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Tylectomy for Intraocular Retinoblastoma: Five-Year Outcomes
Junyang Zhao, MD1,2*; Zhao Xun Feng3*; Qiyan Li, MD4*; Songyi Wu, MD5; Liwen Jin,
MD5; and Brenda L. Gallie, MD, FRCSC6-9
AFFILIATIONS
1Department of Ophthalmology, Liuzhou Maternity and Child Healthcare Hospital,
Guangxi, China
2Pediatric Oncology Center, Beijing Children’s Hospital, Beijing, China
3Faculty of Medicine, University of Ottawa, Ottawa, Canada
4Department of Ophthalmology, Beijing Tongren Hospital, Beijing, China
5Quanzhou Aier Eye Hospital, Quanzhou, China
6Department of Ophthalmology, Hospital for Sick Children, Toronto, Canada
7Krembil Research Institute, Toronto, Canada
8Techna Institute, Toronto, Canada
9Departments Ophthalmology, Medical Biophysics, Molecular Genetics, University of
Toronto, Canada
* Co-first authors: Junyang Zhao, Zhao Xun Feng and Qiyan Li
Senior author: Junyang Zhao
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CORRESPONDING AUTHOR
Brenda L. Gallie, MD, Department of Ophthalmology and Vision Science, Hospital for
Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G1X8; email:
[email protected]; telephone: 14162949729
PRIOR PRESENTATION
The data was presented in part in a paper at the 2019 International Society of Ocular
Oncology meeting in Marina del Rey, Los Angeles and Poster presentation at AACR
Special Conference on Advances in Pediatric Cancer Research, Montreal, Quebec,
Canada, September 19, 2019.
CONFLICT OF INTEREST
No conflicting relationship exists for any author
RUNNING HEAD
Safety and Efficacy of Vitrectomy Tylectomy for Retinoblastoma
NUMBER OF FIGURES AND TABLES
2 tables, 3 figures, 3 online only tables and 1 online only figure
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Key Points: 78/? words
Question: What are the safety and efficacy of intraocular tumor excision (tylectomy) for
retinoblastoma?
Findings: Retrospective cohort study of 225 children with intraocular retinoblastoma
treated after completion of standard chemotherapy with tylectomy for retinoblastoma
showedhad 95% 5-year Overall Survival of 95% and 96% 5-year Cause-Sspecific
Survival of 96%. The 5-year eye salvage rate was 81%; and 45% of eyes avoided
complete blindness.
Meaning: Tylectomy in carefully selected Patients with tylectomy included in eye
salvage therapy can offerexperienced similar survival similar to primary enucleation,
with lifelong benefits of vision and eye retention.aining the eye and vision.
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Abstract 400 words
Importance: Intraocular surgery has been taboo in the management of retinoblastoma
due toin concern of for extraocular spread. We showed Intraocular excision (tylectomy)
of retinoblastoma (tylectomy) can contributed to care in well-selectedof patients with
retinoblastoma with survival rates similar to those published for other treatments.
Objective: We studied survival, eye salvage and visual acuity of a large cohort of
retinoblastoma children/eyes treated with secondary tylectomy following after systemic
chemotherapy.
Design: Retrospective cohort study. Children treated with tylectomy between in 2013 to
and 2014 with 5-years follow-up.
Setting: Three Chinese tertiary referral centers.
Participants: Consecutive children with retinoblastoma treated with secondary
tylectomy following after primary standard of care chemotherapy. Children with Clinical
or radiologic evidence of extraocular disease were was an absolute contraindication to
tylectomy.
Exposures: Consolidation Tylectomy was defined as intraocular excision of non-
calcified or partially calcified tumor within two<2 months of finalafter completion of
chemotherapy session. Salvage Tylectomy was defined as resection of active recurrent
tumor >2 months after completion of final chemotherapy session. Data reviewed
included age, sex, clinical IIRC Group at diagnosis, time from diagnosis and from end of
chemotherapy to tylectomy, pre-op and post-op chemotherapy, extent of retina excised,
enucleation, and length of follow-up.
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Main Outcome Measures: The primary outcomes were Overall Survival (OS) and
Cause-Specific Survival (CSS, survival relative to metastasis from the tylectomy eye).
