Plain Language Summaries of Scientific Articles

Backgound

The retinoblastoma community decided to host a “Cup or Tea” to address the Canadian Retinoblastoma Research Advisory Board (CRRAB) aim of sharing research results. Cup of Tea is an event intended to bring the Canadian retinoblastoma community together for an informal discussion about a research article. Discussions center around plain language summaries created by CRRAB members.​

Plain language summaries are created by a patient partner (survivor or caregiver) with the help of a researcher of health professional. This process is guided by the Parent in Research. Each article topic is selected by the patient partner and a relevant and recent article is selected.

All plain language summaries from Cup of Tea events are listed here and past recordings can be found on YouTube and Spotify under the Retinoblastoma Research accounts.

List of available summaries

Click on the article title below to be directed to already written plain language summaries with patients or scroll down to see summaries written by participants of CRRAB.

Title	Authors	Publish Date
The top 10 retinoblastoma research priorities in Canada as determined by patients, clinicians and researchers: a patient-oriented priority-setting partnership	Flegg K, Gelkopf MJ, Johnson SA, Dimaras H; Canadian Retinoblastoma Research Advisory Board Priority Setting Steering Committee	June 9, 2020
The Canadian Retinoblastoma Research Advisory Board: A Framework for Patient Engagement	Gelkopf MJ, Avramov I, Baddeliyanage R, Ristevski I, Johnson SA, Flegg K, Dimaras H	February 28, 2020
Lessons for Patient Engagement in Research in Low- and Middle-Income Countries	Janic A, Kimani K, Olembo I, Dimaras H	March 28, 2020
Patients, Public and Service Users are Experts by Experience: An Overview from Ophthalmology Research in Canada, UK and Beyond	Skilton AM, Low LG, Dimaras H	February 29, 2020
Impact of an education program on late diagnosis of retinoblastoma in Honduras	Leander C, Fu LC, Peña A, Howard SC, Rodriquez-Galindo C, Wilimas JA, Ribeiro RC, Haik B	September 28, 2006
Knowledge, experiences and attitudes concerning genetics among retinoblastoma survivors and parents	Hill JA, Gedleh A, Lee S, Hougham KA, Dimaras H	January 28, 2018
Long-term evaluation of outcomes and survival of patients treated for retinoblastoma	Morawski K, Janosz-Maduzia A, Haładus T, Jędrychowska-Jamborska J	April 28, 2020
Screening for Pineal Trilateral Retinoblastoma Revisited	de Jong MC, Kors WA, Moll AC, de Graaf P, Castelijns JA, Jansen RW, Gallie BL, Soliman SE, Shaikh F, Dimaras H, Kivelä TT	November 9, 2019
Global Retinoblastoma Treatment Outcomes: Association with National Income Level	Tomar AS, Finger PT, Gallie BL, Kivelä TT, Mallipatna A, Zhang C, Zhao J, Wilson MW, Brenna RC, Burges M, Kim J, Khetan V, Ganesan S, Yarovoy A, Yarovaya V, Kotova E, Yousef YA, Nummi K, Ushakova TL, Yugay OV, Polyakov VG, Ramirez-Ortiz MA, Esparza-Aguiar E, Chantada G, Schaiquevich P, Fandino A, Yam JC, Lau WW, Lam CP, Sharwood P, Moorthy S, Long QB, Essuman VA, Renner LA, Semenova E, Català J, Correa-Llano G, Carreras E; American Joint Committee on Cancer Ophthalmic Oncology Task Force	September 29, 2020
Knowledge, Experiences, and Attitudes Concerning Genetics Among Retinoblastoma Survivors and Parents	Hill JA, Gedleh A, Lee S, Hougham KA, Dimaras H	January 29, 2018
Early monocular enucleation selectively disrupts neural development of face perception in the occipital face area	Kelly KR, Gallie BL, Steeves JKE	October 3, 2018
Secondary Prevention of Retinoblastoma Revisited: Laser Photocoagulation of Invisible New Retinoblastoma	Soliman SE, VandenHoven C, MacKeen LD, Gallie BL	August 21, 2019

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Plain Language Summaries Written by CRRAB Members

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Long-term evaluation of outcomes and survival of patients treated for retinoblastoma

Plain language summary written by Jeanne McKay and Helen Dimaras

Purpose of the Study

The purpose of this study, by a group in Poland, was to take a retrospective look at 42 patients (58 eyes) who had been treated for retinoblastoma. They described the three goals of treatment as first of all survival of the patient, secondly saving eyes and finally preserving vision. They reviewed the effectiveness of treatment based on survival rate, visual acuity, preservation of the affected eyeball, and tumor reactivation inside and outside of the eye, after initial treatment.

Summary of the Study

The researchers studied outcomes from patients who were diagnosed between 1997 and 2012. All of the patients had been treated at the Department of Ophthalmology and Ocular Oncology at University Hospital Krakow, Poland. The Reese-Ellsworth (RE) Classification for intraocular retinoblastoma, at diagnosis, ranged from I to V. All had received standard chemotherapy drugs vincristine, etoposide and carboplatin (VEC Protocol) as well as other local treatments. Some were bilaterally affected and some unilaterally and there was a mix of males and females.

In information collected from 1997 to 2019, the researchers looked at the types of local treatment the patients received as well as the spread of the disease.

Conclusions from the Study

Early diagnosis and treatment with chemotherapy is very effective in saving lives, eyes and visual acuity. Of the 42 patients, only 1 patient died. The earlier a patient was diagnosed, the more effective chemotherapy was when used with local treatments, there was a much better chance of saving eyes and vision. Even patients with an RE Classification of V had a good survival rate, although eyes were more likely to be enucleated and there was more vision loss. In all cases it was important to have regular examinations and treatment. The one patient who did not survive died because of the spread of disease outside of the eye after initial enucleation. There is no indication that pathology was done after enucleation to check for spread outside the eye and to determine if chemotherapy treatment should be changed.

Personal Comment

This article emphasizes the need for early diagnosis and treatment but also gives hope that even a later diagnosis can save life and vision. The information is not new but it may be the first time the group in Poland has studied their own patients. The RE Classification system for tumors has been replaced by IPC and TNM classification in many centres now. These other classifications take into account more than just the size of the primary tumour.

It is encouraging to know that chemotherapy in conjunction with other local treatments continues to be effective in aiding survival, saving eyes and preserving vision. It also reinforces the need for skilled physicians in understanding the treatment of retinoblastoma.

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Screening for Pineal Trilateral Retinoblastoma Revisited

Plain language summary written by Barbra Mohan

I was interested this article because my son Jasper, who was successfully treated for bilateral retinoblastoma (Rb) as an infant, and then developed a cancerous pineal tumour at the age of 13. Despite aggressive treatment, he passed away just after his 15th birthday. I know that his was a highly unusual case, and there will probably never be a good explanation of how or why his pineal tumour developed, and whether it may have been related to his earlier Rb. However, it helps me give meaning to his life and our experience by supporting research into actions that may be taken to prevent another child from succumbing to a similar fate.

This paper was a meta-analysis, which is a systematic review of a number of previous research efforts. It is often done to achieve statically more reliable results or to provide a new interpretation using more data. The article makes clear that in this case, because of the limited nature of the prior research, the findings are not considered reliable enough to strongly influence decision-making.

The study reminds us that trilateral retinoblastoma (TRb) is a form of Rb that happens mostly in patients with the heritable form of the disease, which is 45% of all Rb cases. Among Rb patients with heritable disease, about 3% develop TRb and it is “an important cause of death” in those patients. Currently, most children diagnosed with Rb are screened for trilateral retinoblastoma (TRb) upon initial Rb diagnosis, and 50% of TRb cases are detected this way. It is unclear if additional screening after that is useful, and if so, up until what age. This study asked questions that might help make it more clear;

Q: Until what age is the likelihood of developing TRb greatest?

A: 95% of the TRb patients studied were diagnosed before 40 months of age – and this is shorter than what was assumed before this study.

Q: Does TRb develop earlier if the Rb develops earlier?

A: There is no relationship between the age of diagnosis of Rb (bilateral or unilateral) and the age of diagnosis of TRb.

Q: How long does it take for a tumour that would be detectable in an MRI actually result in symptoms?

A: Approximately 1 year.

The study comments that if a screening program is thought necessary for patients with heritable Rb, it would only really be useful if it was every six months until the age of 3.

