Aggressive angiomyxoma: irradiation for recurrent disease.

BACKGROUND: Aggressive angiomyxoma (AAM) is a tumor of the soft tissues predominately occurring in the genital and pelvic area with a strong propensity to local recurrences. The entity was first described in 1983. The tumor is regarded as low-grade sarcoma by some authors; its cause and pathogenesis are presently unknown. PATIENT AND METHOD: This is a case report on a 27-year-old man who underwent 4 surgical procedures of the left lower extremity because of a recurrent soft tissue neoplasm, initially (August 1993) diagnosed as a myxolipoma. The patient suffered from recurrences in February 1995, September 1996 and February 1998. The diagnosis was revised at the time of the latest recurrence. A palliative resection with macroscopic residuals left was performed in February 1998, followed by a radiation therapy with 56 Gy total dose and a concomitant administration of the radiosensitizer razoxane per os. The single radiation doses were 200 cGy 5 times a week. RESULTS: The small residuals of the tumor obviously regressed although an objective response could not be shown because the lesion was not clearly measurable. A follow-up 2 years after the radiation treatment revealed no recurrence. The time of the local control achieved as yet is already longer than any former time to regrowth between the surgical procedures. This is, to our knowledge, the first description of a therapeutic irradiation of a recurrent aggressive angiomyxoma. CONCLUSION: Radiation therapy combined with the sensitizer razoxane is able to control a recurrent AAM for an unknown time. It remains open whether a radiation treatment alone would have had a similar effect.

[The histology of the primary tumor and metastatic behavior. The implications for the radio-oncologist with examples]. / Histologie des Primärtumors und Metastasenverhalten. Implikationen für den Radioonkologen anhand von Beispielen.

BACKGROUND: In the past, little attention has been given to the relationship of the histology of a primary tumor to its possible subsequent pattern of metastasis. The knowledge of these relations, however, is of importance for the radio-oncologist for several reasons. MATERIALS AND METHODS: A review on the relation between the histology of a primary tumor and the pattern of subsequent metastasis has been worked out. The review is based on references personally collected during the past 25 years, a MEDLINE screen (1988 to 1997) and own analyses related to the topic. RESULTS: Strong relationships seem to exist between the histology of certain primary tumors and their subsequent pattern of metastasis. Examples demonstrate those relations which are presently known about the main solid tumors of the upper part of the body and the skin. Some implications for the radio-oncologist were pointed out. CONCLUSIONS: Besides a better understanding of a disease, the use of these data may be helpful for treatment planning and decision findings in conformal radiotherapy. Moreover, the data are of considerable importance to the follow-up of patients: imaging procedures may be more accurately applied in the areas with a high probability of recurrence or metastasis.

[Correlation of histology of the primary tumor with liver metastases in colorectal carcinoma]. / Beziehung zwischen der Histologie des Primärtumors und der Lebermetastasierung beim kolorektalen Karzinom.

The histology of colorectal tumors was correlated with the presence of liver metastases in a retrospective study performed on 179 patients who were autopsied between 1975 and 1990. For the analysis of metastatic patterns, 116 cases with at least one distant metastatic site were selected. A distinct relationship between mucin expression of colorectal tumors and liver involvement was found. Pure adenocarcinomas and their papillary variants showed the highest affinity to the hepatic tissue regarding the frequency as well as extent of involvement. A subtotal replacement of the liver by metastases was restricted to these two variants. An extracellular mucin component was associated with a lower frequency of liver involvement and a tendency to solitary or oligotopic metastases. Ten cases of signet ring cell carcinomas had no metastases in the liver. The results described here for colorectal cancers are similar to those previously reported for gastric cancer. The therapeutic implications were discussed. A detailed link between these clinical findings and the results found at the level of molecular biology is yet to be determined.

[Angiosarcoma of the right atrium: local control via low radiation doses and razoxane. A case report]. / Angiosarkom des rechten Vorhofs: lokale Kontrolle durch niedrige Strahlendosen und Razoxan. Ein Fallbericht.

