Results of whole lung irradiation and chemotherapy in comparison with partial lung irradiation in metastasizing, undifferentiated soft tissue sarcomas

The poor prognosis of patients with unresectable pulmonary metastases of soft tissue sarcoma is well known. In order to evaluate the beneficial effect of radiotherapy, we have treated 44 patients with pulmonary metastases of grade 3 soft tissue sarcoma from 1980 to 1986. In 36 patients the treatment volume was restricted to the single metastases up to a dose of 50 to 60 (9 to 10 Gy/week). The survival rate at one year was 18% and at two years 6%. Eight patients were treated with a combined regimen, consisting of cisplatin and ifosfamide with simultaneous whole lung irradiation. Irradiation was performed with 8 or 16 MV photons at a hyperfractionation of 2 x 0.8 Gy/day (8 Gy/week). After a dose of 12 Gy, the single metastases were boosted up to 50 to 60 Gy, with a second course of chemotherapy. In six of eight patients complete remissions were achieved, one patient showed a partial remission. The survival rate at 27 months was 50%. The patients with partial remission died from pulmonary progression at 23 months. One patient died after twelve months from a loco-regional recurrence in the tonsillar fossa without evidence of pulmonary disease. Side effects included alopecia and moderate bone marrow suppression approximately twelve days after each chemotherapy cycle. Pulmonary fibrosis was observed only at the high dose volume without impairment of respiratory function. From these observations the conclusion is drawn that whole lung irradiation simultaneously with cisplatin and ifosfamide chemotherapy provides good palliative results without relevant morbidity in patients with high grade unresectable pulmonary metastases of soft tissue sarcomas.     

Results of radiation therapy in brain metastases with reference to computerized tomography

Between 1979 and 1985, 193 patients were submitted to radiotherapy of the brain for formation of metastases. A primary irradiation was performed in 159 patients, 34 patients had been treated by surgery. The median survival time after diagnosis of all irradiated patients (40 to 60 Gy within four to six weeks) was 4.9 months, 22% of the patients survived one year. Patients with mammary carcinomas and patients with bronchial carcinomas showed marked differences in median survival times (4.2 and 6.9 months, respectively) and one-year survival rate (11% and 32%, respectively). In histologic examination, the extent of extracerebral formation of metastases was the decisive parameter for survival. At the end of radiotherapy, 47% of patients showed an amelioration in neurologic deficiency, 16% deteriorated. A follow-up by computed tomography with observation periods between four and 34 months was possible in 84 patients. Most of these patients showed improvement in computed tomography during a period of four to twenty weeks after the beginning of radiotherapy. Later on, about two thirds of the controlled patients had again deterioration with local progression or new formation of metastases in spite of total brain irradiation. A long-term normalization (greater than one year) was observed only in patients with mammary carcinomas.     

Merkel Cell Carcinoma: The Role of Radiation Therapy in General Management

BACKGROUND: Merkel cell carcinoma (MCC) is a rare malignant, locally aggressive tumor of the skin. Because few data exist about the clinical course of irradiated patients, we reviewed the 17 patients treated at our institution since 1982. PATIENTS AND METHODS: The median age at diagnosis was 71 years (range 47 to 88 years). Twelve patients presented with lymph node involvement (Stage II), 5 patients with negative lymph nodes (Stage I). Five patients were irradiated immediately after initial surgical excision of the primary tumor. Eleven patients underwent a surgical treatment of recurrence prior to the first irradiation. Only 1 patient received primary radiotherapy. A median dose of 52.8 Gy (range 40 to 60 Gy) in the region of the primary tumor and a median dose of 49.5 Gy (range 30 to 54 Gy) in the regional lymph nodes were delivered. RESULTS: The median overall survival after first diagnosis was 45 months. Three-year overall survival was 57%, 5-year cause-specific survival was 73% (Kaplan Meier). Local control could be achieved in the 5 patients irradiated immediately after surgical treatment of the primary tumor. In contrast, an in-field recurrence occurred in 5 of 12 patients irradiated after surgical excision of relapsed disease. Five patients developed distant metastases. None of these patients was irradiated immediately after surgical excision of the primary tumor. CONCLUSIONS: With respect to our experience, a local control can be achieved with an immediate postoperative radiotherapy of the primary tumor site and the adjacent lymph nodes.     

