The Ave-Rec Trial: Phase II Trial of PDL1/PD1 Blockade with Avelumab after Chemoradiotherapy for Locally Advanced Resectable T3B-4/N1-2 Rectal Cancer.

Purpose: Long-course chemoradiotherapy (LCCRT) for locally advanced rectal cancer (LARC) achieves a pathologic complete response (pCR) in approximately 10% to 30% of cases. Radiotherapy exerts both immunostimulatory and immunosuppressive effects. Inhibition of PDL1 may augment the immunostimulatory response.

Node-positive carcinoma of the vulva treated with curative-intent radiotherapy.

Objective: This study aimed to evaluate the outcomes of patients with node-positive vulvar carcinoma treated with radiotherapy, with or without chemotherapy, administered with curative intent, focusing on patterns of first failure, locoregional control, and overall survival.

Methods: Patients were eligible if they had a histologic diagnosis of node-positive vulvar cancer and were referred for curative-intent radiotherapy, with or without chemotherapy, either as the primary treatment or in the adjuvant setting following definitive surgery between January 2000 and December 2019 at our institution. Eligible patients were selected from the prospective database of the gynecology oncology unit, where clinical, histopathologic, treatment, and follow-up data were systematically collected for analysis.

Baseline Nodal Status on Ga-PSMA-11 Positron Emission Tomography/Computed Tomography in Men with Intermediate- to High-risk Prostate Cancer Is Prognostic for Treatment Failure: Follow-up of the proPSMA Trial.

Background And Objective: There is uncertainty regarding the clinical significance of Ga-PSMA-11 positron emission tomography (PET) computed tomography (CT) findings in men with prostate cancer. In this prespecified objective of the proPSMA study, we report the prognostic value of PET-defined nodal involvement.

Methods: Men with intermediate- to high-risk prostate cancer (grade group 3-5, prostate-specific antigen [PSA] ≥20 ng/ml, or clinical stage ≥T3) underwent Ga-PSMA-11 PET-CT or CT and bone scanning as first- or second-line imaging.

A phase 1 clinical trial of the repurposable acetyllysine mimetic, n-methyl-2-pyrrolidone (NMP), in relapsed or refractory multiple myeloma.

Background: N-methyl-2-pyrrolidone (NMP) is an epigenetically active chemical fragment and organic solvent with numerous applications including use as a drug-delivery vehicle. Previously considered biologically inert, NMP demonstrates immunomodulatory and anti-myeloma properties that are partly explained by acetyllysine mimetic properties and non-specific bromodomain inhibition. We therefore evaluated orally administered NMP in a phase 1 dose-escalation trial to establish its maximum tolerated dose (MTD) in patients with relapsed/refractory multiple myeloma (RR-MM).

A Phase Ib/II Trial of Combined BRAF and EGFR Inhibition in BRAF V600E Positive Metastatic Colorectal Cancer and Other Cancers: The EVICT (Erlotinib and Vemurafenib In Combination Trial) Study.

Purpose: BRAF V600E mutant metastatic colorectal cancer represents a significant clinical problem, with combination approaches being developed clinically with oral BRAF inhibitors combined with EGFR-targeting antibodies. While compelling preclinical data have highlighted the effectiveness of combination therapy with vemurafenib and small-molecule EGFR inhibitors, gefitinib or erlotinib, in colorectal cancer, this therapeutic strategy has not been investigated in clinical studies.

Patients And Methods: We conducted a phase Ib/II dose-escalation/expansion trial investigating the safety/efficacy of the BRAF inhibitor vemurafenib and EGFR inhibitor erlotinib.

Increased risk of diaphragmatic herniation following esophagectomy with a minimally invasive abdominal approach.

Objective: Diaphragmatic herniation is a rare complication following esophagectomy, associated with risks of aspiration pneumonia, bowel obstruction, and strangulation. Repair can be challenging due to the presence of the gastric conduit. We performed this systematic review and meta-analysis to determine the incidence and risk factors associated with diaphragmatic herniation following esophagectomy, the timing and mode of presentation, and outcomes of repair.

Evaluation of pharmacogenomics and hepatic nuclear imaging-related covariates by population pharmacokinetic models of irinotecan and its metabolites.

