IMRT using simultaneously integrated boost (SIB) in head and neck cancer patients.

BACKGROUND: Preliminary very encouraging clinical results of intensity modulated radiation therapy (IMRT) in Head Neck Cancer (HNC) are available from several large centers. Tumor control rates seem to be kept at least at the level of conventional three-dimensional radiation therapy; the benefit of normal tissue preservation with IMRT is proven for salivary function. There is still only limited experience with IMRT using simultaneously integrated boost (SIB-IMRT) in the head and neck region in terms of normal tissue response.The aim of this work was (1) to establish tumor response in HNC patients treated with SIB-IMRT, and (2) to assess tissue tolerance following different SIB-IMRT schedules. RESULTS: Between 1/2002 and 12/2004, 115 HNC patients have been curatively treated with IMRT. 70% received definitive IMRT (dIMRT), 30% were postoperatively irradiated. In 78% concomitant chemotherapy was given. SIB radiation schedules with 5-6 x 2 Gy/week to 60-70 Gy, 5 x 2.2 Gy/week to 66-68.2 Gy (according to the RTOG protocol H-0022), or 5 x 2.11 Gy/week to 69.6 Gy were used. After mean 18 months (10-44), 77% of patients were alive with no disease. Actuarial 2-year local, nodal, and distant disease free survival was 77%, 87%, and 78%, respectively. 10% were alive with disease, 10% died of disease. 20/21 locoregional failures occurred inside the high dose area. Mean tumor volume was significantly larger in locally failed (63 cc) vs controlled tumors (32 cc, p <0.01), and in definitive (43 cc) vs postoperative IMRT (25 cc, p <0.05); the locoregional failure rate was twofold higher in definitively irradiated patients. Acute reactions were mild to moderate and limited to the boost area, the persisting grade 3/4 late toxicity rate was low with 6%. The two grade 4 reactions (dysphagia, laryngeal fibrosis) were observed following the SIB schedule with 2.2 Gy per session. CONCLUSION: SIB-IMRT in HNC using 2.0, 2.11 or 2.2 Gy per session is highly effective and safe with respect to tumor response and tolerance. SIB with 2.2 Gy is not recommended for large tumors involving laryngeal structures.

A 12 country field study of the EORTC QLQ-C30 (version 3.0) and the head and neck cancer specific module (EORTC QLQ-H&N35) in head and neck patients. EORTC Quality of Life Group.

This study tests the reliability and validity of the European Organization for Research and Treatment of Cancer (EORTC) head and neck cancer module (QLQ-H&N35) and version 3.0 of the EORTC Core Questionnaire (QLQ-C30) in 622 head and neck cancer patients from 12 countries. The patients completed the QLQ-C30, the QLQ-H&N35 and a debriefing questionnaire before antineoplastic treatment or at a follow-up. 232 patients receiving treatment completed a second questionnaire after treatment. Compliance was high and the questionnaire was well accepted by the patients. Multitrait scaling analysis confirmed the proposed scale structure of the QLQ-H&N35. The QLQ-H&N35 was responsive to differences between disease status, site and patients with different Karnofsky performance status, and to changes over time. The new physical functioning scale (with a four-point response format) of version 3.0 of the QLQ-C30 was shown to be more reliable than previous versions. Thus, the QLQ-H&N35, in conjunction with the QLQ-C30, appears to be reliable, valid and applicable to broad multicultural samples of head and neck cancer patients.

Localized prostate cancer in elderly patients. Outcome after radiation therapy compared to matched younger patients.

PURPOSE: To detect a difference in outcome (disease-specific survival, local tumor progression, late toxicity, quality of life) after curative radiotherapy for localized prostate cancer in elderly as compared to younger patients. PATIENTS AND METHODS: In a retrospective analysis 59 elderly patients (> 74 years old) were matched 1:2 with younger patients from the data base according to tumor stage, grading, pre-treatment PSA values and year of radiotherapy. Surviving patients were contacted to fill in a validated questionnaire for quality of life measurement (EORTC QLQ-C30). Median follow-up for elderly and younger patients was 5.2 and 4.5 years, respectively. RESULTS: Overall survival at 5 years was 66% for the elderly and 80% for younger patients. Intercurrent deaths were observed more frequently in the elderly population. There was no age-specific difference in disease-specific survival (78% vs 82%), late toxicity or quality of life. Clinically meaningful local tumor progression was observed in 15% and 14%, respectively, corresponding to data from the literature following hormonal ablation. CONCLUSIONS: There is no obvious difference in outcome including disease-specific survival, late toxicity and quality of life in elderly patients, compared to a matched younger population. A clinically meaningful local tumor progression following radiotherapy or hormonal ablation only is rare. Local radiotherapy or, alternatively, hormonal ablation is recommended to preserve local progression-free survival in elderly patients except for very early stage of disease (i.e. T1 G1-2 M0).