Secondary outcomes were recurrence-free survival, eye salvage and visual acuity.
Results: A total of 245 eyes from 225 patients had Consolidation Tylectomy (151,
61.6%) or Salvage Tylectomy (94, 38.4%). Median age at diagnosis was 18.3 months
(range, 1.0–99.8 months). At The 5-year follow-up, Overall Survival rateOS was 94.5%
(95% CI: 91.5%–97.6%) and . The 5-year Cause-specific Survival (CSS) was 96.3%
(95% CI: 93.8%–98.9%). Children who hadWith Consolidation or Salvage Tylectomy 5-
year CSS was similar (96.3% vs 96.3%, P = .988) had similar survival to those with
Salvage Tylectomy (5-year CSS 96.3% vs 96.3%, P = .988)and. Children who received
adjuvant systemic chemotherapy following tylectomy had 5-year CSS similar to those
treated without adjuvant chemotherapy (100% vs 94.8%, P = .102). The 5-year eye
salvage rate following tylectomy was 80.6% (95% CI: 75.4%–85.8%), similar for
Consolidation Tylectomy and Salvage Tylectomy (78.6% vs 83.9%, P = .274). Children
treated with or without adjuvant systemic chemotherapy following tylectomy had similar
5-year CSS (100% vs 94.8%, P = .102). The 37.6% of eyes that required a total
retinectomy for globe salvage had, as expected, no light perception following tylectomy.
Vision was better than 20/200 (not blind) in 19.0% of all eyes, and better than light
perception in 60.2% of eyes with partial or no retinal resectionOf eyes with partial or no
retinal resection, 60.2% avoided complete blindness (better than no light perception)
and 19.0% avoided legal blindness (better than 20/200 vision).
Conclusions: Tylectomy secondary tofollowing standard chemotherapy alloweds for
preservation of eye and vision in appropriately selected retinoblastoma patients.
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Survival after tylectomy was similar to published reports of other treatment modalities
for retinoblastoma.
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INTRODUCTION:
The high mortality of extraocular retinoblastoma compared to primary enucleation led to
the dogma that intraocular procedures hashave no role in an eyes with retinoblastoma.1
This waswas successfully challenged with the emergence of intravitreal
chemotherapy.by planned intravitreal pars plana injections through pars plana
demonstratinge effectivenesssuccess in treating vitreous seeds with low risk (<1%) of
extraocular tumor spread.2 Considering the efficacy of intravitreal melphalan3,4 and
recenttechnical advances in small gauge vitrectomy system,5 we now incorporated
tylectomyretinoblastoma resection as a useful part of the in multimodal retinoblastoma
management.6
Tylectomy is defined as the surgical removal of a tumor or cyst. The term, now obsolete,
was used synonymously with lumpectomy to refer to a limited resection of breast as
oppose to total mastectomy. There has been a shift in Modern cancer practice has
embraced toward organ conserving surgery such as breast cancer lumpectomy,7 penile
cancer glansectomy,8,9 kidney cancer partial nephrectomy8,9 and testis cancer partial
orchiectomy.10 While lumpectomy officially refers only to breast cancer, the little-known
word “tylectomy” refers to We now revive the term, tylectomy, to refer to surgical
excision removal of a tumor (tulos, Greek for lump). of We propose the word tylectomy
to describe organ conserving, surgical resection retinoblastomaretinoblastoma as an
organ conserving surgery of the eye that offers both cosmetic and functional
advantages in comparison to enucleation.
The high mortality of extraocular retinoblastoma compared to primary enucleation led to
the dogma that intraocular procedure has no role in an eye with retinoblastoma.7 This
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was successfully challenged with the emergence of intravitreal chemotherapy. Planned
intravitreal injections through pars plana demonstrate effectiveness in treating vitreous
seeds with low risk (<1%) of extraocular tumor spread.8 Considering the efficacy of
intravitreal melphalan9,10 and recent advances in small gauge vitrectomy system,11 we
now incorporated tylectomy as a useful part of the multimodal retinoblastoma
management.12
Despite trial attempted eye salvage with combinations of chemotherapy (systemic
chemotherapy,11 intra-arterial chemotherapy (IAC)12 and intravitreal3,13{Francis, 2017
#20106;Munier, 2012 #8588}) refractory disease and tumor recurrence remain common.
