Radiation Therapy and Considerations for Internal Fixation Devices

Malignant tumors of the lower oral cavity with infiltration of the mandible frequently require segmental bone resections. The resulting loss of continuity in the mandibular arch causes a significant functional and esthetic deficit. A decisive step in the improvement of quality of life in these patients was the development of alloplastic defect bridging devices. Various techniques and materials can be applied.1–8

However, some authors9 consider subsequent tumor irradiation in the presence of metal implants to be problematic, especially in exposed areas such as the mandible.

As a result of backscatter phenomena, dose enhancement may arise at the interface with denser material. Known as hot spots, these areas of increased radiation exposure are considered clinically relevant when in tissue cross section they exceed an area of approximately 2 cm2 and attain dose values of more than 100% of the intended dosage of the target volume.10

The interface problem between more and less radiodense materials has been known for a long time. Measurements for a depth–dose curve at these borderlines of different materials have already been described.11–25

The question is whether there exists the danger of increased dosage (“hot spots”) when using metal reconstruction plates as mandibular bridging devices during irradiation of head and neck tumors. Are there further differences related to the density of the material that may, as a result, possess other characteristics with respect to transmission and backscatter? Are there differences reflecting the type of radiation used? Furthermore, does the possibility of osseointegration of metal screws used for fixation of reconstruction plates exist at all? How do the covering soft tissues react to external beam radiation, especially with respect to hardware exposure (extrusion) through the skin?

All of these questions are controversially discussed and still open. Since there is a need for reproducible results, it seems prudent to perform simulations by means of an irradiation phantom model. There exist three main measurement designs such as thermoluminescence dosimetry,26–30 ionization cham- ber,30–35 and film dosimetry.24,27,31,35,36 Also, calculations us-

ing the Monte Carlo method are reported in the literature.34,37 More or less imprecise, however, are the reports on the distance between measuring point and metal (Table 38.1).

The question of whether irradiation can disturb or hinder osseointegration of metal screws, however, cannot finally be answered without animal experimental studies. Schweiger38 inserted titanium implants into irradiated mandibles (60 Gy) of male beagle dogs. Although statistical significance cannot be related to the results, osseointegration was achieved in half of the irradiated specimens.

Montag39 reports a study with rabbits, which were irradiated after the insertion of titanium implants (Co60, 60 Gy). His results show a significant reduction of osseointegration, which was normalized after a 150-day survival period compared to a 90-day survival period without irradiation.

Lange et al.40 report on a study involving female dogs, in which the insertion of titanium implants into the mandible was performed before and after irradiation. The results demonstrate problems with osseointegration when the implants are inserted immediately before or a few months after irradiation. Six months after irradiation, the osteogenic activity has recovered and is sufficient to integrate titanium implants.

To now draw a conclusion concerning radiation therapy and implants, clinical results and experiences have to be compared with the results obtained in phantom measurements and animal studies. Until the present, radiation therapy is consi-dered to diminish the osseointegration process of implanted alloplastic materials owing to its effect on osseous cellular regenerative properties. Since a considerable number of continuity defects bridged with bone plates function well, radiation therapy does not seem to be an absolute contraindication with respect to the presence of implanted metallic foreign bodies.41–50 It would then appear to be obvious that the reduced regenerative capacity of irradiated bone is not a major risk factor for the long-term osseointegration of screw implants according to the aforementioned studies.

If the assumption that radiation-induced altered bone meta-

bolic processes exhibit a dynamic character is true, then the timing of alloplastic reconstruction should not coincide with maximum bone damage (i.e., loss of vitality). This emphasizes the importance of understanding the time course of radiation-induced changes in the bone. The influence of dose, fractionation, and radiation field on bone regeneration, as well as the patient’s individual response, need to be taken into consideration.

In the scope of this article phantom measurements, animal studies, and clinical experiences and results are highlighted.

Dosimetry on an Irradiation Phantom

This investigation is performed using four different metals, each subjected to telecobalt-60 irradiation (Philips cobalt device, 1.3-MeV photons) and 8-MeV photon irradiation (Philips Linac SL 75/20). The field size is 20 20 cm2; the focus surface distances are 80 cm and 100 cm, respectively.

1.Titanium (pure)

2.Steel (DIN 4435)

3.Lead (pure)

4.Aluminum (pure)

The metals used exhibit the form of 2- and 3-mm-thick square plates with an edge length of 5 and 6 cm, respectively. To determine the influence of screw holes, customary stainless steel and titanium AO-reconstruction plates were examined as well. Edge effects were investigated using strips of steel and titanium, which differed from the reconstruction plates only in that they did not have any holes.

