[Early detection of prostate cancer: harm verified, benefit not verifiable]. / Früherkennung des Prostatakarzinoms : Schaden belegt, Nutzen nicht belegbar.

The results of randomized studies on the early detection of prostate cancer and those of a systematic Cochrane review are compiled and interpreted. Some fundamental and inherent weaknesses of screening studies are pointed out and discussed. The meta-analysis of studies involving a total of 321,594 participants shows no reduction in prostate cancer mortality or all-cause mortality, but describes disadvantages such as unnecessary biopsies, overdiagnosis, and overtreatment. A relevant increase in overall mortality cannot be excluded. Even in future trials, the possible reduction of prostate cancer mortality or all-cause mortality by prostate cancer screening will not be detectable because of inherent methodological problems, e.g., an extremely high number of participants are needed. Furthermore, by nature, studies on the early detection of cancer last very long, such that the results are inevitably outdated at the end of the study. There is a risk that studies on the early detection of cancer suggest an advantage and at the same time overlook a relevant increase in overall mortality. Prostate cancer screening also ignores important WHO criteria for screening programs: There is evidence that early treatment of prostate cancer is not better than late treatment. There is no suitable or reliable test to identify the early stages of the disease. The benefit-risk ratio is not clearly favorable, and there is doubt whether the costs and the benefits are in an acceptable balance. There are valid reasons to advise against population-based prostate cancer screening.

[Authorship of scientific publications. Audit of the periodical "Strahlentherapie und Onkologie"]. / Autorenschaft wissenschaftlicher Veröffentlichungen. Analyse der Zeitschrift "Strahlentherapie und Onkologie".

BACKGROUND: The quality of the contributions to "Strahlentherapie und Onkologie" is assessed, aiming for improvement of the journal and consequently its impact factor. MATERIAL AND METHODS: All 164 articles published during 1999 and 2000 in the categories "review", "original article", and "short communication" were analyzed concerning the handling of authorship. RESULT: A median number of five authors and two institutions contribute to one publication. In no case the contribution of individual authors was specified. The proportion of women in radiooncological research is significantly less than their proportion in the German radiooncological society DEGRO (p < 0.0001). There were only eight female senior authors which is also significantly less than expected (p = 0.001). The fraction of female first authors corresponds to their fraction among authors. CONCLUSION: The criteria for authorship of the Deutsche Forschungsgemeinschaft should be regarded for. The contribution of individual authors should be specified. Women appear to be underrepresented in research and in leading positions in radiooncology.

Radiobiological hypoxia, oxygen tension, interstitial fluid pressure and relative viable tumour area in two human squamous cell carcinomas in nude mice during fractionated radiotherapy.

Very little is known about the correlation between the radiobiological hypoxic fraction (rHF) and other measures of tumour oxygenation during fractionated irradiation. In the present study the rHF is determined in untreated human FaDu and GL squamous cell carcinoma in nude mice and in tumours irradiated with 10 fractions in 2 weeks and 20 fractions in 4 weeks, using tumour control as the experimental endpoint. The results were compared with measurements of the pO2, the interstitial fluid pressure (IFP) and the relative viable tumour area. In FaDu tumours the radiobiological hypoxic fractions (rHFs) before and during irradiation were not statistically different from 100%. Depending on the assumptions made for D0, the rHFs of GL tumours were between 0.2 and 4% or 30 and 53%. The median pO2 values were 2.8 mmHg for untreated FaDu tumours and 0.2 mmHg for GL tumours (p < 0.001). The median IFP values were 2.6 mmHg in FaDu and 5.3 mmHg in GL tumours (p = 0.01). No important changes in the pO2 and IFP values were observed during fractionated irradiation. The relative viable tumour area during irradiation decreased by 83% in FaDu tumours (p = 0.002) and by 54% in GL tumours (p = 0.003). It is concluded that differences in rHF exist between FaDu and GL tumours before and during fractionated irradiation and that these differences are not reflected by pO2 and IFP values and the relative viable tumour area.

Impact of treatment acceleration and its timing on the response of the rhabdomyosarcoma R1H of the rat to fractionated irradiation.

