OBJECTIVE: Non-muscle-invasive bladder cancer (NMIBC) can recur, partly due to seeding of free tumour cells after transurethral resection of bladder tumour (TURBT). Intravesical chemotherapy post-TURBT can reduce the risk but is used infrequently and inconsistently due to cost, complexity and side effects. The objective of this study was to prospectively assess continuous bladder irrigation using water, which may be a safer and easier alternative with comparable effectiveness.
METHODS: WATIP was a prospective, single-arm phase 2 study of water irrigation during and for at least 3 h after TURBT for bladder tumours noted on imaging or flexible cystoscopy. Participants were assessed clinically for adverse effects and with blood tests within 24 h for sodium, haemoglobin and lactate dehydrogenase. The primary endpoints were safety (defined as < 10% adverse events of CTCAE grade ≥ 3), and feasibility (defined as the intervention being delivered as planned in > 90% of cases) and secondary endpoint was recurrence-free rates (RFR).
RESULTS: Water irrigation was delivered as planned in 29 (97%) of 30 participants (median age 67 years, 25 (83%) males). The only adverse event (grade 2) was clot retention in one (3.3%) participant. Water irrigation significantly reduced urothelial cell counts in catheter effluent over time, unlike saline irrigation which did not. RFR was 56.2% (9/16 participants with low-risk NMIBC) at first cystoscopy (median interval 108 days) and 62.5% (5/8 evaluable low-risk NMIBC) at 12 months.
CONCLUSIONS: Water irrigation during and after TURBT is feasible and safe. Prospective assessment of its effect on NMIBC recurrence compared to post-TURBT intravesical chemotherapy is needed before recommending its use in routine clinical practice. Trial registration ANZCTR registration ID ACTRN12619000517178 on 1 April 2019.

UNASSIGNED: The objective of this work is to evaluate the additional oncological benefit of photodynamic diagnosis (PDD) using blue-light cystoscopy in transurethral resection (TURBT) for primary non-muscle-invasive bladder cancer (NMIBC) based on the International Bladder Cancer Group (IBCG)-defined progression and the subsequent pathological pathways.
UNASSIGNED: We reviewed 1578 consecutive primary NMIBC patients undergoing white-light TURBT (WL-TURBT) or PDD-TURBT during 2006-2020. One-to-one propensity score-matching was performed using multivariable logistic regression to obtain balanced groups. IBCG-defined progression of NMIBC included stage-up and grade-up as well as conventional definitions such as the development of muscle-invasive BC or metastatic disease. Nine oncological endpoints were evaluated. Sankey diagrams were generated to visualize follow-up pathological pathways after the initial TURBT.
UNASSIGNED: Comparison of event-free survival between the matched groups revealed that PDD use decreased the bladder cancer recurrence risk and IBCG-defined progression risk, whereas no significant difference was noted in conventionally defined progression. This was attributable to a reduced risk of stage-up, from Ta to T1, and grade-up. Sankey diagrams of the matched groups showed that patients with primary Ta low-grade tumour and first-recurrence Ta low-grade tumour did not have bladder recurrence or progression, while some of those in the WL-TURBT group developed recurrence after treatment.
UNASSIGNED: The multiple survival analysis demonstrated that the risk of IBCG-defined progression was significantly decreased by PDD use in NMIBC patients. Sankey diagrams revealed possible differences in pathological pathways after the initial TURBT between the two groups, demonstrating that repeated recurrence could be prevented by PDD use.

