An unrandomized prospective comparison of urinary continence, bowel symptoms and the need for further procedures in patients with and with no adjuvant radiation after radical prostatectomy.

OBJECTIVE: To prospectively assess, using a questionnaire-based study, the relative differences and changes in urinary continence and bowel symptoms, and the need for further surgery, within the first year after radical retropubic prostatectomy (RRP) in patients with and with no adjuvant radiotherapy (aRT). PATIENTS AND METHODS: The study included 96 men with clinically organ-confined adenocarcinoma of the prostate who underwent RRP between March 1998 and June 1999. A subset of 36 patients was recommended aRT of the prostatic fossa (median dose 54 Gy) because of positive surgical margins and/or seminal vesicle involvement. Using a mailed questionnaire all patients were prospectively assessed at 4-month intervals for the first year after RRP. RESULTS: Valid data were analysed from 83 patients (overall response rate 86%), of whom 30 (36%) had received aRT. At 4 months a significantly lower proportion used no pads and significantly more used 1 pad/day in the aRT than in the RRP group (both P < 0.05). Eight and 12 months after RRP there was no statistically significant difference between the groups in urinary incontinence. However, 53% of men in the aRT group had stool urgency and 13% reported fecal incontinence at 4 months, compared with 1.9% and none (both P < 0.01) of the RRP group. At 1 year after RRP bowel symptoms and fecal continence improved in the aRT group and there was no significant difference for these symptoms between the groups. Starting aRT early (< or = 12 weeks after RP) or late (> 12 weeks) had no significant effect on urinary continence, bowel symptoms and fecal incontinence. Apart from dilatation of urethral strictures in one patient in each group, no further procedures were reported during the follow-up. CONCLUSION: A moderate dose of aRT after RRP had a temporary effect on subjective urinary continence at 4 months but not at 8 and 12 months. More patients receiving aRT reported significant bowel symptoms at 4 and 8 months than those with RRP only, but at 1 year most of these symptoms had resolved and there were no significant differences between the groups.

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.

[Primary radiotherapy of laryngeal carcinoma. An analysis of the therapeutic results and of the the relapse behavior in 283 patients]. / Primäre Strahlentherapie des Larynxkarzinoms. Eine Analyse der Therapieergebnisse und des Rezidivverhaltens bei 283 Patienten.

PURPOSE: In the treatment of laryngeal carcinoma definitive radiotherapy results in a similar outcome as surgical treatment in the early stages with a lower morbidity rate and good functional results. In fact no randomized studies exist, so far, and the optimal treatment concept for the different stages is not well defined. The following study analyses retrospectively the treatment results and the recurrence data in patients with a squamous cell carcinoma of the larynx treated with definitive radiotherapy. PATIENTS AND METHOD: Two hundreds and eighty-three patients with carcinoma of the larynx were treated with radiation therapy in the department of radiology of the LMU München between September 1971 and June 1986. Twenty-six patients (9.2%) were female and 257 (73.1%) male. The median age was 68.5 years, respectively 70 years. All patients had a histologically confirmed squamous cell carcinoma of the larynx. No true subglottic cases were observed. Forty-one (14.5%) tumors were localized supraglottically, 207 (73.1%) glottically. Thirty-five patients had a T4 tumor with glottic and supraglottic involvement. In 147 patients the histopathological grading was evaluable: 32 tumors were classified as G1, 95 as G2, 15 as G3 and 5 as G4. According to the UICC classification of 1979 25 patients had a carcinoma in situ (Tis), 93 patients had a stage T1, 90 stage T2, 40 stage T3 and 35 stage T4. Two hundreds and thirty-three of 283 (82.3%) had no lymph node involvement. In 50 patients clinically a lymph node involvement was observed. 22 patients had a stage N1, 5 patients stage N2 and 23 patients stage N3. An external beam radiation mostly with cobalt-60 was performed with a mean dose of 61.9 Gy. RESULTS: The 5-years relapse-free survival for the whole group was 61.7%. The probability for "no evidence of disease" (NED) depended on tumor stage and localisation (glottic tumors: Tis/T1 90.5%: T2 59.4%: T3 39.6%: [5-year NED]; supraglottic tumors T1 64.2%: T2/3 28.6%: T4/N3 24.7% [3-year NED]). Other significant prognostic factors besides T-stage were N-stage (NO vs. N1-3: 3-year recurrence-free survival 68% vs. 37.2%, p < 0.001) and histopathologic grading (G1 vs. G3/4: 3-year recurrence-free survival 74% vs. 37.1%, p < 0.01). One hundred and twenty-two (43.1%) patients had a recurrence, which occurred in 75.4% local, in 12.3% loco regional, in 8.2%, with distant metastases and 4.1% combined. In 50 patients with a recurrent disease a salvage therapy was carried out. Thereby 17 patients achieved a complete response. CONCLUSION: Even for the here described negatively selected patient group with a high median age and multimorbidity, good local control rates could be achieved especially in early stages with definitive radiation therapy. In more advanced stages even in elderly patients a combined surgical-radiotherapeutic treatment should be performed.

[Primary radiotherapy of nasopharyngeal carcinoma]. / Primäre Strahlentherapie des Nasopharynxkarzinoms.