Intraocular complications such as cataract, retinal detachment, vitreous hemorrhage,
and vitreous seeding further hinder eye salvage by precluding visualization of active
tumor and focal therapy (laser, cryotherapy, brachytherapy).14,15 In comparison to
chemotherapy, tylectomy physically excisesfor intraocular tumorretinoblastoma, could
remove tumor offering promising potential to circumvent chemotherapy resistance while
simultaneously treating ocular complications.
Our prior tylectomy case series showed promise in treating resection of refractory
retinoblastoma6 but concerns of iatrogenic tumor spread remained, given small sample
size. Indeed, Intraocular surgery in eyes with unsuspected retinoblastoma are has been
associated with metastatic disease,16,17 but metastasis was not identified in case reports
of planned tumor excision.6,18-22 We propose that planned tylectomy with intention to
cure may be safer than intraocular surgery with coincidental discovery of
retinoblastoma. The primary objective of the current study is was to evaluate Overall
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Survival (OS) and Cause-Specific Survival (CSS, survival relative to metastasis from the
tylectomy eye). Secondary outcomes were eye salvage rate and visual acuity.
METHODS:
Date collection and Ethics
This is a retrospective cohort study of patients with intraocular retinoblastoma was
treated with by tylectomy at three Chinese treatment centers between February 1, 2013
and December 13, 2014. Date of last follow-up was June 16, 2019. Retrospective
review of medical records without research consent of medical records was approved
by the Ethics Boards of Liuzhou Maternity and Child Healthcare Hospital, Beijing
Tongren Hospital, and Quanzhou Aier Eye Hospital in accordance with the Declaration
of Helsinki.
Clinical information collected included age at diagnosis, sex, disease laterality,
International Intraocular Retinoblastoma Classification (IIRC)23 clinical Group, pTNM 8th
edition histopathologic staging,24 type and regimen of chemotherapy, causes of death,
and dates of diagnosis, chemotherapy, tylectomy, recurrence, enucleation, last follow-
up and death. We considered patients lost to follow-up when parents could not be
contacted ≥2 years after last follow-up.
Treatment
Standard treatments preceding before tylectomy was considered are illustrated outlined
in Fig 1. All 245 eyes were treated with primary chemotherapy (systemic or intra-
arterial) with follow-up every 1-2 months during active treatment. Children with no active
tumor after treatment were followed every month for the first 4 months, every 2 months
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for the next 8 months and then longer intervals. The most common primary
chemotherapy, and adjuvant chemotherapy after tylectomy (when selected by parents),
was systemic (intravenous carboplatin 560 mg/m2 Day 1, etoposide 150 mg/m2 Days 1
and 2 or teniposide 230 mg/m2 Day 2, and vincristine 1.5 mg/m2 Day 2 on a 28-day
cycle).
Indications for tylectomy were consolidation after chemotherapy or salvage of eyes that
developed tumor recurrence. Consolidation Tylectomy was defined as resection of
noncalcified or partially calcified retinoblastoma within <2 months of after last
chemotherapy session. Salvage Tylectomy Salvage tumorectomy was defined as
resection of recurrent active tumor delivered >2 months of last chemotherapy session.
For Consolidation Tylectomy, Confirmation of Tumor activity was not confirmed in the
Consolidation Tylectomy cohort, due to lack of extended observation precluded by lack
of extended observation of tumor stability prior to surgerytylectomy. Tylectomy was
offered at the clinician’s’ discretion, considering factors including lack of significant
regression, progression or new tumor activity (new subretinal, epiretinal or vitreous
seeds) while on chemotherapy, opacities obscuring tumor visualization, parent
preference and refusal of enucleation (Fig 1).
In 2013-2014 IAC was available in only two Chinese centers. If parents chose primary
intra-arterial chemotherapyIAC, prompt referrals were made; few parents pursued
IACchose this therapy because of long travel distance and high treatment cost. Tumor
that manifest as only vitreous seeds without evident active retinal tumor was treated
with intravitreal chemotherapy. Simultaneous presentation presence of vitreous seeds
and active retinal tumor may bewas considered for tylectomy.
