SUPPLEMENTARY INFORMATION

Supplementary Methods

Recruitment and consent. Approval was obtained from the institutional review board (IRB) at the Peter MacCallum Cancer Centre (PMCC) and the Royal Women’s Hospital (RWH); specialist clinical centres that draw patients from a wide geographic area, including metropolitan Melbourne (2000-2500 km2). Eligible patients have a verified diagnosis of ovarian, breast, prostate cancer or melanoma, are 18 years or older and aware of their terminal prognosis.

Signed consent is obtained from potential participants by treating oncologists and/or palliative care physicians when it was felt the patient accepted their prognosis, and would be receptive to a discussion about the program. Consent was only obtained when a next-of-kin (NOK) was present, to witness the decision and be made aware of the post-death logistics. Consistent with Victorian State guidelines for non-coronial post-mortem examination, the consent form (Supplementary Information) clearly describes the rapid autopsy collection, including the implications for open-casket viewing. Consent for brain examination is specifically obtained or denied. Participants understand that the program does not involve permanent donation of a body and that the family would remain responsible for interment. Participants and family are informed that the autopsy should be complete within 24 hours, and although unlikely to delay interment, could impact on some cultural practices. Family members have the opportunity to opt-out of the program at the time of the participant’s death.

Autopsy procedure. Autopsies are performed at the Victorian Institute of Forensic Medicine (VIFM; Melbourne, Victoria) by qualified pathology and mortuary technical staff. VIFM operates under the auspices of the Department of Justice of the Australian State of Victoria, and performs approximately 2500 autopsies per annum. Research team members received inductive training at VIFM, and had counselling services available to them if required.

A post mortem whole-body computed tomography (CT) scan is performed to document the extent of disease and presence of prostheses that may present a hazard during autopsy. This complements the clinical summary, completed at the time of consent, which provides a detailed description of the extent of disease, including cerebral metastatic spread, known sites of metastasis for sampling, and noted hazards such as implanted objects and infectious disease. Copies of the participant’s consent, death certificate and clinical summary are provided to VIFM.

Upon completion, all remaining tissues and organs are returned to the body, and the deceased readied for collection by the funeral service nominated by the family.

Sample processing. Blood is collected in acid citrate dextrose and EDTA tubes (Greiner Bio-One) at consent prior to participant death where possible, and processed within hours to obtain a blood pellet, plasma and serum (http://www.kconfab.org/Collection/Biospecimen_protocol.shtml) for genomic, proteomic and/or circulating tumor DNA analyses. Additional blood samples are collected at post-mortem.

At autopsy, tissue is snap frozen in liquid nitrogen, or collected into neutral buffered formalin for routine clinical histo-pathology processing for Formalin Fixed Paraffin Embedded (FFPE) blocks. Snap frozen tumor tissue is used for nucleic acid isolation. For both DNA and RNA, serial tumor sections were cut at -20ºC for tumor content assessment and needle dissection enrichment. DNA and RNA extractions are performed as described previously 1. NanoDrop1000 (Thermo Scientific) and the Qubit® dsDNA BR assays are used for DNA quantitation. RNA quality is assessed using the RNA 6000 Nano kit on the BioAnalyzer (Agilent). FFPE tissue is sectioned and stained with

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hematoxylin and eosin for pathological review of tumor content and necrosis. Additional tumor specific immunohistochemistry for p53 (Leica), ER (Ventana), S100 (Dako) is performed to determine protein expression, as per manufacturer directions.

To allow xenografting into immune compromised mice, tissue is collected into either RPMI 1640 or Hanks Buffered Salt Solution, and kept on ice. Patient derived xenografts (PDXs) are transplanted into NOD-SCID or NOD-SCID-IL-2Rγ (NSG) mice within a few hours of collection as described previously 2-6. All PDX experiments were performed according to animal ethics approvals and in accord with institutional guidelines (PMCC (E525; E421; E526; E457); Monash University (MARP-2014-085); Walter and Eliza Hall Institute (WEHI) AEC 2013.024rl)).

