Differentiated thyroid cancer: prognostic factors and influence of treatment on the outcome in 441 patients.

BACKGROUND: Differentiated thyroid cancer (DTC) is a rare tumor entity with excellent prognosis. Thus, assessment of the efficacy of different treatment modalities requires follow-up for such a long period that the validity of the conclusion may be limited because diagnostic and therapeutic standards have changed substantially. Accordingly, the indication for external radiotherapy is still controversial. The aim of the present retrospective study is to evaluate prognostic factors and the influence of treatment on outcome of differentiated thyroid cancer from a large data base. PATIENTS AND METHODS: Records of 441 patients (317 females, 124 males; mean age 46 years) with 270 follicular and 171 papillary thyroid carcinomas (pT1-4, pN0-3) were reviewed. Treatment was surgery in 440, radioiodine therapy in 338, postoperative external radiotherapy (50-60 Gy) in 223 patients. In 182 cases the three modalities were combined. RESULTS: The 5-year actuarial survival rate of the whole study population was 95%, 10-year survival 92%. 10-year survival was significantly influenced by: tumor stage (pT1: 100%, pT2: 94%, pT3: 94%, pT4: 79%; p = 0.0005), age (< 40 years: 100%, 41-60 years: 91%, > 60 years: 79%; p = 0.0001) and the presence of lymph node metastases in the follicular subtype (pN0: 96%, pN1-3: 81%; p = 0.02). No significant differences in survival were found according to gender or histological subtype. External radiotherapy yielded a non-significant (p = 0.06) increase in the 10-year survival rate (87% vs 46%; p = 0.06) in patients with pT4 tumors (n = 60). CONCLUSION: Prognostic factors predominantly confirmed those reported in the literature. Further clinical studies should clarify, if the trend towards better survival in irradiated patients with pT4 tumors can be confirmed in larger patient groups.

[The radiotherapy of heterotopic ossifications in paraplegics. The preliminary results]. / Strahlentherapie heterotoper Ossifikationen bei Querschnittsgelähmten. Präliminäre Ergebnisse.

BACKGROUND/AIM: Mobilisation of patients with paraplegia is frequently associated with acute inflammatory processes of soft tissues and muscles in the neighbourhood of joints, where subsequently heterotopic bone formation develops. Rehabilitation is then seriously compromised. For this clinical situation, no local therapeutic options exist so far except extensive resection. To evaluate if radiotherapy early in the course of the disease prevents heterotopic bone formation or if--in case of already manifest ossification and consecutive resection--recurrence can be avoided. PATIENTS AND METHODS: In 20 patients with paralysis, 25 regions were irradiated with (mostly) 10 Gy in single fractions of 2 to 2.5 Gy using 8 MV photons. In 15 patients radiotherapy was performed as a primary treatment in the status of myositis; 7 patients were treated after (subtotal) resection of already manifest ossifications (2 patients were treated twice, primarily and postoperatively). RESULTS: In a minimum follow-up of 12 weeks, none of the 20 irradiated patients showed any progression of the developing or already manifest ossification; thus mobilisation and rehabilitation could be carried out as desired. No side effects occurred. CONCLUSION: The preliminary results of the present study suggest that radiotherapy is an effective local treatment with minimal side effects for the prevention of heterotopic bone formation in patients with paraplegia. Treatment should be started early in the course of the disease. Further evaluation in a prospective study seems desirable.

[Analgetic irradiation of degenerative-inflammatory skeletal diseases. Benefits and risks]. / Analgetische Bestrahlung degenerativentzündlicher Skeletterkrankungen. Nutzen und Risiko.

Between 1980 and 1991, ionizing radiation was applied for analgesic purposes to 181 patients (97 men, 84 women, mean age 54 [29-81] years) with degenerative-inflammatory skeletal disease. The long-term effects were evaluated by questionnaire. Radiation of 2.5 to 6.0 Gy achieved lasting pain relief in 21 of 30 patients (70%) with arthritis of the shoulder or humeroscapular periarthritis, 15 of 21 (71%) with arthritis of the hip, in 12 of 15 (80%) with heel spurs or Achilles tendon bursitis and 10 of 11 (91%) with epicondylitis. Pain relief lasted for longer than two years in 41 of the 77 patients (53%). There were no side effects at the stated dosage. According to dose measurements the theoretical risk of malignant tumour induction is 20-40/million radiated patients and thus four orders of magnitude below the spontaneous malignant tumour incidence rate. The genetic risk is even lower. Ionizing radiation of degenerative-inflammatory diseases is thus an effective form of treatment with few side effects.

