Better Oncological Outcomes After Prostate-specific Membrane Antigen Positron Emission Tomography-guided Salvage Radiotherapy Following Prostatectomy.

Background And Objective: Up to 50% of patients with prostate cancer experience prostate-specific antigen (PSA) relapse following primary radical prostatectomy (RP). Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) is increasingly being used for staging after RP owing to its high detection rate. Our aim was to compare outcomes for patients who received salvage radiotherapy (sRT) with versus without PSMA PET guidance.

Lipophilic compounds restore function to neurodevelopmental-associated KCNQ3 mutations.

A major driver of neuronal hyperexcitability is dysfunction of K channels, including voltage-gated KCNQ2/3 channels. Their hyperpolarized midpoint of activation and slow activation and deactivation kinetics produce a current that regulates membrane potential and impedes repetitive firing. Inherited mutations in KCNQ2 and KCNQ3 are linked to a wide spectrum of neurodevelopmental disorders (NDDs), ranging from benign familial neonatal seizures to severe epileptic encephalopathies and autism spectrum disorders.

Are bone targeted agents still useful in times of immunotherapy? The SAKK 80/19 BTA pilot study.

Background: Patients with bone metastases from solid tumors often have additional treatment with bone targeted agents (BTAs) to avoid symptomatic skeletal events (SSEs) such as clinically significant pathological fracture leading toradiation therapy or surgery to the bone, spinal cord compression, or hypercalcemia. The absolute value of BTA treatment in the era of immunotherapy (IO) is unknown.

Methods: Patients with bone metastases treated with immunotherapy within the Alpine Tumor Immunology Registry were compared based on whether they received an additional BTA such as denosumab or zoledronic acid.

Prevention of taxane chemotherapy-induced nail changes and peripheral neuropathy by application of extremity cooling: a prospective single-centre study with intrapatient comparison.

Purpose: Common side effects of taxane chemotherapy are nail toxicity and peripheral neuropathy (CIPN) causing severe impact on the quality of life. Different methods of cryotherapy to prevent these side effects have been tested. We investigated the use of machine-controlled cooling of hands and feet to reduce nail toxicity and CIPN in patients receiving taxane chemotherapy.

Erectile function preservation after salvage radiation therapy for biochemically recurrent prostate cancer after prostatectomy: Five-year results of the SAKK 09/10 randomized phase 3 trial.

Objectives: To evaluate effects of dose intensified salvage radiotherapy (sRT) on erectile function in biochemically recurrent prostate cancer (PC) after radical prostatectomy (RP).

Materials And Methods: Eligible patients had evidence of biochemical failure after RP and a PSA at randomization of ≤ 2 ng/ml. Erectile dysfunction (ED) was investigated as secondary endpoint within the multicentre randomized trial (February 2011 to April 2014) in patients receiving either 64 Gy or 70 Gy sRT.

Efficacy and tolerability of bacillus Calmette-Guérin strain Russia for the treatment of non-muscle-invasive bladder cancer Analysis of a prospective registry.

Introduction: Little is known about the efficacy and tolerability of intravesical bacillus Calmette-Guérin (BCG) strain Russia for treatment of non-muscle-invasive bladder cancer (NMIBC) in a middle-European population.

Methods: A prospective collection of outcomes of 101 BCG-naive patients with urothelial bladder carcinoma was carried out between January 2013 and October 2023 at the University Hospital Basel, Basel, Switzerland. Patients underwent BCG (ONCO-BCG-SIIL, Serum Institute of India, Pune, India) induction and a maximum of three maintenance cycles within one year.

Safety and quality of cystectomy and pelvic lymph node dissection after neoadjuvant durvalumab and cisplatin/gemcitabine.

Objective: To report on the surgical safety and quality of pelvic lymph node dissection (PLND) in patients treated with radical cystectomy (RC) and PLND for muscle-invasive bladder cancer (MIBC) after neoadjuvant chemo-immunotherapy.

Patients And Methods: The Swiss Group for Clinical Cancer Research (SAKK) 06/17 was an open-label single-arm phase II trial including 61 cisplatin-fit patients with clinical stage (c)T2-T4a cN0-1 operable urothelial MIBC or upper urinary tract cancer. Patients received neoadjuvant cisplatin/gemcitabine and durvalumab followed by surgery.

Opportunistic Prostate Cancer Screening with Biparametric Magnetic Resonance Imaging (VISIONING).

Background: This study investigates the use of biparametric magnetic resonance imaging (bpMRI) as primary opportunistic screening for prostate cancer (PCa) without using a prostate-specific antigen (PSA) cut-off.

Objective: The primary endpoint was to assess the efforts and effectiveness of identifying 20 participants with clinically significant prostate cancer (csPCa) using bpMRI.

Design, Setting, And Participants: Biopsy-naïve men aged over 45 yr were included.

TLD-1, a novel liposomal doxorubicin, in patients with advanced solid tumors: Dose escalation and expansion part of a multicenter open-label phase I trial (SAKK 65/16).

Background: TLD-1 is a novel liposomal doxorubicin that compared favorably to conventional doxorubicin liposomal formulations in preclinical models. This phase I first-in-human study aimed to define the maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), safety and preliminary activity of TLD-1 in patients with advanced solid tumors.

Patients And Methods: We recruited patients with advanced solid tumors who failed standard therapy and received up to 3 prior lines of palliative systemic chemotherapy.

Deep inspirational breast hold (DIBH) for right breast irradiation: Improved sparing of liver and lung tissue.

Objective: To reduce liver and lung dose during right breast irradiation while maintaining optimal dose to the target volume. This dose reduction has the potential to decrease acute side effects and long-term toxicity.

Materials And Methods: 16 patients treated with radiation therapy for localized carcinoma of the right breast were included retrospectively.

