Simultaneous radiochemotherapy versus radiotherapy alone in advanced head and neck cancer: a randomized multicenter study.

PURPOSE: A prospective randomized multicenter trial was performed to evaluate the contribution of simultaneously administered chemotherapy (CT) and radiotherapy (RT) in previously untreated patients with unresectable stage III/IV head and neck cancer. PATIENTS AND METHODS: Patients with locoregionally advanced head and neck cancer were treated either with RT alone (arm A) or simultaneous RT plus CT (RCT; arm B). RT was identical in both arms and administered in three courses with 13 fractions of 1.8 Gy each twice daily. During one course, from day 3 to 11, 23.4 Gy was delivered. In arm B, cisplatin (CDDP) 60 mg/m2, fluorouracil (5-FU) 350 mg/m2 by intravenous (i.v.) bolus, and leucovorin (LV) 50 mg/m2 by i.v. bolus were given on day 2, and 5-FU 350 mg/m2/24 hour by continuous infusion and LV 100 mg/m2/24 hours by continuous infusion were given from day 2 to 5. Treatment was repeated on days 22 and 44; a total RT dose of 70.2 Gy was administered. Treatment breaks were scheduled from days 12 to 21 and days 34 to 43. RESULTS: From 1989 to 1993, 298 patients were enrolled and 270 patients were assessable. Acute mucositis grade 3 or 4 was more frequent in arm B (38%) than in arm A (16%) (P < .001). Total treatment time was significantly longer in arm B than in arm A (P < .001) due to prolonged breaks. According to hematologic toxicity, scheduled drug doses were given in 74% of patients for the second course and 46% for the third course. The 3-year overall survival rate was 24% in arm A and 48% in arm B (P < .0003). The 3-year locoregional control rate was 17% in arm A and 36% in arm B (P < .004). Both arms showed similar distant failure patterns (arm A, 13 of 140; arm B, 12 of 130). Serious late side effects were not significantly different between treatment arms (arm A, 6.4%; arm B, 10%; not significant). CONCLUSION: Concomitant CT offered improved disease control and survival in advanced head and neck cancer patients. Due to increased acute toxicity, more supportive care is demanded when CT is given simultaneously. Increased total treatment time does not exert a negative impact on outcome in this combined modality regimen.

Sequential chemo-radiotherapy in locally advanced squamous cell carcinoma of the head and neck.

Between 1982 and 1983, 32 patients were treated for locally advanced inoperable squamous cell carcinoma (SCC) of the head and neck in a prospective pilot study. Patients received two to five courses of chemotherapy consisting of methotrexate, bleomycin and cis-dichlorodiammine-platinum (II). Radical radiotherapy was performed two weeks after administration of chemotherapy. Despite the high initial response rate to chemotherapy of 62.5%, long-term results remained poor. After a median follow-up of 10.5 months (3-39 months), 15 patients were still alive, but only 4 were clinically free of disease. Aggressive chemotherapy does not prevent delivery of full-dose radiotherapy for SCC of the head and neck. Furthermore, our study does not suggest that chemotherapy has a great influence on long-term results.

Accelerated split-course radiotherapy and simultaneous cis-dichlorodiammine-platinum and 5-fluorouracil chemotherapy with folinic acid enhancement for unresectable carcinoma of the head and neck.

Thirty-four (6 stage III, 28 stage IV) patients with advanced squamous cell carcinoma of the head and neck were treated by simultaneous radio-chemotherapy. Treatment was divided into three cycles. Chemotherapy consisted of cis-diamminedichloroplatinum(II) (cis-DDP) 60 mg/sqm i.v., 5-fluorouracil (5-FU) 350 mg/sqm i.v. and folinic acid (FA)-50 mg/sqm i.v. on day 2 and 5-FU 350 mg/sqm per 24 h and FA 100 mg/sqm/24 h on days 2-5. Radiotherapy consisted of 23.4 Gy/9 days divided in 13 fractions of 1.8 Gy delivered twice a day from day 3 through day 11. This regimen was repeated on days 22 and 44. Total radiation dose amounted to 70.2 Gy/51 days. Mean follow-up of surviving patients was 21 (14-34) months. 28/32 patients achieved complete response, 4/32 partial response. Actuarial one and two years survival were 88 and 58% including two early deaths from tumour bleeding. Local control rates at one and two years were 87 and 81%, respectively. This protocol produces excellent palliation and the chance of improved long term tumour control. Two patients developed distant metastases. Overall toxicity was tolerable. Since the treatment breaks were inserted after low radiation doses, acute mucositis healed rapidly and was not a limiting factor.

