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ABSTRACT: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The development of side effects characteristic for the different treatment methods with impact on the patients' quality of life plays a growing role for individual patients with early stage prostate cancer. Using permanent brachytherapy a high dose to the prostate can be applied with a steep dose gradient to the normal tissue. However, small partial volumes of normal tissue may be exposed to high doses inducing special side effects including lower urinary tract symptoms and/or erectile dysfunction. In the literature there are only few publications so far regarding segmental dosimetry and its influence on side effects and the results are conflicting. We could not identify any dosimetric parameter in segmental dosimetry that may have an influence at certain time intervals on the development of side effects such as lower urinary tract symptoms or erectile dysfunction. However, we could state clearly that the preoperative situation is the most important factor for postoperative outcome. OBJECTIVE: To report on the side effects of patients with low to low-intermediate risk prostate cancer treated with permanent interstitial brachytherapy with special emphasis on segmental dosimetry. PATIENTS AND METHODS: A series of 186 consecutive patients treated for early stage prostate cancer receiving definitive I-125 brachytherapy (permanent seed implantation) between November 2001 and April 2005 at our institution were examined for the development of side effects. Morbidity was assessed prospectively using the International Prostate Symptom Score (IPSS) and the International Index of Erectile Function (IIEF-5) in a mean follow-up interval of 30 months. The scores were correlated with segmental dosimetry performed 6 weeks after the implantation. RESULTS: The mean postoperative dose to 90% of the prostate volume (D90) was 180.2 Gy, the mean preoperative IPSS 7.2 and the mean IIEF-5 14.35, with all scores showing a maximum deterioration after 6 weeks with normalization after 24 months. After correlating the segmental dosimetry and the scores at different time intervals, only the baseline scores remained statistically significant in multivariate regression analysis at all time intervals (P < 0.00). CONCLUSIONS: We could not demonstrate a correlation of segmental dosimetry with induction of side effects. There is no relationship between dose exposure of partial volumes and the development of radiation-induced toxicities. The preoperative situation regarding lower urinary tract symptoms and erectile function are the most important factors for postoperative outcome.
BJU International 01/2013; · 2.84 Impact Factor
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ABSTRACT: After renal transplantation, patients have a higher incidence of developing cancer necessitating pelvic radiotherapy, but there is a lack of data for such therapy in this patient group.
Nine patients with pelvic renal transplants were treated with pelvic radiotherapy between 04/2002 and 06/2011. Treatment was carried out for prostate (n=4), rectal (n=2), and anal cancer (n=1), osseous metastasis (n=1), and Hodgkin's disease (n=1). The mean age of the transplants was 12.6 years.
The mean total dose to the target volume was 60.2 Gy, the mean maximum dose to the transplant was 10.0 Gy, with a mean dose of 2.1 Gy. The mean creatinine clearance before start of radiotherapy was 48.9 ml/min. After a mean follow-up of 23 months, no patient showed failure of the transplant and the mean creatinine clearance was 64.2 ml/min.
Using modern radiotherapy techniques, low doses to the transplant can be achieved without compromising target treatment and without transplant failure. A mean dose of <4 Gy seems to be well-tolerated by the graft.
Anticancer research 11/2012; 32(11):5083-6. · 1.73 Impact Factor
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Maren Weischer,
Børge G Nordestgaard,
Paul Pharoah,
Manjeet K Bolla,
Heli Nevanlinna,
Laura J Van't Veer,
Montserrat Garcia-Closas,
John L Hopper,
Per Hall,
Irene L Andrulis, [......],
Simon S Cross,
Laura Baglietto,
Christof Sohn,
Xianshu Wang,
Vesa Kataja,
Anne-Lise Børresen-Dale, Andreas Meyer,
Douglas F Easton,
Marjanka K Schmidt,
Stig E Bojesen
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ABSTRACT: PURPOSEWe tested the hypotheses that CHEK2*1100delC heterozygosity is associated with increased risk of early death, breast cancer-specific death, and risk of a second breast cancer in women with a first breast cancer. PATIENTS AND METHODS
From 22 studies participating in the Breast Cancer Association Consortium, 25,571 white women with invasive breast cancer were genotyped for CHEK2*1100delC and observed for up to 20 years (median, 6.6 years). We examined risk of early death and breast cancer-specific death by estrogen receptor status and risk of a second breast cancer after a first breast cancer in prospective studies.ResultsCHEK2*1100delC heterozygosity was found in 459 patients (1.8%). In women with estrogen receptor-positive breast cancer, multifactorially adjusted hazard ratios for heterozygotes versus noncarriers were 1.43 (95% CI, 1.12 to 1.82; log-rank P = .004) for early death and 1.63 (95% CI, 1.24 to 2.15; log-rank P < .001) for breast cancer-specific death. In all women, hazard ratio for a second breast cancer was 2.77 (95% CI, 2.00 to 3.83; log-rank P < .001) increasing to 3.52 (95% CI, 2.35 to 5.27; log-rank P < .001) in women with estrogen receptor-positive first breast cancer only. CONCLUSION
Among women with estrogen receptor-positive breast cancer, CHEK2*1100delC heterozygosity was associated with a 1.4-fold risk of early death, a 1.6-fold risk of breast cancer-specific death, and a 3.5-fold risk of a second breast cancer. This is one of the few examples of a genetic factor that influences long-term prognosis being documented in an extensive series of women with breast cancer.
