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Summary Background We previously reported the 5-year results of the phase 3 IBCSG 23-01 trial comparing disease-free survival in patients with breast cancer with one or more micrometastatic (≤2 mm) sentinel nodes randomly assigned to either axillary dissection or no axillary dissection. The results showed no difference in disease-free survival between the groups and showed non-inferiority of no axillary dissection relative to axillary dissection. The current analysis presents the results of the study after a median follow-up of 9·7 years (IQR 7·8–12·7). Methods In this multicentre, randomised, controlled, open-label, non-inferiority, phase 3 trial, participants were recruited from 27 hospitals and cancer centres in nine countries. Eligible women could be of any age with clinical, mammographic, ultrasonographic, or pathological diagnosis of breast cancer with largest lesion diameter of 5 cm or smaller, and one or more metastatic sentinel nodes, all of which were 2 mm or smaller and with no extracapsular extension. Patients were randomly assigned (1:1) before surgery (mastectomy or breast-conserving surgery) to no axillary dissection or axillary dissection using permuted blocks generated by a web-based congruence algorithm, with stratification by centre and menopausal status. The protocol-specified primary endpoint was disease-free survival, analysed in the intention-to-treat population (as randomly assigned). Safety was assessed in all randomly assigned patients who received their allocated treatment (as treated). We did a one-sided test for non-inferiority of no axillary dissection by comparing the observed hazard ratios (HRs) for disease-free survival with a margin of 1·25. This 10-year follow-up analysis was not prespecified in the trial's protocol and thus was not adjusted for multiple, sequential testing. This trial is registered with ClinicalTrials.gov, number NCT00072293. Findings Between April 1, 2001, and Feb 8, 2010, 6681 patients were screened and 934 randomly assigned to no axillary dissection (n=469) or axillary dissection (n=465). Three patients were ineligible and were excluded from the trial after randomisation. Disease-free survival at 10 years was 76·8% (95% CI 72·5–81·0) in the no axillary dissection group, compared with 74·9% (70·5–79·3) in the axillary dissection group (HR 0·85, 95% CI 0·65–1·11; log-rank p=0·24; p=0·0024 for non-inferiority). Long-term surgical complications included lymphoedema of any grade in 16 (4%) of 453 patients in the no axillary dissection group and 60 (13%) of 447 in the axillary dissection group, sensory neuropathy of any grade in 57 (13%) in the no axillary dissection group versus 85 (19%) in the axillary dissection group, and motor neuropathy of any grade (14 [3%] in the no axillary dissection group vs 40 [9%] in the axillary dissection group). One serious adverse event (postoperative infection and inflamed axilla requiring hospital admission) was attributed to axillary dissection; the event resolved without sequelae. Interpretation The findings of the IBCSG 23-01 trial after a median follow-up of 9·7 years (IQR 7·8–12·7) corroborate those obtained at 5 years and are consistent with those of the 10-year follow-up analysis of the Z0011 trial. Together, these findings support the current practice of not doing an axillary dissection when the tumour burden in the sentinel nodes is minimal or moderate in patients with early breast cancer. Funding International Breast Cancer Study Group.

Purpose To establish the feasibility and tolerability of gefitinib (ZD1839, Iressa) with radiation (RT) or concurrent chemoradiation (CRT) with cisplatin (CDDP) in patients with advanced non–small cell lung cancer (NSCLC). Patients and Methods In this multicenter Phase I study, 5 patients with unresectable NSCLC received 250 mg gefitinib daily starting 1 week before RT at a dose of 63 Gy (Step 1). After a first safety analysis, 9 patients were treated daily with 250 mg gefitinib plus CRT in the form of RT and weekly CDDP 35 mg/m 2 (Step 2). Gefitinib was maintained for up to 2 years until disease progression or toxicity. Results Fourteen patients were assessed in the two steps. In Step 1 (five patients were administered only gefitinib and RT), no lung toxicities were seen, and there was no dose-limiting toxicity (DLT). Adverse events were skin and subcutaneous tissue reactions, limited to Grade 1–2. In Step 2, two of nine patients (22.2%) had DLT. One patient suffered from dyspnea and dehydration associated with neutropenic pneumonia, and another showed elevated liver enzymes. In both steps combined, 5 of 14 patients (35.7%) experienced one or more treatment interruptions. Conclusions Gefitinib (250 mg daily) in combination with RT and CDDP in patients with Stage III NSCLC is feasible, but CDDP likely enhances toxicity. The impact of gefitinib on survival and disease control as a first-line treatment in combination with RT remains to be determined.