With the answers to these questions, and the information and statistics known about how uncommon TRb is and its generally low survivability, the study concluded that 311 scans would have to be performed to detect a single asymptomatic case, and 776 scans would have to be performed save a single life. This invites a cost-benefit analysis of such frequent scanning – which is a harsh statement for a bereaved parent to read, but a fact of life in managing limited medical resources. They also mention that so many scans would result in false-positives, leading to over-treatment with high dose chemotherapy and stem cell rescue, which can also have their own deadly outcomes.

A final brief conclusion from this study was a reference to data that showed that the use of systemic chemotherapy or radiation treatment did not affect the time between diagnoses of Rb and diagnosis of TRb.

I found this study incredibly interesting. It leaves my son as an “outlier”, where he was before I read it. In fact, I’ve always known Jasper was an outlier in every respect! The article helped me feel a little more at ease with the realization that more frequent scanning would not have necessarily saved his life and may have put it at risk earlier. It also helped me discount the idea that his early systemic chemotherapy might have delayed the diagnosis. And reviewing it and writing about it for others does help me provide some meaning to our experience.

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Global Retinoblastoma Treatment Outcomes: Association with National Income Level

Plain language summary written by Jay Kiew and Ashwin Mallipatna

Click here to display the below booklet fullscreen

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Knowledge, Experiences, and Attitudes Concerning Genetics Among Retinoblastoma Survivors and Parents

Plain language summary written by Mary Connolly-Wilson and Jessica Hill

As an individual with an RB1 mutation who practiced as a genetic counsellor in Canada for thirty years, I was very interested in this study to see from both a personal and professional perspective how genetic counselling for Retinoblastoma (RB) is received by patients, parents and families.

The genetics of retinoblastoma may be complicated for affected individuals and families to understand, as some RB is heritable and others non-heritable and the management of RB and the implications for the affected individual and family members may be quite different depending on their specific genetic test results. Genetic counselling, therefore, is essential to help patients and families to interpret and understand test results, so that they can truly understand their unique risks, make informed reproductive and lifestyle decisions and cope with the diagnosis.

The goal of this study was to learn more about adult RB survivors and parents of children with RB in terms of their knowledge of RB genetics, their experiences with RB genetics, and their attitudes about RB genetics. This information will help physicians, genetic counsellors, and other allied health professionals to determine what might prevent survivors and parents from understanding and using genetic information. As a result, it will inform health care professionals how to provide better care.

The researchers collected information about survivors’ and parents’ knowledge, experiences, and attitudes through focus group discussions. A total of 15 participants took part in the study, 14 had a child with RB and two were RB survivors.

The results of the study showed that participants understood that RB is a genetic disease, but some had trouble understanding certain genetic concepts related to the disease. For example, some participants did not fully understand the terms ‘heritability’ and ‘laterality’, and were not aware that unilateral RB could be inherited by the next generation. Some participants also believed that RB could be caused by environmental factors (not genetics/mutations).

Regarding patient experiences, the focus group discussions revealed that genetic testing and counselling was beneficial in helping to reduce parents’ guilt and determine the risk for other cancers. Some participants had difficulty getting information on RB genetics, and most said that they use social media and general search engines (e.g., Google). While this may be a way to access RB information, inaccurate or inapplicable information may be shared on these sites. It is essential that RB families understand what applies to their own specific situation

Participants also shared that they had trouble coping with the RB diagnosis, and many parents felt guilty or responsible for their children’s RB. As a result, social support (e.g., support from family and friends) was very important for participants. Some participants also felt they needed support from health professionals to communicate with extended family about RB genetics. 

The results of the study showed that future consequences of RB are a constant worry for participants (e.g., wanting children to lead a normal life, risk of second cancers or further vision loss, family planning). Improved communication of genetic information is needed, in terms of timing, format and complexity. Most patient families receive genetic counselling at the time of diagnosis when it is very difficult for them to understand and retain the complex information they receive.  Participants suggested improvements to the timing of genetic counselling and suggested development of easy and empowering resources for children, and regular follow-ups with genetics. Parents and survivors feel they may benefit from further genetic counselling as adults in order to receive more information on reproductive options and the potential genetic effects of the disease on family members. Formal psychosocial support and peer-to-peer support for caregivers is also needed.

The researchers suggested that it is important to continue to assess the understanding of RB survivors and parents of children with RB in order to enhance genetic counselling for RB in Canada.

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Early monocular enucleation selectively disrupts neural development of face perception in the occipital face area

Plain language summary written by Mitch Hendry and Jennifer Steeves

As a survivor of unilateral retinoblastoma who was enucleated at a young age, I was interested in this article for two reasons: first, it’s always fun to see yourself represented in research; second, I was surprised by the title, “Disrupted neural development of face perception” did not sound like something that described me. I’ve never had much trouble telling one face from another, so I was curious to read the article and learn more about what was happening.

This study is a follow-up to a previous study by the same group which found that unilaterally enucleated retinoblastoma survivors process images of faces more slowly than people who still have both eyes. The first study found a small but consistent decrease in the processing speed of faces but no difference in the processing speed of other images, like houses. This finding was consistent with results from other studies investigating similar outcomes in people who had monocular vision during their early lives for other reasons (e.g., cataracts, amblyopia). The observations lead to the hypothesis that the decreased processing speed could be due changes in the brain brought on by having monocular vision during important periods of visual development.

The researchers used functional MRI scanning to examine both brain structure and brain activation while participants looked at images of faces or other objects. Blood oxygenation in different regions of the brain was used to measure brain activation levels. Blood was found to be less oxygenated in face-identifying brain regions of unilaterally enucleated RB survivors than in non-enucleated participants.

Despite the findings of this study and the earlier study, most retinoblastoma survivors (including
myself!) do not feel that their ability to distinguish faces is impaired. This makes sense since the difference was only found to be fractions of a second. Other recent studies have found evidence of neuroplasticity—the ability of specialized brain regions to take on new functions—in people with one eye. These studies have found that the brains of people with long-term monocular vision are structured differently and function differently than those of people who have seen through two eyes all their lives. This study adds to that developing story of how monocular brains are different than binocular brains. This greater understanding of visual development could be important for improving retinoblastoma treatment outcomes.

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Secondary Prevention of Retinoblastoma Revisited: Laser Photocoagulation of Invisible New Retinoblastoma

Plain language summary written by Alena Vincent and Sameh Soliman

Introduction

Pre-natal DNA testing has now led to the ability to diagnose RB1 mutation carriers before birth. When these infants are induced early and have their eyes monitored with the handheld Optical Coherence Tomography (OCT) scanner, tumours can be discovered at such tiny sizes they are subclinical and pose a very reduced threat to a child’s vision.

Method

The handheld OCT scanner pinpoints the location in retina where a tumour is forming, which appears as a bump in the retinal layers of the scanned images. Doctors can then use lasers to treat this exact location, with one laser shot and then use of the OCT scanner as a double check to ensure they have lasered in exactly the correct location. This method minimizes the scarring and damage to the eye. In this study this method was used with 11 new tumours in 7 eyes of 5 children.

Results

The results showed that all (100%) tumours treated with this method were successful. In 91% of the cases, a maximum of two laser therapy sessions resulted in some small permanent scarring. Two of the treated tumours had recurrence within four months, but were successfully treated after one laser session. No tumours scars showed enlargement in size or affected to the retinal centre of vision.

Discussion

This study showed that the use of the handheld OCT scanner precisely located tiny tumours resulting in correctly applied laser treatment with less scarring and, therefore, less adverse effects to the child’s vision. This widened the scope of early treatment of infants at risk of developing retinoblastoma.

Personal Comment

I have known, for as long as I can remember that I am a carrier of the RB1 gene mutation. My mom was diagnosed when she was a toddler and lost both her eyes to retinoblastoma. When my brother and I were born in the 1980s, my parents’ only choice was to have us monitored by an ophthalmologist to see if tumours would form and if treatment would be required. I was four months old when the first tiny tumours were discovered, but, after many eye exams, it became clear that tumours would never develop for my older brother. DNA testing and the isolation of the RB1 gene would later prove my brother didn’t inherit the RB1 mutation, and that I did. I was extremely lucky when it came to where my tumours formed and with laser and cryotherapy treatments my tumours were killed and my vision was saved. I still have 20/20 vision to this day.

I thought this knowledge and experience would help prepare me for when I would have children and if they too would carry the genetic mutation. We decided we would have our children’s DNA tested in utero, and with our son found out he wasn’t a carrier. Unfortunately, at 15 weeks pregnant, we found out our daughter was “affected” and we were devastated. I was told the best option would be to induce at 36 weeks and that Violet would have to be seen at SickKids, as at the time they had the only handheld OCT scanner in Canada. We didn’t know it then, but this device was critical in Violet’s treatment. Doctor Gallie, Doctor Soliman, and their team used OCT to diagnosis and treat Violet’s five tumours at the subclinical level. One of these tumours was the smallest ever discovered and successfully treated. Despite one of her tumours forming in the center of her vision, this device helped discover it at such a tiny size that today she has 20/20 vision in one eye and 20/25 in the other. I credit a group of amazing doctors, DNA testing, and the handheld OCT scanner with the incredible results of my daughter’s treatment. She is now two years cancer free and is a fearless and feisty 4 year old.