Quality of life in patients cured from a carcinoma of the head and neck by radiotherapy: the importance of the target volume.

PURPOSE: To assess the health-related quality of life (QOL) of long-term survivors of carcinomas of different subsites of the head and neck following curative radiotherapy (RT). PATIENTS AND METHODS: Patients continuously free from recurrence or second primary tumors treated 1988-1994 were contacted 5.1 to 5.9 years after RT and asked to fill in the EORTC QLQ-C30 core questionnaire and the H&N cancer module. RT had been restricted to the glottis (group A; carcinomas of the vocal cord T1-2 N0), or had included bilateral neck nodes and the primary tumor outside the nasopharynx (group B; AJC Stage II to IV) or within the nasopharynx, respectively (group C; Stage II to IV). Response rate was 97% (group A; n = 41), 69% (group B; n = 26) and 71% (group C; n = 12), respectively. The groups were different with respect to age (older in group A), alcohol consumption (absent in group C) and proportion of females (more in group C). RESULTS: Patients with nasopharyngeal cancer reported the highest morbidity on the H&N module (dry mouth, sticky saliva, trismus, problems with teeth, trouble eating). However, these symptoms did not have a high impact on global QOL or function scores on the QLQ-C30 core questionnaire. Patients in group B reported a lower global QOL but less severe symptoms on the module. CONCLUSION: The high morbidity of patients treated for a nasopharyngeal cancer may be explained by the location of the target volume which included the bilateral temporo-mandibular joints and the salivary glands. These patients require appropriate care during follow-up and will probably profit most from new RT techniques with sparing of normal tissues.

Curative radiotherapy in elderly patients with endometrial cancer. Patterns of relapse, toxicity and quality of life.

PURPOSE: To assess survival, disease-specific survival, acute and late toxicity and quality of life in patients with curable endometrial carcinoma treated with adjuvant or primary radiotherapy at the age > or = 75 years. PATIENTS AND METHODS: In a prospective study, outcome was regularly assessed in 49 patients treated between 1991 and 1995 at a median age of 78.4 years. Radiotherapy was applied using the same concept as in younger patients. Thirty-eight patients received postoperative adjuvant radiotherapy (vaginal insertions only: n = 18; external and vaginal insertions: n = 17; external radiotherapy only: n = 3), 8 patients were treated for a vaginal recurrence. Three patients received primary radiotherapy. Median pelvic dose was 39.6 Gy (ICRU) with 1.8 Gy per fraction (4 fields). Vaginal HDR radiotherapy consisted of 5 times 5 Gy at 0.5 cm depth in cases with no external radiotherapy, and of 3 times 5 Gy in addition to pelvic radiotherapy, respectively. Median follow-up was 3.2 years. The EORTC QLQ-C30 was used for self-assessment of quality of life. RESULTS: Survival and disease-specific survival at 5 years was 64% and 84%, respectively. There was no pelvic or vaginal recurrence in patients with Stage IA to IIB. Patients with positive adnexa and those treated for vaginal recurrence relapsed in 50%. Two patients (4%) did not complete radiotherapy because of severe diarrhea. Grade 4 late complications were observed in 1/38 patients following adjuvant radiotherapy and in 2/8 patients treated for a recurrence. The actuarial rate of Grade 3 to 4 complications was 7% at 3 years. Quality of life was good in most cases and remained constant over time. CONCLUSIONS: Elderly patients with endometrial cancer may be treated following the same guidelines as younger patients. Radiotherapy for a vaginal recurrence is less effective and more toxic.

Prognostic value of cerebrospinal fluid cytology in pediatric medulloblastoma. Swiss Pediatric Oncology Group.