[The value of a new IRMA for determining thyroglobulin]. / Wertigkeit eines neuen IRMA zur Thyreoglobulinbestimmung.

A total of 277 patients suffering from differentiated thyroid carcinoma with individual follow-up periods of up to five years had been investigated. More than 1,000 sera were collected. The present paper reports on the results of the parallel serum Tg determinations by means of a recently introduced Tg-IRMA system in comparison with the previously used, well established Tg-RIA method. The intra- and the interassay variation of the IRMA were found at 37% and 46%, respectively, for 4 ng Tg/ml, and 3% and 6%, respectively, for Tg values above 40 ng/ml. Several effects that could interfere with the serum Tg determination (freezing or repeated freezing and thawing of sera, hemolysis or lipemia or dilution of sera, preanalytical use of serum separating tubes) were examined. Although statistically significant in some instances, at least, all of the above mentioned effects were without any practical relevance for the clinical routine use of the IRMA. In patients being in complete remission and on complete TSH suppressive thyroid hormone treatment but having no residual thyroid tissue (n = 70), the level of clinical significance was 1 ng Tg/ml for the IRMA system, resulting in a sensitivity of 99% and a specificity of 90%, respectively. For the RIA system, however, the level of clinical significance was found to be 10 ng Tg/ml with a sensitivity of 89% and a specificity of 95%. We could additionally define the grey-zone for the practical use of the IRMA (1-3 ng Tg/ml). The IRMA system is significantly more sensitive and detects more sera correctly positive than the Tg-RIA.(ABSTRACT TRUNCATED AT 250 WORDS)

Late cervical lymph node recurrence in differentiated thyroid carcinoma. An inherent problem of 131I beta dose distribution in small tumor deposits?

In differentiated thyroid carcinoma, postoperative radioiodine therapy is an undisputed element of the integral therapeutic concept. Sometimes, however, and years after initial diagnosis and therapy, cervical lymph node metastases occur without any evidence of local relapse or distant metastases, indicating that radioiodine therapy has not achieved definite tumor cell sterilization. A Monte Carlo computer simulation of the spatial energy dose distribution of 131I in small functioning tumor manifestations was performed to explain this phenomenon. It appeared that only a small fraction of the total beta-energy dose can be deposited inside the tumor if the latter becomes smaller than 1 mm in diameter: for tumors with homogeneous 131I uptake and diameters of 1.0, 0.5, 0.2, 0.1, 0.05 and 0.02 mm, this value does not exceed 86, 73, 39, 16, 8 and 4%, respectively. These data suggest a potential therapeutic gap for small tumor manifestations not apparent at the time of initial diagnosis and could explain the occasional occurrence of late cervical lymph node metastases.

[The 32P-test in the diagnosis of intraocular melanoma--an obsolete study method?]. / Der 32P-Test zur Diagnose intraokulärer Melanome--eine obsolete Untersuchungs-methode?

Results of the 32P uptake test for the diagnosis of choroidal melanoma in 41 patients are reported. The sensitivity was 80%, the specificity 86%, if a count rate ratio of more than 1.4 between tumor and normal tissue was considered as pathological. Ratios between 1.4 and 1.6 ought to be considered as equivocal in which case specificity increases to 90%. The 32P uptake test still remains a method of clinical relevance in the diagnosis of choroidal melanoma.

[Postoperative external radiotherapy of differentiated thyroid carcinoma: when is radioiodine therapy alone inadequate? The dosimetric considerations with a Monte Carlo simulation]. / Postoperative externe Radiotherapie des differenzierten Schilddrüsenkarzinoms: wann ist eine alleinige Radiojodtherapie unzureichend? Dosimetrische Uberlegungen anhand einer Monte-Carlo-Simulation.