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Replacement Time of Custom Ocular Prosthesis in Children: A Review Article

Plain language summary written by Taline Dorna and Matthew Milne

Personal Story

When my son was nearly 6 months old, he was diagnosed with unilateral non-hereditary retinoblastoma. Just 8 days after diagnosis, my son’s left eye was enucleated as the tumor was quite large and within his peripheral view. A temporary prosthesis was inserted and 6 weeks later a custom prosthesis was made. Within our child’s first year of having a prosthetic eye, we visited our ocularist numerous times for adjustments or infection related reasons. My hope is that this article would answer the recommended number of times one would have to visit an ocularist within the first few years of receiving a prosthetic eye, how often the prosthesis should be maintained, adjusted, and changed completely; and what are the consequences in not doing so.

Research Question

The authors of this article sought out to answer the replacement time needed for ocular prosthesis in children based on the rate of orbital growth related to age. “Orbit” can refer to the bony socket, or it can also be used to imply the contents. The article discusses the optimal time to have the ocular prosthesis replaced and maintained in relevance to the research conducted to show which age(s) the most orbital growth occurs. This information will help give patients and their families clarity about the frequency required to have adjustments and replacements of prostheses in children, and the negative impacts in facial bone growth if not done so.

Methods

This article analyzed the published literature on the replacement time of ocular prostheses in children. Published articles up to November 30, 2020 were analyzed. A total of 910 manuscripts were read through and in the end, 7 manuscripts were selected for this study based on predefined inclusion and exclusion criteria.

Conclusion

The study concluded that rapid growth of the orbit comes to an end by 15 years of age in boys and by 11 years in girls with 95% of the growth of the adult orbit complete. Enucleating the orbit during the growth phase reduces the growth rate of that side but does not stop the growth completely. X-ray images also showed a rapid increase in orbital volume till 3 years of age. All studies researched showed that 75% of orbital growth is observed from 1 to 3 years of age and the remaining 25% growth is observed from 4 to 16 years of age. 

Children with ocular prostheses are recommended to be seen every 4-6 months for routine examination. Yearly replacement or relining of the prosthesis should always be assessed by the ocularist based on orbital change and growth. Various factors, like patient comfort, age, signs, and clinical assessment, should always be considered before relining or replacing the old prosthesis. This study confirms that the most changes in orbital growth occur between ages 0-12 years of age, therefore, custom ocular prosthesis need to be changed till the age of 12 years based on the clinical evaluation and presence of symptoms in coordination with the facial growth. The ocular prosthesis should also be checked every 6 months for fit, size, and comfort till the child is 8 years old.

Discussion

The findings of this research suggest that both CT and MRI diagnostic imaging show that rapid orbital growth is seen in the early ages and slows down in the rate of growth as the patient approaches their mid-teens. As a result, based on the information of this research article and its findings, we can state that periodic enlargement of a custom ocular prosthesis is not only recommended, but required in a growing child. This will in turn assist in the normal development of eyelids and the soft tissues lining the orbital bone margins. The research states that the presence of a prosthesis is not necessary for normal bone growth, but rather for esthetics of facial growth. It is essential that patients come in regularly for evaluation and assessment of ocular prosthesis in relation to facial growth and other contributing factors. Some factors include but are not limited to discomfort, loose fit, prosthesis rotation within the socket, discoloration of the prosthesis, lens symmetry, significant ptosis which is drooping of the upper eye lid, to name a few.

All the studies stressed the fact that in growing children, the ocular prosthesis should be changed periodically over the period of years sated. But there are very few studies that can guide ocularists with proper guidelines as to how often a patient should come in for adjustments/relining and/or complete replacement of prosthesis. Nonetheless, the studies show that updating the prosthesis by adjusting/relining and or replacing it is necessary for facial development to have symmetry, and to avoid any issues in the growing orbit with the enucleated eye. 

The authors of this review article have clearly stated the age groups for replacement time of ocular prosthesis in children, based on the orbital growth rate and facial esthetics. It would be helpful to apply this baseline to factor in the socio-economics of the patients involved. Unfortunately, the cost of an ocular prosthesis is variable depending on country and/or province. In the United States, unless you pay into a private health insurance provider, an ocular prosthesis can range anywhere from $2,000-$8,000. In Canada, some provinces cover to a maximum of an approved list of ocularists, some ranging from 75% to 100% of the cost. The remainder 25% is paid out of pocket or covered through a private insurance provider. There are a few provinces that cover nothing at all. Maintenance of a prosthesis is covered for the most part as well by the same provinces. With this being said, as Canadians, we should have a guideline of how often younger patients need to visit an ocularist and not necessarily rely solely on an “as needed basis”. This ensures that certain things can be rectified before they become problematic later in life, resulting in reconstructive surgery which can be detrimental to the social and emotional component of a patient’s life. A “passport” similar to the yellow immunization card in Ontario, with a timeline of expected routine follow-up appointments would be beneficial for a new patient which should also be reflected in the Retinoblastoma Guidelines of Care. Additionally, universal coverage across Canada should be considered at the federal level to encourage a better pathway of care for follow up after enucleation. This can ensure patients are waiting for an appropriate replacement time in between ocular prosthetics and maintenance of their prosthesis and avoiding any delays. 

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A Review of Literature on Health-Related Quality of Life of Retinoblastoma Survivors

Plain language summary written by Michelle Prunier and Alissa Ulster

While retinoblastoma treatment often occurs in early childhood, retinoblastoma survivors may have long-term effects. In the research article, “A Review of Literature on Health-Related Quality of Life of Retinoblastoma Survivors”, the study team was interested in reviewing the existing research on the Health-Related Quality of Life (HRQOL) of retinoblastoma survivors. HRQOL is a way to describe the physical, mental, and social components of someone’s well-being.

As a bilateral retinoblastoma survivor, I have witnessed the long term impacts of retinoblastoma on both myself and my relatives. With these life experiences in mind, I am very interested in research studies discussing how retinoblastoma impact’s people’s lives later on in life. 

The study team searched through several online databases for peer-reviewed studies that have been published starting in 2005, about topics like “health-related quality of life,” “quality of life,” “outcomes,” and “retinoblastoma.” This search resulted in 15 studies, which came from eight different countries and included both child and adult retinoblastoma survivors.

Out of the 15 studies, HRQOL findings after treatment were varied. 

Four studies contained both a child’s self-reported HRQOL and a parental assessment of the child’s HRQOL; in each of these studies, the parent reported lower HRQOL than the child’s self-reported outcomes.

Several studies identified potential predictors of HRQOL in retinoblastoma survivors. These include factors like the age of diagnosis, visual acuity (like an assessment on the eye chart), and whether the survivor has experienced bullying. Factors like gender, unilateral versus bilateral disease, and whether the tumors were contained in the eye, and type of treatment were not significant predictors of HRQOL.

Other studies did differ HRQOL for bilateral survivors compared to unilateral survivors. Bilateral survivors were more likely to report feelings like fear of getting cancer again, and worry about their children being diagnosed with retinoblastoma. However, bilateral survivors did not report significantly worse psychological and social function than unilateral survivors.

Also, all of the studies that the researchers looked at in this review were done outside of Canada. As these studies took place all over the world, they reflect areas with different healthcare systems and different protocols to treat retinoblastoma. The wait time between the start of symptoms and the time of diagnosis also varies between countries, and survivors may face barriers in access to healthcare. This means that the results of these studies may not represent Canadian people as well as the Asian and European people where the original studies took place. 

Another limitation I found was that siblings were used as the control group. The control group is usually a population that sets the standard which the comparisons are made in a study. From my experience with retinoblastoma and from hearing stories from families in the Canadian Retinoblastoma Research Advisory Board, the siblings often have their own psychosocial needs that are unlike the general population. While I understand why siblings are often used as the control group in these studies, I believe that the unique differences between siblings and the general population should be acknowledged. This may be an area where patient partners can provide valuable input about how research is conducted, using their lived experiences.

Overall, the literature review shows that HRQOL measures varied across the different studies. This may be because there is no consistent “gold standard” way to measure HRQOL, so the studies examined may have used different methods to obtain their results. Further research is needed to clarify what is the best method to measure HRQOL.

