Publications by authors named "Ludwig Plasswilm"

44 Publications

Radiotherapy for lentigo maligna and lentigo maligna melanoma - a systematic review.

Radiat Oncol 2020 Jul 14;15(1):174. Epub 2020 Jul 14.

Department of Radiation Oncology, Kantonsspital St. Gallen, Rorschacherstrasse 95, 9007, St. Gallen, Switzerland.

Lentigo maligna (LM) is the most common subtype of in situ melanoma und occurs frequently in the sun-exposed head and neck region in elderly patients. The therapeutic "gold standard" is surgical excision, as there is the risk of progression to invasive (lentigo maligna) melanoma (LMM). However, surgery is not feasible in certain patients due to age, comorbidities or patient preference. Radiotherapy using Grenz rays or superficial X-rays has been established as non-invasive alternative for the treatment of LM and LMM. We performed a systematic literature search of MEDLINE and Embase databases in September 2019 and identified 14 patient series using radiotherapy for LM or LMM. No prospective trials were found. The 14 studies reported a total of 1243 lesions (1075 LM and 168 LMM) treated with radiotherapy. Local recurrence rates ranged from 0 to 31% and were comparable to surgical series in most of the reports on radiotherapy. Superficial radiotherapy was prescribed in 5-23 fractions with a total dose of 35-57 Gy. Grenz ray therapy was prescribed in 42-160 Gy in 3-13 fractions with single doses up to 20 Gy. Cosmetic results were reported as "good" to "excellent" for the majority of patients.In conclusion, the available low-level evidence suggests that radiotherapy may be a safe and effective treatment for LM and LMM. Data from prospective trials such as the phase 3 RADICAL trial are needed to confirm these promising findings and to compare radiotherapy to other non-surgical therapies and to surgery.
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http://dx.doi.org/10.1186/s13014-020-01615-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7362499PMC
July 2020

Insular Decision Criteria in Clinical Practice: Analysis of Decision-Making in Oncology.

Oncology 2020 19;98(6):438-444. Epub 2020 May 19.

Department of Radiation Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland.

Background: Medical decision-making is complex and involves a variety of decision criteria, many of which are universally recognised. However, decision-making analyses have demonstrated that certain decision criteria are not used uniformly among clinicians.

Aim: We describe decision criteria, which for various contexts are only used by a minority of decision makers. For these, we introduce and define the term "insular criteria".

Methods: 19 studies analysing clinical decision-making based on decision trees were included in our study. All studies were screened for decision-making criteria that were mentioned by less than three local decision makers in studies involving 8-26 participants.

Results: 14 out of the 19 included studies reported insular criteria. We identified 42 individual insular criteria. They could be intuitively allocated to seven major groups, these were: comorbidities, treatment, patients' characteristics/preferences, caretaker, scores, laboratory and tumour properties/staging.

Conclusion: Insular criteria are commonly used in clinical decision-making, yet, the individual decision makers may not be aware of them. With this analysis, we demonstrate the existence of insular criteria and their variety. In daily practice and clinical studies, awareness of insular criteria is important.
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http://dx.doi.org/10.1159/000508132DOI Listing
June 2020

Long-term oncological and functional follow-up in low-dose-rate brachytherapy for prostate cancer: results from the prospective nationwide Swiss registry.

BJU Int 2020 06 12;125(6):827-835. Epub 2020 Feb 12.

Department of Urology, St. Gallen Cantonal Hospital, St. Gallen, Switzerland.

Objective: To evaluate the long-term oncological, functional and toxicity outcomes of low-dose-rate brachytherapy (LDR-BT) in relation to risk factors and radiation dose in a prospective multicentre cohort.

Patients And Methods: Data of patients from 12 Swiss centres undergoing LDR-BT from September 2004 to March 2018 were prospectively collected. Patients with a follow-up of ≥3 months were analysed. Functional and oncological outcomes were assessed at ~6 weeks, 6 and 12 months after implantation and annually thereafter. LDR-BT was performed with I seeds. Dosimetry was done 6 weeks after implantation based on the European Society for Radiotherapy and Oncology recommendations. The Kaplan-Meier method was used for biochemical recurrence-free survival (BRFS). A prostate-specific antigen (PSA) rise above the PSA nadir + 2 was defined as biochemical failure. Functional outcomes were assessed by urodynamic measurement parameters and questionnaires.

Results: Of 1580 patients in the database, 1291 (81.7%) were evaluable for therapy outcome. The median (range) follow-up was 37.1 (3.0-141.6) months. Better BRFS was found for Gleason score ≤3+4 (P = 0.03, log-rank test) and initial PSA level of <10 ng/mL (P < 0.001). D'Amico Risk groups were significantly associated with BRFS (P < 0.001), with a hazard ratio of 2.38 for intermediate- and high-risk patients vs low-risk patients. The radiation dose covering 90% of the prostate volume (D90) after 6 weeks was significantly lower in patients with recurrence. Functional outcomes returned close to baseline levels after 2-3 years. A major limitation of these findings is a substantial loss to follow-up.

Conclusion: Our results are in line with other studies showing that LDR-BT is associated with good oncological outcomes together with good functional results.
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http://dx.doi.org/10.1111/bju.15003DOI Listing
June 2020

Skeletal muscle mass correlates with increased toxicity during neoadjuvant radiochemotherapy in locally advanced esophageal cancer: A SAKK 75/08 substudy.

Radiat Oncol 2019 Sep 11;14(1):166. Epub 2019 Sep 11.

Department of Radiation Oncology, Kantonsspital St Gallen, St Gallen and University of Bern, Bern, Switzerland.

Background: Sarcopenia, the critical depletion of skeletal muscle mass, is an independent prognostic factor in several tumor entities for treatment-related toxicity and survival. In esophageal cancer, there have been conflicting results regarding the value of sarcopenia as prognostic factor, which may be attributed to the heterogeneous patient populations and the retrospective nature of previous studies. The aim of our study was therefore to determine the impact of sarcopenia on prospectively collected specific outcomes in a subgroup of patients treated within the phase III study SAKK 75/08 with trimodality therapy (induction chemotherapy, radiochemotherapy and surgery) for locally advanced esophageal cancer.

Methods: Sarcopenia was assessed by skeletal muscle index at the 3rd lumbar vertebra (L3) in cross-sectional computed tomography scans before induction chemotherapy, before radiochemotherapy and after neoadjuvant therapy in a subgroup of 61 patients from four centers in Switzerland. Sarcopenia was determined by previously established cut-off values (Martin et al., PMID: 23530101) and correlated with prospectively collected outcomes including treatment-related toxicity, postoperative morbidity, treatment feasibility and survival.

Results: Using the published cut-off values, the prevalence of sarcopenia increased from 29.5% before treatment to 63.9% during neoadjuvant therapy (p < 0.001). Feasibility of neoadjuvant therapy and surgery was not different in initially sarcopenic and non-sarcopenic patients. We observed in sarcopenic patients significantly increased grade ≥ 3 toxicities during chemoradiation (83.3% vs 52.4%, p = 0.04) and a non-significant trend towards increased postoperative complications (66.7% vs 42.9%, p = 0.16). No difference in survival according to sarcopenia could be observed in this small study population.

