Dosimetric comparison of intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) in total scalp irradiation: a single institutional experience.

PURPOSE: Total scalp irradiation (TSI) is a rare but challenging indication. We previously reported that non-coplanar intensity-modulated radiotherapy (IMRT) was superior to coplanar IMRT in organ-at-risk (OAR) protection and target dose distribution. This consecutive treatment planning study compared IMRT with volumetric-modulated arc therapy (VMAT). MATERIALS AND METHODS: A retrospective treatment plan databank search was performed and 5 patient cases were randomly selected. Cranial imaging was restored from the initial planning computed tomography (CT) and target volumes and OAR were redelineated. For each patients, three treatment plans were calculated (coplanar/non-coplanar IMRT, VMAT; prescribed dose 50 Gy, single dose 2 Gy). Conformity, homogeneity and dose volume histograms were used for plan. RESULTS: VMAT featured the lowest monitor units and the sharpest dose gradient (1.6 Gy/mm). Planning target volume (PTV) coverage and homogeneity was better in VMAT (coverage, 0.95; homogeneity index [HI], 0.118) compared to IMRT (coverage, 0.94; HI, 0.119) but coplanar IMRT produced the most conformal plans (conformity index [CI], 0.43). Minimum PTV dose range was 66.8% -88.4% in coplanar, 77.5%-88.2% in non-coplanar IMRT and 82.8%-90.3% in VMAT. Mean dose to the brain, brain stem, optic system (maximum dose) and lenses were 18.6, 13.2, 9.1, and 5.2 Gy for VMAT, 21.9, 13.4, 14.5, and 6.3 Gy for non-coplanar and 22.8, 16.5, 11.5, and 5.9 Gy for coplanar IMRT. Maximum optic chiasm dose was 7.7, 8.4, and 11.1 Gy (non-coplanar IMRT, VMAT, and coplanar IMRT). CONCLUSION: Target coverage, homogeneity and OAR protection, was slightly superior in VMAT plans which also produced the sharpest dose gradient towards healthy tissue.

The treatment of extensive scalp lesions using coplanar and non-coplanar photon IMRT: a single institution experience.

BACKGROUND: This clinical study compared four different cases of extensive scalp malignancies treated by intensity-modulated radiation therapy. The merits of coplanar and non-coplanar Step-and-shoot total scalp irradiation techniques were evaluated against the background of the literature. METHODS: Four patients (angiosarcoma, n=2, cutaneous B-cell non-Hodgkin lymphoma, B-NHL, n=1, mycosis fungoides, n=1) treated between 2008 and 2012 at our institution were retrospectively analyzed. For every patient with executed coplanar plan, a non-coplanar plan and vice versa has been calculated additionally for direct comparison. Three patients underwent limited surgery before radiotherapy. Individual adapted bolus material was used for every patient (helmet). Total scalp dose was 30 Gy (B-NHL, mycosis fungoides) and 50 Gy (angiosarcoma) with fractional doses of 2.0-2.5 Gy (without sequential local boost in three patients). Conformity and homogeneity indexes and dose volume histograms were used for treatment plan comparison. RESULTS: Dose hot spots were higher in coplanar plans (110-128% Dmax). Non-coplanar plans showed a more homogeneous dose distribution (HI = .12 - .17) and superior PTV coverage (88 - 96%). Target dose coverage was 81-117% in non-coplanar and 30-128% in coplanar plans. Coplanar plans yielded a stronger dose gradient across the target (.7-1.6 Gy/mm) compared to non-coplanar plans (.8-1.3 Gy/mm). The most conformal plan was a non-coplanar plan (CI = .7). Mean and maximum brain doses were comparable and showed an almost linear decrease between min. and max. dose. The optic chiasm and brain stem was spared most with non-coplanar plans, mean doses to the lenses ranged between 4 and 8 Gy and were higher in non-coplanar plans as were doses to the optic nerves.Radiotherapy tolerance was acceptable and acute side effects included erythema, scalp pain, alopecia and radiodermatitis which all spontaneously resolved. Two patients accomplished partial response, two patients showed complete response after radiotherapy. Three patients had locally controlled tumors without recurrence until their deaths or at last follow up, one patient had local progression shortly after radiotherapy. CONCLUSIONS: Photon-IMRT is an effective and feasible approach to treat extensive scalp malignancies. Non-coplanar beams could increase dose homogeneity and PTV coverage and might reduce doses particularly to the optic chiasm.