BACKGROUND: Although the demonstration of leptomeningeal dissemination is the most important predictor of poor outcome in children with medulloblastoma, there is lack of consensus on the prognostic value of a positive cerebrospinal fluid (CSF) cytology (i.e., stage M1). PATIENTS AND METHODS: Eighty-six pediatric medulloblastoma patients treated in Switzerland between 1972-1991 were retrospectively studied regarding the influence of M-stage on prognosis. 39 were M0, 13 M1, 15 Mx, 17 M2, and 2 M3. RESULTS: Five- and 10-year overall survival rates were 76% and 54% for M0, 68% and 50% for Mx, 36% and 25% for M1, and 22% and 22% for M2-3 (P < 0.001), respectively. No significant survival differences were observed between M1 and M2-3 patients. Among 26 patients with only postoperative CSF cytologies, seven were positive. Their outcome was similar to that of six preoperatively staged M1 and significantly different from that of M0 patients (P = 0.001). In 14 patients both pre- and postoperative CSF cytology was performed. Total agreement was observed between the pre- and postoperative results (six positive and eight negative). Among the 19 M2-3 patients CSF cytology was positive in eight, negative in five, and unknown in six. CONCLUSIONS: A positive CSF cytology either pre- or postoperatively predicts for a poor outcome, similar to that observed in stage M2-3 patients. A postoperative cytology is likely to be concordant with cytologic results obtained preoperatively, and seems to have the same prognostic significance. A negative cytology, however, does not exclude a more advanced stage.

Hyperfractionated radiotherapy and simultaneous cisplatin for stage-III and -IV carcinomas of the head and neck. Long-term results including functional outcome.

PURPOSE: To assess the survival rate, the probability of local control, the patterns of relapse and late sequelae including self-reported quality of life in patients treated with hyperfractionated radiotherapy (RT) and simultaneous CDDP chemotherapy for stage-III to stage-IV carcinomas of the head and neck. METHODS: From 1988 to 1994, 64 patients (median age 55.5 years) with carcinomas of different subsites, excluding the nasopharynx, were treated in a pilot study with 1.2 Gy bid (6 h interval; total dose 74.4 Gy) and simultaneous CDDP (20 mg/m2 daily, 5 days in week 1 and 5) and followed at regular intervals. Overall survival and local control, as well as the rates of late toxicity, were estimated using the actuarial method. Median follow-up was 3.3 years for all and 5.2 years for surviving patients. To assess the quality of life, the EORTC QLQ-C 30 questionnaire and the H&N35 module questionnaire were sent to the patients surviving with no evidence of disease or second primary tumors; they were answered by 15/23 (67%). RESULTS: Overall survival was 37% at 5 years, whereas disease-specific survival was 59%. Twenty-three patients died from uncontrolled head and neck cancer. Second primary tumors were observed in 13 patients, most frequently in the lung. Local control without salvage surgery was 74% at 5 years for all subsites and stages, and loco-regional disease-free survival was 72%. Eleven patients developed distant metastases, which was the only site of failure in 6 cases. Salvage surgery was successful in 2 cases. The actuarial estimates of > or = grade-3 late toxicity was 4% for the mandibular bone and 23% for dysphagia, and 50% of the patients experienced a permanent xerostomy. Self-reported global quality of life in surviving patients was good (mean 68 points on a scale 0 to 100); consequences of impaired salivary function had most impact on nutritional and social aspects. CONCLUSIONS: Hyperfractionated RT with concomitant CDDP is well tolerated and highly efficient in controlling moderately advanced to advanced cancers of the head and neck. Second primary tumors are the main cause of death after 3 years and were observed outside of the irradiated area, most frequently in the lung. Even after RT of large volumes to a high dose, salvage surgery can be successfully performed in individual cases. Self-reported quality of life of surviving patients is good, despite xerostomy-associated nutritional difficulties.

Radiotherapy for metastatic carcinomas of the kidney or melanomas: an analysis using palliative end points.

