Martin Busch

Nucleosomes in serum of patients with benign and malignant diseases.

High quantities of mono‐ and oligonucleosomes circulate in the blood of patients with malignant tumors. For their direct quantification in serum, we modified the Cell Death Detectionplus‐ELISA for its application in liquid materials. We examined sera samples from 590 persons, including 418 patients with malignant tumors, 109 patients with benign diseases and 63 healthy persons. We also observed the kinetics of the concentration of nucleosomes in serum samples from 20 patients undergoing chemotherapy and from 16 patients undergoing radiotherapy. Sera of patients with malignant tumors contained considerably higher concentrations of nucleosomes (mean = 350 arbitrary units [AU], median = 190 AU) compared with those of healthy persons (mean = 36 AU, median = 24 AU; p = 0.0001) and patients with benign diseases (mean = 264 AU, median = 146 AU; p = 0.072). Concerning the follow‐up investigations, the concentration of nucleosomes in serum increased 24–72 hr after the first application of chemotherapy and 6–24 hr after the start of radiotherapy. A subsequent decrease was often correlated with regression of the tumor. In patients undergoing chemotherapy, an increase in the baseline values of circulating nucleosomes >50%, which were determined before each new therapeutic cycle, was correlated with progression of disease; all patients with disease regression showed a decrease >50% of the baseline values. In patients undergoing radiotherapy, an early decrease of the nucleosomal concentration (≤1 day after the initial peak during therapy) to low minimum levels (≤100 AU) correlated with good clinical outcome; a late decrease (>1 day) to higher minimum levels (>100 AU) was associated with a worse clinical outcome. Thus, the concentration of nucleosomes in serum might be a useful tool for monitoring the biochemical response during antitumor therapy, especially for the early estimation of therapeutic efficacy.

Effects of 780 nm diode laser irradiation on blood microcirculation: preliminary findings on time-dependent T1-weighted contrast-enhanced magnetic resonance imaging (MRI).

Laser therapy by low light doses shows promising results in the modulation of some cell functions. Various clinical studies indicate that laser therapy is a valuable method for pain treatment and the acceleration of wound healing. However, the mechanism behind it is still not completely understood. To explore the effect of a low-power diode laser (lambda = 780 nm) on normal skin tissue, time-dependent contrast enhancement has been determined by magnetic resonance imaging (MRI). In the examinations, six healthy volunteers (four male and two female) have been irradiated on their right planta pedis (sole of foot) with 5 J/cm2 at a fluence rate of 100 mW/cm2. T1-weighted magnetic resonance imaging is used to quantify the time-dependent local accumulation of Gadolinium-DPTA, its actual content in the local current blood volume as well as its distribution to the extracellular space. Images are obtained before and after the application of laser light. When laser light is applied the signal to noise ratio increases by more than 0.35 +/- 0.15 (range 0.23-0.63) after irradiation according to contrast-enhanced MRI. It can be observed that, after biomodulation with light of low energy and low power, wound healing improves and pain is reduced. This effect might be explained by an increased blood flow in this area. Therefore, the use of this kind of laser treatment might improve the outcome of other therapeutic modalities such as tumour ionizing radiation therapy and local chemotherapy.

Circulating Nucleosomes in Serum

Abstract: In the nucleus of eukaryotic cells, DNA is associated with several protein components and forms complexes known as nucleosomes. During cell death, particularly during apoptosis, endonucleases are activated that cleave the chromatin into multiple oligo‐ and mononucleosomes. Subsequently, these nucleosomes are packed into apoptotic bodies and are engulfed by macrophages or neighboring cells. In cases of high rates of cellular turnover and cell death, they also are released into the circulation and can be detected in serum or plasma. As enhanced cell death occurs under various pathologic conditions, elevated amounts of circulating nucleosomes are not specific for any benign or malignant disorder. However, the course of change in the nucleosomal levels in circulation of patients with malignant tumors during chemotherapy or radiotherapy is associated with the clinical outcome and can be useful for the therapeutic monitoring and the prediction of the therapeutic efficacy.

Effects on the mitosis of normal and tumor cells induced by light treatment of different wavelengths

Although the background of laser therapy by means of low level energy and power is still only partially understood, there are nevertheless promising reports from clinical studies concerning pain treatment, the acceleration of wound healing, and the modulation of cell functions. In order to contribute to the understanding of such a phototherapeutic procedure cell experiments were performed.