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Indications and Contraindications
All patients were screened for extraocular disease at diagnosis or prior to tylectomy by
computed tomography (CT) or magnetic resonance imaging (MRI). Absolute
contraindications to tylectomy were evidence of optic nerve invasion and extrascleral
invasion. Relative contraindications were obscured optic disc, foveal invasion or
extensive retinal invasion requiring complete retinectomy. The decision to proceed with
tylectomy was individualized for each patient was on the basedis of on clinical
presentation features and parents’ choice. For Group E eyes (advanced intraocular
retinoblastoma) enucleation was presented to parents as the safest treatment option.
Procedure
Under general anesthesia, a dilated fundus exam was performed with scleral
depression. Tumor-free sclerotomies sites were identified. In eyes with poor fundus
visualization due to vitreous opacities, ultrasound biomicroscopy or B-scan
ultrasonography were used to survey sclerotomy sites. To reduce risk of retinal
detachment, laser scars were placed around tumors prior and during surgery.
Standard three-port 23- or 25-gauge non-valved trocar/cannulas were inserted
transconjunctivally at pre-selected sites. Melphalan (5 μg/ml) in balanced salt solution
(dose nontoxic to retina in animal studies25) was infused continuously throughout the
surgery and irrigated onto ocular surface every 3-5 minutes. Using a vitrector, vitreous
seeds were aspirated, and soft tumors were endoresected and aspirated. Any visible
tumor that extended into choroid was resected down to bare sclera via vitrector, after
endodiathermy to occlude choroidal vasculature surrounding the tumor. Lensectomy
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was performed for cataract, and in cases whereif anterior segment tumor seedsing was
were aspirated or invaded ciliary body was resected. Residual calcified tumors were
disrupted by fragmatome through 20-gauge sclerotomies, and either aspirated or
removed from the sclerotomy sites using forceps.
Silicone oil was placed after tylectomy to stabilize residual retina whenever retinal
detachment was threatened, as in a partial retinectomy >3 mm or anterior resection.
After tylectomy, the scleral surface was exposed with peritomy and washed with 5 μg/ml
melphalan irrigation fluid. Tenon’s capsule and conjunctiva were sutured. At end of
surgery, 0.2 ml melphalan (5 μg, 25 μg/ml) was injected subconjunctival at the port
sites.
Statistical Analysis
Sex, age at diagnosis, follow-up, IIRC Group, time from diagnosis to tylectomy,
chemotherapy cycles, indication for tylectomy, degree of retinectomy, and enucleation
after tylectomy were summarized using frequency/percentage for categorical variables
and median/range for continuous variables. Continuous variables were compared
between groups via Mann-Whitney U test. Kaplan-Meier method was used to estimate
Cause-Specific Survival (CSS), Overall Survival (OS), Recurrence Free Eye Salvage
and Eye Salvage rates. CSS included Children who died with metastasis, with or
without radiological evidence of tumor spread from the tylectomy eye, were included in
CSS. Children with MRI evidence of tumor spread onlyexclusively from the non-
tylectomy eye or who died without metastasis, or with MRI evidence of tumor spread
only from the non-tylectomy eye, were not included in the CSS. Log-rank test was
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performed to compare OS, CSS and eye salvage between groups. When a child
received tylectomy for both eyes, for survival analysis, we excluded the eye with the
better IIRC Group in survival analysis if the child received tylectomy for both eyes; if
both tylectomy eyes had the same Group, the right eye was excluded. Children were
censored at last follow-up. All P-values reported are two sided; P < 0.05 indicated
significance. All analysis was performed using SPSS Version 25 (IBM Corp, New York).
RESULTS
Patient and Eye Characteristics and Prior Treatments
A total of 245 eyes (from 225 patients) had Consolidation Tylectomy (151, 61.6%) or
Salvage Tylectomy (94, 38.4%) (Fig 2 and Table 1, online only). Median age at
diagnosis was 18.3 months (range, 1.0–99.8 months). The IIRC Group At diagnosis
IIRC was Group B (13), Group C (21), Group D (172), Group E (38) and one unknown.