PURPOSE: To assess the rate and duration of response to palliative radiotherapy (RT) in patients with metastatic melanoma or renal cell carcinoma. PATIENTS AND METHODS: From 1992 to 1995, 90 patients were entered into a nonrandomized study. Goals of palliative RT were prospectively defined and subjective response was documented at the end of RT, after 2-6 weeks, and every 3 months thereafter. Most patients were treated with 5 x 4 Gy or 10 x 3 Gy. RESULTS: Relief of pain from bone lesions was observed in 26 of 40 cases, with a duration of response of 2.4 months, corresponding to 57% of the remaining lifetime. A total of 55% of patients with persistent neurologic dysfunction despite corticosteroids improved, for a duration of 2.5 months (86% of the further lifespan). Freedom from symptoms in patients treated for impending neurological complications from metastases to the brain, spine, or nerve plexus was documented for 86-100% of their lifetime. CONCLUSIONS: Despite the methodological flaws discussed, the efficacy of a short course of palliative RT for so-called radioresistant tumors is demonstrated.

[Radiotherapy of epipharyngeal carcinoma: successes and limits as examples of new treatment strategies]. / Strahlentherapie des Epipharynxkarzinoms: Erfolge und Grenzen als Beispiel neuer Behandlungsstrategien.

In treating cancer patients, disease free survival and survival have been improved during the last decade by technical progress and new systemic therapies. In radiation therapy as well as in any other cancer treatment potential long-term side effects and complications need special attention. The success of doubling tumour control by radiation therapy in patients with head and neck tumours illustrates the needs of long-term follow-ups. Cost-effectiveness has to be considered, when treatment results of RT equal surgical results, as it is often the case in head and neck tumours as well as in other malignant diseases.

Cardiac risk after mediastinal irradiation for Hodgkin's disease.

PURPOSE: To evaluate the risk of cardiac lesions after conventionally fractionated irradiation (Rt) of the mediastine with or without chemotherapy (Ct) in patients with Hodgkin's disease (HD) and to relate them to known cardiovascular risk factors. PATIENTS AND METHODS: Between 1964 and 1992, 352 (total group) patients with HD were treated with curative intention using Rt with or without Ct including the mediastine and had a follow-up of at least 1 year. More than 96% of the patients had a complete follow-up. One hundred forty-four patients (64% of the living patients, heart study group) have regular follow-up in our department and had a special heart examination including rest and exercise ECG, echocardiography and myocardial perfusion scintigraphy (112 patients). Doses per fraction in the anterior heart region were between 1.3 and 2.1 Gy. Total doses were between 30.0 and 42.0 Gy in 93% of cases. The mean length of follow-up was 11.2 years (range 1.0-31.5 years). Other cardiovascular risk factors evaluated were body mass index, blood pressure, smoking history, diabetes mellitus, hypercholesterolemia and history of coronary artery disease before Rt. RESULTS: In the total group, the risk of fatal cardiac ischemic events and/or of sudden unexpected death was significantly higher than expected with a relative risk of 4.2 for myocardial infarction and 6.7 for myocardial infarction or sudden death. In female patients and in patients without other cardiovascular risk factors, the risk of fatal or non-fatal ischemic cardiac events was not significantly different from the expected value. In the subgroup with no cardiovascular risk factors and treatment without Ct, there was no ischemic or other major cardiac event. Echocardiography showed valvular thickenings in a large amount of the patients (the cumulative risk after 30-year follow-up was above 60%) but mostly without hemodynamic disturbance. In patients without hypertension and without coronary artery disease, findings of perfusion scintigraphy and echocardiographic evaluation of systolic and diastolic function were normal. Treatment with Ct was not a significant risk factor for cardiac events but the number of patients whose treatment included adriamycin and with a follow-up exceeding 10 years is to low for a definitive evaluation. CONCLUSIONS: In patients without the usual cardiovascular risk factors (smoking, hypertension, obesity, hypercholesterolemia, diabetes mellitus) the risk of serious cardiac lesions after conventionally fractionated irradiation of the mediastinum with an intermediate total dose between 30 and 40 Gy is low. Also the cardiac risk of the combination of this irradiation with Ct including adriamycin with a total dose between 200 and 300 mg/m2 seems low but further long-term observation is necessary.

Asymmetry correction equations for hand volume, grip and pinch strengths in healthy working people.