Parotid gland-recovery after radiotherapy in the head and neck region--36 months follow-up of a prospective clinical study.

BACKGROUND: The aim of the present study was to evaluate the recovery potential of the parotid glands after using either 3D-conformal-radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) by sparing one single parotid gland. METHODS: Between 06/2002 and 10/2008, 117 patients with head and neck cancer were included in this prospective, non-randomised clinical study. All patients were treated with curative intent. Salivary gland function was assessed by measuring stimulated salivary flow at the beginning, during and at the end of radiotherapy as well as 1, 6, 12, 24, and 36 months after treatment. Measurements were converted to flow rates and normalized relative to rates before treatment. Mean doses (D(mean)) were calculated from dose-volume histograms based on computed tomographies of the parotid glands. RESULTS: Patients were grouped according to the D(mean) of the spared parotid gland having the lowest radiation exposure: Group I - D(mean) < 26 Gy (n = 36), group II - D(mean) 26-40 Gy (n = 45), and group III - D(mean) > 40 Gy (n = 36). 15/117 (13%) patients received IMRT. By using IMRT as compared to 3D-CRT the D(mean) of the spared parotid gland could be significantly reduced (D(mean) IMRT vs. 3D-CRT: 21.7 vs. 34.4 Gy, p < 0.001). The relative salivary flow rates (RFSR) as a function of the mean parotid dose after 24 and 36 months was in group I 66% and 74%, in group II 56% and 49%, and in group III 31% and 24%, respectively. Multiple linear regression analyses revealed that the parotid gland dose and the tumor site were the independent determinants 12 and 36 months after the end of RT. Patients of group I and II parotid gland function did recover at 12, 24, and 36 months after the end of RT. CONCLUSIONS: If a D(mean) < 26 Gy for at least one parotid gland can be achieved then this is sufficient to reach complete recovery of pre-RT salivary flow rates. The radiation volume which depends on tumor site did significantly impact on the D(mean) of the parotids, and thus on the saliva flow and recovery of parotid gland.

Effect of Cisplatin on parotid gland function in concomitant radiochemotherapy.

PURPOSE: To determine the influence of concomitant radiochemotherapy with cisplatin on parotid gland tissue complication probability. METHODS AND MATERIALS: Patients treated with either radiotherapy (n = 61) or concomitant radiochemotherapy with cisplatin (n = 36) for head-and-neck cancer were prospectively evaluated. The dose and volume distributions of the parotid glands were noted in dose-volume histograms. Stimulated salivary flow rates were measured before, during the 2(nd) and 6(th) weeks and at 4 weeks and 6 months after the treatment. The data were fit using the normal tissue complication probability model of Lyman. Complication was defined as a reduction of the salivary flow rate to less than 25% of the pretreatment flow rate. RESULTS: The normal tissue complication probability model parameter TD(50) (the dose leading to a complication probability of 50%) was found to be 32.2 Gy at 4 weeks and 32.1 Gy at 6 months for concomitant radiochemotherapy and 41.1 Gy at 4 weeks and 39.6 Gy at 6 months for radiotherapy. The tolerated dose for concomitant radiochemotherapy was at least 7 to 8 Gy lower than for radiotherapy alone at TD(50). CONCLUSIONS: In this study, the concomitant radiochemotherapy tended to cause a higher probability of parotid gland tissue damage. Advanced radiotherapy planning approaches such as intensity-modulated radiotherapy may be particularly important for parotid sparing in radiochemotherapy because of cisplatin-related increased radiosensitivity of glands.

The influence of different irradiation doses and desensitizer application on demineralization of human dentin.

The aim of the present study was to evaluate the effect of different irradiation doses after desensitizer application on the onset of initial demineralization of human dentin in situ. The root surfaces of 45 freshly extracted caries-free human molars were cleaned, thereby removing the cementum. From each tooth two root dentin specimens were prepared. The specimens were distributed among the following experimental groups: 0, 0.5, 1, 2 and 5Gy. The irradiation dose was fractionally applied (0.5Gy/day). One dentin specimen of each group was inserted into both buccal aspects of nine intraoral mandibular appliances. On one side the specimens were additionally coated with the desensitizer Hyposen (H). On the other side, the specimens were left untreated (C). The appliances were worn by nine persons for five weeks day and night. During meals, the appliance was stored in 10% sucrose solution. After the in situ period, slabs (150microm) were ground and studied using a polarized light microscope. Concerning radiation dose, significant differences were observed between the control and 5Gy group (p<0.05, Tukey s test). Pairwise comparison showed that lesion depths in groups treated with Hyposen were significantly decreased. Within the limitations of this study it can be concluded that higher radiation doses seem to increase the caries susceptibility of dentin. The additional application of a desensitizer hampers the demineralization and might have a caries-protective effect on exposed irradiated root surfaces.