Conclusions: Trimodality therapy in locally advanced esophageal cancer is feasible in selected patients with sarcopenia. Neoadjuvant chemoradiation increased the percentage of sarcopenia. Sarcopenic patients are at higher risk for increased toxicity during neoadjuvant radiochemotherapy and showed a non-significant trend to more postoperative morbidity.
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http://dx.doi.org/10.1186/s13014-019-1372-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739918PMC
September 2019

[Modern Treatment Concepts in Radiation Oncology].

Ther Umsch 2019 Sep;76(4):209-218

Klinik für Radio-Onkologie, Kantonsspital, Winterthur.

Modern Treatment Concepts in Radiation Oncology Radiotherapy is a widely used form of therapy that is used in half of all cancer patients. Advances in understanding the fundamentals of tumor and radiation biology, in medical physics and computer science as well as technical developments have continuously improved the effectiveness and healing success of radiotherapy. Patients benefit from new treatment concepts such as hypofractionated radiotherapy for breast and prostate cancer, leading to a reduction in the duration of treatment by several weeks. Selected patients with early stages of breast cancer can be treated with partial breast irradiation with focus on the tumor bed after breast conserving surgery increasing tolerability and comfort. High dose stereotactic radiotherapy over five to six sessions of radiation or only one fraction (radiosurgery) have expanded treatment options for common tumor entities leading to long-lasting tumor control resulting in improved survival and quality of life for those affected. In early lung cancer stereotactic radiotherapy is an alternative to primary tumor surgery. For patients with oligometastatic tumor disease stereotactic radiotherapy allows a curative approach by effectively treating metastases. In patients with brain metastases whole-brain irradiation is replaced by stereotactic irradiation of the individual metastases with fewer side effects. Recently, promising results for improved tumor control with the combination of radiotherapy and immunotherapy have been presented. Radioimmunotherapy represents a new therapy combination. However, final assessment of its efficacy and side effects profile is still missing. In order to gain therapeutic certainty, further prospective study data are necessary.
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http://dx.doi.org/10.1024/0040-5930/a001086DOI Listing
September 2019

Pattern of failure after adjuvant radiotherapy following extrapleural pneumonectomy of pleural mesothelioma in the SAKK 17/04 trial.

Radiother Oncol 2019 09 25;138:121-125. Epub 2019 Jun 25.

Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Switzerland.

Postoperative radiotherapy after extrapleural pneumonectomy of malignant pleural mesothelioma was investigated in the randomized phase II trial SAKK17/04. The relapse rate within the high and/or low-dose PTV without previous distant failure was 24%, the isolated in-field-relapse rate within the PTVs was 5% and the distant relapse rate outside of the PTVs was 81%. Clinical outcome was mainly determined by distant disease progression outside of the radiation field.
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http://dx.doi.org/10.1016/j.radonc.2019.05.024DOI Listing
September 2019

Treatment Options in Oncology.

JCO Clin Cancer Inform 2018 12;2:1-10

Cédric M. Panje, Markus Glatzer, Ludwig Plasswilm, and Paul M. Putora, Kantonsspital St Gallen; Charlotta Sirén, Institute of Technology Management, University of St Gallen, St Gallen; and Ludwig Plasswilm and Paul M. Putora, University of Bern, Bern, Switzerland.

Multiple treatment strategies exist for many oncologic problems. In this review, we provide a summary of various reasons for the existence of multiple treatment options in oncology, including factors that concern the treating physician (eg, treatment preferences), environmental factors (eg, financial, regulatory, and scientific aspects), and individual patient-specific factors (eg, medical condition, preferences). We demonstrate the vital role of available treatment options and their origins for clinical decision making and patient communication. These aspects are particularly helpful in the process of shared decision making, which is increasingly favored in situations where there are multiple medically reasonable options.
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http://dx.doi.org/10.1200/CCI.18.00017DOI Listing
December 2018

A cost-effectiveness analysis of consolidative local therapy in oligometastatic non-squamous non-small cell lung cancer (NSCLC).

Radiother Oncol 2018 11 10;129(2):257-263. Epub 2018 Aug 10.

Swiss Group for Clinical Cancer Research Coordinating Centre, Bern, Switzerland; Institute of Pharmaceutical Medicine, University of Basel, Switzerland.

Background: Novel systemic therapies have improved the prognosis of metastatic non-small cell lung cancer (NSCLC), but costs of some of these drugs are a matter of ongoing debate. More recently, local therapies (LT) such as radiotherapy and surgery have been suggested as additional treatment in oligometastatic NSCLC demonstrating an improved progression-free survival (PFS) in a phase II trial compared to maintenance chemotherapy (MC) alone. The aim of this analysis was to assess the cost-effectiveness of local therapies in oligometastatic NSCLC.

Methods: We constructed a Markov model comparing the cost-effectiveness of LT versus MC for oligometastatic NSCLC from the Swiss healthcare payer's perspective. Treatment specifications and PFS were based on the phase II trial (NCT01725165). Overall survival (OS) was inferred from a recent phase III trial. Utilities were taken from published data. Primary outcome was the incremental cost-effectiveness-ratio (ICER, costs in Swiss Francs (CHF) per quality-adjusted life-year (QALY) gained).

Results: PFS in the model was 3.8 months for MC and 11.4 months for LT (compared to 3.9 months and 11.9 months in the trial). OS in the model was 15.5 months in both arms. LT was cost-effective with a gain of 0.24 QALYs at an additional cost of CHF 9641, resulting in an ICER of CHF 40,972/QALY gained. Probabilistic sensitivity analyses demonstrated that LT was dominant or cost-effective at a willingness-to-pay threshold of CHF 100,000 per QALY in 61.7% of the simulations.

Conclusions: LT may be cost-effective for selected patients with oligometastatic NSCLC responding to first-line systemic therapy.
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http://dx.doi.org/10.1016/j.radonc.2018.07.017DOI Listing
November 2018

Late seed migration after prostate brachytherapy with Iod-125 permanent implants.

Prostate Int 2018 Jun 30;6(2):66-70. Epub 2017 Sep 30.

Department of Urology, St. Gallen Cantonal Hospital, St. Gallen, Switzerland.

Background: Seed migration is a common finding after low dose rate brachytherapy of the prostate. It has often been assessed soon after implantation, but little is known about late seed migration. We evaluated the incidence, site, symptoms, and therapeutic consequences of late seed migration more than 3 years postoperatively.

