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Studer Gabriela1                         Risk-adapted dental care
       Glanzmann Christoph1
       Studer Stephan P2
       Grätz Klaus W2
                                                prior to intensity-modulated
       Bredell Marius2
       Locher Michael3                          radiotherapy (IMRT)
       Lütolf Urs M1
       Zwahlen Roger A2                         Results
       1
         Clinic for Radiation Oncology,
         University Hospital, Zurich
       2
         Clinic for Oral and Maxillofacial      Key words: dental care before radiotherapy, osteoradionecrosis
         Surgery, University Hospital, Zurich
       3
         Clinic of Dentistry, Oral Medicine
         and Gnathic Surgery, Clinic for Oral
         Surgery, Center of Dental and Oral
         Medicine, University of Zurich         Summary     Background: At the Clinic for Materials and Methods: In August 2006, RaDC
                                                Radiation Oncology at the Zurich University was clinically implemented and has been
       Corresponding author
       PD Dr. med. Gabriela Studer, LA          Hospital (UniversitätsSpital Zürich [USZ]), used for all HNT patients prior to IMRT since
       RadioOnkologie AN 16                     head-and-neck tumor (HNT) patients have then. Before that (01/2002–07/2006), dental
       UniversitätsSpital Zürich                been treated with intensity-modulated radio- restorations were performed according to the
       Rämistrassse 100
                                                therapy (IMRT) since 01/2002 (n > 800). This usual procedure.
       8091 Zürich
       E-mail: gabriela.studer@usz.ch           method causes less damage to normal tissues Results: The rate of grade-2 ORN was similar
       Tel. 044 255 29 31                       adjacent to the tumor, and thus it was possible in the conventionally treated and RaDC groups
       Fax 044 255 45 47                        in the head/neck region to markedly reduce (2% and 1%, resp.); grade-3 ORN had not
       Schweiz Monatsschr Zahnmed 121:          the rate of osteoradionecrosis (ORN), in addi- occurred by the time the analysis was con-
       216–222 (2011)
                                                tion to reducing the rate of severe xerostomia. ducted. As expected, fewer extractions were
       Accepted for publication:
       18 August 2010                           Based on these results, risk-adapted dental performed in the RaDC cohort (no extractions
                                                care (RaDC) was adopted by our clinic as the in 47% of the RaDC/IMRT cohort vs. 27% in
                                                standard mode of pre-IMRT dental treatment. the IMRT cohort receiving conventional dental
                                                The guidelines as formulated by Grötz et al. care).
                                                were respected.                                 Conclusion: After considerably less invasive
                                                ORN prophylaxis is one of the most important dental treatment, no higher-grade ORN oc-
                                                goals of pre-radiotherapy dental care, and the curred and no ORN-related jaw resections
                                                ORN rate is a measurable parameter for the were required. Based on the present data,
                                                efficacy of dental care, given a certain radia- risk-adapted minimally invasive dental care is
                                                tion technique. The aim of the present study recommended before IMRT.
                                                was therefore to evaluate the efficacy of RaDC
                                                as reflected by the ORN rate of our IMRT pa-
                                                tients.




       Introduction                                                            2010). The greatest clinical advantage of this relatively new
                                                                               technique is that it causes substantially less damage to normal
       In keeping with international guidelines (Grötz 2003; Shaw              tissues while providing equally good or improved tumor con-
       et al. 2000), all head-and-neck tumor (HNT) patients at our             trol rates (Lee et al. 2002; Eisbruch et al. 2003; Eisbruch et
       clinic since more than two decades have undergone standard-             al. 2004; Chao et al. 2004; De Arruda et al. 2006; Puri et al.
       ized focal evaluation and dental treatment prior to all radiation       2005; Studer et al. 2006a–c, Studer et al. 2007c/d).
       therapy.                                                                   Details of the IMRT technique were explained in an earlier
          Since 01/2002, our HNT patients have been treated with in-           publication (Studer et al. 2007a, Tab. I and Fig. 1). Even in
       tensity-modulated radiotherapy (IMRT) (n > 800, status: March,          the first years after implementation of IMRT a diminishment

216   Schweiz Monatsschr Zahnmed Vol. 121          3/2011
Tab. I (corresponds to Fig. 1) Schematic overview of dental treatment for patients with head-and-neck tumors before/during/after IMRT at the University Hospital Zurich (USZ)

                                                               Before IMRT                                                          During IMRT                                                      After IMRT

                             HR       Dental treatment as with conventional radiotherapy (RT)         – Weekly recall (Bornstein et al. 2001)                          – Continue recall for the first year (every 6–8 weeks [Bornstein
                                      – Dental hygiene                                                – Dental hygiene, motivation, monitoring                           et al. 2001])
                                      – Treatment of periodontal pockets                              – Tooth extraction:                                              – Dental hygiene, motivation, monitoring
                                      – Tooth extraction:                                               – after consultation with radiotherapist                       – Dental surgery and periodontal pockets
                                        – 10 days prior to RT (Shaw et al. 2000)                        – antibiotics until wound healing (Shaw et al. 2000)             – antibiotics until wound healing (Shaw et al. 2000)
                                        – nonvital teeth, apical pathology (Bornstein et al. 2001)    – Mucositis prophylaxis (Bepanthen® solution)                      – atraumatic tooth extraction
                                        – advanced periodontal disease, deep caries                   – Candidiasis prophylaxis (Ampho-Moronal®)                         – grinding down sharp bone edges
                                        – smoothing of bone edges and sharp points                    – Mouth-opening exercises (trismus prophylaxis)                    – primary mucous membrane coverage
                                        – primary wound closure                                       – Maintenance of oral cavity moisture with chamomile/sage        – Candidiasis prophylaxis (Ampho-Moronal®)
                                      – Tooth-conserving measures                                       rinses (Ø Glandosan® for the dentate [Nicholls et al. 1998])   – Maintenance of oral cavity moisture with chamomile/sage rinses
                                      – Treatment of oral lesions (e. g. candidiasis, …)              – Application of fluoridation splint 2–3 /d for 5 minutes           (Ø Glandosan® for the dentate [Nicholls et al. 1998])
                                      – Construction of a fluoridation splint                          – Temporary discontinuation of prothesis wear; not with          – Application of fluoridation splint 1 /d for 5 minutes
                                      – New interim support using permanent soft materials              obturators (Shaw et al. 2000)                                  – tooth-conservation measures
                                                                                                                                                                       – Discontinuation of prothesis wear at night (Shaw et al. 2000)
                                                                                                                                                                       – Restoration of masticatory function
                                                                                                                                                                         – implantation ca. 1 year after RT (own data, unpublished)

