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Objectives: We aimed to develop a novel non-linear statistical model integrating primary tumor features on baseline [18F]-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), molecular subtype, and clinical data for treatment benefit prediction in women with newly diagnosed breast cancer using innovative statistical techniques, as opposed to conventional methodological approaches. Methods: In this single-center retrospective study, we conducted a comprehensive assessment of women newly diagnosed with breast cancer who had undergone a FDG-PET/CT scan for staging prior to treatment. Primary tumor (PT) volume, maximum and mean standardized uptake value (SUVmax and SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured on PET/CT. Clinical data including clinical staging (TNM) but also PT anatomical site, histology, receptor status, proliferation index, and molecular subtype were obtained from the medical records. Overall survival (OS), progression-free survival (PFS), and clinical benefit (CB) were assessed as endpoints. A logistic generalized additive model was chosen as the statistical approach to assess the impact of all listed variables on CB. Results: 70 women with newly diagnosed breast cancer (mean age 63.3 ± 15.4 years) were included. The most common location of breast cancer was the upper outer quadrant (40.0%) in the left breast (52.9%). An invasive ductal adenocarcinoma (88.6%) with a high tumor proliferation index (mean ki-67 expression 35.1 ± 24.5%) and molecular subtype B (51.4%) was by far the most detected breast tumor. Most PTs displayed on hybrid imaging a greater volume (12.8 ± 30.4 cm3) with hypermetabolism (mean ± SD of PT maximum SUVmax, SUVmean, MTV, and TLG, respectively: 8.1 ± 7.2, 4.9 ± 4.4, 12.7 ± 30.4, and 47.4 ± 80.2). Higher PT volume (p < 0.01), SUVmax (p = 0.04), SUVmean (p = 0.03), and MTV (<0.01) significantly compromised CB. A considerable majority of patients survived throu, Peer Reviewed

Objectives: We aimed to assess the predictive value of the total metabolic tumor burden prior to treatment in patients with advanced non-small-cell lung cancer (NSCLC) receiving immune checkpoint inhibitors (ICIs). Methods: Pre-treatment 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography (PET/CT) scans performed in two consecutive years for staging in adult patients with confirmed NSCLC were considered. Volume, maximum/mean standardized uptake value (SUVmax/SUVmean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were assessed per delineated malignant lesion (including primary tumor, regional lymph nodes and distant metastases) in addition to the morphology of the primary tumor and clinical data. Total metabolic tumor burden was captured by totalMTV and totalTLG. Overall survival (OS), progression-free survival (PFS) and clinical benefit (CB) were used as endpoints for response to treatment. Results: A total of 125 NSCLC patients were included. Osseous metastases were the most frequent distant metastases (n = 17), followed by thoracal distant metastases (pulmonal = 14 and pleural = 13). Total metabolic tumor burden prior to treatment was significantly higher in patients treated with ICIs (mean totalMTV ± standard deviation (SD) 72.2 ± 78.7; mean totalTLG ± SD 462.2 ± 538.9) compared to those without ICI treatment (mean totalMTV ± SD 58.1 ± 233.8; mean totalTLG ± SD 290.0 ± 784.2). Among the patients who received ICIs, a solid morphology of the primary tumor on imaging prior to treatment was the strongest outcome predictor for OS (Hazard ratio HR 28.04, p < 0.01), PFS (HR 30.89, p < 0.01) and CB (parameter estimation PE 3.46, p < 0.01), followed by the metabolic features of the primary tumor. Interestingly, total metabolic tumor burden prior to immunotherapy showed a negligible impact on OS (p = 0.04) and PFS (p = 0.01) after treatment given the hazard ratios of 1.00, but also on CB (p = 0.01) given the PE < 0.01. Overall, Peer Reviewed

We aimed to assess the frequency of additional primary malignancies detected incidentally on [18F]fluoro-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) at staging in NSCLC patients. Moreover, their impact on patient management and survival was assessed. Consecutive NSCLC patients with available staging FDG-PET/CT between 2020 and 2021 were retrospectively enrolled. We reported whether further investigations of suspicious findings presumably not related to NSCLC were recommended and performed after FDG-PET/CT. Any additional imaging, surgery or multimodal management was considered as an impact on patient management. Patient survival was defined using overall survival OS and progression-free survival PFS. A total of 125 NSCLC patients were included, while 26 findings in 26 different patients were suspicious for an additional malignancy on FDG-PET/CT at staging. The most frequent anatomical site was the colon. A total of 54.2% of all additional suspicious lesions turned out to be malignant. Almost every malignant finding had an impact on patient management. No significant differences were found between NSCLC patients with suspicious findings versus no suspicious findings with regards to their survival. FDG-PET/CT performed for staging might be a valuable tool to identify additional primary tumors in NSCLC patients. Identification of additional primary tumors might have substantial implications for patient management. An early detection together with interdisciplinary patient management could prevent a worsening of survival compared to patients with NSCLC only., Peer Reviewed

