ACRF research grants 2019


We congratulate Professor Michelle Haber, Children’s Cancer Institute Sydney, as a deserving recipient of the 2019 ACRF annual grant for her ground breaking programme incorporating the liquid biopsy.

Reducing the devastating impact of cancer treatment on children 

The current precision medicine treatment recommendations for children are based on an invasive and often painful procedure – tissue biopsy.

The $3.5 Million grant will fund next-generation sequencing technology to develop highly sensitive and minimally-invasive tests for children with cancer- using blood and body fluid samples.

This technology has the potential to benefit paediatric sarcoma patients nationally, and CRBF will be partnering in this exciting initiative over a three year period, to provide a dedicated sarcoma researcher, to work in tandem with this initiative.  The programme is the work of Dr Emmy Fleuren, who has incepted the sarcoma specific Phosphoproteomic study, and will work in tandem with the work of Professor Haber, in the area of liquid biospsy.

 

Read more about the liquid biopsy programme

The ACRF Child Cancer Liquid Biopsy Program

 

The IL23 sarcoma clinical study

The Background

When Cooper was in the hospital fighting for his life in Australia, the 18-year-old was extremely curious about why there were no new treatments. He asked his doctors’ many questions his dad Colin Brading noted.  Cooper passed due to the bone cancer, tragically, but his family set up a foundation to help search for a cure to the disease—it was what Cooper wanted. His life force lives on in his foundation which will persist from now onward to help others that were in his position.

Enter Interleukin-23 (IL23)

Researchers at Garvan Institute of Medical Research uncovered that the immune molecule is key to the growth of the tumor and targeting it in studies successfully shrank cancer in mice reported 9 News in Australia. Immunotherapies targeting IL23 represent an important push in the fight against autoimmune diseases such as arthritis, inflammatory bowel disease, and the skin condition psoriasis.  Professor David Thomas with Garvan Cancer Research and Director of The Kinghorn Cancer Centre noted: “When we blocked IL23 or knocked it out in the mouse in this particular case, we stopped tumors from development.”

Planned Sarcoma Study Powered by the Spirit of Cooper Rice-Brading

The Cooper Rice-Brading foundation is helping to pay for clinical research along with the Garvan Institute of Medical Research to explore existing IL23 therapies for this form of bone cancer. Funds inbound will go towards clinical trials which will commence before the second half of 2020 reports 9 News. Professor Thomas noted, “We hope to treat up to 32 people with advanced, incurable sarcomas.”

The Cooper Rice-Brading Foundation

For those that want to contribute to keeping Cooper’s vision alive, they can follow the link to the Cooper Rice-Brading Foundation and contribute so that we can be certain that this important clinical trial will occur.  Brading’s dad stated, “it is Cooper’s vision becoming a reality.” See the link for the donation page.

The Garvan Institute of Medical Research

Garvan Institute of Medical Research is a leading, multi-disciplinary biomedical research institute in Darlinghurst, Sydney. With some of the brightest minds and best technologies on the planet, they like to look at the big picture of health and disease.

They were founded in 1963 by the Sisters of Charity as a research department of St. Vincent’s Hospital. Now one of Australia’s largest medical research institutions with approximately 750 scientists, students and support staff.

Major focus areas for investigational research include cancer, diabetes, osteoporosis, Alzheimer’s disease, Parkinson’s disease as well as other autoimmune disorders and asthma. They specialize in genetic and molecular technologies and emphasize collaborative research.

In 2014 the institute became part of an elite group that has the ability to sequence the human genome at a base cost below $1,000 each ($1,000 genome) when it purchased the next generation of genome sequencing technology, capable of sequencing 350 genomes a week. 

Long tumour correlation

LTD Changes Correlate With OS in Localised High-Risk Soft Tissue Sarcoma

June 20th 2020
OncLive have last week reported a percentage change in longest tumor diameter of patients with localised high-risk soft tissue sarcoma, treated with neoadjuvant chemotherapy, were found to correlate with overall survival.

A percentage change in longest tumour diameter (LTD) of patients with localised high-risk soft tissue sarcoma (STS) who were treated with neoadjuvant chemotherapy was found to correlate with overall survival (OS), according to updated results from a phase 3 trial presented at the 2020 ASCO Virtual Scientific Program.1

Of the 325 patients who enrolled on the study and were determined to be evaluable for response, 181 received neoadjuvant chemotherapy; 92 of those patients received standard chemotherapy comprised of an Epirubicin and Ifosfamide, while 89 received histology-driven chemotherapy.2 The other 144 patients received concurrent chemoradiotherapy and were excluded from the analysis. RECIST data were available for a total of 176 patients, 90 of whom were in the standard arm and 86 of whom were in the investigational arm.

Results demonstrated a significant link between changes in LTD and OS rate in patients with STS. Specifically, the correlation between survival and response was observed in the overall patient population as well as within the standard and investigative cohorts. Patients in the overall population who experienced any amount of reduction in LTD (n = 101) were noted as having a better prognosis than those who experienced no changes (n = 28) or had an increase in LTD (n = 52). Percentage changes in LTD were also associated with OS within the standard (log-rank, = .023) and the investigative arms (log-rank, = .053), as well; however, different patterns were observed.

For the analysis, investigators set out to determine the prognostic relevance of percentage changes in LTD in patients with STS who were treated with neoadjuvant chemotherapy. In the trial, patients with localised high-risk STS, either of the extremities or the trunk walls, and who had been diagnosed with myxoid liposarcoma, leiomyosarcoma, synovial sarcoma, malignant peripheral nerve sheath tumour, or undifferentiated pleomorphic sarcoma were randomised to receive either 3 cycles of the neoadjuvant standard regimen or the histology-tailored regimen.

Notably, patients with myxofibrosarcoma, pleomorphic liposarcoma, pleomorphic rhabdomyosarcoma, or unclassified spindle cell sarcoma were prospectively registered and received treatment with the standard regimen.

Percentage changes in LTD were found by evaluating these levels at baseline and after 3 cycles of treatment with either regimen before surgery. Investigators evaluated OS in both groups post-surgery through the use of Kaplan-Meier estimates and log-rank tests. Then, they looked for cutoffs that would be allow them to determine prognosis with either an increase or reduction in LTD by applying a proposed change-point method.

Further results from an unplanned analysis within the study were also reported. For this effort, investigators applied cut-point methodology to establish non-significant optimal cutoffs with regard to tumour reduction (20%, = .14), as well as progression (25%, = .47). Although the investigators were able to demonstrate a reasonable survival pattern through these cutoffs, a validation study of the proposed cutoffs is necessary in order to thoroughly evaluate them.

“In our study, RECIST V. 1.1 and any [percent] reduction in LTD of patients treated with neoadjuvant chemotherapy for localised high-risk STS correlated with the outcome,” the investigators wrote. “A [percent]variation cutoff both in increase and decrease in LTD able to predict the outcome could be identified only for the whole patients population. ”

Reference

  1. Stacchiotti S, Morosi C, Braglia L, et al. Prognostic role of % changes in longest tumour diameter (LTD) in localised high-risk soft tissue sarcoma (STS) treated with neoadjuvant chemotherapy in a randomised clinical trial. J Clin Oncol. 10.1200/JCO.2020.38.15_suppl.11558
  2. Localised high-risk soft tissue sarcomas of the extremities and trunk wall in adults: an integrating approach comprising standard vs histotype-tailored neoadjuvant chemotherapy. ClinicalTrials.gov. Updated May 13, 2019. Accessed June 19, 2020. https://clinicaltrials.gov/ct2/show/NCT01710176?term=NCT01710176&draw=2&rank=1
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