                             IR/LR    – Dental hygiene                                                –   Weekly recall (Bornstein et al. 2001)                        – Continue recall (every 6–8 weeks [Bornstein et al. 2001] for
                                      – Treatment of periodontal pockets                              –   Dental hygiene, motivation, monitoring                         the first year)
                                      – No extraction of teeth if:                                    –   Mucositis prophylaxis (Bepanthen® solution)                  – Dental hygiene, motivation, monitoring
                                        – the teeth are otherwise worth conserving                    –   Candidiasis prophylaxis (topische Antimykotika)              – Restoration of masticatory function
                                        – in NR cases, endodontic treatment is possible instead       –   Mouth-opening exercises (trismus prophylaxis)                  – implantation ca. 1 year after RT (own data, unpublished)
                                          of extraction                                               –   Maintenance of oral cavity moisture                          – Dental surgery and treatment of periodontal pockets
                                      – Selective tooth extractions:                                  –   Application of fluoridation splints 2–3 /d for 5 minutes        – preoperative antibiotic prophylaxis (1h preoperatively)
                                        – 10 days before RT (Shaw et al. 2000)                        –   Discontinuation of prosthesis wear at night (Shaw et           – atraumatic tooth extraction
                                        – smoothing of bone edges and sharp points                        al. 2000)                                                      – grinding down sharp bone edges
                                        – primary wound closure                                                                                                          – primary mucous membrane coverage
                                      – Conservative dentistry                                                                                                         – Tooth-conservation measures
                                      – Treatment of oral lesions (e. g. candidiasis, …)                                                                               – Discontinuation of prothesis wear at night (Shaw et al. 2000)
                                      – Construction of a fluoridation splint                                                                                           – Maintenance of oral cavity moisture with chamomile/sage
                                      – New interim support using permanent soft materials                                                                               rinses or substitution with artificial saliva

                             NR       – No restrictions placed on dental treatment                    – No restrictions placed on dental treatment                     –   No restrictions placed on dental treatment
                                      – Dental hygiene                                                – Dental hygiene, motivation, monitoring                         –   Treatment of periodontal diseases
                                      – Treatment of periodontal pockets                              – Tooth extraction:                                              –   Dental hygiene, motivation, monitoring
                                      – Tooth extraction:                                               – of teeth not worth conserving                                –   Extraction of teeth not worth conserving




Schweiz Monatsschr Zahnmed
                                        – of teeth not worth conserving                               – Application of fluoridation splint for 5 minutes                –   Application of fluoridation splint for 5 minutes
                                        – 10 days before RT (Shaw et al. 2000)
                                      – Manufacture of a fluoridation splint




Vol. 121
                                      HR: High-risk areas; IR/LR: intermediate- and low-risk areas; NR: no radiation-specific risk




3/2011
217
of the greatly feared osteoradionecrosis (ORN) was observed                       of radiation. The hypothesis tested was that a constantly low
       (Glanzmann & Grätz, 1995; Studer et al. 2004; Studer et al.                       ORN rate would be found in IMRT patients after RaDC com-
       2006d; Studer et al. 2007a; Ben-David et al. 2007). In con-                       pared to IMRT patients who received conventional dental treat-
       trast to conventional radiation techniques, as applied to a                       ment.
       tonsil carcinoma for instance, in which the jawbone is at risk
       bilaterally due to laterally opposing radiation beams, IMRT can                   Materials and Methods
       much more selectively deliver the required dose to the tumor
       region. During IMRT of tonsil carcinoma the contralateral                         Patient cohorts
       jawbone is no longer endangered and the ipsilateral much less                     In the present study, two patient groups were compared (Tab. III):
       so. Hence, adapting Grötz’s (Tab. II) guidelines for focused                      in group 1, from January 2002 to July 2006, 143 HNT patients
       dental care seemed expedient (Tab. I). This adapted method,                       were given conventional dental care with standard restorations
       termed “risk-adapted dental care” (RaDC), has been employed                       prior to IMRT: 100 patients with oropharyngeal carcinoma and
       on our IMRT patients since mid-2006 (Studer et al. 2007b). It                     43 with a carcinoma of the oral cavity. The mean/median
       requires that ORN risk areas, i. e. IMRT high-dose areas on the                   observation period of this group was 40/33 months (5–86).
       jawbone, be topographically defined by the radiation oncolo-                        In group 2, between August 2006 and December 2008, 161
       gist prior to dental treatment. Areas with low and intermediate                   patients received IMRT: 106 with oropharyngeal carcinoma and
       ORN risk are also defined for the dentist, so that dental resto-                  55 with oral cavity carcinoma. With all patients risk-adapted den-
       rations can be performed conventionally in high-risk areas,                       tal care (RaDC) was performed prior to IMRT. The mean/me-
       but less invasively in the regions that will receive lower doses                  dian observation period of this group was 19/13 months (6–44).




                           Radiation                                                                              Patient ID label
                           oncologist: ………………
                           Pager

                            Diagnosis / TNM
                            stage: ………………………


                                                Dental Care prior to IMRT

                                                                                                                                            UniversitätsSpital Zürich
                                                       risk definition
                                   (to be marked by the responsible radiation oncologist)
                                                       High Risk area: HR (in red)
                                               Intermediate / Low Risk area: MNR (in green)
                                                         No Risk: NR (in yellow)
                                                                                                                                             Klinik für Radio-Onkologie Zürich
                                                                                                                                             Dept. Medizinische Radiologie




       Fig. 1 (corresponds to Tab. I): Zurich University Hospital’s internal form for marking (IMRT dosage-dependent) individual risk areas for dental treatment before
       intensity-modulated radiation therapy (IMRT). The risk areas (high, intermediate/low, no risk of jaw osteonecrosis) for each patient are marked by the radiation
       oncologist as the basis for the dental treatment planned (see Tab. I).

218   Schweiz Monatsschr Zahnmed Vol. 121          3/2011
Tab. II Dental care of patients receiving radiotherapy for head-and-neck tumors (Grötz K A, Strahlenther Onkol 2003;
 179 [4]: 275–278)

                                  Before radiotherapy                               During radiotherapy                              After radiotherapy
                                  Dental treatment                                  Tissue-conserving treatment                      Tissue-conserving treatment
                                  – Removal of hard and soft plaque                 – Mucosa retractors (reduction of surface        – Continuation of fluoride application
                                  – Extraction of nonvital, periodontally             dose to adjacent mucosa via secondary          – Discontinuation of prosthesis wearing for
                                     diseased, carious, partially retained teeth      irradiation)                                     3–6 months after irradiation
                                  – Conservative treatment of remaining             – Fluoridation splint and continuous fluoride     – Tooth- or implant-borne prostheses or
                                     dentition                                        rinsing                                          maxillary prostheses can be re-inserted
                                  – Surgical treatment of                           – Temporary discontinuation of prosthesis          earlier, after mucositis has subsided
 Conventional radiation therapy




