Christoph Glanzmann

Concomitant Cisplatin Significantly Improves Locoregional Control in Advanced Head and Neck Cancers Treated With Hyperfractionated Radiotherapy

PURPOSE To determine whether the application of two courses of cisplatin simultaneously with hyperfractionated radiotherapy improves the outcome in locally advanced and/or node-positive nonmetastatic carcinomas of the head and neck, compared with hyperfractionated radiotherapy alone. PATIENTS AND METHODS From July 1994 to July 2000, 224 patients with squamous cell carcinomas of the head and neck (excluding nasopharynx and paranasal sinus) were randomly assigned to hyperfractionated radiotherapy (median dose, 74.4 Gy; 1.2 Gy twice daily) or the same radiotherapy combined with two cycles of concomitant cisplatin (20 mg/m2 on 5 days of weeks 1 and 5). The primary end point was time to any treatment failure; secondary end points were locoregional failure, metastatic relapse, overall survival, and late toxicity. RESULTS There was no difference in radiotherapy between both treatment arms (74.4 Gy in 44 days). The full cisplatin dose was applied in 93% and 71% of patients during the first and second treatment cycles, respectively. Acute toxicity was similar in both arms. Median time to any treatment failure was not significantly different between treatment arms (19 months for combined treatment and 16 months for radiotherapy only, respectively) and the failure-free rate at 2.5 years was 45% and 33%, respectively. Locoregional control and distant disease-free survival were significantly improved with cisplatin (log-rank test, P = .039 and .011, respectively). The difference in overall survival did not reach significance (log-rank test, P = .147). Late toxicity was comparable in both treatment groups. CONCLUSION The therapeutic index of hyperfractionated radiotherapy is improved by concomitant cisplatin.

Cardiac risk after mediastinal irradiation for Hodgkin's disease

PURPOSE To evaluate the risk of cardiac lesions after conventionally fractionated irradiation (Rt) of the mediastine with or without chemotherapy (Ct) in patients with Hodgkins disease (HD) and to relate them to known cardiovascular risk factors. PATIENTS AND METHODS Between 1964 and 1992, 352 (total group) patients with HD were treated with curative intention using Rt with or without Ct including the mediastine and had a follow-up of at least 1 year. More than 96% of the patients had a complete follow-up. One hundred forty-four patients (64% of the living patients, heart study group) have regular follow-up in our department and had a special heart examination including rest and exercise ECG, echocardiography and myocardial perfusion scintigraphy (112 patients). Doses per fraction in the anterior heart region were between 1.3 and 2.1 Gy. Total doses were between 30.0 and 42.0 Gy in 93% of cases. The mean length of follow-up was 11.2 years (range 1.0-31.5 years). Other cardiovascular risk factors evaluated were body mass index, blood pressure, smoking history, diabetes mellitus, hypercholesterolemia and history of coronary artery disease before Rt. RESULTS In the total group, the risk of fatal cardiac ischemic events and/or of sudden unexpected death was significantly higher than expected with a relative risk of 4.2 for myocardial infarction and 6.7 for myocardial infarction or sudden death. In female patients and in patients without other cardiovascular risk factors, the risk of fatal or non-fatal ischemic cardiac events was not significantly different from the expected value. In the subgroup with no cardiovascular risk factors and treatment without Ct, there was no ischemic or other major cardiac event. Echocardiography showed valvular thickenings in a large amount of the patients (the cumulative risk after 30-year follow-up was above 60%) but mostly without hemodynamic disturbance. In patients without hypertension and without coronary artery disease, findings of perfusion scintigraphy and echocardiographic evaluation of systolic and diastolic function were normal. Treatment with Ct was not a significant risk factor for cardiac events but the number of patients whose treatment included adriamycin and with a follow-up exceeding 10 years is to low for a definitive evaluation. CONCLUSIONS In patients without the usual cardiovascular risk factors (smoking, hypertension, obesity, hypercholesterolemia, diabetes mellitus) the risk of serious cardiac lesions after conventionally fractionated irradiation of the mediastinum with an intermediate total dose between 30 and 40 Gy is low. Also the cardiac risk of the combination of this irradiation with Ct including adriamycin with a total dose between 200 and 300 mg/m2 seems low but further long-term observation is necessary.

