Tanja Langsenlehner

The elevated preoperative platelet-to-lymphocyte ratio predicts poor prognosis in breast cancer patients

Background:The elevation of the platelet-to-lymphocyte ratio (PLR), an easily applicable blood test based on platelet and lymphocyte counts has been associated with poor prognosis in patients with different types of cancer. The present study was aimed to investigate the prognostic significance of the preoperative PLR in a large cohort of breast cancer patients.Methods:Data from 793 consecutive non-metastatic breast cancer patients, treated between 1999 and 2004, were evaluated retrospectively. The optimal cutoff values for the PLR were calculated using receiver operating curve analysis. Cancer-specific survival (CSS), overall survival (OS) as well as distant metastasis-free survival (DMFS) were assessed using the Kaplan–Meier method. To evaluate the independent prognostic significance of PLR, multivariable Cox regression models were applied for all three different end points.Results:Univariable analysis revealed a significant association between the elevated preoperative PLR and CSS (hazard ratio (HR): 2.75, 95% confidence interval (CI): 1.57–4.83, P<0.001) that remained statistically significant in multivariable analysis (HR: 2.03, 95% CI: 1.03–4.02, P=0.042). An increased PLR was also significantly associated with decreased OS in univariable (HR: 2.45, 95% CI: 1.43–4.20, P=0.001) and in multivariable analysis (HR: 1.92, 95% CI: 1.01–3.67, P=0.047). Furthermore, univariable analysis showed a significant impact of increased PLR on DMFS (HR: 2.02, 95% CI: 1.18–3.44, P=0.010). Subgroup analysis revealed significant associations of the elevated PLR on the primary end point CSS for all breast cancer subtypes. This association retained its significance in multivariable analysis in patients with luminal B tumours (HR: 2.538, 95% CI: 1.043–6.177, P=0.040).Conclusions:In this study, we identified the preoperative PLR as an independent prognostic marker for survival in breast cancer patients. Independent validation of our findings is needed.

Association between single nucleotide polymorphisms in the gene for XRCC1 and radiation-induced late toxicity in prostate cancer patients

BACKGROUND AND PURPOSE Polymorphisms in genes responsible for DNA damage signaling and repair might modulate DNA repair capacity and, therefore, affect cell and tissue response to radiation and influence individual radiosensitivity. The purpose of the present prospective investigation was to evaluate the association of single nucleotide polymorphisms in XRCC1 with radiation-induced late side effects in prostate cancer patients treated with radiotherapy. MATERIAL AND METHODS To analyze the role of XRCC1 polymorphisms for late toxicity 603 participants from the Austrian PROCAGENE study treated with three-dimensional conformal radiotherapy were included in the present investigation. Three non-synonymous candidate polymorphisms in the X-ray repair cross-complementing group 1 (XRCC1) gene (Arg194Trp; Arg280His; Arg399Gln) were selected and determined by 5´-nuclease (TaqMan) assays. RESULTS Within a median follow-up time of 35 months, 91 patients (15.7%) developed high-grade late toxicities (defined as late bladder and/or rectal toxicity RTOG≥2). In a Kaplan-Meier analysis, carriers of the XRCC1 Arg280His polymorphism were at decreased risk of high-grade late toxicity (p=0.022), in multivariate analysis including clinical and dosimetric parameters as potential confounders the XRCC1 Arg280His polymorphism remained a significant predictor for high-grade late toxicity (HR=0.221, 95% CI 0.051-0.956; p=0.043). No significant associations were found for the remaining polymorphisms. CONCLUSIONS We conclude that the XRCC1 Arg280His polymorphism may be protective against the development of high-grade late toxicity after radiotherapy in prostate cancer patients.

Long-term follow-up of patients with pituitary macroadenomas after postoperative radiation therapy: analysis of tumor control and functional outcome.

