Gender profile of principal investigators in a large academic clinical trials group

IntroductionGender equity in medicine has become a significant topic of discussion due to consistently low female representation in academia and leadership roles. Gender imbalance directly affects patient care. This study examined the gender and craft group of the Principal Investigators (PI) of clinical trials run by the Australasian Gastro-Intestinal Trials Group (AGITG)MethodsPublicly available data was obtained from the AGITG website. Trials were divided into upper, lower gastrointestinal cancer, miscellaneous (neuroendocrine and gastrointestinal stromal tumours). Where multiple PIs were listed, all were counted. Craft group was assigned as surgical, medical, radiation oncology or other.ResultsThere were 69 trials with 89 PI, where 52 trials were represented exclusively by male PIs. Of all PIs, 18 were women (20.2%); all were medical oncologists. Prior to 2005, all PIs were male. The craft group distribution of PIs was: 79% medical oncologists, 12% surgical oncologists, 8% radiation oncologist, 1% nuclear medicine physicians. Regarding trials with multiple PI's, there were 19 in total. Of these, 11 had only male PIs, which included 5 surgeons. Females were more likely to be a co-PI (42%) as opposed to sole PI (18%). There was no gender policy publicly available on the AGITG website.ConclusionsThere is a low percentage of female PIs in academic oncology trials in the portfolio of this large international trials group. No trial was led by a female surgical or radiation oncologist. There is a need to understand the reasons driving the disparity so that specific strategies can be put in place

Current Utility and Future Applications of ctDNA in Colorectal Cancer

Circulating tumour DNA (ctDNA) shows promise as a minimally invasive biomarker with a myriad of emerging applications including early detection and diagnosis, monitoring of disease and treatment efficacy, and identification of actionable alterations to guide treatment. The potential utility of ctDNA in colorectal carcinoma (CRC) is of particular interest given the limitations of current radiographic imaging and blood-based tumour markers in detecting disease and evaluating therapeutic benefit. While ctDNA has yet to demonstrate clinical utility in CRC, a growing body of research highlights the potential of these novel biomarkers. This chapter provides an overview of the current evidence for employing ctDNA in CRC as well as previewing the future directions that these exciting technologies may take

Endoscopic Ultrasound in Pancreatic Cancer

Endoscopic ultrasound (EUS) has been developed over the course of the last 50 years. This technique has been shown to improve diagnosis, provide more accurate local information with regards to staging and enhance prediction of surgical resectability. Further to this, minimally-invasive local techniques have been developed, and continue to be developed, to provide both active and palliative management within the treatment schema for pancreatic cancer (PC)

Interim position emission tomography-computed tomography during multimodality treatment of locally advanced esophageal cancer: a scoping review.

BACKGROUND Among cancers, esophageal cancer (EC) has one of the highest incidences and mortality in Asia. As recognized in many national guidelines, functional imaging performed with position emission tomography is recommended for patients with locally advanced disease. This review evaluated evidence for the use of fluorodeoxyglucose (FDG) interim positron emission tomography (PETint) in bimodality (chemoradiation) and trimodality (chemoradiation followed by surgery) management of locally advanced esophageal cancer (LAEC), with a focus on its prognostic and predictive value. METHODS The MEDLINE database was searched from January 1, 2001, to January 1, 2022, as part of a scoping review. References of selected articles were manually checked to identify other articles meeting the inclusion criteria; only original articles were included, and reviews, guidelines, letters, editorials, and case reports were excluded. RESULTS A total of 63 articles were included in this review. PET-computed tomography (PET-CT) is recognized as having a significant role in the assessment of treatment response. Studies on the predictive PETint suggest that it has a certain value, particularly for early response. Identification of poor responders or nonresponders soon after commencement of multimodality treatment allows for treatment modification. CONCLUSIONS The scoping review indicated variable utility for the prognostic value of PETint. There is a need to improve its accuracy, which can likely be achieved through greater standardization of measurements and reporting and testing as well as combination with other promising measures of response to residual disease

Strategies for the delay of surgery in the management of resectable hepatobiliary malignancies during the COVID-19 pandemic

Objective: We aimed to review data about delaying strategies for the management of hepatobiliary cancers requiring surgery during the covid-19 pandemic. Background: Given the covid-19 pandemic, many jurisdictions, to spare resources, have limited access to operating rooms for elective surgical activity, including cancer, thus forcing deferral or cancellation of cancer surgeries. Surgery for hepatobiliary cancer is high-risk and particularly resource-intensive. Surgeons must critically appraise which patients will benefit most from surgery and which ones have other therapeutic options to delay surgery. Little guidance is currently available about potential delaying strategies for hepatobiliary cancers when surgery is not possible. Methods: An international multidisciplinary panel reviewed the available literature to summarize data relating to standard-of-care surgical management and possible mitigating strategies to be used as a bridge to surgery for colorectal liver metastases, hepatocellular carcinoma, gallbladder cancer, intrahepatic cholangiocarcinoma, and hilar cholangiocarcinoma. Results: Outcomes of surgery during the covid-19 pandemic are reviewed. Resource requirements are summarized, including logistics and adverse effects profiles for hepatectomy and delaying strategies using systemic, percutaneous and radiation ablative, and liver embolic therapies. For each cancer type, the long-term oncologic outcomes of hepatectomy and the clinical tools that can be used to prognosticate for individual patients are detailed. Conclusions: There are a variety of delaying strategies to consider if availability of operating rooms decreases. This review summarizes available data to provide guidance about possible delaying strategies depending on patient, resource, institution, and systems factors. Multidisciplinary team discussions should be leveraged to consider patient- and tumour-specific information for each individual case.publishedVersio