Owing to their sessile nature, plants are constantly exposed to a multitude of environmental stresses to which they react with a battery of responses. The result is plant tolerance to conditions such as excessive or inadequate light, water, salt and temperature, and resistance to pathogens. Not only is plant physiology known to change under abiotic or biotic stress, but changes in the genome have also been identified. However, it was not determined whether plants from successive generations of the original, stressed plants inherited the capacity for genomic change. Here we show that in Arabidopsis thaliana plants treated with short-wavelength radiation (ultraviolet-C) or flagellin (an elicitor of plant defences), somatic homologous recombination of a transgenic reporter is increased in the treated population and these increased levels of homologous recombination persist in the subsequent, untreated generations. The epigenetic trait of enhanced homologous recombination could be transmitted through both the maternal and the paternal crossing partner, and proved to be dominant. The increase of the hyper-recombination state in generations subsequent to the treated generation was independent of the presence of the transgenic allele (the recombination substrate under consideration) in the treated plant. We conclude that environmental factors lead to increased genomic flexibility even in successive, untreated generations, and may increase the potential for adaptation.

Intermolecular recombination events were monitored in Arabidopsis thaliana lines using specially designed recombination traps consisting of tandem disrupted beta-glucuronidase or luciferase reporter genes in direct repeat orientation. Recombination frequencies (RFs) varied between the different lines, indicating possible position effects influencing intermolecular recombination processes. The RFs between sister chromatids and between homologous chromosomes were measured in plants either hemizygous or homozygous for a transgene locus. The RFs in homozygous plants exceeded those of hemizygous plants by a factor of2, implying that in somatic plant cells both sister chromatid recombination and recombination between homologous chromosomes exist for recombinational DNA repair. In addition, different DNA-damaging agents stimulated recombination in homozygous and hemizygous plants to different extents in a manner dependent on the type of DNA damage and on the genomic region. The genetic and molecular analysis of recombination events showed that most of the somatic recombination events result from gene conversion, although a pop-out event has also been characterized.

PURPOSE: To report results of 18-month follow up of external beam radiation therapy with photons for subfoveal classic or occult choroidal neovascularization (CNV) in age-related macular degeneration (ARMD). DESIGN: Randomized clinical trial. METHODS: A total of 161 patients with subfoveal CNV in ARMD were recruited in a prospective double-masked study. The posterior pole of the afflicted eye was given 1 Gy (4 × 0.25 Gy) in the control group and 8 Gy (4 × 2 Gy) or 16 Gy (4 × 4 Gy) in the treatment groups. At the time of treatment, and 6, 12, and 18 months post treatment, best-corrected visual acuity (BCVA), reading ability, and CNV size were measured. RESULTS: At the completion of the study 150 (93.2%), 139 (86.3%), and 137 (85.1%) patients were followed for 6, 12, and 18 months, respectively. The mean number of lines lost in the BCVA was −1.69, −2.2, and −3.23 in the 1 Gy group; −0.94, −1.25, and −1.73 in the 8 Gy group; −0.51, −0.67, and −1.93 in the 16 Gy group. The difference was significant after 12 months (P = .016 for 8 Gy vs. 1 Gy; P = .006 for 16 Gy vs. 1 Gy), and 18 months (P = .011 for 8 Gy vs. 1 Gy; P = .05 for 16 Gy vs. 1 Gy). The patients with classic CNV, or with an initial distance visual acuity ≥20/100, benefited more from treatment. A significant difference was not found between control group and treatment groups in the reading ability and in the CNV size. No radiation-associated side effects were reported thus far. CONCLUSION: The number of lines lost in the BCVA was less in the 8 Gy and 16 Gy treatment groups than in the control group during the complete follow up examination. Radiation therapy with 8 Gy and 16 Gy, without showing any difference in efficacy, resulted in a near stabilization of the BCVA in patients with subfoveal classic or occult CNV in ARMD. Further studies are necessary to determine the significance of repeated radiotherapy series with a dose of 8 Gy to improve the effect on the CNV size and thereby to prolong stabilization of distance visual acuity.

