DePICT the Cancer Care Journey, Overcome Rarity Through Collaborative Research.
Sunday February 25, 2018
Brenda L. Gallie, global leader in retinoblastoma clinical care, research and innovation, introduces DePICTRB, exciting technology that supports collaboration among the child’s entire circle of care during treatment and beyond.
Why High Quality Care and Research Is So Challenging
Clinical research in retinoblastoma has failed to establish the safety and efficacy of treatments, lacking the high quality clinical trials that have dramatically changed outcomes for children with other cancers. There are many reasons for this:
- retinoblastoma is too rare in any one country
- one or two eyes may be affected each needing a different approach
- each eye may have more than one tumor, each requiring different therapies
- treatment often requires hundreds of clinical encounters, often with general anaesthetic
This complex and multidisciplinary care requires excellent collaboration between ophthalmologists, oncologists and parents to optimize outcomes. Communication across the child’s circle of care is complicated and often fragmented and slow.
Emerging Treatment Options Offer New Hope
Now, in February 2018, we have tremendous opportunities to change care for children affected by retinoblastoma around the world.
First, new treatments have emerged (without rigorous clinical trials) that broaden the array of treatments for each eye and each child.
2018 Treatments for Retinoblastoma include:
- Chemotherapy can be given to the whole child (with the potential to destroy any tumor cells that might have escaped the eye), or
- Chemotherapy can be infused directly into the artery supplying the retina (intra-arterial chemotherapy, IAC), avoiding the whole body side effects of systemic chemotherapy,1 but also not 1treating any potential rogue tumor cells that escaped the eye,2 or
- Chemotherapy can be injected directly into the eye (intra-vitreal chemotherapy, IVitC) to kill floating tumor cells.3
- As a last resort when retinoblastoma has resisted all the conventional therapies, direct surgery (vitrectomy and tumor resection) to remove the recurrent tumor is feasible, with precautions to avoid spread of tumor.4
The Importance of Genetics
Although one of the rarest cancers, retinoblastoma is now the first to fully acknowledge that cancer is caused by genetic mutations. The international system to describe the severity and risk for life at first diagnosis (Tumor Node Metastasis, TNM),5 now for retinoblastoma, uniquely includes “H” for heritable.
Patients with bilateral retinoblastoma all carry a mutation in the retinoblastoma tumor suppressor gene, RB1, and are at diagnosis considered “H1”. Each of their children has a 50/50 risk of being H1, or H0 with the same risk to develop retinoblastoma as the normal population. H0 requires no special care.
The children who are shown by testing to be H1 can be delivered early, and tiny tumors can be treated with minimal therapies.6 Since all persons who are H1 have a lifetime greater risk for other primary malignancies than people who are H0, we look forward today to new research to establish effective surveillance programs to find these second cancers when they are small and easy to treat. Likely, this will include developing technologies such as whole body MRI.
Empowering Collaborative Care
As described February 1 in The Economist,7 the Internet is poised to empower patients and doctors in a New World of collaboration. Over the last 15 years, the retinoblastoma team at the Hospital for Sick Children (SickKids), in partnership with the University Health Network (UHN) Techna in Toronto, Canada, developed a retinoblastoma-specific database to coordinate care. This database, DePICTRB , is now on “the Cloud” in the final stages of governance, privacy, and data security, to be available to every retinoblastoma treatment center world-wide.
DePICTRB stands for Disease-specific electronic Patient Illustrated Clinical Timeline RetinoBlastoma.
Explore DePICTRB for yourself: http://depictrb.technainstitute.com
Username: demo-user | Password: Demo1234
The “home page” of DePICTRB is a timeline, graphically illustrating all the disease-specific care that has taken place for the individual child. The Retinoblastoma Team enters data at the point-of-care, and the parents and others of their choice (e.g., primary care provider, family members and friends) have read-only access to the patient’s account.
Data is collected in DePICTRB, mapping the tumors in drawings, photographic and other medical images (MRI, etc) from the time of diagnosis and through each clinical encounter, including adult follow-up (Figure 1). The data is a summary of the health record and does not replace the health care provider’s paper or electronic medical record.
Figure 1. This child’s treatments are summarized in DePICTRB.
A) The bottom is a “legend” indicating what each symbol on the timeline means. For example, the red vertical line is the staging EUA, when the severity of disease at diagnosis is decided based on clinical examination, to determine the TNMH stage for the child. The TNNH for this child is located in the upper left-hand corner: child is H1 because he has bilateral disease. The upper timeline is for the right eye, staged cT1b; the lower timeline is for the left eye, staged cT2b.