Purpose:Evaluation of long-term tumor control, normalization of hormonal hypersecretion, including incidence and time course of pituitary dysfunction following postoperative radiotherapy of pituitary macroadenomas.Patients and Methods:In a retrospective study, the data of 87 patients with pituitary macroadenomas (61 non-secreting adenomas, 26 secreting adenomas) treated between 1984 and 1994 were analyzed. All patients underwent surgery and received postoperative external-beam radiotherapy with a mean dose of 50.4 Gy (range 46–54 Gy).Results:After a follow-up of 15 years the local tumor control rate achieved was 93.0% for non-secreting adenomas and 100% for secreting adenomas, respectively. Normalization of endocrine hypersecretion was noted in 24 of 26 patients (92%). Detailed endocrinological follow-up data were analyzed by an experienced endocrinologist in 77 patients. After a median follow-up of 10.54 years (mean 10.22; range 1.39–20.75 years), in 75 of 77 patients (97%) a hypopituitarism was observed (partial hypopituitarism, n = 28 [36%], panhypopituitarism, n = 47 [61%]), and 68 out of 77 patients (88%) showed evidence of radiotherapy-induced pituitary disorders. The somatotropic function was most commonly affected, followed by gonadal, thyroid and adrenal function. The gonadal axis showed to be the first to be disturbed. 67 patients (87%) required a hormone replacement therapy.Conclusion:Radiotherapy after pituitary surgery is highly effective in reducing hormonal hypersecretion and preventing recurrences of pituitary adenomas. However, pituitary insufficiencies are commonly observed after radiotherapy requiring a close follow-up to ensure timely diagnosis of pituitary dysfunction and an early inception of hormone replacement therapy.Ziel:Ziel der retrospektiven Analyse war die Evaluation der lokalen Tumorkontrolle sowie der hormonellen Normalisierung nach konventioneller postoperativer Strahlentherapie in der Langzeitbeobachtung. Zusätzlich wurden die Inzidenz und der zeitliche Verlauf von Hypophyseninsuffizienzen untersucht.Patienten und Methodik:Zwischen April 1984 and November 1994 wurden 87 Patienten mit Makroadenomen der Hypophyse (nicht-sezernierende Adenome: n = 61, sezernierende Adenome: n = 26) einer postoperativen Strahlentherapie unterzogen. Die Bestrahlung erfolgte mit einer medianen Dosis von 50,4 Gy (Spannweite 46–54 Gy).Ergebnisse:Nach 15 Jahren betrug die lokale Kontrolle bei nicht-sezernierenden Adenomen 93% und bei sezernierenden Adenomen 100%. Eine Normalisierung der hormonellen Hypersekretion konnte bei 24 von 26 Patienten (92%) erreicht werden. Detaillierte Informationen über die hypophysäre Funktion lagen bei 77 Patienten vor. Nach median 10,54 Jahren wurde bei 75 von 77 Patienten (97%) eine Funktionsstörung des Hypophysenvorderlappens diagnostiziert (partieller Hypopituitarismus: n = 28 [36%], Panhypopituitarismus: n = 47 [61%]). Bei 68 von 77 Patienten (88%) zeigte sich eine radiotherapiebedingte Störung hormoneller Funktionen. Die somatotrope Achse war am häufigsten betroffen, gefolgt von der gonadotropen, der thyreotropen und der adrenokortikotropen Achse. In der Analyse des zeitlichen Verlaufs zeigte die gonadotrope Achse als Erste eine funktionelle Störung. 67 Patienten (87%) entwickelten eine substitutionspflichtige Hypophysenvorderlappeninsuffizienz.Schlussfolgerung:Mit der konventionellen postoperativen Strahlentherapie konnte eine ausgezeichnete lokale Kontrolle in der Langzeitbeobachtung erreicht werden. Die Rate an Hypophyseninsuffizienzen erfordert jedoch in einem hohen Prozentsatz eine Hormonersatztherapie und macht lebenslange endokrinologische Kontrollen notwendig.