Supplementary Table 1: Quality of nucleic acids extracted from fresh-frozen tissue collected at autopsy

Patient Tissue Preparation Site A260/A280

(DNA) A260/A280

(RNA) RIN

Patient 1 Fresh Frozen Whole Section Site 1 1.87 - -

Patient 1 Fresh Frozen Whole Section Site 2 2.01 - -

Patient 1 Fresh Frozen Whole Section Site 3 1.77 - -

Patient 1 Fresh Frozen Whole Section Site 4 1.83 - -

Patient 1 Fresh Frozen Whole Section Site 5 1.96 - -

Patient 1 Fresh Frozen Whole Section Site 6 1.88 - -

Patient 1 Fresh Frozen Whole Section Site 7 1.94 - -

Patient 1 Fresh Frozen Whole Section Site 8 1.75 - -

Patient 2 Fresh Frozen Needle Dissected Site 1 2.06 2.15 4.5

Patient 2 Fresh Frozen Needle Dissected Site 2 - 1.86 6.4

Patient 2 Fresh Frozen Needle Dissected Site 3 2.08 2.11 5.1

Patient 2 Fresh Frozen Whole Section Site 1 - 2.12 NA

Patient 2 Fresh Frozen Whole Section Site 2 - 2.16 6.8

Patient 2 Fresh Frozen Whole Section Site 3 - 2.13 5.9

Patient 3 Fresh Frozen Needle Dissected Site 1 2.05 2.81 1

Patient 3 Fresh Frozen Needle Dissected Site 2 2.13 2.16 5.4

Patient 3 Fresh Frozen Whole Section Site 2 - 2.17 2.4

Patient 3 Fresh Frozen Whole Section Site 1 - 2.11 4.3

Patient 4 Fresh Frozen Whole Section Site 1 2.08 2.08 7.8

Patient 4 Fresh Frozen Needle Dissected Site 2 1.99 2.04 6.9

Patient 5 Fresh Frozen Needle Dissected Site 1 1.99 2.08 6.5

Patient 5 Fresh Frozen Whole Section Site 2 2.07 2.15 7.6

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Patient 6 Fresh Frozen Needle Dissected Site 1 1.97 2.05 3.1

Patient 6 Fresh Frozen Needle Dissected Site 2 1.95 2.1 5.1

Patient 7 Fresh Frozen Needle Dissected Site 1 1.99 1.98 4.3

Patient 7 Fresh Frozen Needle Dissected Site 2 1.99 2.07 6.3

Patient 8 Fresh Frozen Needle Dissected Site 1 2.05 2 NA

Patient 8 Fresh Frozen Needle Dissected Site 2 2.07 2.08 7.4

Patient 9 Fresh Frozen Whole Section Site 1 1.9 - -

Patient 9 Fresh Frozen Whole Section Site 2 1.79 - -

Patient 9 Fresh Frozen Whole Section Site 3 1.91 - -

Patient 9 Fresh Frozen Needle Dissected Site 4 1.89 - -

Patient 9 Fresh Frozen Needle Dissected Site 5 2.04 - -

Patient 9 Fresh Frozen Whole Section Site 6 1.9 - -

Patient 9 Fresh Frozen Whole Section Site 7 1.9 - -

Patient 9 Fresh Frozen Whole Section Site 8 1.91 - -

Patient 10 Fresh Frozen Whole Section Site 1 1.84 - -

Patient 10 Fresh Frozen Whole Section Site 2 1.95 - -

Patient 10 Fresh Frozen Needle Dissected Site 3 1.92 - -

Patient 10 Fresh Frozen Needle Dissected Site 4 1.91 - -

Patient 10 Fresh Frozen Whole Section Site 5 1.88 - -

Patient 11 Fresh Frozen Needle Dissected Site 1 1.86 - -

Patient 11 Fresh Frozen Whole Section Site 2 1.94 - -

Patient 11 Fresh Frozen Whole Section Site 3 1.95 - -

Patient 11 Fresh Frozen Whole Section Site 4 1.84 - -

Patient 11 Fresh Frozen Whole Section Site 5 1.94 - -

Patient 11 Fresh Frozen Whole Section Site 6 1.91 - -

Patient 11 Fresh Frozen Whole Section Site 7 1.8 - -

Patient 11 Fresh Frozen Whole Section Site 8 1.96 - -

Patient 11 Fresh Frozen Whole Section Site 9 1.88 - -

Patient 11 Fresh Frozen Whole Section Site 10 1.92 - -

Patient 11 Fresh Frozen Whole Section Site 11 1.89 - -

Patient 11 Fresh Frozen Whole Section Site 12 1.84 - -

DNA/RNA quality (A260/A280 ratio) assessed by NanoDrop1000 (Thermo Fisher Scientific, Waltham, MA) and RNA 6000 Nano kit on the BioAnalyzer (Agilent Santa Clara, CA; RIN = RNA Integrity Number) for tissue collected by the CASCADE program. Samples from Patients 2 and 3

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were suitable for whole genome sequencing analysis, and RNA of sufficient quality to validate identified mutations 1. RNA quality was consistent with previously published data on post-mortem tissue quality7. (NA = RNA quality was not assessable by software; - = not assessed).