Off-trial evaluation of bisphosphonates in patients with metastatic breast cancer

BACKGROUND: Bisphosphonate therapy has been readily accepted as standard of care for individuals with bone metastases from breast cancer. In this study we determined whether the proportion of patients experiencing a skeletal related event (SRE) in a clinical practice population was similar to that observed in phase III randomized controlled studies. METHODS: A retrospective chart review was conducted of 110 patients receiving intravenous bisphosphonates for advanced breast cancer. The proportion of patients experiencing at least one SRE after 12 months of therapy was determined. SRE included vertebral or non-vertebral fracture, cord compression, surgery and/or radiotherapy to bone. RESULTS: The proportion of patients who had an SRE was 30% (28 individuals) and the median time to first event was greater than 350 days. Non-vertebral events and radiotherapy were the most frequent type of SRE, while cord compression and hypercalcaemia were rare (1%). Most patients in the study had bone-only disease (58.2%) and most had multiple bone lesions. In the first 12 months the mean duration of exposure to intravenous bisphosphonates was 261 days and most patients remained on treatment until just before death (median 27 days). CONCLUSION: This study suggests that the rate of clinically relevant SREs is substantially lower than the event rate observed in phase III clinical trials. We attribute this lower rate to observational bias. In the clinical trial setting it is possible that over-detection of skeletal events occurs due to the utilisation of regular skeletal survey or radionucleotide bone scan, whereas these procedures are not routine in clinical practice. Phase IV observational studies need to be conducted to determine the true benefits of bisphosphonate therapy in order to implement rationale use of bisphosphonates

Three versus six months of adjuvant doublet chemotherapy for patients with colorectal cancer: a multi-country cost-effectiveness and budget impact analysis

Introduction: The Short Course Oncology Treatment (SCOT) trial demonstrated non-inferiority, less toxicity and cost-effectiveness from a UK perspective of 3 versus 6 months of oxaliplatin-based chemotherapy for patients with colorectal cancer. This study assessed the cost-effectiveness of shorter treatment, and the budget impact of implementing trial findings from the perspective of all countries that recruited to SCOT: Australia, Denmark, New Zealand, Spain, Sweden and the UK. Methods: Individual cost-utility analyses (CUAs) were performed from the perspective of each country. Resource, quality of life and survival estimates from the SCOT trial (n=6,065) were used. Probabilistic sensitivity analysis and sub-group analyses were undertaken. Using undiscounted costs from these CUAs, the impact on the country specific healthcare budgets of implementing the SCOT trial findings was calculated over a 5-year period. United States dollars were the currency used, with 2019 as base year. One-way and scenario sensitivity analysis addressed uncertainty within the budget impact analysis. Results: Three months of treatment was cost-saving and cost-effective compared to 6 months from the perspective of all countries. The incremental net monetary benefit per patient ranged from $8,972 (Spain) to$13,884 (Denmark). The healthcare budget impact over 5 years for the base case scenario ranged from $3.6 million (New Zealand) to$61.4 million (UK) and totalled over $150 million across all countries. Discussion: This study has widened the transferability of results from the SCOT trial, showing shorter treatment is cost-effective from a multi-country perspective. The vast savings from implementation could fully justify the investment in conducting the SCOT trial

SCOT: a comparison of cost-effectiveness from a large randomised phase III trial of two durations of adjuvant Oxaliplatin combination chemotherapy for colorectal cancer.