Targeting of the immune system has shown to be a successful therapeutic approach in cancer, with the development of check point inhibitors (ICI) or T-cell engagers (TCE). As immuno-oncology agents modulate the immune system to attack cancer cells and do not act directly on oncogenic vulnerabilities, specific characteristics of these compounds should be taken in consideration during clinical development. In this review we will discuss relevant concepts including limitations of preclinical models, special pharmacologic boundaries, clinical development strategies such as the selection of clinical indication, line of treatment and backbone partner, as well as the endpoints and expected magnitude of benefit required at different stages of the drug development. In addition, future directions for early and late trial designs will be reviewed. Examples from approved drugs or those currently in clinical development will be discussed and options to overcome these limitations will be provided.

The management of prostate cancer is undergoing rapid changes in all disease settings. Novel imaging tools for diagnosis have been introduced, and the treatment of high-risk localized, locally advanced and metastatic disease has changed considerably in recent years. From clinical and health-economic perspectives, a rational and optimal use of the available options is of the utmost importance. While international guidelines list relevant pivotal trials and give recommendations for a variety of clinical scenarios, there is much room for interpretation, and several important questions remain highly debated. The goal of developing a national consensus on the use of these novel diagnostic and therapeutic strategies in order to improve disease management and eventually patient outcomes has prompted a Swiss consensus meeting. Experts from several specialties, including urology, medical oncology, radiation oncology, pathology and nuclear medicine, discussed and voted on questions of the current most important areas of uncertainty, including the staging and treatment of high-risk localized disease, treatment of metastatic hormone-sensitive prostate cancer (mHSPC) and use of new options to treat metastatic castration-resistant prostate cancer (mCRPC).

UNLABELLED Incidental detection of urogenital tumors has increased in recent decades owing to the greater use of ultrasonography and cross-sectional imaging. For patients with low-risk prostate cancer or small renal masses, active surveillance represents a valid treatment option. Similarly, for men with small testicular masses <10 mm, active surveillance has been discussed as an alternative to surgery, although little is known regarding the behavior of small testicular germ cell tumors (GCTs). In the Swiss Austrian German Testicular Cancer Cohort Study we identified 849 patients (546 seminoma, 303 nonseminoma) treated with radical inguinal orchiectomy for GCT with a median tumor diameter of 35 mm. A tumor diameter <10 mm was observed in 25 patients (13 seminoma, 12 nonseminoma). Of these, five patients (20%) presented with primary metastatic disease, all of whom had elevated tumor markers and nonseminomatous GCTs. Two patients (8%) with initially localized disease (1 seminoma, 1 nonseminoma) and without elevated tumor markers experienced relapse at 4 mo (nonseminoma) and 14 mo (seminoma) after orchiectomy, despite the fact that the latter had received adjuvant chemotherapy. These findings highlight the metastatic potential of small testicular GCTs and raise the question of whether active surveillance for small testicular masses is safe. PATIENT SUMMARY This study on testicular cancer assesses the metastatic potential of small testicular germ cell tumors. Men with small testicular masses should be counseled about the malignant potential of small testicular germ cell tumors.

INTRODUCTION Current evidence shows that serum miR-371a-3p can identify disease recurrence in testicular germ cell tumour (TGCT) patients and correlates with tumour load. Despite convincing evidence showing the advantages of including miR-371a-3p testing to complement and overcome the classical serum tumour markers limitations, the successful introduction of a serum miRNA based test into clinical practice has been impeded by a lack of consensus regarding optimal methodologies and lack of a universal protocol and thresholds. Herein, we investigate two quantitative real-time PCR (qRT-PCR) based pipelines in detecting disease recurrence in stage I TGCT patients under active surveillance, and compare the sensitivity and specificity for each method. METHODS Sequential serum samples collected from 33 stage I TGCT patients undergoing active surveillance were analysed for miR-371a-3p via qRT-PCR with and without an amplification step included. RESULTS Using a pre-amplified protocol, all known recurrences were detected via elevated miR-371a-3p expression, while without pre-amplification, we failed to detect recurrence in 3/10 known recurrence patients. For pre-amplified analysis, sensitivity and specificity was 90% and 94.4% respectively. Without amplification, sensitivity dropped to 60%, but exhibited 100% specificity. DISCUSSION We conclude that incorporating pre-amplification increases sensitivity of miR-371a-3p detection, but produces more false positive results. The ideal protocol for quantification of miR-371a-3p still needs to be determined. TGCT patients undergoing active surveillance may benefit from serum miR-371a-3p quantification with earlier detection of recurrences compared to current standard methods. However, larger cross-institutional studies where samples are processed and data is analysed in a standardised manner are required prior to its routine clinical implementation.