Journal of Clinical Oncology 10/2012; · 18.37 Impact Factor
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Ali Amin Al Olama,
Zsofia Kote-Jarai,
Fredrick R Schumacher,
Fredrik Wiklund,
Sonja I Berndt,
Sara Benlloch,
Graham G Giles,
Gianluca Severi,
David E Neal,
Freddie C Hamdy, [......],
Shintaro Narita,
Guang-Wen Cao,
Chavdar Slavov,
Vanio Mitev,
Stephen Chanock,
Henrik Gronberg,
Christopher A Haiman,
Peter Kraft,
Douglas F Easton,
Rosalind A Eeles
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ABSTRACT: Genome-wide association studies (GWAS) have identified multiple common genetic variants associated with an increased risk of prostate cancer (PrCa), but these explain less than one third of the heritability. To identify further susceptibility alleles, we conducted a meta-analysis of four genome-wide association studies (GWAS) including 5,953 cases of aggressive PrCa and 11,463 controls (men without PrCa). We computed association tests for ~2.6M SNPs and followed up the most significant SNPs by genotyping 49,121 samples in 29 studies through the international PRACTICAL and BPC3 consortia. We not only confirmed the association of a PrCa susceptibility locus, rs11672691 on chromosome 19, but also showed an association with aggressive PrCa (OR=1.12 (95% CI 1.03-1.21), P=1.4x10(-8)). This report describes a genetic variant which is associated with aggressive prostate cancer, which is a type of prostate cancer associated with a poorer prognosis.
Human Molecular Genetics 10/2012; · 7.64 Impact Factor
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Maral Jamshidi,
Marjanka K Schmidt,
Thilo Dörk,
Montserrat Garcia-Closas,
Tuomas Heikkinen,
Sten Cornelissen,
Alexandra J van den Broek,
Peter Schürmann, Andreas Meyer,
Tjoung-Won Park-Simon, [......],
Mark Sherman,
Jolanta Lissowska,
Garrett Teoh Hor Keong,
Astrid Irwanto,
Marko Laakso,
Sampsa Hautaniemi,
Kristiina Aittomäki,
Carl Blomqvist,
Jianjun Liu,
Heli Nevalinna
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ABSTRACT: Germ line variation in the TP53 network genes PRKAG2, PPP2R2B, CCNG1, PIAS1 and YWHAQ was previously suggested to have an impact on drug response in vitro. Here, we investigated the effect on breast cancer survival of germ line variation in these genes in 925 Finnish breast cancer patients and further analyzed 5 SNPs in PRKAG2 (rs1029946, rs4726050, rs6464153, rs7789699) and PPP2R2B (rs10477313) for 10-year survival in breast cancer patients, interaction with TP53 R72P and MDM2-SNP309, outcome after specific adjuvant therapy, and correlation to tumor characteristics in 4701 invasive cases from four data sets. We found evidence for carriers of PRKAG2-rs1029946 and PRKAG2-rs4726050 having improved survival in the pooled data (HR 0.53, 95% CI 0.3-0.9; P = 0.023 for homozygous carriers of the rare G-allele and HR 0.85, 95% CI 0.7-0.9; P = 0.049 for carriers of the rare G allele, respectively). PRKAG2-rs4726050 showed a significant interaction with MDM2-SNP309, with PRKAG2-rs4726050 rare G-allele having a dose-dependent effect for better breast cancer survival confined only to MDM2 SNP309 rare G-allele carriers (HR 0.45, 95% CI 0.2-0.7; P = 0.001). This interaction also emerged as an independent predictor of better survival (P = 0.047). PPP2R2B-rs10477313 rare A-allele was found to predict better survival (HR 0.82, 95% CI 0.6-0.9; P = 0.018), especially after hormonal therapy (HR 0.66, 95% CI 0.5-0.9; P = 0.048). These findings warrant further studies and suggest that genetic markers in TP53 network genes such as PRKAG2 and PPP2R2B might affect prognosis and treatment outcome in breast cancer patients.
International Journal of Cancer 10/2012; · 5.44 Impact Factor
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ABSTRACT: Purpose:
To analyze the dosimetric and clinical benefit of a forward planned technique to optimize dose distribution in whole-breast
irradation (WBI) using additional partial-volume segments (PVSeg).
Patients and Methods:
In two separate treatment periods, 265 breast cancer patients received tangential-field WBI and were retrospectively analyzed.
Between 02/2004 and 03/2006, 96 patients were treated with one to two additional low-weighted PVSeg to reduce dose peaks within
the target volume. 169 patients treated between 01/2000 and 12/2001 before implementation of this PVSeg technique served as
comparison group. Total dose was 50–50.4 Gy (single dose, 1.8–2 Gy). The planning target volume (PTV) receiving at least 95%,
105% and 110% of the reference dose (V95–110%) and frequency of moist skin desquamation during radiotherapy were compared uni- and multivariately with patient- and treatment-related
variables.