1. Patch, A.M. et al. Whole-genome characterization of chemoresistant ovarian cancer. Nature 521, 489-494 (2015).

2. Topp, M.D. et al. Molecular correlates of platinum response in human high-grade serous ovarian cancer patient-derived xenografts. Mol Oncol 8, 656-668 (2014).

3. Quintana, E. et al. Phenotypic heterogeneity among tumorigenic melanoma cells from patients that is reversible and not hierarchically organized. Cancer cell 18, 510-523 (2010).

4. Read, M. et al. Intramuscular Transplantation Improves Engraftment Rates for Esophageal Patient-Derived Tumor Xenografts. Annals of surgical oncology (2015).

5. Lawrence, M.G. et al. A preclinical xenograft model of prostate cancer using human tumors. Nature protocols 8, 836-848 (2013).

6. Laidlaw, I.J. et al. The proliferation of normal human breast tissue implanted into athymic nude mice is stimulated by estrogen but not progesterone. Endocrinology 136, 164-171 (1995).

7. van der Linden, A. et al. Post-mortem tissue biopsies obtained at minimally invasive autopsy: an RNA-quality analysis. PloS one 9, e115675 (2014).

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Patient Information & Consent Form, CASCADE Version 8 Date 22 July 2014 PI&CF Page 1 of 10

PARTICIPANT INFORMATION AND CONSENT FORM

Peter MacCallum Cancer Centre

Full Project Title: A CAncer tiSsue Collection After Death (CASCADE) programme to Improve our Understanding of the Progression from Primary Stage Cancer to Metastatic Disease.

Project Principal Investigator: Professor David Bowtell. Peter MacCallum Cancer Centre

This Participant Information Sheet and Consent Form is 10 pages long, please make sure you have all the pages of this document

1. Introduction

We invite you and your family to take part in this research study involving the collection of cancer samples from the body after death. Cancer tissue enables research aimed at understanding how cancer spreads, for improving diagnosis, and for developing more effective cancer therapies. This Participant Information and Consent Form will tell you about the research project and explain the procedures that are involved. Knowing and understanding what is involved will help you decide if you want to take part in the research. Please read the information in this document carefully and feel free to ask questions about anything you do not understand or want to know more about. Before deciding whether or not to participate, we suggest you talk with your family members.

Participating in this research is entirely voluntary. If you and your family do not wish to participate, you don’t have to. You will receive the best possible care whether you take part or not. If you agree to be involved, you can decide to withdraw from the study at a later time.

If you decide you want to participate in the research project, you will be asked to sign the consent section. By signing it, you are telling us that you:

understand what you have read; agree to participate in the research project; agree to participate in the research processes that are described; agree to the use of your personal and health information as described

You will be given a copy of this Participant Information and Consent Form to keep.

We would also like to access the details about your cancer treatment from Medicare, and the Pharmaceutical Benefits Scheme (PBS). A separate information and consent form (attached) is required to access Medicare and PBS information. By gaining access to this information, we will be able to determine what treatments you have received. This will help our research team understand how you responded to various treatments you were given.

2. The purpose of this research projectUnfortunately, not all patients are cured of their cancer, particularly when it spreads to other sites inthe body and becomes resistant to treatment. This study aims to understand the spread of cancer andresistance to treatment.

During life, it is often difficult to obtain tissue samples of cancer from different organs. In this study, we seek permission to obtain and study samples of tissue from patients who have recently

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died of their cancer. We hope this will provide important information to help design more effective therapies for cancer patients in the future.

3. What does participation in this research project involve?If you decide to take part in this project:

We ask that you donate 40 ml of blood (approximately 8 teaspoons) to carry out testing of theDNA taken from your blood cells. The blood will be stored in a central laboratory. Geneticmaterial (e.g. DNA) may be extracted from the blood to provide information about the normaland tumour cells in your body. . We will also use the blood to look for evidence of tumourcells in the circulation.

We ask that you give permission for the doctors conducting the study to access your relevantmedical and pathology records (including tumour material) and clinical cancer genetic testresults (if applicable)

We may want you to complete questionnaires to provide information about health, diet, andlifestyle. Many of the questions will ask about your medical history and any history of cancerin you and your family.

Areas where cancer tissue is growing in your body will be identified after death and removedby specialists who are skilled at performing a post-mortem examination.