Materials And Methods: We retrospectively examined the data of 63 unselected patients with transrectal ultrasound-guided, transperineal low dose rate brachytherapy of the prostate with stranded seeds between 2001 and 2010. A pelvic X-ray was taken the day after implantation and after 6 weeks in combination with a pelvic computed tomography/magnetic resonance imaging scan (image fusion) for dosimetry. Late radiological follow-up with a further pelvic and chest X-ray was conducted 3 or more years postoperatively. We differed between seed loss without anatomical detection and seed migration into another anatomical region.

Results: We found seed loss up to 3 years and more after brachytherapy in 36 of 63 patients (57%). Between one and nine seeds had been lost. Late seed migration after 3 or more years occurred in two of 36 patients (6%), with pelvic migration of one seed and extrapelvic migration of one seed to the lung and two seeds to the liver, respectively. All late seed migrations were asymptomatic and had no therapeutic consequences.

Conclusion: Beside a frequent number of seed losses, seed migration 3 or more years after implantation was as well a frequent finding but seems to be asymptomatic. Long-term follow-up with complementary radiological controls could be helpful in detecting any rare complications.
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http://dx.doi.org/10.1016/j.prnil.2017.09.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6004626PMC
June 2018

Neoadjuvant radiotherapy combined with capecitabine and sorafenib in patients with advanced KRAS-mutated rectal cancer: A phase I/II trial (SAKK 41/08).

Eur J Cancer 2018 01 11;89:82-89. Epub 2017 Dec 11.

University Hospital Zürich, Zürich, Switzerland.

Background: KRAS mutation occurs in ∼40% of locally advanced rectal cancers (LARCs). The multitarget tyrosine kinase inhibitor sorafenib has radiosensitising effects and might improve outcomes for standard preoperative chemoradiotherapy in patients with KRAS-mutated LARC.

Methods: Adult patients with KRAS-mutated T3/4 and/or N1/2M0 LARC were included in this phase I/II study. The phase I dose-escalation study of capecitabine plus sorafenib and radiotherapy was followed by a phase II study assessing efficacy and safety. Primary end-points were to: establish the maximum tolerated dose of the regimen in phase I; determine the pathologic complete response (pCR) rate in phase II defined as Dworak regression grade 3 and 4.

Results: Fifty-four patients were treated at 18 centres in Switzerland and Hungary; 40 patients were included in the single-arm phase II study. Recommended doses from phase I comprised radiotherapy (45 Gy in 25 fractions over 5 weeks) with capecitabine 825 mg/m twice daily × 33 plus sorafenib 400 mg/d. Median daily dose intensity in phase II was radiotherapy 100%, capecitabine 98.6%, and sorafenib 100%. The pCR rate (Dworak 3/4) was 60% (95% CI, 43.3-75.1%) by central independent pathologic review. Sphincter preservation was achieved in 89.5%, R0 resection in 94.7%, and downstaging in 81.6%. The most common grade 3 toxicities during phase II included diarrhoea (15.0%), skin toxicity outside radiotherapy field (12.5%), pain (7.5%), skin toxicity in radiotherapy field, proctitis, fatigue and cardiac ischaemia (each 5%).

Conclusions: Combining sorafenib and standard chemoradiotherapy with capecitabine is highly active in patients with KRAS-mutated LARC with acceptable toxicity and deserves further investigation. www.clinicaltrials.gov: NCT00869570.
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http://dx.doi.org/10.1016/j.ejca.2017.11.005DOI Listing
January 2018

Applied Swarm-based medicine: collecting decision trees for patterns of algorithms analysis.

BMC Med Res Methodol 2017 Aug 16;17(1):123. Epub 2017 Aug 16.

Department of Radiation Oncology, Kantonsspital St. Gallen, Rorschacherstrasse 95, 9007, St. Gallen, Switzerland.

Background: The objective consensus methodology has recently been applied in consensus finding in several studies on medical decision-making among clinical experts or guidelines. The main advantages of this method are an automated analysis and comparison of treatment algorithms of the participating centers which can be performed anonymously.

Methods: Based on the experience from completed consensus analyses, the main steps for the successful implementation of the objective consensus methodology were identified and discussed among the main investigators.

Results: The following steps for the successful collection and conversion of decision trees were identified and defined in detail: problem definition, population selection, draft input collection, tree conversion, criteria adaptation, problem re-evaluation, results distribution and refinement, tree finalisation, and analysis.

Conclusion: This manuscript provides information on the main steps for successful collection of decision trees and summarizes important aspects at each point of the analysis.
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http://dx.doi.org/10.1186/s12874-017-0400-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5559810PMC
August 2017

Secondary malignancies after rectal cancer resection with and without radiation therapy: A propensity-adjusted, population-based SEER analysis.

Radiother Oncol 2017 04 9;123(1):139-146. Epub 2017 Mar 9.

Department of Radiation Oncology, Cantonal Hospital, St.Gallen, Switzerland. Electronic address:

Background: The relationship between radiation therapy for rectal cancer and secondary malignancies is debated. The present study is the first population-based analysis using conventional multivariable analyses as well as propensity score matching to assess this relationship.

Methods: Overall, 77,484 patients after resection of localized or locally advanced rectal adenocarcinoma diagnosed between 1973 and 2012 were identified in the Surveillance, Epidemiology, and End Results (SEER) registry. The occurrence of secondary malignancies diagnosed at least 1 (median follow up 5.8years [1-39.9years]) year after rectal cancer diagnosis was compared in patients who did and did not undergo radiation using stratified and propensity score matched Cox regression analysis.

Results: Of 77,484 patients, 34,114 underwent radiation and 43,370 did not. Ignoring gender and entity, radiation therapy was not associated with secondary malignancies (hazard ratio [HR]=0.97 (95%CI: 0.92-1.02, P=0.269). The risk for prostate cancer was decreased and (HR=0.42, 95%CI: 0.36-0.48, P<0.001) and increased risk for endometrial cancer (HR=1.95, 95%CI: 1.49-2.56, P<0.001). Overall, patients undergoing radiation had higher risks for lung cancer (HR=1.18, 95%CI: 1.06-1.30, P<0.001), bladder cancer (HR=1.54, 95%CI: 1.31-1.80, P<0.001) and lymphomas (HR=1.27, 95%CI: 1.03-1.58, P=0.026).

Conclusions: The present analysis describes the occurence of secondary malignancies after pelvic radiation in patients undergoing rectal cancer surgery. Indeed, radiation for rectal cancer is associated with a significantly decreased risk of prostate cancer, however, an increased risk of endometrial, lung, and bladder cancer as well as lymphomas was observed. Overall, the risk of secondary malignancies was slightly decreased with radiation in patients undergoing rectal cancer resection, this was attributable to lower rates in prostate cancer.
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http://dx.doi.org/10.1016/j.radonc.2017.02.007DOI Listing
April 2017

Haemoglobin and creatinine values as prognostic factors for outcome of concurrent radiochemotherapy in locally advanced head and neck cancers : Secondary results of two European randomized phase III trials (ARO 95-06, SAKK 10/94).

Strahlenther Onkol 2016 Aug 20;192(8):552-60. Epub 2016 Jun 20.