Effect of VEGF receptor inhibitor PTK787/ZK222548 combined with ionizing radiation on endothelial cells and tumour growth

The vascular endothelial growth factor (VEGF) receptor is a major target for anti-angiogenesis-based cancer treatment. Here we report the treatment effect of ionizing radiation in combination with the novel orally bioavailable VEGF receptor tyrosine kinase inhibitor PTK787/ZK222584 on endothelial cell proliferation in vitro and with tumour xenografts in vivo. Combined treatment of human umbilical vein endothelial cells with increasing doses of PTK787/ZK222584 and ionizing radiation abrogated VEGF-dependent proliferation in a dose-dependent way, but inhibition of endothelial cell proliferation was not due to apoptosis induction. In vivo, a combined treatment regimen of PTK787/ZK222584 (4 × 100 mg/kg) during 4 consecutive days in combination with ionizing radiation (4 × 3 Gy) exerted a substantial tumour growth delay for radiation-resistant p53-disfunctional tumour xenografts derived from SW480 colon adenocarcinoma cells while each treatment modality alone had only a minimal effect on tumour size and neovascularization. SW480 tumours from animals that received a combined treatment regimen, displayed not only an extended tumour growth delay but also a significant decrease in the number of microvessels in the tumour xenograft. These results support the model of a cooperative antitumoural effect of angiogenesis inhibitor and irradiation and show that the orally bioavailable VEGF receptor tyrosine kinase inhibitor PTK787/ZK222584 is suitable for combination therapy with irradiation.

Dysphagia in head and neck cancer patients following intensity modulated radiotherapy (IMRT)

BackgroundTo evaluate the objective and subjective long term swallowing function, and to relate dysphagia to the radiation dose delivered to the critical anatomical structures in head and neck cancer patients treated with intensity modulated radiation therapy (IMRT, +/- chemotherapy), using a midline protection contour (below hyoid, ~level of vertebra 2/3).Methods82 patients with stage III/IV squamous cell carcinoma of the larynx, oropharynx, or hypopharynx, who underwent successful definitive (n = 63, mean dose 68.9Gy) or postoperative (n = 19, mean dose 64.2Gy) simultaneous integrated boost (SIB) -IMRT either alone or in combination with chemotherapy (85%) with curative intent between January 2002 and November 2005, were evaluated retrospectively. 13/63 definitively irradiated patients (21%) presented with a total gross tumor volume (tGTV) >70cc (82-173cc; mean 106cc). In all patients, a laryngo-pharyngeal midline sparing contour outside of the PTV was drawn. Dysphagia was graded according subjective patient-reported and objective observer-assessed instruments. All patients were re-assessed 12 months later. Dose distribution to the swallowing structures was calculated.ResultsAt the re-assessment, 32-month mean post treatment follow-up (range 16-60), grade 3/4 objective toxicity was assessed in 10%. At the 32-month evaluation as well as at the last follow up assessment mean 50 months (16-85) post-treatment, persisting swallowing dysfunction grade 3 was subjectively and objectively observed in 1 patient (1%). The 5-year local control rate of the cohort was 75%; no medial marginal failures were observed.ConclusionsOur results show that sparing the swallowing structures by IMRT seems effective and relatively safe in terms of avoidance of persistent grade 3/4 late dysphagia and local disease control.

Osteoradionecrosis of the mandible: Minimized risk profile following intensity-modulated radiation therapy (IMRT)