BACKGROUND: Angiosarcomas of the heart are rare neoplasms bearing an unfavorable prognosis. In recent series, the median survival is about 5 months. The response to radiation therapy is uncertain. CASE REPORT: A 65-year-old copper smith with an angiosarcoma of the right atrium and metastases of the liver received a partial resection of the primary tumor in January 1992. This was followed by a polychemotherapy including ifosfamide, epirubicin and dacarbacin (DTIC). In April 1992, after 5 cycles of this treatment a large regrowth of the primary and multiple pulmonary metastases were observed. After a 4-day pretreatment with the radiosensitizer razoxane, the large tumor of the right heart was irradiated with 25 MV photons of a linear accelerator. Single doses of 200 cGy were given via parallel opposed fields. The total radiation dose at the tumor was 30 Gy. Concomitantly, razoxane was given at a dose of 125 mg twice daily during the radiation days until the end of the radiotherapy. The treatment was well tolerated and the patient went into a subtotal remission. Chest X-rays from September 1992 revealed a progression of the metastases in the lung and the liver, the recurrent tumor of the right atrium remained in a subtotal remission. The patient was retreated with ifosfamide, epirubicin and DTIC. No substantial remission of the metastases occurred and the patient died at the end of January 1993. At autopsy, the recurrent primary and the lung metastases within the region of the former radiation field remained locally controlled. CONCLUSION: Reviewing the literature and considering this case, irradiation seems to be a valid treatment option for the local control of cardiac angiosarcomas. The combination of radiotherapy with razoxane eventually allows a considerable reduction of the radiation dose.

Exposure to polymeric materials in vascular soft-tissue sarcomas.

UNLABELLED: Known etiologic factors related to endothelial angiosarcomas are exposures to arsenic, thorium dioxide, therapeutic irradiation, and certain congenital diseases. Little is known on the etiology of hemangiopericytomas. Since 1974, several reports have appeared on a distinct relationship between the exposure to vinyl chloride monomers and angiosarcomas of the liver. The early reports on this matter provided the reason to collect the occupational histories of vascular sarcomas accumulated since that time. METHODS: Data on the occupational histories of patients with different forms of angiosarcomas, treated between 1975 and 1995 in two institutions, were prospectively collected and analyzed. In this personal series the only selection criteria were the referral of patients for postoperative or palliative irradiation and their personal care by the author. FINDINGS: Among 21 adult cases of vascular sarcomas there were 4 patients with occupational exposure to vinyl chloride (VC) either alone or together with other artificial polymers. Seven other patients showed exposure to several plastics or resins other than VC. Altogether, 11 of 21 (52%) of the explored patients were found to have been exposed to artificial polymeric materials over a mean period of 18 years. The patients without such exposure were 4 farmers, 2 house-wives, and 1 woodworker, telephonist, mason, and inland revenue official, respectively. Two cases were radiation-induced. The series contained no angiosarcoma of the liver. INTERPRETATION: This study offers new evidence of the occurrence of vinyl-chloride-induced angiosarcomas outside the liver and confirms observations that have previously been published in case reports. Moreover, it may be suspected from this analysis that polyvinyl chloride and its monomers are not the only polymeric materials that may contribute to an induction of angiosarcomas in humans. Repeated occupational histories have to be taken from the patients to achieve data of the greatest value, since there are many professional activities that do not primarily lead to the assumption of specific exposure to polymeric materials.

[Malignant hemangioendothelioma of the thyroid gland: new results on pathogenesis, therapy and prognosis]. / Das maligne Hämangioendotheliom der Schilddrüse: Neue Resultate zur Pathogenese, Therapie und Prognose.

BACKGROUND: Malignant hemangioendothelioma of the thyroid is a rare tumor predominantly described in areas with endemic goiter like the Alpine regions. The estimated incidence of the disease is between 0.15 and 0.25 per 100,000 inhabitants per year for Western Austria. The prognosis is reported to be dismal. MATERIALS AND METHODS: Between 1982 and 1995, 10 cases with immunohistochemically confirmed malignant hemangioendotheliomas of the thyroid were referred to our department for postoperative or palliative treatment. Two patients with clear margins at surgery received no adjuvant radiotherapy and were only observed. By surgery, clear margins (R-0 resection) were achieved in 5, microscopic residuals (R-1) were left in 3, and gross residual disease in 1 patient. One patient had an inoperable primary tumor. Postoperative radiotherapy was administered in 6 cases, 4 of them additionally received the radiosensitizer razoxane. Total tumor doses ranged between 58 and 65 Gy. RESULTS: Local tumor control was achieved in 9 of 10 patients; 4 of 10 lived longer than 4 years. The median survival time has not yet been reached and is presently between 7.5 and 21+ months.--Noteworthy is a complete regression of 2 lung metastases in a 72-year-old man by a combination of vindesine, razoxane and radiotherapy. The patient is still in complete remission under a maintenance therapy with vindesine and razoxane since 14 months.--It may also be of interest that 4 of the 10 patients were strongly exposed to vinyl chloride and other polymeric materials during their occupational life. CONCLUSIONS: This small series may indicate that the outcome of this disease may not be uniformly deleterious, and that the resistance to radiotherapy reported in the literature may be questioned.--The data offer new evidence of the occurrence of vinyl chloride-induced angiosarcomas outside the liver, and support observations which have already been published in case reports.