Departments of Radiation Oncology, Charité Universitaetsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.

Background: To determine the influence of baseline laboratory values on treatment outcome in patients with locally advanced head and neck cancer (HNSCC).

Methods: Data of the randomized trials ARO 95 -06 (n = 384) and SAKK 10 /94 (n = 224) were pooled for a total sample size of 608 patients. Haemoglobin (Hb) and creatinine (Cr) were available at baseline and their association with locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), cancer-specific survival (CSS), and overall survival (OS) was analyzed using univariable and multivariable Cox regression models.

Results: A total of 580 and 564 patients were available with baseline Hb and Cr values in the pooled analysis. Univariable analyses revealed that lower baseline Hb values were significantly associated with decreased LRRFS, DMFS, CSS and OS. This effect remained significant for OS when the treatment arms (radiotherapy [RT] alone vs. chemoradiation [CRT]) were analyzed separately. Higher baseline Cr was associated with improved OS in the pooled analysis. Interestingly, the prognostic value of baseline Cr appeared to be limited to the subgroup of 284 patients who were treated with CRT. In the multivariable Cox regression model lower baseline Hb remained associated with decreased OS both in the patients who received CRT (HR 0.79, 95 % CI 0.66-0.94, p = 0.009) and in those patients who underwent RT alone (HR 0.67, 95 % CI 0.58-0.78, p < 0.001). Increased baseline Cr remained significantly associated with improved OS in patients who underwent CRT (HR 0.79, 95 % CI 0.69-0.92, p = 0.002) but not in those patients who underwent RT alone.

Conclusions: An association between lower baseline Hb and inferior treatment outcome was confirmed. Baseline Cr was introduced as a prognosticator of outcome after CRT for locally advanced HNSCC.
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http://dx.doi.org/10.1007/s00066-016-0999-3DOI Listing
August 2016

Volumetric regression ratio of the primary tumor and metastatic lymph nodes after induction chemotherapy predicts overall survival in head and neck squamous cell carcinoma: a retrospective analysis.

J BUON 2016 Jan-Feb;21(1):175-81

Department of Radiation Oncology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland.

Purpose: We looked for any predictive value of change in primary tumor and metastatic lymph node volumes after induction chemotherapy (IC) on oncologic outcome in head and neck squamous cell carcinoma (HNSCC).

Methods: Nineteen patients with stage IVA/B HNSCC treated between 2004 and 2010 with at least one cycle of IC (docetaxel, cisplatin and 5-fluorouracil/TPF) and concomitant chemoradiotherapy (CRT) with cisplatin were retrospectively analyzed. Volumes were calculated separately for primary tumor (Vtm), lymph node metastases (Vln) and their sum (Vsum) on computed tomography (CT) images before and after IC. The effect of volumetric changes on locoregional failure (LRF), distant metastasis (DM) and overall survival (OS) was assessed. P values <0.05 were considered as statistically significant.

Results: The median follow-up of surviving patients was 25 months (range: 10.7-83.3). The median number of cycles and duration of TPF was 3 (range: 1-4) and 44 days (range: 4-116), respectively. Empirical area under the curve (AUC) analyses for death, LRF and DM revealed optimal cut-off values of Vtm diminution (30.54%, AUC: 87%) and Vsum decrease (35.45%, AUC: 64.55%) only for OS (p <0.05). Among those, a reduction in Vsum more than 35.4% between pre- and post-IC was significantly correlated with better OS (100 vs 43% at 2 years, p <0.05).

Conclusion: Volumetric shrinkage of the tumor load after IC assessed with CT seems to predict OS. The assessment of volumetric shrinkage upon IC might be used to decide whether to offer patients alternative strategies like palliative/de-intensified treatments or more aggressive combined modalities after IC.
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May 2016

Acute Toxicity and Quality of Life After Dose-Intensified Salvage Radiation Therapy for Biochemically Recurrent Prostate Cancer After Prostatectomy: First Results of the Randomized Trial SAKK 09/10.

J Clin Oncol 2015 Dec 2;33(35):4158-66. Epub 2015 Nov 2.

Pirus Ghadjar, Jürg Bernhard, George N. Thalmann, and Daniel M. Aebersold, Inselspital, Bern University Hospital, and University of Bern; Stefanie Hayoz, Lukas Stalder, and Christine Biaggi-Rudolf, Swiss Group for Clinical Cancer Research Coordinating Center; Jürg Bernhard, International Breast Cancer Study Group Coordinating Center, Bern; Daniel R. Zwahlen, Kantonsspital Graubünden, Chur; Philipp Gut, Kantonsspital Luzern, Luzern; Ludwig Plasswilm, Kantonsspital St Gallen, St Gallen; Alexandros Papachristofilou, University Hospital Basel, Basel; Marcin Sumila, Hirslanden Hospital Group, Zürich; Helmut Kranzbühler, Stadtspital Triemli, Zürich; Yousef Najafi, University Hospital Zürich, Zürich; Ngwa C. Azinwi, Istituto Oncologico della Svizzera Italiana, Bellinzona; Christiane Reuter, Kantonsspital Münsterlingen, Münsterlingen; Stephan Bodis, Kantonsspital Aarau, Aarau; Khanfir Kaouthar, Hôpital Valais, Sion, Switzerland; Pirus Ghadjar and Peter Wust, Charité Universitätsmedizin, Berlin; Tobias Hölscher, University Hospital Dresden, Dresden; Matthias Gluckenberger, University Hospital Würzburg, Würzburg; Guido Hildebrandt, University Hospital Rostock, Rostock; Arndt-Christian Müller, University Hospital Tübingen, Tübingen, Germany; and Piet Ost, Ghent University Hospital, Ghent, Belgium.

Purpose: Patients with biochemical failure (BF) after radical prostatectomy may benefit from dose-intensified salvage radiation therapy (SRT) of the prostate bed. We performed a randomized phase III trial assessing dose intensification.

Patients And Methods: Patients with BF but without evidence of macroscopic disease were randomly assigned to either 64 or 70 Gy. Three-dimensional conformal radiation therapy or intensity-modulated radiation therapy/rotational techniques were used. The primary end point was freedom from BF. Secondary end points were acute toxicity according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0) and quality of life (QoL) according to the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires C30 and PR25.

Results: Three hundred fifty patients were enrolled between February 2011 and April 2014. Three patients withdrew informed consent, and three patients were not eligible, resulting in 344 patients age 48 to 75 years in the safety population. Thirty patients (8.7%) had grade 2 and two patients (0.6%) had grade 3 genitourinary (GU) baseline symptoms. Acute grade 2 and 3 GU toxicity was observed in 22 patients (13.0%) and one patient (0.6%), respectively, with 64 Gy and in 29 patients (16.6%) and three patients (1.7%), respectively, with 70 Gy (P = .2). Baseline grade 2 GI toxicity was observed in one patient (0.6%). Acute grade 2 and 3 GI toxicity was observed in 27 patients (16.0%) and one patient (0.6%), respectively, with 64 Gy, and in 27 patients (15.4%) and four patients (2.3%), respectively, with 70 Gy (P = .8). Changes in early QoL were minor. Patients receiving 70 Gy reported a more pronounced and clinically relevant worsening in urinary symptoms (mean difference in change score between arms, 3.6; P = .02).

