after TLM for patients alive was 87.9 months. Twenty-two patients (42%) were cured by the first TLM procedure, but one of them underwent total laryngectomy after TLM due to chondronecrosis without evidence of residual tumor. Thirty-one patients (58%) developed another recurrence after TLM. Ten of them were cured by further laser procedures alone. Therefore, in 31 patients (58%), local recurrences were successfully treated by TLM alone. In 20 patients, recurrences could not be controlled by TLM: 14 patients underwent salvage laryngectomy and six palliative treatment. Three- and five-year loco-regional control rates for all patients were 46.1 and 38.8%. Three- and five-year overall survival rates were 67.5 and 53.3%. The corresponding 3- and 5-year disease specific survival rates were 68.6%, each. There was no statistically significant difference in loco-regional control or survival between patients presenting initially with early and advanced recurrence. Further recurrence after the first TLM procedure was associated with a statistically significant decrease in 3- and 5-year overall (56.6% vs. 81.8% and 40.2% vs. 70.5%; p=0.03) and disease specific (48.9% vs. 100%, each; p=0.001) survival. Ultimate local control rate including repeated TLM and salvage laryngectomy was 77.4%. CONCLUSIONS Many patients with recurrent glottic carcinoma after primary radiotherapy can be cured by single or repeated TLM as an organ-preserving procedure. However, in case of failure after TLM for the first recurrence, salvage laryngectomy should be considered early as local control by further laser surgery is unfavorable.

Repeated transoral laser microsurgery for early and advanced recurrence of early glottic cancer after primary laser resection

OBJECTIVES To analyze the oncological results of repeated transoral laser microresection (TLM) in case of failure after primary laser resection of early glottic cancer (pTis-pT2). METHODS Fifty-six patients with local or loco-regional recurrence of early glottic cancer were treated between 1988 and 2005 by repeated TLM followed, if necessary, by neck dissection and/or adjuvant radio- or radiochemotherapy. Data on overall survival, disease-specific survival, and loco-regional control rates were analyzed retrospectively and calculated by the Kaplan-Meier method. RESULTS Forty-four patients (78.6%) presented with early local recurrence (rTis-rT2N0; Stage I/II) and 12 patients (21.4%) had advanced local or loco-regional recurrence (pT3 and pT4N0/N+; Stage III/IV). Three- and five-year overall survival rates for patients with early and advanced recurrence were 75.1% vs. 51.6% and 61.6% vs. 25.8%, respectively. The corresponding three- and five-year disease-specific survival rates were 87.2% vs. 85.7% and 81.0% vs. 85.7%, respectively. Three- and five-year loco-regional control was significantly higher for patients treated for early recurrence (67.6% vs. 27.5% and 63.6% vs. 27.5%, respectively; p=0.02). Salvage laryngectomy rates for patients with early and advanced recurrence were 9.1 and 25.0%, respectively. In patients with early local recurrence, anterior commissure involvement (n=11) did not affect the oncological results. CONCLUSIONS In case of early local recurrence after primary TLM of early glottic cancer, further TLM seems to be justified as an organ-preserving treatment option. In contrast, salvage laryngectomy should be considered early for patients with advanced local or loco-regional recurrence.

Cortical Representation of the Orbicularis Oculi Muscle as Assessed by Transcranial Magnetic Stimulation (TMS)

Objectives To analyze characteristic features and details on motor‐evoked potentials (MEPs) of the orbicularis oculi muscle resulting from cortical transcranial magnetic stimulation (TMS) in normal subjects as a basis for further investigations on motorcortical representation in patients presenting with facial nerve diseases.

Transoral Laser Microsurgery for Carcinoma in situ of the Glottic Larynx

Background: To investigate long-term results of transoral CO2 laser microresection (TLM) in glottic carcinoma in situ (CIS). Methods: A retrospective study of 34 patients with glottic CIS treated initially with TLM between 1986 and 2004. Median post-operative follow-up time was 62 months. Results: Three- and 5-year local control rates were 97 and 93%, respectively. Four patients developed local recurrence (rTis, rTis, rT1, rT4) that could be salvaged by repeated TLM in all cases. Neither adjuvant radiotherapy nor open partial or total laryngectomy was performed. There was no tumour-related death in this series. Conclusion: TLM can be considered as an effective method in the treatment of glottic CIS not only for the primary therapy, but also in cases of local recurrence.