Background and Purpose:Osteoradionecrosis (ON) of the mandible is a serious late complication of high-dose radiation therapy for tumors of the oropharynx and oral cavity. After doses between 60 and 72 Gy using standard fractionation, an incidence of ON between 5% and 15% is reported in a review from 1989, whereas in more recent publications using moderately accelerated or hyperfractionated irradiation and doses between 69 and 81 Gy, the incidence of ON is between < 1% and ~ 6%. Intensity-modulated radiation therapy (IMRT) is expected to translate into a further important reduction of ON. The aim of this descriptive study was to assess absolute and relative bone volumes exposed to high IMRT doses, related to observed bone tolerance.Patients and Methods:Between December 2001 and November 2004, 73 of 123 patients treated with IMRT were identified as subgroup “at risk” for ON (> 60 Gy for oropharyngeal or oral cavity cancer). 21/73 patients were treated in a postoperative setting, 52 patients underwent primary definitive irradiation. In 56 patients concomitant cisplatin-based chemotherapy was applied. Mean follow-up time was 22 months (12–46 months). Oral cavity including the mandible bone outside the planning target volume was contoured and dose-volume constraints were defined in order to spare bone tissue. Dose-volume histograms were obtained from contoured mandible in each patient and were analyzed and related to clinical mandible bone tolerance.Results:Using IMRT with doses between 60 and 75 Gy (mean 67 Gy), on average 7.8, 4.8, 0.9, and 0.3 cm3 were exposed to doses > 60, 65, 70, and 75 Gy, respectively. These values are substantially lower than when using three-dimensional conformal radiotherapy. The difference has been approximately quantified by comparison with a historic series. Additional ON risk factors of the patients were also analyzed. Only one grade 3 ON of the lingual horizontal branch, treated with lingual decortication, was observed.Conclusion:Using IMRT, only very small partial volumes of the mandibular bone are exposed to high radiation doses. This is expected to translate into a further reduction of ON and improved osseointegration of dental implants.Hintergrund und Ziel:Die Osteoradionekrose (ON) des Unterkiefers ist eine schwerwiegende Komplikation kurativer normofraktionierter Radiotherapie von Oropharynx- und Mundhöhlenkarzinomen. Nach Dosen zwischen 60 und 72 Gy besteht gemäß den Angaben einer Übersicht aus dem Jahr 1989 eine ON-Inzidenz von 5–15%, während laut neueren Arbeiten über leicht akzelerierte oder hyperfraktionierte Behandlungsschemata mit Dosen von 69–81 Gy die ON-Inzidenz zwischen < 1% und ca. 6% beträgt. Intensitätsmodulierte Radiotherapie (IMRT) dürfte die ON-Rate weiter reduzieren. Ziel dieser deskriptiven Arbeit war, absolute und relative Knochenvolumina mit hoher Dosisexposition zu evaluieren und in Beziehung zur beobachteten Knochentoleranz der eigenen Patienten nach IMRT-Behandlung zu setzen.Patienten und Methodik:Zwischen Dezember 2001 und November 2004 wurden an der eigenen Klinik 123 Patienten mit Tumoren der Kopf-Hals-Region mit IMRT behandelt; hiervon waren 73 einer Untergruppe von Patienten mit Risiko für ON zuzurechnen (Karzinome des Oropharynx oder der Mundhöhle und Herddosen > 60 Gy). 21 Patienten wurden postoperativ, 52 primär kurativ bestrahlt; 56 erhielten eine simultane cisplatinbasierte Chemotherapie. Die mittlere Beobachtungszeit betrug 22 Monate (12–46 Monate). Die Mundhöhle inkl. Kieferknochen außerhalb des Planungszielvolumens wurde konturiert, und Dosis-Volumen-Bedingungen zur Organschonung wurden festgelegt. Retrospektiv wurde für jeden Patienten das gesamte Kieferknochenvolumen konturiert, und die Dosis-Volumen-Histogramme wurden im Hinblick auf die klinische Knochentoleranz ausgewertet.Ergebnisse:Durch IMRT in Dosen zwischen 60 und 75 Gy (Mittelwert 67 Gy) wurden im Mittel 7,8, 4,8, 0,9 und 0,3 cm3 einer Dosis von > 60, 65, 70 und 75 Gy ausgesetzt (Tabelle 1 und Abbildung 1). Diese Werte sind deutlich kleiner als nach konventioneller Bestrahlung. Der Unterschied wurde im Vergleich mit einer historischen Serie näherungsweise quantifiziert (Abbildung 3). Zusätzliche Risikofaktoren der eigenen Patienten wurden analysiert (Abbildung 2). Nur ein ON-Ereignis (Grad 3) im Bereich des lingualen Horizontalasts der Mandibula wurde beobachtet und erfolgreich mit einer lingualen Dekortikation behandelt.Schlussfolgerung:Mittels IMRT werden nur sehr kleine Knochenvolumina hohen Bestrahlungsdosen ausgesetzt. Durch diese Knochenschonung werden eine weitere Reduktion des ON-Risikos und eine höhere Erfolgsrate rekonstruktiver Zahnimplantate (Tabelle 2) erwartet.

