John Zalcberg

Monash University (Australia) · Department of Epidemiology and Preventive Medicine

The optimal treatment approach in very-early and early-stage hepatocellular carcinoma (HCC) is not precisely defined, and there is ambiguity in the literature around the comparative efficacy of surgical resection versus ablation as curative therapies for limited disease. We performed this real-world propensity-matched, multi-centre cohort study to...

Background Horizon scanning (HS) is the systematic identification of emerging therapies to inform policy and decision-makers. We developed an agile and tailored HS methodology that combined multi-criteria decision analysis weighting and Delphi rounds. As secondary objectives, we aimed to identify new medicines in melanoma, non-small cell lung cance...

Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a poor prognosis. Accurate preoperative assessment using computed tomography (CT) to determine resectability is crucial in ensuring patients are offered the most appropriate therapeutic strategy. Despite the use of classification guidelines, any interobserver variabil...

Unlabelled: Metastatic colorectal cancer (mCRC) is a heterogeneous disease that can evoke discordant responses to therapy among different lesions in individual patients. The Response Evaluation Criteria in Solid Tumors (RECIST) criteria do not take into consideration response heterogeneity. We explored and developed lesion-based measurement respon...

The lung cancer Optimal Care Pathway recommends supportive care and palliative care integration throughout its various steps, with early referral to appropriate services improving the quality of life in advanced stage non‐small cell lung cancer patients. Using Victorian Lung Cancer Registry data and linked administrative datasets, this retrospectiv...

Purpose: In the INTRIGUE trial, ripretinib showed no significant difference versus sunitinib in progression-free survival for patients with advanced gastrointestinal stromal tumour (GIST) previously treated with imatinib. We compared the impact of these treatments on health-related quality of life (HRQoL). Patients and methods: Patients were ran...

Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a poor prognosis. Accurate preoperative assessment using computed tomography (CT) to determine resectability is crucial in ensuring patients are offered the most appropriate therapeutic strategy. Despite the use of classification guidelines, any interobserver variabil...

Objectives: To report stage-specific patterns of treatment and the influence of management and treatment type on survival rates for people newly diagnosed with small cell lung cancer (SCLC). Design: Cross-sectional patterns of care study; analysis of data prospectively collected for the Victorian Lung Cancer Registry (VLCR). Setting, participan...

Oesophageal adenocarcinoma is a poor prognosis cancer and the molecular features underpinning response to treatment remain unclear. We investigate whole genome, transcriptomic and methylation data from 115 oesophageal adenocarcinoma patients mostly from the DOCTOR phase II clinical trial (Australian New Zealand Clinical Trials Registry-ACTRN1260900...

Purpose Despite the benefits of palliative care (PC) in pancreatic cancer, little is known about patients who access PC. This observational study examines the characteristics of patients with pancreatic cancer at their first episode of PC. Methods First-time, specialist PC episodes captured through the Palliative Care Outcomes Collaboration (PCOC)...

Background Registry-derived stage (RD-Stage) provides a mechanism to capture cancer stage at diagnosis from routinely captured data available to population-based cancer registries (PBCRs). In 2021, a project was undertaken to develop business rules to capture RD-Stage for endometrial cancer, understand current capacity to capture this information a...

Background Advanced gastro-oesophageal cancer (AGOC) carries a poor prognosis. No standard of care treatment options are available after first and second-line therapies. Regorafenib is an oral multi-targeted tyrosine kinase inhibitor targeting angiogenic, stromal, and oncogenic receptor tyrosine kinases. Regorafenib 160 mg daily prolonged progressi...

Introduction: Cancer treatment planning in older adults is complex and requires careful balancing of survival, quality of life benefits, and risk of treatment-related morbidity and toxicity. As a result, treatment selection in this cohort tends to differ from that for younger patients. However, there are very few studies describing cancer treatment...

Background Ripretinib is a novel switch-control kinase inhibitor that inhibits KIT and PDGFRA signaling. In the INVICTUS phase 3 trial, ripretinib increased median progression-free survival and prolonged overall survival vs. placebo in ≥ fourth-line advanced GIST. Here, we report prespecified analysis of quality of life (QoL) as assessed by patient...

