Josef Hammer

The Use of F-18 Choline PET in the Assessment of Bone Metastases in Prostate Cancer: Correlation with Morphological Changes on CT

AimF-18 fluor choline-positron emission tomography/computed tomography (FCH-PET/CT) has emerged as a new diagnostic tool for the imaging of prostate cancer. In this study, we have evaluated the potential role of FCH-PET/CT for the assessment of bone metastases in patients with prostate cancer. Furthermore, we assessed the pattern of metabolic uptake by FCH in relation to morphologic changes on CT.MethodsSeventy men with biopsy-proven prostate cancer underwent FCH-PET/CT for preoperative staging or follow-up evaluation. Thirty-two patients were evaluated preoperatively, and 38 patients were referred for post operative evaluation of suspected recurrence or progression based on clinical algorithms. PET imaging consisted of a dynamic PET/CT acquisition of the pelvic region during 8xa0min (1-min frames) starting 1xa0min after i.v. injection of 4.07xa0MBq/kg/bw FCH which was followed immediately by a semi whole body acquisition.ResultsOverall, 262 lesions showed increased uptake on FCH-PET. Two hundred ten lesions (210/262) were interpreted as bone metastases. The mean standardized uptake values (SUV) in all malignant lesions was 8.1u2009±u20093.9. Forty-nine lesions (24%) had no detectable morphological changes on CT—probably due to bone marrow metastases. Fifty-six sclerotic lesions (having a Hounsfield unit (HU) level of more than 825) were interpreted as highly suspicious for metastatic bone disease on CT and/or other imaging modalities such as the bone scan but showed no FCH uptake. There was a significant correlation between tracer uptake as assessed by SUV and the density of sclerotic lesions by HU (ru2009=u2009−0.52, pu2009<u20090.001). The sensitivity, specificity, and accuracy of FCH-PET/CT in detecting bone metastases from prostate cancer was 79%, 97%, and 84%, respectively.ConclusionFCH-PET/CT showed promising results for the early detection of bone metastases in prostate cancer patients. We have found that a HU level of above 825 is associated with an absence of FCH uptake. Almost all of the FCH-negative sclerotic lesions were detected in patients who were under hormone therapy, which raises the possibility that these lesions might no longer be viable. However, clarification and the prognostic value of such lesions require further research.

Accelerated Partial Breast Irradiation: 5-Year Results of the German-Austrian Multicenter Phase II Trial Using Interstitial Multicatheter Brachytherapy Alone After Breast-Conserving Surgery

PURPOSEnTo evaluate the impact of accelerated partial breast irradiation on local control, side effects, and cosmesis using multicatheter interstitial brachytherapy as the sole method for the adjuvant local treatment of patients with low-risk breast cancer.nnnMETHODS AND MATERIALSn274 patients with low-risk breast cancer were treated on protocol. Patients were eligible for the study if the tumor size was < 3 cm, resection margins were clear by at least 2 mm, no lymph node metastases existed, age was >35 years, hormone receptors were positive, and histologic grades were 1 or 2. Of the 274 patients, 175 (64%) received pulse-dose-rate brachytherapy (D(ref) = 50 Gy). and 99 (36%) received high-dose-rate brachytherapy (D(ref) = 32.0 Gy).nnnRESULTSnMedian follow-up was 63 months (range, 9-103). Only 8 of 274 (2.9%) patients developed an ipsilateral in-breast tumor recurrence at the time of analysis. The 5-year actuarial local recurrence-free survival probability was 98%. The 5- year overall and disease-free survival probabilities of all patients were 97% and 96%, respectively. Contralateral in-breast malignancies were detected in 2 of 274 (0.7%) patients, and distant metastases occurred in 6 of 274 (2.2%). Late side effects ≥ Grade 3 (i.e., breast tissue fibrosis and telangiectasia) occurred in 1 patient (0.4%, 95%CI:0.0-2.0%) and 6 patients (2.2%, 95%CI:0.8-4.7%), respectively. Cosmetic results were good to excellent in 245 of 274 patients (90%).nnnCONCLUSIONSnThe long-term results of this prospective Phase II trial confirm that the efficacy of accelerated partial breast irradiation using multicatheter brachytherapy is comparable with that of whole breast irradiation and that late side effects are negligible.