In a prospective study with a 5-year follow-up, we assessed the effect of a single series of low-dose radiation on the distance visual acuity in eyes with angiographically confirmed subfoveal choroidal neovascularization (CNV) in age-related macular degeneration (ARMD). The posterior pole of 12 eyes was treated with 5 Gy (4 x 1.25 Gy), and 34 eyes treated with 8 Gy (4 x 2 Gy). The best corrected distance visual acuity was measured at the time of treatment, and annually thereafter for 5 years. The study obtained complete follow-up for 11 patients in the 5-Gy group (nine classic, two occult CNVs), and 29 patients in the 8-Gy group (12 classic, 17 occult CNVs). At baseline, the mean distance visual acuity of the treated eyes was 0.16 (20/125) in the 5-Gy group, and 0.2 (20/100) in the 8-Gy group. Five years later, an average loss of 3.2 lines was present in the 5-Gy group, and 4 lines in the 8-Gy group. After 5 years, an average loss of 2 lines was found in a control group consisting of 18 second eyes with low stage dry ARMD, with a mean distance visual acuity of 0.5 (20/40) at baseline. Statistical analyses with Wilcoxon and Mann-Whitney U-tests showed that a single series of low dose radiation with either 5 Gy or 8 Gy was not able to stabilize the distance visual acuity of eyes with subfoveal CNV in ARMD during a 5-year follow-up.

Plants are continuously subjected to UV-B radiation (UV-B; 280–320 nm) as a component of sunlight causing damage to the genome. For elimination of DNA damage, a set of repair mechanisms, mainly photoreactivation, excision, and recombination repair, has evolved. Whereas photoreactivation and excision repair have been intensely studied during the last few years, recombination repair, its regulation, and its interrelationship with photoreactivation in response to UV-B-induced DNA damage is still poorly understood. In this study, we analyzed somatic homologous recombination in a transgenic Arabidopsis line carrying a β-glucuronidase gene as a recombination marker and in offsprings of crosses of this line with a photolyase deficient uvr2–1 mutant. UV-B radiation stimulated recombination frequencies in a dose-dependent manner correlating linearly with cyclobutane pyrimidine dimer (CPD) levels. Genetic deficiency for CPD-specific photoreactivation resulted in a drastic increase of recombination events, indicating that homologous recombination might be directly involved in eliminating CPD damage. UV-B irradiation stimulated recombination mainly in the presence of photosynthetic active radiation (400–700 nm) irrespective of photolyase activities. Our results suggest that UV-B-induced recombination processes may depend on energy supply derived from photosynthesis.

Long-term depletion of the stratospheric ozone layer contributes to an increase in terrestrial solar ultraviolet-B radiation$^{1,2,3}$. This has deleterious effects on living organisms, such as DNA damage$^{4,5}$. When exposed to elevated ultraviolet-B radiation (UV-B; 280–315 nm), plants display a wide variety of physiological and morphological responses characterized as acclimation and adaptation$^{6}$. Here we show, using special sun simulators, that elevated solar UV-B doses increase the frequency of somatic homologous DNA rearrangements in Arabidopsis and tobacco plants. Increases in recombination are accompanied by a strong induction of photolyase and Rad51 gene expression. These genes are putatively involved in major DNA repair pathways, photoreactivation and recombination repair$^{7,8}$. In mutant Arabidopsis plants that are deficient in photoreactivating ultraviolet-induced cyclobutane pyrimidine dimers, recombination under elevated UV-B regimes greatly exceeds wild-type levels. Our results show that homologous recombination repair pathways might be involved in eliminating UV-B-induced DNA lesions in plants. Thus, increases in terrestrial solar UV-B radiation as forecasted for the early 21st century may affect genome stability in plants.

To assess the prognostic factors in patients with transitional-cell carcinoma of the renal pelvis and/or ureter, a series of 138 patients with transitional-cell carcinoma of the renal pelvis and/or ureter was collected in a retrospective multicentre study. 12 patients with distant metastases were excluded from the statistical evaluation. All but 3 patients underwent radical surgery: nephroureterectomy (n = 71), nephroureterectomy and lymphadenectomy (n = 20), nephroureterectomy and partial bladder resection or transurethral resection (n = 20), nephrectomy (n = 10), and ureterectomy (n = 5). Sixty-one per cent (n = 77) of the tumours were located in the renal pelvis, and 21% (n = 27) in the ureter (both in 22 [17%]). Following surgery, residual tumour was still present in 33 patients (16 microscopic and 17 macroscopic). Postoperative radiotherapy was given to 45 (36%) patients. The median follow-up period was 39 months. In a median period of 9 months, 66% of the patients relapsed (34 local, 7 locoregional, 16 regional, and 24 distant). The 5- and 10-year survival were 29% and 19%, respectively, in all patients. In univariate analyses, statistically significant factors influencing the outcome were Karnofsky index, pT-classification, pN-classification, tumour localisation, grade, and residual tumour after surgery. Multivariate analysis revealed that independent prognostic factors influencing outcome were pT-classification, the existence of residual tumour, and tumour localisation. In patients with urothelial renal pelvis and/or ureter tumours, a radical surgical attitude is mandatory; and the presence of tumour in the ureter is associated with a poorer prognosis.