Cancer treatment planning in older adults is complex and requires careful balancing of survival, quality of life benefits, and risk of treatment-related morbidity and toxicity. As a result, treatment selection in this cohort tend to differ from younger patients. However, there are very few studies describing cancer treatment patterns in older cohor...

Background Previous studies suggest a possible sex-specific response to bevacizumab in metastatic colorectal carcinoma, showing a benefit in males, while the effect in females is less significant. Methods Data from 3369 metastatic colorectal carcinoma patients enrolled on four first-line randomized trials testing chemotherapy with or without bevac...

Introduction: Analyzing longitudinal cancer quality-of-life (QoL) measurements and their impact on clinical outcomes may improve our understanding of patient trajectories during systemic therapy. We applied an unsupervised growth mixture modeling (GMM) approach to identify unobserved subpopulations ("patient clusters") in the CO.20 clinical trial...

Background Higher body mass index is associated with a higher incidence of colorectal cancer (CRC) but also with improved survival in metastatic CRC (mCRC). Whether weight change after mCRC diagnosis is associated with survival remains largely unknown. Methods We analysed individual patient data for previously untreated patients enrolled in five p...

Oesophageal adenocarcinoma (OAC) is a deadly disease with an increasing incidence globally. Treatment outcomes with traditional therapy have largely plateaued and responses to immunotherapy are modest at best, necessitating the need for better biomarker driven selection. We aimed to unravel the tumour neoantigen landscape and immune microenvironmen...

The incidence of oesophageal adenocarcinoma (OAC) is rising in Western countries, with a 5-year overall survival (OS) rate of 14%. Curative treatment based on oesophagectomy is only suitable for ~50% of patients due to late-stage diagnosis. While the addition of preoperative chemotherapy or chemoradiotherapy has improved OS in OAC patients, little...

Introduction Australia has the highest incidence of melanoma in the world with variable care provided by a diverse range of clinicians. Clinical quality registries aim to identify these variations in care and provide anonymised, benchmarked feedback to clinicians and institutions to improve patient outcomes. The Australian Melanoma Clinical Outcome...

Although there are several established international guidelines on the management of hepatocellular carcinoma (HCC), there is limited information detailing specific indicators of good quality care. The aim of this study was to develop a core set of quality indicators (QIs) to underpin the management of HCC. We undertook a modified, two‐round, Delph...

Background: Non-metastatic pancreatic ductal adenocarcinoma (PDAC) is classified as resectable (R), borderline resectable (BR) or locally advanced (LA). International Consensus Guidelines on these definitions exist, but have not been integrated into everyday Australian practice. The anatomical features on CT imaging lend themselves to synoptic rep...

PURPOSE Sunitinib, a multitargeted tyrosine kinase inhibitor (TKI), is approved for advanced gastrointestinal stromal tumor (GIST) after imatinib failure. Ripretinib is a switch-control TKI approved for advanced GIST after prior treatment with three or more TKIs, including imatinib. We compared efficacy and safety of ripretinib versus sunitinib in...

Purpose of Review Cardiovascular disease is long-term complication of both cancer and anti-cancer treatment and can have significant ramifications for health-related quality of life and mortality. This narrative review explores the current evidence linking cardiovascular disease and cancer, as well as exploring strategies for the prevention and man...

Gastric cancer is one of the deadliest cancers worldwide. Accurate prognosis is essential for effective clinical assessment and treatment. Spatial patterns in the tumor microenvironment (TME) are conceptually indicative of the staging and progression of gastric cancer patients. Using spatial patterns of the TME by integrating and transforming the m...

Colorectal cancer (CRC) chemoprevention is an area of interest. Non-steroidal anti-inflammatory drugs (NSAIDs) are anti-inflammatory agents which have been identified as cancer chemoprevention agents given that inflammation is thought to contribute to tumorigenesis. Most studies have demonstrated that the NSAID, aspirin, plays a beneficial role in...

Objective: There is limited evidence on the development of pancreatic and oesophagogastric cancer, how patients decide to seek help and the factors impacting help-seeking. Our study, the first in Australia, aimed to explore symptom appraisal and diagnostic pathways in these patients. A secondary aim was to examine the potential to recruit cancer p...