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Patients with Retinoblastoma and Chromosome 13q Deletions have Increased Chemotherapy-related Toxicities

Plain language summary written by Jillian Purdy and Furqan Shaikh

Personal Story

I selected this article because I wanted to learn more about 13q deletion syndrome. There are many articles, much research and a whole organized community related to RB but there is little research to be found related to 13q deletion. This article relates to our lived experience with RB treatment. Samson experienced dose delays and dose reductions during his chemotherapy treatment. This article also raised many questions for discussion with the CRRAB community. 

Background

While most patients with retinoblastoma (RB) have a gene mutation in the RB1 gene, a small percentage (6%) of retinoblastoma patients have a deletion of chromosome 13q (13q-). The 13q chromosome includes the RB1 gene as well as other genes.

Patients with 13q- have a spectrum of intellectual disability and/or congenital malformations. Some examples are: variable developmental delays, language and communication impairment and low muscle tone. 

The impact of this deletion on therapy and outcome for RB patients, including treatment related side-effects is unknown. We know that 13q- negatively impacts outcome for patients with other cancers. The impact is not known for RB patients since treatment has evolved since previous studies.

Methods

Over a five year period, a total of 105 patients with intraocular RB were enrolled in the study. Of those, 68 received chemotherapy; 11 had 13q- and 57 did not. More serious side-effects were compared between groups. Hematologic, infectious, and gastrointestinal (GI) toxicities were compared between patients. Demographic, clinical and outcome information was reviewed, including duration of each therapy related event and impact on subsequent therapy. The association of 13q- and dose delay, dose reduction and specific toxicities was examined. 

Results

Demographics and exposure to chemotherapy were similar among study patients. The overall frequency of 13q- in RB patients was 10%. Dose reductions due to hematologic toxicities, specifically prolonged neutropenia (low levels of neutrophils in the blood, that weakens the immune system), were more frequent in patients with 13q- (5/11 or 45%) than non-13q- patients (4/57 or 7%). GI toxicities and infectious complications were similar between groups. The authors found that the 13q- RB patients did not have increased treatment failure. Overall survival was similar between groups and all patients were alive at follow-up.

Discussion

The authors concluded that aggressive supportive care and careful consideration of reduction in chemotherapy for RB patients with 13q- will provide similar responses to treatment and disease outcomes. However, they do not know why.

After reading this article, I was happy to learn that there was a positive outcome for all RB patients, including those with 13q-. However, I am left with more questions about the causes of increased toxicities from chemotherapy in 13q- patients and what other aspects of the treatment journey may be unique to 13q- patients, such as secondary cancers. 

When thinking about other causes of increased toxicities related to the characteristics of 13q-, I wondered if poor metabolism of chemotherapy, body size and organ function may play a role. I also wondered if there could be a link between treatment related toxicities and the size and/or region of the deletion. 

When reading about the methods, I wondered if the study results could have been influenced by subjective decisions by physicians throughout the treatment process regarding who needed treatment reductions or delays?

According to the authors, 13q- RB patients did not have increased treatment failure. This made me wonder about how to measure treatment success and if 13q- patients had increased treatment length or other negative effect such as increased damage to the eye and vision. 

Lastly, when thinking about the study size, I wondered if 11 patients with 13q- is enough to draw an accurate conclusion? With the understanding that the population of 13q- patients is very small, would the study have come to the same conclusion if they had more participants, drawn from multiple centres? With so few articles and studies related to 13q-, how do we overcome barriers to research and collaboration across centres? 

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An exploratory study of sleep habits in school-aged survivors of retinoblastoma

Plain language summary written by Leslie Low and Kimberly Courtney

Personal Story

I am a mom to triplets with bilateral RB who each lost an eye during treatment. I often worry what physical and emotional side effects they may encounter as a result of their treatments. My triplets have always been sufficiently good sleepers; however, going to sleep at night has always been a struggle for them. I have always believed that their difficulty falling asleep is because they share a room with their 2 best friends; I did not consider that there could be any connection to their cancer journey. I am interested in this article because it is studying a potential psychosocial impact that Retinoblastoma may have on patients. It reminds me that there may be many potential side effects, such as quality of sleep, that could have an impact on my children’s quality of life. It reminds me to keep an open mind in order to ensure they are coping well and have access to resources when they need them. 

I often interact with other RB parents whose children have a variety of physical and emotional struggles post-treatment. Often parents post on social media looking for others who can relate to their situation. While finding someone to relate to can be very helpful and can lead to some great solutions, proven research gives a patient more capacity to advocate and potentially access other helpful resources. It helps me recognize the importance of research because it can provide very important information to improve treatments, outcomes, and long-lasting effects. Knowledge is power!

Background

We often hear how important sleep is and how much it can impact quality of life. Many retinoblastoma survivors and parents of survivors are interested to know more about the physical and emotional functioning of survivors. This includes the impact on sleep and sleep related-difficulties and how much they are affected after treatment. The purpose of this research study is to answer three main questions: (1) How school age retinoblastoma survivors sleep?, (2) Are there any links between sleep and quality of life (including being healthy, comfortable, and able to enjoy life events)?, (3) Do parents and children report sleep habits the same or differently?

Methods

Sixty-nine children with retinoblastoma and their caregivers were enrolled in the study. Twenty-six of the children were bilateral. Forty-six children had a unilateral enucleation and two had a bilateral enucleation. 

The participants were asked to fill out questionnaires about sleep patterns as reported by the children, sleep patterns reported by the parents about their child, and quality of life. Their medical information was pulled from their charts.

The surveys used were:

1. Children’s Report of Sleep Patterns (CRSP) which is a validated survey used to measure 3 categories including sleep patterns, sleep hygiene, and sleep disturbances. Only the children filled out this survey. The average age of the children was about 11  years old.
2. Children’s Sleep Habits Questionnaire (CSHQ) is a psychometrically strong questionnaire used to measure behavioural and medical sleep concerns. This questionnaire was filled out by the parents.
3. Pediatric Quality of Life Inventory (PedsQL) is completed by the children and the parents which measures physical, emotional, social, and school functioning.

Results

The study team identified key findings when comparing the data to the regular population, specific differences based on demographics, analysis of the questionnaire filled out by the children, and analysis filled out by the parents.

The most impactful findings include:

• Compared to a non-RB survivor population, reports from parents of children with retinoblastoma indicated that they observed:
  • More bedtime resistance 
  • Delay to the start of sleep
  • Increased daytime sleepiness
• Compared to a non-RB survivor population, reports from children with retinoblastoma indicated:
  • More sleep problems with sleep location
  • More restless leg syndrome 
  • More parasomnia (a sleep disorder which may involve movements such as sleep terrors, sleepwalking, nightmares, and sleep-related eating disorder which happens while you are asleep but it would seem to others as though you are awake)
• Within the RB population it has been observed:
  • RB survivors with unilateral RB report greater caffeine consumption
  • RB survivors who underwent enucleation report more electronic use before bed
  • Parents of RB survivors who underwent enucleation report increased sleep-disorder breathing
  • Male RB survivors reported more parasomnia than female RB survivors (consistent with general population)
  • Female RB survivors reported higher levels of insomnia than male RB survivors (consistent with general population)
• Comparing the reports of children versus their parents:
  • Generally, the results of the parents matched the results of the children with retinoblastoma 
• Looking at sleep patterns and relationship to quality of life:
  • Both parents and RB survivors report that poor sleep habits were associated with decreased quality of life. In particular, the child report showed high fear and worry which correlated to parents reporting negative effects on emotional and social quality of life.

Conclusion

Sleep-related difficulties are present in children with retinoblastoma. Sleep is a very important function of life and impacts executive functioning (including self-control, following directions, etc) as well as impact on relationships. The research team recommends targeted psycho-education on healthy sleep habits and routine screening during follow-up appointments. 

Further research is also needed to better understand the changes that occur during the school years and how they differ by sex in order to provide better support. 

Discussion

After studying this article and having the opportunity to discuss the findings with professionals, I believe there are some really interesting findings that would benefit from more research being performed. This study is an “exploratory study” which means it is investigating a topic that has not been studied in depth yet. The intention of exploratory research is to lay the groundwork to determine if further analysis could potentially find worthwhile data. Based on some of the data found, we believe there may be some interesting information that could be uncovered with further studies. More in depth information that we felt might be especially beneficial to expand on was:

• Larger and more diverse sample
  • gather data from more centers to increase diversity and number of patients in study
  • studying more age ranges
• More in depth analysis of the treatments received and whether they correlate to sleep quality (ie number of times under anesthesia, number of months receiving active treatments, types of treatments received, whether they had an enucleation, unilateral or bilateral presentation, visual acuity score, etc)
• Comparing the results to similar research of childhood cancer survivors or the visually impaired (the article states that studies have already been performed for these demographics, and both have reduced quality of sleep compared to the general population)
• Comparing to a parent’s assessment of themselves (do parents who report a higher level of stress and anxiety over treatments report worse sleep outcomes in their children?) 
• Determine if there is a significantly higher usage of things like screen time or caffeine consumption before bed that are already proven to lower sleep quality.