Conclusion: Dose-intensified SRT was associated with low rates of acute grade 2 and 3 GU and GI toxicity. The impact of dose-intensified SRT on QoL was minor, except for a significantly greater worsening in urinary symptoms.
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http://dx.doi.org/10.1200/JCO.2015.63.3529DOI Listing
December 2015

PSA bounce after ¹²⁵I-brachytherapy for prostate cancer as a favorable prognosticator.

Strahlenther Onkol 2015 Oct 23;191(10):787-91. Epub 2015 Jun 23.

Department of Radiation Oncology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.

Background: Permanent low-dose-rate brachytherapy (BT) with iodine 125 is an established curative treatment for localized prostate cancer. After treatment, prostate-specific antigen (PSA) kinetics may show a transient rise (PSA bounce). Our aim was to investigate the association of PSA bounce with biochemical control.

Patients And Methods: Patients treated with BT in Switzerland were registered in a prospective database. Only patients with a follow-up of at least 2 years were included in our analysis. Clinical follow-up and PSA measurements were assessed after 1.5, 3, 6, and 12 months, and annually thereafter. If PSA increased, additional follow-up visits were scheduled. Cases of PSA bounce were defined as a rise of at least 0.2 ng/ml above the initial PSA nadir with a subsequent decline to or below the initial nadir without treatment. Biochemical failure was defined as a rise to nadir + 2 ng/ml.

Results: Between March 2001 and November 2010, 713 patients with prostate cancer undergoing BT with at least 2 years of follow-up were registered. Median follow-up time was 41 months. Biochemical failure occurred in 28 patients (3.9 %). PSA bounce occurred in 173 (24.3 %) patients; only three (1.7 %) patients with PSA bounce developed biochemical failure, in contrast to 25 (4.6 %) patients without previous bounce (p < 0.05). The median time to bounce was 12 months, the median time to biochemical failure was 30 months. The median bounce increase was 0.78 ng/ml. Twenty-eight patients with bounce (16.5 %) had a transient PSA rise of + 2 ng/ml above the nadir.

Conclusion: In most cases, an early increase in PSA after BT indicates PSA bounce and is associated with a lower risk of biochemical failure.
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http://dx.doi.org/10.1007/s00066-015-0860-0DOI Listing
October 2015

Design and implementation of a "cheese" phantom-based Tomotherapy TLD dose intercomparison.

Strahlenther Onkol 2015 Nov 19;191(11):855-61. Epub 2015 Jun 19.

Department of Radiation Oncology, Kantonsspital St. Gallen, 9007, St. Gallen, Switzerland.

Background: The unique beam-delivery technique of Tomotherapy machines (Accuray Inc., Sunnyvale, Calif.) necessitates tailored quality assurance. This requirement also applies to external dose intercomparisons. Therefore, the aim of the 2014 SSRMP (Swiss Society of Radiobiology and Medical Physics) dosimetry intercomparison was to compare two set-ups with different phantoms.

Materials And Methods: A small cylindrical Perspex phantom, which is similar to the IROC phantom (Imaging and Radiation Oncology Core, Houston, Tex.), and the "cheese" phantom, which is provided by the Tomotherapy manufacturer to all institutions, were used. The standard calibration plans for the TomoHelical and TomoDirect irradiation techniques were applied. These plans are routinely used for dose output calibration in Tomotherapy institutions. We tested 20 Tomotherapy machines in Germany and Switzerland. The ratio of the measured (Dm) to the calculated (Dc) dose was assessed for both phantoms and irradiation techniques. The Dm/Dc distributions were determined to compare the suitability of the measurement set-ups investigated.

Results: The standard deviations of the TLD-measured (thermoluminescent dosimetry) Dm/Dc ratios for the "cheese" phantom were 1.9 % for the TomoHelical (19 measurements) and 1.2 % (11 measurements) for the TomoDirect irradiation techniques. The corresponding ratios for the Perspex phantom were 2.8 % (18 measurements) and 1.8 % (11 measurements).

Conclusion: Compared with the Perspex phantom-based set-up, the "cheese" phantom-based set-up without individual planning was demonstrated to be more suitable for Tomotherapy dose checks. Future SSRMP dosimetry intercomparisons for Tomotherapy machines will therefore be based on the "cheese" phantom set-up.
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http://dx.doi.org/10.1007/s00066-015-0850-2DOI Listing
November 2015

Consensus and differences in primary radiotherapy for localized and locally advanced prostate cancer in Switzerland: A survey on patterns of practice.

Strahlenther Onkol 2015 Oct 19;191(10):778-86. Epub 2015 May 19.

Department of Radiation Oncology, Kantonsspital St. Gallen, Rorschacherstrasse 95, 9007, St. Gallen, Switzerland.

Introduction: External beam radiotherapy (EBRT), with or without androgen deprivation therapy (ADT), is an established treatment option for nonmetastatic prostate cancer. Despite high-level evidence from several randomized trials, risk group stratification and treatment recommendations vary due to contradictory or inconclusive data, particularly with regard to EBRT dose prescription and ADT duration. Our aim was to investigate current patterns of practice in primary EBRT for prostate cancer in Switzerland.

Materials And Methods: Treatment recommendations on EBRT and ADT for localized and locally advanced prostate cancer were collected from 23 Swiss radiation oncology centers. Written recommendations were converted into center-specific decision trees, and analyzed for consensus and differences using a dedicated software tool. Additionally, specific radiotherapy planning and delivery techniques from the participating centers were assessed.

Results: The most commonly prescribed radiation dose was 78 Gy (range 70-80 Gy) across all risk groups. ADT was recommended for intermediate-risk patients for 6 months in over 80 % of the centers, and for high-risk patients for 2 or 3 years in over 90 % of centers. For recommendations on combined EBRT and ADT treatment, consensus levels did not exceed 39 % in any clinical scenario. Arc-based intensity-modulated radiotherapy (IMRT) is implemented for routine prostate cancer radiotherapy by 96 % of the centers.

Conclusion: Among Swiss radiation oncology centers, considerable ranges of radiotherapy dose and ADT duration are routinely offered for localized and locally advanced prostate cancer. In the vast majority of cases, doses and durations are within the range of those described in current evidence-based guidelines.
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http://dx.doi.org/10.1007/s00066-015-0849-8DOI Listing
October 2015

Guidance of treatment decisions in risk-adapted primary radiotherapy for prostate cancer using multiparametric magnetic resonance imaging: a single center experience.

Radiat Oncol 2015 Feb 22;10:47. Epub 2015 Feb 22.

Department of Radiation Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland.