Results:
The mean PTV was 1,144 ml (range, 235–2,365 ml). Moist skin desquamations developed in 16 patients (17%) with PVSeg compared
to 30 patients (18%) without PVSeg (p = 0.482). In breast volumes > 1,100 ml, the corresponding figures were 19% versus 29%
(p = 0.133). V105% was significantly reduced by the use of PVSeg (82 ± 51 ml vs. 143 ± 129 ml; p < 0.0001). In univariate analysis, the following
variables had significant influence on the development of moist skin desquamation: V95% (p < 0.0001), V105% (p < 0.001), V110% (p = 0.012) adjuvant chemotherapy (p = 0.02), and single dose (p = 0.009). In multivariate analysis, only V95% (p = 0.002) remained significant.
Conclusion:
The use of PVSeg in WBI reduced dose peaks within the PTV while breast volumes > 1,100 ml benefited most. V95% was strongly correlated to the risk of developing moist skin desquamations.
Ziel:
Untersuchung des Nutzens einer einfachen vorwärts geplanten Bestrahlungstechnik mit Partialvolumensegmenten (PVSeg) bei der
Ganzbrustbestrahlung.
Patienten und Methodik:
Es wurden 265 Brustkrebspatientinnen aus zwei Behandlungszeiträumen analysiert, die nach brusterhaltender Therapie eine Ganzbrustbestrahlung
mit tangentialen Feldern erhielten. Von 02/2004 bis 03/2006 erhielten 96 Patientinnen ein bis zwei zusätzliche, niedriggewichtete
PVSeg zur Reduzierung von Dosisspitzen im Zielvolumen. Als Vergleich dienten 169 Patientinnen im Zeitraum von 01/2000 bis
12/2001 vor Einführung der PVSeg-Technik. Die Gesamtdosis betrug 50–50,4 Gy (Einzeldosis: 1,8–2 Gy). Das Planungszielvolumen
(PTV), welches mindestens 95%, 105% und 110% der Referenzdosis (V95–110%) erhielt, und die Häufigkeit feuchter Epitheliolysen während der Bestrahlung wurden mittels uni- und multivariater Analyse
mit Patienten- und Behandlungsparametern verglichen.
Ergebnisse:
Das mittlere PTV betrug 1 144 ml (Streubreite: 235–2 365 ml). Feuchte Epitheliolysen traten bei 16 Patientinnen (17%) mit
PVSeg versus 30 Patientinnen (18%) ohne PVSeg auf (p = 0,482). Bei Brustvolumina > 1 100 ml wurden feuchte Epitheliolysen
mit und ohne PVSeg bei 19% versus 29% beobachtet (p = 0,133). Mit der PVSeg-Technik wurde V105% signifikant gesenkt (82 ± 51 ml vs. 143 ± 129 ml; p < 0,0001). In der univariaten Analyse beeinflussten folgende Faktoren
die Entwicklung feuchter Epitheliolysen signifikant: V95 (p < 0,0001), V105% (p < 0,001), V110% (p = 0,012), eine adjuvante Chemotherapie (p = 0,02) und die Höhe der Einzeldosis (p = 0,009). In der
multivariaten Analyse blieb nur V95% (p = 0,002) signifikant.
Schlussfolgerung:
Die vorgestellte PVSeg-Technik reduzierte Dosisspitzen im PTV, wobei Patientinnen mit Brustvolumina > 1 100 ml am meisten
profitierten. Es konnte eine starke Korrelation zwischen V95% und dem Auftreten feuchter Epitheliolysen gefunden werden.
Key Words:
Breast cancer-Whole-breast radiotherapy-Partial-volume segmentation-Dose optimization-Moist skin desquamation
Schlüsselwörter:
Brustkrebs-Ganzbrustbestrahlung-Partialvolumensegmentierung-Dosisoptimierung-Feuchte Epitheliolysen
Strahlentherapie und Onkologie 04/2012; 186(1):40-45. · 3.56 Impact Factor
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ABSTRACT: Background:
The internet as a source of medical information has emerged during the last years. There is a confusing amount of medical
websites with a great diversity of quality. Websites of radiotherapy institutions could offer a safe and an easy-to-control
way to assist patients’ requests.
Material and Methods:
205 internet appearances of German radiotherapy institutions were analyzed in June 2009 (nonuniversity hospitals n = 108,
medical practices n = 62, university hospitals n = 35). For the evaluation of each homepage verifiable criteria concerning
basic information, service and medical issues were used.
Results:
The quality of information published via internet by different radiotherapy institutions showed a large variety. Basic information
like telephone numbers, operating hours, and direction guidance were provided in 96.7%, 40%, and 50.7%, respectively. 85%
of the websites introduced the staff, 50.2% supplied photos and 14% further information on the attending physicians. The mean
amount of continuative links to other websites was 5.4, the mean amount of articles supplying medical information for patients
summed up to 4.6. Medical practices and university hospitals had statistically significant more informative articles and links
to other websites than nonuniversity hospitals. No statistically significant differences could be found in most other categories
like service issues and basic information.
Conclusion:
Internet presences of radiotherapy institutions hold the chance to supply patients with professional and individualized medical
information. While some websites are already using this opportunity, others show a lack of basic information or of user-friendliness.
Hintergrund:
Das Internet als Quelle für medizinische Informationen hat in den letzten Jahren an Relevanz gewonnen. Es existiert eine unübersichtliche
Anzahl von medizinischen Internetseiten mit großen Qualitätsunterschieden. Webseiten radiotherapeutischer Institute könnten
dabei eine sichere und leicht zu kontrollierende Hilfe für Patienten sein.