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Considerations for the use of circulating tumour DNA sequencing as a screening tool in cancer predisposition syndromes

Plain language summary written by Mary Connolly-Wilson and Stephanie Kletke

Here are some basic definitions of concepts discussed throughout the paper.

• DNA is naturally found in cells. Small pieces of DNA are released into the blood when cells die. This is referred to as cell free DNA (cfDNA). 
• When a cancer is present, tumour cells also release cfDNA into the blood. This is referred to as circulating tumour DNA (ctDNA). 
• Liquid biopsy is a lab test done on blood or other body fluid to look for ctDNA (cancer signals). This test can tell us about the genetic changes of a cancer, without directly taking a biopsy of the tumour. This testing can be repeated over time to see what genetic changes are taking place in a tumour. By looking for tumour signals in the blood, we may also find cancer at an early stage. ctDNA testing may also be used to help plan treatment, to find out how well treatment is working, or to find out if cancer has come back.
• A person with a Cancer Predisposition Syndrome is someone who has a genetic mutation (such as the RB1 mutation found in people with hereditary retinoblastoma) that increases their chances of developing cancer at an earlier age compared to the general population.
• A screening protocol is a document providing detailed plans for using tests to find out whether or not a person has a specific health condition before it causes any symptoms

This paper highlights the potential use of cfDNA blood testing to study, find and track cancer. It also explains how cfDNA can be used to find cancer before signs appear in people who have a higher chance of having second cancers, like retinoblastoma survivors.

Many Cancer Predisposition Syndromes have screening protocols to find cancers at an early stage. At this time, there is no protocol to screen for second cancers for retinoblastoma survivors. As a person with an RB1 mutation, I am very interested in any type of screening for second cancers that might lead to finding the cancer early and having a better chance to cure it.. 

A test that checks the blood is not difficult for a person to do and does not have the same risks which can be found with other screening methods. For example, MRIs may need anaesthesia in young children and the use of contrast agents, which have a higher chance of potentially being exposed to long term toxicity. Tests such as CT scans and mammograms have an added chance of being exposed to radiation. Cell-free DNA blood testing does not have these risks and also has the potential to produce fewer chances that the test would show there is cancer when there actually is not than standard imaging alone.

A variety of strategies can be used for cfDNA blood testing. The paper describes the technique, basic concept, advantages and limitations of these strategies in a large chart in this paper and I welcome you to explore it for yourself. The paper also describes a small number of studies exploring various approaches to test the blood for cancer. The DETECT-A study showed that doing cfDNA blood testing and clinical imaging can safely find cancer in people who did not already have a cancer diagnosis. The Taizhou Longitudinal study found that cfDNA blood testing was able to predict cancer as early as 4 years before diagnosis. The CHARM study, based in Canada, is comparing ctDNA testing to standard screening protocols to find cancer early. 

The authors acknowledge many questions and problems that need to be addressed by researchers and health professionals before cfDNA blood testing can be used. It is important to consider the costs and how this test compares to other tests already in clinical use. They conclude that including the cfDNA testing as part of the screening protocol can potentially change patient care, especially for people who have a genetic mutation.

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Group Medical Play and Children’s Self-Reported Fear in the Pre-Operative Setting

Plain language summary written by Lindsey Robinson, Jocelyn Leworthy and Morgan Livingstone

My daughter was diagnosed with unilateral non-hereditary retinoblastoma in January 2021, at the age of 3.5 years. Her treatment included 3 cycles of intra arterial chemotherapy, 6 weeks of chemo plaque, and surgeries for a detached retina, cataract, and tumor extraction.  I related to this article because over the course of 26 months of treatment and surgeries, she had visited the pre-operative waiting area at the hospital 27 times in preparation for procedures requiring general anesthesia.  Quite often this was a very upsetting experience for her as she would become anxious, irritated, and scared while in the waiting area and often to the point of hysteria after administering eye drops and pre-anesthesia medicine.  I was interested in the results of the article because I often wondered had my daughter been exposed to medical play with a child life specialist while at the hospital and prior to her procedure, would it have provided her with a less traumatizing hospital experience. 

Background

The purpose of the study was to explore the impact of a group medical play intervention on children’s self-reported fear and observed anxiety, while considering whether offering group medical play intervention as a clinical or research intervention is feasible within the bounds of typical child life staffing.  Past studies have only included one-on-one medical play sessions provided in the days leading up to surgery, rather than the day of scheduled surgical intervention. The authors sought out to address the following research questions: How do young children in the pre-operative waiting area experience a group medical play intervention facilitated by a Certified Child Life Specialist? What is the feasibility of offering group medical play as a clinical or research intervention in the pre-operative setting?  

Methods

Twenty children between the ages of 5 to 10 years who were scheduled for a sedated surgical or medical procedure in the pre-operative services waiting area of a children’s hospital participated in a 30-minute group medical play session facilitated by a Certified Child Life Specialist.  On average, participants had previously undergone 3.5 surgical procedures and were scheduled to undergo a range of surgeries or procedures including dental, eye, ear, nose and throat, gastrointestinal, cardiac or other.  At the conclusion of the group activity, participants used a pictorial scale to rate their level of fear about surgery at two distinct timepoints: prior to and after the medical play session.  In addition, participants also responded to three open-ended prompts about their perceptions of the activity.

During the intervention one of the two members of the research team rated the children’s -Modified-Yale Preoperative Anxiety (m-YPAS).  YPAS assesses pre-operative behaviours of children that may be indicative of anxiety at a particular period in time rather than a more generalized state of anxiety that can persist across time and events.  

Results

While participating in the group medical play, participants demonstrated an average m-YPAS score of 5.65 (low = 5, high = 22) that reflected their overall anxiety from start to finish.  This means that children showed relatively low levels of pre-operative anxiety throughout the medical play interaction.  When asked to report their feelings of fear about their surgery or procedure prior to and after the medical play intervention, findings showed a signification decrease in fear. Specifically, children reported an average fear rating of 2.35 prior to the intervention and an average of 1.7 after playing doctor (happy =1, very afraid = 5).  

With regards to the open-ended questions, overall, 90% of participants reported positive feelings about their medical play experience.  When participants were asked how they felt about their scheduled surgery that day, 40% reported feeling positive.  

The research team, through consensus discussion and efficacy of data collection found this study and the group medical play intervention to be feasibly while balancing clinical child life care.

Discussion

The authors concluded that the results of the study align with foundational principles of child life practice, namely, the emphasis placed on play as a coping tool for children undergoing stressful health care experiences.  The children in this study reported a decrease in fear about surgery or their procedure after engaging in the child-directed group medical play activity.  The authors also stated that the medical play presented in this study provided participants with a nonthreatening opportunity to handle, explore, and investigate real and pretend medical equipment, which they may or may not have been exposed to before.  The format of the intervention appeared to foster a sense of trust and most participants were observed to feel comfortable enough to ask a question about an item they were not familiar with.  While past studies highlight the use of medical play intervention in the days leading up to the surgery, this study reveals a significant decrease in anxiety when the intervention is implemented on the day of surgery.  

Questions to Consider

For Those with Lived Experience:​

• Has your child participated in group play? ​
• How has your experience been in the waiting room?​
• How have you prepared your child for their appointment (OR or eye clinic)?​
• What are your child’s biggest psychosocial concerns related to RB medical experiences?  How can they be better supported?​
• Are you surprised by the level of anxiety reported in the study?​
• What do you feel your child could have gained or has gained from taking part in group medical play with a Child Life Specialist?​

For Healthcare Professionals​

• What do you perceive to be psychosocial concerns for your patients during their medical encounters? ​
• How do children arrive to the OR and how are different situations handled? Is there anything that you have noticed that makes a difference?​
• What experience have you had with offering support to children before procedures and how does your experience compare to this study ?​
• What process or criteria is used to ensure psychosocial support is offered to your patients?​

For Researchers​

• How does the children’s anxiety compare to parent anxiety for RB?​

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Eye-related quality of life and activities of daily living in pediatric retinoblastoma patients: a single-center, non-controller, cross-sectional analysis 

Plain language summary written by Genevieve McCarthy and Margaret Reynolds

As a survivor of unilateral retinoblastoma (RB) with left eye enucleation, I was always told by my parents that I could do anything that others could do. I believed that was true and enjoyed many extra-curricular activities, attended camps, played sports and took on life despite my early medical experiences. As I got older and wiser, I recognized that was not everyone’s story and it made me curious about other survivors’ experiences. The important topic of quality of life following an RB diagnosis was of interest to me and I wanted to know more about how others have been impacted.  