[Is axillary dissection in clinically lymph node-negative breast carcinoma further indicated?]. / Ist die Axilladissektion beim klinisch nodal negativen Mammakarzinom weiter indiziert?

BACKGROUND: In the treatment of breast cancer, the indication for adjuvant systemic treatment was extended also to nodal negative tumor stages in the last years. For that reason, the indicator status of axillary dissection lost some of its importance. Therefore, in node negative patients, the necessity of axillary dissection and the use of definitive axillary radiotherapy, which causes less morbidity, may be reconsidered. METHODS: In a review of the related literature, we present international treatment experiences related to axillary dissection, axillary radiotherapy and "sentinel node dissection" (SLND). In addition, our long-term experiences in 19 patients with clinically negative axillary nodes treated by conservative surgery without axillary dissection but axillary radiotherapy, are reported. RESULTS: The median rate of axillary recurrences with axillary radiotherapy is 2.0%, the regional (supraclavicular and retrosternal) recurrence rate 2.7%. With axillary dissection, axillary recurrences occur in 1 to 2%, in nodal negative stages in 0 to 1%, the median regional recurrence rate is 2.2%. A meta-analysis presented in 1995 by the Early Breast Cancer Study Group showed no significant difference in the regional recurrence rate or the overall survival between axillary dissection and axillary radiotherapy. With SLND, usually only one axillary node is excised. With the help of molecular and immunohistochemical methods, SLND may predict axillary involvement with high precision. CONCLUSIONS: Definitive radiotherapy of the axilla is a valid treatment option for patients without palpable axillary nodes with the potential advantage of being less cost intensive and better tolerated. If the indication for systemic therapy is no more dependent on the axillary status, axillary dissection may be replaced by axillary radiotherapy. In small tumors without risk factors and without indication for systemic therapy, SLND seems to be the best treatment option.

Radiotherapy vs. radiotherapy and razoxane in the treatment of soft tissue sarcomas: final results of a randomized study.

PURPOSE: The effect of the sensitizer razoxane on soft tissue sarcomas (STS) was prospectively evaluated in a randomized, controlled trial. The main purpose of the study was to determine the response rates and local control under the combined treatment compared to irradiation alone. METHODS AND MATERIALS: Between 1978 and 1988, 144 patients entered the study; 130 were evaluable for response, toxicity, or survival. The patients were randomized to receive radiotherapy alone or radiotherapy with razoxane. They were divided into postoperative cases and patients with gross disease (unresectable primaries, recurrent disease, or metastatic disease). The median radiation dose was 60 Gy postoperatively, and 56-58 Gy in patients with gross disease. The dose difference has palliative reasons. Razoxane was given orally at a daily dose of 150 mg/m2 during the time of the radiotherapy, starting 5 days before the first irradiation. In general, the groups were comparable as to their prognostic factors. There was some imbalance, however, in favor of the postoperative group reveiving radiotherapy alone. RESULTS: Between the patient groups treated postoperatively in an adjuvant form, there were no substantial differences in local control and survival. Among 82 patients with gross disease, the treatment with radiotherapy and razoxane led to an increased response rate compared to photon irradiation alone (74 vs. 49%). The local control rate was likewise improved (64 vs. 30%;p < 0.05). The acute toxicity was somewhat higher in the sensitizer arm, but there was no difference in the occurrence of late complications. CONCLUSIONS: Radiotherapy combined with razoxane seems to improve the local control in inoperable, residual, or recurrent STS compared to radiotherapy alone. The combined treatment is a fairly well tolerated procedure at low costs. It can be recommended for inoperable primary STS or gross disease after incomplete resection, conditions which are still associated with limited local control and a grave prognosis.

[Generalized osteopathy with pathological fractures in a patient with long-term exposure to fluorine-containing plastics]. / Generalisierte Osteopathie mit pathologischen Frakturen bei einem Patienten mit Langzeitexposition gegenüber fluorhaltigen Kunststoffen.

In a 68-year-old man with a painful syndrome of the lower extremities which began at the age of 64 years, workup revealed a generalized osteopathy with sclerosis of the axial skeleton and osteopenia at the extremities associated with pathologic fractures. The occupational history showed exposure to several synthetics such as vinyl chloride, polyethylene, delrine and polyamides over 30 years. However, a presumptive connection between the skeletal disorder and the occupational exposure could not initially be substantiated. In a later analysis of the bone biopsies from 1991, a significant increase of fluorine in the tibia and fibula of the patient was detected and thus the diagnosis of industrial fluorosis established. The fluorine presumably originated from the workup of polytetrafluorethylene plates. A detailed analysis of the workplace is ongoing. The fluorosis may obviously appear as a variable skeletal disease. The clinical picture of fluorosis is incompletely described in most of the German textbooks. It calls for an extended description of the X-ray findings associated with fluorosis and a new definition of the disease.