BIOMODULATIVE EFFECTS INDUCED BY 805 NM LASER LIGHT IRRADIATION OF NORMAL AND TUMOR CELLS

The influence of light emitted from a diode laser centred at lambda = 805 nm was investigated on murine skeletal myotubes (C2), normal urothelial cells (HCV29), human squamous carcinoma cells of the gingival mucosa (ZMK) and urothelial carcinoma cells (J82) in a computer-controlled irradiation chamber. Cells were treated with varying fluences between 0 and 20 J cm-2. The response was tested by analysis of the mitotic index using single cell counting after Orcein staining and proliferation index based on BrdU incorporation during DNA synthesis. While the mitotic index of C2, HCV29 and J82 cells increased at a fluence of 4 J cm-2, irradiation with fluences of 20 J cm-2 resulted in a slight decrease. ZMK tumor cells showed a decrease of the mitotic index with both fluences. No significant differences could be determined when using irradiances between 10 mW cm-2 and 150 mW cm-2. The BrdU test after irradiation showed no significant effects compared to the controls in each cell line.

Long term results of definitive radiotherapy for cervical carcinoma using four applications of high dose rate afterloading

In definitive radiotherapy for cervical carcinoma, combined modality treatment using external beam radiotherapy and brachytherapy is standard. Although the optimal number of afterloading applications is controversial, the majority of authors recommend three applications.

Einsatz von G-CSF (Neupogen®) bei multimodalen Therapiekonzepten in der Strahlentherapie

