Roger A. Zwahlen

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.

Comparison of different registration methods for surgical navigation in cranio-maxillofacial surgery

BACKGROUND Surgical navigation requires registration of the pre-operative image dataset with the patient in the operation theatre. Various marker and marker-free registration techniques are available, each bearing an individual level of precision and clinical practicability. In this study the precision of four different registration methods in a maxillofacial surgical setting is analyzed. MATERIALS AND METHODS A synthetic full size human skull model was registered with its computer tomography-dataset using (a) a dentally mounted occlusal splint, (b) the laser surface scanning, (c) five facial bone implants and (d) a combination of dental splint and two orbital bone implants. The target registration error was computed for 170 landmarks spread over the entire viscero- and neurocranium in 10 repeats using the VectorVision2 (BrainLAB AG, Heimstetten, Germany) navigation system. Statistical and graphical analyses were performed by anatomical region. RESULTS An average precision of 1mm was found for the periorbital region irrespective of registration method (range 0.6-1.1mm). Beyond the mid-face, precision linearly decreases with the distance from the reference markers. The combination of splint with two orbital bone markers significantly improved precision from 1.3 to 0.8mm (p<0.001) on the viscerocranium and 2.3-1.2mm (p<0.001) on the neurocranium. CONCLUSIONS An occlusal splint alone yields poor precision for navigation beyond the mid-face. The precision can be increased by combining an occlusal splint with just two bone implants inserted percutaneously on the lateral orbital rim of each side.

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 and dyadic adjustment in oral cancer patients and their female partners

The diagnosis of cancer affects not only the lives of patients, but also the lives of their family members. The purpose of this study was to examine the impact of oral cancer on quality of life (QoL), psychological distress and marital satisfaction in a sample of patients and their wives. Thirty-one men treated for oral cancer (mean time since diagnosis 3.7 years) and their female partners (n = 31) were assessed by questionnaires with regard to QoL (WHOQOL-BREF), anxiety and depression (Hospital Anxiety and Depression Scale, HADS), quality of relationship (Dyadic Adjustment Scale, DAS) and physical complaints (EORTC QOL-H&N35). Quality of life was remarkably high in patients and their partners. In patients, lower QoL was associated with more physical complaints and higher levels of psychological distress (HADS), whereas in wives, QoL was found to be related to marital quality (DAS) and levels of distress. In couples with highly discrepant ratings of marital satisfaction, wives reported more psychological distress. The findings indicate that overall QoL is considerably high in patients treated for oral cancer and their partners living in stable relationships. Quality of life correlates stronger with the quality of relationship in spouses than in patients. Generally, marital satisfaction appears to be an important moderating factor regarding QoL and psychological distress.

Coping processes relevant to posttraumatic growth: an evidence-based review

ObjectiveThis study aims to perform an evidence-based review on the quantitative data regarding coping processes related to posttraumatic growth in the field of oncology to facilitate understanding of posttraumatic growth in oral cavity cancer (OCC) patients.Material and methodsPubmed, Medline, and PsycINFO were used for the search and the reference list checked for each selected article. Full articles meeting the inclusion criteria were retrieved. Only English articles were included.ResultsThe initial search yielded 934 publications; 64 “potentially relevant papers” and 21 “effective” papers formed the basis of this review. Personality traits and social support lead to development of positive coping methods in cancer patients. Overriding influences are benefit finding and meaning making. Specific coping processes were identified to be significantly associated with posttraumatic growth in patients suffering from different cancers and a need for additional prospective research regarding specific processes and outcomes among oral cavity cancer patients. A proposed theoretical model based on the evidence of management of other cancer research fields is suggested for patients with OCC.ConclusionAn evidence-based review of coping strategies related to posttraumatic growth was performed which identified key coping strategies and factors that enhance coping processes. A conceptual model of coping strategies to enhance posttraumatic growth in OCC patients based on the scientific evidence attained is suggested to provide a more holistic approach to OCC management.