                                     – mucosal lesions                                wearing due to sore spots or denture ulcers    – Restoration of masticatory function is often
                                     – removal of sharp bone ridges                 – Mucositis prophylaxis especially due to          impossible due to xerostomia or jaw lesions
                                        (mylohyoid line)                              xerostomia (Candida colonization)              – Special guidelines for dental surgery after
                                  Extent of extractions depends on inclusion          – Bepanthen®                                     radiotherapy to avoid osteoradionecrosis:
                                  of salivary glands in the irradiated field; four     – topical antimycotics                           – Perioperative, systemic antibiotic prophy-
                                  groups:                                                (Nystatin = Moronal®)                           laxis (e. g., Amoxicillin), at the latest 24 h
                                  – Edentulous patients without mucosal               – mouth rinses (chamomile, sage,                   pre-operatively
                                     lesions = no pre-irradiation therapy                chloramine tea); Sucralfat suspension         – Atraumatic tooth extraction without
                                  – If conservative treatment is impossible         – Diflucan® (local & systemic yeast infections)       osteotomy, if possible
                                     = total extraction, clearing                   – Discontinue consumption of external noxae      – Removal of sharp bone ridges
                                  – Conservative caries treatment possible            – alcohol, nicotine                            – Primary plastic mucosal closure
                                     = elective extraction                            – no hot, spicy, or acidic drinks              – Xerostomia treatment
                                  – No active caries, good oral hygiene             – Dermatitis prophylaxis                         – Artificial saliva (warning: Glandosan®
                                     = no tooth extractions                         – Mouth-opening exercises, if masticatory          = mineral loss; mucine-containing
                                                                                      muscles and TMJ lie in irradiated field           Saliva-medac® and lysozyme-containing
                                                                                    – Xerostomia treatment                             BioXtra® products)
                                                                                    – Ethyol (Amifostin®) or Cumarin/Troxerutin      – Salivary gland stimulants Sialor®
                                                                                      (Venalot-Depot®)                               – Mouth-opening exercises against trismus



                                                                                                           areas, i. e. high ORN-risk areas, prior to treatment, the dentist
 Tab. III Overview comparing the two subgroups of                                                          can use this information to know regions requiring risk-adapted
 patients. RT: radiotherapy; FU: follow-up; RaDC: risk-                                                    dental care in each individual patient (see Studer et al. 2007b ).
 adapted dental care                                                                                       The patient form used for marking risk areas for RaDC is shown
                                                                                                           in Figure 1 and Table I.
 Parameter                                                       Group 1                 Group 2
                                                                 n = 143                 n = 161
                                                                                                           a) High-risk regions:
 Dental treatment                                                 standard                 RaDC
                                                                                                             60 Gy to the mandibular bone and/or > 50 Gy to gingival
 RT technique                                                      IMRT                    IMRT            areas.
 Timespan of treatment                                       1/2002–7/2006          8/2006–12/2008
 Diagnosis                                                                                                 b) Intermediate-risk regions:
   Oropharynx (n = 206)                                             100                    106             > 45 Gy to the gingiva, mandibular bone < 60 Gy, or: man-
   Oral cavity (n = 98)                                              43                     55             dibular bone < 60 Gy, and relevant reduction of salivation
 Average/median                                                                                            caused by irradiating mucous membranes and salivary glands
 FU time in months                                                 40/33                  19/33            (no ORN risk, but increased caries risk – for instance after cer-
                                                                                                           tain types of cervical irradiation in Hodgkins lymphoma).
  Only patients at risk of developing ORN – that is, patients
with a tumor of the oropharynx (n total = 206) and the oral                                                c) Low-risk regions:
cavity (n total = 98) – were evaluated.                                                                    Mandible < 60 Gy or only ascending ramus in the RT field, and
                                                                                                           gingiva < 45 Gy and at least a parotid volume equivalent with
Methods                                                                                                    an intermediate dose of 26 Gy.
The ORN incidence in the clinic’s IMRT cohort since RaDC was
introduced (08/2006–12/2008, group 2) was compared with                                                    d) No radiotherapy-specific risk:
the incidence after conventional dental treatment (01/2002–                                                Mandibular bone < 50 Gy, gingiva < 40 Gy, and both parotids
07/2006, group 1). We expected to find an unchanged, low                                                   outside the RT field (< 10 Gy intermediate dose).
incidence of ORN in group 2 vs. group 1, since ORN occurs in
areas exposed to high doses (usually at doses > 66 Gy), in which                                           Examination for ORN (Tab. IV) was conducted as part of the
lesion extirpation was performed according to the usual stan-                                              routine oncological follow-up examinations (by the clinics
dard.                                                                                                      for Oral and Maxillofacial Surgery, ENT, and Radiation Oncol-
  Based on the various known tolerance thresholds of different                                             ogy, University Hospital, Zurich) that were performed regularly
normal tissues for a given radiation dose, it was possible to                                              4–6 weeks after completion of treatment, then every 2 to
define the risk level for patients scheduled for oral cavity ra-                                           3 months during the first 2 years. In suspected or positively
diation treatment (see below, a–d). Because the radiation on-                                              identified cases of ORN patients are referred to the Clinic for
cologist can identify and mark topographic IMRT high-dose                                                  Maxillofacial Surgery for further evaluation and treatment.

                                                                                                                                     Schweiz Monatsschr Zahnmed        Vol. 121    3/2011   219
Only three patients in this study group failed to participate                      5 cases observed also correspond to the NCI and EORTC classi-
      in the routine progress check-ups, and therefore could not be                        fication of a grade-2 ORN. Table Vl presents details on the
      evaluated.                                                                           5 sequester patients. All ORN events were found in the high-
                                                                                           dose region. Other, unexpected reactions of the mucosa or
      Results                                                                              teeth outside the high-dose areas were not observed; the less
                                                                                           invasive tooth restorations outside the high-dose areas in
      Tumor control                                                                        RaDC group 2 did not demonstrate any clinically apparent,
      In 90% of the patients, chemotherapy (Cisplatin or Cetuximab)                        unfavorable results.
      was also performed simultaneously. At the last performed fol-
      low-up examination (“last time seen”), 74% of the patients                           Tooth extractions
      were living tumor-free, 12% were living with cancer, 12% had                         Table VII lists the number of teeth extracted in each group. As
      died of cancer, and 3% had died of other causes. The 2-year                          expected/by definition, fewer teeth were extracted in the RaDC
      local control rate of the entire patient group was 85% among                         cohort. In this context, the clinically relevant (but not quanti-
      patients with oropharyngeal cancer, and 65% among patients                           fied) fact must be mentioned that almost no radiation plann-
      with cancer of the oral cavity.                                                      ing computed tomography (“planning CT”) had to be delayed
                                                                                           due to pronounced facial soft-tissue swelling after multiple
      ORN incidence                                                                        extractions performed as part of the prior dental care. This was,
      ORN incidence is shown in Table V. The rates of grade-2 ORN                          however, frequently the case in the period of conventional
      (sequester formation) were identical in groups 1 and 2; all                          dental treatment (group 1), with an ensuing delay of 1 to 2 weeks
                                                                                           until the swelling had gone down; thus, the start of radio-
        Tab. IV Grades of osteoradionecrosis (Glanzmann &                                  therapy was also delayed.
        Grätz 1995)                                                                           In addition, a tendency of more frequently possible dental
                                                                                           rehabilitation was observed (no statistical analysis of these
        Classification of osteoradionecrosis (ORN) by grade                                 retrospective data).
        Grade      Event
        1          Exposed bone without signs of infection for at least                    Discussion
                   3 months
                                                                                           In addition to severe xerostomia, ORN is the most important
        2          Exposed bone with signs of infection or sequester, but not
                   grades 3–5                                                              criterion for radiation tolerance in oral cavity and oropharyn-
                                                                                           geal carcinoma patients, and is the main justification for
        3          Osteonecrosis, treated with mandibular resection, with
                                                                                           consistently performing dental treatment prior to the start of
                   satisfactory result
                                                                                           radiotherapy. Comprehensive dental and/or oral surgery treat-
        4          Osteonecrosis with persistent problems despite mandibular
                                                                                           ment prior to radiotherapy in the orofacial region is of funda-
                   resection
                                                                                           mental importance in the prevention of osteonecrosis of the
        5          Death due to osteoradionecrosis                                         irradiated jaw.
                                                                                              ORN has been variously classified according to different
                                                                                           definitions in earlier publications. In our clinics, the classifica-
        Tab. V Occurrence of osteoradionecrosis (ORN) after
                                                                                           tion by Glanzmann and Grätz is used (Glanzmann & Grätz
        conventional or risk-adapted dental care (RaDC)
                                                                                           1995, Tab. lV). The advantage of this classification vs. that of
                           conventional            risk-adapted                            EORTC (LENT/SOMA) or NCI (Jereczek-Fossa et al. 2002) is
                          1/2002–7/2006          8/2006–12/2008            Total           its connection to therapeutic and clinical consequences;
                             n = 143                  n = 161             n = 304          nevertheless, grade-2 events mutually correspond in all of the
        Grade-1 ORN                0                       0                  0            named classification systems.
        Grade-2 ORN                3                       2              5 (1.6%)            With the radiotherapeutic technology of the past the re-
                                                                                           quired tumor dosage was chiefly delivered via laterally opposed
        Grade-3 ORN                0                       0                  0
                                                                                           fields, which also simultaneously irradiated most of the oral