Although aspirin has been considered a promising agent for prevention of colorectal cancer, recent data suggest a lack of benefit among older individuals. Whether some individuals with higher risk of colorectal cancer may benefit from aspirin remains unknown. We used a 95-variant colorectal cancer polygenic risk score (PRS) to explore the associati...

Background AGITG DOCTOR was a randomised phase 2 trial of pre-operative cisplatin, 5 fluorouracil (CF) followed by docetaxel (D) with or without radiotherapy (RT) based on poor early response to CF, detected via PET, for resectable oesophageal adenocarcinoma. This study describes PROs over 2 years. Methods Participants ( N = 116) completed the EOR...

Gastrointestinal stromal tumours (GISTs) are the most common gastrointestinal tract mesenchymal tumours. Tyrosine kinase inhibitors (TKIs) have transformed the management of advanced GIST. Imatinib was the first TKI to gain approval as management for patients with advanced GIST, establishing a new standard of care. Since then, as a result of severa...

Simple Summary Older patients with cancer are more likely to experience a deterioration in their functional status than are their similar-aged, cancer-free counterparts. Such functional decline can be accelerated by cancer treatment. With adequate long-term care comprising routine functional assessment and evidence-based interventions, functional s...

Background: We evaluated the time to progression (TTP) and survival outcomes of second-line therapy for metastatic colorectal cancer among adults aged 70 years and older compared with younger adults following progression on first-line clinical trials. Methods: Associations between clinical and disease characteristics, time to initial progression...

Purpose Colorectal cancer (CRC) affects many older adults. We investigated the efficacy and safety of adding anti-epidermal growth factor receptor (EGFR) agents to doublet chemotherapy (DC) in older patients. Methods Patients with RAS wild-type (WT) metastatic CRC (mCRC) receiving first-line DC + anti-EGFR (n = 1191) or DC alone (n = 729) from sev...

Background Pancreatic and oesophagogastric (OG) cancers have a dismal prognosis and high symptom burden, with supportive care forming an integral component of the care provided to patients. This study aimed to explore the supportive care experiences of patients and caregivers living with pancreatic and OG cancers in order to identify perceived oppo...

Introduction: Pancreatic cancer (PC) has a dismal prognosis, with identified disparities in survival outcomes based on demographic characteristics. These disparities may be ameliorated by equitable access to treatments and health services. This systematic review identifies patient and service-level characteristics associated with PC health service...

Background Pancreatic ductal adenocarcinoma (PDAC) has poor survival. Current treatments offer little likelihood of cure or long-term survival. This systematic review evaluates prognostic models predicting overall survival in patients diagnosed with PDAC. Methods We conducted a comprehensive search of eight electronic databases from their date of...

Meta-analysis based upon individual participant data (IPD) is a powerful methodology for synthesizing evidence by combining information drawn from multiple trials. Hitherto, its principal application has been in questions of clinical management, but an increasingly important use is in clarifying trials methodology, for instance in the selection of...

Background Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer death and lacks effective treatment options. Diagnostic endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) biopsies represent an appealing source of material for molecular analysis to inform targeted therapy, as they are often the only available tissue for pa...

It is well recognized that randomized controlled trials (RCTs) are a powerful tool to investigate causal relationships, and are considered the gold standard level of research evidence. However, RCTs can be expensive and time-consuming, and when they employ strict eligibility criteria, it results in an unrepresentative population and limited externa...

Background: This study: (i) assessed compliance with a consensus set of quality indicators (QIs) in pancreatic cancer (PC); and (ii) evaluated the association between compliance with these QIs and survival. Methods: Four years of data were collected for patients diagnosed with PC. Cox proportional hazards models were used to estimate hazard rati...

Purpose: Most patients with gastrointestinal stromal tumor (GIST) have activating mutations in KIT/PDGFRA and are initially responsive to tyrosine kinase inhibitors (TKIs). The acquisition of secondary mutations leads to refractory/relapsed disease. This study reports the results of an analysis from the phase 3 INVICTUS study (NCT03353753) charact...

Background: Ripretinib 150 mg once daily (QD) is indicated for advanced gastrointestinal stromal tumor (GIST) as ≥fourth-line therapy. In INVICTUS, ripretinib intra-patient dose escalation (IPDE) to 150 mg twice daily (BID) was allowed after progressive disease (PD) on 150 mg QD by blinded independent central review using modified RECIST 1.1. We r...