In preliminary tests, the angle of the incident beams was varied in order to evaluate any possible effects resulting from a deviation from the perpendicular. The effects to be examined are limited to the immediate vicinity of the metal–tissue interface (i.e., less than 2 mm). This created complications for both the measurements made using ionization chambers and with thermoluminescence dosimeters (TLD)27–30,51 since the measured volumes in both methods do not correspond to the dimensions of the areas to be measured.

Customary TLDs have a diameter of 1 mm. If these have to be protected from moisture in simulations with a plastic coat, the diameter is increased up to 1.8 mm.

Therefore, we selected an experimental arrangement of the following construction (Figure 38.1). Water and polystyrene were chosen as a tissue substitute since muscle and other soft tissues have the same physical density as these materials. The metal specimens lay in a water bath on a plastic foil 0.1 mm thick. Placed under the water bath one on top of the other were three originally packed Kodak-X-Omat-V2 films on 1- (for cobalt irradiation) or 2-cm-thick (for 8-MeV photon irradiation) polystyrene plates. Irradiation is conducted from below to determine the backscatter effect, whereas the absorption can be measured conducting irradiation from above. The distance in water was also 1 cm for cobalt irradiation and 2 cm for 8-MeV photon irradiation. The film cover and the

plastic foil at the bottom of the water bath leads to measuring points (middle of the film) of 0.45 mm, 1.15 mm, and 1.85 mm either in front or behind the metal test object.

The dose in front of or behind the metal specimens was registered by film blackening. As the metal specimens had enough space between them, there are large enough areas of undisturbed film blackening, which can be compared with the areas at the edges or the holes or with the regions behind or in front of the metal surfaces. Quantification can be obtained when calculating the ratios of the relative dose values on the depth–dose curves of the two irradiation devices, which corresponded to the blackening of films registered in a polystyrene phantom parallel to the beam direction and which has the same optical density as the metal specimen sites of the experimental films. For all optical densities, mean values of several points are taken, which are measured on places where constant dose distribution can be assumed. The mean of several measured values taken independent of the metal test objects is used as a reference value.

Animal Studies

In the scope of an animal study, bilateral mandibular continuity resections were performed between the canines and premolar teeth in 28 full-grown sheep. The defect on the left side was bridged with a conventional AO reconstruction plate, the one on the right with a THORP plate (Figure 38.2). The 3-mm-thick resected bone pieces served as autogenous grafts, were turned 180°, and then reinserted into the gaps.

On the left side, the resected bone was wedged under eccentric compression drilling because of the ovally shaped holes of the AO plate (spherical gliding hole principle). This was not possible on the right side, where the THORP system was used.

FIGURE 38.2 Basal teleradiography showing the two different plate systems applied (12 weeks postoperatively, the resected bone pieces served as bone grafts and have already healed).

The plates were fixed with plasma-coated hollow screws (THORP system) and solid titanium screws (conventional AO reconstruction plate). Postoperatively, the animals were permitted full masticatory function. To simulate the clinical situation, some of the animals were additionally irradiated with 60Co gamma rays with a dose up to the equivalent of 60 Gy.52 The observation period was as long as 24 weeks.

The sample was divided into four groups. Three groups (I–III) were subjected to fractionated lateral counterfield irradiation with 60Co gamma rays (Philips cobalt-60 radiation generator). The isocenter of the irradiation was in the mediosagittal plane at a distance of 76 cm between the focus and the skin. The line between the animal’s lips served as the cranial boundary. The fractionation schedule (Figure 38.3) shows the different irradiation modifications. Single dose was 4 Gy. Irradiation was performed three times a week. Postoperative

irradiation was not begun until 14 days after bridging osteosynthesis.

According to Ellis52 the fractionation of 3 4 Gy per week selected for the animal experiment corresponds to an effective total dose of 20 Gy (Group I) and 60 Gy (Group II and III) as compared with the 5 2 Gy per week fractionation normally used for clinical application. For comparison, a nonradiated control group (Group O) was used.

Incorporation of the implants was demonstrated by means of sequential fluorochrome labeling of the osteogenic activity53 during the observation period of 24 weeks. After sacrifice of the animals, thin grind sections54 of the screw-bear- ing areas were made, and the osteogenic activity indicated by different fluorochrome marker areas was quantified using digital planimetry.