OBJECTIVE: Neoadjuvant systemic therapy (NST) is increasingly used in breast cancer patients and depending on subtype, 10-89% of patients will attain pathologic complete response (pCR). In patients with pCR, risk of local recurrence (LR) after breast conserving therapy is low. Although adjuvant radiotherapy after breast conserving surgery (BCS) reduces LR further in these patients, it may not contribute to overall survival. However, radiotherapy may cause early and late toxicity. The aim of this study is to show that omission of adjuvant radiotherapy in patients with a pCR after NST will result in acceptable low LR rates and good quality of life.
METHODS: The DESCARTES study is a prospective, multicenter, single arm study. Radiotherapy will be omitted in cT1-2N0 patients (all subtypes) who achieve a pCR of the breast and lymph nodes after NST followed by BCS plus sentinel node procedure. A pCR is defined as ypT0N0 (i.e. no residual tumor cells detected). Primary endpoint is the 5-year LR rate, which is expected to be 4% and deemed acceptable if less than 6%. In total, 595 patients are needed to achieve a power of 80% (one-side alpha of 0.05). Secondary outcomes include quality of life, Cancer Worry Scale, disease specific and overall survival. Projected accrual is five years.
CONCLUSIONS: This study bridges the knowledge gap regarding LR rates when adjuvant radiotherapy is omitted in cT1-2N0 patients achieving pCR after NST. If the results are positive, radiotherapy may be safely omitted in selected breast cancer patients with a pCR after NST.
BACKGROUND: This study is registered at ClinicalTrials.gov on June 13th 2022 (NCT05416164). Protocol version 5.1 (15-03-2022).

BACKGROUND. Posttreatment recurrence is an unpredictable complication after liver transplant for hepatocellular carcinoma (HCC) that is associated with poor survival. Biomarkers are needed to estimate recurrence risk before organ allocation. OBJECTIVE. This proof-of-concept study evaluated the use of machine learning (ML) to predict recurrence from pretreatment laboratory, clinical, and MRI data in patients with early-stage HCC initially eligible for liver transplant. METHODS. This retrospective study included 120 patients (88 men, 32 women; median age, 60.0 years) with early-stage HCC diagnosed who were initially eligible for liver transplant and underwent treatment by transplant, resection, or thermal ablation between June 2005 and March 2018. Patients underwent pretreatment MRI and posttreatment imaging surveillance. Imaging features were extracted from postcontrast phases of pretreatment MRI examinations using a pretrained convolutional neural network. Pretreatment clinical characteristics (including laboratory data) and extracted imaging features were integrated to develop three ML models (clinical model, imaging model, combined model) for predicting recurrence within six time frames ranging from 1 through 6 years after treatment. Kaplan-Meier analysis with time to recurrence as the endpoint was used to assess the clinical relevance of model predictions. RESULTS. Tumor recurred in 44 of 120 (36.7%) patients during follow-up. The three models predicted recurrence with AUCs across the six time frames of 0.60-0.78 (clinical model), 0.71-0.85 (imaging model), and 0.62-0.86 (combined model). The mean AUC was higher for the imaging model than the clinical model (0.76 vs 0.68, respectively; p = .03), but the mean AUC was not significantly different between the clinical and combined models or between the imaging and combined models (p > .05). Kaplan-Meier curves were significantly different between patients predicted to be at low risk and those predicted to be at high risk by all three models for the 2-, 3-, 4-, 5-, and 6-year time frames (p < .05). CONCLUSION. The findings suggest that ML-based models can predict recurrence before therapy allocation in patients with early-stage HCC initially eligible for liver transplant. Adding MRI data as model input improved predictive performance over clinical parameters alone. The combined model did not surpass the imaging model\'s performance. CLINICAL IMPACT. ML-based models applied to currently underutilized imaging features may help design more reliable criteria for organ allocation and liver transplant eligibility.