ACCELERATED PARTIAL BREAST IRRADIATION WITH INTERSTITIAL IMPLANTS: RISK FACTORS ASSOCIATED WITH INCREASED LOCAL RECURRENCE

PURPOSEnTo analyze patient, disease, and treatment-related factors regarding their impact on local control after interstitial multicatheter accelerated partial breast irradiation (APBI).nnnMETHODS AND MATERIALSnBetween November 2000 and April 2005, 274 patients with early breast cancer were recruited for the German-Austrian APBI Phase II trial (ClinicalTrials.gov identifier: NCT00392184). In all, 64% (175/274) of the patients received pulsed-dose-rate (PDR) brachytherapy and 36% (99/274) received high-dose-rate (HDR) brachytherapy. Prescribed reference dose for HDR brachytherapy was 32 Gy in eight fractions of 4 Gy, twice daily. Prescribed reference dose in PDR brachytherapy was 49.8 Gy in 83 consecutive fractions of 0.6 Gy each hour. Total treatment time was 3 to 4 days.nnnRESULTSnThe median follow-up time was 64 months (range, 9-110). The actuarial 5-year local recurrence free survival rate (5-year LRFS) was 97.7%. Comparing patients with an age <50 years (49/274) vs. ≥50 years (225/274), the 5-year LRFS resulted in 92.5% and 98.9% (exact p = 0.030; 99% confidence interval, 0.029-0.032), respectively. Antihormonal treatment (AHT) was not applied in 9% (24/274) of the study population. The 5-year LRFS was 99% and 84.9% (exact p = 0.0087; 99% confidence interval, 0.0079-0.0094) in favor of the patients who received AHT. Lobular histology (45/274) was not associated with worse local control compared with all other histologies (229/274). The 5-year LRFS rates were 97.6% and 97.8%, respectively.nnnCONCLUSIONSnLocal control at 5 years is excellent and comparable to therapeutic successes reported from corresponding whole-breast irradiation trials. Our data indicate that patients <50 years of age ought to be excluded from APBI protocols, and that patients with hormone-sensitive breast cancer should definitely receive adjuvant AHT when interstitial multicatheter APBI is performed. Lobular histology need not be an exclusion criterion for future APBI trials.