The cancer tissues will be used for laboratory studies following approval by the PeterMacCallum Cancer Centre Human Research Ethics Committee.

You will not be paid for your participation in this research. There will be no additionalcharges to you for participation in this research.

4. What will happen to my donated samples?Your blood and cancer tissue samples will be stored in the Research Department at the PeterMacCallum Cancer Centre. Your blood and cancer tissue samples will be labelled with a codenumber, and your name will not appear on the label.

Your blood sample will be used to prepare DNA that will be analysed by the researchers at the same time as DNA prepared from your cancer tissue. Your DNA samples, which will be securely stored, will be coded so that they are able to be linked with your name. This will be done to enable us to contact your designated next-of-kin if we find information about your cancer that may be of relevance to your blood relatives. Where possible, we may attempt to keep cancer cells alive in the laboratory so we can test the significance of any findings – for example, the role that certain genes play in controlling resistance to chemotherapy.

Researchers will be granted access to your samples only after approval by the Peter MacCallum Cancer Centre Human Research Ethics Committee. The types of research will vary, but will include techniques to identify genes that influence the risk of developing cancer, studies to determine the genes and proteins that influence spread of cancer and resistance to therapy, and the growth and testing in the laboratory of cells derived from cancer samples. We have asked that you consent to a range of studies as the technologies for cancer research are evolving rapidly and we cannot anticipate all uses at this time. The Peter MacCallum Cancer Centre Human Research Ethics Committee will approve the use of all tissue samples on an ongoing basis.

For a researcher applying to gain access to the database or to use your samples, the following requirements will be essential:

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The researcher must demonstrate that there are adequate resources, including funding, tocomplete the project satisfactorily. That will usually mean that the work is funded by aresearch grant, which means in turn that the project has been subject to strict scientificscrutiny. The project must have been examined by appropriately qualified scientists andjudged to be of good scientific merit.

The Human Research Ethics Committee of the researcher’s hospital, university or institutionmust have approved the project.

Samples may be sent to researchers overseas for ethically approved studies. Research studies with these samples may be performed in academic or industry settings. A researcher who gains approval to use information or samples stored in the database may

have access to your pedigree (diagram of your family tree) and the samples from you held instorage.

Clinical details about your cancer and your treatment might be released. However, in mostcases, researchers will not be given any information that might identify you. Theinformation and samples are coded and in most cases, researchers will know you only by anumber.

In any publication and/or presentation of the research, information will always be providedin a way that does not identify you.

5. What are the potential benefits of this study?We cannot guarantee that there will be any benefits from this research. However, we may makediscoveries that will be of significance to future patients and that could be relevant to your relatives.In the latter case, should you have relatives who wish to be informed of such findings and discusswhat their meaning is, you should nominate them and have them sign at the end of this document.

6. What are the possible risks?Having a blood sample taken may cause some discomfort or bruising. Sometimes, the blood vesselmay swell, or blood may clot in the blood vessel, or the spot from which tissue is taken couldbecome inflamed. Rarely, there could be a minor infection or bleeding. If this happens, it can beeasily treated.

Information may be obtained that is relevant to your family, for example, the identification of genes that influence the risk of developing cancer. Your family members can choose to receive this information or not. Any information will be provided by qualified Peter MacCallum Cancer Centre staff, who can help interpret the findings.

It is possible that information about your sample will be published in one or more scientific journals. Neither your name nor other personal details will appear in these articles.

7. What does a CASCADE tissue donation involve?If consent has been given, cancer tissues being donated will be removed after death by a post-mortem examination. A post-mortem examination is an orderly procedure performed by a dedicatedspecialist. Ideally, the procedure takes place within 24 hours after death, although can be performedlater than this.

A family member or the treating clinician will notify us when a patient enrolled in the study dies and we will organise the transport of the body to and from the centre where the post-mortem examination is performed, returning the body to the funeral home required by the family.

For this research, the post-mortem examination will involve incisions being made in the skin to provide access to cancer tissues. Your cancer specialist will communicate closely with the specialist performing the tissue collection to ensure that the procedure is performed with the minimum

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amount of manipulation of your body required to obtain the cancer tissue. Unless you state otherwise (see ‘Conditions to the post-mortem procedure’ on page 6 of this document), this will as a rule involve large incisions typical of a full autopsy. This usually involves an initial incision made in a “Y” shape from near the shoulders, meeting at the centre of the chest and extending to the abdomen. Where cancer has spread to the brain, an incision through the scalp will also be made. In order to obtain adequate tissue sample, the post-mortem examination may require removal of whole organs for examination. We may also collect a blood sample. Samples of cancer tissue will be handled and stored for future research by the CASCADE project team.