BACKGROUND: Stage III melanoma is associated with poor outcomes. We studied the characteristics and outcomes of patients with resected Stage III melanoma before the routine use of adjuvant immunotherapy. Some of these patients received adjuvant nodal radiation with modern radiation techniques.
METHODS: We retrieved data of patients with resected Stage III melanoma treated in Christchurch over 10 years. Overall survival (OS), melanoma-specific survival (MSS), recurrence-free survival (RFS) and nodal recurrence-free rate (NRFR) were determined, and the association of these outcomes with tumour and treatment factors was investigated.
RESULTS: We identified 178 patients (110 male and 68 female), of whom 61 received adjuvant radiation. The median age was 66.6 years, and the median follow-up was 2.7 years. First recurrences occurred in 108 (61%) patients. There were 42 (24%) nodal field relapses and 103 (58%) distant relapses. One-half of nodal relapses in patients treated with adjuvant radiation were infield. The 5-year OS, RFS, MSS and NRFR were 46.4%, 26.8%, 53.7% and 69.6%, respectively. Adjuvant radiation was associated with improved RFS and no OS benefit. T4 disease and extranodal spread were associated with poorer OS, while extranodal spread and >3 involved nodes were associated with worse RFS.
CONCLUSIONS: Patients treated with adjuvant radiation remain at moderate risk of regional and high risk of distant relapse, despite the use of modern radiation techniques. Adjuvant radiation was associated with improved local control but infield recurrence rates remained a problem. The role of combined adjuvant radiation and immunotherapy in improving these outcomes requires further investigation.

OBJECTIVE: Taxane-based chemotherapy is the primary treatment for premenopausal breast cancer. Although being inconsistent, research suggests that variant alleles alter pharmacokinetics through reduced function of OATP transporters (limiting hepatic uptake), CYP-450 enzymes (hampering drug metabolism), and ABC transporters (decreasing clearance). Reduced function of DNA repair enzymes may hamper effectiveness through dose-limiting toxicities. We investigated whether single-nucleotide polymorphisms (SNPs) were associated with breast cancer recurrence or mortality in premenopausal women diagnosed with breast cancer.
METHODS: We conducted a population-based cohort study of premenopausal women diagnosed with non-distant metastatic breast cancer in Denmark during 2007‒2011, when guidelines recommended adjuvant combination chemotherapy (taxanes, anthracyclines, and cyclophosphamide). Using archived formalin-fixed paraffin-embedded primary tumor tissue, we genotyped 26 SNPs using TaqMan assays. Danish health registries provided data on breast cancer recurrence (through September 25, 2017) and death (through December 31, 2019). We fit Cox regression models to calculate crude hazard ratios (HRs) and 95% confidence intervals (CIs) for recurrence and mortality across genotypes.
RESULTS: Among 2,262 women, 249 experienced recurrence (cumulative incidence: 13%) and 259 died (cumulative incidence: 16%) during follow-up (median 7.0 and 10.1 years, respectively). Mortality was increased in variant carriers of GSTP1 rs1138272 (HR: 1.30, 95% CI 0.95-1.78) and CYP3A rs10273424 (HR: 1.33, 95% CI 0.98-1.81). SLCO1B1 rs2306283 (encoding OATP1B1) variant carriers had decreased recurrence (HR: 0.82, 95% CI 0.64-1.07) and mortality (HR: 0.77, 95% CI 0.60-0.98).
CONCLUSIONS: Docetaxel effectiveness was influenced by SNPs in GSTP1, CYP3A, and SLCO1B1 in premenopausal women with non-distant metastatic breast cancer, likely related to altered docetaxel pharmacokinetics. These SNPs may help determine individual benefit from taxane-based chemotherapy.

Obesity-associated breast cancer recurrence is mechanistically linked with elevated insulin levels and insulin resistance. Exercise and weight loss are associated with decreased breast cancer recurrence, which may be mediated through reduced insulin levels and improved insulin sensitivity. This is a secondary analysis of the WISER Survivor clinical trial examining the relative effect of exercise, weight loss and combined exercise and weight loss interventions on insulin and insulin resistance. The weight loss and combined intervention groups showed significant reductions in levels of: insulin, C-peptide, homeostatic model assessment 2 (HOMA2) insulin resistance (IR), and HOMA2 beta-cell function (β) compared to the control group. Independent of intervention group, weight loss of ≥10% was associated with decreased levels of insulin, C-peptide, and HOMA2-IR compared to 0-5% weight loss. Further, the combination of exercise and weight loss was particularly important for breast cancer survivors with clinically abnormal levels of C-peptide.

