Neoadjuvant anti-PD-1 alone or in combination with anti-TIGIT or an oncolytic virus in resectable stage IIIB-D melanoma: a phase 1/2 trial.

Neoadjuvant immunotherapies have shown antitumor activity in melanoma. Substudy 02C of the global, rolling-arm, phase 1/2, adaptive-design KEYMAKER-U02 trial is evaluating neoadjuvant pembrolizumab (anti-PD-1) alone or in combination, followed by adjuvant pembrolizumab, for stage IIIB-D melanoma. Here we report results from the first three arms: pembrolizumab plus vibostolimab (anti-TIGIT), pembrolizumab plus gebasaxturev (coxsackievirus A21) and pembrolizumab monotherapy.

Real-world impact of pembrolizumab availability for deficient mismatch repair metastatic colorectal cancer.

Background: Immunotherapy has emerged as a standard treatment for deficient mismatch repair (dMMR) metastatic colorectal cancer (mCRC). Pembrolizumab became widely available as a first-line (1L) option in Australia following the Pharmaceutical Benefits Scheme (PBS) listing in August 2021. The uptake of new treatment options can be lengthy.

Total Neoadjuvant Therapy in Locally Advanced Rectal Cancer: Insights from the Western Australian Context.

Background: Recent studies have associated total neoadjuvant therapy (TNT) with better treatment adherence, decreased toxicity, improved complete clinical response and anal sphincter preservation rates in patients with locally advanced rectal cancer (LARC). However, real-world experience with TNT in the management of LARC remains limited.

Aim: This study aimed to evaluate the efficacy and safety outcomes of TNT for LARC in Western Australia.

Audit of the Acute Management of Renal Colic in District Hospitals Within a National Health Service Trust.

Introduction: Renal colic is a prevalent acute urological emergency caused by urinary stones and commonly manifests as severe loin pain. This audit assesses the management of acute renal colic at a National Health Service (NHS) Trust in the West Midlands, England, comparing practices against the National Institute for Clinical Excellence (NICE) and the British Association of Urological Surgeons (BAUS) guidelines.

Method: This retrospective audit reviewed 417 patients with suspected renal colic over a month.

Evaluating the Quality of Primary Transurethral Resection of Bladder Tumor: A Nine-Year Review at a Tertiary Healthcare Center.

Objective: This study aimed to assess the quality of primary transurethral resection of bladder tumor (TURBT) procedures performed at Aga Khan University Hospital (AKUH) over nine years, focusing on proper documentation, completeness of tumor resection, quality of histopathology reports, complication rates, and adherence to European Association of Urology (EAU) guidelines.

Materials And Methods: A retrospective analysis of patients aged 25-75 who underwent primary TURBT at AKUH between 2010 and 2019 was done. Patients with incomplete records, concomitant procedures, or those who underwent emergency TURBT were excluded.

Perineal Wound Healing Following Abdominoperineal Resection of the Rectum.

Objective: This study aimed to investigate perineal wound healing rates following abdominoperineal resection (APR) or extralevator abdominoperineal excision (ELAPE) for rectal cancer, with a focus on identifying associated risk factors and outcomes.

Methodology: A retrospective analysis was conducted on patients undergoing APR or ELAPE for rectal cancer in a tertiary centre between 2013 and 2020. Data on demographics, comorbidities, surgical techniques, and perineal wound outcomes were collected and analyzed using Statistical Package for the Social Sciences (IBM SPSS Statistics for Windows, IBM Corp.

Current Practices and Challenges in the Management of Complex Renal Stones in Africa: A Scoping Review.

This study reviews the challenges and management strategies for complex renal stones in Africa. Historically viewed as infection or struvite stones, recent studies highlight diverse compositions of staghorn stones. These complex stones pose significant risks, including recurrent urinary tract infections and renal impairment.

Pembrolizumab Versus Placebo as Adjuvant Therapy in Resected Stage IIB or IIC Melanoma: Final Analysis of Distant Metastasis-Free Survival in the Phase III KEYNOTE-716 Study.

JCO Pembrolizumab adjuvant therapy was shown to significantly improve recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) in patients with resected stage IIB or IIC melanoma in earlier analyses of the randomized, double-blind, phase III KEYNOTE-716 study (ClinicalTrials.gov identifier: NCT03553836). We report results of the protocol-specified final analysis of DMFS for KEYNOTE-716.

Immune checkpoint inhibitor therapy for advanced cutaneous squamous cell carcinoma in Australia: a retrospective real world cohort study.

Objectives: To review the outcomes of immune checkpoint inhibitor (ICI) treatment of advanced cutaneous squamous cell carcinoma (CSCC) outside clinical trials.

Study Design: Retrospective observational study; review of patient records in fifteen Australian institutions.

Setting, Participants: All Australian adults with locally advanced or metastatic CSCC not amenable to curative surgery or radiotherapy treated with ICIs, 5 May 2017 - 23 May 2022, through a cemiplimab compassionate access scheme (Therapeutic Goods Administration Special Access Scheme) or who personally covered the cost of pembrolizumab prior to the start of the access scheme.

Feasibility of supervised telehealth exercise for patients with advanced melanoma receiving checkpoint inhibitor therapy.

Purpose: To determine the feasibility, safety and preliminary efficacy of a telehealth supervised exercise programme in patients with advanced melanoma receiving checkpoint inhibitor therapy.

Methods: A 8-week non-randomised feasibility pilot trial utilising a telehealth delivered multimodal exercise programme undertaken thrice weekly with assessments at baseline and post-intervention. The study was considered feasible if there were no severe or life-threatening adverse events as a result of exercise, and three or more of the following criteria were met: the recruitment rate was >50%, completion rate was >80%, median programme attendance was >75%, median exercise compliance >75%, and average tolerance was >70%.