        Tab. VI Details on the 5 patients with grade-2 ORN: comparable grade-2 ORN rates in oropharyngeal and oral-cavity
        cancer patients with 2% (4/206) vs 1% (1/98), resp.

                Diagnosis              Stage              ORN location            ORN therapy                    outcome       Occurrence      Duration
                                                                                                                               after IMRT      (months)
        1       Oropharynx             cT4cN2c            Boost region            O                              Healed        12              20
        2       Oropharynx             cT3cN2b            Boost region            Partial decortication          Regenerated    4               5
        3       Oropharynx             cTcN2b             Boost region            O                              Healed        22              30
        4       Floor of mouth         pT2pN0             Boost region            Partial decortication          Regenerated    0               6
        5       Oropharynx             cT3cN2b            Boost region            O                              Healed         6              20

        Patients 4 and 5 received risk-adapted dental care (RaDC) before IMRT
        In terms of local radiation dose, nothing remarkable was found compared to other patients without ORN.
        The 5 events were located in region 37/retromolar left/31–32/37/47.
        pTpN: postoperative stage
        cTcN: definitive IMRT without prior surgery



220 Schweiz Monatsschr Zahnmed Vol. 121             3/2011
Tab. VII Retrospective overview of the number of teeth extracted during dental treatment prior to radiotherapy and
 during dental care after IMRT (dental implants, removable partial or complete dentures)

 Parameter                                                             Conventional dental care                   RaDC
                                                                           (IMRT group 1)                     (IMRT group 2)
 Edentulous patients                                                            17%                                 15%
 Dentate patients
 – no extractions                                                               27%                                 47%
 – 1–3 teeth extracted                                                          36%                                 29%
 – 4–15 teeth extracted                                                         37%                                 24%
 Dental rehabilitation                                                          23%                                 36%


cavity and/or jawbone. This resulted in a greater radiation             mor, and is performed as soon as possible after dental treat-
impact on the jawbone, associated with a higher ORN rate,               ment. This CT is conducted with a custom-modelled fixation
than seen today in the IMRT era; accordingly, the entire den-           facial mask made of plastic (for the purpose of reproducibly
tate jaw usually had to be considered a “region at risk” and            positioning the patient over the weeks of treatment, every
correspondingly dentally treated. IMRT is a method which                radiotherapy session is carried out using this mask). If the mask
makes it possible to restrict the high-risk region to the volume        is made on a swollen face, it will be loose after the swelling has
of jawbone adjacent to the tumor. IMRT enabled the ORN rate             subsided; both the fixation mask and the millimeter-exact
to be reduced from ca. 5–10% to 1% (Glanzmann & Graetz,                 radiation plan are thus rendered worthless.
1995; Studer et al. 2004; Studer et al. 2006d; Studer et al.               Experience has shown that careful manipulations/interven-
2007a; Ben-David et al. 2007), a success of considerable rele-          tions on the jawbone and its mucous membrane covering are
vance in the attempt to reduce late complications of radiation          well tolerated after radiation doses of up to ~ 50 Gy, but at
treatment. The “focussed” high-dose exposure and the pro-               doses over > 50 Gy, invasive interventions are accompanied by
nounced drop in the ORN rate after IMRT shown in our patients           an increased risk of ORN and lower tissue tolerance. If the
in 2006 indicated the logic of also keeping dental treatment            status of the remaining dentition and surrounding tissues is
“focussed”, which our center has therefore done since mid-              better, this greatly improves the outlook for any subsequent
2006. Table I shows the steps of dental treatment in RaDC: ad-          dental care, which in turn positively influences the tumor
aptation of methods to the local risk for jawbones and soft tis-        patient’s quality of life (Zwahlen et al 2008). The retrospective
sues before/during/after IMRT; Table II summarizes the standard         data on dental treatment seems to confirm this (Tab. VII).
procedures which have existed up to now. As already mentioned,             From an economic point of view, avoiding a grade-3 or
the main difference lies in the focussed approach of RaDC.              -4 ORN amounts to a savings of about € 30,000 (based on Swiss
   After an observational period of over 3 years since introduc-        conditions); the improved possibilities for dental treatment
ing the guidelines for pre-IMRT RaDC, no detrimental effects            and the advantages of more remaining teeth are more difficult
have yet been found in patients of group 2, most importantly,           to express in terms of costs. Nevertheless, the health advan-
no increase in ORN incidence compared to the IMRT group 1,              tages and improved quality of life for the patients are indisput-
which in the previous years had undergone focal treatment ac-           able. It is interesting to note that the incidence of bisphospho-
cording to the conventional standard. Although the duration             nate-associated osteonecrosis currently considerably exceeds
of observation differed in the two groups, the results are con-         that of ORN after IMRT (18.6%, Walter et al. 2008; Dannemann
sidered reliable because both groups are IMRT cohorts, i. e., it        et al. 2008 ).
was possible to very conservatively treat jawbones in both
groups and include only relatively low volumes of bone in the           Conclusion
high-dosage area. Thus, due to the use of the IMRT technique,
an increase in ORN was not expected. As already mentioned,              Following much less invasive dental treatment, no higher-
dental treatment in the high-risk regions in the RaDC groups            grade ORN or ORN-related jaw resections occurred in our IMRT
was also performed in accordance with the general standard.             patient cohort, as before. The more invasive standard guide-
Less invasively treated intermediate or low-risk areas by defini-       lines for dental treatment prior to radiotherapy which have
tion receive intermediate or very low radiation doses, so that,         been valid up to now no longer appear justifiable for IMRT
theoretically, only limited side-effects are expected in these          patients. Based on the data presented here, a risk-adapted, less
tissue areas in RaDC group 2. In fact, 3 years of RaDC experi-          invasive approach to pre-IMRT dental care is recommended.
ence confirmed this. However, due to the paucity of data in
literature, comparisons cannot be made.                                 Résumé
   Thanks to RaDC, it was possible to reduce the number of or
even totally avoid tooth extractions in the majority of patients        Introduction: L’IMRT est implémentée au Département de
(50% more patients with no extractions, Tab. VII), since IMRT           radio-oncologie de l’Hôpital de Zurich depuis 2002. Outre une
creates more low- and intermediate-risk areas (that would               diminution de la xérostémie, son avantage principal dans les
previously have been high-dose areas), allowing less invasive           régions de la tête et du cou réside dans une réduction substan-
dental treatment to be performed.                                       tielle du RON (de ~ 5–10% à ~ < 1%).
   In this context, the rarity of facial swelling after RaDC is also       Les procédures standards lors des soins dentaires préradio-
clinically relevant. This is yet another advantage of RaDC,             thérapeutiques ont été ajustées afin d’être moins invasives
since time is no longer lost waiting for swelling to abate: the         pour les patients soumis à l’IMRT depuis août 2006.
planning CT serves as the basis for computer-assisted 3-dimen-             Patients et méthode: Cet article présente les résultats d’une
sional calculation of radiation dose delivery to the tissues/tu-        période d’un suivi de 3 ans pour des patients qui ont reçu des