Assessments of oedema and decrease in hand strength are useful for patients with a hand lesion. This study examined the asymmetry of the arms and determined the estimates of the unknown prior to lesion values for hand volume, grip strengths assessed with a Jamar dynamometer (GS[J]) and a Collins dynamometer (GS[C]), and pinch strength with a Jamar pinch gauge (PS) in 100 healthy working people. Hand volume, GS(J), GS(C) and PS of the dominant hand were respectively 3.6 +/- 4.1%, 6.6 +/- 9.2%, 11.7 +/- 11.2%, and 8.0 +/- 13.2% higher than those of the non-dominant hand (p < 0.001). Very good estimates were obtained with the values of the contralateral arm for all the indices studied. The correlation coefficient equalled 0.95 for hand volume, 0.91 for GS(J), 0.83 for GS(C), and 0.72 for PS. These estimates allow us to evaluate the evolution of oedema and hand strengths in patients with hand injury, especially to determine whether they could return to work as they are mostly manual workers with demanding jobs.

Comparison between estimates of hand volume and hand strengths with sex and age with and without anthropometric data in healthy working people.

Edema and hand strength measurements are useful for the recovery assessment of patients with a hand lesion. This work determined and compared estimates of hand volume, grip strengths (measured with a Jamar and a Collins dynamometer), and pinch strength (with a Jamar pinch gauge) in terms of sex and age with or without anthropometric indices in healthy working people. The sample included 100 subjects from within the staffs of two rehabilitation centres. For both grip strengths, multiple linear regression models including body height, weight, and arm muscle area were very good (multiple correlation coefficient R of about 0.84) and clearly better than those obtained with sex and age only. For pinch strength, the best estimate was obtained with sex and arm muscle area (R of 0.76); for hand volume, the model with sex, body height, and weight provided the best result (R of 0.93). These findings suggested that anthropometric indices easy to measure must be taken into account to estimate hand volume and hand strengths.

Pediatric medulloblastoma: radiation treatment technique and patterns of failure.

PURPOSE: In this study factors are analyzed that may potentially influence the site of failure in pediatric medulloblastoma. Patient-related, disease-related, and treatment-related variables are analyzed with a special focus on radiotherapy time-dose and technical factors. METHODS AND MATERIALS: Eighty-six children and adolescents with a diagnosis of medulloblastoma were treated in Switzerland during the period 1972-1991. Postoperative megavoltage radiotherapy was delivered to all patients. Simulation and portal films of the whole-brain irradiation (WBI) fields were retrospectively reviewed in 77 patients. The distance from the field margin to the cribiform plate and to the floor of the temporal fossa was carefully assessed and correlated with supratentorial failure-free survival. In 19 children the spine was treated with high-energy electron beams, the remainder with megavoltage photons. Simulation and port films of the posterior fossa fields were also reviewed in 72 patients. The field size and the field limits were evaluated and correlated with posterior fossa failure-free survival. RESULTS: In 36 patients (47%) the WBI margins were judged to miss the inferior portion of the frontal and temporal lobes. Twelve patients failed in the supratentorial region and 9 of these patients belonged to the group of 36 children in whom the inferior portion of the brain had been underdosed. On multivariate analysis only field correctness was retained as being significantly correlated with supratentorial failure-free survival (p = 0.049). Neither the total dose to the spinal theca nor the treatment technique (electron vs. photon beams) were significantly correlated with outcome. Posterior fossa failure-free survival was not influenced by total dose, overall treatment time, field size, or field margin correctness. Overall survival was not influenced by any of the radiotherapy-related technical factors. CONCLUSION: A correlation between WBI field correctness and supratentorial failure-free survival was observed. Treatment protocols should be considered that limit supratentorial irradiation mainly to subsites at highest risk of relapse. Optimized conformal therapy or proton beam therapy may help to reach this goal. Treating the spine with electron beams was not deletereous. A significant correlation between local control and other technical factors was not observed, including those relating to posterior fossa treatment. The use of small conformal tumor bed boost fields may be prefered to the larger posterior fossa fields usually considered as the standard treatment approach.

Synthesis and biochemical evaluation of N-(4-phenylthiazol-2-yl)benzenesulfonamides as high-affinity inhibitors of kynurenine 3-hydroxylase.