The aim of our pilot study was to test the effect of low dose radiation on classic and occult subfoveal choroidal neovascularization (CNV) in age-related macular degeneration (AMD). The posterior pole of the afflicted eye of 12 patients was irradiated with 5 Gray (Gy), and that of 34 patients with 8 Gy. The radiotherapy was done by a linear accelerator (6 MV X-rays) during 4 consecutive days with daily doses of 1.25 Gy and 2 Gy respectively. At the time of treatment, and 6 weeks, 6 months and 1 year after, a simultaneous fluorescein and ICG angiography of both eyes were carried out, and the distance visual acuity was measured. In none of the cases were we able to note a reduction in the subfoveal membrane's size. With regards to the visual acuity, the evolution was slightly better than the spontaneous courses described in existing literature. Further prospective randomized studies with higher dose radiation are necessary in order to determine the significance of radiotherapy in the treatment of this pathology.

Aim of the study The aim of this study is to test the effect of low dose radiation on the subfoveal neovascular membranes (SNVM) and to analyse visual acuity in age-related macular degeneration. Methods and patients From November 1993 through to August 1994, 10 patients, on the one hand, were given a dose of 5 Gy followed by controls 6 weeks and 6 months later. On the other hand, 21 patients were treated with a dose of 8 Gy and were subjected to controls 6 weeks later. Before the radiotherapy and during the control sessions, all patients were required to be measured for different parameters of visual acuity and to receive a simultaneous fluorescein and indocyanine green angiography. The radiotherapy was done by a linear accelerator 6MeV and through a lateral port 3x4 cm in half beam technic. Results In the 5 Gy group, no changes in the parameters for visual acuity were noted in most cases after 6 months. In 9 of the cases, the membranes had increased in size and in 1 case, they had remained unchanged. In the 8 Gy group, no changes in the visual acuity or in the membrane size were diagnosed. Of all the patients treated, only one refused the angiography control. Discussion and conclusions Given the low dose used and the period of observation, the visual acuity of all patients remained stable. The size of the membranes increased in most cases for those 5 Gy patients and in this respect, no changes at all were noted in the 8 Gy patients. In order to better evaluate the potential of radiotherapy, this study must be pursued and coupled with further studies analysing the effect of different doses on patients.

Only sparse reports have been made about radiation exposure of the treating physician during prostate seed implantation. Therefore, thermoluminescence dosimeter (TLD) measurements on the index fingers and the backs of both hands were conducted.Stranded iodine-125 seeds with a mean apparent activity of 27.4 MBq per seed were used. During application, the treating physician manipulated the loaded needle with the index fingers, partially under fluoroscopic control. Four physicians with varying experience treated 24 patients. The radiation exposure was determined with TLD-100 chips attached to the index fingertips and the backs of hands. Radiation exposure was correlated with the physician's experience.The average brachytherapy duration by the most experienced physician was 19.2 min (standard deviation sigma = 1.2 min; novices: 34.8 min [sigma = 10.2 min]). The mean activity was 1,703 MBq (sigma = 123 MBq), applied with 16.3 needles (sigma = 2.5 needles; novices: 1,469 MBq [sigma = 229 MBq]; 16.8 needles [sigma = 2.3 needles]). The exposure of the finger of the "active hand" and the back of the hand amounted to 1.31 mSv (sigma = 0.54 mSv) and 0.61 mSv (sigma = 0.23 mSv), respectively (novices: 2.07 mSv [sigma = 0.86 mSv] and 1.05 mSv [sigma = 0.53 mSv]).If no other radiation exposure needs to be considered, an experienced physician can perform about 400 applications per year without exceeding the limit of 500 mSv/year; for novices, the corresponding figure is about 200.