[The value of magnetic resonance tomography during radiotherapy of childhood tumors in the posterior fossa and the pineal region]. / Der Wert der Kernspintomographie bei der Strahlen-therapie kindlicher Tumoren der hinteren Schädelgrube und der Pinealisregion.

MRT is a highly sensitive method for the diagnosis of childhood tumours in the posterior fossa. Since it demonstrates tumour extent better than does CT, MRT is the method of choice for radiotherapy planning. The result of treatment can be judged morphologically and by measuring relaxation times. Changes due to treatment can be recognised more easily than by CT. A disadvantage of MRT is lack of specificity, since various processes may lead to an equal increase in T1 and T2 times.

[Experimental studies on the accuracy of mineral content assessment in spongiosa bone using quantitative CT (single energy measurement)]. / Experimentelle Untersuchungen zur Genauigkeit der Mineralsalzgehaltsbestimmung spongiöser Knochen mit Hilfe der quantitativen CT (Einenergiemessung).

The mineral content of 42 lumbar vertebral bodies (using a phantom to simulate living conditions) and of 30 calcanea was measured by quantitative CT. The bones were subsequently ashed and the calcium and fat content determined chemically. The mineral concentration (calibrated against a K2HPO4 solution) showed good correlation with the calcium content (for the lumbar vertebrae, r = 0.963 and for the calcanea r = 0.94. The fat content of the bone marrow leads to a systematic under-estimation of the mineral content, if one uses single energy CT measurements. The experimental findings can be satisfactorily treated in a quantitative way with the help of a model which contains the three components of spongy bone (mineral, fat and fat-free connective tissue.

[Mineral content of the peripheral skeleton in patients with diabetes mellitus ]. / Ergebnisse der Bestimmung des Mineralsalzgehaltes am peripheren Skelett bei Patienten mit Diabetes mellitus.

In order to determine the effect of diabetes mellitus on bone mineral content, measurements with the iodine 125 isotope method of Cameron were carried out in the distal ulna and calcaneus of 40 patients. 38% of female and 20% of male diabetic patients showed abnormally low values. The most severe changes were found in patients with complications of diabetes. There was a correlation between the duration of the diabetes and the severity of the mineral loss.

[Lung function scintigraphy in the diagnosis of regional disturbances of ventilation (author's transl)]. / Lungenfunktionsszintigraphie zur Erkennung regionaler Ventilationsstörungen

Lung function scintigraphy is the method of choice for the diagnosis of regional ventilation disturbances. The aim of this study was to determine which of various parameters is the most reliable. Sensitivity of the 3-minute retension test is 96%, of the single breath 45%, equilibration 32% and of the ventilation index, only 28%. Sensitivity of the various parameters for demonstrating multi-focal ventilation abnormalities is 100% for the 3 minute retention test, 32% for single breath, 19% for equilibration and 21% for the ventilation index. The underlying basis for these findings is discussed and it is concluded that it is possible to simplify the technique when dealing with regional ventilation abnormality in obstructive airway disease, but not when dealing with other restrictive changes.

[Functional scintigraphy of pulmonary ventilation with 133Xe in juvenile scoliosis (author's transl)]. / Die Funktionsszintigraphie der Lungenventilation mit 133Xe bei juveniler Skoliose.

Twenty children with severe scoliosis underwent spirometry, chest X-ray and 133Xe ventilation studies before surgical correction by the Harrington operation. By means of functional scintigraphy the relative distribution of the functional residual capacity (FRC) and the wash-out curves (3-min-retention without background correction, mean time constant, effectivity index after background correction) were analysed quantitatively. The chest X-ray and the single-breath-phase of the ventilation study remained mostly unchanged, whereas the shifting of the FRC distribution towards the lung of the concave side indicated in all cases a regional ventilation restriction of the convex side. In addition the analysis of the wash-out curves showed a regional impairment of the alveolar ventilation of the convex side which exceeded the shifting of FRC distribution. Even in the cases with normal spirometric values all scintigraphic parameters were slightly pathological, probably due to the decreased lung function caused by the scoliosis. The effectivity index taking into account the respiration frequency, the tidal volume, the FRC and the dead space, was found to be the most accurate and sensitive parameter for the evaluation of regional ventilation impairment.

[A combination surgical-radiological approach for the treatment of carcinoma of the hepatic duct bifurcation with involvement of both hepatic duct trunks]. / Ein kombiniert chirurgisch-radiologisches Konzept zur Behandlung des Hepaticusgabelcarcinoms mit Befall beider Hepaticusstämme.