Indications for and results of postoperative radiotherapy of vulvar cancer

Between 1968 and 1979, 132 patients with squamous cell carcinomas of the vulva were submitted to a more or less radical operation. Then they were irradiated at the Radiologic Center of the GHS Essen. All patients received irradiations of the vulvar region with high energy electrons combined with photons (n = 78) as well as photons or electrons alone (n = 15 and 39, respectively). The dose was generally 40 to 60 Gy. 81 patients (61.4%) were additionally irradiated in the inguinal region. The overall three-year and five-year survival rate is 48.5 and 34.1%, respectively. The median survival time is 31.5 months. Contrary to expectation there were no significantly different recurrence rates after radical vulvectomy and large excision combined with postoperative irradiation. This is attributed to the favorable effect of radiotherapy. A graduated conception has been elaborated based on the results of our retrospective analysis and the communications of literature. Radical vulvectomy and inguinal lymphadenectomy is the therapy of choice. Radiotherapy in the vulvar region should be applied if radical surgery seems problematic or is not possible. Irradiation of lymph node regions is indicated if they are involved or if a resection is not possible.     

Serum proteins in rats after combined neutron and gamma irradiation

Quantitative changes of some selected serum proteins in rats irradiated with a single dose of 2 Gy neutrons were compared with protein changes in rats irradiated with an equal single neutron dose and subsequent continuous gamma irradiation using daily dose rate of 0.574 Gy up to the total dose of 6 Gy. On the basis of the values obtained from the diagrams of two-dimensional immunoelectrophoresis it was found that both irradiations entailed approximately equal quantitative changes of the serum concentrations of the proteins followed. The differences found concerned time intervals of the adjustment of the changes produced. After neutron irradiation reparation of the serum albumin occurred on 14th day, of A1-globulin concentrations on 28th day and of haptoglobin on 90th day, yet after combined neutron and gamma irradiation reparation of the changes in albumin on 15th and A1-globulin occurred on 40th day and in haptoglobin only on 100th day after neutron irradiation.     

Long-term results of pulsed irradiation of skin metastases from breast cancer. Effectiveness and sequelae.

PURPOSE: The concept of pulsed brachytherapy suggested by Brenner and Hall requires an unusual fractionation scheme. Effectiveness and sequelae of this new irradiation method were observed in patients with disseminated cutaneous metastases of breast cancer. PATIENTS AND METHODS: A flexible, reusable skin mold (weight 110 g) was developed for use with a pulsed dose rate (PDR) afterloader. An array of 18 parallel catheters (2 mm diameter) at equal distances of 10 or 12 mm was constructed by fixation of the catheters in a plastic wire mesh. The array is sewn between 2 foam rubber slabs of 5 mm thickness to provide a defined constant distance to the skin. Irradiations are possible up to a maximum field size of 20 x 23.5 cm using a nominal 37 GBq Ir-192 source. Pulses of 1 Gy reference dose at the skin surface are applied at a rate of 1 pulse every 1.2 hours (0.8 Gy per hour). The dose distribution is geometrically optimized to provide a homogeneous skin dose (100% +/- 10%). The 80% dose level lies at 5 mm below the skin surface. Between April 1994 and December 1997, 52 patients suffering from cutaneous metastases at the thoracic wall were treated with 54 fields and total doses of 38 to 50 Gy (median 42 Gy) applying 2 PDR courses with a pause of 4 to 5 weeks. RESULTS: Forty-six patients (48 fields) were eligible for evaluation in June 1998. The median follow-up was 16 months (range 7.1 to 46.2 months). Local control was achieved in 40 out of 48 fields (83%) or 41 of 46 patients (89%), respectively. Moist desquamation occurred in 52% of the patients. Late reactions were judged after a minimum follow-up of 6 months. Thirty-two fields had been previously irradiated with external beam therapy to doses of 40 to 60 Gy. Regardless of whether the skin was preirradiated or not all patients surviving long enough developed telangiectasia within 2 years after PDR irradiation. In preirradiated patients (n = 32) skin contractures and/or skin necrosis occurred in 12% each. In newly irradiated patients (n = 14) no contractures or skin necrosis were observed. CONCLUSIONS: Pulsed brachytherapy is an effective and time-sparing method for the treatment of cutaneous metastases from breast cancer. Skin reactions are comparable to the sequelae of orthovoltage therapy. Two sessions of approximately 20 Gy PDR were tolerated on preirradiated skin without severe sequelae.     