Objective: To evaluate quality of life (QOL) after radical retropubic prostatectomy (RP) and low-dose-rate brachytherapy (BT). Methods: Between 2001 and 2004, RP or BT was performed in 212 patients. QOL data were evaluated with the European Organization for Research and Treatment of Cancer QLQ-C30 version 3.0, the International Prostate Symptom Score (IPSS) and the International Index of Erectile Function-5 questionnaires. QOL data were compared. Results: RP and BT were performed in 142 and 70 patients, respectively. The mean follow-up was 24 months (5–53). The mean overall global health score for patients after RP was 78 (0–100) and after BT it was 83 (33–100), and it showed a trend in favour of BT. The follow-up lasted at most 53 months, and the period was divided into yearly categories. Patients who underwent BT showed worse global health in the first year after operation, but thereafter they showed better health. Patients who received BT showed a trend towards having lower functional-scale and symptom-scale scores in the first year after operation, and then higher scores for any subsequent year of follow-up. Only diarrhoea was temporarily worse in the second year after BT compared to RP. The mean total IPSS and QOL score for BT and RP patients during follow-up showed no significant difference. Conclusion: Patients treated with BT or RP have similar QOL scores. QOL after BT is worse in the first year after treatment, but thereafter it is better than QOL after RP.

Purpose: A multi-centre study to assess the value of combined surgical resection and radiotherapy for the treatment of desmoid tumours. Patients and methods: One hundred and ten patients from several European countries qualified for this study. Pathology slides of all patients were reviewed by an independent pathologist. Sixty-eight patients received post-operative radiotherapy and 42 surgery only. Median follow-up was 6 years (1 to 44). The progression-free survival time (PFS) and prognostic factors were analysed. Results: The combined treatment with radiotherapy showed a significantly longer progression-free survival than surgical resection alone (p smaller than 0.001). Extremities could be preserved in all patients treated with combined surgery and radiotherapy for tumours located in the limb, whereas amputation was necessary for 23% of patients treated with surgery alone. A comparison of PFS for tumour locations proved the abdominal wall to be a positive prognostic factor and a localization in the extremities to be a negative prognostic factor. Additional irradiation, a fraction size larger than or equal to 2 Gy and a total dose larger than 50 Gy to the tumour were found to be positive prognostic factors with a significantly lower risk for a recurrence in the univariate analysis. This analysis revealed radiotherapy at recurrence as a significantly worse prognostic factor compared with adjuvant radiotherapy. The addition of radiotherapy to the treatment concept was a positive prognostic factor in the multivariate analysis. Conclusion: Postoperative radiotherapy significantly improved the PFS compared to surgery alone. Therefore it should always be considered after a non-radical tumour resection and should be given preferably in an adjuvant setting. It is effective in limb preservation and for preserving the function of joints in situations where surgery alone would result in deficits, which is especially important in young patients. © 2007 Baumert et al; licensee BioMed Central Ltd., SCOPUS: ar.j, info:eu-repo/semantics/published

AIM OF THE STUDY The aim of this pilot study is to test the effect of low dose radiation on classic and occult subfoveal neovascular membranes (SNVM) in age-related macular degeneration. METHODS AND PATIENTS From November 1993 through to May 1995 the macula of the affected eye was irradiated with 5 Gy for 12 patients and with 8 Gy for 34 patients. The radiotherapy was done ambulatorily by a linear accelerator 6 MeV during 4 consecutive days with daily 1.25 Gy and 2 Gy respectively. A "half beam technic" was used to protect the lens. Before the treatment, 6 weeks and 6 months later different parameters of the visual acuity were measured and a simultaneous Fluo- and ICG-angiography was done. RESULTS In the 5 Gy group, all the planned controls were done for 11 patients. 9 membranes were classic and 2 occult. After 6 months the vision in the distance remained the same in 7 cases, was better in 2 cases and worse in 2 cases. The size of the membrane increased in 10 cases and remained unchanged in 1 case. In the 8 Gy group, all the planned controls were done for 29 patients. 12 membranes were classic and 17 occult. The vision in the distance remained the same in 17 cases, was better in 4 cases and worse in 8 cases. The size of the membrane increased in 12 cases and there was no change in 17 cases. DISCUSSION AND CONCLUSION Exact comparisons between the 5 Gy and 8 Gy group are not possible because of the different composition of these groups. In no case were we able to note a reduction of the size of the membrane. Concerning the visual acuity, our results are better than the spontaneous evolutions described in the literature. Meanwhile, affirmations about possible stabilisation of the visual acuity are too early. A further study which is being done in our hospital may possibly bring new information.