ZusammenfassungHintergrundBei multimodalen Therapiekonzepten in der Strahlentherapie werden wiederholt therapiebedingte Leukopenien mit entsprechenden Folgen beobachtet. Bei fehlender Zulassung wurde in der Strahlentherapie dennoch unter individuellen Gesichtspunkten G-CSF (granulocyte-colony-stimulating-factor) mit Erfolg appliziert. In kleineren Patientenkollektiven konnten diese Ergebnisse in der Therapie von Leukopenien bestätigt werden. In dieser Arbeit sollten die Ergebnisse früherer Studien bei einem größeren Kollektiv überprüft, die postulierten unerwünschten Wirkungen verifiziert und insbesondere ein kosteneffektiver Einsatz des Wachstumfaktors (Neupogen®) aufgezeigt werden.Patienten und MethodeEs wurden 50, teils vortherapierte Patienten mit unterschiedlichen malignen Tumoren im Rahmen einer Anwendungsbeobachtung mit G-CSF (Neupogen®) supportiv behandelt. G-CSF wurde, bei der Wahrscheinlichkeit eines Leukozytenabfalles unter 1000/mm3, bereits unter einem Leukozytenwert von 2500/mm3 (500/mm3 bis 2450/mm3), körpergewichtsabhängig, subkutan, jeden zweiten Tag bis zum Erreichen des Normwertes appliziert.ErgebnisseEin Anstieg der Leukozytenwerte erfolgte zu 92% bereits in den ersten 24 Stunden. Es wurden durchschnittlich 4,9 G-CSF-Gaben pro Patient benötigt. Patienten ohne Vortherapien und mit weniger komplexen Therapien bedurften weniger G-CSF-Gaben (3,5 zu 5,8 Gaben). Die Leukozytenwerte aller Patienten lagen bei Beginn der G-CSF-Therapie aufgrund der unterschiedlichen Verläufe und Interventionseinschätzungen zwischen 500/mm3 und 2450/mm3. Die Patienten, die bis zu drei G-CSF-Gaben erhielten, hatten bei Beginn der G-CSF-Therapie höhere Leukozytenwerte als die, die vier und mehr G-CSF-Gaben benötigten (1620/mm3 zu 1250/mm3). Leukopeniebedingte Infekte, Therapieunterbrechungen oder-abbrüche traten nicht auf. Bis auf Gliederschmerzen, die bei 14% der Patienten auftraten, ließen sich keine unerwünschten Wirkungen durch das Neupogen® nachweisen.SchlußfolgerungBei einem zu erwartendem Abfall der Leukozytenwerte unter 1000/mm3 ist die interventionelle Gabe von G-CSF bereits bei Leukozytenwerten um 1600/mm3 am kosteneffektivsten. Leukopenien können in der Strahlentherapie effektiv, nebenwirkungsarm und bei rechtzeitiger Gabe mit G-CSF kostengünstig behandelt werden.AbstractBackgroundTherapy-induced leucopenias with corresponding consequences repeatedly occur in radiotherapy using combined modalities treatment. In radiotherapy, where G-CSF (granulocyte-colony-stimulating-factor) is not licensed, G-CSF has been used successfully under individual circumstances. These results were confirmed in several studies with small patient groups. The aim of this study was to check former results in a larger patient group, to verify postulated side effects and specially to define a cost-effective schedule in the treatment with G-CSF (Neupogen®).Patients and MethodsIn this surveillance trial 50, partially previously treated patients with different malignant tumors were treated with G-CSF. According to the probability of a leucocytosis lower than 1000/mm3, G-CSF (Neupogen®) was already given at leucocyte values lower than 2500/mm3 (500/mm3 bis 2450/mm3). It was administered subcutaneously, every other day, based on body weight until reaching normal leucocyte levels.ResultsIn 92% of the patients the increase of leucocytes occurred in the first 24 hours. On average G-CSF was given 4.9 times per patient. Patients without prior therapies or less complex therapies needed less G-CSF applications (3.5 to 5.8 applications). Due to individually varying leucocyte courses the G-CSF therapy was started with leucocyte values between 500/mm3 and 2450/mm3. Patients who were treatet with up to 3 G-CSF applications had higher leucocyte levels than those with 4 or more applications (1620/mm3 to 1250/mm3). Leucopenia related infections, therapy interruptions or break-offs did not occur. Besides light “flu like” symptoms in 14% of the patients, no side effects were observed.ConclusionsWhen a decrease of leucocyte values lower than 1000/mm3 is expected, the most cost-effective treatment is given when starting the interventional G-CSF administration already at leucocyte values around 1600/mm3. Leucopenias can be treated effectively, with little side effects and in a cost-effective way when G-CSF is given on time.BACKGROUNDnTherapy-induced leukopenias with corresponding consequences repeatedly occur in radiotherapy using combined modalities treatment. In radiotherapy, where G-CSF (granulocyte-colony-stimulating-factor) is not licensed, G-CSF has been used successfully under individual circumstances. These results were confirmed in several studies with small patient groups. The aim of this study was to check former results in a larger patient group, to verify postulated side effects and specially to define a cost-effective schedule in the treatment with G-CSF (Neupogen).nnnPATIENTS AND METHODSnIn this surveillance trial 50, partially previously treated patients with different malignant tumors were treated with G-CSF. According to the probability of a leucocytosis lower than 1000/mm3, G-CSF (Neuropogen) was already given at leukocyte values lower than 2500/mm3 (500/mm3 bis 2450/mm3). It administered subcutaneously every other day, based on body weight until reaching normal leucocyte levels.nnnRESULTSnIn 92% of the patients the increase of leucocytes occurred in the first 24 hours. On average G-CSF was given 4.9 times per patient. Patients without prior therapies or less complex therapies needed less G-CSF applications (3.5 to 5.8 applications). Due to individually varying leucocyte courses the G-CSF therapy was started with leucocyte values between 500/mm3 and 2450/mm3. Patients who were treated with up to 3 G-CSF applications had higher leucocyte levels than those with 4 or more applications (1620/mm3 to 1250/mm3). Leucopenia related infections, therapy interruptions or break-offs did not occur. Besides light flu like symptoms in 14% of the patients, no side effects were observed.nnnCONCLUSIONSnWhen a decrease of leucocyte values lower than 1000/mm3 is expected, the most cost-effective treatment is given when starting the interventional G-CSF administration already at leucocyte values around 1600/mm3. Leucopenias can be treated effectively, with little side effects and in a cost-effective way when G-CSF is given on time.