Te place of radiotherapy in the treatment of local recurrences of rectal cancer

A retrospective study was conducted on 67 patients irradiated between 1976 and 1983 at the Medical Radiologic Institute of Tübingen for local recurrences of primarily operated carcinomas of the rectum. Generally, a total dose of 50 to 60 Gy was applied partially in form of a rotational therapy with individual doses of 2 Gy each. The irradiation was well tolerated by most of the patients. The troubles which were mostly severe and progressive before radiotherapy could be relieved by the irradiations in 91% of the patients. This palliative effect lasted for twelve months on an average. The prognosis quoad vitam is unfavorable with a median survival time of 21 months and a three-year survival rate of 15%. A clear dependence on the dose was not found for any of these parameters. Our own results are compared to those communicated by other authors. It is shown that better results can only be achieved by re-operation performed in sano.     

不纯泊松分布法在6 MV X射线局部照射剂量估算中的应用

目的从离体和活体两方面探索不纯泊松分布法估算6MV X射线局部受照射剂量和受照射份额的适用性。方法2、4Gy6MV X射线离体照射健康人外周血，受照射份额为20％、50％和80％模拟局部照射；选择2、3Gy6MV X射线局部放射治疗的肿瘤病人，观察首次放射治疗前、后24h外周血淋巴细胞染色体畸变，采用不纯泊松分布法，估算受照射剂量和份额。结果2Gv离体照射50％、80％份额和4Gy照射20％、50％、80％份额的淋巴细胞双着丝粒 环(dic r)畸变呈过分散分布，受照射剂量和份额估算值与实际值基本吻合。单次2Gy盆腔照射、受照射局部红骨髓比例大于20％或3Gy全颅照射放射治疗病人的外周血淋巴细胞dic r畸变呈过分散分布，估算的受照射份额与受照射局部红骨髓比例相接近，较大剂量3Gy放疗时估算的受照射剂量较为准确。患者局部放射治疗后与放射治疗前离体模拟的实验结果都显示较好的一致性。结论采用不纯泊松分布法可以比较准确的估算离体和活体局部受照射剂量和份额，适用于照射剂量较高和照射份额不是太小的低LET射线，受照射局部红骨髓占全身的比例可大致反映局部照射的份额。     

Radiotherapy of choroid metastases in breast carcinoma

From 1975 to 1984, thirteen patients were submitted to radiotherapy for choroid metastases of mammary carcinoma. Bilateral manifestation was found in three cases, thus sixteen eyes have been treated. All irradiations were performed with high voltage equipment. The posterior section of the eye was irradiated with 25 to 50 Gy over 2.5 to 5 weeks. Complete regression was achieved in nine out of sixteen cases, five patients showed an improvement of at least 50%, no considerable effect was found in two cases. The survival is 4 to 48 months (median survival 20 months) from the beginning of radiotherapy. Radiotherapy is a quick, efficient, and sparing treatment in choroid metastases. If applied in due time, it can prevent a visual disorder or amaurosis, thus improving the patients' quality of life.     