All 225 patients had primary chemotherapy; 206 (84.1%) had received only systemic
chemotherapy pre-tylectomy (median 3, range 1–15 cycles), 11 (4.5%) received only
IAC pre-tylectomy (median 2, range 1–3 cycles) and 28 (11.4%) received both
(medians, systemic chemotherapy 3 cycles, IAC 2 cycles). In addition to systemic
chemotherapy and/or IAC, prior to tylectomy 16 (6.5%) eyes received intravitreal
chemotherapy, 2 (0.8%) external beam radiation and 1 (0.4%) I125 plaque radiotherapy.
Median time from diagnosis to tylectomy was 4.3 months (range 0.3–78.2 months),
longer for Salvage Tylectomy than Consolidation Tylectomy (medians 11.2 2.8 v 2.8
11.2 months; P < .001). Median follow-ups were 67.8 months (range 1.0–150.2 months)
after diagnosis and 63.6 months, (range 0.6–76.6 months) after tylectomy. Lost to
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follow-up were 8 children with 9 eyes (follow-up after tylectomy median 6.6 months,
range 1.1–28.0).
The Degree of retina resected depended on the extent of tumor invasion: 6 (2.4%) eyes
had only tumor resection with no retinectomy, 147 (60.0%) had partial retinectomy and
92 (37.6%) had complete retinectomy by parental choice to avoid enucleation.
Simultaneous lensectomy was performed for 51 (20.8%) eyes. On fundus examination,
151 (61.6%) eyes had obscured optic disc, 44 (17.9%) eyes had vitreous hemorrhage,
67 (27.3%) eyes had vitreous or epiretinal seeding, 62 (25.3%) eyes had exudative or
rhegmatogenous retinal detachment, and 8 (3.2%) eyes had cataract. Silicone oil
taHmponade was used in 89 (36.3%) eyes. Following tylectomy, 58 (23.7%) eyes
received adjuvant systemic chemotherapy (median 1 cycle, range 1–5).
Survival
The 5-year CSS was 96.3% (95% CI: 93.8%–98.9%) (8/225 children died of disease
from the eye that had tylectomy). The 5-year Overall SurvivalOS rate was 94.5% (95%
CI: 91.5%–97.6%) (overall 12/225 children died) (Fig 3). For only Group D/E eyes, the
CSS and 5-year OS Overall Survival rates were 95.8% and 94.8% respectively. If we
assume all 8 (8/225 (4%) lost-to-follow-up patients have died, the 5-year CSS and
Overall Survival were 92.8% and 88.9% respectively.
Patients who had Consolidation and Salvage Tylectomy had Similar Consolidation and
Salvage Tylectomy 5-year Overall Survival OS (95.6% v 92.7; P = 0.361) and 5-year
CSS (96.3 v 96.3%; P = 0.988) were recorded. For Patients who hadtreated with
adjuvant systemic chemotherapy, had 5-year CSS was 100% (95% CI: 96.6–100%),
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not different from those who received without no adjuvant chemotherapy (94.8%, 95%
CI: 91.4%–98.2%, P = .102).
Characteristics of Patients Who Died
Death of 4/12 patients was unrelated to the eye that had tylectomy:; 3 had extraocular
tumor extension evident on head MRI from the non-tylectomy eye but not the tylectomy
eye and 1 child died from infection (Table 2, online only). Of 8 deaths related to
tylectomy eye, 4 had posterior tumor extension into the orbit, with no tumor clinically
observed at the sclerotomy sites; 1 had optic nerve invasion; and the extension site was
unknown for 3 children (Study IDs #49, 144, 208). All children who developed
metastasis have died.
All 8 children who died with metastasis attributable to the tylectomy eye had received
pre-tylectomy systemic chemotherapy (median 5.5 cycles; range 2–9); none had
received adjuvant IAC or systemic chemotherapy.
Tumor Recurrence Following Tylectomy
Following tylectomy, the 5-year recurrence-free eye salvage was 69.7% (95% CI:
63.7%–75.7%) (Fig 4), not significantly different between those with Consolidation and
Salvage Tylectomy (69.6 v 70.1%; P = 0.858). Seventy-two eyes had tumor recurrence,
median 6.6 months (range 0.8–52.8) after tylectomy. The Locations of recurrence were
anterior chamber (13), posterior chamber (3), peripheral posterior segment (23),
posterior pole (27), vitreous (3), both posterior pole and vitreous (2), and both anterior
chamber and posterior pole (1). Details of the 72 eyes with tumor recurrence after PPV
tylectomy are presented in Table 3, online only.