Background

The researchers aimed to determine whether school aged survivors of RB had impacted activities of daily living and eye-related quality of life.  The relation between topics had not been explored previously and could inform if support is needed for RB children to help them lead normal lives. 

Methods

Sample of 65 children diagnosed at St. Louis Children’s Hospital. Children who were excluded from the study had any of the following: 

• in active treatment within the last 6 months  
• diagnosed with pre-existing condition associated with cognitive impairment, compromised visual function 
• impaired activities of daily living (ADL) which includes basic skills required to take care for oneself, such as eating, bathing, and mobility 
• underwent bilateral enucleation 

There were 23 children enrolled in the study but only 19 children and their parents completed surveys. Researchers administered questionnaires childhood RB survivors between 5-17 years old.  

• Pediatric Eye Questionnaire (PedEyeQ) assessing the quality of life from eye perspective geared towards kids which includes 3 components: patient responses, parent responses, and parent on behalf of their child responses. This questionnaire focused on 4 topics: functional vision, social, bothered by eyes/vision and frustration/worry.  
• Roll Evaluation Activities of Life (REAL) assesses activities of daily living, independence skills and school deficits. It is completed by a caregiver only.  
• School Demographics identifies child’s school performance such as whether child repeated a grade or requires special attention in the school setting.  
• Visual Testing for visual acuity, eye tracking and contrast sensitivity were also assessed at child’s follow up appointments.  
• Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) measures how well people can take care of themselves and live on their own. 

Researchers analysed visual outcomes and demographics for eye-related QOL and compared it’s impact on ADL among school aged RB survivors. Further analysis provided insight into relationships between ADL, QOL, demographics, type of treatment and visual outcomes.   

Results

The demographics of the children who completed the study included: 

• Mean age of 9.6 
• 48% bilateral 
• 35% female 

• 83% underwent systemic chemo 
• 70% enucleation 

Main findings 

• Strongest relationship occurred with QOL and ADL testing in regards to parent worry, parent responses on behalf of their children for eyecare, child function, ADLs and IADLs 
• strong relationships were parent focused (ex. parent worry most impacted by visual acuity and contrast sensitivity) 
• When children scored low on visual tests, they also had trouble with functional activities 
• When children scored low on eye function tests, parents experienced more worry about the child’s ability to function and interact with their surroundings 
• When ADL scores were low, they were related to demographics (rage, age, laterality)
• Germline positive had more burden of eye care – worse quality of life for parents 

Discussion

This study concluded that school age RB survivors have decreased QOL and majority have ADL scores lower than 75% of the population. Decreased visual acuity, contrast sensitivity and eye tracking were linked to impaired QOL.  

Given the visual impairments and high frequency of ADL impairment of these patients in the report, authors suggest that ADL assessment, programming and strategies may result in improvement of child’s QOL. The authors concluded that further investigation and exploration into how rehabilitation efforts with occupational therapy could improve QOL.  

Visual function beyond acuity have not been related to ADL and QOL previously. Further investigation into relations between specific visual function and school performance could help increase supports and resources.  

When reading this article, I felt that parent reported worry may be impacting child’s engagement in ADL and IADL, therefore resulting in impacted overall QOL. Not intentional by nature however more innate and protective regarding fears.  As a small and young sample group, it is difficult to determine accurate information on ADL.   

Questions to Consider

1. What additional topics of focus could be generated from this study?  

2. Do the results lead toward parent perspectives impacting children’s function? 

3. If demographics are more related to ADL impact, is culture or familial standards more relevant?  

4. Barriers to following through with study – feedback from families – best way to contact and engage 

5. How to communicate with families to keep in contact 

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Recommendations for Long-Term Follow-up of Adults with Heritable Retinoblastoma

Plain language summary written by Ella Bowles, Dan Gombos, and Ivana Ristevski

Terms from the Article

Germline mutation : Changes to the DNA that happen in the reproductive cells of the body. If one of the parents has the mutation it can be passed on to the next generation and would affect all the cells in their body. Unlike somatic mutations which do not affect the reproductive cells and are not passed to the next generation. These are the two main types of RB1 gene mutations among the RB population.

Heritable retinoblastoma: The passing on of the mutated gene to the child.

Subsequent malignant neoplasms (SMNs): Development of a new, unrelated cancer later in life. Secondary cancerous tumors which can spread into nearby tissues are malignant. Benign neoplasms are not cancerous growths and do not spread into nearby tissues. 

National Comprehensive Cancer Network Categories of Evidence and Consensus: System of grading guideline development with uniform expert opinion.

Dysplastic nevi: A mole that looks different than usual and may develop into melanoma that should be examined by a health professional. These moles have irregular edges and are larger in size. It can range in colour and may be raised. Also referred to as irregular moles.

Sarcoma: A broad term for a type of cancer that develops in the bone or the soft tissues of the body. Soft tissues include cartilage, fat, muscle, blood vessels, fibrous tissue, or other connective or supportive tissue.

Ella’s Personal Story

I (Ella Bowles) am 42 years old, had bilateral retinoblastoma (RB) and have a germline mutation. Early last year I began to develop lumps in my neck, and now have eight or so. Because of past work with RB cancer and care I had some knowledge of the increased risks that I have as a patient with the germline mutation, but I have been out of the literature loop for about a decade and so was not entirely sure how concerned I should be about the lumps and what I should do about them. I moved to Ottawa in 2022, and despite significant efforts have not been able to find a family physician. I have also moved around the country a lot for education and work, so I have had intermittent access to GPs and have inconsistent paper records. I’ve never been able to secure access to a long-term follow up clinic, but have had consistent ophthalmic care. Ultimately it took quite some effort to get imaging done on the lumps, and my experience lit a fire under me to take the time to understand what my risks really are and what screening I should advocate for. Here I am, doing just that.

Background

RB survivors with the germline mutation have an increased risk of developing a new, unrelated cancer later in life. This risk is even higher for those who also had external beam radiotherapy. 

Surveillance for RB survivors varies,  with context, within each country, with no universal guidelines available. To address this problem, a diverse group of health professionals, including ocular oncologists, epidemiologists, survivorship specialists, pediatric oncologists, radiologists, and a geneticist, from RB centres around the world met to conduct a comprehensive review of published findings. Using an evidence-based approach, they analyzed published articles to assess the risk associated with retinoblastoma survivors across various cancer types and utilized a grading scale to determine the level of risk. Recommendations for long-term follow-up were formulated based on these study findings. 

Main Idea

This article discussed nine SMNs with varied degrees of risk. We will highlight only the highest risk SMNs in our summary.

RB survivors face the highest risk of developing bone (osteosarcoma) and soft tissue sarcomas (fibrosarcoma, rhabdomyosarcoma, late-onset leiomyosarcoma and malignant fibrous histiocytoma), melanoma, and uterine leiomyosarcoma, regardless of whether they underwent radiotherapy. 

Bone and Soft Tissue Sarcomas

Recommended surveillance for bone and soft tissue sarcomas includes annual history and physical examinations with specific attention to bones and prompt evaluation of signs and symptoms of pain or tenderness. While three is no evidence to support the use of whole-body MRI for early cancer detection there are also concerns regarding additional testing, gadolinium (solution used for contrast in images) deposition, and psychosocial distress.

Melanoma

Melanoma surveillance should start before the age of 8 to identify irregular moles, followed by annual skin exams after adolescence, emphasizing skin protection measures and awareness of irregular moles. 

Uterine Leiomyosarcoma (Uterine Cancer)

Published research identified that the age of diagnosis ranges from 32 to 51 years and one study reported that out of 525 heritable RB survivors, 7 had uterine leiomyosarcoma. While the risk is evident, there is no imaging surveillance of the uterus that has shown to be beneficial. 

Additionally, RB survivors have a moderate risk of breast cancer after the age of 40 and lung cancer, with no evidence linking radiation from mammography to increased risk, though non-radiation imaging methods should be prioritized when possible. RB survivors with a history of smoking should undergo surveillance as recommended by local health professionals, with smoking prevention and cessation support advocated.RB survivors who received radiotherapy face an additional risk of brain and central nervous system tumors.