We may take photographs of tumours at the time of the post-mortem examination, to help us record where the cancer has spread. These photographs will usually be taken after the tumour has been removed from your body. We will not take photos of your face or any other bodily features that could identify you to others. Photographs may be used in presentations or publications but, like all data collected as part of the CASCADE program, will be carefully presented in a way that hides your identity.

After the post-mortem, the body will be carefully prepared for transfer back to the care of the funeral director. The whole procedure should not affect the ability to have a viewing or open casket funeral, as the incisions will be made in such a way as to minimise visible marks.

If you have concerns about the post-mortem procedure, including the taking of photographs, but would still like to donate cancer tissue, please talk to your doctors about making a conditional donation.

8. What effect will making a CASCADE tissue donation have on funeral arrangements?The tissue acquisition procedure should take less than 24 hours, and other than this delay it should not interfere with the course of events associated with a funeral. The procedure should not affect the ability to have a viewing or open casket funeral.

9. When should plans be made to ensure the CASCADE tissue donation occurs afterdeath?It is important to make the necessary arrangements well in advance, since you and family membersneed time to discuss this very important issue. Discussion with your next of kin and familymembers will also help ensure your wishes are considered. You should state any specific wishes inwriting in the section entitled ‘Conditions to the post-mortem procedure’ towards the end of thisdocument.

10. Does my doctor need to know that I intend to donate cancer tissue for the CASCADEprogramme upon my death?Your family doctor may be asked to complete the death certificate at the time of death. It isimportant that your doctor is aware of your wish to donate tissues in order to complete the deathcertificate in an expedient manner. In addition, your doctor will provide medical information usefulfor researchers. By signing the consent section, you agree to your local doctor being notified of yourdecision to participate in this research project. Information about your participation in this researchproject may be recorded in your health records.

11. Do I have to take part in this research project?Participation in any research project is completely voluntary. If you do not wish to participate in theCASCADE programme, you do not have to. If you decide to participate, and later change yourmind, you are free to withdraw from the project at any stage.

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Your decision on whether to participate or not, or to participate and then withdraw, will not affect your treatment, your relationship with those treating you or your relationship with the Peter MacCallum Cancer Centre.

12. What if I want to withdraw from this research project?If you decide to withdraw, please tell your doctors or a member of the CASCADE research teamand they will send you a “Withdrawal of Consent” form. A “Revocation of Consent” form isadditionally attached for this purpose at the end of this consent form, which you can fill in and sendto us at any time.

If after your death your family is concerned about your involvement in this research and refuses the procedure to be performed, we will respect their wishes.

13. Could this research project be stopped prematurely?All research projects, including this one, depend on the availability of adequate research funds. Theresearchers involved in the project are highly committed and will do their best to secure thenecessary funding.

14. How will next of kin be informed of the results of this research project?As the project proceeds, information that may be relevant to your family could be discovered from your blood or tissue samples. Any significant information will be provided to your designated next of kin by qualified Peter MacCallum Cancer Centre staff, who can help interpret the findings. Upon request, your next of kin will be able to access a report describing the tissue sampling performed at the post-mortem examination. If your next of kin wishes to obtain a copy of the research report, they can contact the Project Manager, who will arrange a time for your clinician to meet with them, and explain the document.

15. What will happen to information about me?We wish to access information stored in your medical records, in Medicare and in the PBS toconfirm details about any cancer diagnosis and treatments you may have received. With yourpermission, we would like you to tell us who your close relatives are (e.g. parents, sisters, brothers,children over 18 years, grandparents), and whether or not they have had cancer. Please feel free todecline to answer any questions or approaches.

One person (called the Keeper of the Database) is responsible for maintaining the security of the database so that no-one may have access to it, except according to set rules and procedures. No-one will have access to your personal details, except the Keeper, support staff and clinical researchers named on this application, all of whom understand that they have a duty of confidentiality that must be strictly observed. As your data could be used in the future for ethically-approved research, it will not be destroyed unless you wish us to destroy it at a particular time.

16. What happens if I am injured as a result of participating in this research project?If you suffer an injury as a result of donating blood as part of this research project, hospital care andtreatment will be provided by the public health service at no extra cost to you, if you elect to betreated as a public patient.

17. Is this research project approved?The ethical aspects of this research project have been approved by the Human Research EthicsCommittee of the Peter MacCallum Cancer Centre.