Quality of care is defined by a range of dimensions (safe, effective, efficient, timely, patient-centred and equitable care) and components (structure, process, outcome). From a clinical perspective, quality of care is measured through the development of core-sets of quality indicators that is based on current evidence and best practice. In additio...

Background Accurate pre-operative imaging plays a vital role in patient selection for surgery and in allocating stage-appropriate therapies to patients diagnosed with pancreatic cancer (PC). This study aims to: (1) understand the current diagnosis and staging practices for PC; and (2) explore the factors (barriers and enablers) that influence the u...

Background Evidence-based clinical practice guidelines recommend discussion by a multidisciplinary team (MDT) to review and plan the management of patients for a variety of cancers. However, not all patients diagnosed with cancer are presented at an MDT. Objectives (1) To identify the factors (barriers and enablers) influencing presentation of all...

Purpose: Expanded RAS/BRAF mutations have not been assessed as predictive for single-agent cetuximab in metastatic colorectal cancer (mCRC), and low mutant allele frequency (MAF) mutations are of unclear significance. We aimed to establish cetuximab efficacy in optimally selected patients using highly sensitive beads, emulsion, amplification, and...

Sarcomas are a heterogeneous group of malignancies with mesenchymal lineage differentiation. The discovery of neurotrophic tyrosine receptor kinase (NTRK) gene fusions as tissue-agnostic oncogenic drivers has led to new personalized therapies for a subset of patients with sarcoma in the form of tropomyosin receptor kinase (TRK) inhibitors. NTRK gen...

Background: Second-line (2 L) chemotherapies for advanced or metastatic gastric cancer have shown improved survival but there is no commonly accepted standard of care. This study examines real-world patient characteristics, treatment patterns, healthcare resource use (HCRU) and clinical outcomes in this setting. Methods: Retrospective chart revi...

Background: Patients with oesophageal/gastro-oesophageal junction adenocarcinoma (EAC) not showing early metabolic response (EMR) to chemotherapy have poorer survival and histological response rates <5%. We investigated whether tailoring neoadjuvant therapy can improve outcomes in these patients. Patients and methods: Patients with resectable EA...

Ripretinib (DCC-2618) is a novel, type II tyrosine switch control inhibitor designed to broadly inhibit activating and drug-resistant mutations in KIT and PDGFRA. Ripretinib has emerged as a promising investigational agent for the treatment of gastrointestinal stromal tumor owing to targeted inhibition of secondary resistance mutations that may dev...

Background Ripretinib is a switch-control kinase inhibitor that broadly inhibits KIT- and PDGFRA-mutated kinases by regulating the kinase switch pocket and activation loop. Methods Patients (pts) with advanced GIST who received prior treatment with at least imatinib, sunitinib, and regorafenib were enrolled. Pts were randomized 2:1 to ripretinib 1...

Background AGOC has a poor prognosis with limited benefits from treatments following failure of chemotherapy (CT). Regorafenib (BAY 73-4506)(REG) is an oral multi-kinase inhibitor targeting kinases involved in angiogenesis (VEGFR1-3, TIE-2), tumor microenvironment (PDGFR-β, FGFR), and oncogenesis (RAF, RET and KIT). INTEGRATE (phase 2) demonstrated...

Importance Tumor measurements can be used to estimate time to nadir and depth of nadir as potential surrogates for overall survival (OS). Objective To assess time to nadir and depth of nadir as surrogates for OS in metastatic colorectal cancer. Design, Setting, and Participants Pooled analysis of 20 randomized clinical trials within the Aide et R...

Purpose The Upper Gastrointestinal Cancer Registry (UGICR) was developed to monitor and improve the quality of care provided to patients with upper gastrointestinal cancers in Australia. Participants It supports four cancer modules: pancreatic, oesophagogastric, biliary and primary liver cancer. The pancreatic cancer (PC) module was the first modu...

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. The aim of...

Background: Estimating prognosis on the basis of clinicopathologic factors can inform clinical practice and improve risk stratification for clinical trials. We constructed prognostic nomograms for one-year overall survival and six-month progression-free survival in metastatic colorectal carcinoma by using the ARCAD database. Methods: Data from 2...