Based on long-term experience in our hospital with low dose radiotherapy of age-related macular degeneration (AMD), we performed a prospective randomized study between November 1994 and February 1999. The aim of this double-blind study was to evaluate the extent of subfoveal choroidal neovascularization (CNV) and analyze the level of visual acuity after treatment-with different radiation doses.

Background & Aims: Hepatitis B e antigen (HBeAg) and hepatitis B core antigen (HBcAg) seem to play different roles in the induction and regulation of the antiviral immune response, although the two antigens share all major CD4 + T-cell epitopes, and these epitopes can be processed from both antigens via the exogenous antigen-presenting pathway. The aim of this study was to test the ability of antigen-presenting cells to present epitopes from endogenously synthesized HBcAg/HBeAg on HLA class II molecules. Methods: Lymphoblastoid cell lines infected with recombinant vaccinia viruses containing various HBcAg or HBeAg constructs and stable transfectants were tested for their ability to stimulate HBcAg/HBeAg-specific CD4 + T-cell clones. Results: Only antigen-presenting cells infected with HBeAg constructs but not those infected with HBcAg constructs were able to stimulate HBcAg/HBeAg-specific CD4 + T-cell clones. T-cell activation by HBeAg constructs was completely inhibited by brefeldin A but not affected by chloroquin. In contrast, T-cell activation by exogenous, recombinant HBcAg was inhibited by chloroquin but not by brefeldin A. Conclusions: The findings indicate that processing and HLA class II–associated presentation of endogenously synthesized HBeAg in virus-infected cells, including hepatocytes, may occur. This mechanism may be involved in the regulation of the CD4 + T-cell response to HBcAg/HBeAg. GASTROENTEROLOGY 1999;116:650-657

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.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.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.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.

To clarify the controversy about the management and prognosis of human chorionic gonadotropin-producing seminoma, the records of 132 patients with abnormal human chorionic gonadotropin values treated with radiotherapy were analyzed.The records of 1169 patients with pure seminoma treated in 10 institutions were screened for serum or urinary human chorionic gonadotropin. One hundred and thirty two patients with elevated human chorionic gonadotropin were found: 96 Stage I, 20 IIA, 7 IIB, 8 III and 1 IV. Median age was 34 y., mean follow-up was 5.0 years [range 1-12 y]. All received infradiaphragmatic radiotherapy (median dose 30 Gy), 25 (2 Stage I, 11 IIA, 5 IIB and 7 III) supradiaphragmatic radiotherapy (median dose: 28.5 Gy) and 10 had also initial chemotherapy (3 Stage IIB 6 III and 1 IV). Patients were allocated to three groups according to human chorionic gonadotropin values: (a) moderate elevation: up to 10 times (104 pts), (b) high elevation: 10 to 100 times (20 pts), (c) very high elevation: over 100 times the upper limit of normal value (8 pts).The proportion of Stage I, II and III was 76%, 19%, 5% in the ME group versus 50%, 35%, 15% in the high elevation group (p0.05). In the very high elevation group there were 7 Stage I and 1 Stage IV. Of 132 patients, six died (three dead of disease, two suicides, one acquired immunodeficiency syndrome). The 5 years overall survival probability was 94%. There were seven recurrences (initial stage: 1 Stage I, 2 IIB, 3 III and 1 IV). Of these, there were one in-field recurrence, 3 out of field and 3 in both sites. In 5 of 7, the human chorionic gonadotrophin level was again elevated at recurrence. The 5 years recurrence-free-survival probability was 94% (98% for Stage I, 100% for Stage IIA and 65% for Stage IIB and III [p0.001 between I and IIB + III, p0.05 between IIA and IIB + III]). Four of the 7 recurrences were salvaged by chimiotherapy +/- radiotherapy. In the high elevation and very high elevation groups, the 5 years recurrence-free-survival was 88%, vs. 96% for the moderate elevation group (p = 0.10).Based on this series of patients, human chorionic gonadotropin production is not an unfavorable prognostic factor in pure seminoma. Even in the subgroups with high or very high human chorionic gonadotropin levels (who had a higher proportion of advanced stages), the prognosis remained excellent. In Stage I and IIA seminoma with abnormal human chorionic gonadotropin levels, recurrence rate after post-operative radiotherapy alone is extremely low.