Search

Introduction: Even though randomized controlled trials could not show a significant survival benefit for the use of neoadjuvant systemic therapy (NST), it is increasingly recommended for patients with clinically node-positive breast cancer due to its implications on prognosis, locoregional downstaging and response-driven adjuvant systemic therapy. The aim of this study was to assess the need for international standardization of treatment recommendations by evaluating clinical practice heterogeneity in use of NST for patients with clinically node-positive breast cancer in Europe. Methods: The study was preplanned in the international multicenter phase-III OPBC-03/TAXIS trial (ClinicalTrials.gov Identifier: NCT03513614) after randomization of the first 500 patients with clinically node-positive breast cancer who underwent axillary lymph node dissection (ALND) or axillary radiation (ART) without ALND after tailored axillary surgery (TAS) in the context of extended regional nodal irradiation. Clinically node-positive breast cancer was defined by confirmed nodal disease at the time of initial diagnosis; in case of neoadjuvant therapy, residual nodal disease was mandatory. Investigators were encouraged to enroll all eligible patients consecutively. However, TAXIS is unique inasmuch as its pragmatic design allows both the neoadjuvant and adjuvant setting according to the preferences of the treating physicians and institutions and thus provides an excellent opportunity to study patterns and trends in use of NST in patients with clinically positive nodes in Europe. Results: A total of 500 patients with a median age of 57 years (IQR: 48-69 years) were included at 44 breast centers in 6 European countries from August 2018 to June 2022. Subtype was hormone receptor (HR) positive (+) and human epidermal growth factor receptor 2 (HER2) negative (-) in 393 (80.0%), HR+/HER2+ in 52 (10.6%), HR-/HER2+ in 5 (1.0%) and HR-/HER2- in 34 (6.9%) patients. The rate of patients undergoing NST was 31.4% with a significant upward trend over time during the study period (from 20.0% in 2018 to 38.1% in 2022; p=0.044). The use of NST varied significantly by country (p=< 0.001) and by site (p=0.015). For patients with clinical AJCC tumor stage II and III, the rates of patients undergoing NST in Switzerland were 26.5% (18 of 68) and 35.9% (92 of 256), in Germany 22.2% (2 of 9) and 30.4% (7 of 23), in Austria 50% (7 of 14) and 60% (9 of 15) and in Hungary 0% (0 of 15) and 20.7% (18 of 87), respectively (p=0.019 and 0.004). Large differences by country were found for ER+/HER2- breast cancer, ranging from 13.1% (11 of 84) in Hungary to 47.8% (11 of 23) in Austria (p=0.007). Within Switzerland, which was the country with most included patients (328 of 500) and participating sites (n=25), the rate of patients undergoing NST for ER+/HER2- breast cancer varied considerably by site, ranging from 10% (2 of 20) to 50% (11 of 22). Discussion: This study revealed substantial heterogeneity in clinical practice in Europe, indicating the need for development of and adherence to consistent guidelines to standardize the international use of NST. Citation Format: Walter P. Weber, Zoltan Matrai, Stefanie Hayoz, Guido Henke, Daniel R. Zwahlen, Günther Gruber, Frank Zimmermann, Thomas Ruhstaller, Simone Muenst, Markus Ackerknecht, Christian Kurzeder, Sherko Küemmel, Vesna Bjelic-Radisic, Viktor Smanykó, Conny Vrieling, Rok Satler, Inna Meyer, Charles Becciolini, Susanne Bucher, Colin Simonson, Peter M. Fehr, Natalie Gabriel, Robert Maráz, Dimitri Sarlos, Konstantin J. Dedes, Cornelia Leo, Gilles Berclaz, Hisham Fansa, Christopher Hager, Klaus Reisenberger, Ákos Sávolt, Christian F. Singer, Roland Reitsamer, Jelena Winkler, Giang Thanh Lam Lam, Mathias K. Fehr, Tatiana Naydina, Magdalena Kohlik, Karine Clerc, Valerijus Ostapenko, Florian Fitzal, Martin Heidinger, Nadia Maggi, Alexandra Schulz, Pagona Markellou, Loïc Lelièvre, Daniel Egle, Jörg Heil, Michael Knauer, Christoph Tausch. Trends in neoadjuvant systemic therapy rates in Europe: Pre-planned substudy of TAXIS (OPBC-03, SAKK 23/16, IBCSG 57-18, ABCSG-53, GBG 101) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-14-08.

PURPOSE To assess the efficacy and safety of darolutamide maintenance after successful taxane chemotherapy in patients with metastatic castration-resistant prostate cancer (mCRPC). PATIENTS AND METHODS Swiss Group for Clinical Cancer Research (SAKK) 08/16 is a randomized phase II study. Patients with mCRPC who received prior androgen-receptor pathway inhibitors (ARPIs) and subsequently had nonprogressive disease on a taxane were randomly assigned to darolutamide 600 mg twice a day or placebo twice a day. The primary end point was radiographic progression-free survival (rPFS) at 12 weeks. Secondary end points were rPFS, event-free survival, overall survival (OS), prostate-specific antigen (PSA) 50% response rate, and adverse events. RESULTS Overall, 92 patients were recruited by 26 centers. Prior taxane was docetaxel in 93% and cabazitaxel in 7%. Prior ARPI was abiraterone in 60%, enzalutamide in 31%, and both in 9%. rPFS at 12 weeks was significantly improved with darolutamide (64.7% v 52.2%; P = .127). Median rPFS on darolutamide was 5.5 versus 4.5 months on placebo (hazard ratio [HR], 0.54; 95% CI, 0.32 to 0.91; P = .017), and median event-free survival was 5.4 versus 2.9 months (HR, 0.46; 95% CI, 0.29 to 0.73; P = .001). PSA 50% response rate was improved (22% v 4%; P = .014). Median OS for darolutamide was 24 versus 21.3 months for placebo (HR, 0.62; 95% CI, 0.3 to 1.26; P = .181). Treatment-related adverse events were similar in both arms. CONCLUSION SAKK 08/16 met its primary end point, showing that switch maintenance with darolutamide after prior taxane chemotherapy and at least one ARPI resulted in a statistically significant but clinically modest rPFS prolongation with good tolerability. The median OS with darolutamide maintenance appears promising. Should these findings be confirmed in a larger trial, maintenance treatment could be a novel strategy in managing patients with mCRPC, especially those who responded well to prior ARPI.