Material und Methodik:
Im Juni 2009 wurden 205 Internetauftritte deutscher Strahlentherapieinstitutionen untersucht (nichtuniversitäre Kliniken n
= 108, Praxen n = 62, Universitätskliniken n = 35). Zur Evaluation jeder einzelnen Homepage wurden verifizierbare Kriterien
im Hinblick auf allgemeine Informationen, Serviceaspekte und medizinische Belange untersucht (Tabelle 1).
Ergebnisse:
Die Qualität der Informationen auf den Internetseiten verschiedener radiotherapeutischer Einrichtungen zeigte eine große Bandbreite.
Allgemeine Informationen wie Telefonnummern, Öffnungszeiten und Orientierungshilfen wurden in 96,7%, 40% bzw. 50,7% bereitgestellt.
Auf 85% der Webseiten wurden die Mitarbeiter vorgestellt, 50,2% davon mit Fotos und 14% mit weiterführenden Informationen
zu den behandelnden Ärzten. Die mittlere Anzahl weiterführender Links zu anderen Webseiten betrug 5,4, die mittlere Anzahl
von medizinischen Informationstexten belief sich auf 4,6. Praxen und Universitätskliniken stellten statistisch signifikant
mehr Informationstexte und Links zu anderen Webseiten bereit als nichtuniversitäre Kliniken. Keine statistisch signifikanten
Unterschiede gab es im Servicebereich und bei den allgemeinen Informationen.
Schlussfolgerung:
Internetauftritte radiotherapeutischer Institutionen bieten die Möglichkeit, Patienten mit professionellen und individualisierten
medizinischen Informationen zu versorgen. Während einige Webseiten diese Chance bereits nutzen, weisen andere noch Mängel
im Bereich der allgemeinen Informationen und Benutzerfreundlichkeit auf.
Key WordsWebsites–Internet–Radiotherapy–Patient information
SchlüsselwörterInternetseiten–Internet–Strahlentherapie–Patienteninformation
Strahlentherapie und Onkologie 04/2012; 186(12):700-704. · 3.56 Impact Factor
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ABSTRACT: Purpose:
Efficacy and safety of the own single-center experience with moderately dosed radiosurgery (SRS) for limited (one to four)
brain metastases were analyzed and correlated with patient- and treatment-related variables.
Patients and Methods:
Between 05/1998 and 10/2006, 93 patients received SRS for a total of 142 brain metastases. The median number of brain metastases
treated per patient was one (range, one to four). 46 patients (49%) received initial SRS alone, 13 patients (14%) SRS with
up-front whole-brain radiotherapy (WBRT), and 34 patients (37%) SRS for recurrent metastases after WBRT. Median dose was 16
Gy (range, 10–20 Gy).
Results:
Median overall survival (OS) was 7.5 months. The actuarial 6- and 12-month data for OS were 60% and 35%, for local brain control
(LBC) 87% and 79%, and for distant brain control (DBC) 48% and 37%, respectively. Only ten of 46 patients (22%) with initial
SRS alone ultimately received WBRT. Ten patients suffered from seizures within 3 months after SRS, six of them showed brain
progression on magnetic resonance imaging (MRI). 20 patients required reinstitution of steroids following SRS, 16 of these
due to brain progression. Five patients received positron emission tomography scan of the brain revealing radionecrosis in
two patients. In uni- and multivariate analysis, only time interval between diagnosis of primary and brain metastases (p =
0.031) and volume of treated metastasis (p = 0.02) were significant predictors of OS. Neither up-front WBRT nor dose had a
significant influence on LBC.
Conclusion:
Moderately dosed SRS of limited brain metastases was found to be both effective and safe. Initial SRS only may be offered
to informed patients complying with MRI-based follow-up.
Ziel:
Wirksamkeit und Verträglichkeit der moderat dosierten stereotaktischen Einzeitbestrahlung (SRS) bei limitierten (ein bis vier)
Hirnmetastasen sollte am eigenen Patientenkollektiv untersucht und mit patienten- und behandlungsbezogenen Parametern verglichen
werden.
Patienten und Methodik:
Von 05/1998 bis 10/2006 erhielten 93 Patienten eine SRS von 142 Hirnmetastasen. Median wurde pro Patient eine Hirnmetastase
bestrahlt (Streubreite: ein bis vier). Bei 46 Patienten (49%) erfolgte die SRS als alleinige Primärtherapie, bei 13 Patienten
(14%) mit früher Ganzhirnbestrahlung (WBRT) und bei 34 Patienten (37%) wegen einer Rezidivmetastase nach WBRT. Die Dosis betrug
median 16 Gy (Streubreite: 10–20 Gy).
Ergebnisse:
Das Gesamtüberleben nach SRS lag bei median 7,5 Monaten. Nach 6 bzw. 12 Monaten betrugen das Gesamtüberleben (OS) aktuarisch
60% und 35%, die lokale Kontrolle (LBC) 87% und 79% sowie die distale zerebrale Kontrolle (DBC) 48% und 37%. Nur zehn von
46 Patienten (22%) mit alleiniger SRS erhielten später eine WBRT. Zehn Patienten hatten Krampfanfälle innerhalb von 3 Monaten
nach SRS, sechs davon zeigten im Magnetresonanztomogramm einen zerebralen Progress. 20 Patienten benötigten ein Wiedereinsetzen
von Steroiden nach der SRS, 16 davon wegen zerebralem Progress. Bei fünf Patienten wurde eine Positronenemissionstomographie
des Kopfes durchgeführt, bei zwei wurde eine Radionekrose diagnostiziert. In der uni- und multivariaten Analyse hatten nur
das Zeitintervall zwischen Diagnose von Primärtumor und Hirnmetastase (p = 0,031) und das Volumen der bestrahlten Metastase
(p = 0,02) signifikanten Einfluss auf das Überleben. Weder der frühe Einsatz der WBRT noch die Dosis beeinflussten die LBC
signifikant.