Wide Tangential Fields Including the Internal Mammary Lymph Nodes in Patients with Left-Sided Breast Cancer

Purpose:To evaluate the impact of wide-tangent fields including the internal mammary chain during deep inspiration breath-hold (DIBH) radiotherapy in patients with left-sided breast cancer on cardiac exposure.Patients and Methods:Eleven patients with left-sided breast cancer were irradiated postoperatively and underwent CT scans during free breathing and DIBH. For scientific interest only, treatment plans were calculated consisting of wide tangents including the ipsilateral mammary lymph nodes using both, the free breathing and respiratory-controlled CT scan. The resulting dose-volume histograms were compared for irradiated volumes and doses to organs at risk.Results:The mean patient age was 51 years (range: 37–65 years). Radiotherapy using wide tangents with DIBH as compared to free breathing led to a significantly lower cardiac exposure. Mean irradiated heart volumes (≥ 20 Gy) were 14 cm3 (range: 0–51.3 cm3) versus 35 cm3 (range: 2.1–78.7 cm3; p = 0.01). For eight patients, DIBH reduced irradiated relative lung volume, while in three patients, the lung volume slightly increased.Conclusion:Radiation exposure of organs at risk can significantly be reduced for breast cancer patients using the DIBH technique. If radiotherapy of the internal mammary lymph nodes is considered necessary, DIBH may be the preferable technique.Ziel:Untersuchung des Stellenwerts einer atemgesteuerten (DIBH) Strahlenbehandlung bei Verwendung flacher tangentialer Felder und Einschluss der Lymphknoten entlang der A. mammaria interna bei Patientinnen mit linksseitigem Mammakarzinom im Hinblick auf die Herzbelastung.Patienten und Methodik:Bei elf Patientinnen mit linksseitigem Mammakarzinom wurde postoperativ eine lokale Strahlenbehandlung durchgeführt. Für diese CT-Studie wurden unter Bedingungen der Normalatmung und in tiefer Inspiration (Abbildung 1) ein Planungs-CT durchgeführt und jeweils ein optimierter Bestrahlungsplan mit zwei flachen tangentialen Bestrahlungsfeldern unter Berücksichtigung der ipsilateralen Lymphknoten entlang der A. mammaria interna erstellt. Die Dosis-Volumen-Histogramme für die Risikoorgane wurden zwischen beiden Atmungstechniken verglichen.Ergebnisse:Der Mittelwert des Alters lag bei 51 Jahren (Range: 37–65 Jahre). Die Bestrahlung mit flachen Tangenten und DIBH erbrachte im Vergleich zur Normalatmung eine signifikant geringere Herzbelastung. Die mittlere Herzbelastung (≥ 20 Gy) ergab 14 cm3 (Range: 0–51,3 cm3) im Vergleich zu 35 cm3 (Range: 2,1–78,7 cm3; p = 0,01; Tabelle 1). Bei acht Patientinnen reduzierte die atemgetriggerte Bestrahlung auch das bestrahlte Lungenvolumen (%), wobei es bei drei Patientinnen geringfügig anstieg (Tabelle 2).Schlussfolgerung:Die atemgetriggerte Bestrahlung in tiefer Inspiration reduziert signifikant die Strahlenbelastung an Risikoorganen. Bei Indikation des Einschlusses der Lymphknoten entlang der A. mammaria interna kann die Bestrahlung in DIBH von Vorteil sein.