Clinical Studies

In 20 patients with carcinomas of the floor of the mouth, continuity resections of the mandible were necessary. The patient’s mandibles were reconstructed immediately by means of a bridging titanium bone plate (AO-3DBRP system). All patients were subjected to postoperative full-dose irradiation therapy (60 Gy) with 60Co.

For various reasons it was possible to harvest bone specimens at different time periods after termination of irradiation therapy. Here, of course, the incorporation of the fixation screws could not be demonstrated by means of any fluorochrome marking. Thin ground sections of the specimens were made, and the vital osteocytes at the interface between the screw and the bone were quantitatively recorded. By means of this method the time period of maximum bone damage could be detected.

In another sample of 140 patients we studied the clinical situation and especially the soft tissue condition using the THORP reconstruction plate. Out of this sample, 64 patients were prospectively evaluated.55 The plates were left in place for an average time of 13.4 months. Since there has been no standardized documentation sheet available, the Freiburg documentation sheet for the THORP reconstruction plate was created. The sheet designed for entry into a personal com-

puter (PC) for statistical analysis comprises a total of six sections (patient data, history, therapy, complications and healing process, function, results) to provide information useful for describing and explaining causal problems.

To understand the entire problem, these three variables— dosimetry, animal, and clinical studies—must be evaluated and their correlations factored together. The question of increased dosage at the interface of bone and metal implant (i.e., screw and plate) can clearly be answered. Quantitative record of backscatter when using plates 2 mm thick at a distance of 0.45 mm for 60Co irradiation (Figure 38.4a) was 46% of the applied dose for lead, 14.5% for steel, 12.5% for titanium, and 7% for aluminum. When using 8-MeV photons (Figure

38.4b) backscattering of 58% for lead, 16% for steel, 12.5% for titanium, and 8% for aluminum could be recorded. At a distance of 1.85 mm from the metal test objects the values dropped to 8%, 2.5%, 3%, and 2.5% for 60Co irradiation and to 31%, 5%, 4%, and 4.5% for 8-MeV photon irradiation respectively. This data obtained from a phantom model, however, do not answer the question as to whether they are important as well in a biological system.

The dose values behind the metal plates (transmission) at a distance between 0.45 mm and 1.85 mm already approached the values determined corresponding to the absorption of the material thickness asymptotically (Figure 38.5).

The type of radiation used—in this case 60Co and 8-MeV

photons—showed no significant difference regarding backscatter and transmission. The calculations made by Rosendahl and Kirschner37 and Mian et al.34 agree with our results24,56 very closely, although it should be noted that when extrapolating our measurements at a distance of 0.03 mm in front of the metal test object, we would observe greater dose enhancement ( 16 2%). Mian et al.34 found corresponding results in their investigations between calculation and measurements.

There is no essential influence on backscatter exhibit size or perforation of the individual test objects. In preliminary tests, the direction of transmission was seen to depend upon the thickness of the material used. The metal/screw hole in-

terface behaves like the interface at the edges. When varying the angle of the incident beam (deviation from the perpendicular to an angle of 30°) there proved to be no significantly measurable difference in dose increase in front or dose decrease behind the metal specimen.

The differences related to the density of the material are, with respect to backscatter phenomena, clinically irrelevant. Only lead exhibits, both in close proximity to the metal plate and approximately 2 mm far from it, a different behavior as far as backscatter phenomena are concerned.

Under 60Co irradiation, the comparison between titanium and stainless steel plates shows no decisive radiophysical advantage for titanium. As far as irradiation with 8-MeV pho-

tons is concerned titanium (12.5%) provides to be slightly better than steel (16%). With regard to the degree of relative dose enhancement the angle of incident beam appears to be of relatively minor importance, as has already been described by other authors.17,33,37,57 However, it must be presumed that in the case of irradiation perpendicular to the metal test object, the phenomena of backscatter and decreased transmission at maximum intensity can be measured.36

This implies that for postoperative irradiation significant dose enhancement owing to backscatter can be observed in a range of under 1 mm in front of the implanted metal plate. In most cases backscatter is compensated by employing the opposing field technique, which reduces the dose behind the plate (Figure 38.6). Care should be taken, however, in singlefield irradiation treatment when the implant is in the region of maximum dose, especially when this lies above the target volume dose, and in fractionated schedules58,59 in which the biological effect of the dose is greater.