Primäre Strahlentherapie des Larynxkarzinoms

ZusammenfassungHintergrundIn der Therapie des Larynxkarzinoms erbringt die primäre Strahlentherapie bei geringer Morbidität und guten funktionellen Ergebnissen in den frühen Stadien ähnlich gute Erfolge wie die operative Behandlung. Allerdings liegen hierzu keine randomisierten Studien vor, so daß das optimale Behandlungskonzept für die verschiedenen Stadien nicht gut definiert ist und kontrovers diskutiert wird. Die folgende Studie ist eine retrospektive Analyse der Behandlungsergebnisse der Patienten mit einem Plattenepithelkarzinom des Larynx, die in der Radiologischen Klinik der Ludwig-Maximilians-Universität München primär bestrahlt wurden.Patienten und MethodeIm Zeitraum vom 1. 9. 1971 bis zum 1. 6. 1986 wurden 283 Patienten mit einem Plattenepithelkarzinom des Larynx einer primären Strahlentherapie zugeführt. 26 Patienten (9,2%) waren weiblich und 257 (90,8%) männlich. Das mediane Alter der Frauen betrug 68,5 Jahre, das der Männer 70 Jahre. Histologisch handelte es sich in allen Fällen um Plattenepithelkarzinome. 41 Tumoren (14,5%) waren rein supraglottisch lokalisiert, 207 (73,1%) rein glottisch. 35 Patienten (12,4%) hatten einen T4-Tumor mit sowohl glottischem als auch supraglottischem Befall. In 147 Fällen war ein histopathologisches Grading zu eruieren. Dabei wurden 32 Tumoren als G1, 95 als G2, 15 als G3 und 5 als G4 klassifiziert. Entsprechend der UICC-Klassifikation von 1979 hatten 25 Patienten ein Carcinoma in situ (Tis), 93 Patienten ein Stadium T1, 90 ein Stadium T2, 40 ein Stadium T3 und 35 Patienten ein Stadium T4. Von den 283 Patienten lag bei 233 (82,3%) kein Lymphknotenbefall vor. Bei 50 Patienten fand sich ein Lymphknotenbefall; davon hatten 22 Patienten Stadium N1, fünf Patienten Stadium N2 und 23 Patienten Stadium N3. Es wurde überwiegend eine Telekobalt-60-Therapie mit einer mittleren Gesamtherddosis von 61,9 Gy durchgeführt.ErgebnisseFür das Gesamtkrankengut betrug die rezidivfreie Fünf-Jahres-Überlebenswahrscheinlichkeit 61,7%. Die Wahrscheinlichkeit der Tumorfreiheit („no evidence of disease”, NED) war stadien- und lokalisationsabhängig: glottische Tumoren: Tis/T1 90,5%, T2 59,4%, T3 39,6% (fünf Jahre NED); supraglottische Tumoren: T1 64,2%, T2/T3 28,6%, T4/N3 24,7% (drei Jahre NED). Als signifikante prognostisch bedeutsame Faktoren erwiesen sich weiterhin das N-Stadium (N0 vs. N+: Drei-Jahres-Lokalrezidivfreiheit 68% vs. 37,2%, p<0,001) und das pathohistologische Grading (G1 vs. G3/4: Drei-Jahres-Lokalrezidivfreiheit 74% vs. 37,1%, p<0,01). 122 Patienten (43,1%) erlitten ein Rezidiv: in 75,4% der Fälle nur lokal, in 12,3% lokoregionär, in 8,2% als Fernmetastasen und in 4,1% kombiniert. Bei 50 Rezidivpatienten wurde der Versuch einer Zweitbehandlung unternommen. Dabei erreichten noch einmal 17 Patienten eine komplette Remission.SchlußfolgerungAuch für das beschriebene, negativ selektionierte Patientengut mit hohem Durchschnittsalter und zahlreichen internistischen Kontraindikationen gegen einen operativen Eingriff führt die primäre Strahlentherapie des Larynxkarzinoms besonders im frühen Stadium des glottischen Karzinoms zu guten lokalen Kontrollraten. In fortgeschrittenen Stadien sollte auch für ältere Patienten ein kombiniertes chirurgisch-radiotherapeutisches Vorgehen angestrebt werden.AbstractPurposeIn 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 MethodTwo 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.ResultsThe 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 signifikant prognostic factors besides T-stage were N-stage (N0 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% locoregional, 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.ConclusionEven for the here described negatively selected patient group with a high median age and multimorbidity, good local controlrates could be achieved escpecially in early stages with definitive radiation therapy. In more advanced stages even in elderly patients a combined surgical-radiotherapeutic treatment should be performed.PURPOSEnIn 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.nnnPATIENTS AND METHODnTwo 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.nnnRESULTSnThe 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.nnnCONCLUSIONnEven 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.