OBJECTIVE Surgical treatment of locally advanced non-small cell lung cancer including single or multilevel N2 remains a matter of debate. Several trials demonstrate that selected patients benefit from surgery if R0 resection is achieved. We aimed to assess resectability and outcome of patients with locally advanced clinical T3/T4 (American Joint Committee on Cancer 8th edition) tumors after induction treatment followed by surgery in a pooled analysis of 3 prospective multicenter trials. METHODS A total of 197 patients with T3/T4 non-small cell lung cancer of 368 patients with stage III non-small cell lung cancer enrolled in the Swiss Group for Clinical Cancer Research 16/96, 16/00, 16/01 trials were treated with induction chemotherapy or chemoradiation therapy followed by surgery, including extended resections. Univariable and multivariable analyses were applied for analysis of outcome parameters. RESULTS Patients' median age was 60 years, and 67% were male. A total of 38 of 197 patients were not resected for technical (81%) or medical (19%) reasons. A total of 159 resections including 36 extended resections were performed with an 80% R0 and 13.2% pathological complete response rate. The 30- and 90-day mortality were 3% and 7%, respectively, without a difference for extended resections. Morbidity was 32% with the majority (70%) of minor grading complications. The 3-, 5-, and 10-year overall survivals for extended resections were 61% (95% confidence interval, 43-75), 44% (95% confidence interval, 27-59), and 29.5% (95% confidence interval, 13-48), respectively. R0 resection was associated with improved overall survival (hazard ratio, 0.41; P

Aim We developed tailored axillary surgery (TAS) to reduce the axillary tumor volume in patients with clinically node-positive breast cancer to the point where radiotherapy can control it. The aim of this study was to quantify the extent of tumor load reduction achieved by TAS. Methods International multicenter prospective study embedded in a randomized trial. TAS is a novel pragmatic concept for axillary surgery de-escalation that combines palpation-guided removal of suspicious nodes with the sentinel procedure and, optionally, imaging-guided localization. Pre-specified study endpoints quantified surgical extent and reduction of tumor load. Results A total of 296 patients were included at 28 sites in four European countries, 125 (42.2%) of whom underwent neoadjuvant chemotherapy (NACT) and 71 (24.0%) achieved nodal pathologic complete response. Axillary metastases were detectable only by imaging in 145 (49.0%) patients. They were palpable in 151 (51.0%) patients, of whom 63 underwent NACT and 21 had residual palpable disease after NACT. TAS removed the biopsied and clipped node in 279 (94.3%) patients. In 225 patients with nodal disease at the time of surgery, TAS removed a median of five (IQR 3–7) nodes, two (IQR 1–4) of which were positive. Of these 225 patients, 100 underwent ALND after TAS, which removed a median of 14 (IQR 10–17) additional nodes and revealed additional positive nodes in 70/100 (70%) of patients. False-negative rate of TAS in patients who underwent subsequent ALND was 2.6%. Conclusions TAS selectively reduced the tumor load in the axilla and remained much less radical than ALND., Highlights • Tailored axillary surgery is a novel concept for clinically node-positive breast cancer • Tailored axillary surgery selectively removes positive lymph nodes • Tailored axillary surgery is much less radical than axillary dissection • Tailored axillary surgery removes the clipped node in the vast majority of patients

Background Salvage radiotherapy (SRT) is utilized for biochemical progression of prostate cancer after radical prostatectomy (RP). Objective To report the outcomes of the SAKK 09/10 trial comparing conventional and dose-intensified SRT. Design, setting, and participants SAKK 09/10 was a randomized, multicenter, phase 3 trial that recruited men with biochemical progression after RP. Intervention Patients were randomly assigned to conventional-dose (64 Gy) or dose-intensified SRT (70 Gy) to the prostate bed without hormonal therapy. Outcome measurements and statistical analysis The primary endpoint was freedom from biochemical progression (FFBP). Secondary endpoints included clinical progression-free survival (PFS), time to hormonal treatment, overall survival (OS), acute and late toxicity (Common Terminology Criteria for Adverse Events v4.0), and quality of life (QoL). Results and limitations Between February 2011 and April 2014, 350 patients were randomly assigned to 64 Gy (n = 175) or 70 Gy (n = 175). Median prostate-specific antigen at randomization was 0.3 ng/ml. After median follow-up of 6.2 yr, the median FFBP was 8.2 yr in the 64 Gy arm and 7.6 in the 70 Gy arm (log-rank p = 0.4), with a hazard ratio of 1.14 (95% confidence interval 0.82–1.60). The 6-year FFBP rates were 62% and 61%, respectively. No significant differences in clinical PFS, time to hormonal treatment, or OS were observed. Late grade 2 and 3 genitourinary toxicity was observed in 35 (21%) and 13 (7.9%) patients in the 64 Gy arm, and 46 (26%) and seven (4%) in the 70 Gy arm, respectively (p = 0.8). Late grade 2 and 3 gastrointestinal toxicity was observed in 12 (7.3%) and seven patients (4.2%) in the 64 Gy arm, and 35 (20%) and four (2.3%) in the 70 Gy arm, respectively (p = 0.009). There were no significant differences in QoL. Conclusions Conventional-dose SRT to the prostate bed is sufficient in patients with early biochemical progression of prostate cancer after RP. Patient summary The optimal radiation therapy dose for patients who have increased tumor markers after surgery for prostate cancer is unclear. We found that administering a higher dose only increased the gastrointestinal side effects without providing any benefits to the patient. This clinical trial is registered on ClinicalTrials.gov as NCT01272050.

Monitoring population salt intake is operationally and economically challenging. We explored whether a questionnaire assessment and a prediction of Na intake from spot-urine could replace or complement the recommended measurement of Na in 24-h urine (24-h U).Compare the agreement of a Na-specific food record checklist (FRCL) and a late-afternoon spot-urine measurement (PM-spot) with 24-h U measurement in estimating Na intake at group level. Each participant's use of these methods extended over 3 d. Agreement was assessed using mean (95 % CI) differences, linear regression models and Bland-Altman plots.The validation study was part of a 1-year workplace intervention trial to lower salt intake in Switzerland.Seventy women and 71 men, aged 21-61 years, completed three FRCL, and acceptable PM-spot and 24-h U samples at baseline (April-October 2015).Mean Na intake estimates varied slightly across methods (3·5-3·9 g/d). Mean Na intake differences from 24-h U were 0·2 (95 % CI (0, 0·5)) g/d for FRCL and 0·4 (95 % CI (0·2, 0·6)) g/d for PM-spot. Linear regression models and Bland-Altmann plots more clearly depicted differences by sex and discretionary salt use.Although 24-h U remains the best reference method for monitoring Na intake at the population level, PM-spot and FRCL might be more practical instruments for frequent, periodic Na intake assessments. Population-specific prediction models to estimate 24-h U could be developed and evaluated.