The irradiation action on human dental tissue by X-rays and electrons--a nanoindenter study.

It is known that ionizing radiation is used in medicine for Roentgen diagnostics and for radiation therapy. The radiation interacts with matter, in particular with biological one, essentially by scattering, photoelectric effect, Compton effect and pair production. To what extent the biological material is changed thereby, depends on the type and the amount of radiation energy, on the dose and on the tissue constitution. In modern radiation therapy two different kinds of radiation are used: high energy X-rays and electron radiation. In the case of head-neck tumors the general practice is an irradiation with high energy X-rays with absorbed dose to water up to 70 Gy. Teeth destruction has been identified as a side effect during irradiation. In addition, damage to the salivary glands is often observed which leads to a decrease or even the complete loss of the salivary secretion (xerostomia). This study shows how the different energy and radiation types damage the tooth tissue. The effects of both, high X-ray energy and high energy electrons, on the mechanical properties hardness and elasticity of the human dental tissue are measured by the nanoindentation technique. We compare these results with the effect of the irradiation of low X-ray energy on the dental tissue.

Parotid-gland-sparing 3D conformal radiotherapy in patients with bilateral radiotherapy of the head and neck region--results in clinical practice.

The aim was to improve the prediction rate of hyposalivation after using a modern 3D-conformal-radiotherapy-technique (3D-CRT) by sparing of the contralateral parotid gland. Between June 2002 and October 2006, 107 patients (90 male, 17 female, average age: 58 years) with squamous cell carcinoma of the head and neck were included in a prospective, non-randomized study. All patients were treated using 3D-CRT. Parotid function was assessed by measuring stimulated salivary flow before, during and at the end of radiotherapy, as well as 1, 6 and 12 months after radiotherapy. Measurements were converted to flow rates and normalized relative to that before treatment. Mean doses (D(mean)) were calculated from dose-volume histograms (DVHs) based on computed tomographies (CTs) for the left and right parotid gland separately. Patients were grouped according to the D(mean) of the lowest irradiated parotid gland. Group I included all patients who received a D(mean)<26Gy (n=23), group II D(mean) 26-40Gy (n=38) and group III D(mean)>40Gy (n=46). By the time of 6 months after irradiation, salivary flow rates decreased continuously during the therapy. In group I the flow rate decreased to 59%, in group II to 40% and in group III to 14%, p<0.05. One year after irradiation a recovery effect could be measured in all groups. A sufficient saliva flow rate can be proven if one parotid gland is spared with a D(mean) dose <26Gy. Approximately, one quarter of the participants showed a significant improvement.

Effect of tumor therapeutic irradiation on the mechanical properties of teeth tissue.

Tumor irradiation of the head-neck area is accompanied by the development of a so-called radiation caries in the treated patients. In spite of conservative therapeutic measures, the process results in tooth destruction. The present study investigated the effects of irradiation on the demineralization and remineralization of the dental tissue. For this purpose, retained third molars were prepared and assigned either to a test group, which was exposed to fractional irradiation up to 60 Gy, or to a non-irradiated control group. Irradiated and non-irradiated teeth were then demineralized using acidic hydroxyl-cellulose gel; afterwards the teeth were remineralized using either Bifluorid12 or elmex gelee. The nanoindentation technique was used to measure the mechanical properties, hardness and elasticity, of the teeth in each of the conditions. The values were compared to the non-irradiated control group. Irradiation decreased dramatically the mechanical parameters of enamel and dentine. In nonirradiated teeth, demineralization had nearly the same effects of irradiation on the mechanical properties. In irradiated teeth, the effects of demineralization were negligible in comparison to non-irradiated teeth. Remineralization with Bifluorid12 or elmex gelee led to a partial improvement of the mechanical properties of the teeth. The enamel was more positively affected by remineralization than the dentine.