Schlussfolgerung:
Die moderat dosierte SRS bei limitierter Hirnmetastasierung war ausreichend wirksam und verträglich. Die alleinige primäre
SRS eignet sich für informierte Patienten, die zu MRT-basierten Verlaufskontrollen bereit sind.
Key Words:
Radiosurgery-Brain metastases-Moderate dose-Outcome data
Schlüsselwörter:
Stereotaktische Einzeitbestrahlung-Hirnmetastasen-Moderate Dosis-Behandlungsergebnisse
Strahlentherapie und Onkologie 04/2012; 186(2):76-81. · 3.56 Impact Factor
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ABSTRACT: The aim of this study is to determine prognostic factors that influence further outcome in patients with glioma.
Between 01/2002 and 08/2008, 153 patients with malignant gliomas of WHO-grade 3 or 4 who were treated with external beam radiotherapy with or without chemotherapy.
In univariate analysis, following factors were ascertained as statistically significant prognostic parameters: grade (p = 0.000), time between operation and radiotherapy >24 days (p = 0.044) for progression-free survival; grade (p = 0.000), age<58 years (p = 0.001), extent of surgery (p = 0.011), time between operation and radiotherapy >24 days (p = 0.009), overall treatment time >68 days (p = 0.003), use of chemotherapy (p = 0.015) for overall survival. A longer time period between resection and start of radiotherapy showed to be associated with improved outcome. After multivariate analysis, only grade (p = 0.000) remained a statistically significant factor for progression-free and grade (p = 0.000) and use of chemotherapy (p = 0.031) for overall survival.
We were able to recognize grade and use of chemotherapy as statistically significant prognostic determinants, but not time intervals or overall treatment time.
Clinical neurology and neurosurgery 01/2012; 114(6):617-21. · 1.30 Impact Factor
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Manuel Luedeke,
Irina Coinac,
Carmen M Linnert,
Natalia Bogdanova,
Antje E Rinckleb,
Mark Schrader,
Walther Vogel,
Josef Hoegel, Andreas Meyer,
Thilo Dörk,
Christiane Maier
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ABSTRACT: Prostate cancer susceptibility has previously been associated with truncating germline variants in the gene TP53AIP1 (tumor protein p53 regulated apoptosis inducing protein 1). For two apparently recurrent mutations (p.Q22fs and p.S32X) a remarkable OR of 5.1 was reported for prostate cancer risk. Since these findings have not been validated so far, we genotyped p.Q22fs and p.S32X in two German series with a total of 1,207 prostate cancer cases and 1,495 controls. The truncating variants were not significantly associated with prostate cancer in none of the two cohorts, nor in the combined analysis [odds ratio (OR) = 1.16; 95% confidence interval (CI 95%) = 0.62-2.15; p = 0.66]. Carriers showed no significant differences in family history of prostate cancer, age at diagnosis, Gleason score or PSA at diagnosis when compared to non-carrier prostate cancer cases. The large sample size of the combined cohort rejects a high-risk effect greater than 2.2 and indicates a limited role of TP53AIP1 in prostate cancer predisposition.
PLoS ONE 01/2012; 7(3):e34128. · 4.09 Impact Factor
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ABSTRACT: Local hypofractionated stereotactic radiation treatment (hfSRT) of early stage non-small cell lung cancer (NSCLC) represents a highly effective treatment alternative in medically inoperable patients.
Between June 2007 and December 2010, 65 patients with NSCLC were treated with image-guided hypofractionated radiotherapy. The Union Internationale Contre le Cancer (UICC) stage distribution was: IA, n = 19; IB, n = 15; IIB, n = 5; IIIA, n = 10; IIIB, n = 6; and IV, n = 10. The fractionation schedule used was 3 × 12.5 Gy (n = 36) prescribed to the encompassing 67% isodose line for peripheral primary tumours, and 8 × 6 Gy (n = 26) or 8 × 5 Gy (n = 3) prescribed to the encompassing 80% isodose line for centrally located tumours.
Mean follow-up was 13.8 months (range 1-41 months). Until now 6 patients developed a local recurrence, 2 of them in combination with mediastinal lymph node failure. The 1-year actuarial local control rate was 93% and overall survival 79%. Pneumonitis was seen in 14 patients (21.5%) (Common Terminology Criteria for Adverse Events (CTCAE) grade I: n = 12, and II: n = 2) after a median time period of 9.5 months. No patient developed pneumonitis of CTCAE grade III or higher.
Image-guided hfSRT is effective and feasible in patients with non-operable NSCLC, even in higher stages, whenever local control is crucial and there are contraindications against systemic therapy.