The only curative treatment to proximal bile duct cancers with involvement of both hepatic ducts is liver transplantation. A curative resection with wide lateral clearance is limited due to the neighbourhood of vital anatomic structures in the liver hilum. The majority of patients with bile duct cancers is over 60 years of age and due to concomitant disease, they do not fulfill the requirements for liver transplantation. Our treatment strategy in adequate cases is palliative tumor resection and reconstruction of bile passage by sutureless biliodigestive anastomosis as proposed by Rodney Smith. We treated 11 patients with this method, in 5 patients an additive combined radiotherapy by percutaneous radiation and intraluminal after-loading therapy was performed. Our results indicate that this strategy leads to effective palliation in cases provided that only microscopic residual tumor is left in situ (R1-resection). Our observed survival times compare favorably to survival times after liver transplantation (average survival time 11.5 months median survival time 10 months).

Properties of fiber optics for application in astronomical interferometry.

We tested such properties of single-mode and multimode fiber optics that are relevant for use in a long-baseline astronomical interferometer, and we give quantitative values for modulation, transmission, and stability of the fiber optics as measured in a Mach-Zehnder interferometer configuration. Only polarization-maintaining single-mode fibers gave satisfying results. Good preservation of modulation and ease of beam combining are strong features of these fibers, whereas the light losses that are due to imperfect coupling may present a serious problem.

[Changes in the serum level of female sex hormones following radiocastration using different total doses]. / Veränderungen der Serumspiegel weiblicher Geschlechtshormone nach Strahlenkastration mit unterschiedlicher Gesamtdosis.

We determined serum levels of estradiol, FSH and LH over a period of six to eight weeks after ovarian irradiation for castration with different doses (2 x 2.5 Gy/3 x 2.5 Gy/4 x 2.5 Gy) in 15 patients with metastatic breast cancer as compared to changes after ovariectomy in five patients. The time course of the changing estradiol-, FSH and LH-serum levels significantly depends on the ovarian dose. After radiological castration with a dose of 4 x 2.5 Gy = 10 Gy in four days the estrogen levels decrease within two to three weeks, and the FSH- and LH-levels increase after three to four weeks into the postmenopausal range. Therefore, the time course is not very different from changes after ovariectomy.

[Simultaneous radio- and chemotherapy of squamous cell carcinoma of the esophagus]. / Simultane Radio-Chemotherapie beim Plattenepithelkarzinom des Osophagus.

Between 1983 and 1986, 41 patients with a squamous cell carcinoma of the oesophagus without hematogenic metastases were treated with a combination of radio- and chemotherapy preoperatively. Treatment consisted of mitomycin C (10 mg/sqm/day 1) and continuous infusion of 5 fluorouracil (1000 mg/sqm/day-day 1 to 4) with a maximum of 1500 mg per day. On day 2 radiotherapy was started. After the administration of 36 Gy all patients were restaged. Nine patients were referred to surgery. In 13 cases surgery was refused, because of inoperability, due to local or distant metastases. In these patients radiotherapy was continued up to 50 to 60 Gy for palliation. Although the disease was confined to the oesophagus no surgery was performed in 19 patients, because of age, enhanced risk of anaesthesia or refusal by the patient. These patients were treated with radiotherapy alone (60 Gy) with curative intention. 32 patients treated without surgery were followed up. For the patients treated with curative intent, the one year survival rate was 62%, the two year survival rate was 42%. Compared to a group treated in 1970 bis 1982 with the same dosage of irradiation without the combination of chemotherapy the median survival could be raized from nine to 24 months, the two year survival rate improved from 18% to 42%. Patients treated for palliation only did not survive the first year after therapy.

[The development of radiation caries after high doses of irradiation]. / Die Entstehung der Strahlenkaries nach hochdosierter Bestrahlung.

39 patients, who were irradiated with doses of 50 to 70 Gy for ENT-tumors over a period of 3.5 months to three years prior to the examination, showed a rapidly progressing caries of the teeth inside the target volume. The teeth outside the target volume developed a caries of less extent. Radiation induced xerostomia, effects of the irradiation of the soft tissues, nutrition habits and hygiene are discussed as causes for the damage of the teeth.

[Individual face masks as aids in quasi-3-D planning and completion of irradiation of tumors of the head and neck]. / Individuelle Gesichtsmasken als Hilfsmittel bei der Quasi-3-D-Planung und Durchführung der Bestrahlung von Tumoren im Kopf-Hals-Bereich.

Apparatus for immobilizing the patient's head in an identically reproducible position is required, if the advantages of exact quasi-3-D-therapy planning are to be fully exploited for the irradiation of irregular target volumes in the head and neck area. The topics of this report are the production and application of individual thermoplastic masks in connection with special head supports for CT planning scans, simulation and irradiation.