OBJECTIVE: To analyse healthcare utilisation in colorectal cancer (CRC) survivors in the 12 months preceding a diagnosis of CRC recurrence.
METHODS: This register-based cohort study included curatively treated survivors of CRC diagnosed in 2008-2018. Survivors with CRC recurrence were matched 1:5 with recurrence-free survivors. We estimated the monthly frequency of healthcare utilisation before the recurrence diagnosis and a corresponding index date assigned to the matched population. A regression model was used to compare healthcare utilisation between groups.
RESULTS: We included 3045 survivors with recurrence and 15,225 recurrence-free survivors. At study entry, both groups had on average one contact per month to general practice. Compared with recurrence-free survivors, survivors with recurrence had more contacts to general practice from 10 months before the diagnosis and more haemoglobin measurements from 4 months before the diagnosis. They had more contacts to hospitals and follow-up clinics from 7 months before the diagnosis and more diagnostic investigations from 2 months before the diagnosis.
CONCLUSIONS: General practitioners have regular contact with CRC survivors and are involved in detecting recurrence. The increased number of contacts in the months before the rise in diagnostic investigations indicates an opportunity to expedite referral to diagnostics and the diagnosis of CRC recurrence.

OBJECTIVE: Data regarding hepatocellular carcinoma (HCC) recurrence after directly acting antivirals for hepatitis C are contradictory. Our aim was to study the HCC recurrence in patients who received directly acting antivirals after tumor ablation.
METHODS: This retrospective study included all Child-Pugh A and B patients with hepatitis C related < 5 cm single or up to 3 HCC without any vascular or extrahepatic involvement whose lesions were managed using microwave or radiofrequency ablation at the Internal Medicine Department of Alexandria Faculty of Medicine, in the period from 1 January 2016 to 31 December 2016, and then received directly acting antivirals.
RESULTS: Data from 52 patients were analyzed. Throughout the 2 years from ablation, 42.3% of patients experienced tumor recurrence (22 out of 52 patients). In addition, two subjects died and 4 subjects were lost to follow-up before any tumor recurrence.
CONCLUSIONS: Although our study included both modified Child-Pugh A and B patients and included lesions up to 5 cm treated using thermal ablation, the 2-year HCC recurrence rate was similar to that previously reported after surgical resection or radiofrequency ablation of lesions up to 3 cm in Child-Pugh A patients before development of directly acting antivirals.

The present study attempted to analyse human papillomavirus (HPV) genotype distribution and its association with cervical cytology results in women in western China. The present retrospective analysis was performed in 1089 female outpatients with a positive HPV test result who had undergone a cervical cytology test at the gynaecological clinic, West China Second Hospital, Sichuan University, China, between January 2014 and December 2016. Of the 1089 patients with HPV infection, multiple HPV genotypes were detected in 220 patients (20.20%). Among the 1368 HPV genotypes detected, 1145 (83.70%) were high-risk subtypes. The most common genotypes were HPV-52 (18.64%), HPV-16 (16.59%), HPV-58 (13.23%), HPV-18 (6.80%), HPV-56 (5.56%) and HPV-59 (5.56%). Cervical cytology revealed abnormal cells in 430 (39.49%) patients. The most common diagnoses were atypical squamous cells of undetermined significance (ASC-US; 236 cases, 54.88%), low-grade squamous intraepithelial lesions (LSIL; 151 cases, 35.12%), high-grade squamous intraepithelial lesions (HSIL; 63 cases, 14.65%) and atypical glandular cells (AGC; 21 cases, 4.88%). HPV-66 was significantly associated (P = 0.037) with ASC; HPV-52 and HPV-56 were significantly associated with LSIL (P = 0.009 and 0.026, respectively); HPV-16 (P < 0.001), HPV-33 (P = 0.014) and HPV-58 (P = 0.003) were significantly associated with HSIL; and HPV-16 (P = 0.005) was significantly associated with AGC. HPV-16, HPV-52 and HPV-58 are associated with different diagnoses in patients with positive cervical cytological findings.