Over the two years showing in DePICTRB, this child received systemic chemotherapy (purple vertical lines), laser therapy (blue diamonds) to both eyes, local radiation plaque (grey triangle) to the right eye, intra-vitreal chemotherapy to the right eye (blue triangles) and three treatments with intra-arterial chemotherapy (red triangles) to the left eye. But after 1.5 years treatment the left eye was removed (yellow triangle) because the cancer could not be safely controlled in an eye with only 20/400 vision, when the right eye had 20/40 vision. DePICTRB makes all this information available to the circle of care, at a glance.
B) The drawings of the retina and the wide-angle photographs of the back of the eye are shown in DePICTRB. The red outlined box and arrow indicate the staging EUA at diagnosis in November 2015. The blue outlined box and arrow indicate the removal of the left eye in June 2017 when all treatments had ultimately failed to control the retinoblastoma
Enhancing Patient Care and Research
DePICTRB will enhance communication and understanding of the retinoblastoma treatment course, and support life-long multidisciplinary and shared care (Figure 2). Both care-givers and families will discover enhanced efficiency and disease understanding through the accessible clear data, rewarding their participation, so indexing every child diagnosed with retinoblastoma – globally – is feasible.
A very important additional goal of DePICTRB is to provide data to support global research fostering high-level, evidence-based care. With the goal to include ALL children and families affected by retinoblastoma, the next step will be to develop algorithms that iteratively become a Learning Health system. Beyond retinoblastoma, this project illustrates a 2018 approach to healthcare optimization that can well be applied to other complex, rare, and not so rare diseases.
Combined with fresh new approaches to treatment and public awareness of rare, but lethal, retinoblastoma, the global collaboration supported by DePICTRB can envision a day when retinoblastoma is a “Zero Death” cancer.
Figure 2. This diagram shows how DePICTRB assists the circle of care for each child with retinoblastoma to understand all the care, including parents and family. The retinoblastoma team at each Retinoblastoma Center includes for example, ophthalmologists, oncologists, clinical coordinator, social worker, radiologists, genetic counsellor, anaesthetists, pathologists, radiotherapists, and ocularists, but perhaps most important, child life specialists. DePICTRB also functions as a checklist for the clinical team, with data fields giving some guidance to standardize treatment protocols between visits and treatments. The family, controls view-only access to DePICTRB for their child that would commonly include family doctor, paediatrician, parents, legal guardians and ultimately the patient.
Currently, DePICTRB and related support services are provided by the International Retinoblastoma Consortium (IRbC), a non-profit entity situated in Toronto, Canada.
Explore DePICTRB for yourself: http://depictrb.technainstitute.com
Username: demo-user | Password: Demo1234
- Munier FL, Mosimann P, Puccinelli F, et al. First-line intra-arterial versus intravenous chemotherapy in unilateral sporadic group D retinoblastoma: evidence of better visual outcomes, ocular survival and shorter time to success with intra-arterial delivery from retrospective review of 20 years of treatment. Br J Ophthalmol. 2017;101(8):1086-1093.
- Yousef YA, Soliman SE, Astudillo PP, et al. Intra-arterial Chemotherapy for Retinoblastoma: A Systematic Review. JAMA ophthalmology. 2016;134(6):584-591.
- Munier FL, Gaillard MC, Balmer A, et al. Intravitreal chemotherapy for vitreous disease in retinoblastoma revisited: from prohibition to conditional indications. Br J Ophthalmol. 2012;96(8):1078-1083.
- Zhao J, Li Q, Wu S, et al. Pars Plana Vitrectomy and Endoresection of Refractory Intraocular Retinoblastoma. Ophthalmology. 2018;125(2):320-322.
- Mallipatna A, Gallie BL, Chévez-Barrios P, et al. Retinoblastoma. In: Amin MB, Edge SB, Greene FL, eds. AJCC Cancer Staging Manual. Vol 8th Edition. New York, NY: Springer; 2017:819-831.
- Soliman SE, Dimaras H, Khetan V, et al. Prenatal versus Postnatal Screening for Familial Retinoblastoma. Ophthalmology. 2016;123(12):2610-2617.
- Editors. Doctor You: A digital revolution in health care is coming. Welcome it. The Economist. 2018:9.
About the Author
Brenda L. Gallie, MD, FRCS(C), CM, OOnt is Director of the Retinoblastoma Program in the Department of Ophthalmology and Vision Science at the Hospital for Sick Children (SickKids) in Toronto, Canada. She is Associate Scientist at the TECHNA Institute, University Health Network; Professor in the Departments of Ophthalmology, Medical Biophysics and Molecular Genetics at the University of Toronto.
Brenda’s research and clinical practice is focused uniquely on retinoblastoma. Her pioneering work has contributed to fundamental understanding of cancer development, and provided affordable genetic tests that enhance patient care. She has fully integrated science into patient care, and looked globally to achieve an evidence base for care and equal access to patient care. Through Point-of-care clinical data with outcomes on all patients with secure Internet access, the stage is set for a global learning health system, iteratively advancing care based on evidence from the bedside, everywhere.