Indication for postoperative external radiation of differentiated thyroid cancer has remained an issue of controversial discussion and is generally restricted to those cases where local tumor control by I-131 therapy alone seems doubtful. This may be the case when lymph node metastases are present or occult micrometastasis are suspected, as the beta(-)-radiation caused by the incorporated I-131 may be deposited partly outside the tumor. This problem of dose distribution is analysed in a simulation model by Monte Carlo techniques where tumors are tissue equivalent spheres of various size (r = 20 microns to 2 cm). Homogeneous I-131 distribution in the whole tumor volume (a) is analysed as well as peripheral deposition confined to the tumour surface (b). In tumors of r = 0.5 mm or less, the percentage of the total dose deposited inside the tumor rapidly decreases, r = 20 microns: 4.1% (a) and 0.9% (b), respectively. Furthermore, extensive dose inhomogeneities appear in tumors of similar sizes. As in local lymph node metastases tumoricidal radiation doses are not necessarily achievable by I-131 therapy alone, postoperative external radiation should be taken into account in the above mentioned clinical situations.

[The place of 99mTc-MDP skeletal scintigraphy in neuroblastoma. Is a new assessment necessary?]. / Stellenwert der 99mTc-MDP-Skelettszintigraphie beim Neuroblastom. Ist eine Neubewertung nötig?

The present study compares the reliability of MIBG and MDP bone scans in detecting bone metastases of neuroblastoma. Out of 57 patients, 23 had both 99mTc-MDP and 123I/131I-MIBG scans within a 2-week period. In 10 patients at primary diagnosis there was an underestimation of skeletal involvement by MIBG in 1/5, in 13 patients at follow-up in 3/9; 99mTc-MDP scans were able to visualize skeletal involvement in all those cases. There was only one false positive MDP scan. These results suggest that MIBG alone may fail to visualize skeletal involvement of neuroblastoma and should therefore be complemented by additional 99mTc-MDP scintigraphy.

[Radiotherapy of glioblastoma: is shortening of the treatment time justifiable?]. / Strahlentherapie des Glioblastoms: Ist eine Verkürzung der Behandlungszeit vertretbar?

Survival of glioblastoma patients can be double by postoperative radiation but nevertheless rarely exceeds one year. It is therefore desirable to minimize treatment time and hospitalisation. Aim of our study is to investigate the feasibility of a reduction of treatment time by accelerated fractionation. Out of 110 patients treated for glioblastoma from 1975 to 1988 in our institution postoperative radiation was performed in 79 patients using three different fractionation schedules: 60 Gy in six weeks, single fractions 2 Gy (n = 38), 35 Gy in two weeks, single fractions 3.5 Gy (n = 27), 45.5 Gy in 2.5 weeks, single fractions 3.5 Gy (n = 14). No statistically significant differences in both the mean overall and disease free survival were evaluated between the three groups. The larger fraction size was well tolerated and no relevant increase of early or late adverse reactions occurred. As the duration of treatment can be reduced from six to two weeks, this accelerated fractionation schedule seems to be a reasonable alternative to conventional fractionation.

[Iodine-131 therapy of autonomous adenoma of the thyroid. 7-year results]. / 131Jod-Therapie des autonomen Adenoms der Schilddrüse. Ergebnisse aus 7 Jahren.

Between 1977 and 1984 a total of 301 patients with autonomous thyroid adenoma were irradiated with an individually calculated one-time dose of 400 Gy units of 131I. Repeated follow-up tests were made in 217 patients (up to 7.2 years, mean of two years). Pre- and post-treatment diagnosis in all patients consisted of determining T3 and T4, one TRH test, one 131I two-phase test to determine treatment, including quantified scintigraphy (under suppression, if necessary), as well as post-treatment scintigraphy and (post-treatment) 99mTc scintigraphy. The treatment was successful in 98% of patients; there was no difference between compensated and decompensated forms. Euthyroid state was achieved in 87% of patients, with typical findings of compensated T3 oversecretion, as is known to occur with endemic goiter in regions of iodine deficiency. The ability of the thyroid for autoregulatory adaptation to such iodine deficiency is thus preserved. Preclinical hypothyroidism occurred in 11% of patients: it could have been avoided in about half of them. Persistent or recurring autonomous adenoma was observed in 2% of patients as a result of under-dosage. One should thus aim at a dose of 400 Gy, to obtain optimal elimination. Radiation-induced carcinogenesis was not observed: radioiodine treatment and operation are thus of equal value in the causal treatment of autonomous adenoma. Radioiodine treatment is indicated in patients aged over 40 years with additional diseases and increased risk of anaesthesia and operation. It is preferred treatment if there are multiple autonomous adenomas.