[Presentation of a 3D conformal radiotherapy technique for head-and-neck tumors resulting in substantial protection of the parotid glands]. / Etablierung einer 3D-Konformationstechnik zur Radio therapie von Kopf-Hals-Tumoren unter Berücksichtigung der Parotisschonung.

PURPOSE: The aim of this study was to improve the irradiation technique for the treatment of head-and-neck tumors and, in particular, to make use of the advantages found in modern 3D planning to protect the parotid glands. PATIENTS AND METHODS: For this investigation the 3D dataset of a standard patient with oropharyngeal carcinoma of UICC stage IVA was used. In the CT scans (slice thickness 5 mm) the planning target volume (PTV), the boost volume and both parotids were delineated. Three different techniques were calculated for two different dose levels (50 Gy for PTV and 64 Gy for boost volume, using single doses of 2 Gy). For technique 1 (T1) a parallel opposed field photon/electron irradiation was designed, for technique 2 (T2) an opposed/arc field irradiation was employed, and for technique 3 (T3) a combination of a static coplanar and arc field irradiation was designed. The sum doses D(min), D(max) and D(mean) for PTV, boost volume, and ipsilateral and contralateral parotid gland were evaluated, and the time needed for calculation of the plans was also determined. RESULTS: For all techniques used, the calculated doses in the PTV (D(min) 5.6 +/- 0.1 Gy, D(max) 73.7 +/- 0.1 Gy, and D(mean) 57.9 +/- 0.5 Gy) and in the boost volume (D(min) 46.9 +/- 1.5 Gy, D(max) 73.8 +/- 0.12 Gy, and D(mean) 65.8 +/- 0.9 Gy) were equal. Significant differences were found regarding the three different techniques, e.g., for the ipsilateral parotid gland D(min) (T1 = 47.4, T2 = 50.6, and T3 = 38.4 Gy) as well as for the contralateral parotid gland D(min) (T1 = 42.1, T2 = 44.2, and T3 = 17.8 Gy) and D(mean) (T1 = 51.3, T2 = 52.8, and T3 = 32.6 Gy). Regarding the three different techniques, significant differences were found in favor of T3. The determined planning times were as follows: T1 = 90, T2 = 60, and T3 = 90 min. CONCLUSION: The combination of static coplanar and arc field technique (T3) resulted in a substantially better protection as compared to both other techniques. This was especially the case with regard to the contralateral parotid gland, when the dose distributions were calculated equally for PTV and boost volume. In this study, the D(mean) dose of the contralateral parotid gland was lower than the TD(50) of 37 Gy (95% confidence interval 32-43 Gy) previously assumed by the authors. Therefore, it can be concluded that in the present study a more intensive protection of this gland and a reduction in xerostomia were possibly obtained.

[Quantitative and qualitative investigations of salivary gland function in dependence on irradiation dose and volume for reduction of xerostomia in patients with head-and-neck cancer]. / Quantitative und qualitative Speicheldrüsenfunktionsuntersuchungen in Abhängigkeit von Dosis und Volumen einer Radiotherapie zur Verringerung der Xerostomie bei Kopf-Hals-Tumoren.