Osteoradionecrosis of the Mandible

Background and Purpose:Osteoradionecrosis (ON) of the mandible is a serious late complication of high-dose radiation therapy for tumors of the oropharynx and oral cavity. After doses between 60 and 72 Gy using standard fractionation, an incidence of ON between 5% and 15% is reported in a review from 1989, whereas in more recent publications using moderately accelerated or hyperfractionated irradiation and doses between 69 and 81 Gy, the incidence of ON is between < 1% and ~ 6%. Intensity-modulated radiation therapy (IMRT) is expected to translate into a further important reduction of ON. The aim of this descriptive study was to assess absolute and relative bone volumes exposed to high IMRT doses, related to observed bone tolerance.Patients and Methods:Between December 2001 and November 2004, 73 of 123 patients treated with IMRT were identified as subgroup “at risk” for ON (> 60 Gy for oropharyngeal or oral cavity cancer). 21/73 patients were treated in a postoperative setting, 52 patients underwent primary definitive irradiation. In 56 patients concomitant cisplatin-based chemotherapy was applied. Mean follow-up time was 22 months (12–46 months). Oral cavity including the mandible bone outside the planning target volume was contoured and dose-volume constraints were defined in order to spare bone tissue. Dose-volume histograms were obtained from contoured mandible in each patient and were analyzed and related to clinical mandible bone tolerance.Results:Using IMRT with doses between 60 and 75 Gy (mean 67 Gy), on average 7.8, 4.8, 0.9, and 0.3 cm3 were exposed to doses > 60, 65, 70, and 75 Gy, respectively. These values are substantially lower than when using three-dimensional conformal radiotherapy. The difference has been approximately quantified by comparison with a historic series. Additional ON risk factors of the patients were also analyzed. Only one grade 3 ON of the lingual horizontal branch, treated with lingual decortication, was observed.Conclusion:Using IMRT, only very small partial volumes of the mandibular bone are exposed to high radiation doses. This is expected to translate into a further reduction of ON and improved osseointegration of dental implants.Hintergrund und Ziel:Die Osteoradionekrose (ON) des Unterkiefers ist eine schwerwiegende Komplikation kurativer normofraktionierter Radiotherapie von Oropharynx- und Mundhöhlenkarzinomen. Nach Dosen zwischen 60 und 72 Gy besteht gemäß den Angaben einer Übersicht aus dem Jahr 1989 eine ON-Inzidenz von 5–15%, während laut neueren Arbeiten über leicht akzelerierte oder hyperfraktionierte Behandlungsschemata mit Dosen von 69–81 Gy die ON-Inzidenz zwischen < 1% und ca. 6% beträgt. Intensitätsmodulierte Radiotherapie (IMRT) dürfte die ON-Rate weiter reduzieren. Ziel dieser deskriptiven Arbeit war, absolute und relative Knochenvolumina mit hoher Dosisexposition zu evaluieren und in Beziehung zur beobachteten Knochentoleranz der eigenen Patienten nach IMRT-Behandlung zu setzen.Patienten und Methodik:Zwischen Dezember 2001 und November 2004 wurden an der eigenen Klinik 123 Patienten mit Tumoren der Kopf-Hals-Region mit IMRT behandelt; hiervon waren 73 einer Untergruppe von Patienten mit Risiko für ON zuzurechnen (Karzinome des Oropharynx oder der Mundhöhle und Herddosen > 60 Gy). 21 Patienten wurden postoperativ, 52 primär kurativ bestrahlt; 56 erhielten eine simultane cisplatinbasierte Chemotherapie. Die mittlere Beobachtungszeit betrug 22 Monate (12–46 Monate). Die Mundhöhle inkl. Kieferknochen außerhalb des Planungszielvolumens wurde konturiert, und Dosis-Volumen-Bedingungen zur Organschonung wurden festgelegt. Retrospektiv wurde für jeden Patienten das gesamte Kieferknochenvolumen konturiert, und die Dosis-Volumen-Histogramme wurden im Hinblick auf die klinische Knochentoleranz ausgewertet.Ergebnisse:Durch IMRT in Dosen zwischen 60 und 75 Gy (Mittelwert 67 Gy) wurden im Mittel 7,8, 4,8, 0,9 und 0,3 cm3 einer Dosis von > 60, 65, 70 und 75 Gy ausgesetzt (Tabelle 1 und Abbildung 1). Diese Werte sind deutlich kleiner als nach konventioneller Bestrahlung. Der Unterschied wurde im Vergleich mit einer historischen Serie näherungsweise quantifiziert (Abbildung 3). Zusätzliche Risikofaktoren der eigenen Patienten wurden analysiert (Abbildung 2). Nur ein ON-Ereignis (Grad 3) im Bereich des lingualen Horizontalasts der Mandibula wurde beobachtet und erfolgreich mit einer lingualen Dekortikation behandelt.Schlussfolgerung:Mittels IMRT werden nur sehr kleine Knochenvolumina hohen Bestrahlungsdosen ausgesetzt. Durch diese Knochenschonung werden eine weitere Reduktion des ON-Risikos und eine höhere Erfolgsrate rekonstruktiver Zahnimplantate (Tabelle 2) erwartet.