BackgroundPremature trial discontinuation and non-publication of trial results are still major issues negatively affecting reliable evidence generation.ObjectivesTo investigate trial completion and publication rate of cancer trials conducted within the Swiss Group for Clinical Cancer Research (SAKK).DesignCohort study of clinical trials.SettingCohort of interventional cancer trials conducted in Switzerland with accrual closure between 1986 and 2021 identified from the SAKK trial management system.OutcomesPremature trial discontinuation and publication in peer-reviewed journal.ResultsWe included 261 trials; median number of recruited patients was 150.5 (range 1–8028). Most trials (67.0%) were randomised. Overall, 76 of 261 (29.1%) trials were prematurely closed for accrual. The three main reasons for premature closure were insufficient accrual in 28 trials, followed by stopping for futility in 17 or efficacy in 8 trials. We included 240 trials for the publication status (21 excluded, because 8 still in follow-up, for 10 the primary completion date was less than a year ago and for 3 the manuscript was submitted, but to accepted yet). 216 of 240 (90.0%) were published as a full article, 14 were published in other formats, leading to an overall publication rate of 95.8%. The rate of premature discontinuation declined over time, with 34.2%, 27.8% and 23.5% in trials activated before 2000, between 2000 and 2009, and since 2010, respectively. We observed an increasing publication rate in peer-reviewed journals over time: 79.2% (closed before 2000), 95.7% (closed between 2000 and 2009) and 93.2% (closed after 2010).ConclusionInsufficient patient recruitment is still the major reason for premature trial discontinuation. SAKK has continuously improved its quality management of trial conduct over time leading to increased successful trial completion and publication. However, there is still room for improvement to increase the number of trials reaching their target sample size.

Introduction: Chemotherapy is recommended for patients with luminal breast cancer and more than three positive nodes. In addition, recent landmark trials raised the question if the exact number of positive nodes is required to indicate genomic testing. In the neoadjuvant setting, response-driven therapy is increasingly used and may be influenced by surgical staging of the axilla. The present study addressed the role of axillary lymph node dissection (ALND) as decision aid for systemic therapy in a contemporary cohort of patients with clinically node-positive breast cancer in the adjuvant and neoadjuvant setting. Methods: The study was preplanned in the international multicenter phase-III OPBC-03/TAXIS trial (ClinicalTrials.gov Identifier: NCT03513614). The first 500 patients with clinically node-positive breast cancer who were randomized after tailored axillary surgery (TAS) to undergo ALND or axillary radiotherapy (ART) without ALND in the context of extended regional irradiation were included from August 2018 to June 2022. Clinically node-positive breast cancer was defined by confirmed nodal disease at the time of initial diagnosis; in case of neoadjuvant therapy, the finding of residual nodal disease was mandatory for randomization. TAS consisted of removal of palpably suspicious findings and the sentinel nodes with the option of image guidance. In the ART arm, the total number of positive nodes was not known. We analyzed the impact of ALND on rate and type of systemic therapy. Results: A total of 500 patients with a median age of 57 years (IQR: 48-69 years) were included at 44 breast centers from six European countries. Subtype was hormone receptor (HR) positive (+) and human epidermal growth factor receptor 2 (HER2) negative (-) in 393 (80.0%), HR+/HER2+ in 52 (10.6%), HR-/HER2+ in 5 (1.0%) and HR-/HER2- in 34 (6.9%) patients. Of 343 patients (68.6%) who were treated in the adjuvant setting, 297 had HR+/HER2- disease. Of these 297 patients, 145 (48.8%) underwent ART without ALND and 152 (51.2%) underwent ALND after TAS. In the ART arm, the median number of lymph nodes removed was five (IQR 4-8), three (IQR 1-4) of which were positive and in the ALND arm, the number was 19 (IQR 14-26), four (IQR 2-9) of which were positive (p < 0.001). The use of ALND had no significant impact on the rate of patients with HR+/HER2- disease undergoing adjuvant chemotherapy (51.0% in the ART and 57.9% in the ALND arm, p=0.2), and there were no significant differences in type of systemic therapy with the exception of tamoxifen, which was 18.4% with ALND versus 9.0% without (p=0.018). A total of 143 patients (28.6%) underwent neoadjuvant chemotherapy, 13 had neoadjuvant antihormonal treatment and one had neoadjuvant double HER2-blockade without chemotherapy. Of the 143 patients who received neoadjuvant chemotherapy, 71 (49.7%) underwent ART without ALND and 72 (50.3%) underwent ALND. In the ART arm, the median number of lymph nodes removed was four (IQR 3-6), one (IQR 1-3) of which was positive and in the ALND arm, the number was 16 (IQR 12-19), two (IQR 1-5) of which were positive (p < 0.001). The use of ALND in patients after neoadjuvant treatment had no significant impact on the rate of adjuvant systemic therapy (71.8% in the ART and 65.3% in the ALND arm, p=0.4), with no significant differences in type of chemotherapy (e.g., capecitabine: 11.3% vs 12.5%, p=0.8; T-DM1: 11.3% vs. 11.1%, p>0.9) or antihormonal therapy (e.g., aromatase inhibitors: 49.3% vs. 41.7%, p=0.4; tamoxifen: 11.3% vs. 5.6%, p=0.2). Discussion: This study showed that although ALND significantly increased the number of positive nodes removed in the adjuvant and neoadjuvant setting, it had no relevant impact on rate and type of adjuvant systemic therapy. Citation Format: Walter P. Weber, Zoltan Matrai, Stefanie Hayoz, Christoph Tausch, Guido Henke, Daniel R. Zwahlen, Günther Gruber, Frank Zimmermann, Thomas Ruhstaller, Simone Muenst, Markus Ackerknecht, Sherko Küemmel, Vesna Bjelic-Radisic, Viktor Smanykó, Conny Vrieling, Rok Satler, Inna Meyer, Charles Becciolini, Susanne Bucher, Colin Simonson, Peter M. Fehr, Natalie Gabriel, Robert Maráz, Dimitri Sarlos, Konstantin J. Dedes, Cornelia Leo, Gilles Berclaz, Hisham Fansa, Christopher Hager, Klaus Reisenberger, Ákos Sávolt, Christian F. Singer, Roland Reitsamer, Jelena Winkler, Giang Thanh Lam Lam, Mathias K. Fehr, Tatiana Naydina, Magdalena Kohlik, Karine Clerc, Valerijus Ostapenko, Florian Fitzal, Martin Heidinger, Nadia Maggi, Alexandra Schulz, Pagona Markellou, Loïc Lelièvre, Daniel Egle, Jörg Heil, Michael Knauer, Christian Kurzeder. PD15-11 Axillary dissection to determine nodal burden to inform systemic therapy recommendations in patients with clinically node-positive breast cancer: Pre-planned substudy of TAXIS (OPBC-03, SAKK 23/16, IBCSG 57-18, ABCSG-53, GBG 101) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD15-11.