Background: Magnetic resonance imaging (MRI) of the prostate is considered to be the most precise noninvasive staging modality for localized prostate cancer. Multiparametric MRI (mpMRI) dynamic sequences have recently been shown to further increase the accuracy of staging relative to morphological imaging alone. Correct radiological staging, particularly the detection of extraprostatic disease extension, is of paramount importance for target volume definition and dose prescription in highly-conformal curative radiotherapy (RT); in addition, it may affect the risk-adapted duration of additional antihormonal therapy. The purpose of our study was to analyze the impact of mpMRI-based tumor staging in patients undergoing primary RT for prostate cancer.

Methods: A total of 122 patients admitted for primary RT for prostate cancer were retrospectively analyzed regarding initial clinical and computed tomography-based staging in comparison with mpMRI staging. Both tumor stage shifts and overall risk group shifts, including prostate-specific antigen (PSA) level and the Gleason score, were assessed. Potential risk factors for upstaging were tested in a multivariate analysis. Finally, the impact of mpMRI-based staging shift on prostate RT and antihormonal therapy was evaluated.

Results: Overall, tumor stage shift occurred in 55.7% of patients after mpMRI. Upstaging was most prominent in patients showing high-risk serum PSA levels (73%), but was also substantial in patients presenting with low-risk PSA levels (50%) and low-risk Gleason scores (45.2%). Risk group changes occurred in 28.7% of the patients with consequent treatment adaptations regarding target volume delineation and duration of androgen deprivation therapy. High PSA levels were found to be a significant risk factor for tumor upstaging and newly diagnosed seminal vesicle infiltration assessed using mpMRI.

Conclusions: Our findings suggest that mpMRI of the prostate leads to substantial tumor upstaging, and can considerably affect treatment decisions in all patient groups undergoing risk-adapted curative RT for prostate cancer.
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http://dx.doi.org/10.1186/s13014-015-0338-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4344745PMC
February 2015

Impact of weight loss on survival after chemoradiation for locally advanced head and neck cancer: secondary results of a randomized phase III trial (SAKK 10/94).

Radiat Oncol 2015 Jan 17;10:21. Epub 2015 Jan 17.

Background: To analyze the impact of weight loss before and during chemoradiation on survival outcomes in patients with locally advanced head and neck cancer.

Methods: From 07/1994-07/2000 a total of 224 patients with squamous cell carcinoma of the head and neck were randomized to either hyperfractionated radiation therapy alone or the same radiation therapy combined with two cycles of concomitant cisplatin. The primary endpoint was time to any treatment failure (TTF); secondary endpoints were locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS) and overall survival (OS). Patient weight was measured 6 months before treatment, at treatment start and treatment end.

Results: The proportion of patients with >5% weight loss was 32% before, and 51% during treatment, and the proportion of patients with >10% weight loss was 12% before, and 17% during treatment. After a median follow-up of 9.5 years (range, 0.1 - 15.4 years) weight loss before treatment was associated with decreased TTF, LRRFS, DMFS, cancer specific survival and OS in a multivariable analysis. However, weight loss during treatment was not associated with survival outcomes.

Conclusions: Weight loss before and during chemoradiation was commonly observed. Weight loss before but not during treatment was associated with worse survival.
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http://dx.doi.org/10.1186/s13014-014-0319-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4324674PMC
January 2015

Prognostic significance of histology after resection of brain metastases and whole brain radiotherapy in non-small cell lung cancer (NSCLC).

Clin Exp Metastasis 2015 Feb 28;32(2):143-9. Epub 2015 Jan 28.

Department of Radiation Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland,

Brain metastases from non-small cell lung cancer (NSCLC) are associated with a poor prognosis. In selected cases, surgical resection of brain metastases may be indicated, but the identification of patients suitable for surgery remains difficult. We collected data on patient and tumour characteristics known or suspected to be associated with survival by chart review. Data was merged with available data from the local cancer registry. We identified 64 NSCLC patients with resected brain metastases. Median overall survival after resection was 9.1 months with only two patients (3%) surviving more than 71 and 80 months. One and 2-year survival were 42 and 12.5%. Median survival for males and patients with more comorbidities was shorter (8 vs. 10 months [p = 0.11] and 6 vs. 9 months [p = 0.06]). Patients with squamous cell carcinomas (33% of the patients) had a significantly worse survival than patients with other histologies (7 vs. 10 months [p = 0.02]) with no patient living longer than 2 years. Squamous cell histology was associated with worse prognosis after resection of brain metastases in patients with non-small cell lung cancer. Histology, among other parameters, may also be taken into account when choosing the appropriate patients for resection of brain metastases.
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http://dx.doi.org/10.1007/s10585-015-9699-0DOI Listing
February 2015

Objective consensus from decision trees.

Radiat Oncol 2014 Dec 5;9:270. Epub 2014 Dec 5.

Department of Radiation Oncology, Kantonsspital St. Gallen, Rorschacherstr. 95, 9007, St. Gallen, Switzerland.

Background: Consensus-based approaches provide an alternative to evidence-based decision making, especially in situations where high-level evidence is limited. Our aim was to demonstrate a novel source of information, objective consensus based on recommendations in decision tree format from multiple sources.

Methods: Based on nine sample recommendations in decision tree format a representative analysis was performed. The most common (mode) recommendations for each eventuality (each permutation of parameters) were determined. The same procedure was applied to real clinical recommendations for primary radiotherapy for prostate cancer. Data was collected from 16 radiation oncology centres, converted into decision tree format and analyzed in order to determine the objective consensus.

Results: Based on information from multiple sources in decision tree format, treatment recommendations can be assessed for every parameter combination. An objective consensus can be determined by means of mode recommendations without compromise or confrontation among the parties. In the clinical example involving prostate cancer therapy, three parameters were used with two cut-off values each (Gleason score, PSA, T-stage) resulting in a total of 27 possible combinations per decision tree. Despite significant variations among the recommendations, a mode recommendation could be found for specific combinations of parameters.

Conclusion: Recommendations represented as decision trees can serve as a basis for objective consensus among multiple parties.
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http://dx.doi.org/10.1186/s13014-014-0270-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4269842PMC
December 2014

Surface dose characterisation of the Varian Ir-192 HDR conical surface applicator set with a vertically orientated source.

Strahlenther Onkol 2014 Nov 1;190(12):1163-8. Epub 2014 Aug 1.

Department of Radiation Oncology, Kantonsspital St. Gallen, 9007, St. Gallen, Switzerland,

Background: Conical surface applicators with an Ir-192 high-dose-rate brachytherapy source are a common modality for the treatment of non-melanomatous skin cancer with high tumour control rates. Surface dose characterisation of the Varian Varisource GammaMed+ IX afterloader vertical type surface applicators is performed two dimensionally using high-resolution film dosimetry.

Aim: The focus of this study was to determine if Varian surface applicators with a vertical source suffer from the dose distribution irregularities reported for comparable applicators. Our goal was to evaluate if the irregularities found affected treatment and dose output verification procedures.