Quality of life in patients cured from a carcinoma of the head and neck by radiotherapy : The importance of the target volume

PURPOSE To assess the health-related quality of life (QOL) of long-term survivors of carcinomas of different subsites of the head and neck following curative radiotherapy (RT). PATIENTS AND METHODS Patients continuously free from recurrence or second primary tumors treated 1988-1994 were contacted 5.1 to 5.9 years after RT and asked to fill in the EORTC QLQ-C30 core questionnaire and the H&N cancer module. RT had been restricted to the glottis (group A; carcinomas of the vocal cord T1-2 N0), or had included bilateral neck nodes and the primary tumor outside the nasopharynx (group B; AJC Stage II to IV) or within the nasopharynx, respectively (group C; Stage II to IV). Response rate was 97% (group A; n = 41), 69% (group B; n = 26) and 71% (group C; n = 12), respectively. The groups were different with respect to age (older in group A), alcohol consumption (absent in group C) and proportion of females (more in group C). RESULTS Patients with nasopharyngeal cancer reported the highest morbidity on the H&N module (dry mouth, sticky saliva, trismus, problems with teeth, trouble eating). However, these symptoms did not have a high impact on global QOL or function scores on the QLQ-C30 core questionnaire. Patients in group B reported a lower global QOL but less severe symptoms on the module. CONCLUSION The high morbidity of patients treated for a nasopharyngeal cancer may be explained by the location of the target volume which included the bilateral temporo-mandibular joints and the salivary glands. These patients require appropriate care during follow-up and will probably profit most from new RT techniques with sparing of normal tissues.

Osteoradionecrosis of the Mandibula in Patients Treated with Different Fractionations