                                                                                             Schweiz Monatsschr Zahnmed    Vol. 121   3/2011   221
soins dentaires adaptés aux risques avant l’IMRT pour des                       currence de degré 3, et pas de résection de la mandibule), et
      cancers de la tête et du cou (n = 161). Des patients traités avec               moins d’extractions dentaires grâce au traitement dentaire
      des soins dentaires standards (n = 143) avant l’IMRT de 01/2002                 adapté aux risques.
      à 07/2006 ont servi de contrôle.                                                  Conclusion: Sur la base des données présentées ici, le traite-
        Résultats: Les analyses du RON ont révélé des taux d’inci-                    ment dentaire adapté aux risques est fortement recommandé
      dence égaux pour les deux périodes (1,5% degré 2, pas d’oc-                     pour les patients soumis à l’IMRT.




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Cure odontoiatriche prima della radioterapia ad intensità modulata

  • 1. Studer Gabriela1 Risk-adapted dental care Glanzmann Christoph1 Studer Stephan P2 Grätz Klaus W2 prior to intensity-modulated Bredell Marius2 Locher Michael3 radiotherapy (IMRT) Lütolf Urs M1 Zwahlen Roger A2 Results 1 Clinic for Radiation Oncology, University Hospital, Zurich 2 Clinic for Oral and Maxillofacial Key words: dental care before radiotherapy, osteoradionecrosis Surgery, University Hospital, Zurich 3 Clinic of Dentistry, Oral Medicine and Gnathic Surgery, Clinic for Oral Surgery, Center of Dental and Oral Medicine, University of Zurich Summary Background: At the Clinic for Materials and Methods: In August 2006, RaDC Radiation Oncology at the Zurich University was clinically implemented and has been Corresponding author PD Dr. med. Gabriela Studer, LA Hospital (UniversitätsSpital Zürich [USZ]), used for all HNT patients prior to IMRT since RadioOnkologie AN 16 head-and-neck tumor (HNT) patients have then. Before that (01/2002–07/2006), dental UniversitätsSpital Zürich been treated with intensity-modulated radio- restorations were performed according to the Rämistrassse 100 therapy (IMRT) since 01/2002 (n > 800). This usual procedure. 8091 Zürich E-mail: gabriela.studer@usz.ch method causes less damage to normal tissues Results: The rate of grade-2 ORN was similar Tel. 044 255 29 31 adjacent to the tumor, and thus it was possible in the conventionally treated and RaDC groups Fax 044 255 45 47 in the head/neck region to markedly reduce (2% and 1%, resp.); grade-3 ORN had not Schweiz Monatsschr Zahnmed 121: the rate of osteoradionecrosis (ORN), in addi- occurred by the time the analysis was con- 216–222 (2011) tion to reducing the rate of severe xerostomia. ducted. As expected, fewer extractions were Accepted for publication: 18 August 2010 Based on these results, risk-adapted dental performed in the RaDC cohort (no extractions care (RaDC) was adopted by our clinic as the in 47% of the RaDC/IMRT cohort vs. 27% in standard mode of pre-IMRT dental treatment. the IMRT cohort receiving conventional dental The guidelines as formulated by Grötz et al. care). were respected. Conclusion: After considerably less invasive ORN prophylaxis is one of the most important dental treatment, no higher-grade ORN oc- goals of pre-radiotherapy dental care, and the curred and no ORN-related jaw resections ORN rate is a measurable parameter for the were required. Based on the present data, efficacy of dental care, given a certain radia- risk-adapted minimally invasive dental care is tion technique. The aim of the present study recommended before IMRT. was therefore to evaluate the efficacy of RaDC as reflected by the ORN rate of our IMRT pa- tients. Introduction 2010). The greatest clinical advantage of this relatively new technique is that it causes substantially less damage to normal In keeping with international guidelines (Grötz 2003; Shaw tissues while providing equally good or improved tumor con- et al. 2000), all head-and-neck tumor (HNT) patients at our trol rates (Lee et al. 2002; Eisbruch et al. 2003; Eisbruch et clinic since more than two decades have undergone standard- al. 2004; Chao et al. 2004; De Arruda et al. 2006; Puri et al. ized focal evaluation and dental treatment prior to all radiation 2005; Studer et al. 2006a–c, Studer et al. 2007c/d). therapy. Details of the IMRT technique were explained in an earlier Since 01/2002, our HNT patients have been treated with in- publication (Studer et al. 2007a, Tab. I and Fig. 1). Even in tensity-modulated radiotherapy (IMRT) (n > 800, status: March, the first years after implementation of IMRT a diminishment 216 Schweiz Monatsschr Zahnmed Vol. 121 3/2011
  • 2. Tab. I (corresponds to Fig. 1) Schematic overview of dental treatment for patients with head-and-neck tumors before/during/after IMRT at the University Hospital Zurich (USZ) Before IMRT During IMRT After IMRT HR Dental treatment as with conventional radiotherapy (RT) – Weekly recall (Bornstein et al. 2001) – Continue recall for the first year (every 6–8 weeks [Bornstein – Dental hygiene – Dental hygiene, motivation, monitoring et al. 2001]) – Treatment of periodontal pockets – Tooth extraction: – Dental hygiene, motivation, monitoring – Tooth extraction: – after consultation with radiotherapist – Dental surgery and periodontal pockets – 10 days prior to RT (Shaw et al. 2000) – antibiotics until wound healing (Shaw et al. 2000) – antibiotics until wound healing (Shaw et al. 2000) – nonvital teeth, apical pathology (Bornstein et al. 2001) – Mucositis prophylaxis (Bepanthen® solution) – atraumatic tooth extraction – advanced periodontal disease, deep caries – Candidiasis prophylaxis (Ampho-Moronal®) – grinding down sharp bone edges – smoothing of bone edges and sharp points – Mouth-opening exercises (trismus prophylaxis) – primary mucous membrane coverage – primary wound closure – Maintenance of oral cavity moisture with chamomile/sage – Candidiasis prophylaxis (Ampho-Moronal®) – Tooth-conserving measures rinses (Ø Glandosan® for the dentate [Nicholls et al. 1998]) – Maintenance of oral cavity moisture with chamomile/sage rinses – Treatment of oral lesions (e. g. candidiasis, …) – Application of fluoridation splint 2–3 /d for 5 minutes (Ø Glandosan® for the dentate [Nicholls et al. 1998]) – Construction of a fluoridation splint – Temporary discontinuation of prothesis wear; not with – Application of fluoridation splint 1 /d for 5 minutes – New interim support using permanent soft materials obturators (Shaw et al. 2000) – tooth-conservation measures – Discontinuation of prothesis wear at night (Shaw et al. 2000) – Restoration of masticatory function – implantation ca. 1 year after RT (own data, unpublished) IR/LR – Dental hygiene – Weekly recall (Bornstein et al. 2001) – Continue recall (every 6–8 weeks [Bornstein et al. 2001] for – Treatment of periodontal pockets – Dental hygiene, motivation, monitoring the first year) – No extraction of teeth if: – Mucositis prophylaxis (Bepanthen® solution) – Dental hygiene, motivation, monitoring – the teeth are otherwise worth conserving – Candidiasis prophylaxis (topische Antimykotika) – Restoration of masticatory