Radiotherapy of locally recurring colorectal tumors. Prognostic factors, follow-up diagnosis and results

From 1979 through April, 1985, 74 patients were treated by percutaneous irradiation for local recurrences of colorectal carcinomas. The treatment consisted of a contralateral irradiation up to a dose of 40 Gy and a small-volume boost up to 60 to 66 Gy. In case of progressive remote metastases, the treatment was finished at 50 Gy. 53 patients received a dose of 50 Gy or more and were followed for at least six months. The decisive prognostic parameter was the presence of remote metastases when the recurrence appeared (n = 32). The median survival was six months, in patients without remote metastases at this moment it was 15 months. A complete or considerable relief of pain was obtained in 78%; it continued for a median period of 8.5 months, although most of the patients showed a new local tumor progression after an interval of three to 26 months. Computed tomography showed only small regressions or, in most cases, unchanged volumes of the tumors.     

Delayed vascular injury after single high-dose irradiation in the rat brain: histologic immunohistochemical, and angiographic studies.

PURPOSE: To investigate structural and functional changes in rats after focal brain irradiation by using histologic, immunohistochemical, and angiographic methods. MATERIALS AND METHODS: Sixty rats were irradiated stereotactically with photons from a 15-MeV linear accelerator. Two collimators and single doses ranging from 20 to 100 Gy were used to treat stereotactically defined areas of 3.7- and 4.7-mm cross section (80% isodose) in the right frontal lobe. The dose-response relationship for the end-point necrosis at 19 months revealed a mean tolerance dose (D50) of 34.2 Gy (standard errors: +4.1, -3.7 Gy). Histologic, immunohistochemical, and angiographic examinations were performed to evaluate delayed radiation effects. RESULTS: All animals irradiated with 100 Gy developed radiation necrosis after 9 months. Microangiography and immunohistochemical fluorescence staining of the endothelial cells revealed dose-dependent vascular dilatation and rarefaction. Animals irradiated with 20-50 Gy showed no morphologic changes after 9 months. With irradiation of 30-50 Gy, histologic vascular changes that increased with dose were found after 19 months. At that time, no changes were detected after irradiation with 20 Gy with both field sizes and after irradiation with 30 Gy and the 2-mm collimator. Radiation-induced functional disturbances of the brain vasculature could be demonstrated by extravasation of contrast medium by using a microangiographic technique. CONCLUSION: The observed effect had a definite dependence on dose, volume, and time after treatment.     

Preoperative short-term irradiation in rectal cancer

From 1979 through 1983, 78 patients underwent short-term preirradiation before primary operation for rectal carcinoma at the Medical Radiation Institute of Tübingen. A hyperfractionated total dose of 16 Gy was applied within a maximum time of 36 hours in four fractions of 4 Gy each. Surgery was performed at the last irradiation day. The medium observation time of the total group of patients was five years and three months, at least 40 months. The local recurrence rate of all patients followed up is 9% (7/78), for stage Dukes A it is 6% (2/32), for stage Dukes B 0%(0/25), for stage Dukes C 27% (3/11), and for stage Dukes D 20% (2/10). In the group of 68 patients showing no metastases at the moment of surgery, the rate of formation of remote metastases amounts to 21%, in stage Dukes A to 13% (4/32), in stage Dukes B to 24% (6/25), and in stage Dukes C to 36% (4/11). The relapse-free survival during the follow-up period is 66% (45/68), for stage Dukes A 69% (22/32), for stage Dukes B 68% (17/25), and for stage Dukes C 55% (6/11). There were no acute or late radiogenic complications. Compared to publications about cases treated only by surgery, the present preirradiated patient's group shows a considerable lower local recurrence rate and an increased relapse-free survival rate. These improved treatment results are probably due to preoperative irradiation. The incidence of perioperative complications was not increased by preoperative irradiation.     

Results of percutaneous transluminal irradiation of biliary tract carcinoma with 192Iridium

In 22 patients with bile duct carcinoma's intratumoral irradiation was performed through a percutaneous biliary drainage. 17 of them had been found to be inoperable at laparotomy, 5 others had recurrent carcinoma at the site of a biliodigestive anastomosis. The applied dose ranged from 60 to 80 Gy at 6 mm distance of the centre of the Iridium source. In 12/22 patients a clear reduction in the degree of tumor stenosis could be established. Regarding the survival of the patients (8.6 months) results were relatively poor, due to extensive metastases. Patients with a documented dilatation of tumor stenosis showed a low significant longer survival period (12.3 months) than those without detectable response (4.2 months).     