Purpose: These are the final results of a national registry on cancer patients with COVID-19 in Switzerland. Methods: We collected data on symptomatic COVID-19-infected cancer patients from 23 Swiss sites over a one-year period starting on 1 March 2020. The main objective was to assess the outcome (i.e., mortality, rate of hospitalization, ICU admission) of COVID-19 infection in cancer patients; the main secondary objective was to define prognostic factors. Results: From 455 patients included, 205 patients (45%) had non-curative disease, 241 patients (53%) were hospitalized for COVID-19, 213 (47%) required oxygen, 43 (9%) invasive ventilation and 62 (14%) were admitted to the ICU. Death from COVID-19 infection occurred in 98 patients, resulting in a mortality rate of 21.5%. Age ≥65 years versus

BACKGROUND VPM1002BC is a genetically modified Mycobacterium bovis bacillus Calmette-Guérin (BCG) strain with potentially improved immunogenicity and attenuation. OBJECTIVE To report on the efficacy, safety, tolerability and quality of life of intravesical VPM1002BC for the treatment of non-muscle-invasive bladder cancer (NMIBC) recurrence after conventional BCG therapy. DESIGN, SETTING, AND PARTICIPANTS We designed a phase 1/2 single-arm trial (NCT02371447). Patients with recurrent NMIBC after BCG induction ± BCG maintenance therapy and intermediate to high risk for cancer progression were eligible. INTERVENTION Patients were scheduled for standard treatment of six weekly instillations with VPM1002BC followed by maintenance for 1 yr. Treatment was stopped in cases of recurrence. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary endpoint was defined as the recurrence-free rate (RFR) in the bladder 60 wk after trial registration. The sample size was calculated based on the assumption that ≥30% of the patients would be without recurrence at 60 wk after registration. RESULTS AND LIMITATIONS After exclusion of two ineligible patients, 40 patients remained in the full analysis set. All treated tumours were of high grade and 27 patients (67.5%) presented with carcinoma in situ. The recurrence-free rate in the bladder at 60 wk after trial registration was 49.3% (95% confidence interval [CI] 32.1-64.4%) and remained at 47.4% (95% CI 30.4-62.6%] at 2 yr and 43.7% (95% CI 26.9-59.4%) at 3 yr after trial registration. At the same time, progression to muscle-invasive disease had occurred in three patients and metastatic disease in four patients. Treatment-related grade 1, 2, and 3 adverse events (AEs) were observed in 14.3%, 54.8%, and 4.8% of the patients, respectively. No grade ≥4 AEs occurred. Two of the 42 patients did not tolerate five or more instillations during induction. Limitations include the single-arm trial design and the low number of patients for subgroup analysis. CONCLUSIONS At 1 yr after treatment start, almost half of the patients remained recurrence-free after therapy with VPM100BC. The primary endpoint of the study was met and the therapy is safe and well tolerated. PATIENT SUMMARY We conducted a trial of VPM100BC, a genetically modified bacillus Calmette-Guérin (BCG) strain for treatment of bladder cancer not invading the bladder muscle. At 1 year after the start of treatment, almost half of the patients with a recurrence after previous conventional BCG were free from non-muscle-invasive bladder cancer (NMIBC). The results are encouraging and VPM1002BC merits further evaluation in randomised studies for patients with NMIBC.

The relapse of follicular lymphoma (FL) within 24 months (POD24) of chemoimmunotherapy has been associated with poor survival. We analyzed a pooled dataset of three randomized trials including FL patients with advanced disease, conducted by the Swiss Group for Clinical Cancer Research (SAKK). Overall, POD24 was observed in 27% of 318 patients, but rate variance among studies suggested that the rituximab schedule might affect POD24 rate. POD24 was associated with lower 10-year overall survival rates than in the reference group (69% vs. 77%; hazard ratio, 3·12; 95% confidence interval, 1·73-5·65). POD24 retains its prognostic validity in patients treated without chemotherapy and may represent a useful end-point for future studies.

Several functional parameters from baseline (18)F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography have been proposed as promising biomarkers of treatment efficacy in diffuse large B-cell lymphoma (DLBCL). We tested their ability to predict outcome in 2 cohorts of DLBCL patients receiving conventional immunochemotherapy (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone [R-CHOP] regimen), either every 14 (R-CHOP14) or 21 days (R-CHOP21). Baseline PET analysis was performed in 141 patients with DLBCL treated with R-CHOP14 in the prospective SAKK38/07 study (NCT00544219) of the Swiss Group for Clinical Cancer Research (testing set). Reproducibility was examined in a validation set of 113 patients treated with R-CHOP21. In the SAKK38/07 cohort, progression-free survival (PFS) at 5 years was 83% for patients with low metabolic tumor volume (MTV) and 59% for those with high MTV (hazard ratio [HR], 3.4; 95% confidence interval [CI], 1.6-7.0; P = .0005), whereas overall survival (OS) was 91% and 64%, respectively (HR, 4.4; 95% CI, 1.9-10; P = .0001). MTV was the most powerful predictor of outcome also in the validation set. Elevated metabolic heterogeneity (MH) significantly predicted poorer outcomes in the subgroups of patients with elevated MTV. A model integrating MTV and MH identified high-risk patients with shorter PFS (testing set: HR, 5.6; 95% CI, 1.8-17; P < .0001; validation set: HR, 5.6; 95% CI, 1.7-18; P = .0002) and shorter OS (testing set: HR, 9.5; 95% CI, 1.7-52; P < .0001; validation set: HR, 7.6; 95% CI, 2.0-28; P = .0003). This finding was confirmed by an unsupervised regression tree analysis indicating that prognostic models based on MTV and MH may allow early identification of refractory patients who might benefit from treatment intensification. This trial was registered at www.clinicaltrials.gov as #NCT00544219.