High frequency of metalworkers among patients with seminomatous tumors of the testis: a case-control study.

Occupational analyses were conducted between 1971 and 1978 comparing 165 cases of testicular cancer in the Hannover region of Germany with 187 controls without neoplastic diseases admitted to the Hannover University Medical School during the same period. The results showed a significantly higher risk of metal workers developing seminomas and mixed seminomatous tumors compared to the controls (odds ratio 2.05; 1.17-3.58). There was a lack of risk for the nonseminomatous tumors as a whole group, and cases with a history of metal work may have a decreased risk for embryonal carcinomas. No definite single noxious substance responsible for the development of testicular tumors could be detected. In view of the results in animal experiments, cadmium and zinc are especially considered in the discussion.

[Osteogenesis imperfecta and breast carcinoma. A case study of radiobiological interest]. / Osteogenesis imperfecta und Mammakarzinom. Eine Fallstudie von radiobiologischem Interesse.

PURPOSE: Osteogenesis imperfecta (OI) is an inherited disorder of connective tissue with abnormal quality and/or quantity of type 1 collagen. The frequency of the association of OI and breast cancer as well as the frequency of radiation induced side-effects in patients with OI are not known. Certain diseases with widespread collagen alterations such as systemic lupus erythematodes or dermatomyositis--although not exactly comparable to congenital OI--carry a high risk for radiation injuries in case of irradiation with normal doses. The report of a patient with osteogenesis imperfecta type I and postmastectomy irradiation might therefore be of some radiobiological interest. METHODS: Report of a 46-year-old women with OI type I and breast cancer with a 14-year follow-up time after mastectomy and external beam irradiation. RESULTS: During all the follow-up time there was no radiation injury in this patient with OI type I and breast cancer. CONCLUSION: Mostly it is not possible to draw a valid conclusion from a case report, but with this experience the combination of OI type I and radiotherapy seems not to cause unusual radiation injury. Contrary to OI of type II and III, in the majority of the cases of OI type I there is a normal quality, but diminished quantity of collagen type I. This could be one of the possible reasons for the absence of adverse radiation effects. Finally, it might be of interest, that the gene-locus of the two alpha-1(I)-chains of collagen type I is situated at chromosome 17q21-22, where also the location of the "breast-cancer gene" is supposed to be. A genetic examination was, unfortunately, refused by the patient.

Inoperable recurrent rectal cancer: results of a prospective trial with radiation therapy and razoxane.

PURPOSE: The effect of the sensitizer razoxane was prospectively evaluated in recurrent rectal cancer. Endpoints of the study were mainly local response rates and survival. METHODS AND MATERIALS: From 1984 to 1990 razoxane was given together with radiation therapy to 40 patients with recurrent inoperable rectal cancer. Loco-regional relapses in the pelvis were isolated in 24 and associated with distant metastases in 16 patients. Special attention was given to the subset of 24 patients with isolated local recurrences. This group was compared with historical controls treated with radiotherapy alone. The dosage of razoxane was 150 mg/m2 daily orally starting 5 days before the first irradiation. The drug was then given each radiation day until the end of treatment. The median radiation dose was 60 (40-62) Gy in the evaluable patients. The minimum follow-up was 32 months and the median 72 months. RESULTS: The rates of complete plus partial responses were 57% and 54%, respectively, for recurrent patients without and with distant metastasis. The 23 evaluable patients with isolated local relapses had a median survival of 24 months (12-94+); all patients surviving at least 1 year. CONCLUSION: The combination of radiotherapy and razoxane may lead to better local control and improved median survival compared to our historical controls and literature reports where radiotherapy alone was used. The treatment is easy to administer and is associated with a moderate toxicity.

[Prognosis and epidemiology of malignant hemangioendotheliomas of the thyroid gland]. / Zur Prognose und Epidemiologie des malignen Hämangio-endothelioms der Schilddrüse.