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This project will be carried out according to the National Statement on Ethical Conduct in Human Research (2007) produced by the National Health and Medical Research Council of Australia. This statement has been developed to protect the interests of people who agree to participate in human research studies.

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CONSENT (Note: All parties signing the consent section must date their own signature)

I have read, or have had read to me in a language that I understand, this document and I understand the purposes, procedures and risks of this research project as described within.

I give permission for my doctors, other health professionals, hospitals or laboratories outside this hospital to release information to the CAncer tiSsue Collection After Death (CASCADE) programme concerning my disease and treatment that is needed for this project. I understand that such information will remain confidential.

I have had an opportunity to ask questions and I am satisfied with the answers that I have received.

I freely agree to participate in this research project as described.

I acknowledge that my family or next of kin are aware of my wish to participate in the CASCADE programme.

I understand that I will be given a signed copy of this document to keep.

By signing this consent, I give permission for storage of my blood and tissue samples, and for these to be used in ethically-approved research

Conditions to the post-mortem procedure:

Participant's name (printed)………………………………………………………

Participant signature Date

Nominated next of kin to receive information (printed): ………………………

Address:

Relationship to participant:

I wish to receive notification of any clinically significant research results that may be important to me and my family:

Yes No

Next of Kin signature as witness: Date

If the witness is not the nominated Next of Kin:

Witness name (printed) : ………………………

Relationship to participant:

Witness signature: Date

* Declaration by researcher: I have given a verbal explanation of the research project, its procedures and risks and Ibelieve that the participant has understood that explanation.

Researcher's name (printed)……………………………………

Researcher signature Date

* A senior member of the research team must provide the explanation and provision of information concerning theresearch project.

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Who can I contact? Who you may need to contact will depend on the nature of your query, therefore, please note the following:

For further information or appointments:

If you want any further information concerning this project or if you have any medical problems that may be related to your involvement in the project (for example, any side effects), you can contact the principal researcher on (03) 9656 xxxx or any of the following people: [list the names and contact phone numbers of other appropriate persons involved in the project including research nurses and research project coordinators. The name and contact phone number of a person who can act as a 24-hour medical contact must be provided and clearly denoted].

Name: Kathryn Alsop

Role: Project Manager

Telephone: (03) 9656 xxxx (24 Hour CASCADE Contact)

For complaints: If you have any complaints about any aspect of the project, the way in which it is being conducted or any questions about being a research participant in general, then you may contact:

Ethics Coordinator:

Telephone: (03) 9656 xxxx.

Patient Advocate:

Telephone: (03) 9656 xxxx.

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REVOCATION OF CONSENT FORM

(TO BE USED BY PARTICIPANTS WHO WISH TO WITHDRAW FROM THE PROJECT.)

Full Project Title: CAncer tiSsue Collection After Death (CASCADE) programme.

I hereby wish to WITHDRAW my consent and do not wish to donate tissue after death. All data and samples that have been collected as part of my participation in CASCADE will be destroyed.

I understand that such withdrawal WILL NOT jeopardise any treatment or my relationship with the Peter MacCallum Cancer Centre.

Participant’s Name (printed) …………………………………………………….

Signature Date

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Supplementary Figure 2: Time between death of participant and start of autopsy, depicted based on distance from autopsy site (VIFM) at time of participant’s death. Time to autopsy was dependent of the time to release of the participant by the family, priority workloads of VIFM and Tobin Brothers, geographical distance to cover during transfer, and/or time to arrange the death certificate. A clear communication line between the research team and palliative care teams, as well an alert to the imminent death of a participant, helped minimize delay (dashed line = median time to autopsy; 5.5 hours).

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Ovarian Melanoma Prostate

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Supplementary Figure 3: Success of PDX engraftment of post-mortem tissue. Metastatic tumour tissue collected at the time of post mortem for 25 participants has been engrafted; tissues from 17 of these cases have been followed for more than 300 days. Time from implantation to successful engraftment, producing serially transplantable PDXs, varied per case. Plotted is the average time from transplant to success in each case where successful engraftment/s have occurred (mean ± standard deviation). In many instances, multiple tumour deposits were engrafted for each case. At least one PDX has been developed for 13 of the 17 (76.5%) participants followed for >300 days post implantation. Data for series is tabulated and overall sucess rate summarised. *Extensive tumour burden was detected in the liver of one mouse 2-3 months post primarytransplantation. However, this failed to take upon re-transplantation.

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