Purpose:The incidence of osteonecrosis of the mandibula (ON) after irradiation using modern three-dimensional planning as well as hyperfractionation or moderately accelerated irradiation has been evaluated and compared with the incidence of the preceding period.Patients and Methods:The records of 268 head and neck cancer patients irradiated between January 1, 1980 and December 31, 1998 with a dose to the mandibula of at least 60 Gy were retrospectively analyzed. All patients had CT-based treatment planning, computerized dose calculation with isodose charts also in several off-axis planes, and regular verification films.Results:The long-term cumulative incidence of ON needing mandibular resection was as follows: after conventional fractionation 6.2% (between 60 and 66.6 Gy target dose) or 20.1% (between > 66.6 and 72 Gy); after hyperfractionated irradiation with a target dose between 72 and 78.8 Gy 6.6%; after concomitant boost irradiation according to the MDA/Houston regime with a dose between 63.9 and 70.5 Gy: no case; after 6 × 2 Gy/week or 7 × 1.8 Gy/week and a total target dose between 66 and 72 Gy approximately 17% or higher (small patient number).Conclusion:Comparison of the incidence of ON during the period between 1980 and 1990 with the following period between 1990 and 1998 shows a decrease in risk to a value of approximately 5% using modern three-dimensional techniques as well as hyperfractionation or moderately accelerated fractionation.Ziel:Die Inzidenz von Osteonekrosen (ON) der Mandibula nach Radiotherapie im Bereich von Mundhöhle und Pharynx nach Anwendung moderner dreidimensionaler Bestrahlungsplanung und veränderten Fraktionierungen wurde ermittelt und mit den Erfahrungen der unmittelbar vorausgegangenen Periode verglichen.Patienten und Methodik:Es handelt sich um eine retrospektive Analyse der Inzidenz von Mandibulanekrosen bei 268 Patienten mit Karzinomen der Mundhöhle oder des Pharynx, die zwischen dem 01.01.1980 und dem 31.12.1998 im Rahmen einer primären oder postoperativen Radiotherapie eine Dosis von mindestens 60 Gy auf die Mandibula erhalten hatten (Tabelle 1). Alle Patienten erhielten eine CT-unterstützte computerisierte Bestrahlungsplanung mit Isodosenkarten auch in mehreren Ebenen außerhalb des Zentralstrahls und regelmäßigen Feldkontrollaufnahmen.Ergebnisse:Die kumulative Inzidenz einer mit Mandibularesektion behandelten ON nach Bestrahlung betrug nach konventioneller Fraktionierung (Abbildung 1a) 6,2% (60–66,6 Gy) bzw. 20,1% (> 66,6–72 Gy), nach hyperfraktionierter Bestrahlung (Abbildung 1c) mit 72–78,8 Gy 6,6%; nach akzelerierter Bestrahlung (Abbildung 1b) gemäß dem Schema des MDA-Hospitals in Houston, TX, USA, mit einer Dosis von 63,9–70,5 Gy wurde keine ON beobachtet, während nach 6 × 2 Gy/Woche bzw. 7 × 1,8 Gy pro Woche und einer Gesamtdosis zwischen 66 und 72 Gy etwa 17% ON beobachtet wurden.Schlussfolgerung:Ein Vergleich der Inzidenz von ON der Mandibula nach Anwendung moderner dreidimensionaler Bestrahlungsplanung und hyperfraktionierter oder mäßig akzelerierter Bestrahlung mit gleichzeitigem Boost nach dem Schema des MDA-Hospitals zeigt gegenüber der Inzidenz in der vorausgegangenen Periode zwischen 1980 und etwa 1987 einen Rückgang auf Werte von etwa 5% (Tabelle 2).

IMRT using simultaneously integrated boost (SIB) in head and neck cancer patients

BackgroundPreliminary very encouraging clinical results of intensity modulated radiation therapy (IMRT) in Head Neck Cancer (HNC) are available from several large centers. Tumor control rates seem to be kept at least at the level of conventional three-dimensional radiation therapy; the benefit of normal tissue preservation with IMRT is proven for salivary function. There is still only limited experience with IMRT using simultaneously integrated boost (SIB-IMRT) in the head and neck region in terms of normal tissue response.The aim of this work was (1) to establish tumor response in HNC patients treated with SIB-IMRT, and (2) to assess tissue tolerance following different SIB-IMRT schedules.ResultsBetween 1/2002 and 12/2004, 115 HNC patients have been curatively treated with IMRT. 70% received definitive IMRT (dIMRT), 30% were postoperatively irradiated. In 78% concomitant chemotherapy was given.SIB radiation schedules with 5–6 × 2 Gy/week to 60–70 Gy, 5 × 2.2 Gy/week to 66–68.2 Gy (according to the RTOG protocol H-0022), or 5 × 2.11 Gy/week to 69.6 Gy were used.After mean 18 months (10–44), 77% of patients were alive with no disease. Actuarial 2-year local, nodal, and distant disease free survival was 77%, 87%, and 78%, respectively. 10% were alive with disease, 10% died of disease. 20/21 locoregional failures occurred inside the high dose area. Mean tumor volume was significantly larger in locally failed (63 cc) vs controlled tumors (32 cc, p <0.01), and in definitive (43 cc) vs postoperative IMRT (25 cc, p <0.05); the locoregional failure rate was twofold higher in definitively irradiated patients.Acute reactions were mild to moderate and limited to the boost area, the persisting grade 3/4 late toxicity rate was low with 6%. The two grade 4 reactions (dysphagia, laryngeal fibrosis) were observed following the SIB schedule with 2.2 Gy per session.ConclusionSIB-IMRT in HNC using 2.0, 2.11 or 2.2 Gy per session is highly effective and safe with respect to tumor response and tolerance. SIB with 2.2 Gy is not recommended for large tumors involving laryngeal structures.