BACKGROUND AND PURPOSE: Radiation treatment of head-and-neck tumors mostly leads to a damage to the salivary glands and a consequential permanent loss of saliva. The aim of this investigation was to establish a modern three-dimensional conformal radiotherapy (3D-CRT) to show a decrease in severe xerostomia in contrast to the proven conventional technique (K-RT) with photons and electrons. PATIENTS AND METHODS: Between April 2002 and September 2003, 32 patients (25 male, seven female, mean age: 58 years) with malignant tumors of the head and neck were included-after surgery or in case of inoperability with curative intent-in a prospective, nonrandomized study. 10/32 patients (31%) received K-RT with photons and electrons, and 22/32 patients (69%) 3D-CRT (six to eight photon portals). The quantity of saliva was measured as stimulated saliva flow rate (ml/5 min) prior to treatment, at the end, and 1, 6, and 12 months after termination of treatment. To find out the resulting mean dose of both parotid glands for every patient in Gray (D(mean) doses), the D(mean) doses of the ipsilateral and the contralateral parotid gland, determined by dose-volume histograms (DVHs), were averaged over. For calculation of the NTCP (normal tissue complication probability), the logistic model was used. RESULTS: In the trend the stimulated salivary flow rates were higher in the group with 3D-CRT than in the group with K-RT during the whole observation period (at 10 weeks after the start of radiotherapy 3D-CRT vs. K-RT with 1.56 +/- 1.6 vs. 0.82 +/- 1.2 ml/5 min; p < 0.1). The patients treated with the K-RT had, on average, significantly higher averaged D(mean) values than those irradiated with 3D-CRT (p < 0.012). Patients, who were irradiated with 3D-CRT for tumors of the larynx or hypopharynx, showed, on average, significantly lower D(mean) values than patients, who were treated with 3D-DRT because of oral cavity or oropharynx carcinomas or with K-RT irrespective of the primary tumor site (p < 0,003). The resulting dose for 50% complication probability (TD(50)) of the salivary glands was 36.9 Gy (30.9-43.5 Gy; 95% confidence interval). The gradient k of the curve located in point TD(50) was 7.7 (4.8-15.8; 95% confidence interval). CONCLUSION: Basically, 3D-CRT seems to be suitable as a standard for all patients with carcinomas of the oral cavity, oro- and hypopharynx. Especially in patients with tumors located in the larynx and hypopharynx, averaged D(mean) doses of both parotids during irradiation can be reached, to conserve salivary flow rates, which are similar to baseline flow rates.

[Prognostic factors after surgery and adjuvant radiotherapy in cervical cancers. A retrospective analysis of 298 patients after surgery and adjuvant radiotherapy]. / Prognosefaktoren beim operierten und adjuvant bestrahlten Zervixkarzinom. Eine retrospektive Analyse von 298 operierten und nachbestrahlten Patientinnen.

PURPOSE: To determine prognostic factors in patients with cervical cancer treated with surgery followed by radiotherapy. PATIENTS AND METHODS: In a retrospective analysis, patients treated at the Department of Radiotherapy, University of Halle-Wittenberg, Germany, from 1980 through 1993 were evaluated for local control, survival and treatment sequelae with special emphasis on prognostic factors. 298 patients (age 23-81 years, median 46 years) with cervical cancers were treated with surgery followed by radiotherapy to a minimum of 50 Gy. 250 patients received radiotherapy after radical hysterectomy with pelvic lymphadenectomy and 48 patients after hysterectomy. Most of the cancers were squamous cell carcinomas (81%) with few adenocarcinomas (12.4%). Grading was G1/G2 in 28.9% of the patients and G3/G4 in 39.6%. RESULTS: The 5-year overall survival was 68.8% for the whole group, 70.5% for squamous cell carcinomas (n = 241), 64.4% for adenocarcinomas (n = 37; not significant), 80% for G1/G2 tumors (n = 86), and 69% for G3/G4 carcinomas (n = 118; p = 0.074). Survival dependent on tumor size and positive nodes was 76.2% (n = 94) for pT1N0, 65.8% for pT1N+ (n = 31), 68.2% for pT2N0 (n = 62), and 41.4% for pT2N+ (n = 35). An impact of grading on 5-year survival was only found in patients with positive nodes: G1/G2N0 84% (n = 62) versus G1/G2N+ 64.8% (n = 23); G3/G4N0 79.6% (n = 71) versus G3/G4N+ 39.9% (n = 31). The number of positive nodes was the strongest prognostic factor. Multivariate analysis (Cox regression) established a risk factor of 3.06 (p < 0.01) for positive nodes, of 1.7 for grading G1/G2 versus G3/G4 (p = 0.087), and of 1.3 for tumor size (pT1 vs. pT2; p = 0.079). There were no differences in the clinical outcome between patients in stage pT1 with or without lymphadenectomy (75% [n = 130] vs. 79% [n = 39]). CONCLUSION: In patients with cervical cancers treated with surgery and radiotherapy, positive nodes were an independent prognostic factor for local control and survival and should be an indication for additional chemotherapy. A value of lymphadenectomy for survival in this group of irradiated patients could not be established.

The influence of dentin adhesives on the demineralization of irradiated and non-irradiated human root dentin.