4515 Background: SAKK 06/17 investigated the addition of perioperative immunotherapy with the anti-PD-L1 antibody durvalumab (Durva) in the multimodality treatment of resectable MIUC. While most similar trials had a primary endpoint of pathological complete remission rate, this study evaluated the clinically more relevant primary endpoint of event-free survival (EFS) at 2 years (yrs). Methods: SAKK 06/17 was an open-label, single-arm phase II study including 61 cisplatin-fit patients (pts) with stage cT2-T4a cN0-1 operable MIUC. Pts received four cycles of neoadjuvant Cis/Gem q3w in combination with 4 cycles Durva 1500mg q3w followed by complete resection. Adjuvant Durva 1500mg q4w was given for 10 cycles or a maximum of 40 weeks. The primary endpoint was EFS at 2 yrs after neoadjuvant trial treatment (NAT) start. An event was defined as progression during NAT, appearance of metastases, locoregional recurrence after surgery or death from any cause. 58 pts were needed based on one-sided type I error 10% and power 80% for H1 EFS at 2 yrs ≥ 65% compared to H0 EFS at 2 yrs ≤ 50%. Secondary endpoints included pathological response, recurrence free survival after R0 resection (RFS), overall survival (OS) and safety. We report the primary analysis of the full analysis set (FAS, received at least one dose of Durva). Results: 61 pts were included between July 2018 and September 2019 at 12 sites. Median follow up is 28.1 months (95%CI 27.8-28.4). FAS consisted of 58 pts (79% male, median age 68 yrs) with bladder cancer (95%) or upper urinary tract/urethral cancer (5%). Clinical T2, T3, T4 stage was present at diagnosis in 69%, 21%, 10%, respectively, and 17% had cN1. Resection was performed in 53 pts (91%; 4 refused, 1 unresectable) with R0 resection in 52 pts (98%). 48 (91%) of resected pts started adjuvant Durva and 32 (67%) completed it. Pathological response < ypT2 ypN0 was achieved in 32 pts (18 pts ypT0 and 14 pts ypT1/a/is), corresponding to 60% of resected pts and 55% of the FAS. EFS at 2 yrs was overall 76.1% (one-sided 90% CI (lower bound): 67.6%; 95% CI 62.3% - 85.3%), for ypT1/a/is 92.9% and for ypT0 100%. RFS at 2 yrs after R0 resection (N=52) was 83.5% (95% CI 69.6% - 91.4%) and OS at 2 yrs for the FAS population was 87.3% (95% CI 73.8% - 94.1%). Grade 1, 2, 3, 4 adverse events attributed to Durva during overall treatment were 14%, 35%, 19%, 7%, respectively. Conclusions: The addition of perioperative Durvalumab to the standard of care for pts with resectable MIUC results in a high EFS, RFS and OS at 2 yrs, especially for pts with downstaging to

Purpose Our aim is to describe the role of immune checkpoint inhibitors (ICI) in clinical practice by providing the patient and tumor characteristics as well as survival and toxicity rates by sex. Methods We used electronic health records to identify patients treated at the Cancer Center of the University Hospital Bern, Switzerland between January 1, 2017 and June 16, 2021. Results We identified 5109 patients, 689 of whom (13.5%) received at least one dose of ICI. The fraction of patients who were prescribed ICI increased from 8.6% in 2017 to 22.9% in 2021. ICI represented 13.2% of the anticancer treatments in 2017 and increased to 28.2% in 2021. The majority of patients were male (68.7%), who were older than the female patients (median age 67 vs. 61 years). Over time, adjuvant and first line treatments increased for both sexes. Lung cancer and melanoma were the most common cancer types in males and females. The incidence of irAEs was higher among females (38.4% vs. 28.1%) and lead more often to treatment discontination in females than in males (21.1% vs. 16.8%). Independent of sex, the occurrence of irAEs was associated with greater median overall survival (OS, not reached vs. 1.1 years). Female patients had a longer median OS than males (1.9 vs. 1.5 years). Conclusions ICI play an increasingly important role in oncology. irAEs are more frequent in female patients and are associated with a longer OS. More research is needed to understand the association between patient sex and toxicity and survival.

To evaluate the results of the radiation therapy (RT) quality assurance (QA) program of the phase 3 randomized SAKK 09/10 trial in patients with biochemically recurrent prostate cancer after prostatectomy.Within the Schweizerische Arbeitsgemeinschaft für Klinische Krebsforschung (SAKK) 09/10 trial testing 64-Gy versus 70-Gy salvage RT, a central collection of treatment plans was performed and thoroughly reviewed by a dedicated medical physicist and radiation oncologist. Adherence to the treatment protocol and specifically to the European Organization for the Research and Treatment of Cancer (EORTC) guidelines for target volume definition (classified as deviation observed yes vs no) and its potential correlation with acute and late toxicity (Common Terminology Criteria for Adverse Events version 4.0) and freedom from biochemical progression (FFBP) were investigated.The treatment plans for 344 patients treated between February 2011 and April 2014 depicted important deviations from the EORTC guidelines and the recommendations per trial protocol. For example, in up to half of the cases, the delineated structures deviated from the protocol (eg, prostate bed in 48.8%, rectal wall [RW] in 41%). In addition, variations in clinical target volume (CTV) and planning target volume (PTV) occurred frequently (eg, CTV and PTV deviations in up to 42.4% and 25.9%, respectively). The detected deviations showed a significant association with a lower risk of grade ≥2 gastrointestinal acute toxicity when the CTV did not overlap the RW versus when the CTV overlapped the RW (odds ratio [OR], 0.43; 95% confidence interval [CI], 0.22-0.85; P = .014), and a higher rate of grade ≥2 late genitourinary (GU) toxicity when the CTV overlapped the RW (OR, 2.58; 95% CI, 1.17-5.72; P = .019). A marginally significant lower risk of grade ≥2 late GU toxicity was observed when the prostate bed did not overlap versus did overlap the RW (OR, 0.51; 95% CI, 0.25-1.03; P = .06). In addition, a marginally significant decrease in FFBP was observed in patients with PTV not including surgical clips as potential markers of the limits of the prostate bed (hazard ratio, 1.44; 95% CI, 0.96-2.17; P = .07).Despite a thorough QA program, the central review of a phase 3 trial showed limited adherence to treatment protocol recommendations, which was associated with a higher risk of toxicity by means of acute or late gastrointestinal or GU toxicity and showed a trend toward worse FFBP. Data from this QA review might help to refine future QA programs and prostate bed delineation guidelines.