Methods: Ionisation chamber-based verification of applicator output was established according to guidelines provided by the manufacturer. For additional measurement of surface dose Gafchromic EBT3 film dosimetry was used. The term "therapeutic dose" was defined as 85% of the prescribed dose level.

Results: For the 10 different applicator inserts evaluated, cold spots were observed. Mean cold spot size was 2.0 mm × 3.6 mm (± 0.6 mm). The cold spots were dosimetrically well below 85% of the prescribed dose. The cold spot was situated 2.2 mm (1.4-2.7 mm) unilaterally from the central axis and caused general asymmetry in the dose profiles intersecting the cold spot area. A source tilt of approximately 8° (± 1°) was determined for the source used for irradiation.

Conclusions: A central underdosed area exceeding 15 % of the prescribed dose has not been previously reported. Source tilt was observed and found to affect clinical use and possibly treatment outcome in applicators using a vertically arranged source. Surface applicators with a vertically orientated source were subject to dose irregularities that could impact on chamber-based applicator output verification procedures. We recommend film dosimetry-backed applicator commissioning to avoid systematic errors.
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http://dx.doi.org/10.1007/s00066-014-0713-2DOI Listing
November 2014

A treatment planning study comparing Elekta VMAT and fixed field IMRT using the varian treatment planning system eclipse.

Radiat Oncol 2014 Jul 10;9:153. Epub 2014 Jul 10.

Department of Radiation Oncology, Kantonsspital St, Gallen, Rorschacherstrasse 95, 9007 St, Gallen, Switzerland.

Background: The newest release of the Eclipse (Varian) treatment planning system (TPS) includes an optimizing engine for Elekta volumetric-modulated arc therapy (VMAT) planning. The purpose of this study was to evaluate this new algorithm and to compare it to intensity-modulated radiation therapy (IMRT) for various disease sites by creating single- and double-arc VMAT plans.

Methods: A total of 162 plans were evaluated in this study, including 38 endometrial, 57 head and neck, 12 brain, 10 breast and 45 prostate cancer cases. The real-life IMRT plans were developed during routine clinical cases using the TPS Eclipse. VMAT plans were generated using a preclinical version of Eclipse with tumor-region-specific optimizing templates without interference of the operator: with one full arc (1A) and with two full arcs (2A), and with partial arcs for breast and prostate with hip implant cases. All plans were evaluated based on target coverage, homogeneity and conformity. The organs at risk (OARs) were analyzed according to plan objectives, such as the mean and maximum doses. If one or more objectives were exceeded, the plan was considered clinically unacceptable, and a second VMAT plan was created by adapting the optimization penalties once.

Results: Compared to IMRT, single- and double-arc VMAT plans showed comparable or better results concerning the target coverage: the maximum dose in the target for 1A is the same as that for IMRT; for 2A, an average reduction of 1.3% over all plans was observed. The conformity showed a statistically significant improvement for both 1A (+3%) and 2A (+6%). The mean total body dose was statistically significant lower for the considered arc techniques (IMRT: 16.0 Gy, VMAT: 15.3 Gy, p < 0.001). However, the sparing of OARs shows individual behavior that depends strongly on the different tumor regions. A clear difference is found in the number of monitor units (MUs) per plan: VMAT shows a reduction of 31%.

Conclusion: These findings demonstrate that based on optimizing templates with minimal interaction of the operator, the Eclipse TPS is able to achieve a plan quality for the Elekta VMAT delivery technique that is comparable to that of fixed-field IMRT. Plans with two arcs show better dose distributions than plans with one arc.
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http://dx.doi.org/10.1186/1748-717X-9-153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4107584PMC
July 2014

Use of EORTC target definition guidelines for dose-intensified salvage radiation therapy for recurrent prostate cancer: results of the quality assurance program of the randomized trial SAKK 09/10.

Int J Radiat Oncol Biol Phys 2013 Nov 22;87(3):534-41. Epub 2013 Aug 22.

Department of Radiation Oncology and Division of Medical Radiation Physics, Bern University Hospital, Switzerland.

Purpose: Different international target volume delineation guidelines exist and different treatment techniques are available for salvage radiation therapy (RT) for recurrent prostate cancer, but less is known regarding their respective applicability in clinical practice.

Methods And Materials: A randomized phase III trial testing 64 Gy vs 70 Gy salvage RT was accompanied by an intense quality assurance program including a site-specific and study-specific questionnaire and a dummy run (DR). Target volume delineation was performed according to the European Organisation for the Research and Treatment of Cancer guidelines, and a DR-based treatment plan was established for 70 Gy. Major and minor protocol deviations were noted, interobserver agreement of delineated target contours was assessed, and dose-volume histogram (DVH) parameters of different treatment techniques were compared.

Results: Thirty European centers participated, 43% of which were using 3-dimensional conformal RT (3D-CRT), with the remaining centers using intensity modulated RT (IMRT) or volumetric modulated arc technique (VMAT). The first submitted version of the DR contained major deviations in 21 of 30 (70%) centers, mostly caused by inappropriately defined or lack of prostate bed (PB). All but 5 centers completed the DR successfully with their second submitted version. The interobserver agreement of the PB was moderate and was improved by the DR review, as indicated by an increased κ value (0.59 vs 0.55), mean sensitivity (0.64 vs 0.58), volume of total agreement (3.9 vs 3.3 cm(3)), and decrease in the union volume (79.3 vs 84.2 cm(3)). Rectal and bladder wall DVH parameters of IMRT and VMAT vs 3D-CRT plans were not significantly different.

Conclusions: The interobserver agreement of PB delineation was moderate but was improved by the DR. Major deviations could be identified for the majority of centers. The DR has improved the acquaintance of the participating centers with the trial protocol.
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http://dx.doi.org/10.1016/j.ijrobp.2013.06.2053DOI Listing
November 2013

Re-implantation after insufficient primary 125-i permanent prostate brachytherapy.

Radiat Oncol 2013 Aug 6;8:194. Epub 2013 Aug 6.

Department of Radiation Oncology, Kantonsspital St, Gallen, 9007 St, Gallen, Switzerland.

Introduction: We describe five patients receiving a re-implantation (RI) after post-operative dosimetry of the primary 125-I permanent prostate brachytherapy (BT) for prostate cancer revealed an insufficient dose coverage.

Materials And Methods: Five out of 222 consecutive patients treated (from March, 2001 to August, 2012) with 125-I BT, received a RI after dosimetric verification by CT and MRI fusion four to eight weeks after implantation displayed an insufficient dose coverage. RIs were performed with 10 to 19 seeds, three to four months after primary intervention. Dosimetry after RI showed an improved and sufficient total dose coverage in all patients.

Results: At last follow-up (18 to 99 months, median 57 months), none of the patients had relevant implant associated side-effects. Functional outcome was comparable to patients after one-time implantation. PSA levels post intervention showed a decreasing tendency in 4 patients. One patient had a local recurrence after 12 months.