The roles of hope and optimism on posttraumatic growth in oral cavity cancer patients

To investigate the association of the positive coping strategies, hope and optimism, on posttraumatic growth (PTG) in oral cavity (OC) cancer patients. A retrospective cross-sectional study was conducted and performed in the outpatient station of the Oral and Maxillofacial Surgery at the University of Hong Kong, Hong Kong SAR, PR China. Fifty patients successfully treated for OC cancer were recruited after their informed consents had been obtained during the review clinic. During their regular follow-up controls in the outpatient clinic, the patients compiled the posttraumatic growth inventory (PTGI) questionnaire, hope scale (HS) and the life orientation scale-revised (LOT-R). Hope and optimism correlated significantly positive with PTG and accounting together for a 25% variance of posttraumatic growth. Hope positively correlated with posttraumatic growth (r=.49, p<.001) as well as optimism (r=.31, p<.05). When compared to unmarried patients, married patients showed high levels of PTG and hope (married participants: mean=53.15, SD=11.04; unmarried participants: mean=41.00, SD=6.36; t (48)=2.403, p<.05). Hope and optimism represent important indicators for PTG in OC cancer patients. An intact dyad relationship seems to be important for hope and consecutive higher levels of PTG when compared to unmarried patients. Supportive psychological treatment strategies related to these two coping factors might be beneficial for OC cancer patients.

IMRT in oral cavity cancer

BackgroundExcept for early T1,2 N0 stages, the prognosis for patients with oral cavity cancer (OCC) is reported to be worse than for carcinoma in other sites of the head and neck (HNC). The aim of this work was to assess disease outcome in OCC following IMRT.Between January 2002 and January 2007, 346 HNC patients have been treated with curative intensity modulated radiation therapy (IMRT) at the Department of Radiation Oncology, University Hospital Zurich. Fifty eight of these (16%) were referred for postoperative (28) or definitive (30) radiation therapy of OCC.40 of the 58 OCC patients (69%) presented with locally advanced T3/4 or recurred lesions. Doses between 60 and 70 Gy were applied, combined with simultaneous cisplatin based chemotherapy in 78%. Outcome analyses were performed using Kaplan Meier curves.In addition, comparisons were performed between this IMRT OCC cohort and historic in-house cohorts of 33 conventionally irradiated (3DCRT) and 30 surgery only patients treated over the last 10 years.ResultsOCC patients treated with postoperative IMRT showed the highest local control (LC) rate of all assessed treatment sequence subgroups (92% LC at 2 years). Historic postoperative 3DCRT patients and patients treated with surgery alone reached LC rates of ~70–80%. Definitively irradiated patients revealed poorest LC rates with ~30 and 40% following 3DCRT and IMRT, respectively.T1 stage resulted in an expectedly significantly higher LC rate (95%, n = 19, p < 0.05) than T2-4 and recurred stages (LC ~50–60%, n = 102).Analyses according to the diagnosis revealed significantly lower LC in OCC following definitive IMRT than that in pharyngeal tumors treated with definitive IMRT in the same time period (43% vs 82% at 2 years, p < 0.0001), while the LC rate of OCC following postoperative IMRT was as high as in pharyngeal tumors treated with postoperative IMRT (>90% at 2 years).ConclusionPostoperative IMRT of OCC resulted in the highest local control rate of the assessed treatment subgroups. In conclusion, generous indication for IMRT following surgical treatment is recommended in OCC cases with unfavourable features like tight surgical margin, nodal involvement, primary tumor stage >T1N0, or already recurred disease, respectively.Loco-regional outcome of OCC following definitive IMRT remained unsatisfactory, comparable to that following definitive 3DCRT.