Locoregional Failure Analysis in Head-and-Neck Cancer Patients Treated with IMRT

Purpose:Purpose: Analysis of locoregional failure in head-and-neck cancer (HNC) following intensity-modulated radiation therapy (IMRT), with focus on the location of locoregional failures in relation to the chosen planning target volumes (PTVs) and dose distributions.Patients and Methods:Between January 2002 and May 2006, 280 HNC patients were subjected to IMRT at the authors’ institution. Mean follow-up was 23.2 months (3–59.3 months). Definitive IMRT was performed in 75% of all patients. In 71%, simultaneous cisplatin-based chemotherapy was given. 70% of patients presented with T3/4, T1–2 N2c/3 or recurred disease. Locoregional failure patterns were analyzed.Results:2-year local, nodal, distant, disease-free, and overall survival rates were 80%, 87%, 87%, 73%, and 82%, respectively. 46 local (16%) and 31 nodal (11%) failures have been observed so far. Local tumor persistence was seen in 23/46 cases (50%), and nodal persistence in 12/31 (39%), respectively. One marginal local failure developed in a patient referred for a recurred oral cavity tumor. Three nodal failures developed outside the PTVs at unexpected locations. All other failures have been confirmed “in field”. No failure occurred in level Ib or upper level II. Local failure occurred mainly following definitive IMRT for large tumors, nodal failure only in nodally positive patients with nodal high-risk features.Conclusion:The dose-volume concept as used here has shown to be adequate, with disease failure developing at the site of the initial gross tumor manifestation inside the boost volume.Ziel:Analyse des lokoregionalen Tumorversagens nach intensitätsmodulierter Radiotherapie (IMRT), mit Fokus auf den Ort des Versagens in Bezug auf die konturierten Volumina bzw. die Dosisverteilung.Patienten und Methodik:Zwischen Januar 2002 und Mai 2006 wurden an der eigenen radioonkologischen Klinik 280 Patienten mit Kopf-Hals-Tumoren einer IMRT unterzogen. Die mittlere Beobachtungszeit beläuft sich auf 23,2 Monate (3–59,3 Monate). Bei 75% der Patienten wurde eine definitive IMRT durchgeführt. 71% der Patienten erhielten eine simultane Chemotherapie mit Cisplatin. 70% wurden mit fortgeschrittenen Stadien T3/4, T1–2 N2c/3 oder einem Rezidiv zugewiesen (Tabelle 2). Das lokoregionale Ereignismuster wurde analysiert.Ergebnisse:Die Lokal-, Nodal- und Fernkontrollraten nach 2 Jahren beliefen sich auf 80%, 87% und 87%, die krankheitsfreie bzw. Gesamtüberlebensrate betrug 73% und 82% (Tabelle 4). 46 Fälle (16%) lokalen und 31 (11%) nodalen Versagens wurden bislang festgestellt, die in 23/46 Fällen (50%) einer lokalen und in 12/31 Fällen (39%) einer nodalen Tumorpersistenz entsprachen. Nur ein Patient mit einem bereits rezidivierten Mundhöhlentumor entwickelte ein Feldrandrezidiv (Tabelle 1). Dreimal fand sich ein nodales Versagen außerhalb der Planungszielvolumina an unerwarteten Lokalisationen. Alle anderen Fälle von Versagen konnten als „im Feld“ befindlich bestätigt werden. Kein Versagen wurde im Lymphknotenlevel I oder kranial im Level II gefunden (Tabellen 5 und 6). Lokales Versagen erfolgte hauptsächlich bei primär bestrahlten Patienten mit großem Tumorvolumen (Abbildungen 1 und 2a); nodales Versagen fand sich ausschließlich bei initial nodal positiven Patienten mit nodalen Risikofaktoren (Tabelle 3, Abbildung 2b).Schlussfolgerung:Das hier verwendete Dosis-Volumen-Konzept erwies sich als adäquat, da der Großteil der Rückfälle am Ort der initialen Tumormanifestation, innerhalb des Boostvolumens, auftrat.