Local Relapse after Breast-Conserving Surgery and Radiotherapy

Purpose:This retrospective analysis of 1,610 women treated for breast cancer and 88 patients with local relapse aims to show the poor survival parameters after local failure and to evaluate risk factors and compare them with other studies and analyses published.Patients and Methods:Between 1984 and 1997, 1,610 patients presenting with a total of 1,635 pT1–2 invasive and noninvasive carcinomas of the breast were treated at the authors’ institution. The mean age was 57.1 years (range 25–85 years). Treatment protocols involved breast-conserving surgery with or without systemic therapy and whole-breast radiotherapy in all women, followed by a boost dose to the tumor bed according to risk factors for local recurrence. All axillary node-positive patients underwent systemic therapy (six cycles of classic CMF or tamoxifen 20 mg/day for 2–5 years). The time of diagnosis of local relapse was defined as time 0 for the survival curves after local failure. The association of clinicopathologic factors was studied using uni- and multivariate analyses. Survival and local control were calculated by the Kaplan-Meier actuarial method and significance by the log-rank test.Results:After a mean follow-up of 104 months, 88 local failures were recorded (5.4%). Calculated from the time of diagnosis of local relapse, 5-year overall survival (OS) was 62.8%, metastasis-free survival 60.6%, and disease-specific survival 64.2%. In patients with failure during the first 5 years after treatment, the survival parameters were worse (OS 50.6%) compared to those who relapsed after 5 years (OS 78.8%; p < 0.028). Significances were also found for initial T- and N-stage and type of failure (solid tumor vs. diffuse spread).Conclusion:This analysis again shows that the survival parameters are worsening after local relapse, especially in case of early occurrence. In breast cancer treatment, therefore, the goal remains to avoide local failure.Ziel:In dieser retrospektiven Analyse von 88 Lokalrezidiven bei 1610 Patientinnen mit Brustkrebs werden die ungünstigen Überlebensraten nach Auftreten eines Lokalrezidivs aufgezeigt, um auf die Bedeutung der Verhinderung jedes einzelnen Rezidivs hinzuweisen. Einzelne Risikofaktoren werden evaluiert und die eigenen Ergebnisse mit der vorhandenen Literatur verglichen.Patienten und Methodik:Im Zeitraum von 1984 bis 1997 wurden an der Institution der Autoren 1610 Patientinnen mit invasivem und nichtinvasivem Brustkrebs in den Stadien T1–2 behandelt. Das durchschnittliche Alter betrug 57,1 Jahre (Bereich 25–85 Jahre). Alle Frauen wurden brusterhaltend operiert und erhielten eine Bestrahlung der gesamten Brust, gefolgt von einem risikoadaptierten Boost auf das Tumorbett. Alle nodal positiven Patientinnen wurden einer Chemotherapie unterzogen (sechs Zyklen des klassischen CMF-Schemas oder 20 mg Tamoxifen pro Tag für 2–5 Jahre). Der Zeitpunkt der Diagnose des Lokalrezidivs galt als Tag 0 für die Kaplan-Meier-Kurven. Einzelne klinisch-pathologische Faktoren wurden mittels uni- und multivariater Analyse untersucht. Für die Berechnung der lokalen Kontrollrate und der Überlebensparameter wurde die Kaplan-Meier-Methode und für die Signifikanz der Log-Rank-Test herangezogen.Ergebnisse:Nach einer durchschnittlichen Beobachtungszeit von 104 Monaten wurden 88 Lokalrezidive beobachtet (5,4%).nAusgehend vom Tag der Diagnose des Rezidivs als Tag 0, betrugen das Gesamtüberleben (OS) nach 5 Jahren 62,8%, die metastasenfreienÜberlebensrate 60,6% und das krankheitsspezifische Überleben 64,2%. Trat das Rezidiv innerhalb der ersten 5 Jahre auf,nso ergab sich ein wesentlich schlechteres Überleben als bei Patientinnen mit einem verzögerten Auftreten nach > 5 Jahren (OSn50,6% vs. 78,8%; p < 0,028). Signifikante Unterschiede in Bezug auf das Auftreten eines Lokalrezidivs fanden sich auch bezüglichndes initialen T- und N-Stadiums und beim Ausbreitungsmuster der Rezidive (solid vs. diffus).Schlussfolgerung:Diese retrospektive Studie weist erneut auf das beträchtlich reduzierte Überleben bei Patientinnen mitnLokalrezidiv hin, speziell bei zeitlich frühem Auftreten. Auch wenn die wenigen Lokalrezidive die Überlebensparameter einesngroßen Kollektivs nur geringfügig beeinflussen, so bedeutet das Rezidiv eine massive Verschlechterung der Lebenserwartung fürndie individuelle Patientin. Es gilt daher die Zielsetzung, jedes einzelne Lokalrezidiv zu verhindern.

Total body irradiation with volumetric modulated arc therapy: Dosimetric data and first clinical experience.

BackgroundTo implement total body irradiation (TBI) using volumetric modulated arc therapy (VMAT). We applied the Varian RapidArc™ software to calculate and optimize the dose distribution. Emphasis was placed on applying a homogenous dose to the PTV and on reducing the dose to the lungs.MethodsFrom July 2013 to July 2014 seven patients with leukaemia were planned and treated with a VMAT-based TBI-technique with photon energy of 6 MV. The overall planning target volume (PTV), comprising the whole body, had to be split into 8 segments with a subsequent multi-isocentric planning. In a first step a dose optimization of each single segment was performed. In a second step all these elements were calculated in one overall dose-plan, considering particular constraints and weighting factors, to achieve the final total body dose distribution. The quality assurance comprised the verification of the irradiation plans via ArcCheck™ (Sun Nuclear), followed by in vivo dosimetry via dosimeters (MOSFETs) on the patient.ResultsThe time requirements for treatment planning were high: contouring took 5–6xa0h, optimization and dose calculation 25–30xa0h and quality assurance 6–8xa0h. The couch-time per fraction was 2xa0h on day one, decreasing to around 1.5xa0h for the following fractions, including patient information, time for arc positioning, patient positioning verification, mounting of the MOSFETs and irradiation. The mean lung dose was decreased to at least 80xa0% of the planned total body dose and in the central parts to 50xa0%. In two cases we additionally pursued a dose reduction of 30 to 50xa0% in a pre-irradiated brain and in renal insufficiency. All high dose areas were outside the lungs and other OARs. The planned dose was in line with the measured dose via MOSFETs: in the axilla the mean difference between calculated and measured dose was 3.6xa0% (range 1.1–6.8xa0%), and for the wrist/hip-inguinal region it was 4.3xa0% (range 1.1–8.1xa0%).ConclusionTBI with VMAT provides the benefit of satisfactory dose distribution within the PTV, while selectively reducing the dose to the lungs and, if necessary, in other organs. Planning time, however, is extensive.