This phase 1 study evaluated safety, tolerability, and preliminary efficacy of obinutuzumab in combination with venetoclax in patients with previously untreated grade 1-3a follicular lymphoma in need of systemic therapy. Two DLs of venetoclax were evaluated with an expansion cohort at the recommended phase 2 dose. Twenty-five patients were enrolled. The recommended phase 2 dose was venetoclax 800 mg OD continuously for 6 cycles starting on day 2 of cycle 1, with obinutuzumab 1000 mg on days 1, 8, and 15 of cycle 1 and on day 1 of cycles 2 to 6, followed by obinutuzumab maintenance every 2 months for 2 years. Only 1 patient had a DLT consisting of grade 4 thrombocytopenia after the first obinutuzumab infusion. Neutropenia was the most common adverse event of grade ≥3 at least possibly attributed to study treatment. Twenty-four patients were evaluable for response after cycle 6 by computed tomography (CT) and 19 by positron emission tomography/CT (PET/CT): overall and complete response rates were 87.5% (95% CI, 67.6% to 97.3%) and 25% (95% CI, 9.8% to 46.7%) in the CT-evaluated patients and 84.2% (95% CI, 60.4% to 96.6%) and 68.4% (95% CI, 43.4% to 87.4%), respectively, in the PET/CT-evaluated patients. One-year progression-free survival was 77.8% (95% CI, 54.6% to 90.1%) and 79% (95% CI, 47.9% to 92.7%) for CT and PET/CT-evaluable patients, respectively, whereas progression-free survival at 30 months was 73.2% (95% CI, 49.8%, 87.0%) as assessed by CT and 79.0% (95% CI, 47.9%, 92.7%) by PET/CT. Despite the activity observed, our results do not support further development of the combination in this patient population. This trial was registered at www.clinicaltrials.gov as #NCT02877550.

BACKGROUND Recurrent oesophageal cancer after the initial curative multimodality treatment is a disease condition with a poor prognosis. There is limited evidence on recurrence patterns and on the optimal therapeutic approach. METHODS We analysed the pattern of disease recurrence and subsequent therapies in patients with recurrent oesophageal cancer based on prospectively collected data within a predefined subproject of the randomised phase 3 trial Swiss Group for Clinical Cancer Research (SAKK) 75/08. RESULTS Among 300 patients included in the SAKK 75/08 trial, tumour recurrence was observed in 103 patients with a median follow-up of 5.8 years. Locoregional recurrence only was found in 26.2% of the patients, 21.4% of patients had both distant and locoregional recurrence and 52.4% of patients had distant recurrence only. Fifty-nine patients (58%) received at least one line of systemic therapy at recurrence, most commonly oxaliplatin-based combination therapies for adenocarcinoma and single-agent chemotherapy for squamous cell carcinoma. Local therapies, most commonly palliative radiotherapy, were used in 49 patients (48%). Six patients underwent a second curative resection or radiochemotherapy. We found no significant overall survival difference for isolated locoregional recurrence versus distant recurrence (15.1 versus 8.7 months, p = 0.167). In a multivariable Cox regression model, time from oesophagectomy to recurrence and the number of recurrence sites as well as the use of systemic therapy or a second curative local therapy significantly correlated with overall survival. CONCLUSIONS Recurrent oesophageal cancer remains a disease with a poor prognosis and requires multidisciplinary management. A second curative approach for localised disease recurrence may be an option for highly selected patients.

353 Background: Pre-clinical and retrospective clinical data support an interaction of metformin (MET) and radiotherapy. Thus, MET may represent a cost-effective means to improve radiotherapy outcomes. We sought to investigate whether MET increases time to progression (TTP) when combined with salvage radiation therapy (SRT) in men with recurrent prostate cancer after radical prostatectomy (RP). Methods: Non-diabetic men with biochemical recurrence after RP were enrolled into an open label, randomized, phase 2 study in 17 hospitals in Switzerland, France, and Germany. The randomization (1:1) was stratified by Gleason score ( 0.5 vs ≤ 0.5 ng/mL), ADT use, and evidence of local recurrence. Following randomization, patients received either prostate bed SRT (70Gy) or prostate bed SRT (70Gy) + MET. MET 850mg PO QD was given for 4 weeks before SRT, then 850mg PO QD for 48 weeks. The primary endpoint was TTP. Secondary endpoints were progression-free survival, undetectable PSA under normal testosterone levels, 50% PSA response, clinical progression-free survival, time to further systemic therapy, prostate cancer-specific survival, overall survival, and adverse events (AE). The trial design was powered for a HR 0.65 with planned enrollment of 170 patients. The trial was prematurely closed by the sponsor due to financial reasons. Data is reported after patients reached a minimum follow-up of 12 months after SRT and corresponds to the final analysis. Results: A total of 111 patients were randomized (106 evaluable) between 10/2017 and 11/2020. The median PSA at randomization was 0.3 ng/mL (range, 0.03-1.5 ng/mL), 19 patients (17.9%) had Gleason ≥8, 54 (50.9%) pT3 disease, and 50 (47.2%) positive surgical margins. Twenty-four patients (22.6%) used short-term ADT. Trial arms were well balanced. At a median follow-up of 27.1 months (95% CI: 26.7-27.8), a total of 16 progression events occurred. The median TTP was not reached in either treatment arm. The hazard ratio adjusted by stratification factors was 1.25 (95% CI: 0.40-3.94; one-sided 80% CI: 2.05; log-rank p=0.62). Two-year TTP was 89% (95% CI: 76%-96%) in the SRT arm vs 82% (95% CI: 67%-91%) in the SRT + MET arm. No statistically significant differences were found for the secondary endpoints. Most common AE during treatment was grade 1-2 diarrhea (24.1% SRT vs 54.6% SRT + MET). Grade 2 and 3 AE (gastrointestinal and/or urinary) were 25.9% and 3.7% with SRT vs 34.5% and 7.3% with SRT + MET (p=0.41 and p=0.68), respectively. Conclusions: Adding MET to SRT did not result in a significant improvement in TTP in non-diabetic men with recurrent prostate cancer post-RP. Because of early trial closure and fewer than expected events, the trial may have been underpowered for this endpoint. Additional correlative studies will be pursued. Clinical trial information: NCT02945813 .

Accurate estimation of the progression risk after first-line therapy represents an unmet clinical need in diffuse large B-cell lymphoma (DLBCL). Baseline (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) parameters, together with genetic analysis of lymphoma cells, could refine the prediction of treatment failure. We evaluated the combined impact of mutation profiling and baseline PET/CT functional parameters on the outcome of DLBCL patients treated with the R-CHOP14 regimen in the SAKK38/07 clinical trial (NCT00544219). The concomitant presence of mutated SOCS1 with wild-type CREBBP and EP300 defined a group of patients with a favorable prognosis and 2-year progression-free survival (PFS) of 100%. Using an unsupervised recursive partitioning approach, we generated a classification-tree algorithm that predicts treatment outcomes. Patients with elevated metabolic tumor volume (MTV) and high metabolic heterogeneity (MH) (15%) had the highest risk of relapse. Patients with low MTV and favorable mutational profile (9%) had the lowest risk, while the remaining patients constituted the intermediate-risk group (76%). The resulting model stratified patients among three groups with 2-year PFS of 100%, 82%, and 42%, respectively (p < 0.001).