BACKGROUND: The Short Course Oncology Therapy (SCOT) study is an international, multicentre, non-inferiority randomised controlled trial assessing the efficacy, toxicity, and cost-effectiveness of 3 months (3 M) versus the usually given 6 months (6 M) of adjuvant chemotherapy in colorectal cancer. METHODS: In total, 6088 patients with fully resected high-risk stage II or stage III colorectal cancer were randomised and followed up for 3-8 years. The within-trial cost-effectiveness analysis from a UK health-care perspective is presented using the resource use data, quality of life (EQ-5D-3L), time on treatment (ToT), disease-free survival after treatment (DFS) and overall survival (OS) data. Quality-adjusted partitioned survival analysis and Kaplan-Meier Sample Average Estimator estimated QALYs and costs. Probabilistic sensitivity and subgroup analysis was undertaken. RESULTS: The 3 M arm is less costly (-£4881; 95% CI: -£6269; -£3492) and entails (non-significant) QALY gains (0.08; 95% CI: -0.086; 0.230) due to a better significant quality of life. The net monetary benefit was significantly higher in 3 M under a wide range of monetary values of a QALY. The subgroup analysis found similar results for patients in the CAPOX regimen. However, for the FOLFOX regimen, 3 M had lower QALYs than 6 M (not statistically significant). CONCLUSIONS: Overall, 3 M dominates 6 M with no significant detrimental impact on QALYs. The results provide the economic case that a 3 M treatment strategy should be considered a new standard of care

ICECREAM: randomised phase II study of cetuximab alone or in combination with irinotecan in patients with metastatic colorectal cancer with either KRAS, NRAS, BRAF and PI3KCA wild type, or G13D mutated tumours

BACKGROUND: Patients with metastatic colorectal cancer whose disease has progressed on oxaliplatin- and irinotecan-containing regimens may benefit from EGFR-inhibiting monoclonal antibodies if they do not contain mutations in the KRAS gene (are &quot;wild type&quot;). It is unknown whether these antibodies, such as cetuximab, are more efficacious in refractory metastatic colorectal cancer as monotherapy, or in combination with irinotecan. Lack of mutation&nbsp;in KRAS, BRAF and PIK3CA predicts response to EFGR-inhibitors. The ICECREAM trial examines the question of monotherapy versus combination with chemotherapy in two groups of patients: those with a &quot;quadruple wild type&quot; tumour genotype (no mutations in KRAS, NRAS, PI3KCA or BRAF genes) and those with the specific KRAS mutation in codon G13D, for whom possibly EGFR-inhibitor efficacy may be equivalent. METHODS AND DESIGN: ICECREAM is a randomised, phase II, open-label, controlled trial comparing the efficacy of cetuximab alone or with irinotecan in patients with &quot;quadruple wild type&quot; or G13D-mutated metastatic colorectal cancer, whose disease has progressed on, or who are intolerant of oxaliplatin- and fluoropyrimidine-based chemotherapy. The primary endpoint is the 6-month progression-free survival benefit of the treatment regimen. Secondary endpoints are response rate, overall survival, and quality of life. The tertiary endpoint is prediction of outcome with further biological markers. International collaboration has facilitated recruitment in this prospective trial of treatment in these infrequently found molecular subsets of colorectal cancer. DISCUSSION: This unique trial will yield prospective information on the efficacy of cetuximab and whether this is further enhanced with chemotherapy in two distinct populations of patients with metastatic colorectal cancer: the &quot;quadruple wild type&quot;, which may \u27superselect\u27 for tumours sensitive to EGFR-inhibition, and the rare KRAS G13D mutated tumours, which are also postulated to be sensitive to the drug. The focus on establishing both positive and negative predictive factors for the response to targeted therapy is an attempt to improve outcomes, reduce toxicity and contain treatment costs. Tissue and blood will yield a resource for molecular studies. Recruitment, particularly of patients with the rare G13D mutation, will demonstrate the ability for international collaboration to run prospective trials in small colorectal cancer molecular subgroups.<br /

Management of Asymptomatic Sporadic Nonfunctioning Pancreatic Neuroendocrine Neoplasms (ASPEN) <= 2 cm: Study Protocol for a Prospective Observational Study

Introduction: The optimal treatment for small, asymptomatic, nonfunctioning pancreatic neuroendocrine neoplasms (NF-PanNEN) is still controversial. European Neuroendocrine Tumor Society (ENETS) guidelines recommend a watchful strategy for asymptomatic NF-PanNEN <2 cm of diameter. Several retrospective series demonstrated that a non-operative management is safe and feasible, but no prospective studies are available. Aim of the ASPEN study is to evaluate the optimal management of asymptomatic NF-PanNEN ≤2 cm comparing active surveillance and surgery. Methods: ASPEN is a prospective international observational multicentric cohort study supported by ENETS. The study is registered in ClinicalTrials.gov with the identification code NCT03084770. Based on the incidence of NF-PanNEN the number of expected patients to be enrolled in the ASPEN study is 1,000 during the study period (2017–2022). Primary endpoint is disease/progression-free survival, defined as the time from study enrolment to the first evidence of progression (active surveillance group) or recurrence of disease (surgery group) or death from disease. Inclusion criteria are: age >18 years, the presence of asymptomatic sporadic NF-PanNEN ≤2 cm proven by a positive fine-needle aspiration (FNA) or by the presence of a measurable nodule on high-quality imaging techniques that is positive at 68Gallium DOTATOC-PET scan. Conclusion: The ASPEN study is designed to investigate if an active surveillance of asymptomatic NF-PanNEN ≤2 cm is safe as compared to surgical approach