John Zalcberg

• MB BS, PhD, FRACP, FRACMA, FAHMS, FAICD
• Head of Department at Monash University (Australia)

Background Pancreatic cancer is the third leading cause of cancer-related death in Australia, with a persistently poor 5-year survival rate of around 13%. Symptoms arising from the disease and chemotherapy such as epigastric pain, anorexia, bloating and fat-malabsorptive diarrhoea cause poor oral intake and weight loss, and reduce an individual’s q...

Background Surgery combined with chemotherapy provides the best chance of survival in pancreatic cancer. This study investigated whether increasing the resection rate at a population level improves overall survival and modelled the interaction between resection rate, perioperative mortality rate, and population survival. Methods A systematic review...

Backgrounds Streamlined, expedited clinical research is fundamental to rapidly test, translate and implement novel treatments into routine care to improve patient outcomes. The National Mutual Acceptance (NMA) scheme was designed to expedite the ethics approval process, however, growing concerns exist about the fragmented time‐consuming governance...

PURPOSE Treatment options for refractory advanced gastric and esophagogastric junction cancer (AGOC) are limited. Regorafenib, an oral multikinase inhibitor, prolonged progression-free survival (PFS) versus placebo in the INTEGRATE I phase II trial. INTEGRATE IIa was designed to examine whether regorafenib improved overall survival (OS). METHODS A...

Background Cancer survivors can be at risk of cardiovascular disease (CVD) because of either their malignancy or its treatment. Although studies linking cancer and CVD exist, few examine risk in older adults, the impact of cancer treatment, or the effect of aspirin on reducing risk in this cohort. Methods The authors conducted a secondary analysis...

Background: In Western countries, the current standard of care for resectable gastric cancer is perioperative chemotherapy. Preoperative chemoradiotherapy has been considered, but data are limited regarding this treatment as compared with perioperative chemotherapy alone. Methods: We conducted an international, phase 3 trial in which patients wi...

Executive summary Disease overview & management Gastrointestinal stromal tumor (GIST) is the most common gastrointestinal sarcoma, with approximately 80% of cases driven by activating mutations in KIT. Sunitinib is a multitargeted tyrosine kinase inhibitor (TKI) approved as a second-line therapy for advanced GIST after disease progression on or in...

Simple Summary Single small primary liver cancers are curable with treatments such as surgical resection, ablation, and liver transplant; however, many patients initially receive trans-arterial chemo-embolisation (TACE), which is generally not considered a curative treatment in itself, and often go on to receive further follow-up treatments. Little...

Background Complete surgical removal of pancreatic ductal adenocarcinoma (PDAC) is central to all curative treatment approaches for this aggressive disease, yet this is only possible in patients technically amenable to resection. Hence, an accurate assessment of whether patients are suitable for surgery is of paramount importance. The SCANPatient t...

Simple Summary Little is known about the differences in liver cancer care between liver cancer referral centres, with and without an integrated liver transplant program. Even after adjusting for other important factors, such as tumour stage and patient characteristics, we found that liver transplant centres systematically used different local cance...

Background Unlike many other types of cancer, improvements in the treatment of pancreatic cancer have been very limited, in part due to the inability to deliver chemotherapy to the tumor at efficacious concentrations for a prolonged time. PTM-101 is a novel biodegradable film containing paclitaxel and is designed to continuously release high concen...

Objective Lung cancer is the leading cause of cancer‐related death globally and provides a major disease burden likely to substantially impact quality of life (QoL). Patient‐reported outcome measures (PROMs) have been identified as effective methods of evaluating patient QoL. Existing lung cancer–specific PROMs however have uncertain utility and mi...

Background KRAS mutations in metastatic colorectal cancer (mCRC) are used as predictive biomarkers to select therapy with EGFR monoclonal antibodies (mAbs). Other factors may be significant determinants of benefit. Methods Individual patient data from randomised trials with a head-to-head comparison between EGFR mAb versus no EGFR mAb (chemotherap...

Background Up to 70% of people diagnosed with upper gastrointestinal (GI) tract or hepato-pancreato-biliary (HPB) cancers experience substantial reductions in quality of life (QoL), including high distress levels, pain, fatigue, sleep disturbances, weight loss and difficulty swallowing. With few advocacy groups and support systems for adults with u...

INTRIGUE was an open-label, phase 3 study in adult patients with advanced gastrointestinal stromal tumor who had disease progression on or intolerance to imatinib and who were randomized to once-daily ripretinib 150 mg or sunitinib 50 mg. In the primary analysis, progression-free survival (PFS) with ripretinib was not superior to sunitinib. In clin...

Purpose Sidedness is prognostic and predictive of anti-EGFR efficacy in metastatic colorectal cancer (mCRC). Transverse colon has been historically excluded from several analyses of sidedness and the optimal division between left- and right-sided colorectal cancer is unclear. We investigated transverse colon primary tumor location as a biomarker in...

Introduction Stage of pancreatic carcinoma at diagnosis is a strong prognostic indicator of morbidity and mortality, yet is poorly notified to population-based cancer registries (”cancer registries”). Registry-derived stage (RD-Stage) provides a method for cancer registries to use available data sources to compile and record stage in a consistent w...

Background Capture of cancer stage at diagnosis is important yet poorly reported by health services to population-based cancer registries. In this paper we describe current completeness of stage information for endometrial cancer available in Australian cancer registries; and develop and validate a set of rules to enable cancer registry medical cod...

Simple Summary Cure is the goal of treatment in early primary liver cancer with surgical resection and ablation therapy being the two most common modalities used. This real-world multi-centre Australian study demonstrates that surgical treatment results in superior outcomes. We observed a significantly reduced risk of death from any cause and of re...

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...

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...

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...

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...