Long-Term Follow-up of Patients with Pituitary Macroadenomas after Postoperative Radiation Therapy

Purpose:Evaluation of long-term tumor control, normalization of hormonal hypersecretion, including incidence and time course of pituitary dysfunction following postoperative radiotherapy of pituitary macroadenomas.Patients and Methods:In a retrospective study, the data of 87 patients with pituitary macroadenomas (61 non-secreting adenomas, 26 secreting adenomas) treated between 1984 and 1994 were analyzed. All patients underwent surgery and received postoperative external-beam radiotherapy with a mean dose of 50.4 Gy (range 46–54 Gy).Results:After a follow-up of 15 years the local tumor control rate achieved was 93.0% for non-secreting adenomas and 100% for secreting adenomas, respectively. Normalization of endocrine hypersecretion was noted in 24 of 26 patients (92%). Detailed endocrinological follow-up data were analyzed by an experienced endocrinologist in 77 patients. After a median follow-up of 10.54 years (mean 10.22; range 1.39–20.75 years), in 75 of 77 patients (97%) a hypopituitarism was observed (partial hypopituitarism, n = 28 [36%], panhypopituitarism, n = 47 [61%]), and 68 out of 77 patients (88%) showed evidence of radiotherapy-induced pituitary disorders. The somatotropic function was most commonly affected, followed by gonadal, thyroid and adrenal function. The gonadal axis showed to be the first to be disturbed. 67 patients (87%) required a hormone replacement therapy.Conclusion:Radiotherapy after pituitary surgery is highly effective in reducing hormonal hypersecretion and preventing recurrences of pituitary adenomas. However, pituitary insufficiencies are commonly observed after radiotherapy requiring a close follow-up to ensure timely diagnosis of pituitary dysfunction and an early inception of hormone replacement therapy.Ziel:Ziel der retrospektiven Analyse war die Evaluation der lokalen Tumorkontrolle sowie der hormonellen Normalisierung nach konventioneller postoperativer Strahlentherapie in der Langzeitbeobachtung. Zusätzlich wurden die Inzidenz und der zeitliche Verlauf von Hypophyseninsuffizienzen untersucht.Patienten und Methodik:Zwischen April 1984 and November 1994 wurden 87 Patienten mit Makroadenomen der Hypophyse (nicht-sezernierende Adenome: n = 61, sezernierende Adenome: n = 26) einer postoperativen Strahlentherapie unterzogen. Die Bestrahlung erfolgte mit einer medianen Dosis von 50,4 Gy (Spannweite 46–54 Gy).Ergebnisse:Nach 15 Jahren betrug die lokale Kontrolle bei nicht-sezernierenden Adenomen 93% und bei sezernierenden Adenomen 100%. Eine Normalisierung der hormonellen Hypersekretion konnte bei 24 von 26 Patienten (92%) erreicht werden. Detaillierte Informationen über die hypophysäre Funktion lagen bei 77 Patienten vor. Nach median 10,54 Jahren wurde bei 75 von 77 Patienten (97%) eine Funktionsstörung des Hypophysenvorderlappens diagnostiziert (partieller Hypopituitarismus: n = 28 [36%], Panhypopituitarismus: n = 47 [61%]). Bei 68 von 77 Patienten (88%) zeigte sich eine radiotherapiebedingte Störung hormoneller Funktionen. Die somatotrope Achse war am häufigsten betroffen, gefolgt von der gonadotropen, der thyreotropen und der adrenokortikotropen Achse. In der Analyse des zeitlichen Verlaufs zeigte die gonadotrope Achse als Erste eine funktionelle Störung. 67 Patienten (87%) entwickelten eine substitutionspflichtige Hypophysenvorderlappeninsuffizienz.Schlussfolgerung:Mit der konventionellen postoperativen Strahlentherapie konnte eine ausgezeichnete lokale Kontrolle in der Langzeitbeobachtung erreicht werden. Die Rate an Hypophyseninsuffizienzen erfordert jedoch in einem hohen Prozentsatz eine Hormonersatztherapie und macht lebenslange endokrinologische Kontrollen notwendig.

Wide tangential fields including the internal mammary lymph nodes in patients with left-sided breast cancer. Influence of respiratory-controlled radiotherapy (4D-CT) on cardiac exposure.