Background: Body surface area (BSA)-based dosing of irinotecan (IR) does not account for its pharmacokinetic (PK) and pharmacodynamic (PD) variabilities. Functional hepatic nuclear imaging (HNI) and excretory/metabolic/PD pharmacogenomics have shown correlations with IR disposition and toxicity/efficacy. This study reports the development of a nonlinear mixed-effect population model to identify pharmacogenomic and HNI-related covariates that impact on IR disposition to support dosage optimization.

Pharmacogenomics and functional imaging to predict irinotecan pharmacokinetics and pharmacodynamics: the predict IR study.

Purpose: Irinotecan (IR) displays significant PK/PD variability. This study evaluated functional hepatic imaging (HNI) and extensive pharmacogenomics (PGs) to explore associations with IR PK and PD (toxicity and response).

Methods: Eligible patients (pts) suitable for Irinotecan-based therapy.

Single well, single-common primer pair, dual probe, duplex qPCR assay for the quantification of mRNA splicing variants.

Quantifying the ratio of alternatively spliced mRNA variants of genes with known alternative splicing variants is highly relevant for many applications. Herein, we describe the validation of a quantitative PCR design for the simplified quantification of known mRNA splice variants. The assay uses a single-common primer pair, dual probe design for the determination of splicing variants in a single well configuration.

Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): a prospective, randomised, multicentre study.

Background: Conventional imaging using CT and bone scan has insufficient sensitivity when staging men with high-risk localised prostate cancer. We aimed to investigate whether novel imaging using prostate-specific membrane antigen (PSMA) PET-CT might improve accuracy and affect management.

Methods: In this multicentre, two-arm, randomised study, we recruited men with biopsy-proven prostate cancer and high-risk features at ten hospitals in Australia.

Quality of life after breast-conserving therapy and adjuvant radiotherapy for non-low-risk ductal carcinoma in situ (BIG 3-07/TROG 07.01): 2-year results of a randomised, controlled, phase 3 trial.

Background: BIG 3-07/TROG 07.01 is an international, multicentre, randomised, controlled, phase 3 trial evaluating tumour bed boost and hypofractionation in patients with non-low-risk ductal carcinoma in situ following breast-conserving surgery and whole breast radiotherapy. Here, we report the effects of diagnosis and treatment on health-related quality of life (HRQOL) at 2 years.

Expression of Tryptophan 2,3-Dioxygenase in Metastatic Uveal Melanoma.

Uveal melanoma (UM) is the most common primary eye malignancy in adults and up to 50% of patients subsequently develop systemic metastasis. Metastatic uveal melanoma (MUM) is highly resistant to immunotherapy. One of the mechanisms for resistance would be the immune-suppressive tumor microenvironment.

The INTERNET STUDY: A phase II study of everolimus in patients with fluorodeoxyglucose ( F) positron-emission tomography positive intermediate grade pancreatic neuroendocrine tumors.

Aims: This multicenter phase II trial evaluates the efficacy of everolimus in poor prognosis grade 2 (G2) pancreatic neuroendocrine tumors (PNETs), defined by 2-[fluorine-18]fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET) avidity. FDG-PET avidity in NETs is associated with a significantly higher risk of death, outperforming Ki-67 index or liver metastases as a poor prognostic factor. We hypothesized that everolimus has efficacy in patients with FDG-PET-avid G2 PNETs and prospectively evaluated progression-free survival (PFS) and response in the first-line setting.

International comparison of cosmetic outcomes of breast conserving surgery and radiation therapy for women with ductal carcinoma in situ of the breast.

Purpose: To assess the cosmetic impact of breast conserving surgery (BCS), whole breast irradiation (WBI) fractionation and tumour bed boost (TBB) use in a phase III trial for women with ductal carcinoma in situ (DCIS) of the breast.

Materials And Methods: Baseline and 3-year cosmesis were assessed using the European Organization for Research and Treatment of Cancer (EORTC) Cosmetic Rating System and digital images in a randomised trial of non-low risk DCIS treated with postoperative WBI +/- TBB. Baseline cosmesis was assessed for four geographic clusters of treating centres.