BACKGROUND AND PURPOSE: In clinical practice a concomitant boost is usually given as a second daily dose to a reduced field. The question arises which part of treatment should be accelerated to achieve optimal tumor control. An experiment was performed on tumor bearing rats to determine the optimal timing of treatment acceleration for this experimental tumor system. MATERIAL AND METHODS: Rhabdomyosarcoma R1H of the rat were treated applying 30 fractions in an overall treatment time of 40-42 days, up to total doses ranging from 67.5 to 97.5 Gy were administered. For control a standard treatment was given as continuous treatment applying one fraction per day. A boost of five additional fractions was given as a second fraction during 5 days. Three experimental arms received a boost either in the 1st, 4th, or in the last week of treatment. Treatment outcome was assessed using tumor control as endpoint. RESULTS: All experimental arms proved more effective than the standard treatment. Treatment was most effective when the boost was administered in the 1st week of treatment. A TCD37% of 87.1 Gy (95% CI: 82.8 ... 92.7 Gy), 96.5 Gy (89.9 ... 107.1), and 107.3 Gy (97.2 ... 131.0) was determined, when the boost was given in the 1st, 4th, or last week of treatment, respectively. The observed difference between the experimental arms was statistically significant (p = 0.004). CONCLUSIONS: Initially accelerated treatment schedules were found to be more effective for tumor control in an experimental tumor system.

Split-course radiotherapy: where do we stand?

BACKGROUND: Split-course radiotherapy is only rarely applied in curative radiotherapy and there might be a number of arguments to believe that continuous radiotherapy is superior to split-course treatment. In order to point out the evidence current treatment practice is based on, the available randomized trials and some prominent retrospective analyses on split-course radiotherapy were critically assessed. MATERIAL AND METHODS: The analysis of the clinical results was based on published data only. Publications were searched in a Medline database. RESULTS: Assessment of 13 randomized trials, including the data of 2,112 patients, revealed no significant difference between continuous-course and split-course radiotherapy. Astonishingly, the outcome of 77 radiotherapy studies on split-course, most of which are retrospective, seems to depend on the year of publication, suggesting publication bias. CONCLUSIONS: No clinically relevant difference between continuous and split-course radiotherapy could be found. This, of course, does not proof that there are indeed no differences but the data do not allow to draw clear-cut conclusions in favor of or against split-course radiotherapy due to methodological shortcomings of the studies.

[Citation in scientific publications. Analysis of the publication "Strahlentherapie und Onkologie"]. / Zitierung wissenschaftlicher Veröffentlichungen. Analyse der Zeitschrift "Strahlentherapie und Onkologie".

BACKGROUND: The quality of the contributions to "Strahlentherapie und Onkologie" is assessed, aiming for improvement of the journal and consequently its impact factor. MATERIAL AND METHODS: All 164 articles published during 1999 and 2000 in the categories "review article", "original article", and "short communication" were analyzed concerning number and age of references. RESULT: In 1999 and 2000 there was a median number of 26 citations per article (range: 0-264). The median age of the cited articles was 4 years. CONCLUSION: The work of other authors should properly be referred to. Citation of the same journal might influence the impact factor of the journal.

[Multiple significance tests and their importance in the judging of results. A quality analysis of the journal Strahlentherapie und Onkologie]. / Multiple Signifikanztests und ihre Bedeutung bei der Beurteilung von Resultaten. Qualitätsanalyse der Zeitschrift "Strahlentherapie und Onkologie".

BACKGROUND: The statistical quality of the contributions to "Strahlentherapie und Onkologie" is assessed, aiming for improvement of the journal and consequently its impact factor. MATERIAL AND METHODS: All 181 articles published during 1998 and 1999 in the categories "review", "original contribution", and "short communication" were analyzed concerning the appropriate use of multiple tests. RESULT: One hundred and four publications were excluded from analysis, because they did not contain quantitative data or because no or only 1 statistical test was performed. In 77 publications multiple tests were done which was adequately considered in only 3 of these papers, corresponding to a fraction of 4% (95% CI: 0.8 to 11%). CONCLUSION: Authors, peer reviewers, and editors could contribute to improve the quality of the journal by setting value on correction for multiple tests.

[Confidence intervals and their relevance for the interpretation of results. Audit of the journal "Strahlentherapie und Onkology"]. / Konfidenzintervalle und ihre Bedeutung für die Beurteilung von Resultaten. Qualitätsanalyse der Zeitschrift "Strahlentherapie und Onkologie".

BACKGROUND: The statistical quality of the contributions to "Strahlentherapie und Onkologie" is assessed, aiming for improvement of the journal and consequently its impact factor. MATERIAL AND METHODS: All 181 articles published during 1998 and 1999 in the categories "review", "original contribution", and "short communication" were analysed concerning the appropriate use of confidence intervals. RESULT: Forty-four publications were excluded from analysis, because they did not contain quantitative data or because the quotation of a confidence interval would not have been meaningful for other reasons. Of the remaining 137 publications only 27 presented all relevant results with clearly defined and correctly interpreted confidence intervals. This corresponds to a fraction of 20% (95% CI: 13-28%). CONCLUSION: Authors, peer reviewers, and editors could contribute to improve the quality of the journal by setting value on the documentation of confidence intervals.