Accuracy of MRI-Targeted in-Bore Prostate Biopsy According to the Gleason Score with Postprostatectomy Histopathologic Control--a Targeted Biopsy-Only Strategy with Limited Number of Cores.

RATIONALE AND OBJECTIVESnAccuracy of ultrasound-guided biopsy and Gleason score is limited, and diagnosis of insignificant cancer with Gleason score ≤6 is frequent when extended biopsy schemes are used. We evaluated whether the magnetic resonance imaging (MRI)-targeted in-bore prostate biopsy correctly identifies the Gleason score of prostate cancer in histopathologic correlation after prostatectomy. Simultaneously a targeted concept is expected to keep down the rate of insignificant cancer.nnnMATERIALS AND METHODSnWe compared retrospectively the Gleason score of the MRI-targeted in-bore biopsy with prostatectomy specimens in 50 men with prostate cancer. Endorectal MRI included T2-weighted imaging, diffusion-weighted imaging, dynamic contrast-enhanced imaging, and spectroscopy. Lesions with a prostate imaging-reporting and data system (PI-RADS) score ≥3 were considered. Upgrading and downgrading of tumors was evaluated, and significant upgrading was defined as a shift in Gleason score from 6 to 7 or more.nnnRESULTSnGleason score was concordant in 66% of the patients, overall upgraded in 30% of patients, and downgraded in 4% of patients. Significant upgrading of the Gleason score from 6 to 7 occurred in eight patients; upgrading did not exceed one step in the Gleason score. After prostatectomy the Gleason score 6 was found in 20% of patients. The median number of cores obtained was 4 (range 2-6), and the median number of positive cores was 2 (range 1-4).nnnCONCLUSIONSnIn-bore MRI-targeted biopsy offers good accuracy in the Gleason score with postprostatectomy histopathologic control when compared to the literature. A limited number of cores are sufficient to achieve these results. The fraction of insignificant cancer identified by targeted only-biopsy is low. Upgrading is restricted to one step in the Gleason score. Clinicians should be aware of positive findings in MRI and the biopsy technique used when assessing prostate biopsy results.

Long-term impact of postoperative radiotherapy in carcinoma of the vulva FIGO I/II.

PURPOSEnBetween 1953 and 1978, postoperative radiotherapy was used as an adjuvant therapy for carcinoma of the vulva that had not been treated with radical vulvectomy. We evaluated long-term results and possible prognostic factors.nnnMETHODS AND MATERIALSnNinety-two patients were treated. Surgical procedures were simple vulvectomy, electrocoagulation, or local excision. Radiotherapy doses to the vulva ranged from 0 to 90 Gy. All patients received radiotherapy to the inguinal lymph nodes, ranging from 30 to 60 Gy. Thirty-year retrospective follow-up was done evaluating the records and statistical survival rates.nnnRESULTSnFive-year actuarial survival rates in T1 patients were 71% (77% cause-specific survival rate), for T2 patients 43% (48% cause-specific survival rate). The difference between T1 and T2 patients was significant (p < 0.05). Patients with tumors of the labia minora had a significantly higher survival rate than those with different sites affected. Doses of 45 Gy or more to the vulva were sufficient to increase the 5-year cause-specific survival rate from 55% to 88%. The results in three subgroups were analyzed, group 1 having received electrocoagulation, but no radiotherapy of the vulva; group 2, local excision and doses of 40 Gy to the vulva; group 3, local excision and doses of 60 Gy to the vulva. There was a significant effect on 10-year cause-specific survival rates: 48% in group 1, 11% in group 2, and 88% in group 3. In multivariate analysis, the significant independent factors were T classification, tumor sites and-with only marginal significance-radiation doses to the vulva.nnnCONCLUSIONSnThe prognosis in early vulva carcinoma after nonradical surgery primarily depends on T classification and the site of the primary tumor. With univariate analyses, the dose has a significant effect on survival. In multivariate analyses the dose is a marginal independent factor in the whole group of patients. After nonradical surgery of early vulva carcinoma, the vulva should be irradiated resulting in better long-term survival.