function – in NR cases, endodontic treatment is possible instead – Mouth-opening exercises (trismus prophylaxis) – implantation ca. 1 year after RT (own data, unpublished) of extraction – Maintenance of oral cavity moisture – Dental surgery and treatment of periodontal pockets – Selective tooth extractions: – Application of fluoridation splints 2–3 /d for 5 minutes – preoperative antibiotic prophylaxis (1h preoperatively) – 10 days before RT (Shaw et al. 2000) – Discontinuation of prosthesis wear at night (Shaw et – atraumatic tooth extraction – smoothing of bone edges and sharp points al. 2000) – grinding down sharp bone edges – primary wound closure – primary mucous membrane coverage – Conservative dentistry – Tooth-conservation measures – Treatment of oral lesions (e. g. candidiasis, …) – Discontinuation of prothesis wear at night (Shaw et al. 2000) – Construction of a fluoridation splint – Maintenance of oral cavity moisture with chamomile/sage – New interim support using permanent soft materials rinses or substitution with artificial saliva NR – No restrictions placed on dental treatment – No restrictions placed on dental treatment – No restrictions placed on dental treatment – Dental hygiene – Dental hygiene, motivation, monitoring – Treatment of periodontal diseases – Treatment of periodontal pockets – Tooth extraction: – Dental hygiene, motivation, monitoring – Tooth extraction: – of teeth not worth conserving – Extraction of teeth not worth conserving Schweiz Monatsschr Zahnmed – of teeth not worth conserving – Application of fluoridation splint for 5 minutes – Application of fluoridation splint for 5 minutes – 10 days before RT (Shaw et al. 2000) – Manufacture of a fluoridation splint Vol. 121 HR: High-risk areas; IR/LR: intermediate- and low-risk areas; NR: no radiation-specific risk 3/2011 217
  • 3. of the greatly feared osteoradionecrosis (ORN) was observed of radiation. The hypothesis tested was that a constantly low (Glanzmann & Grätz, 1995; Studer et al. 2004; Studer et al. ORN rate would be found in IMRT patients after RaDC com- 2006d; Studer et al. 2007a; Ben-David et al. 2007). In con- pared to IMRT patients who received conventional dental treat- trast to conventional radiation techniques, as applied to a ment. tonsil carcinoma for instance, in which the jawbone is at risk bilaterally due to laterally opposing radiation beams, IMRT can Materials and Methods much more selectively deliver the required dose to the tumor region. During IMRT of tonsil carcinoma the contralateral Patient cohorts jawbone is no longer endangered and the ipsilateral much less In the present study, two patient groups were compared (Tab. III): so. Hence, adapting Grötz’s (Tab. II) guidelines for focused in group 1, from January 2002 to July 2006, 143 HNT patients dental care seemed expedient (Tab. I). This adapted method, were given conventional dental care with standard restorations termed “risk-adapted dental care” (RaDC), has been employed prior to IMRT: 100 patients with oropharyngeal carcinoma and on our IMRT patients since mid-2006 (Studer et al. 2007b). It 43 with a carcinoma of the oral cavity. The mean/median requires that ORN risk areas, i. e. IMRT high-dose areas on the observation period of this group was 40/33 months (5–86). jawbone, be topographically defined by the radiation oncolo- In group 2, between August 2006 and December 2008, 161 gist prior to dental treatment. Areas with low and intermediate patients received IMRT: 106 with oropharyngeal carcinoma and ORN risk are also defined for the dentist, so that dental resto- 55 with oral cavity carcinoma. With all patients risk-adapted den- rations can be performed conventionally in high-risk areas, tal care (RaDC) was performed prior to IMRT. The mean/me- but less invasively in the regions that will receive lower doses dian observation period of this group was 19/13 months (6–44). Radiation Patient ID label oncologist: ……………… Pager Diagnosis / TNM stage: ……………………… Dental Care prior to IMRT UniversitätsSpital Zürich risk definition (to be marked by the responsible radiation oncologist) High Risk area: HR (in red) Intermediate / Low Risk area: MNR (in green) No Risk: NR (in yellow) Klinik für Radio-Onkologie Zürich Dept. Medizinische Radiologie Fig. 1 (corresponds to Tab. I): Zurich University Hospital’s internal form for marking (IMRT dosage-dependent) individual risk areas for dental treatment before intensity-modulated radiation therapy (IMRT). The risk areas (high, intermediate/low, no risk of jaw osteonecrosis) for each patient are marked by the radiation oncologist as the basis for the dental treatment planned (see Tab. I). 218 Schweiz Monatsschr Zahnmed Vol. 121 3/2011
  • 4. Tab. II Dental care of patients receiving radiotherapy for head-and-neck tumors (Grötz K A, Strahlenther Onkol 2003; 179 [4]: 275–278) Before radiotherapy During radiotherapy After radiotherapy Dental treatment Tissue-conserving treatment Tissue-conserving treatment – Removal of hard and soft plaque – Mucosa retractors (reduction of surface – Continuation of fluoride application – Extraction of nonvital, periodontally dose to adjacent mucosa via secondary – Discontinuation of prosthesis wearing for diseased, carious, partially retained teeth irradiation) 3–6 months after irradiation – Conservative treatment of remaining – Fluoridation splint and continuous fluoride – Tooth- or implant-borne prostheses or dentition rinsing maxillary prostheses can be re-inserted – Surgical treatment of – Temporary discontinuation of prosthesis earlier, after mucositis has subsided Conventional radiation therapy – mucosal lesions wearing due to sore spots or denture ulcers – Restoration of masticatory function is often – removal of sharp bone ridges – Mucositis prophylaxis especially due to impossible due to xerostomia or jaw lesions (mylohyoid line) xerostomia (Candida colonization) – Special guidelines for dental surgery after Extent of extractions depends on inclusion – Bepanthen® radiotherapy to avoid osteoradionecrosis: of salivary glands in the irradiated field; four – topical antimycotics – Perioperative, systemic antibiotic prophy- groups: (Nystatin = Moronal®) laxis (e. g., Amoxicillin), at the latest 24 h – Edentulous patients without mucosal – mouth rinses (chamomile, sage, pre-operatively lesions = no pre-irradiation therapy chloramine tea); Sucralfat suspension – Atraumatic tooth extraction without – If conservative treatment is impossible – Diflucan® (local & systemic yeast infections) osteotomy, if possible = total extraction, clearing – Discontinue consumption of external noxae – Removal of sharp bone ridges – Conservative caries treatment possible – alcohol, nicotine – Primary plastic mucosal closure = elective extraction – no hot, spicy, or acidic drinks – Xerostomia treatment – No active caries, good oral hygiene – Dermatitis prophylaxis – Artificial saliva (warning: Glandosan® = no tooth extractions – Mouth-opening exercises, if masticatory = mineral loss; mucine-containing muscles and TMJ lie in irradiated field Saliva-medac® and lysozyme-containing – Xerostomia treatment BioXtra® products) – Ethyol (Amifostin®) or Cumarin/Troxerutin – Salivary gland stimulants Sialor® (Venalot-Depot®) – Mouth-opening