Discussion

This article has highlighted that there is a lack of evidence for routine surveillance for most SMNs. Large-scale, multi-site studies with long-term follow-up of heritable RB survivors, which could include periodic protocol-guided imaging, are essential to understand long-term risks associated with RB1 mutation type, treatment modalities, and other genetic factors.

It was recommended that patient partners be included in subsequent endeavors, though they were not part of the initial team.

As we found out through our article discussion with Dr. Gombos, this article is of particular interest to the RB community because it utilizes the data from 2 of the largest retinoblastoma survivorship databases. The retinoblastoma research teams in the Netherlands and New York, USA led by Dr.Moll and Dr. Abramson respectively have been studying second cancer among retinoblastoma survivors for a long time and are considered leaders in this area of research.

After reading this article, the scope of what I should be monitoring consistently, actively avocating for anything concerning, and well check-ups with a physicianan was more clear to me. It is important to know which cancers you are at risk for and what to watch for so you can take actionable steps. This is especially true for uterine leiomyosarcoma which is not screened for during a Pap test.

Questions to Consider

Questions for those with Lived Experience with RB:

1. Do you feel you have a good understanding of the SMNs risks and what to watch for?
2. What questions do you still have about SMNs after discussing the article?
3. How can your RB team help you better understand SMNs risks and what to watch for?
4. Does whole-body MRI imaging give you more or less stress, considering the lack of evidence to suggest benefit for SMNs surveillance?
5. Were you surprised by any aspects of the article?

Questions for those with Professional Experience with RB:

1. How can patients best connect with a follow-up clinic?
2. What strategies can you give patients to advocate for attention to any concerns they have (e.g., skin abnormalities) when they are dealing with walk-in clinics and/or family physicians in general?
3. How does your centre monitor for SMNs?
4. How much does level of treatment affect risk of SMNs?
5. Do RB survivors with chromosome 13 deletion have different level of risk for SMNs?
6. Is research underway to address the gaps in science regarding surveillance for SMNs among the RB survivors?
7. Which other predisposition syndromes have surveillance and can we learn anything from them?
8. What concerns about SMN surveillance do you hear about the most from RB families?
9. What SMNs have you encountered in your practice among RB survivors? How were these SMNs identified?
10. How are non germline RB survivors affected?

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Applications of three-dimensional printing in ophthalmology

Plain language summary written by Mark Scanlon, Noha Soloman, and Ivana Ristevski

Mark’s Personal Story

Having lost my right to RB when I was five, I grew up navigating life with a prothesis. It was always a challenge to try to get a new prothesis, when one was needed, to fit properly in my socket around the implant that was placed following the enucleation. In my early 30s, the implant became infected and had to be removed, meaning that a prothesis not was longer a viable option for me and leaving me to cover the open socket with eye patches. Advancements such as these offer new opportunities not only for myself but also others in similar situations when it comes to options for prosthetics, and I think it is very exciting to see what sort of advancements are being made in this area.

Background

Three-dimensional (3D) printing technology has revolutionized various fields of medicine, including ophthalmology, by providing innovative solutions for complex clinical challenges. In ophthalmology, 3D printing offers potential applications ranging from the creation of customized surgical instruments and implants to the development of patient-specific models for surgical planning and education.

By exploring the advancements and challenges in the integration of 3D printing into ophthalmic practice, the study aims to inform clinicians, researchers, and medical device developers about the potential benefits and limitations of this technology. The goal is to encourage further research and development in this area, ultimately leading to improved patient outcomes and advancements in the field of ophthalmology.

Main Idea

The article covers all aspects of 3D printing in ophthalmology but we will only focus on the topics relevant to retinoblastoma. 

Clinical Devices

Ocular prosthetics can be created with the use of 3D printing technology. While setup costs are quite high, this technology has the potential to cut manufacturing times and cost of prosthetics. The process for developing a prosthetic eye can include: 3D scanner to image the socket, 3D printing of prosthesis, photograph and print 2D photo of the other eye to create matching image and transfer to prosthesis. While the production time is reduced, the overall cost of 3D printed prosthetics is similar to the traditional method. Through our discussion with Noha, 3D printing requires an engineer to create and use the software, technician to scan the socket and upload the data to the printer, 3D printer operator, and the materials.

Surgical planning has been used to visualize and simulate the procedure. This can potentially be used in retinoblastoma treatment in mapping the tumor and for fitting the orbital implant.

Medical Education

The use of 3D printing in medical education for retinoblastoma is not covered in this article but from our discussion, there is an opportunity to use 3D printed models of the eye to diagnose retinoblastoma cases earlier by using them as educational tools for new clinicians.

Challenges of 3D Printing in Ophthalmology

Despite its promising applications, 3D printing in ophthalmology faces several challenges:

• Regulatory Hurdles: The approval process for 3D-printed medical devices can be complex and time-consuming, as regulatory bodies require comprehensive testing to ensure safety and quality.
• Precision and Reproducibility: Achieving the high level of precision required for ophthalmic applications can be difficult. Variations in the printing process can lead to inconsistencies in the final product, impacting its reliability and effectiveness.
• Cost and Accessibility: While 3D printing can reduce costs in the long run, the initial investment in equipment and technology can be high. Additionally, access to advanced 3D printing technology may be limited in low-resource settings.
• Ethical Challenges: There have been some religious objections to the technology and concerns that the host cost would widen the disparity in healthcare. The main concern is regarding intellectual property.
• Legal Challenges: There is no regulation in 3D printing which could result in varying quality of products and related safety issues. 

Future Work

Future advancements in 3D printing for ophthalmology are likely to address current limitations and expand its applications. Key areas of focus include:

• Material Development: Research into new biocompatible materials that better replicate the properties of natural ocular tissues will be crucial. This includes developing materials that are suitable for long-term implantation and that can integrate seamlessly with surrounding tissues.
• Improved Printing Techniques: Advances in printing technology will enhance the precision and reproducibility of 3D-printed devices. Techniques are expected to improve the quality and functionality of ophthalmic implants and instruments.
• Personalized Medicine: The integration of 3D printing with imaging technologies (e.g., MRI, CT scans) will further enable the creation of highly personalized medical devices tailored to individual patient anatomies.
• Regulatory Frameworks: Establishing streamlined regulatory pathways for the approval of 3D-printed medical devices will facilitate their clinical adoption. Collaboration between regulatory bodies, researchers, and industry stakeholders will be essential in developing these frameworks.
• Educational and Training Tools: The use of 3D-printed models for surgical training and education is expected to grow, providing more realistic and customizable training tools for ophthalmologists.

By addressing these challenges and pursuing future research directions, 3D printing has the potential to significantly advance the field of ophthalmology, improving patient care and surgical outcomes.

Discussion

Primarily, advancements in 3D printing may be able to have a great effect on a patient’s post-RB quality of life. One of the greatest challenges rare diseases such as RB pose is the adjustment to a sense of normalcy following treatment, especially heading into and navigating adolescence. Aside from other critical factors such as accessibility and cost implications in the long run, I see the greatest impact being on the ability to bring prosthetic eyes that are indistinguishable from the “real thing”. Adolescence is difficult enough. Experiencing adolescence post RB, where it is very easy to feel isolated from your peer group, is an even greater challenge. I’m excited to see where advancements such as this lead in terms of the quality of life of the patients this affects.

Questions to Consider

Questions for those with lived experience:

1. What aspect of 3D printing are you most excited about for use in retinoblastoma treatment and care?
2. How can 3D printing technology improve the design and comfort of prosthetic eyes for individuals who have undergone enucleation due to retinoblastoma? 
3. How can advancements in 3D printing technology contribute to the psychosocial well-being of retinoblastoma patients who require ocular prosthetics?
4. What role can patient partners have in the education and training of ophthalmologists with 3D printed models who treat retinoblastoma and manage ocular prosthetics?

Questions for those with professional experience:

1. How can 3D printing technology improve the design and comfort of prosthetic eyes for individuals who have undergone enucleation due to retinoblastoma? 
2. What are the potential cost implications of 3D printed ocular prosthetics compared to traditional methods, and how might this affect accessibility for retinoblastoma survivors?
3. Are there any other challenges preventing the use of 3D printing in ophthalmology (ie. insurance coverage, security of image data being used in printer, etc)
4. Is there a need for 3D printing of surgical tools (ex. For use on very small babies)?