Functional parameters from positron emission tomography (PET) seem promising biomarkers in various lymphoma subtypes. This study investigated the prognostic value of PET radiomics in diffuse large B-cell lymphoma (DLBCL) patients treated with R-CHOP given either every 14 (testing set) or 21 days (validation set). Using the PyRadiomics Python package, 107 radiomics features were extracted from baseline PET scans of 133 patients enrolled in the Swiss Group for Clinical Cancer Research 38/07 prospective clinical trial (SAKK 38/07) [ClinicalTrial.gov identifier: NCT00544219]. The international prognostic indices, the main clinical parameters and standard PET metrics, together with 52 radiomics uncorrelated features (selected using the Spearman correlation test) were included in a least absolute shrinkage and selection operator (LASSO) Cox regression to assess their impact on progression-free (PFS), cause-specific (CSS), and overall survival (OS). A linear combination of the resulting parameters generated a prognostic radiomics score (RS) whose area under the curve (AUC) was calculated by receiver operating characteristic analysis. The RS efficacy was validated in an independent cohort of 107 DLBCL patients. LASSO Cox regression identified four radiomics features predicting PFS in SAKK 38/07. The derived RS showed a significant capability to foresee PFS in both testing (AUC, 0.709; p

The SAKK 35/10 phase 2 trial, developed by the Swiss Group for Clinical Cancer Research and the Nordic Lymphoma Group, compared the activity of rituximab vs rituximab plus lenalidomide in untreated follicular lymphoma patients in need of systemic therapy. Patients were randomized to rituximab (375 mg/m2 IV on day 1 of weeks 1-4 and repeated during weeks 12-15 in responding patients) or rituximab (same schedule) in combination with lenalidomide (15 mg orally daily for 18 weeks). Primary end point was complete response (CR)/unconfirmed CR (CRu) rate at 6 months. In total, 77 patients were allocated to rituximab monotherapy and 77 to the combination (47% poor-risk Follicular Lymphoma International Prognostic Index score in each arm). A significantly higher CR/CRu rate at 6 months was documented in the combination arm by the investigators (36%; 95% confidence interval [CI], 26%-48% vs 25%; 95% CI, 16%-36%) and confirmed by an independent response review of computed tomography scans only (61%; 95% CI, 49%-72% vs 36%; 95% CI, 26%-48%). After a median follow-up of 4 years, significantly higher 30-month CR/CRu rates and longer progression-free survival (PFS) and time to next treatment (TTNT) were observed for the combination. Overall survival (OS) rates were similar in both arms (≥90%). Toxicity grade ≥3 was more common in the combination arm (56% vs 22% of patients), mainly represented by neutropenia (23% vs 7%). Addition of lenalidomide to rituximab significantly improved CR/CRu rates, PFS, and TTNT, with expected higher, but manageable toxicity. The excellent OS in both arms suggests that chemotherapy-free strategies should be further explored. This trial was registered at www.clinicaltrials.gov as #NCT01307605.

Background Monthly Denosumab (DN) has shown superiority over zoledronic acid (ZA) in delaying skeletal related events. Randomized trials have shown that ZA given every 12 weeks (q12w) is non-inferior to ZA given every 4 weeks (q4w). The primary endpoint of the REDUSE-trial is non-inferiority for SSE for DN q12w versus q4w. Here we present early data for hypocalcemia (HC), a secondary endpoint. Methods Patients with bone metastasis from breast cancer (BC) not pretreated with DN or Bisphosphonates were randomized 1:1 to receive DN q4w (Arm A) versus q12w (Arm B) after a 3-month induction phase with q4w therapy for both arms. All patients received vitamin D 400 U (VitD) and calcium (Ca) 500 mg daily. Measurement of albumin-corrected serum-Ca was mandatory before each DN injection (HC defined as Results 351 BC-patients are currently included (177 in Arm A, 174 in Arm B). HC was the most common side effect with a rate of 20% in the first 16 weeks (during the induction phase with DN q4w for both Arms) and 19% afterwards (combined for Arms A and B). After week 16 HC-prevalence differed between the two arms: while HC was present in 25% in Arm A (q4w), the rate was only 12% in Arm B (q12w). Grade 3 HC (i.e. corrected Ca 1.5 - 1.74 mmol/l or hospitalisation indicated) was rare (0.3%), no grade 4 HC occurred. After 1 year of treatment, the rate of HC compared to the induction phase had decreased in Arm B but not in Arm A (A: 25%, B: 12%). Since HC improved in more patients in Arm B than in Arm A whereas it worsened in more patients in Arm A than in Arm B, a remarkable difference for HC resulted between the two arms. Rates of hypocalcemia and change of severity after week 16* Arm A (N = 177)Arm B (N = 174)Rates of hypocalcemian (%)n (%)Patients with hypocalcemia at any time49 (28%)46 (26%)Patients with hypocalcemia after week 16*44 (25%)21 (12%) Change in hypocalcemia grade after week 16*for the 49 patients with hypocalcemiafor the 46 patients with hypocalcemiaWorsening25 (51%)8 (17%)Stable10 (20%)9 (20%)Improving14 (29%)29 (63%) *week 16: i.e. the time where the schedules of DN begin to differ between Arm A and Arm BArm A: DN q4w for weeks 1 - 12 and likewise thereafter / Arm B: DN q4w for weeks 1 - 12 and q12w thereafter Conclusions In our trial up to 20% of all BC patients treated with DN experienced HC in the q4w induction phase despite mandatory supplementation of VitD and Ca. This rate is considerably higher than the numbers reported in the registration trials of DN (where it was 5.5% for BC). After the induction phase, HC is markedly reduced in the q12w arm compared to q4w. This suggests that DN given q12w has a more favorable long-term safety profile in terms of HC compared to DN q4w. Citation Format: Müller A, Templeton AJ, Hayoz S, Hawle H, Hasler-Strub U, Schwitter M, Pestalozzi BC, Pagani O, Bützberger P, Wehrhahn T, Rauch D, Inauen R, Betticher D, Zaman K, Bodmer A, Popescu RA, Rothschild S, Schardt J, Borner M, Fuhrer A, Schär C, Gillessen S, von Moos R, For the Swiss Group for Clinical Cancer Research (SAKK). Incidence of hypocalcemia in patients with metastatic breast cancer under treatment with denosumab: A non-inferiority phase III trial assessing prevention of symptomatic skeletal events (SSE) with denosumab administered every 4 weeks versus every 12 weeks: SAKK 96/12 (REDUSE) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-18-01.