exercises against trismus areas, i. e. high ORN-risk areas, prior to treatment, the dentist Tab. III Overview comparing the two subgroups of can use this information to know regions requiring risk-adapted patients. RT: radiotherapy; FU: follow-up; RaDC: risk- dental care in each individual patient (see Studer et al. 2007b ). adapted dental care The patient form used for marking risk areas for RaDC is shown in Figure 1 and Table I. Parameter Group 1 Group 2 n = 143 n = 161 a) High-risk regions: Dental treatment standard RaDC 60 Gy to the mandibular bone and/or > 50 Gy to gingival RT technique IMRT IMRT areas. Timespan of treatment 1/2002–7/2006 8/2006–12/2008 Diagnosis b) Intermediate-risk regions: Oropharynx (n = 206) 100 106 > 45 Gy to the gingiva, mandibular bone < 60 Gy, or: man- Oral cavity (n = 98) 43 55 dibular bone < 60 Gy, and relevant reduction of salivation Average/median caused by irradiating mucous membranes and salivary glands FU time in months 40/33 19/33 (no ORN risk, but increased caries risk – for instance after cer- tain types of cervical irradiation in Hodgkins lymphoma). Only patients at risk of developing ORN – that is, patients with a tumor of the oropharynx (n total = 206) and the oral c) Low-risk regions: cavity (n total = 98) – were evaluated. Mandible < 60 Gy or only ascending ramus in the RT field, and gingiva < 45 Gy and at least a parotid volume equivalent with Methods an intermediate dose of 26 Gy. The ORN incidence in the clinic’s IMRT cohort since RaDC was introduced (08/2006–12/2008, group 2) was compared with d) No radiotherapy-specific risk: the incidence after conventional dental treatment (01/2002– Mandibular bone < 50 Gy, gingiva < 40 Gy, and both parotids 07/2006, group 1). We expected to find an unchanged, low outside the RT field (< 10 Gy intermediate dose). incidence of ORN in group 2 vs. group 1, since ORN occurs in areas exposed to high doses (usually at doses > 66 Gy), in which Examination for ORN (Tab. IV) was conducted as part of the lesion extirpation was performed according to the usual stan- routine oncological follow-up examinations (by the clinics dard. for Oral and Maxillofacial Surgery, ENT, and Radiation Oncol- Based on the various known tolerance thresholds of different ogy, University Hospital, Zurich) that were performed regularly normal tissues for a given radiation dose, it was possible to 4–6 weeks after completion of treatment, then every 2 to define the risk level for patients scheduled for oral cavity ra- 3 months during the first 2 years. In suspected or positively diation treatment (see below, a–d). Because the radiation on- identified cases of ORN patients are referred to the Clinic for cologist can identify and mark topographic IMRT high-dose Maxillofacial Surgery for further evaluation and treatment. Schweiz Monatsschr Zahnmed Vol. 121 3/2011 219
  • 5. Only three patients in this study group failed to participate 5 cases observed also correspond to the NCI and EORTC classi- in the routine progress check-ups, and therefore could not be fication of a grade-2 ORN. Table Vl presents details on the evaluated. 5 sequester patients. All ORN events were found in the high- dose region. Other, unexpected reactions of the mucosa or Results teeth outside the high-dose areas were not observed; the less invasive tooth restorations outside the high-dose areas in Tumor control RaDC group 2 did not demonstrate any clinically apparent, In 90% of the patients, chemotherapy (Cisplatin or Cetuximab) unfavorable results. was also performed simultaneously. At the last performed fol- low-up examination (“last time seen”), 74% of the patients Tooth extractions were living tumor-free, 12% were living with cancer, 12% had Table VII lists the number of teeth extracted in each group. As died of cancer, and 3% had died of other causes. The 2-year expected/by definition, fewer teeth were extracted in the RaDC local control rate of the entire patient group was 85% among cohort. In this context, the clinically relevant (but not quanti- patients with oropharyngeal cancer, and 65% among patients fied) fact must be mentioned that almost no radiation plann- with cancer of the oral cavity. ing computed tomography (“planning CT”) had to be delayed due to pronounced facial soft-tissue swelling after multiple ORN incidence extractions performed as part of the prior dental care. This was, ORN incidence is shown in Table V. The rates of grade-2 ORN however, frequently the case in the period of conventional (sequester formation) were identical in groups 1 and 2; all dental treatment (group 1), with an ensuing delay of 1 to 2 weeks until the swelling had gone down; thus, the start of radio- Tab. IV Grades of osteoradionecrosis (Glanzmann & therapy was also delayed. Grätz 1995) In addition, a tendency of more frequently possible dental rehabilitation was observed (no statistical analysis of these Classification of osteoradionecrosis (ORN) by grade retrospective data). Grade Event 1 Exposed bone without signs of infection for at least Discussion 3 months In addition to severe xerostomia, ORN is the most important 2 Exposed bone with signs of infection or sequester, but not grades 3–5 criterion for radiation tolerance in oral cavity and oropharyn- geal carcinoma patients, and is the main justification for 3 Osteonecrosis, treated with mandibular resection, with consistently performing dental treatment prior to the start of satisfactory result radiotherapy. Comprehensive dental and/or oral surgery treat- 4 Osteonecrosis with persistent problems despite mandibular ment prior to radiotherapy in the orofacial region is of funda- resection mental importance in the prevention of osteonecrosis of the 5 Death due to osteoradionecrosis irradiated jaw. ORN has been variously classified according to different definitions in earlier publications. In our clinics, the classifica- Tab. V Occurrence of osteoradionecrosis (ORN) after tion by Glanzmann and Grätz is used (Glanzmann & Grätz conventional or risk-adapted dental care (RaDC) 1995, Tab. lV). The advantage of this classification vs. that of conventional risk-adapted EORTC (LENT/SOMA) or NCI (Jereczek-Fossa et al. 2002) is 1/2002–7/2006 8/2006–12/2008 Total its connection to therapeutic and clinical consequences; n = 143 n = 161 n = 304 nevertheless, grade-2 events mutually correspond in all of the Grade-1 ORN 0 0 0 named classification systems. Grade-2 ORN 3 2 5 (1.6%) With the radiotherapeutic technology of the past the re- quired tumor dosage was chiefly delivered via laterally opposed Grade-3 ORN 0 0 0 fields, which also simultaneously irradiated most of the oral Tab. VI Details on the 5 patients with grade-2 ORN: comparable grade-2 ORN rates in oropharyngeal and oral-cavity cancer patients with 2% (4/206) vs 1% (1/98), resp. Diagnosis Stage ORN location ORN therapy outcome Occurrence Duration after IMRT (months) 1 Oropharynx cT4cN2c Boost region O Healed 12 20 2 Oropharynx cT3cN2b Boost region Partial decortication Regenerated 4 5 3 Oropharynx cTcN2b Boost region O Healed 22 30 4 Floor of mouth pT2pN0 Boost region Partial decortication Regenerated 0 6 5 Oropharynx cT3cN2b Boost region O Healed 6 20 Patients 4 and 5 received risk-adapted dental care (RaDC) before IMRT In terms of local radiation dose, nothing remarkable was found compared to other patients without ORN. The 5 events were located in region 37/retromolar left/31–32/37/47. pTpN: postoperative stage cTcN: definitive IMRT without prior surgery 220 Schweiz Monatsschr Zahnmed Vol. 121 3/2011