Onkologie 01/2012; 35(7-8):408-12. · 0.87 Impact Factor
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ABSTRACT: Introduction. Langerhans cell histiocytosis (LCH) is a rare disease of unknown etiology with different clinical features. A standardised treatment has not been established so far. Case Report. We report a case of a 28-year-old patient who initially presented with hypesthesia of the fifth cranial nerve and pain of the left ear. Diagnosis showed a tumour localised in the cranial base with a maximum diameter of 4.1 cm. The diagnosis of LCH was confirmed histologically by biopsy. Diagnostic workup verified the cranial lesion as the sole manifestation of LCH. A total dose of 9 Gy (single dose 1.8 Gy) was delivered. The symptoms dissolved completely within 6 months after radiation; repeated CT and MRI scans revealed a reduction in size of the lesion and a remineralisation of the bone. After a followup of 13 years the patient remains free of symptoms without relapse or any side effects from therapy. Discussion. Due to the indolent course of the disease with a high rate of spontaneous remissions the choice of treatment strongly depends on the individual clinical situation. In the presented case low-dose radiotherapy was sufficient to obtain long-term local control in a region with critical structures and tissues.
Case reports in oncological medicine. 01/2012; 2012:789640.
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ABSTRACT: SLX4 coordinates three structure-specific endonucleases in the DNA damage response. One subtype of Fanconi anaemia, FA-P, has recently been attributed to biallelic SLX4 gene mutations. To investigate whether monoallelic SLX4 gene defects play some role in the inherited component of breast cancer susceptibility, in this study we resequenced the whole SLX4 coding region and flanking untranslated sections in genomic DNA samples obtained from a total of 52 German or Byelorussian patients with familial breast cancer. Selected variants were subsequently screened by RFLP or TaqMan-based assays in an extended set of 965 German breast cancer cases and 985 healthy female controls. The resequencing study uncovered four new SLX4 missense substitutions, each of them in a single breast cancer patient. Three missense substitutions (p.V197A, p.G700R and p.R1034H) were not found in a subsequent screening of 240 additional breast cancer patients, while one missense substitution (p.R237Q) was more common and was detected in a total of 12 cases (1.3%) and seven controls (0.7%) in the Hannover breast cancer study. The rare missense substitution, p.G700R, resides in the conserved BTB domain and was in silico predicted to be pathogenic. Seven additional missense polymorphisms were correlated and formed one haplotype which was, however, neither associated with breast cancer risk nor with survival from breast cancer. In summary, this study did not reveal truncating or clearly pathogenic mutations, but unravelled four new unclassified missense variants at a low frequency. We conclude that there is no evidence for a major role of SLX4 coding variants in the inherited susceptibility towards breast cancer in German and Byelorussian patients, although very rare mutations such as the p.G700R substitution could make a minor contribution.
Breast Cancer Research and Treatment 07/2011; 130(3):1021-8. · 4.43 Impact Factor
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Andreas Meyer,
Irina Coinac,
Natalia Bogdanova,
Natalia Dubrowinskaja,
Nurzhan Turmanov,
Sabine Haubold,
Peter Schürmann,
Florian Imkamp,
Christoph von Klot,
Axel S Merseburger,
Stefan Machtens,
Michael Bremer,
Peter Hillemanns,
Markus A Kuczyk,
Johann H Karstens,
Jürgen Serth,
Thilo Dörk
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ABSTRACT: BACKGROUND AND OBJECTIVES:: Prostate cancer has a genetic component, and single nucleotide polymorphisms (SNPs) can contribute to the risk. We aimed to investigate the role of polymorphisms in 10 candidate genes with a key function in apoptosis. METHODS AND MATERIALS:: Eight coding SNPs were chosen in ATM (Ser49Cys), BID (Ser56Cys), CASP8 (Asp302His), CASP10 (Val410Ile), LGALS3 (Pro64His), RASSF1 (Ser133Ala), TP53 (Arg72Pro), and TP53AIP1 (Ala7Val), and two non-coding SNPs were selected in BCL2 (-938C/A) and HDM2 (SNP309). A hospital-based case-control series of 510 prostate cancer patients and 490 healthy males from Northern Germany were genotyped for these polymorphisms. RESULTS:: SNP rs4644 in LGALS3 showed evidence for a protective effect of the minor allele, encoding the His64 variant (OR 0.82, 95% CI 0.69;0.99, P = 0.04). Carriers were underrepresented among cases under a dominant model (OR 0.71; 95% CI 0.54;0.92; P = 0.01), and the effect appeared more pronounced in patients diagnosed before the age of 60 years (OR 0.52; 95% CI 0.31;0.85, P = 0.01). The other nine polymorphisms did not vary significantly between cases and controls, though subtle trends were noted for BCL2 (P = 0.07) and CASP10 (P = 0.08). The Asp302His variant of CASP8 tended to associate with a protective effect in the group with higher Gleason score under a dominant model (P = 0.03). Carriers of either the CASP8 or the CASP10 variants were underrepresented in the prostate cancer series (P = 0.02). CONCLUSIONS:: These results provide first evidence to implicate the functional Pro64His variant of galectin-3 (LGALS3) in the genetic susceptibility towards prostate cancer. The potential role of polymorphisms in BCL2, CASP8, and CASP10 merits further investigation.