Gut microbiota diversity and composition in predicting immunotherapy response and immunotherapy-related colitis in melanoma patients: A systematic review.

Background: Gut microbiome (GM) composition and diversity have recently been studied as a biomarker of response to immune checkpoint blockade therapy (ICB) and of ICB-related colitis.

Aim: To conduct a systematic review on the role of GM composition and diversity in predicting response and colitis in patients with melanoma treated with ICB.

Methods: The review protocol was registered in PROSPERO: CRD42021228018.

Adjuvant pembrolizumab versus placebo in resected high-risk stage II melanoma: Health-related quality of life from the randomized phase 3 KEYNOTE-716 study.

Background: Adjuvant pembrolizumab significantly improved recurrence-free survival (RFS) versus placebo in resected stage IIB and IIC melanoma in the phase 3 KEYNOTE-716 study. Health-related quality of life (HRQoL) results are reported.

Methods: Patients were randomly assigned 1:1 to pembrolizumab 200 mg (2 mg/kg, patients ≥12 to <18 years) Q3W or placebo for ≤17 cycles or until disease recurrence, unacceptable toxicity, or withdrawal.

Phase II LEAP-004 Study of Lenvatinib Plus Pembrolizumab for Melanoma With Confirmed Progression on a Programmed Cell Death Protein-1 or Programmed Death Ligand 1 Inhibitor Given as Monotherapy or in Combination.

Purpose: Effective treatments are needed for melanoma that progresses on inhibitors of programmed cell death protein-1 (PD-1) or its ligand (PD-L1). We conducted the phase II LEAP-004 study to evaluate the combination of the multikinase inhibitor lenvatinib and the PD-1 inhibitor pembrolizumab in this population (ClinicalTrials.gov identifier: NCT03776136).

Pembrolizumab versus placebo as adjuvant therapy in completely resected stage IIB or IIC melanoma (KEYNOTE-716): a randomised, double-blind, phase 3 trial.

Background: Pembrolizumab prolongs progression-free and overall survival among patients with advanced melanoma and recurrence-free survival in resected stage III disease. KEYNOTE-716 assessed pembrolizumab as adjuvant therapy in patients with completely resected, high-risk, stage II melanoma. We report results from the planned first and second interim analyses for recurrence-free survival.

Prevalence of antibiotic resistance pattern in shigella isolates procured from pediatric patients at Faisalabad - Pakistan.

Shigella infection (shigellosis) is an intestinal disease caused by a shigella isolates belongs to a family Enterobacteriacea. Watery diarrhea, abdominal pain and tenesmus are the prominent symptoms of shigella infection. The present study was designed to determine period prevalence and antimicrobial susceptibility of Shigella species recovered from stool specimens obtained from diarrheal paediatric patients under 5 years of age.

Associations of Physical Activity and Exercise with Health-related Outcomes in Patients with Melanoma During and After Treatment: A Systematic Review.

Purpose: Although exercise medicine is recommended to counter treatment-related side-effects and improve health-related outcomes of patients affected by different cancers, no specific recommendations exist for patients with melanoma. As a result, we systematically examined the current evidence regarding the effects of physical activity and exercise on objectively-measured and patient-reported outcomes among patients with melanoma.

Methods: Searches were conducted in , , , , and databases.

Detection of clinical progression through plasma ctDNA in metastatic melanoma patients: a comparison to radiological progression.

Background: The validity of circulating tumour DNA (ctDNA) as an indicator of disease progression compared to medical imaging in patients with metastatic melanoma requires detailed evaluation.

Methods: Here, we carried out a retrospective ctDNA analysis of 108 plasma samples collected at the time of disease progression. We also analysed a validation cohort of 66 metastatic melanoma patients monitored prospectively after response to systemic therapy.

Predicting chemotherapy-induced menopause using baseline and post-chemotherapy anti-Müllerian hormone levels: Results of a pilot study.

Background: Chemotherapy can cause premature menopause which may result in adverse effects such as fertility loss, osteoporosis, cardiovascular disease and menopausal symptoms. It is thus very important that women are provided with accurate information regarding their risk of premature menopause as a consequence of proposed chemotherapy. Unfortunately, at present there are no reliable tools which can be applied in clinical practice to estimate the risk of premature menopause in women undergoing chemotherapy, beyond age of the patient and form of chemotherapy utilized.

The Prognostic Impact of Circulating Tumour DNA in Melanoma Patients Treated with Systemic Therapies-Beyond Mutant Detection.

In this study, we evaluated the predictive value of circulating tumour DNA (ctDNA) to inform therapeutic outcomes in metastatic melanoma patients receiving systemic therapies. We analysed 142 plasma samples from metastatic melanoma patients prior to commencement of systemic therapy: 70 were treated with BRAF/MEK inhibitors and 72 with immunotherapies. Patient-specific droplet digital polymerase chain reaction assays were designed for ctDNA detection.

Prognostic value of HLA-I homozygosity in patients with non-small cell lung cancer treated with single agent immunotherapy.

Background: We aimed to assess the impact of genomic human leukocyte antigen (HLA)-I/II homozygosity on the survival benefit of patients with unresectable locally advanced, metastatic non-small lung cancer treated by single-agent programmed cell death protein-1/programmed death ligand 1 (PD1/PDL1) inhibitors.

Methods: We collected blood from 170 patients with advanced lung cancer treated with immunotherapy at two major oncology centers in Western Australia. Genomic DNA was extracted from white blood cells and used for HLA-I/II high-resolution typing.