Five new cases of malignant hemangioendothelioma of the thyroid are reported. This rare malignant tumor is described predominantly in regions with endemic goiter such as the Alpine zone. The estimated incidence of the disease is between 0.15 and 0.25 per 100,000 inhabitants per year for Western Austria. Two of the five patients were heavily exposed to vinyl chloride occupationally for 9 and 30 years respectively. Surgically, a R-0 resection was performed in two patients, R-1 in two, and R-2 in one patient. Postoperative radiotherapy was given in four cases. The tumor doses were between 58 and 65 Gy. Three patients received the sensitizer razoxane in addition. Local tumor control was achieved in 4 of 5 patients. The survival times of the 5 patients were 78, 68+, 38+, 7.5 and 3 months. Two patients are still alive after 68 and 38 months. This small series may indicate that the outcome of the disease may not be uniformly deleterious and the resistance to radiotherapy reported in the literature [3, 10] is debatable.

[Hypertension as risk factor for increased rate of side effects in the framework of breast carcinoma irradiation]. / Hypertonie als Risikofaktor für erhöhte Nebenwirkungsraten im Rahmen der Mammakarzinombestrahlung.

The rate of radiation-induced side-effects is dependent from exogenous technical and endogenous factors. Widespread endogenous factors are arterial hypertension and other cardiovascular diseases. 130 breast cancer patients were retrospectively evaluated for side-effects to estimate the influence of arterial hypertension. All were treated with mastectomy and irradiation (telecobalt) and consecutively followed. 79 patients had normal blood pressure, 51 showed arterial hypertension. Hypertension proved to be the strongest endogenous factor for the development of side-effects. In contrast to the patients with normal blood pressure those with hypertension showed significant more arm lymphedema (p less than 0.005) and telangiectasia (p less than 0.0001). Other endogenous factors, like cardiovascular diseases or obesity, taken together led only to a higher rate of subcutaneous fibrosis (p less than 0.002). Patients with arterial hypertension should receive axillary radiation only for strict indications and perhaps with a reduced dosage.

Radiotherapeutic enhancement by razoxane.

Razoxane blocks cell division in the G2/M phase of the cell generation cycle and appears to normalize tumour neovasculature development. These were the principal reasons for the examination and probably for the demonstration of the radiosensitizing activity of Rz. Specially intriguing has been the finding that radiation of primary tumour implants in animals treated with Rz has a powerful potentiating effect on the antimetastatic activity of the combination. This concept has not yet received any clinical examination. Clinical trials with radiotherapy and Rz have demonstrated the clearest beneficial effects in terms of response rates and maintained local control in soft tissue sarcomas and possibly in recurrent rectal and in bladder carcinomas. Interesting heightened activity has also been found in hepatic metastases from gastrointestinal tumours. Carcinomas of the cervix, bronchus and head and neck, however, have not shown any benefit from the combination compared with radiotherapy alone.

[Radio-oncological treatment possibilities in local recurrence of rectal carcinoma. An interdisciplinary comparison]. / Radioonkologische Behandlungschancen beim Lokalrezidiv des Rektumkarzinoms. Ein interdisziplinärer Vergleich.

Local recurrences of rectal carcinomas are frequently associated with a considerable morbidity and a dismal prognosis. Surgical resection leads to long term tumor control in about 30 to 40%, but surgery can be offered to only 10 to 30% of the patients. Cytotoxic chemotherapy is able to induce local responses in 15 to 40% of the cases--similar figures as achieved by radiation therapy alone. A pilot study is presented using radiation therapy combined with the sensitizing agent razoxane (ICRF 159). There was an objective response rate of 62% and the median survival rose to 24 months (13 months with radiation therapy alone). These data compare almost to results seen in surgical series. However, they need confirmation.

Long-term application of vindesine: toxicity and tolerance.

This is a report on 14 patients receiving vindesine continuously for between 1 and 7 years. Total vindesine doses ranged from 86 mg to 454 mg and the longest treatment duration was 2564 days. Although there was no patient without a transient acute or subacute toxicity, no unequivocal signs of long-term toxicity have been observed so far. Greater caution must be given to the concomitant use of higher radiation doses and vindesine, since local reactions were more pronounced especially at the lung. The drug seems to be tolerated for longer periods without major or cumulative toxicity, which makes it suitable for use in the adjuvant setting, for instance, or within an antimetastatic approach.

Liver metastasis in cancer of the stomach and its dependence on the histology of the primary tumor: an autopsy study on 102 cases.

The case records of 102 patients who had died of gastric cancer between 1975 and 1983 were evaluated. Special emphasis was given to an analysis of the metastatic liver involvement in relation to various histological classifications. The results show a strong preponderance of liver involvement by differentiated adenocarcinomas without intra- or extracellular mucin production, whereas signet ring cell carcinomas or adenocarcinomas with a major extracellular mucin production seem to avoid the liver. If the liver is being involved by the latter tumors, the degree of involvement remains low. Other relationships between certain histologies and the subsequent spread are briefly reported and compared with available data from the literature. The impact on adjuvant therapeutic strategies is discussed.