  • 6. Tab. VII Retrospective overview of the number of teeth extracted during dental treatment prior to radiotherapy and during dental care after IMRT (dental implants, removable partial or complete dentures) Parameter Conventional dental care RaDC (IMRT group 1) (IMRT group 2) Edentulous patients 17% 15% Dentate patients – no extractions 27% 47% – 1–3 teeth extracted 36% 29% – 4–15 teeth extracted 37% 24% Dental rehabilitation 23% 36% cavity and/or jawbone. This resulted in a greater radiation mor, and is performed as soon as possible after dental treat- impact on the jawbone, associated with a higher ORN rate, ment. This CT is conducted with a custom-modelled fixation than seen today in the IMRT era; accordingly, the entire den- facial mask made of plastic (for the purpose of reproducibly tate jaw usually had to be considered a “region at risk” and positioning the patient over the weeks of treatment, every correspondingly dentally treated. IMRT is a method which radiotherapy session is carried out using this mask). If the mask makes it possible to restrict the high-risk region to the volume is made on a swollen face, it will be loose after the swelling has of jawbone adjacent to the tumor. IMRT enabled the ORN rate subsided; both the fixation mask and the millimeter-exact to be reduced from ca. 5–10% to 1% (Glanzmann & Graetz, radiation plan are thus rendered worthless. 1995; Studer et al. 2004; Studer et al. 2006d; Studer et al. Experience has shown that careful manipulations/interven- 2007a; Ben-David et al. 2007), a success of considerable rele- tions on the jawbone and its mucous membrane covering are vance in the attempt to reduce late complications of radiation well tolerated after radiation doses of up to ~ 50 Gy, but at treatment. The “focussed” high-dose exposure and the pro- doses over > 50 Gy, invasive interventions are accompanied by nounced drop in the ORN rate after IMRT shown in our patients an increased risk of ORN and lower tissue tolerance. If the in 2006 indicated the logic of also keeping dental treatment status of the remaining dentition and surrounding tissues is “focussed”, which our center has therefore done since mid- better, this greatly improves the outlook for any subsequent 2006. Table I shows the steps of dental treatment in RaDC: ad- dental care, which in turn positively influences the tumor aptation of methods to the local risk for jawbones and soft tis- patient’s quality of life (Zwahlen et al 2008). The retrospective sues before/during/after IMRT; Table II summarizes the standard data on dental treatment seems to confirm this (Tab. VII). procedures which have existed up to now. As already mentioned, From an economic point of view, avoiding a grade-3 or the main difference lies in the focussed approach of RaDC. -4 ORN amounts to a savings of about € 30,000 (based on Swiss After an observational period of over 3 years since introduc- conditions); the improved possibilities for dental treatment ing the guidelines for pre-IMRT RaDC, no detrimental effects and the advantages of more remaining teeth are more difficult have yet been found in patients of group 2, most importantly, to express in terms of costs. Nevertheless, the health advan- no increase in ORN incidence compared to the IMRT group 1, tages and improved quality of life for the patients are indisput- which in the previous years had undergone focal treatment ac- able. It is interesting to note that the incidence of bisphospho- cording to the conventional standard. Although the duration nate-associated osteonecrosis currently considerably exceeds of observation differed in the two groups, the results are con- that of ORN after IMRT (18.6%, Walter et al. 2008; Dannemann sidered reliable because both groups are IMRT cohorts, i. e., it et al. 2008 ). was possible to very conservatively treat jawbones in both groups and include only relatively low volumes of bone in the Conclusion high-dosage area. Thus, due to the use of the IMRT technique, an increase in ORN was not expected. As already mentioned, Following much less invasive dental treatment, no higher- dental treatment in the high-risk regions in the RaDC groups grade ORN or ORN-related jaw resections occurred in our IMRT was also performed in accordance with the general standard. patient cohort, as before. The more invasive standard guide- Less invasively treated intermediate or low-risk areas by defini- lines for dental treatment prior to radiotherapy which have tion receive intermediate or very low radiation doses, so that, been valid up to now no longer appear justifiable for IMRT theoretically, only limited side-effects are expected in these patients. Based on the data presented here, a risk-adapted, less tissue areas in RaDC group 2. In fact, 3 years of RaDC experi- invasive approach to pre-IMRT dental care is recommended. ence confirmed this. However, due to the paucity of data in literature, comparisons cannot be made. Résumé Thanks to RaDC, it was possible to reduce the number of or even totally avoid tooth extractions in the majority of patients Introduction: L’IMRT est implémentée au Département de (50% more patients with no extractions, Tab. VII), since IMRT radio-oncologie de l’Hôpital de Zurich depuis 2002. Outre une creates more low- and intermediate-risk areas (that would diminution de la xérostémie, son avantage principal dans les previously have been high-dose areas), allowing less invasive régions de la tête et du cou réside dans une réduction substan- dental treatment to be performed. tielle du RON (de ~ 5–10% à ~ < 1%). In this context, the rarity of facial swelling after RaDC is also Les procédures standards lors des soins dentaires préradio- clinically relevant. This is yet another advantage of RaDC, thérapeutiques ont été ajustées afin d’être moins invasives since time is no longer lost waiting for swelling to abate: the pour les patients soumis à l’IMRT depuis août 2006. planning CT serves as the basis for computer-assisted 3-dimen- Patients et méthode: Cet article présente les résultats d’une sional calculation of radiation dose delivery to the tissues/tu- période d’un suivi de 3 ans pour des patients qui ont reçu des Schweiz Monatsschr Zahnmed Vol. 121 3/2011 221
  • 7. soins dentaires adaptés aux risques avant l’IMRT pour des currence de degré 3, et pas de résection de la mandibule), et cancers de la tête et du cou (n = 161). Des patients traités avec moins d’extractions dentaires grâce au traitement dentaire des soins dentaires standards (n = 143) avant l’IMRT de 01/2002 adapté aux risques. à 07/2006 ont servi de contrôle. Conclusion: Sur la base des données présentées ici, le traite- Résultats: Les analyses du RON ont révélé des taux d’inci- ment dentaire adapté aux risques est fortement recommandé dence égaux pour les deux périodes (1,5% degré 2, pas d’oc- pour les patients soumis à l’IMRT. 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