Urologic Oncology 03/2011; · 3.22 Impact Factor
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Xiaohong R Yang,
Jenny Chang-Claude,
Ellen L Goode,
Fergus J Couch,
Heli Nevanlinna,
Roger L Milne,
Mia Gaudet,
Marjanka K Schmidt,
Annegien Broeks,
Angela Cox, [......],
John L Hopper,
Fleur Hammet,
Helen Tsimiklis,
Letitia D Smith,
Melissa C Southey,
Manjeet K Humphreys,
Douglas Easton,
Paul Pharoah,
Mark E Sherman,
Montserrat Garcia-Closas
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ABSTRACT: Previous studies have suggested that breast cancer risk factors are associated with estrogen receptor (ER) and progesterone receptor (PR) expression status of the tumors.
We pooled tumor marker and epidemiological risk factor data from 35,568 invasive breast cancer case patients from 34 studies participating in the Breast Cancer Association Consortium. Logistic regression models were used in case-case analyses to estimate associations between epidemiological risk factors and tumor subtypes, and case-control analyses to estimate associations between epidemiological risk factors and the risk of developing specific tumor subtypes in 12 population-based studies. All statistical tests were two-sided.
In case-case analyses, of the epidemiological risk factors examined, early age at menarche (≤12 years) was less frequent in case patients with PR(-) than PR(+) tumors (P = .001). Nulliparity (P = 3 × 10(-6)) and increasing age at first birth (P = 2 × 10(-9)) were less frequent in ER(-) than in ER(+) tumors. Obesity (body mass index [BMI] ≥ 30 kg/m(2)) in younger women (≤50 years) was more frequent in ER(-)/PR(-) than in ER(+)/PR(+) tumors (P = 1 × 10(-7)), whereas obesity in older women (>50 years) was less frequent in PR(-) than in PR(+) tumors (P = 6 × 10(-4)). The triple-negative (ER(-)/PR(-)/HER2(-)) or core basal phenotype (CBP; triple-negative and cytokeratins [CK]5/6(+) and/or epidermal growth factor receptor [EGFR](+)) accounted for much of the heterogeneity in parity-related variables and BMI in younger women. Case-control analyses showed that nulliparity, increasing age at first birth, and obesity in younger women showed the expected associations with the risk of ER(+) or PR(+) tumors but not triple-negative (nulliparity vs parity, odds ratio [OR] = 0.94, 95% confidence interval [CI] = 0.75 to 1.19, P = .61; 5-year increase in age at first full-term birth, OR = 0.95, 95% CI = 0.86 to 1.05, P = .34; obesity in younger women, OR = 1.36, 95% CI = 0.95 to 1.94, P = .09) or CBP tumors.
This study shows that reproductive factors and BMI are most clearly associated with hormone receptor-positive tumors and suggest that triple-negative or CBP tumors may have distinct etiology.
CancerSpectrum Knowledge Environment 02/2011; 103(3):250-63. · 14.07 Impact Factor
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Zsofia Kote-Jarai,
Ali Amin Al Olama,
Graham G Giles,
Gianluca Severi,
Johanna Schleutker,
Maren Weischer,
Daniele Campa,
Elio Riboli,
Tim Key,
Henrik Gronberg, [......],
James Farnham,
Heiko Muller,
Dietrich Rothenbacher,
Norihiko Tsuchiya,
Shintaro Narita,
Guang-Wen Cao,
Chavdar Slavov,
Vanio Mitev,
Douglas F Easton,
Rosalind A Eeles
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ABSTRACT: Prostate cancer (PrCa) is the most frequently diagnosed male cancer in developed countries. We conducted a multi-stage genome-wide association study for PrCa and previously reported the results of the first two stages, which identified 16 PrCa susceptibility loci. We report here the results of stage 3, in which we evaluated 1,536 SNPs in 4,574 individuals with prostate cancer (cases) and 4,164 controls. We followed up ten new association signals through genotyping in 51,311 samples in 30 studies from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. In addition to replicating previously reported loci, we identified seven new prostate cancer susceptibility loci on chromosomes 2p11, 3q23, 3q26, 5p12, 6p21, 12q13 and Xq12 (P = 4.0 × 10(-8) to P = 2.7 × 10(-24)). We also identified a SNP in TERT more strongly associated with PrCa than that previously reported. More than 40 PrCa susceptibility loci, explaining ∼25% of the familial risk in this disease, have now been identified.
Nature Genetics 01/2011; 43(8):785-91. · 35.53 Impact Factor
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ABSTRACT: the internet as a source of medical information has emerged during the last years. There is a confusing amount of medical websites with a great diversity of quality. Websites of radiotherapy institutions could offer a safe and an easy-to-control way to assist patients' requests.
205 internet appearances of German radiotherapy institutions were analyzed in June 2009 (nonuniversity hospitals n = 108, medical practices n = 62, university hospitals n = 35). For the evaluation of each homepage verifiable criteria concerning basic information, service and medical issues were used.
the quality of information published via internet by different radiotherapy institutions showed a large variety. Basic information like telephone numbers, operating hours, and direction guidance were provided in 96.7%, 40%, and 50.7%, respectively. 85% of the websites introduced the staff, 50.2% supplied photos and 14% further information on the attending physicians. The mean amount of continuative links to other websites was 5.4, the mean amount of articles supplying medical information for patients summed up to 4.6. Medical practices and university hospitals had statistically significant more informative articles and links to other websites than nonuniversity hospitals. No statistically significant differences could be found in most other categories like service issues and basic information.
internet presences of radiotherapy institutions hold the chance to supply patients with professional and individualized medical information. While some websites are already using this opportunity, others show a lack of basic information or of user-friendliness.