Conclusion: In our series, approximately 2% of the patients treated with permanent prostate BT required a RI due to insufficient dose coverage. None of the patients who underwent RI experienced complications. Our series, although only with 5 cases and limited follow-up, along with other published reports, demonstrates good tolerability.
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http://dx.doi.org/10.1186/1748-717X-8-194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3851561PMC
August 2013

Relevance of incidental colorectal FDG-PET/CT-enhanced lesions.

Onkologie 2013 18;36(4):200-4. Epub 2013 Mar 18.

Department of Radiation Oncology, Kantonsspital St. Gallen, Switzerland.

Introduction: Positron emission tomography/computed tomographies (PET/CTs) may result in incidental findings of fluorodeoxyglucose (FDG)-avid lesions in the colon. The aim of this study was to assess the relevance of a colonoscopic workup of such lesions.

Patients And Methods: We retrospectively analysed all PET/CT reports (n = 4,973) generated in our nuclear medicine department between May 2006 and May 2011; in 69 cases a colonoscopic evaluation was recommended for incidental FDG-avid lesions.

Results: Of these 69 cases, 51 underwent colonoscopy because of the potential need for further treatment. The maximum standardized uptake values (SUVmax) ranged from 5.0 to 42.0 with an average of 10.9. In 44 of the 51 patients, a histopathological abnormality was found on colonoscopy, 44 in the location described by PET/CT. A further 38 lesions were identified that were not visible on PET/CT. The histopathological evaluation in the 51 patients revealed 14 hyperplastic polyps, 27 adenomas with low-grade and 4 with high-grade dysplasia, 3 adenocarcinomas and 1 neuro-endocrine tumour.

Conclusion: Incidental findings of focal colorectal FDG uptake should lead to further workup with colonoscopy. The SUVmax was not predictive for higher grade histologies. With an SUV of 5 the yield was high for colonic premalignant and malignant lesions. However, malignancy cannot be ruled out in focal lesions with an SUV of less than 5, and for individual patients a colonoscopy should not be ruled out.
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http://dx.doi.org/10.1159/000350302DOI Listing
September 2013

Re-irradiation with and without bevacizumab as salvage therapy for recurrent or progressive high-grade gliomas.

J Neurooncol 2013 Mar 12;112(1):133-9. Epub 2013 Jan 12.

Department of Neurology, Cantonal Hospital St. Gallen, Rorschacherstr. 95, 9007 St. Gallen, Switzerland.

The optimal treatment for recurrent high-grade gliomas is unknown and a standard of care does not exist. Re-irradiation with concomitant bevacizumab represents an option. Retrospectively, we analyzed a cohort of heavily pretreated patients (n = 14) with relapsing HGGs who underwent re-irradiation with conventional 3D-conformal or intensified modulated radiotherapy (IMRT). Ten of them received re-irradiation in combination with bevacizumab. The study population consisted of eight GBMs and six anaplastic gliomas. All patients had previously undergone irradiation for first-line therapy, including seven patients with radiochemotherapy with temozolomide. Patients without contraindications started with two infusions of bevacizumab (10 mg/kg of body weight every other week) prior to re-irradiation and continued through re-irradiation until progression. The median patient age was 45 years with a median Karnofsky performance scale of 70. The median dose of re-irradiation was 41.6 Gy [39-55 Gy]. The median physical cumulative radiation dose was 101.6 Gy [65-110.4 Gy]. The median PFS from re-irradiation was 5.1 months [1.6-17.4] based on clinical and RANO criteria. Median OS from re-irradiation was 9.0 months [6.4-17.8]. We detected radionecrosis due to advanced imaging in one patient. Other toxicities were expected and attributable well known side effects of bevacizumab. This retrospective study provides additional feasibility and safety data of conventional 3D-conformal re-irradiation and IMRT in combination with bevacizumab in relapsing high-grade gliomas.
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http://dx.doi.org/10.1007/s11060-013-1044-3DOI Listing
March 2013

Compensability index for compensation radiotherapy after treatment interruptions.

Radiat Oncol 2012 Dec 8;7:208. Epub 2012 Dec 8.

Department of Radiation Oncology, Kantonsspital St. Gallen, Rorschacherstrasse 95, St. Gallen 9000, Switzerland.

Background: The goal of our work was to develop a simple method to evaluate a compensation treatment after unplanned treatment interruptions with respect to their tumour- and normal tissue effect.

Methods: We developed a software tool in java programming language based on existing recommendations to compensate for treatment interruptions. In order to express and visualize the deviations from the originally planned tumour and normal tissue effects we defined the compensability index.

Results: The compensability index represents an evaluation of the suitability of compensatory radiotherapy in a single number based on the number of days used for compensation and the preference of preserving the originally planned tumour effect or not exceeding the originally planned normal tissue effect. An automated tool provides a method for quick evaluation of compensation treatments.

Conclusions: The compensability index calculation may serve as a decision support system based on existing and established recommendations.
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http://dx.doi.org/10.1186/1748-717X-7-208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3539912PMC
December 2012

Extrapulmonary small cell carcinoma: An indication for prophylactic cranial irradiation? A single center experience.

Strahlenther Onkol 2011 Sep 27;187(9):561-7. Epub 2011 Jun 27.

Department of Oncology/Hematology, Kantonsspital St. Gallen, St. Gallen, Switzerland.

Background: Information about extrapulmonary small cell carcinoma (EPSCC) is limited and the role of prophylactic cranial irradiation (PCI) is unknown.

Patients And Methods: Disease presentation and outcome of all EPSCC at our hospital between 1990 and 2009 were retrospectively analyzed.

Results: Of 30 EPSCC, the male:female ratio was 58%:42%; 83% had a performance status of 0-2. Median age was 71 years (32-80). Seventeen (57%) had limited stage (LS), 13 (43%) extensive stage (ES). The location of the primary tumor was gastrointestinal (n = 8), unknown (6), gynecological (6), urogenital (5), and ear nose throat (5). Four (13%) developed brain metastases (2 ES, 2 LS). In ES, first line chemotherapy (CT) was given in 85%, mostly platinum-etoposide (64%). Response rate was 90%. In LS, CT and radiotherapy (RT) ± resection resulted in persistent remissions in 67% of patients. Median survival was 16 months (1-107 months), 18 months (1-107 months), and 9 months (0.4-25 months) for LS + ES, LS, and ES, respectively. Weight loss ≥5 % and ECOG performance status 3 + 4 were associated with poorer survival (p < 0.001 and p < 0.01, respectively).

Conclusion: The incidence of brain metastases was relatively low (13%). More studies are necessary, before routinely offering PCI to patients with EPSCC. Best survival outcomes in LS were achieved with multimodality treatment including CT and RT. Prognosis was poor in patients with ES.
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http://dx.doi.org/10.1007/s00066-011-2222-xDOI Listing
September 2011