The Use of F-18 Choline PET in the Assessment of Bone Metastases in Prostate Cancer: Correlation with Morphological Changes on CT (vol 11, pg 446, 2009)

Erratum to: The Use of F-18 Choline PET in the Assessment of Bone Metastases in Prostate Cancer: Correlation with Morphological Changes on CT Mohsen Beheshti, Reza Vali, Peter Waldenberger, Friedrich Fitz, Michael Nader, Josef Hammer, Wolfgang Loidl, Christian Pirich, Ignac Fogelman, Werner Langsteger Nuclear Medicine & Endocrinology, PET/CT Center Linz, St. Vincent’s Hospital, Linz, Austria Radiology, St. Vincent’s Hospital, Linz, Austria Radiation Oncology, St. Vincent’s Hospital, Linz, Austria Urology, St. Vincent’s Hospital, Linz, Austria Nuclear Medicine & Endocrinology, Paracelsus Private Medical University, Salzburg, Austria Division of Imaging, King’s College, London, UK

Risk Factors for Local Relapse and Inferior Disease-free Survival After Breast-conserving Management of Breast Cancer: Recursive Partitioning Analysis of 2161 Patients

Micro‐Abstract Recursive partitioning analysis was found to be a suitable method to assign patients with early stage breast cancer to different risk groups who had considerable variation in local relapse rates and disease‐free survival. Lymph node ratio was associated with both endpoints. Background: The purpose of this study was to analyze risk factors for ipsilateral in‐breast relapse and inferior disease‐free survival (DFS) after standard adjuvant whole‐breast radiotherapy (± boost and systemic treatment) as part of a multimodal breast‐conserving approach. Patients and Methods: Decision trees were built through recursive partitioning analysis (RPA). The median follow‐up for all 2161 patients was 114 months (9.5 years). Results: Local relapse in the treated breast was uncommon (actuarial rates after 5 and 10 years were 2.7% and 5.8%, respectively). In RPA, the first split was related to age (52 years), with younger patients having a significantly higher risk of local relapse. The younger patients were stratified further by lymph node ratio (LNR). In patients older than 52 years, lack of endocrine treatment was associated with significantly higher risk. DFS was 80.7% at 10 years. The first split was caused by LNR, and the group with unfavorable LNR (> 0.20) could not be stratified further. Ten‐year DFS in this group was as low as 50.6%. Patients with favorable LNR (0‐0.20) could be stratified by additional risk factors, in particular primary tumor size. Conclusion: RPA is a suitable method to assign patients with early stage breast cancer to different risk groups, both regarding local relapse and DFS. Although age was a major risk factor for local relapse after breast‐conserving management, LNR was associated with both endpoints. The systemic treatment approaches used in this study failed to provide satisfactory DFS in patients with LNR > 0.20 and 2 other subgroups.

Local Relapse after Breast-Conserving Surgery and Radiotherapy@@@Lokalrezidiv nach brusterhaltender Chirurgie und Radiotherapie. Auswirkungen auf das Überleben: Effects on Survival Parameters