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Eye Salvage
Overall 5-year eye salvage rate following tylectomy was 80.6% (95% CI: 75.4%–
85.8%), including eyes having treated with additional salvage therapies. Patients who
had Consolidation and Salvage Tylectomy had similar eye salvage rates (5-year eye
salvage rate, 78.6% v 83.9%; P = .274). Patients with IIRC B/C eyes had significantly
higher eye salvage rate than those with IIRC D/E eyes (5-year eye salvage rates
respectively 100% v 78.0%; P = .005).
Of 245 eyes, ocular complications (some of these complications coincided with tumor
recurrence). following tylectomy included cataract (75, 30.6%), band keratopathy (42,
17.1%), vitreous hemorrhage (41, 16.7%), retinal detachment (6, 2.4%) and phthisis
bulbi (4, 1.6%). Some of these complications coincided with tumor recurrence.
Vision
Complete retinectomy at choice of parents to avoid enucleation was performed on 92
eyes, all which (as expected) had no light perception (NLP); 14/92 (15.2%) were
subsequently enucleated. Tylectomy with partial or no retinectomy was performed for
153 eyes with 31/153 (20.3%) subsequently enucleated. Snellen visual acuity was
undetermined for 28/153 eyes (18.3%) mostly due to young age. Of 94 eyes
successfully salvaged with partial or no retinectomy and documented visual acuity,
visual acuities at last follow-up were 20/20–20/60 (23, 24.5%); 20/80–20/160 (6, 6.4%);
20/200–20/400 (9, 9.6%); finger counting, hand motion or light perception vision (42,
44.7%); and NLP (14, 14.9%). If we count enucleated eyes as NLP, 23.2% of eyes
intended for vision salvage avoided legal blindness (visual acuity better than 20/200),
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14.1% for Group D/E eyes. Overall, 55.9% of eyes are NLP because of complete
retinectomy or poor vision following partial retinectomy or enucleation.
DISCUSSION
Tylectomy is a component of an organ salvage therapy in order aims to maximize the
cosmetic and functional outcomes of eyes with retinoblastoma without compromising
survival. Currently, three Chinese centers routinely perform tylectomy as part of the
multimodal treatment of retinoblastoma. The main concern of tylectomy is increased
mortality from iatrogenic tumor spread. Our study evaluated survival, eye salvage and
vision of 225 children (245 eyes) treated with tylectomy with 5-year follow-up. The
concern that tylectomy would increase mortality from iatrogenic tumor spread was not
observed.
Retinoblastoma resection was considered a viable option because of two major
advances in retinoblastoma care. With recognition ofSince intravitreal melphalan as is
an effective agent to treat retinoblastoma,3,4 during surgery a non-toxic concentration of
melphalan was continuously infused into the eye and periodically irrigated onto the
ocular surface. Submersion of tumor cells even in sterile distilled water is has been
suggested to render retinoblastoma cells nonviable. Second, small gauge non-valved
cannula was considered to reduce risk of subconjunctival and scleral wall seeding by
directing intraocular content to the outer conjunctival surface where melphalan irrigation
is applied.
For the 225 consecutive patients treated with tylectomy, we observed 5-year CSS of
96.3% and 5-year Overall SurvivalOS of 94.5%,. These are similar to survival rates
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reported for other treatment modalities including primary enucleation (Table 4).26-29 It is
evident that there are social factors beyond treatment modality that affect
retinoblastoma survival including national income level, delay to diagnosis, social stigma
against enucleation and treatment abandonment.30,31 Enucleation is commonly regarded
as the safest treatment for intraocular retinoblastoma, so. For comparison, we
retrospectively reviewed all 920 consecutive Chinese patients treated with primary
enucleation by J.Z from 2006 to 2015, the observing 5-year Overall Survival was 92.6%
(unpublished; raw data included in Table 5, online only). Enucleation is commonly
regarded as the safest treatment for intraocular retinoblastoma. The comparable
survival to enucleation supports tylectomy as a reasonable contribution to the treatment
of retinoblastoma.