Purpose:To evaluate the impact of wide-tangent fields including the internal mammary chain during deep inspiration breath-hold (DIBH) radiotherapy in patients with left-sided breast cancer on cardiac exposure.Patients and Methods:Eleven patients with left-sided breast cancer were irradiated postoperatively and underwent CT scans during free breathing and DIBH. For scientific interest only, treatment plans were calculated consisting of wide tangents including the ipsilateral mammary lymph nodes using both, the free breathing and respiratory-controlled CT scan. The resulting dose-volume histograms were compared for irradiated volumes and doses to organs at risk.Results:The mean patient age was 51 years (range: 37–65 years). Radiotherapy using wide tangents with DIBH as compared to free breathing led to a significantly lower cardiac exposure. Mean irradiated heart volumes (≥ 20 Gy) were 14 cm3 (range: 0–51.3 cm3) versus 35 cm3 (range: 2.1–78.7 cm3; p = 0.01). For eight patients, DIBH reduced irradiated relative lung volume, while in three patients, the lung volume slightly increased.Conclusion:Radiation exposure of organs at risk can significantly be reduced for breast cancer patients using the DIBH technique. If radiotherapy of the internal mammary lymph nodes is considered necessary, DIBH may be the preferable technique.Ziel:Untersuchung des Stellenwerts einer atemgesteuerten (DIBH) Strahlenbehandlung bei Verwendung flacher tangentialer Felder und Einschluss der Lymphknoten entlang der A. mammaria interna bei Patientinnen mit linksseitigem Mammakarzinom im Hinblick auf die Herzbelastung.Patienten und Methodik:Bei elf Patientinnen mit linksseitigem Mammakarzinom wurde postoperativ eine lokale Strahlenbehandlung durchgeführt. Für diese CT-Studie wurden unter Bedingungen der Normalatmung und in tiefer Inspiration (Abbildung 1) ein Planungs-CT durchgeführt und jeweils ein optimierter Bestrahlungsplan mit zwei flachen tangentialen Bestrahlungsfeldern unter Berücksichtigung der ipsilateralen Lymphknoten entlang der A. mammaria interna erstellt. Die Dosis-Volumen-Histogramme für die Risikoorgane wurden zwischen beiden Atmungstechniken verglichen.Ergebnisse:Der Mittelwert des Alters lag bei 51 Jahren (Range: 37–65 Jahre). Die Bestrahlung mit flachen Tangenten und DIBH erbrachte im Vergleich zur Normalatmung eine signifikant geringere Herzbelastung. Die mittlere Herzbelastung (≥ 20 Gy) ergab 14 cm3 (Range: 0–51,3 cm3) im Vergleich zu 35 cm3 (Range: 2,1–78,7 cm3; p = 0,01; Tabelle 1). Bei acht Patientinnen reduzierte die atemgetriggerte Bestrahlung auch das bestrahlte Lungenvolumen (%), wobei es bei drei Patientinnen geringfügig anstieg (Tabelle 2).Schlussfolgerung:Die atemgetriggerte Bestrahlung in tiefer Inspiration reduziert signifikant die Strahlenbelastung an Risikoorganen. Bei Indikation des Einschlusses der Lymphknoten entlang der A. mammaria interna kann die Bestrahlung in DIBH von Vorteil sein.

The Glu228Ala polymorphism in the ligand binding domain of death receptor 4 is associated with increased risk for prostate cancer metastases.

Death receptor 4, encoded by the TNFRSF10A gene, is an important mediator of apoptosis and its dysfunction may be related to cancer development and distant tumor spread. A single nucleotide polymorphism in TNFRSF10A (Glu228Ala, rs20576) within a conserved region of the extracellular cysteine‐rich domain of death receptor 4 has been associated with an increased risk for a variety of tumor entities. Aim of the present study was to evaluate the role of the TNFRSF10A polymorphism in metastatic progression of prostate cancer after radiation therapy.