PURPOSE/OBJECTIVE(S) Presalvage PSA is an important prognostic and a predictive factor for salvage radiotherapy (SRT) and androgen deprivation therapy (ADT) post-prostatectomy. GC can independently prognosticate prostate cancer outcomes and may help individualize treatment intervention. Herein, we assessed the role of the GC in patients treated within a contemporary phase 3 trial. MATERIALS/METHODS The SAKK 09/10 trial (NCT01272050) is an open-label, multicenter, randomized phase 3 trial performed in 24 centers in Switzerland, Germany, and Belgium. Patients with biochemical progression (PSA > 0.1 to 2 ng/mL at randomization) were randomized to 64 Gy vs 70 Gy to the prostate bed. No patients received ADT or pelvic nodal radiotherapy. A pre-specified statistical plan was developed to assess the impact of the GC on clinical outcomes. GC score range is 0 to 1, with locked cut points of 0.6 for low, intermediate, and high, respectively. In this sub-analysis, the primary endpoint was freedom from biochemical progression (FFBP) according to PSA at randomization (≤0.5 vs > 0.5, a trial stratification variable). Cox multivariable analysis (MVA) adjusting for age, T-category, Gleason score, persistent PSA after RP, and randomization arm were performed. Secondary endpoints included clinical progression-free survival (CPFS) and time to salvage ADT. RESULTS Of 233 patients with tissue available, 1 was ineligible and 6 failed QC. The remaining 226 were included for analysis with a median follow-up of 6.3 years (IQR 6.0-7.2). High- vs. low/intermediate-GC had an HR of 2.22 (95% CI 1.37-3.58, P = 0.001) for FFBP, 2.29 (95% CI 1.32-3.98, P = 0.003) for CPFS, and 2.99 (95% CI 1.50-5.95, P = 0.002) for use of salvage ADT. In patients with PSA ≤0.5 ng/mL (165/226, 73%), the 5-year FFBP was 74% [95% CI 66-82] for low-intermediate GC compared to 59% [95% CI 43-74] in patients with high-GC. High-GC patients had 5-year FFBP of 13% [95% CI 0-32] when SRT was delivered at PSA > 0.5 ng/mL compared to 59% [95% CI 43-74] when PSA ≤0.5 ng/mL. CONCLUSION In a contemporary phase 3 trial, patients with a high-GC were more than twice as likely than patients with low/intermediate-GC to experience biochemical and clinical progression and receive salvage ADT. High-GC patients who received SRT with PSA > 0.5 ng/mL had nearly 90% risk of recurrence by 5-years post-SRT. This data validates the clinical utility of the GC for tailoring treatment in the salvage setting.

Positron emission computed tomography (PET/CT) in patients with diffuse large B-cell lymphoma (DLBCL) enrolled in a prospective clinical trial were reviewed to test the impact of quantitative parameters from interim PET/CT scans on overall (OS) and progression-free (PFS) survival. We centrally reviewed baseline and interim PET/CT scans of 138 patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone given every 14 days (R-CHOP14) in the SAKK38/07 trial (ClinicalTrial.gov identifier: NCT00544219). Cutoff values for maximum standardized uptake value (SUVmax ), metabolic tumor volume (MTV), total lesion glycolysis (TLG) and metabolic heterogeneity (MH) were defined by receiver operating characteristic analysis. Responses were scored using the Deauville scale (DS). Patients with DS 5 at interim PET/CT (defined by uptake >2 times higher than in normal liver) had worse PFS (P = 0.014) and OS (P < 0.0001). A SUVmax reduction (Δ) greater than 66% was associated with longer PFS (P = 0.0027) and OS (P < 0.0001). Elevated SUVmax , MTV, TLG, and MH at interim PET/CT also identified patients with poorer outcome. At multivariable analysis, ΔSUVmax and baseline MTV appeared independent outcome predictors. A prognostic model integrating ΔSUVmax and baseline MTV discriminated three risk groups with significantly (log-rank test for trend, P < 0.0001) different PFS and OS. Moreover, the integration of MH and clinical prognostic indices could further refine the prediction of OS. PET metrics-derived prognostic models perform better than the international indices alone. Integration of baseline and interim PET metrics identified poor-risk DLBCL patients who might benefit from alternative treatments.

Purpose:Leydig cell tumors are rare but they are the most common nongerm cell testicular tumors. Only limited evidence exists for reliably differentiating between benign and malignant Leydig cell t...

IntroductionThe high prevalence of overweight and obese adults in Switzerland (men: 55.5%; women: 31%) and the development of associated comorbidities requires innovative primary health care interventions. Smartphone applications offer interesting possibilities. However, most are not designed for use in nutritional counselling. Oviva developed an application for dietitians to support overweight or obese clients, online. The aim of the following research was to compare short- and long-term anthropometric effects of a one-year, online, lifestyle intervention by dietitians with overweight or obesity adults.MethodsThe pilot study, conducted in the German-speaking region of Switzerland, started in April 2016 and was completed in May 2018. Initially, 43 overweight and obese individuals were included, 36 completed the study. During this intervention, participants received individualized, remote counselling from dietitians through the application Oviva. Interactions focused on increasing motivation, providing feedback regarding photo-based food logs and education that was aligned with the individual's lifestyle goals. In addition to the primary outcome of weight change, the following anthropometric outcomes were examined: body mass index (BMI), waist circumference and body fat. The study measured changes from baseline at three and twelve months (M0/M3/M12).ResultsOver the course of the study, the median weight loss was 4.9 kg (-21.9–7.5 kg) and 58% of participants achieved a weight loss of ≥ 5%. Additional anthropometric measurements showed the following results (median (min–max)) at timepoints M0/M3/M12: body weight (kg) M0: 83.5 (67.7–105)/M3: 80.3 (64.5–105)/M12: 78.7 (62.8–107.5); BMI (kg/m2): M0:30.2 (26.4–33)/M3: 28.4 (24.3–33.5)/M12: 28.0 (24.1–33.5); waist circumference (cm) M0: 92 (74–112)/M3: 85.9 (73.3–108)/M12: 86.5 (78.5–110.5); and body fat (%) M0: 40.5 (27.8–48.5)/M3: 39.0 (22.2–45.0)/M12: 37.9 (21.3–46.9). A significant improvement was observed in all measurements from M0–M3 and M0–M12. A non-significant trend was observed between M3 and M12 in the measurements, except for waist circumference.DiscussionThese promising results suggest new approaches to support overweight and obese adults in changing their lifestyle through assistance by dietitians in Switzerland. Nevertheless, long-term, randomized control trials are needed to examine its efficacy and cost-effectiveness. Additionally, this type of remote counselling offers greater flexibility for clients who are unable and/or unwilling to engage in face-to-face counselling and thus, also has the potential to increase patient adherence, in order to attain sustained weight loss.