[Radiotherapy of precancerous conditions in the ENT area]. / Strahlentherapie von Präkanzerosen im HNO-Bereich.

Precancerous lesions of the oral cavity and the larynx are usually treated by surgery, because a complete histological examination for detecting an invasive carcinoma is important and, on the other hand, modern surgery procedures yield very satisfactory functional results. High-dose irradiation of inoperable high-risk precancerous lesions of the larynx may be taken into account. Experiences in the irradiation of inoperable low-risk lesions with different doses are very rare. The carcinoma in situ should be treated like an invasive carcinoma. 10 years of experience in radiotherapy of precancerous lesions of the larynx in 23 patients are reported.

[Determination of 131-J-hippuran clearance in renal camera functional scintigraphy using simplified Oberhausen's method]. / Bestimmung der 131-J-hippuran-Clearance im Rahmen der Kamerafunktionsszingigraphie der Nieren nach vereinfachten Modifikationen der Methode von Oberhausen

The determination of 131-I-Hippuran clearance in connection with renography or renal camera sequential scintigraphy will give a quantitative evaluation of total and individual renal function. The "single shot" method of Oberhausen yields clearance values corresponding very well to the PAH standard clearance. To simplify this method for routine use in connection with camera sequential scintigraphy, we studied some modifications of the method, using regional activity curves instead of the activity curve of the partially shielded whole body. Simultaneously with the camera sequential scintigraphy we measured activity curves of the partially shielded whole body (lead-shielding of kidneys and bladder, two probes), the shoulder (one probe), the head (one probe) and a background region of the camera (ROI) above the kidneys for 30 min. All four curves were analyzed, using computer analysis (bi-exponential curve fitting) as well as tables of Oberhausen, and his formula was used for clearance calculation. Under two conditions a) taking blood samples between 15 and 25 min. p.i. b) using the tables of Oberhausen for curve analysis, the clearance out of the regional activity curves correlates well with the clearance out of the partially shielded whole body activity curve (r greater than 0,97). Therefore, it is possible determine 131-I-Hippuran clearance in a simple manner without lead-shielding of kidneys and bladder, either with one additional probe measurement at shoulder or head or without any probe measurement, using the camera and measuring a background curve (ROI) above the kidneys. This simple clearance method can easily be performed simultaneously with 131-I-Hippuran renography or renal camera sequential scintigraphy in routine.

[Results of interstitial radiotherapy using I-125 seeds in the treatment of prostatic cancer]. / Ergebnisse nach interstitieller Strahlentherapie mit J-125-Seeds bei der Behandlung des Prostatakarzinoms.

30 patients with localized adenocarcinoma of the prostate were treated with pelvic lymphadenectomy and I-125 interstitial implantation from 1980 to 1985 (21/30 T3-tumors and 14/30 with poor differentiation). The mean follow-up is 59.5 months (range 18 to 88 months). The crude, progression-free and local progression-free survival rates (Kaplan-Meier) for all patients are 68%, 61% and 71% respectively. But, the progression-free survival is 39% in patients with G3-tumors after five years and only 25% in patients with T3 G3-tumors after four years. The local progression rate was 33% in patients with T3-tumors. We did not observe any late intestinal side-effects, but 11/30 (37%) patients suffered from later urinary flow problems caused mainly by local tumor progression. Therefore, we regard interstitial implantation with I-125-seeds as an alternative treatment to radical prostatectomy in patients with T1, 2 G1, 2-tumors but as insufficient in patients with T3 G3-tumors.

[A ventral mantle technic with dorsolateral mediastinal saturation in the radiotherapy of Hodgkin's disease]. / Ventrale Mantelfeldtechnik mit dorsolateraler Mediastinalaufsättigung bei der Strahlentherapie des Morbus Hodgkin.

Between 1975 and 1981 69 patients suffering from Hodgkin's disease stage I to III were treated by radiotherapy exclusively. In contrast to the standard modalities the mantle was treated only through a ventral portal with dorsolateral boost to the posterior mediastinum. The geometrical treatment arrangement and the modalities of dose application yielded favourable dose distributions and single doses within the target volume. The analysis of failures showed no in field-failure, six marginal recurrences, and 17 distant failures, which are not related to the technique of irradiation. The described technique of mantle irradiation seems to be equivalent to the standard technique with regard to tumor control and side effects.

[Bone density determination using 125I-densitometry in idiopathic scoliosis]. / Knochendichtebestimmung mit der 125J-Densitometrie bei der idiopathischen Skoliose.

The aim of the present study was to find out whether idiopathic scoliosis is associated with a general reduction of the calcium salt content of the bones. The study was conducted in a scoliosis patient group of 48 individuals, using 125I densitometry.