Perioperative high-dose-rate brachytherapy in locally advanced and recurrent gynecologic cancer: Initial results of a phase II trial

BACKGROUND: This study was undertaken to determine the feasibility of perioperative high-dose-rate brachytherapy (PHDRB) as an adjunct to salvage surgery in primary advanced or recurrent gynecologic cancer. METHODS: Twenty-five patients with either locally advanced (n = 4) or recurrent (n = 21) gynecologic cancer suitable for salvage surgery were included. Unirradiated patients were treated with preoperative chemoradiation followed by salvage surgery and PHDRB (R0 and R1 resections receiving 16 or 24 Gy, respectively). Previously irradiated patients were treated with salvage surgery and PHDRB alone with 32 or 40 Gy for R0 or R1 resections, respectively. RESULTS: Resections were categorized as R0 in 9 patients (36.0%) and R1 in 16 (64.0%). Four previously irradiated patients suffered fatal pelvic bleeding between 8 and 13 months after surgery and PHDRB. After a median follow-up of 20 months (3-55+), the 4-year actuarial local and pelvic controls were 88.1% and 80.8%, respectively. The 4-year distant metastases-free survival was 40.9%. Four-year actuarial overall survival was 34.0%, with a median survival of 27.1 months (95% confidence interval: 17.5-36.8). CONCLUSIONS: Local and pelvic control results are excellent for this very high-risk-disease population. PHDRB dose in previously irradiated patients has been shifted to the closest lower level due to unacceptable vascular toxicity.     

肾上腺转移瘤的伽马刀治疗

目的探讨肾上腺转移瘤的伽马刀治疗效果。方法对20例肾上腺转移瘤病人,用伽马刀进行肾上腺转移瘤适形放射外科治疗,以50%~60%等剂量曲线包绕病灶,周边剂量3.5Gy~4.5Gy,隔日1次,共8~10次。结果除2例因全身多处转移伴全身衰竭未完成治疗外,18例患者完成治疗。5例患者治疗后有2例生存超过1年,1年生存率为40%(2/5)。治疗后超过6个月的12例患者中,10例生存;6个月生存率为83.3%(10/12)。随访患者平均生存时间10个月。伽马刀治疗后3个月后复查,根据B超和CT检查肾上腺转移瘤,88.9%(16/18)患者的转移瘤有不同程度的缩小。77.8%(14/18)患者原有的腰痛症状逐步减轻。结论肾上腺转移瘤对放射治疗敏感,伽马刀治疗肾上腺转移瘤是比较安全有效的姑息治疗,无严重并发症。     

Pre- and postoperative radiotherapy of oral carcinoma of a locally advanced stage. An analysis of the results and complications

The combination of radiotherapy and surgery in the treatment of advanced oral carcinoma (T3 and T4 lesions) yields good possibilities of recovery; whether radiotherapy should be given before or after surgery is still debated. Fifty patients with advanced oral carcinomas were analyzed: 24 of them were irradiated before and 26 after surgery; doses ranged from 40 to 56 Gy for the first group of patients, and from 50 to 68 Gy for the second one. The disease-free survival 48 months after the diagnosis was 36% in patients who received preoperative irradiation, and 53.6% in patients who received postoperative radiotherapy; the latter allowed local control of the disease to be significantly improved (chi 2 3.99, 0.01 less than p less than 0.05). The quality of survival was worse in the group receiving preoperative irradiation, because of radiation-induced surgical complications, which were especially observed in patients with diffuse disease. Our findings suggest that postoperative radiotherapy may be advisable if the tumor is resectable, since tolerance and local control rate were acceptable. On the contrary, nearly inoperable masses and massive neck diseases often require preoperative irradiation.     