The elevated C-reactive protein level is associated with poor prognosis in prostate cancer patients treated with radiotherapy

BACKGROUND C-reactive protein (CRP) is a sensitive marker of inflammation that has been linked with prognosis in various solid tumours. In the present study, we analysed the prognostic relevance of elevated plasma CRP levels in prostate cancer patients treated with radiotherapy. METHODS A total of 261 prostate cancer patients treated with 3D-conformal radiotherapy were evaluated retrospectively. Cancer specific survival (CSS), overall survival (OS) and clinical disease-free survival (DFS) were assessed using Kaplan-Meier analysis. To evaluate the independent prognostic significance of CRP plasma levels, multivariate Cox regression models were applied. RESULTS The median follow-time was 80months. Applying receiver operating characteristics (ROC) analysis, the optimal cut-off level for the plasma CRP was 8.6mgl(-1). An elevated CRP level was associated with decreased CSS in univariate (hazard ratio (HR) 3.36, 95% confidence interval (CI) 1.42-7.91; p=0.006) and multivariate analysis (HR 4.31, 95% CI 1.22-15.1; p=0.023). Furthermore, a significant association with OS was detected in univariate (HR 2.69, 95% CI 1.57-4.59; p<0.001) and multivariate analyses (HR 3.24, 95% CI 1.84-5.71, p<0.001). Multivariate analysis also showed a significant association between plasma CRP and clinical DFS (HR 2.07, 95% CI 1.02-4.17; p=0.043). CONCLUSIONS In the present study, an elevated plasma CRP (⩾8.6mgl(-1)) has been identified as a prognostic factor for poor CSS, OS and DFS in prostate cancer patients undergoing radiotherapy. The association between elevated CRP levels and poor prognosis was independent of other measures of prognosis such as tumour stage, Gleason grading and prostate specific antigen (PSA) level at diagnosis. If confirmed by additional studies, our findings may contribute to future individual risk assessment in prostate cancer patients.

Evaluation of the platelet-to-lymphocyte ratio as a prognostic indicator in a European cohort of patients with prostate cancer treated with radiotherapy

OBJECTIVES Recent evidence suggests that the presence of a systemic inflammatory response plays an important role in the progression of several solid tumors. The platelet-to-lymphocyte ratio (PLR) has been proposed as an easily assessable marker of systemic inflammation and has been shown to represent a prognostic marker in different cancer entities. To evaluate the prognostic value of the PLR in prostate cancer, we performed the present study. METHODS AND MATERIALS Data from 374 consecutive patients with prostate cancer, treated with 3D conformal radiotherapy from 1999 to 2007, were analyzed. Distant metastases-free survival (MFS), cancer-specific survival (CSS), overall survival (OS), biochemical disease-free survival, and time to salvage systemic therapy were assessed using the Kaplan-Meier method. Cox proportional hazards analysis was performed to calculate hazard ratio (HR) and 95% CI. Multivariate Cox regression analysis was performed to adjust for other covariates. RESULTS Using receiver operating characteristics analysis, the optimal cutoff level for the PLR was 190. Kaplan-Meier analyses revealed that PLR≥190 was a prognostic factor for decreased MFS (P = 0.004), CSS (P = 0.004), and OS (P = 0.024) whereas a significant association of an elevated PLR with biochemical disease-free survival (P = 0.740) and time to salvage systemic therapy (P = 0.063) was not detected. In multivariate analysis, an increased PLR remained a significant prognostic factor for poor MFS (HR = 2.24, 95% CI: 1.06-4.76, P = 0.036), CSS (HR = 3.99, 95% CI: 1.19-13.4, P = 0.025), and OS (HR = 1.87, 95% CI: 1.02-3.42, P = 0.044). CONCLUSIONS Our findings indicate that the PLR may predict prognosis in patients with prostate cancer and may contribute to future individual risk assessment in them.

Impact of VEGF gene polymorphisms and haplotypes on radiation-induced late toxicity in prostate cancer patients.