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A Scoping Review of Vision Rehabilitation Services in Canada

Plain language summary written by Charles Campbell and Atul Jaiswal

Key Terms
Vision Loss: Uncorrectable, partial or complete impairment of vision.
Comprehensive Vision Rehabilitation (VR): refers to a multidisciplinary endeavour that encompasses the full spectrum of a patient’s rehabilitation journey after vision loss from the initial assessment through intensive rehabilitation therapy.
Vision Loss Rehabilitation Canada (VLRC): Vision Loss Rehabilitation Canada (VLRC) is a not-for-
profit national healthcare organization and the leading provider of rehabilitation therapy and healthcare services for individuals with vision loss.

Personal Story
My name is Charles Campbell, I’m the father of 10 year old RB survivor Katelyn, who was diagnosed with bilateral RB at 3 months old. Immediate enucleation of her right eye was conducted with further treatment on her left eye including Chemo, Cryo, Laser and finally brachytherapy (radiation plaque). Katelyn transitioned to the eye clinic in 2019 for ongoing surveillance. Katelyn has additional challenges caused by a 13q deletion (13q deletion syndrome/global development delay/autism spectrum disorder). In April of 2023, Katelyn began experiencing severe headaches along with a significant loss of vision. CT and MRI scans showed a significant tumor in her left orbit behind her eye, causing pressure on her optic nerve. Post biopsy, Katelyn had complete vision loss for a period of time with gradual improvement over the next year. She would be diagnosed with Langerhan’s Cell Histiocytosis (LCH), a condition that causes abnormal white blood cells to clump together, causing a tumor. She was again treated with systemic chemo and now a targeted gene therapy that is ongoing.

This article is quite relevant to our situation as we became involved with services such as Vision Loss Rehabilitation Canada and CNIB to name a few. Having little prior knowledge of the services available at the time, I wasn’t sure what could be offered or what assistance or equipment would be available to Katelyn, especially with transitioning back to school after her diagnosis (I didn’t know what I didn’t know). This article confirms that this is a common barrier to obtaining vision rehabilitation services.

Background
Around 1.5 million Canadians live with some form of vision impairment and the demand for vision rehabilitation services is expected to increase as the number of older adults with age related vision loss rises. The purpose of this research paper was aimed to answer two questions: (1) How are vision rehabilitations services delivered in Canada and (2), If gaps exist in the delivery of vision rehabilitation services, how can they be characterized. The purpose of the study was to inform programmes and polices for vision rehabilitation.

Methods
The authors of the article conducted a scoping review in several stages including identifying the above research questions; identifying the relevant studies found in various scientific databases; selecting relevant studies; data charting; and, data reporting. 62 studies were included in this
research article.

Results
The findings of the study revealed that although there are differences in how services are delivered by each province, there are gaps in service delivery of vision rehabilitation at the level of service providers, users and delivery systems. These gaps include lack of awareness about the benefit of vision rehabilitation, limited collaboration and coordinated services between eye care and vision rehabilitation services, delayed referral to vision rehabilitation, shortage of specialists and insufficient funding and training for vision devices.

Gaps in delivery services are characterized into 3 main groups:

1. Gaps at the level of service providers (i.e. poor knowledge of vision rehabilitation services available and lack of collaboration with other eye care professionals = lack of referral to vision rehabilitation)
2. Gaps at the level of service users (i.e. stigma, lack of awareness, misconceptions and lack of perceived need for vision rehabilitation)
3. Gaps at the system level (i.e. funding, geographical considerations, lack of specialists, outdated training etc.)

Discussion
Although the study identified 3 significant gaps in the service delivery of vision rehabilitation, in my experience, vision rehabilitation services were readily available and were highly coordinated after diagnosis. Coordination began with the SickKids POGO interlink nurse who put us in contact with VLRC, contacted the school board and Vision Itinerant for vision devices (magnifiers, angle boards, tablets etc.) and coordinated with our local paediatric therapy centre. Other services were offered through VLRC including cane training (not needed) and safety and indoor navigation planning. If there was a gap, it was certainly at the service user level, where misconceptions about the degree of vision loss was a barrier to obtaining services (she wasn’t completely blind, so what could she possibly need? – LOTS!).

The research indicates that there are gaps in service delivery of vision rehabilitation services in Canada. With an increasing number of Canadians experiencing some level of vision loss, this study aims to better inform policy to ensure that both eye care experts and patients not only have access to vision rehabilitation but are aware of the services available to them. Vision loss often leads to unemployment, restricted mobility, falls, injuries, medication errors and early placement into long term care. Enhancing access to vision rehabilitation could reduce the associated costs with the health and social care associated with vision loss. Future work to address gaps and develop and evaluate interventions to facilitate optimal vision rehabilitation services is imperative.

Questions to Consider

Questions for persons with lived experience
1) Have you experienced a gap in the delivery of vision rehabilitation services?
2) Is there or should there be vision rehabilitation services specific to RB patients?

Questions for researchers
1) Is there any research regarding vision rehabilitation services specific to RB? Would further research benefit RB survivors?
2) Would you expect there to be a correlation between vision rehabilitation services and long term prognosis of RB or other eye cancers, where early detection of vision loss or indicators of cancer recurrence could be detected?

Questions for professionals
1) Specific to the SickKids RB program, is there coordination between the healthcare providers and vision rehabilitation services? Is VR part of a treatment plan?
2) What role does vision rehabilitation play in the ongoing treatment and care of children with RB?

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Trauma-focused to Support Caregivers of Children with Severe Illness: A Caregiver-Initiated Systematic Review

Plain language summary written by BC Pomeroy

Key Terms

Trauma: Trauma is a deep emotional response to a distressing event that makes someone feel overwhelmed, unsafe, or helpless, like an accident, loss, or ongoing hardship. It can affect how people think, feel, and act.

Trauma-informed care: A way of providing support that recognizes and respects how past difficult or harmful experiences (trauma) may affect a person’s feelings, behaviours, and needs. It’s about creating an environment where people feel safe, respected, and understood.

Cognitive Behavioural Therapy (CBT): a type of talk therapy that helps people understand and change unhelpful patterns in their thoughts, feelings, and behaviors. It focuses on identifying negative thinking, challenging it, and replacing it with more realistic and positive ways of thinking to improve mental health and well-being.

Acceptance and Commitment Therapy (ACT): a type of therapy that helps people accept difficult thoughts and feelings instead of fighting them, while focusing on what truly matters to them. It encourages mindfulness, self-compassion, and taking actions aligned with personal values to build a meaningful life.

Written Disclosure Therapy: writing about difficult thoughts, feelings, or experiences to process emotions and reduce stress. It helps people make sense of their experiences, promoting healing and emotional well-being.

Background
Taking care of a child with a serious or complex medical condition was very challenging for families and often caused emotional distress. Trauma-informed care, which focused on understanding and addressing the psychological impact of these experiences, helped caregivers cope better. This review aimed to gather and summarize research on how trauma-informed care reduced stress and trauma in these caregivers.

Methods
We reviewed studies that examined how trauma-informed care helped family caregivers manage stress and trauma. To do this, we searched several medical and social science databases for research on the topic. The studies were carefully reviewed by multiple people, including caregivers with personal experience. Any disagreements during the process were resolved by these caregivers. We also analyzed the findings from the studies to evaluate the effectiveness of the interventions and identify any challenges.

Results

This review analyzed 48 studies on different therapies to help family caregivers cope with stress and trauma while caring for children with serious illnesses. Researchers looked at therapies like problem-solving skills training, cognitive behavioral therapy (CBT), family therapy, acceptance and commitment therapy (ACT), and guided self-help.

• Therapies that worked well:
  • Problem-solving skills training and guided self-help were the most effective, showing improvements in nearly all symptoms like stress, anxiety, and depression.
  • ACT and CBT also helped, but the effects varied depending on the caregiver’s situation or therapy approach.
• Mixed results:
  • Family therapy and written disclosure had limited success, and improvements were often specific to certain symptoms or caregiver roles (e.g., fathers vs. mothers).
• Other findings:
  • Therapies delivered online or remotely were generally well-received, and many caregivers valued peer support and emotional validation.
  • Some suggested improvements included longer sessions, more frequent meetings, and group activities.

Discussion
This project, which was led and guided by family caregivers, reviewed and evaluated the effectiveness of trauma-informed care programs in reducing stress among caregivers of children with serious medical conditions. The interventions we identified showed promise in helping caregivers manage stress and improve their mental health, though results varied depending on the method and caregiver needs. The results can provide valuable insights to inform the design of better care services to support families in similar situations.

Questions to Consider

Questions for persons with lived experience
1) What kind of support have you received?

2) What kind of support would you have like to have tried?

Questions for researchers
1) How does providing support compare to providing resources help caregivers?
2) What kinds of needs do different groups have?

Questions for health professionals
1) What process is in place to assist caregivers in the hospital and from external sources?

2) How do you identify if a caregiver needs support?