One hundred twenty-one patients treated for nasopharyngeal carcinoma with radiation therapy were analyzed; 85 were male, 36 were female. Twenty-one percent had tumour stage T0/T1; 32.5%, T2; 27.5%, T3; and 19%, T4. In 75% of the cases, the lymph nodes were involved. Twelve patients underwent a neck dissection. Histology showed squamous cell carcinoma in 38%, lymphoepitheloid carcinoma in 41.4%, undifferentiated carcinoma in 19%, and adenocarcinoma in 2%. Beginning in 1980, a modified radiation technique with large portals and an increase of the dose from 57.1 Gy to 61.5 Gy targe volume dose was used. Five year overall survival was 32.1%, recurrence-free survival, 30.7%; and local recurrence free survival, 45.8%. Age, sex, and T stage had no significant influence on survival. Multivariate analysis (Cox model) showed that involvement of the lymph nodes, histology, and the new irradiation technique with the higher total dose significantly influenced survival.

Is aggressive surgical palliation of proximal bile duct cancer with involvement of both main hepatic ducts worthwhile?

The only curative treatment for proximal bile duct cancer with involvement of both main hepatic ducts is liver transplantation. Most patients do not fulfill the requirements for liver transplantation. Our treatment strategy in appropriate cases is palliative tumor resection and reconstruction of the biliary passage by sutureless bilioenteric anastomosis. We have treated 12 patients, 5 in combination with intraluminal and percutaneous radiotherapy. Our results indicate that this strategy leads to effective palliation in some cases provided that only microscopic residual tumor is left in-situ. Our survival times compare favourably with survival after liver transplantation.

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.

[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).

[Long-term follow-up of 52 endoluminal irradiated patients with central lung tumors]. / Langzeitverlauf von 52 endoluminal bestrahlten Patienten mit zentralen Lungentumoren.

The results of a prospective follow-up study comprising 52 patients with central tumours of the lung submitted to endoluminal irradiation are reported. Additional external irradiation was possible in 30 patients (group A), but not in 22 patients (group B). Satisfactory immediate results were observed, together with a one-year survival rate of 39.3% (group A) and 12.5% (group B).

[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.

[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.

[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.

Prognostic risk factors in advanced Hodgkin's lymphoma. Report of the German Hodgkin Study Group.

In a national multicentre trial in the FRG patients with Hodgkin's lymphoma in stages CS/PS III B/IV were entered into the HD 3 protocol and received induction chemotherapy with 3 x (COPP + ABVD). Patients in complete remission (CR) received consolidation therapy by either radiotherapy (20 Gy IF) or chemotherapy (COPP + ABVD). Patients not in CR received salvage therapy (40 Gy in case of persisting nodal disease, else 4 x CEVD chemotherapy). Between July 1983 and May 1987 230 untreated patients aged 15 to 60 qualified for this HD 3 protocol. This analysis is based on the first 137 patients evaluable for response. Of these, 86 (63%) achieved CR after induction chemotherapy. Including salvage therapy a total of 104 patients (76%) achieved CR. Univariate and multivariate prognostic risk factor analyses were performed using freedom from treatment failure (FFTF) as endpoint. Sex, age, splenectomy, bone marrow, liver and bone involvement had no prognostic impact nor had stage according to the Ann Arbor classification. In contrast, a pretreatment erythrocyte sedimentation rate (ESR) above 80 mm/h and a serum alkaline phosphatase (AP) above 230 IU/ml appeared as significant risk factors (p less than 0.01, relative risk 2.3). The two parameters were not independent. Comparing a group A (ESR less than or equal to 80 and AP less than or equal to 230) versus a pooled group B (ESR greater than 80 and/or AP greater than 230) increased the difference (p less than 0.001, relative risk of 2.8) which was also significant for survival (p less than 0.04).

[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.

[Intraoperative electron irradiation of malignant pancreatic tumors--initial experiences at Grosshadern]. / Intraoperative Elektronenbestrahlung (IORT) maligner Pankreastumoren--erste Grosshaderner Erfahrungen.

15 patients with locally unresectable pancreatic carcinomas were treated by IORT and bypass surgery. 13 patients without distant metastases were additionally treated by external beam irradiation. Although only one patient had a local failure, the median survival was only eight months. Severe complications were seen in eight patients, gastrointestinal bleeding occurred in six patients and was the cause of death in three patients. The stop of weight loss and the impressive pain relief within ten days after IORT demonstrate the significance of this treatment modality with respect to palliative effects.

[Endoluminal irradiation of tracheobronchial tumors using a high dose rate iridium-192 afterloading device]. / Endoluminale Bestrahlung mit dem HDR-Iridium-192-Afterloadingverfahren bei tracheobronchialen Tumoren.

We report about 50 patients with inoperable bronchus tumors treated since March 1986 in a prospective non randomized study with high dose rate iridium-192 afterloading (AL) irradiation in 140 applications. 26 patients were treated combined with external irradiation. 32 were treated before with laser therapy, one with chemotherapy (small cell carcinoma). The actuarial survival rate (Kaplan-Meier) was 26% after 36 weeks for all patients; 38% for combined endoluminal and external irradiation and 9% for patients treated with AL alone. Death was caused by the local tumor in 85%. In 41% lethal bleeding was seen.

[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.

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.