Irradiation damage to the skin as a result of an increased dose due to backscatter has implications when inserting metal implants and can only really occur in this small area. However, even this small area is important for the incorporation and osseointegration of metal screws. Therefore, it is of high interest whether the bone is able to recreate its vitality and within which time period it does so. Regarding the covering soft tissue layer, percutaneous radiation therapy should theo- retically—as a result of the phantom experiments—not have any influence on the integrity of the implant, if it is of sufficient thickness.

Concerning the animal studies the comparative group receiving no irradiation (group 0) exhibits bony regeneration progresses smoothly without interruption during the entire observation period (Figure 38.7a). The sample with preoperative irradiation (Group I) presents a low initial osteogenic activity, which is steadily increasing throughout the follow-up period (Figure 38.7b). In our opinion this finding should be interpreted such that the preoperative irradiation has hit a noninjured bone. The osteoblasts apparently respond by reducing their normal activity. Not until the implantation trauma occurs, does the regenerative processes begin to prevail over the irradiation damage. A constant increase in osteogenic activity continues beyond the 24-week observation period.

The same phenomenon just described can initially be observed under preoperative and postoperative irradiation (Group II).

Here, too, increasing osteoblast activity begins after implantation, despite irradiation, but then decreases between the 12th and 16th week before it begins to increase again. It is surprising that in this group, too, there is an overall increase in osteogenic activity throughout the entire observation period (Figure 38.7c). It therefore must be assumed that the regenerative processes induced by the drilling trauma prevails over the irradiation damage.

Another fact that possibly contributes to this phenomenon is that the so-called sandwich technique used for irradiation gives the bone a chance to recuperate for 2 weeks between the sessions. Generally, however, in Group I and II the bone regeneration seems to be sufficient even initially to provide secure anchorage of the fixation screws at the bone/implant interface.

Postoperative irradiation (Group III) shows high osteogenetic activity immediately after the implantation comparable to Group 0 (Figure 38.7d). It decreases only slightly up to the 8th or 10th week, after which time it weakens rapidly. Not until the 20th week is an increase in activity resumed. In other words, when the maximum irradiation response begins, the osteogenic activity slows down after the implant has already healed in. Still, at least in the animal model, recuperation can be observed again after a relatively short period. Figure 38.8a,b shows examples of characteristic fluorescent-optic images of the bone structures around solid titanium screws. To the naked eye, the osteogenic activity in the two samples appears to be nearly identical. The differences described earlier do not show up until the morphometric analysis. Scanning electron microscopic images also exhibit direct contact between the implant and bone with no intermediate tissue in all the groups, independent of the irradiation dose.

No differences within the individual groups with regard to the type of screw, either hollow or solid, are observed in quantitative evaluation of osseointegration (Figure 38.7a–d). Radiographs of the screws in the harvested mandibular segments prior to its embedment confirm these findings (Figures 38.9a,b).

The clinical results correspond well to the results obtained in the animal studies. In the group of the 20 patients we could harvest bone specimens at different times within the follow-

FIGURE 38.7 Osteogenetic activity/mm2 over 24 weeks after implantation. Solid titanium screw (in front), hollow titanium screw (behind). (a) Group 0 control group. (b) Group I preoperative

up period of 600 days after termination of full-dose irradiation (60 Gy 60Co). We could register a minimum of vital osteocytes per square unit at 180 days. At that time the number of vital osteocytes has been diminished to 20% of the initial value. In the following time period, we can observe a slow

irradiation. (c) Group II preand postoperative irradiation. (d) Group III postoperative irradiation.

but constant increase of the rate of vital osteocytes. The initial value, however, is reached only to approximately 80% within the entire follow-up period (Figure 38.10). Nevertheless, osteoneogenesis into the hollow screws is observed even under high irradiation dosage (Figure 38.11).

FIGURE 38.8 (a) Bony structure around a solid titanium screw 24 weeks after bone plating (sheep bone specimen, fluorescent microscopy, magnification 60 , control group). (b) Bony structure

around a solid screw 24 weeks after bone plating (sheep bone specimen, fluorescent microscopy, magnification 60 , postoperative full dose irradiation 48 Gy, 60Co).

FIGURE 38.9 (a) Radiograph of a solid screw after full-dose irradiation (48 Gy, 60Co) 24 weeks after implantation showing osseointegration (sheep). (b) Radiograph of a hollow screw after full-dose ir-

Soft tissue complications were the main problem. Interesting differences were found with regard to the parameters in the early ( 4 weeks postoperatively) and in the late phase ( 4 weeks postoperatively). In the early phase the relevant factors were primarily the patient’s constitution, so-called mechanical functionalfactorsinconjunctionwiththeoperation(i.e.anteriorplate location, bridging of large defects, extensive lymph node resections), and factors that interfered with primary wound healing (e.g., alcohol abuse, smoking, poor oral hygiene).