Strahlentherapie und Onkologie 12/2010; 186(12):700-4. · 3.56 Impact Factor
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ABSTRACT: Primary extramedullary plasmocytomas (EMPs) are plasma cell tumours that arise outside the bone marrow. As these tumours are rare and can present without a typical clinical picture, correct diagnosis is difficult to confirm, particularly when the lesions occur at uncommon sites.
This is a case report of a 63-year-old patient who initially presented with an isolated lump on his left knee. Biopsy showed an anaplastic tumour which was first diagnosed as localised rhabdomyosarcoma; therefore, a combined approach with neoadjuvant radiotherapy followed by surgery was recommended. Shortly before radiotherapy started, the patient suffered a stroke with hemiplegia. CT and MRI of the head revealed a single brain lesion. A resection of this cerebral lesion was performed and surprisingly revealed a cerebral EMP. After comprehensive review of this specimen and the previous biopsy, the diagnosis was changed to anaplastic bifocal EMP. Generalised myeloma was excluded; therefore the patient was treated with definitive radiotherapy of the left knee region and postoperative partial brain irradiation. Unfortunately, the patient died several months later due to fulminant progressive disease at both treated sites despite rapidly initiated chemotherapy.
Correct diagnosis of EMP may be difficult, particularly as this disease is rare and can present with atypical clinical picture and immunophenotype. Review of the specimen by a histopathologist with special interest in soft tissue tumours or lymphoproliferative disorders is strongly recommended.
Anticancer research 05/2010; 30(5):1779-81. · 1.73 Impact Factor
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ABSTRACT: Efficacy and safety of the own single-center experience with moderately dosed radiosurgery (SRS) for limited (one to four) brain metastases were analyzed and correlated with patient- and treatment-related variables.
Between 05/1998 and 10/2006, 93 patients received SRS for a total of 142 brain metastases. The median number of brain metastases treated per patient was one (range, one to four). 46 patients (49%) received initial SRS alone, 13 patients (14%) SRS with up-front whole-brain radiotherapy (WBRT), and 34 patients (37%) SRS for recurrent metastases after WBRT. Median dose was 16 Gy (range, 10-20 Gy).
Median overall survival (OS) was 7.5 months. The actuarial 6- and 12-month data for OS were 60% and 35%, for local brain control (LBC) 87% and 79%, and for distant brain control (DBC) 48% and 37%, respectively. Only ten of 46 patients (22%) with initial SRS alone ultimately received WBRT. Ten patients suffered from seizures within 3 months after SRS, six of them showed brain progression on magnetic resonance imaging (MRI). 20 patients required reinstitution of steroids following SRS, 16 of these due to brain progression. Five patients received positron emission tomography scan of the brain revealing radionecrosis in two patients. In uni- and multivariate analysis, only time interval between diagnosis of primary and brain metastases (p = 0.031) and volume of treated metastasis (p = 0.02) were significant predictors of OS. Neither up-front WBRT nor dose had a significant influence on LBC.
Moderately dosed SRS of limited brain metastases was found to be both effective and safe. Initial SRS only may be offered to informed patients complying with MRI-based follow-up.
Strahlentherapie und Onkologie 02/2010; 186(2):76-81. · 3.56 Impact Factor
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ABSTRACT: : To analyze the dosimetric and clinical benefit of a forward planned technique to optimize dose distribution in whole-breast irradation (WBI) using additional partial-volume segments (PVSeg).
: In two separate treatment periods, 265 breast cancer patients received tangential-field WBI and were retrospectively analyzed. Between 02/2004 and 03/2006, 96 patients were treated with one to two additional low-weighted PVSeg to reduce dose peaks within the target volume. 169 patients treated between 01/2000 and 12/2001 before implementation of this PVSeg technique served as comparison group. Total dose was 50-50.4 Gy (single dose, 1.8-2 Gy). The planning target volume (PTV) receiving at least 95%, 105% and 110% of the reference dose (V(95-110%)) and frequency of moist skin desquamation during radiotherapy were compared uni- and multivariately with patient- and treatment-related variables.
: The mean PTV was 1,144 ml (range, 235-2,365 ml). Moist skin desquamations developed in 16 patients (17%) with PVSeg compared to 30 patients (18%) without PVSeg (p = 0.482). In breast volumes > 1,100 ml, the corresponding figures were 19% versus 29% (p = 0.133). V(105%) was significantly reduced by the use of PVSeg (82 +/- 51 ml vs. 143 +/- 129 ml; p < 0.0001). In univariate analysis, the following variables had significant influence on the development of moist skin desquamation: V(95%) (p < 0.0001), V(105%) (p < 0.001), V(110%) (p = 0.012) adjuvant chemotherapy (p = 0.02), and single dose (p = 0.009). In multivariate analysis, only V(95%) (p = 0.002) remained significant.
: The use of PVSeg in WBI reduced dose peaks within the PTV while breast volumes > 1,100 ml benefited most. V(95%) was strongly correlated to the risk of developing moist skin desquamations.
Strahlentherapie und Onkologie 01/2010; 186(1):40-5. · 3.56 Impact Factor