We observed that The anterior segment is was a common area for tumor recurrence
following tylectomy, possibly related to limited access during vitrectomy to tumors
seeded on iris, ciliary body and zonules. Despite complete retinectomy and resection of
diseased choroid during tylectomy, invisible choroidal seedings may persist and recur.
Furthermore, as with IAC,32 tylectomy is localized only to the eye and lacks any
systemic chemoprotection. For these reasons, since 2017 we have recommended 2
cycles of adjuvant systemic chemotherapy following tylectomy. In the present study,
CSS of patients who received adjuvant systemic chemotherapy was 100%, but not
statistically different from those who received no adjuvant chemotherapy, 95%.
Hope for eye salvage and visual outcome can influence parents’ choice between
enucleation and trial eye salvage. Most tylectomy was performed with the intent of
vision salvage, but some parents refused enucleation despite no possibility of vision due
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to extensive disease. We did not recommend tylectomy for such eyes, but nevertheless
respected parents’ decision to preserve a non-seeing eye, in order to avoid treatment
abandonment.
In low- and middle income settings like China, it is not uncommon for children to be lost-
to-follow-up for a variety of reasons including unwillingness to enucleate, financial
constraints, long distance from treatment center and perception that disease was
cured.33 Instead of risking loss of patients with active tumor inside their eyes, most
parents were receptive to tylectomy prior to cessation of follow-up. While death is the
uniform outcome of untreated retinoblastoma, lost children who had tylectomy may
survive despite cessation of follow-up.
We compiled results from recent published series reporting eye salvage rate and
Snellen visual acuity following systemic chemotherapy or IAC, compared to our current
study (Table 5).11,34,35 An exact comparison of our results with other studies is not
possible due to selection bias and non-uniform clinical classification.
The strengths of this study are the large sample size and uniform protocols performed
by a single highly specialized multidisciplinary team, led by the vitreoretinal surgeon and
retinoblastoma specialist. A limitation of this study is the lack of histopathology on
material aspirated during tylectomy. Furthermore, histopathologic evaluation of
sclerotomy sites was not performed because the standard histopathology sections did
not contain the sclerotomy sites. For all of these children, the safest approach is primary
enucleation. However, when parents chose eye and/or vision salvage over enucleation,
tylectomy may be considered in patients who showed poor response to chemotherapy
or when treatment abandonment is a risk. Absolute contraindications were CT/MRI
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evidence of optic nerve invasion and extrascleral extension. Tylectomy of
retinoblastoma without careful selection of sclerotomy sites, continual melphalan
infusion, dedicated retinoblastoma expertise and appropriate consent from the family
has potential to be dangerous.
In 1989, Fisher et al showed that lumpectomy with adjuvant irradiation for Stage I and II
breast cancer yield non-inferior survival compared to mastectomy.7 Similar to the
lumpectomy in breast cancer, we now showed tylectomy in well-selected patients
(radiography excluding extraocular tumor) had similar survival to those treated with
enucleation, with lifelong benefits of retaining the eye, vision and maximizing quality of
life for many children.
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LEGENDS
FIG 1. Standard care for IIRC Group retinoblastoma leading to eligibility for tylectomy.
IVC, intravenous chemotherapy; IAC, intra-arterial chemotherapy
FIG 2 (Online only). Consort diagram.
*We elected to perform endoresection on retinoma for one child because he lived in a
remote rural community with no access to ophthalmology service for serial monitoring of
tumor progression.
FIG 3. Kaplan-Meier curves of patient survival following tylectomy. (A) Cause-specific
survival, (B) Overall survival.
CSS, cause-specific survival; OS, overall survival
FIG 4. Kaplan-Meier curves of eye salvage following tylectomy. (A) Recurrence free
eye salvage (B) Eye salvage rate
RF, recurrence free
Table 1 (Online Only). Clinical characteristics of patients and eyes
Table 2 (Online Only). Clinical characteristic of patients who died
Table 3 (Online Only). Treatments and outcomes of tumor recurrence after PPV
Table 4. Recent published series reporting survival rate following specific treatment
modalities
Table 5. Recent published series reporting snellen visual acuity in eyes with
retinoblastoma.
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