In this paper we describe the synthesis, structure-activity relationship (SAR), and biochemical characterization of N-(4-phenylthiazol-2-yl)benzenesulfonamides as inhibitors of kynurenine 3-hydroxylase. The compounds 3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl]benzenesulfonamide 16 (IC50 = 37 nM, Ro-61-8048) and 4-amino-N-[4-[2-fluoro-5-(trifluoromethyl)phenyl]-thiazol-2-yl] benzenesulfonamide 20 (IC50 = 19 nM) were found to be high-affinity inhibitors of this enzyme in vitro. In addition, both compounds blocked rat and gerbil kynurenine 3-hydroxylase after oral administration, with ED50's in the 3-5 mumol/kg range in gerbil brain. In a microdialysis experiment in rats, 16 dose dependently increased kynurenic acid concentration in the extracellular hippocampal fluid. A dose of 100 mumol/kg po led to a 7.5-fold increase in kynurenic acid outflow. These new compounds should allow detailed investigation of the pathophysiological role of the kynurenine pathway after neuronal injury.

Acute toxicity of curative radiotherapy in elderly patients.

AIM: One reason for obvious differences in cancer treatment of elderly patients, compared to younger patients, may be the fear of reduced tolerance at a higher age. The purpose of the study was to document acute tolerance of radiotherapy with curative intent in patients > 74 years old. Special emphasis was given to 72 patients treated to large volumes and/or high doses for gynecological carcinomas, prostate cancer of subsites of the head and neck requiring bilateral treatment of the neck including major parts of the pharynx and larynx. PATIENTS AND METHOD: From January 1991 to May 1995, 210 consecutive patients entered a prospective study to assess acute toxicity of radiotherapy given with curative intent. Median age was 79.3 (74.4 to 93.7) years. Fifty-three percent received postoperative radiotherapy, 47% radiotherapy alone. Radiation technique, fractionation and doses were the same as applied in younger patients. Tolerance was scored using a 5-point scale; in addition, pre- and post-treatment Karnofsky performance status and body weight were assessed. RESULTS: Acute toxicity leads to a dose reduction in 3 patients. The death of 1 patient with Hodgkin's disease was attributable to large field radiotherapy, and 1 case of grade 4 cystitis was noted in a patient with prostate cancer. Radiotherapy for breast cancer with or without lymph nodes imposed no problem. With appropriate supportive measures, even hyperfractionated or accelerated radiotherapy regimens for carcinomas of the head and neck were feasible in elderly patients. Radiotherapy to the pelvic region lead to severe diarrhea requiring medication in 20% of the patients. For all areas treated, higher age within the range of > 74 to < 94 years did not increase the severity of the acute radiation reactions. CONCLUSIONS: Using the same treatment schedules and techniques of radiotherapy as for younger patients, curative radiotherapy is well tolerated in patients aged > 74 years treated even when major parts of the pharynx and larynx or large volumes of the pelvis are included. Small bowel reaction (diarrhea) and pharyngeal mucositis deserve special attention and supportive care in elderly patients prone to a rapidly symptomatic dehydration.

Radiotherapy for carcinomas of the head and neck in elderly patients.

BACKGROUND/AIM: One fourth of patients with carcinomas of the head and neck present at the age of > or = 75 years, but tolerance and outcome of radiotherapy in this population is unknown from the literature. Our aim was to assess the overall survival rate in comparison to the survival probability of the normal population, and to document the efficacy of local treatment. PATIENTS AND METHODS: From 1980 to 1993, 75 patients aged 75 years or more (median 78.5 years) were treated with curative intent for carcinomas of the head and neck excluding the nasopharynx, paranasal sinuses, salivary glands and lips. Seventeen received postoperative radiotherapy, 58 were treated with radiotherapy alone. Early stage disease (T1 or T2 N0) was present in 26 patients, 27 patients presented with stage T3 and T4 any N. Eight patients received hyperfractionated radiotherapy to 74.4 Gy with 1.2 Gy twice daily. All others were treated with 1.8 to 2 Gy to a median total dose of 70 Gy in 6 to 8 weeks. RESULTS: All but 6 patients completed radiotherapy. Local control at 3 years was 83% for early stage disease, and 39% for T3 and T4 tumors. Actuarial overall survival was 30% at 5 years, compared to 63% for age-matched male and 69% for female Swiss residents, respectively. The survival curve of the patients followed the curve of the normal population after a rapid drop in survival within the first 2 years. Median time to local relapse was 3 and 4 months, respectively, for early and advanced stages, and 6 months for glottic carcinomas. Except 1 case of bone necrosis, there was no severe late toxicity observed. CONCLUSION: Although retrospective, the results suggest that the ultimate outcome in elderly patients with carcinomas of the head and neck is comparable to the course of the disease in younger patients.