Constitutive and evoked release of ATP in adult mouse olfactory epithelium.

In adult olfactory epithelium (OE), ATP plays a role in constant cell turnover and post-injury neuroregeneration. We previously demonstrated that constitutive and ATP-evoked ATP release are present in neonatal mouse OE and underlie continuous cell turn-over and post-injury neuroregeneration, and that activation of purinergic P2X receptors is involved in the evoked release. We hypothesized that both releases are present in adult mouse OE.

Neuroimmune interplay in kidney health and disease: Role of renal nerves.

Renal nerves and their role in physiology and disease have been a topic of increasing interest in the past few decades. Renal inflammation contributes to many cardiorenal disease conditions, including hypertension, chronic kidney disease, and polycystic kidney disease. Much is known about the role of renal sympathetic nerves in physiology - they contribute to the regulation of sodium reabsorption, renin release, and renal vascular resistance.

Impact of Imaging-Guided Localization on Performance of Tailored Axillary Surgery in Patients with Clinically Node-Positive Breast Cancer: Prospective Cohort Study Within TAXIS (OPBC-03, SAKK 23/16, IBCSG 57-18, ABCSG-53, GBG 101).

Background: Tailored axillary surgery (TAS) is a novel surgical concept for clinical node-positive breast cancer. It consists of the removal of the sentinel lymph nodes (LNs), as well as palpably suspicious nodes. The TAS technique can be utilized in both the upfront and neoadjuvant chemotherapy (NACT) setting.

Perioperative Chemoimmunotherapy With Durvalumab for Muscle-Invasive Urothelial Carcinoma: Primary Analysis of the Single-Arm Phase II Trial SAKK 06/17.

Purpose: The integration of immunotherapy in the perioperative setting of muscle-invasive urothelial carcinoma (MIUC) appears promising. SAKK 06/17 investigated the addition of neoadjuvant durvalumab to gemcitabine/cisplatin (GC) chemotherapy followed by radical surgery and adjuvant checkpoint inhibition with durvalumab.

Patients And Methods: SAKK 06/17 was an investigator-initiated, open-label, single-arm phase II study including cisplatin-fit patients with stage cT2-T4a cN0-1 operable MIUC.

Association of Axillary Dissection With Systemic Therapy in Patients With Clinically Node-Positive Breast Cancer.

Importance: The role of axillary lymph node dissection (ALND) to determine nodal burden to inform systemic therapy recommendations in patients with clinically node (cN)-positive breast cancer (BC) is currently unknown.

Objective: To address the association of ALND with systemic therapy in cN-positive BC in the upfront surgery setting and after neoadjuvant chemotherapy (NACT).

Design, Setting, And Participants: This was a prospective, observational, cohort study conducted from August 2018 to June 2022.

Neoadjuvant treatment does not influence PD-L1 expression in stage III non-small-cell lung cancer: a retrospective analysis of tumor samples from the trials SAKK 16/96, 16/00, 16/01, and 16/14.

Background: The inclusion of immune checkpoint inhibitors (ICIs) in the treatment of operable stage III non-small-cell lung cancer is becoming a new standard. Programmed death-ligand 1 (PD-L1) protein expression on tumor cells has emerged as the most important biomarker for sensitivity to ICIs targeting the programmed cell death protein 1 (PD-1)-PD-L1 axis. Little is known about the impact of neoadjuvant treatment on PD-L1 expression.

Trends in use of neoadjuvant systemic therapy in patients with clinically node-positive breast cancer in Europe: prospective TAXIS study (OPBC-03, SAKK 23/16, IBCSG 57-18, ABCSG-53, GBG 101).

Purpose: The aim of this study was to evaluate clinical practice heterogeneity in use of neoadjuvant systemic therapy (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) to include the first 500 randomized patients with confirmed nodal disease at the time of surgery.

Novel sequential treatment strategy for patients with muscle-invasive bladder cancer (MIBC): intravesical recombinant BCG, followed by neoadjuvant chemoimmunotherapy, radical cystectomy plus pelvic lymphadenectomy and adjuvant immunotherapy - protocol of a multicentre, single arm phase 2 trial (SAKK 06/19).

Introduction: The combination of checkpoint inhibition and cisplatin-based chemotherapy is investigated in muscle invasive bladder cancer (MIBC) and results from phase 2 trials have been presented. Intravesical BCG has been used for non-MIBC (NMIBC) in patients with carcinoma in situ and high-grade Ta/T1 tumours. BCG induces innate and adapted immune response and upregulation of PD-L1 in preclinical models.

Completion and publication of clinical trials in a cooperative group: a cohort study of trials of the Swiss Group for Clinical Cancer Research (SAKK).

Background: Premature trial discontinuation and non-publication of trial results are still major issues negatively affecting reliable evidence generation.

Objectives: To investigate trial completion and publication rate of cancer trials conducted within the Swiss Group for Clinical Cancer Research (SAKK).

Design: Cohort study of clinical trials.

Predictive value of radiological response, pathological response and relapse-free survival for overall survival in neoadjuvant immunotherapy trials: pooled analysis of 29 clinical trials.

Background: An increasing number of clinical trials are being conducted exploring the efficacy of neoadjuvant immune checkpoint inhibitors. Surrogate end-points for overall survival (OS) are urgently needed.

Methods: Phase II or III trials of neoadjuvant immunotherapy that reported data on OS and surrogate end-points were identified from January 1, 2000, to November 25, 2022.

Darolutamide Maintenance in Patients With Metastatic Castration-Resistant Prostate Cancer With Nonprogressive Disease After Taxane Treatment (SAKK 08/16).

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.

Patterns of care for relapsed oesophageal cancer after initial curative trimodality therapy: Long-term follow-up of the SAKK 75/08 trial.

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.