Background and PurposeVascular endothelial growth factor (VEGF) is an important determinant of microvascular permeability and angiogenesis and has been shown to be up-regulated during the late phase of radiation injury. The present prospective study was performed to evaluate the role of VEGF gene polymorphisms and haplotypes in the development of radiation-induced late side effects in prostate cancer patients.Patients and MethodsThe association of VEGF gene polymorphisms and haplotypes with high-grade late rectal or urinary toxicity (defined as late toxicity EORTC/RTOG ≥2) was analyzed using 493 prostate cancer patients from the Austrian PROCAGENE study treated with definitive radiotherapy. Seven candidate polymorphisms in the VEGF gene were selected and determined by 5’-nuclease (TaqMan) assays.ResultsWithin a median follow-up time of 48 months, 42 patients (8.6%) developed high-grade late rectal and 47 patients (9.6%) urinary toxicity, respectively. In a Kaplan–Meier analysis, carriers of the VEGF -7C > T polymorphism were at increased risk of high-grade late rectal toxicity (p = 0.003) and in a multivariate analysis including clinical and dosimetric parameters as potential confounders the VEGF -7C > T polymorphism remained a significant predictor (HR = 2.8, 95% CI 1.349–5.813; p = 0.006). Furthermore, the ATTGT haplotype formed by five polymorphisms upstream of the coding sequence demonstrated a significant association with late rectal toxicity grade ≥2 (p = 0.001). No significant associations were found for the remaining polymorphisms and haplotypes.ConclusionWe conclude that genetic variants in the VEGF gene may influence the risk of high-grade late rectal toxicity after definitive radiotherapy for prostate cancer.ZusammenfassungHintergrundVascular endothelial growth factor (VEGF) ist ein wichtiger Regulator der Gefäßpermeabilität und Angiogenese, und in der chronischen Strahlenreaktionsphase wurde die Hochregulation von VEGF gezeigt. Ziel der vorliegenden prospektiven Studie war die Analyse des Zusammenhangs von VEGF-Genpolymorphismen und -Haplotypen mit dem Auftreten von radiogenen Spätfolgen bei Prostatakarzinompatienten.Patienten und MethodenDer Zusammenhang zwischen VEGF-Genpolymorphismen und -Haplotypen und höhergradigen rektalen und urogenitalen Spätfolgen (definiert als Spättoxizität EORTC/RTOG ≥2) wurde bei 493 Prostatakarzinompatienten der PROCAGENE-Studie, die einer definitiven Strahlentherapie unterzogen wurden, untersucht. 7 Kandidatenpolymorphismen wurden ausgewählt und mittels 5´-Nuklease-Assays (TaqMan) analysiert.ErgebnisseWährend einer medianen Nachbeobachtungszeit von 48 Monaten entwickelten 42 Patienten (8,6%) höhergradige rektale und 47 Patienten (9,6%) urogenitale Nebenwirkungen. In der Kaplan-Meier-Analyse zeigten Träger des VEGF -7C > T-Poly-morphismus ein erhöhtes Risiko für höhergradige rektale Spätfolgen (p = 0,003; Abbildung 2) und in der multivariaten Analyse, in welche klinische und dosimetrische Faktoren eingeschlossen wurden, blieb der VEGF -7C > T-Polymorphismus ein signifikanter Prediktor (HR = 28; 95%-CI 1,349–5,813; p = 0,006, Tabelle 4). Zusätzlich zeigte sich für den ATTGT-Haplotyp, bestehend aus 5 vor der kodierenden Sequenz liegenden Polymorphismen, eine signifikante Assoziation mit höhergradiger rektaler Spättoxizität (p = 0,001; Abbildung 3). Keine signifikanten Assoziationen wurden für die übrigen untersuchten Polymorphismen und Haplotypen gefunden (Tabellen 3 und 4).SchlussfolgerungDie vorliegenden Daten zeigen, dass Varianten im VEGF-Gen möglicherweise das Auftreten von höhergradigen rektalen Spätfolgen nach definitiver Radiotherapie des Prostatakarzinoms beeinflussen.