[Low-dose radiotherapy of localized prostate neoplasms: How low is high enough?]. / Kleinvolumige Bestrahlung lokalisierter Prostata-karzinome: Wie klein ist gross genug?

BACKGROUND: According to the American Patterns of Care Studies, at least 70 Gy are required to achieve local control of large or undifferentiated carcinomas of the prostate. More recent data on repeated measurements of the prostate-specific antigen (PSA) cast doubt on the radiocurability of tumors with markedly elevated PSA. PATIENTS AND METHODS: With a retrospective analysis, the treatment results of local radiotherapy to mid-sized pelvic volumes with a median dose of 66 Gy (1979 to 1988, n = 118) are compared to the outcome after radiotherapy to small prostatic volumes with a median dose of 70.2 Gy (1989 to 1992, n = 126). RESULTS: Overall survival at 5 years was 65.9% and 82.3%, respectively. Patients treated at a later time had the same life expectancy as expected for the normal population. Distant disease-free survival was identical in both groups (70.4 and 74.3% at five years). Local control could not be assessed by digital rectal examination in a large part of the patients. However, in 50 patients without any pretreatment, the course of PSA was followed. Pretreatment values of > 30 ng/ml were highly predictive for "biochemical relapse" (rising values) within 2 years. Despite individual shielding of the rectum, the rate of symptomatic proctitis rose from 1.7% to 5.6% in patients treated 1989 to 1992. CONCLUSIONS: We found no negative impact of decreasing the target volume on the overall and distant disease-free survival. The rate of symptomatic proctitis has increased with higher target doses despite better shielding of the rectum, but has remained within an acceptable range. Considering the high rate of biochemical relapse and therefore the poor prognosis associated with initial PSA values > 30 ng/ml, the application of a potentially toxic dose of > 70 Gy in these patients seems hardly justified.

Radiation studies on B cell differentiation marker CD24/SCLC Cluster-4 antigen expressing and non-expressing lung cancer cell lines and mouse fibroblasts.

A correlation between CD24 expression and higher intrinsic radiation sensitivity has been described in B-lineage acute lymphoblastic leukaemia (B-ALL). We recently identified the SCLC surface antigen Cluster-4 (CL-4) to be identical to the B cell differentiation marker CD24, except for one amino acid residue. The CD24/CL-4 antigen is highly expressed on SCLC, but rarely on NSCLC cells. In order to investigate the influence of the expression of CD24/CL-4 on the radiation sensitivity in a non-leukaemic cell system, sublines of the human SCLC H249 cell line transfected with mutated ras oncogene, and differing in their CD24/CL-4 expression, were studied. In addition, we stably transfected the NSCLC A125 cell line and the mouse fibroblast NIH3T3 cell line with the CL-4 cDNA. The differential expression of CD24/CL-4 on the cells had no influence on morphology, proliferation and cloning efficiency. Radiation studies were done with cells in exponential growth phase. In the highly resistant NSCLC A125 cells no difference in radioresponsiveness was observed between CD24/CL-4 expressing and non-expressing cells. In the rather radiosensitive cells, similar responses to radiation were observed between CD24/CL-4 expressing and non-expressing SCLC H249-ras cells, whereas the CL-4 transfected NIH3T3 mouse fibroblasts showed a substantially higher radioresistance than the CD24/CL-4 non-expressing control cells. In conclusion, the correlation between CD24/CL-4 expression and radiation sensitivity is controversial and depends on the cell type.

[Radiotherapy in prostatic carcinoma]. / Radiotherapie beim Prostatakarzinom.

Treatment of patients with prostate cancer has become one of the most frequent indications in radiation oncology. Reasons for this fact may be the increasing number of elderly patients, early diagnosis and urologists who are familiar with the possibility of tumor control by radiation. The treatment results and side effects of modern techniques are presented. Many questions concerning treatment policy remain unanswered. Due to the long natural history of prostate cancer we will have to endorse clinical trials and wait many years for their results.