Pierre Robin sequence: appearances and 25 years of experience with an innovative treatment protocol

PURPOSE The aim of the study was to evaluate the largest number of Pierre Robin sequence (PRS) cases to date and its treatment outcome. DESIGN This is a retrospective study. SETTINGS The study was conducted in a tertiary care university hospital. PATIENTS One hundred eighty-eight patients with PRS have been subjected to analysis, defined by the clinical triad of glossoptosis, retro/micrognathia, and cleft or agenesis of the palate, for incidence, risk factors, associated syndromes, other concomitant abnormalities, airway and feeding difficulties, and outcome regarding the neonatal and perinatal surgical and nonsurgical management. RESULTS The incidence of PRS was 6.02%. Risk factors were found in 41.5% of mothers with children with PRS. Eleven other syndromes/appearances were associated. Feeding difficulties were seen in 51.8% of the patients. Glossopexy (6.9%) and tracheotomy (2.13%) for airway management were performed very seldom. The suction and drinking plate as well as the surgical treatment protocol may be considered to be the reasons for reduced airway (up to 91.0%), feeding problems (up to 79.9%), and mortality rate (2.1%). CONCLUSION The Pierre Robin sequence, as seen as a heterogeneous group, presents with variation of the cleft palate defects with glossoptosis and concomitant micrognathic mandible. The surgical management and certain prepalatal intervention as nonsurgical management with an innovative treatment strategy were evaluated.

Influence of nicotine on the biological activity of rabbit osteoblasts

OBJECTIVES To assess the influence of nicotine on the proliferation and gene expression of osteogenic and angiogenic mediators of osteoblasts. MATERIAL AND METHODS Rabbit primary osteoblasts were exposed to various concentrations of nicotine (0.001, 0.1 and 10 μmol/l). The cell proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. The gene expression of transforming growth factor (TGF)-β(1), bone morphogenetic protein (BMP)-2, platelet-derived growth factor (PDGF)-AA and vascular endothelial growth factor (VEGF) was evaluated using real-time reverse transcription - polymerase chain reaction. RESULTS The osteoblast proliferation was inhibited by nicotine at the concentration of 0.001-10 μM at 48 and 72 h of culture, but with no significant effect at 24 h. The expression of TGF-β(1), BMP-2, PDGF-AA and VEGF was inhibited by nicotine at the concentrations of 0.1 and 10 μM, but with no significant difference at the low concentration of 0.001 μM. CONCLUSIONS Nicotine suppresses osteoblast proliferation and inhibits the expression of some key osteogenic and angiogenic mediators in the in vitro experimental model. These inhibitory effects of nicotine on the osteoblast activity may reflect, to a certain degree, the overall detrimental effects of tobacco use on the survival rate of dental implants.

Aneurysmal Bone Cysts of the Jaws: Analysis of 17 Cases

PURPOSE Aneurysmal bone cysts (ABCs) are benign osteolytic lesions that occur relatively rarely in the jaws. The aim of the present study was to investigate the clinical and radiographic characteristics, pathologic features, and treatment results of ABCs of the jaws (JABCs). MATERIALS AND METHODS A retrospective analysis of a 20-year database, including 17 cases of JABC, was performed. RESULTS A total of 17 patients, 9 males and 8 females, aged 7 to 47 years (mean 20.4, median 14), were included. Of the 17 lesions, 15 (88.2%) were located in the mandible and 2 (11.8%) in the maxilla. A painless (12 of 17, 70.6%) or painful (3 of 17, 17.6%) swelling was the most common clinical finding. The pathologic analyses revealed that 13 JABCs (76.5%) were secondary in nature, including 11 cases associated with ossifying fibroma. Radiologically, the lesions frequently presented as multilocular (58.8%), well-defined (70.6%) radiolucencies (82.4%). Two lesions (11.8%) recurred. CONCLUSIONS Our results suggest that most JABCs are secondary in nature and frequently associated with ossifying fibroma. The patients with JABCs presented with various clinical and radiographic features and therefore often posed a diagnostic dilemma. Resection is the preferred treatment of JABCs.