[Type two error and its relevance for interpretation of results. Quality audit of the Journal "Strahlentherapie und Onkologie]. / Der Fehler zweiter Art und seine Bedeutung bei der Beurteilung von Resultaten. Qualitätsanalyse der Zeitschrift "Strahlentherapie und Onkologie".

BACKGROUND: The statistical quality of the contributions to "Strahlentherapie und Onkologie" is assessed, aiming for improvement of the journal and consequently its impact factor. MATERIAL AND METHODS: All 181 articles published during 1998 and 1999 in the categories "review", "original contribution", and "short communication" were analyzed concerning the appropriate consideration of Type II error. RESULT: Ninety-nine publications were excluded from analysis for different specified reasons. In none of the remaining 82 clinical publications Type II error was considered. CONCLUSION: Authors, peer reviewers, and editors could contribute to improve the quality of the journal by setting value on adequate consideration of Type II error.

[Actuarial analysis of time-failure data and its rrelevance for interpretation of results. Audit of the journal "Strahlentherapie und Onkologie" (Radiotherapy and Oncology)]. / Aktuarische Auswertung von Zeit-Ereignis-Daten und ihre Bedeutung bei der Beurteilung von Resultaten. Qualitätsanalyse der Zeitschrift "Strahlentherapie und Onkologie".

BACKGROUND: The statistical quality of the contributions to "Strahlentherapie und Onkologie" is assessed, aiming for improvement of the journal and consequently its impact factor. MATERIAL AND METHODS: All 181 articles published during 1998 and 1999 in the categories "review", "original contribution", and "short communication" were analyzed concerning actuarial analysis of time-failure data. RESULT: One hundred and twenty-three publications without time-failure data were excluded from analysis. Forty-five of the remaining 58 publications with time-failure data were evaluated actuarially. This corresponds to 78% (95% confidence interval: 64 to 88%) of papers, in which data were adequately analyzed. Complications were reported in 16 of 58 papers, but in only 3 cases actuarially. The number of patients at risk during the course of follow-up was documented adequately in 22 of the 45 publications with actuarial analysis. CONCLUSION: Authors, peer reviewers, and editors could contribute to improve the quality of the journal by setting value on acturial analysis of time-failure data.

Tumor volume: a basic and specific response predictor in radiotherapy.

BACKGROUND AND PURPOSE: Predictive assays of the response of tumor and normal tissues in individual patients offer the possibility of individualized prognosis and treatment decisions. For this purpose a variety of assays are currently being explored. The impact of tumor volume on radiotherapy outcome has long been recognized and in this paper its predictive potential is investigated. METHODS: Re-evaluation of clinical data from the literature. RESULTS: Tumor volume significantly influences radiotherapy outcome and in many sites it is likely a superior prognostic indicator to tumor stage, which reflects tumor size only partially and is mainly correlated to operability. Tumors even of identical stage may vary by factors of more than 100 in volume and neglect of this heterogeneity clearly reduces the power of a study considerably. The precision requirements for the measurement of tumor volume are small; +/-50% is sufficient for reasonable results. CONCLUSION: The data evaluated here suggest that tumor volume is the most precise and most relevant predictor of radiotherapy outcome. Its determination is achievable with sufficient accuracy in most radiotherapy departments. Individual tumor volume should always be reported in clinical studies and considered in data analyses.

Linear-quadratic analysis of tumour response to fractionated radiotherapy: a study on human squamous cell carcinoma xenografts.

PURPOSE: To compare values for the alpha/beta ratio in experimental tumours irradiated either under conditions of clamping and short overall time or under more 'clinically realistic' conditions. MATERIALS AND METHODS: Human squamous cell carcinomas, FaDu and GL, were grown in nude mice. Alpha/beta values were determined from local tumour control data after treatment with single doses and 2, 4, and 8 fractions under clamp hypoxia in 3.5 days, using maximum likelihood analysis. Effective alpha/beta values (alpha/beta(eff)) were determined from treatment with 12, 30, and 60 fractions under ambient conditions in a constant overall treatment time of 6 weeks. RESULTS: After correction for an oxygen enhancement ratio of 2.7 the alpha/beta values were 15 Gy (95% CI 9; 24) for FaDu and 49 Gy (26; 122) for GL. In FaDu the TCD50 values after 12 to 60 fractions were not significantly different, the alpha/beta(eff) value was infinite (52; inf.). Unexpected from the high alpha/beta value, the TCD50 values of GL tumours increased from 37 Gy (28; 47) after 12 fractions to 59 Gy (52; 67) after 60 fractions: the alpha/beta(eff) value was 3 Gy (0.6; 12 Gy). CONCLUSIONS: The results support the view that mechanisms other than recovery from sublethal radiation damage and repopulation of clonogenic tumour cells may importantly impact on treatment outcome when the number of fractions is changed in clinical radiotherapy.