Extrathyroidal synthesis and biologic action of thyroid receptor antibody (TRAb) in Graves' disease.

In a patient with Graves' disease who underwent thyroidectomy with subsequent radioiodine therapy thyroid receptor antibody could be detected by radioligand assay. No thyroid tissue could be detected by 131I-scintiscanning. Thyroglobulin was repeatedly negative. Biologic activity of this patients serum could be demonstrated in the nude mice bio assay. 131I-incorporation and secretion of human thyroglobulin could be stimulated by injecting thymusdysplastic nude mice with transplants of thyroid tissue from a patient with Graves' disease with the athyroid patients serum. These results demonstrate evidence for extrathyroidal production and biological activity of TRAb in vivo.

[131I-therapy of Basedow's disease and nonimmunogenic hyperthyroidism]. / 131J-Therapie des Morbus Basedow und der nicht-immunogenen Hyperthyreose.

From 1977 to 1982, 315 patients suffering from thyrotoxicosis with diffuse and/or nodular goitre or Graves' disease were treated with 131I. In 246 patients, the results of treatment after 7 months to 5 1/2 years could be evaluated. After a single treatment with 131I, 72% of the patients with hyperthyroid nodular goitre and 61% of those with diffuse goitre, but only 36% of the patients with Graves' disease showed normal thyroid function. By repeated 131I treatments--as many as 5 for those with Graves' disease--normal thyroid function could be achieved in nearly all patients examined. Patients with immune thyrotoxicosis, type Graves' disease, showed a high resistance to therapy. A dependence was found between the results of these treatments and previous antithyroidal drug therapy or surgery. The rate of hypothyroidism varied between 4 and 15%. The highest rate of hypothyroidism was observed in operated patients with persistent or recurring thyrotoxicosis.

[Growth rate of pulmonary metastases (author's transl)]. / Die Wachstumsgeschwindigkeit von Lungenmetastasen.

The growth of 148 untreated metastases to the lung was determined in 47 patients. Pulmonary metastases of squamous-cell carcinomas, sarcomas and malignant melanomas exhibited exponential growth, the doubling times were distributed log-normally, the geometric mean amounted to six weeks. The growth rate of adenocarcinomas decreased with increasing tumor size approximately in accordance with a Gompertzian function.

[Clinical result of thyroid scintigraphy and iodine estimations using a fluorescent technique (author's transl)]. / Klinische Ergebnisse der Schilddrüsenszintigraphie und Jodbestimmung mit Fluoreszenztechnik.

The new technique of quantitative fluorescent scintigraphy was used for determining the regional distribution and concentration of stable intrathyroid iodine (127 I) in 96 patients. Average iodine concentration in normal people (20 individuals) without thyroid enlargement living in the Bavarian iodine-deficiency area was 0.38 +/- 0.07 mg/g. In 32 patients with simple goitres it was significantly lower at 0.17 +/- 0.06 mg/g. With this technique it was possible to separate two types of hyperthyroidism amongst 21 patients: those with low iodine concentration in the thyroid (0.15 +/- 0.08 mg/g) and those with high iodine concentration (0.42 +/- 0.12 mg/g) after iodine administration. The iodine concentration in decompensated autonomous adenomas in twelve patients was usually low (0.12 +/- 0.12 mg/g). On the other hand iodine concentration was high in the paranodular tissues and could be demonstrated on the fluorescent scintigram. The quality of the scintigram using this technique for concentrations below 0.1 mg/g is inadequate. In this situation good imates can be obtained by radionucleid scintgrams. The situation is reversed by previous administration of iodine.