Purpose:This retrospective analysis of 1,610 women treated for breast cancer and 88 patients with local relapse aims to show the poor survival parameters after local failure and to evaluate risk factors and compare them with other studies and analyses published.Patients and Methods:Between 1984 and 1997, 1,610 patients presenting with a total of 1,635 pT1–2 invasive and noninvasive carcinomas of the breast were treated at the authors’ institution. The mean age was 57.1 years (range 25–85 years). Treatment protocols involved breast-conserving surgery with or without systemic therapy and whole-breast radiotherapy in all women, followed by a boost dose to the tumor bed according to risk factors for local recurrence. All axillary node-positive patients underwent systemic therapy (six cycles of classic CMF or tamoxifen 20 mg/day for 2–5 years). The time of diagnosis of local relapse was defined as time 0 for the survival curves after local failure. The association of clinicopathologic factors was studied using uni- and multivariate analyses. Survival and local control were calculated by the Kaplan-Meier actuarial method and significance by the log-rank test.Results:After a mean follow-up of 104 months, 88 local failures were recorded (5.4%). Calculated from the time of diagnosis of local relapse, 5-year overall survival (OS) was 62.8%, metastasis-free survival 60.6%, and disease-specific survival 64.2%. In patients with failure during the first 5 years after treatment, the survival parameters were worse (OS 50.6%) compared to those who relapsed after 5 years (OS 78.8%; p < 0.028). Significances were also found for initial T- and N-stage and type of failure (solid tumor vs. diffuse spread).Conclusion:This analysis again shows that the survival parameters are worsening after local relapse, especially in case of early occurrence. In breast cancer treatment, therefore, the goal remains to avoide local failure.Ziel:In dieser retrospektiven Analyse von 88 Lokalrezidiven bei 1610 Patientinnen mit Brustkrebs werden die ungünstigen Überlebensraten nach Auftreten eines Lokalrezidivs aufgezeigt, um auf die Bedeutung der Verhinderung jedes einzelnen Rezidivs hinzuweisen. Einzelne Risikofaktoren werden evaluiert und die eigenen Ergebnisse mit der vorhandenen Literatur verglichen.Patienten und Methodik:Im Zeitraum von 1984 bis 1997 wurden an der Institution der Autoren 1610 Patientinnen mit invasivem und nichtinvasivem Brustkrebs in den Stadien T1–2 behandelt. Das durchschnittliche Alter betrug 57,1 Jahre (Bereich 25–85 Jahre). Alle Frauen wurden brusterhaltend operiert und erhielten eine Bestrahlung der gesamten Brust, gefolgt von einem risikoadaptierten Boost auf das Tumorbett. Alle nodal positiven Patientinnen wurden einer Chemotherapie unterzogen (sechs Zyklen des klassischen CMF-Schemas oder 20 mg Tamoxifen pro Tag für 2–5 Jahre). Der Zeitpunkt der Diagnose des Lokalrezidivs galt als Tag 0 für die Kaplan-Meier-Kurven. Einzelne klinisch-pathologische Faktoren wurden mittels uni- und multivariater Analyse untersucht. Für die Berechnung der lokalen Kontrollrate und der Überlebensparameter wurde die Kaplan-Meier-Methode und für die Signifikanz der Log-Rank-Test herangezogen.Ergebnisse:Nach einer durchschnittlichen Beobachtungszeit von 104 Monaten wurden 88 Lokalrezidive beobachtet (5,4%).nAusgehend vom Tag der Diagnose des Rezidivs als Tag 0, betrugen das Gesamtüberleben (OS) nach 5 Jahren 62,8%, die metastasenfreienÜberlebensrate 60,6% und das krankheitsspezifische Überleben 64,2%. Trat das Rezidiv innerhalb der ersten 5 Jahre auf,nso ergab sich ein wesentlich schlechteres Überleben als bei Patientinnen mit einem verzögerten Auftreten nach > 5 Jahren (OSn50,6% vs. 78,8%; p < 0,028). Signifikante Unterschiede in Bezug auf das Auftreten eines Lokalrezidivs fanden sich auch bezüglichndes initialen T- und N-Stadiums und beim Ausbreitungsmuster der Rezidive (solid vs. diffus).Schlussfolgerung:Diese retrospektive Studie weist erneut auf das beträchtlich reduzierte Überleben bei Patientinnen mitnLokalrezidiv hin, speziell bei zeitlich frühem Auftreten. Auch wenn die wenigen Lokalrezidive die Überlebensparameter einesngroßen Kollektivs nur geringfügig beeinflussen, so bedeutet das Rezidiv eine massive Verschlechterung der Lebenserwartung fürndie individuelle Patientin. Es gilt daher die Zielsetzung, jedes einzelne Lokalrezidiv zu verhindern.