This study determined the caries-protective effects of two different dentin bonding systems (Syntac, Scotchbond) on sound and irradiated root surfaces in vitro. The root surfaces of 30 freshly extracted caries-free human molars were used. The teeth were bisected in the mesio-distal direction and all lingual halves of the teeth were irradiated. The irradiation dose of 60 Gy was fractionally applied over six weeks (2 Gy/day, 5d/wk). All halves were then coated with acid-resistant nail varnish, exposing two rectangular windows 6 mm2 each on the dentinal root surface. One window served as an untreated control, while the other was treated with one of the above mentioned dentin adhesive systems. The specimens were randomly distributed among the four experimental groups as follow: Group A: Syntac, non-irradiated; Group AR: Syntac, irradiated; Group B: Scotchbond, non-irradiated; Group BR: Scotchbond, irradiated. Subsequently, all specimens were demineralized for 14 days with acidified gel (HEC, pH 4.8, 37 degrees C). From each window, two dentinal slabs were cut. The slabs were ground to a thickness of 80 microm and submerged in water. The depth of the lesions was determined using a polarized light microscope. The non-irradiated control specimens showed lesions with an average depth of 63 microm (+/-10,2 microm). In the case of the irradiated control specimen, the lesion depth was not significantly different. In all experimental groups, the lesion depth was significantly reduced compared to the control groups. Statistical analysis revealed no significant differences between the irradiated and non-irradiated specimens. It can be concluded that demineralization of the root surface can be hampered by application of the dentin adhesive systems tested. In this study, no differences between irradiated and sound root surfaces could be detected.

Proteome analysis identified maspin as a special feature of papillary thyroid carcinoma.

This study aimed at investigating new mechanisms of carcinogenesis in thyroid cancer at the molecular level and at finding potential protein markers involved in the initiation of the different histological subtypes. For this, we performed differential proteome analysis on primary cultured thyrocytes (PT) and transformed thyrocytes (TT) derived from 238Pu alpha-particle irradiation using 2-dimensional electrophoresis (2-DE) and peptide mass fingerprinting (PMF) with matrix-assisted laser desorption/ionisation-time of flight mass spectrometry (MALDI-TOF MS). Image analysis showed that one protein was very strongly expressed in TT; 55 proteins were weaker, different in intensity, including 26 spots that were increased in PT, and 29 spots were decreased. The hot spot was identified as maspin, a unique member of the serpin family considered to be a class II tumor suppressor gene. To clarify the role of maspin in thyroid carcinogenesis we searched for protein expression in 20 normal (tumor-free) tissues, as well as in 20 follicular adenomas (FAD), 20 papillary carcinomas (PTC), 20 follicular carcinomas (FTC), 20 poorly differentiated carcinomas (PDTC), and 20 undifferentiated carcinomas (UTC). Maspin protein expression was detectable in none of the cases of normal tumor-free thyroid tissue, nor in FAD, FTC, PDTC and UTC. In contrast 14 of 20 PTC (70%) showed a moderate or strong cytoplasmic staining; 4 of these 14 cases had a moderate cytoplasmic and nuclear staining. In conclusion, we hypothesize that maspin protein expression is a special feature in the cascade of PTC genesis and that the way of initiating PTC is different from other thyroid carcinoma types.

Radiation-induced thyroid carcinogenesis as a function of time and dietary iodine supply: an in vivo model of tumorigenesis in the rat.

It is believed that a combination of environmental factors with mutagens induces carcinomas derived from thyroid follicular cells. In this study we tried to ascertain whether a single short-term exposure to external radiation is sufficient to induce thyroid carcinomas in rats under long-term high or low dietary iodine intake. Rats were tested over a period of 110 wk under high (approximately 10-fold of normal), normal, and low (approximately 0.1-fold of normal) daily iodine intake. Forty-day-old animals were subjected to single external radiation of 4 Gy or sham radiation. Thyroid function was tested weekly, and thyroid morphology was determined after 15, 35, 55, and 110 wk. Iodine deficiency, but not high iodine intake, led to a decrease in T(3) and T(4) plasma levels, but to an increase in TSH, which became significant after 9 and 11 wk of treatment, respectively. Both high and low iodine treatment significantly increased the proliferation rate and induced thyroid adenomas, but no malignancies after 55 and 110 wk. Radiation with 4 Gy resulted in a significant destruction of the follicular structure. Under high and low iodine intakes (50-80% of animals), but not under normal iodine supply, thyroid carcinomas were observed in irradiated rats. Thus, the increased proliferation rate induced under the experimental conditions described in this study is apparently not sufficient to cause thyroid carcinomas, but the presence of a mutagen-like radiation is required. This model may help to define genetic alterations long before histological changes are detectable.