Radiotherapy had the most important influence in the late phase; 39% of the patients exhibited a plate penetration through the surrounding soft tissues. In more than 80% of these patients we observed a skin perforation (Figure 38.12).

We obtained the poorest results following anterior plate bridging in combination with percutaneous irradiation. Under these circumstances 70% of the plates perforated the covering soft tissue. In the lateral (52.4%) and anterolateral area (44.5%) the ratio of perforation and nonperforation was about the same (Figure 38.13a,b). Apparently, irradiation has a major effect on the covering soft tissue in the anterior region. The amount of “tension” tolerated by the soft tissue covering the plate is exceeded when percutaneous irradiation is applied

radiation (48 Gy, 60Co) 24 weeks after implantation showing osseointegration (sheep).

owing to the increase in tissue induration. The soft tissue lying over the plate loses its elasticity and becomes stiff. The rigid plate presses against the altered soft tissue, and after a while perforation results. Extensive lymph node operation (radical neck dissection) also increases the danger of soft tissue perforation. Statistical analysis shows that perforation occurred less frequently when the lymph node operation was more localized (i.e. suprahyoid lymph node removal), despite anterior plate location and postoperative percutaneous irradiation with full-tumor dose (60 Gy).

To solve these problems, two therapeutic procedures may be helpful.

First, to reduce the effect of the percutaneous irradiation therapy, intraoperative radiation therapy (IORT) presents advantages when it is necessary to use a reconstruction plate in the anterior mandible. To date, only few reports on the use of IORT in head and neck surgery have been published.60–63 IORT makes it possible to apply the necessary dose without irritating skin, vessels, nerves, salivary glands, and bone. The irradiation cone is placed directly upon the tumor bed (Figure 38.14). In this way, the benefit of irradiation can be assured without harm to critical structures, particularly skin and

FIGURE 38.11 Growth of newly formed bone into the screw lumen passing the perforations of the side of the screw (human specimen, toluidine blue, magnification 42 , full-dose irradiation 60 Gy, 60Co).

bone. This new therapeutic approach might solve the severe problems of soft tissue complications in these particular cases. Although experience to date with IORT in head and neck surgery does not allow definitive conclusions regarding the

a

FIGURE 38.12 Skin perforation after anterior alloplastic mandibular reconstruction and full-dose percutaneous radiotherapy.

improvement of survival, the advantages of the method cannot be disputed. When myocutaneous flaps or free vascularized grafts are used to cover defects, the lower dose required for postoperative radiotherapy after IORT means less damage to the transplants. In some cases IORT can result in shorter treatment times, allowing the patient to resume his or her social life sooner. The quality of life is significantly improved. More studies are necessary to show whether the currently applied percutaneous dose of 50 Gy after lymphadenectomy can be reduced any further.

We recommend intraoperative histophathological control of the tumor margins using frozen section evaluation of the

b

FIGURE 38.14 Irradiation cone is placed directly upon the tumor bed between both mandibular bone stumps.

borders to be able to achieve total tumor removal. Suspicious areas must be resected again during the same operative session.

IORT in conjunction with postoperative percutaneous radiotherapy seems to be an effective treatment of tumors of the head and neck. The disadvantage, however, is that it requires elaborate technical equipment, which will keep restrictions on the method for some time to come.

Second, concerning rehabilitation therapy with osseointegrated dental implants,64–66 we started to reconstruct the osseous defect primarily. That means that especially in cases with anterior resections of the mandible, there is primary reconstruction using microvascular bone (e.g., fibula bone grafts). Primary bony reconstruction is also favored by many other authors.25 By means of immediate bone repair, we are able to reduce soft tissue tension across the sharp-edged metal plate. The soft tissue heals to the periosteal and soft tissue surface of the graft. Even plate-wrapping, for example with lyodura, is not sufficient to prevent soft tissue perforation in a long-term follow up. Within a short-term interval, however, this technique may be helpful.

To summarize the data and findings of the three investigation compartments of this study the following remarks can be made.