First-in-Human RNA Polymerase I Transcription Inhibitor CX-5461 in Patients with Advanced Hematologic Cancers: Results of a Phase I Dose-Escalation Study.

RNA polymerase I (Pol I) transcription of ribosomal RNA genes (rDNA) is tightly regulated downstream of oncogenic pathways, and its dysregulation is a common feature in cancer. We evaluated CX-5461, the first-in-class selective rDNA transcription inhibitor, in a first-in-human, phase I dose-escalation study in advanced hematologic cancers. Administration of CX-5461 intravenously once every 3 weeks to 5 cohorts determined an MTD of 170 mg/m, with a predictable pharmacokinetic profile.

Feasibility of 5-fluorouracil pharmacokinetic monitoring using the My-5FU PCM™ system in a quaternary oncology centre.

Purpose: 5-Fluorouracil (5FU) drug exposure correlates with treatment response and toxicity in cancer patients. Dosing is based upon body surface area which does not correlate with 5FU pharmacokinetics (PK)/pharmacodynamics. Therapeutic drug monitoring has enabled real-time 5FU dose adjustments: reducing toxicity with increased efficacy.

Idarubicin Dose Escalation During Consolidation Therapy for Adult Acute Myeloid Leukemia.

Purpose Higher doses of the anthracycline daunorubicin during induction therapy for acute myeloid leukemia (AML) have been shown to improve remission rates and survival. We hypothesized that improvements in outcomes in adult AML may be further achieved by increased anthracycline dose during consolidation therapy. Patients and Methods Patients with AML in complete remission after induction therapy were randomly assigned to receive two cycles of consolidation therapy with cytarabine 100 mg/m daily for 5 days, etoposide 75 mg/m daily for 5 days, and idarubicin 9 mg/m daily for either 2 or 3 days (standard and intensive arms, respectively).

Exploring the Association Between Demographics, SLC30A8 Genotype, and Human Islet Content of Zinc, Cadmium, Copper, Iron, Manganese and Nickel.

A widely prevalent single nucleotide polymorphism, rs13266634 in the SLC30A8 gene encoding the zinc transporter ZnT8, is associated with an increased risk for T2DM. ZnT8 is mostly expressed in pancreatic insulin-producing islets of Langerhans. The effect of this variant on the divalent metal profile in human islets is unknown.

Upfront lower dose lenalidomide is less toxic and does not compromise efficacy for vulnerable patients with relapsed refractory multiple myeloma: final analysis of the phase II RevLite study.

The combination of lenalidomide and dexamethasone is an established treatment for patients with multiple myeloma (MM). Increasingly, treatment attenuation is advocated for frail/elderly patients to minimize toxicity even though there have been no prospective studies to demonstrate whether lenalidomide dose attenuation impacts on response and survival outcome. This prospective multicentre phase II study assessed the efficacy and tolerability of lower dose lenalidomide (15 mg) and dexamethasone (20 mg) in 149 eligible patients with relapsed/refractory MM aged over 59 years and/or with renal impairment.

Results of a phase II study of thalidomide and azacitidine in patients with clinically advanced myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML) and low blast count acute myeloid leukemia (AML).

Single agent azacitidine or immunomodulatory drugs are effective in myelodysplastic syndrome (MDS), with differing target mechanisms and toxicities. Objectives of this ALLG MDS3 study in clinically advanced MDS, AMML and low blast AML were to establish safety, response and quality of life of azacitidine and thalidomide. Patients received azacitidine (75mg/m/d sc 7days every 28 days), and oral thalidomide up to 100mg/d for maximum 12months.

Prevalence and Intensity of Pain and Other Physical and Psychological Symptoms in Adolescents and Young Adults Diagnosed with Cancer on Referral to a Palliative Care Service.

Purpose: While adolescent and young adult (AYA) oncology is recognized as a distinct specialty, there remains a paucity of literature documenting symptomatology in this cohort. This study aimed to identify the prevalence, severity, and mechanism of pain and other symptoms in AYA patients referred to a palliative care service in a specialist Australian cancer center.

Methods: A retrospective design analyzed the case file data of 33 eligible AYA patients aged 15-25 years old at diagnosis and two randomly selected control groups of patients >25 years old: unmatched and matched for diagnosis and sex.