Treatment results of surgical and radiologic therapy of penile cancer

A retrospective analysis was made about the results achieved in 64 patients after combined surgical and radiotherapeutic treatment. The tumor areas were irradiated by fast electrons or cobalt 60 with 50 to 55 Gy, the lymph nodes received doses of 45 to 55 Gy. Local tumor control was achieved in 27 out of 28 patients irradiated immediately after surgery (96%). In case of demonstrated lymph node invasion, local control was achieved in 14 out of 19 cases (74%). The median survival was 9.6 years for patients in stage T1/2, N0, M0 and 2.5 years for patients in stage T1-4, N+, M0. The first two years following to therapy were decisive for the prognosis. Among those of our patients who developed recurrences during this period, not one could be cured in the long run. Two years after the end of therapy, the survival probability of patients without lymph node metastases becomes comparable to the survival curve of normal male population of the same age. In the treatment of penile carcinoma, a gradual proceeding depending on the stage is recommended for the combination of surgery and radiotherapy. In case of lymph node metastases, the application of adjuvant chemotherapy should be taken into consideration.     

Retrobulbar irradiation of endocrine ophthalmopathy: a comparison between 10 and 16 Gy total dose

Severe Graves' ophthalmopathy has been treated in 44 cases by orbital irradiation. 36 out of 37 patients showed a good response or a suspend of the progressive disease. In 17 out of 33 primary irradiations a dose of 10 Gy and in 16 cases a dose of 16 Gy was applied. Measured by ophthalmopathy-index significant better results have been achieved by a total dose of 16 Gy. Because of recurrence after primary irradiation of 10 Gy a re-irradiation became necessary in 35% of the cases. Primary irradiation of 16 Gy has required no further treatment during the same time of observation. A single series of 16 Gy irradiation has shown better results than two series of 10 Gy irradiation concerning the proptosis and alleviation of symptoms.     

Impact of pulmonary metastases of the R1H-tumour on radiation tolerance of rat lung

PURPOSE: The aim was to investigate the influence of pulmonary metastases of the rhabdomyosarcoma R1H on the radiation response of the lung of the WAG/Rij rat. MATERIAL AND METHODS: Three groups of animals were investigated: metastases-free animals treated with fractionated irradiation of the lungs; metastases-bearing animals receiving no irradiation; and metastases-bearing animals treated with fractionated irradiation initiated 14, 21 or 28 days after induction of pulmonary metastases of the R1H-tumour by i.v. injection of viable tumour cells. Metastases were thus treated at various well-defined sizes. Total doses of 20-60Gy were applied in fractions of 2 Gy within 11 days. Complication rate and survival time were used as endpoints. RESULTS: About 2 months after onset of irradiation treatment, animals had to be sacrificed because of severe respiratory distress either caused by irradiation-induced lung damage (median 57 days, range 36-77 days), or because of development of lung metastases (65, 20-160 days). A decrease of the ED(50) (dose required to induce lethal lung damage in 50% of irradiated animals) was determined for metastases-bearing animals. This effect increased with metastatic volume. CONCLUSIONS: The results suggest that the presence of tumours in the lung decreased the lung tolerance to radiation. This effect can hardly be explained by a reduction in functional lung volume by metastatic volume.     

Radiotherapy of medulloblastoma

Between 1970 and 1985, 29 patients were postoperatively irradiated for medulloblastoma. Eight out of them received only a local irradiation and 21 a complete CNS irradiation. The posterior fossa was saturated up to a dose of 45 to 49 Gy in nine patients and 50 to 55 Gy in twelve patients. The patients treated by complete CNS irradiation show a three-year survival rate of 47% and a five-year survival rate of 40%. A nonsignificant increase of the three-year survival rate is found in patients whose posterior fossa was exposed to a higher radiation dose. Eleven recurrences were observed, and the posterior fossa was involved in seven out of these cases. Four recurrences confined to the spine were found after a dose of 20 to 30 Gy. Remote metastases, preferentially with a skeletal site, were formed in three out of 29 cases.