The question of local enhancement of dosage following implantation of metallic “foreign bodies” can in correlation to other authors24,26,27,29,30,32–37 be answered in so far that only in a very close distance from the implanted material a mea-

surable increase of dosage is recorded. This finding applies at least to the metallic bone plate material commonly used today. Increased dosage is found as backscattering in front of implanted metal plates (i.e., within the soft tissues), whereas behind the metal plate a slight reduction of dosage, also closely adjacent to the metal surface, is recorded.

The dose values behind the metal plates already reach the values corresponding to the resorption of the material thickness asymptotically at a distance between 0.45 mm and 0.85 mm. A protection of the target volume by means of the relatively thin metal plates is not to be expected. This is at least valid for irradiation using 60Co and 8-MeV photons.

The differences of the radiation quality are of minor importance within this energy range. Since the observed backscatter phenomena already exhibit at a distance of approximately 2 mm from the implanted material a range of less than 5% of the applied dosage, they cannot be made responsible for the often observed extrusions of bridging plates alone.

The animal studies show that under the condition of stable fixation of the implanted material, osseointegration of the fixation screws even under perioperative and postoperative radiation using 60Co gamma rays is possible. It seems plausible to assume that the implantation trauma acts as a stimulus for the osteoblasts and that this stimulus prevails over the irradiation effects upon bone regenerative capacity.

The intensity of the recuperation process is dependent upon the range of the applied dose42 and the time of irradiation.67 As our animal study shows, osseointegration can be achieved before the maximum radiation damage of the bone takes place. It remains unclear as to whether that will happen at the time of the lowest osteogenic activity. Usually bridging plate placement is performed immediately after bone resection so that this problem does not really occur.

In the case of a secondary defect bone grafting, we recommend waiting longer than 6 months. It seems more suitable to perform a secondary grafting procedure as early as 1.5 years after the termination of radiation therapy.

In correlating the results of the animal studies to the clinical conditions the difference in tissue response between animals and humans must, of course, be taken into consideration. Bone regeneration is certainly better in 1-year-old sheep than in tumor patients 40 years of age and older. The results of investigations using rabbits39,67–69 should be interpreted very critically, since these animals have been shown to have a high osteogenic potency per se.

Sheep and dogs, in our opinion, are more suitable for animal models of bone regeneration, implantation of metal screws, and irradiation.

Summary

The application of perioperative or postoperative radiation therapy for malignancies while osteosynthesis material is in place is the subject of much controversy. The reason is that

430

local dose increases in the region of the metallic plates may inadvertently cause damage to the surrounding tissue.

An irradiation phantom was used to measure dose increases concerning backscatter of different metals. We were able to demonstrate that a 12.5% to 16% increase in the radiation dose can be observed for titanium and steel at a distance of 0.45 mm in front of the metal specimen. A comparison between titanium and steel did not demonstrate a relevant advantage for titanium.

In an animal model, mandibular bridging osteosyntheses with autogenous bone grafts were carried out in sheep and the osteogenic activity at the bone/fixation screw interface was assessed qualitatively and quantitatively under perioperative and/or postoperative telecobalt irradiation. The same procedure was followed with human bone sections.

Both the experimental and the clinical results show a reduction in the osteogenic activity that appeared after a time interval depending on the mode and dose of radiation. This reduction appeared at latest after the 12th week concurrently with the radiation-induced vascular lesions. In humans the radiation-induced bone lesions reached the maximum value around 180 days after the end of radiotherapy. A further recovery of the bone cannot be expected until at least 2 years later.

From this it may be concluded that a bridging osteosynthesis should be performed either as a primary procedure (i.e., before the radiolesions of the bone reach the maximum) or as a secondary procedure (i.e., following revitalization of the bone tissue).

Soft tissue complications (i.e., extrusion of the reconstruction plates through the skin) frequently occur in the anterior region. In particular, a thin coverage becomes stiff under fulldose irradiation, and the tension between soft tissue and hard plate can no longer be compensated.

Intraoperative radiation therapy avoids skin damage, since it is directly applied to the tumor bed. Also, immediate microvascular bone repair has a positive influence. Both therapy modifications can help to reduce soft tissue complications.

Acknowledgments The authors would like to thank Prof. Dr. Michael Wannenmacher, former head of the Department of Radiotherapy, University of Freiburg, for his support of this study and Prof. Dr. Herrmann Frommhold, head of the Department of Radiotherapy, University of Freiburg, for his advice in all sorts of questions.

Thanks also to Dr. Norbert Hodapp, Department of Radiotherapy, University of Freiburg, for his extremely valuable help during the phantom measurements.

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