Table 2 Summary of the QOL outcomes by treatment modality

Klingenstein et al. (2013) [43]

CyberKnife (n = 91)

a) 91

b) 48/43

a) QOL

b) SF-12

4–15 months

Yes at some aspects

Physical functioning and role physical decreased significantly after CyberKnife radiosurgery, while mental health improved (P = 0.007, P < 0.0001 and P = 0.023). Mental health and social functioning were significantly increased in the non-glaucoma group (P = 0.0003 and 0.026), and mental health was higher than in glaucoma patients (P = 0.02). At the second follow-up, patients with higher best corrected visual acuity had significantly higher PF and role physical (P = 0.02). Role physical was decreased in patients with best corrected visual acuity < 0.5 log (MAR) (P = 0.013). Viability was significantly increased in patients with preserved best corrected visual acuity (P = 0.031).

Wiley et al. (2013) [47]

Enucleation (n = 16), brachytherapy(n = 79), resection (n = 35), proton beam therapy (n = 3)

a) 99

b) Not mentioned

a) the needs, vision-targeted health, depression, fears

b) CNQ-SF, NEI-VFQ-25, CES-D, CARS

Within the prior 5 years (M = 2.05)

Yes

Although concern about cancer recurrence was elevated, QOL was better than in other oncology samples and comparable with healthy samples on some outcomes. Enucleation was associated with poorer vision-specific QOL, and the presence of comorbidities was associated with poorer vision-specific QOL, depressive symptoms, and worry about cancer recurrence (all P < 0.05). More reported unmet cancer needs were associated with worse vision-specific QOL, depressive symptoms, and more worry about recurrence (all P​<0.05)

Ford et al. (2015) [16]

Adult RB survivors (n = 470) , the Childhood Cancer Survivor Study (n = 2,820)

a) 470

b) 245/225

a) Psychological distress, subjective distress, the extent to perceive personal benefits, fear, facial appearance satisfaction

b) BSI-18, IES, PTGI, Fear of Recurrence Questionnaire, Self-report chronic conditions and satisfaction with facial expressions

/

No

Compared with the Childhood Cancer Survivor Study siblings, the depression, somatization, distress, or anxiety rates of RB survivors did not increase significantly. Among survivors, chronic diseases did not increase the possibility of psychological problems. Compared with unilateral RB survivors, bilateral RB survivors are more likely to experience the fear of cancer recurrence and fear that their children will be diagnosed with RB.

Klingenstein et al. (2015) [37]

Enucleation(n = 32), stereotactic radiosurgery(n = 48) , age-matched control group(n = 35)

a) 115

b) 60/55

a) QOL

b) SF-12

3-year follow-up. 37.9 months After stereotactic radiosurgery versus 42.9 months after enucleation

No between CK and normal group, yes between enucleation and general people at physical functioning, role physical,RE

There was no significant difference in QOL between patients treated by stereotactic radiosurgery and the age-matched control group. After enucleation, patients presented significantly lower values in physical functioning, role physical, and QOL was not significantly different between patients treated with stereotactic radiosurgery and age-matched controls. However, physical functioning, role physical, and role emotional values ​​were significantly lower in the enucleation group compared with radiosurgery and controls. At mid-term follow-up, there were no significant differences between stereotactic radiosurgery, enucleation, and the control group in terms of general health, vitality, social functioning, or mental health. In multivariate analysis, the number of comorbidities had a significant effect on QOL.

Hope-Stone et al. (2016) [40]

Enucleation (n = 117), brachytherapy: ruthenium plaque (n = 174), proton beam radiotherapy (n = 72), local resection (n = 15), endoresection (n = 21), photo dynamic therapy (n = 10), transpupillary thermal therapy (n = 2)

a) 411 b) 218/193

a) Anxiety and depression, HRQOL

b) HADS, FACT-G

6 months, 1 year, and 2 years after treatment

No

In terms of QOL and depression, patients are close to or better than the standard value at all time points, but younger women were more anxious than normative. Results did not differ at any time depending on whether patients were enucleated or not. There were no differences in outcomes at any point depending on whether patients were enucleated or not. Patients with monosomy 3 showed more depressed mood at 6 months, 1 year, and 2 years after treatment (P < 0.05).

Damato et al. (2018) [30]

Enucleation (n = 442) , Radiotherapy (n = 1154 (ruthenium plaque radiotherapy (n = 730) and proton beam radiotherapy (n = 424))

a) 1596

b) 825/771

a) QOL, anxiety and depression, HRQOL

b) EORTC QLQ-OPT30, HADS, FACT-G

6 months, 1 year, and 2 years after treatment

Yes

Enucleation was associated with males, older age, larger tumor diameter, monosomy 3, depression, and decreased physical and mental health. QOL was better in patients who underwent radiation therapy than enucleation, but worse than in the general population. Anxiety scores were lower than those of the general population in the UK. Enucleation patients had better social functioning and poorer emotional functioning than the general population, but better physical functioning than US cancer patients, receiving radiation treatment had better overall FACT-G scores than cancer patients, with poorer QOL independent of treatment modality. Patients receiving radiation were less likely to complain of ocular discomfort (gritty, itching, tearing, discharge), and less concerned about their appearance and the risk of losing their eyes. The radiation therapy group also reported fewer visual difficulties (driving in the dark, pouring, walking in crowds, seeing steps, walking on uneven ground, judging distances).

Frenkel et al. (2018) [44]

Brachytherapy (n = 198), enucleation (n = 19),

local resection (n = 10),

proton beam (n = 6)

a) 233

b) 102/131

a) QOL

b) EORTC QLQ C30, QLQ-OPT30.

2 weeks to 295 months (76 ± 62.4 month)

Yes in some aspects,

no overall

There were no statistically significant differences in general QOL scores for different types of initial treatment. Better QOL was associated with tumors that did not involve the ciliary body and better corrected visual acuity. However, patients who underwent enucleation had lower eye-related QOL compared with those who received brachytherapy and described body image-related issues, but cosmetic concern was not significantly different between treatment groups.

Friedman et al. (2018) [33]

Radiation or Chemotherapy or enucleation (n = 470)

a) 470

b) 225/245

a) Vision-targeted health

b) NEI-VFQ-25

/

Yes in some aspects,

no overall

Overall QOL was not bad, with an overall mean VFQ score of 81.1 for all survivors. Previous radiation therapy was not associated with decreased VFQ, but it was associated with certain subregions of visual function. Bilateral enucleation is associated with lower QOL, unilateral disease also affects QOL (P < 0.001), and enucleation also affects QOL (P = 0.002). Vision-related QOL scores are generally good (unilateral 91.4, bilateral72.3).

van Beek et al. (2018) [45]

Fractionated stereotactic radiation therapy(n = 65) ,. enucleation (n = 48)

a) 113

b) 60/53

a) Anxiety, subjective distress, QOL, vision-targeted health

b) STAI, IES, EORTC-QLQ-C30, NEI-VFQ-25

Before treatment and 2, 6, 12, 24, 36 and 48 months after treatment.

Yes at short-term, no at long-term

The overall global health score was 76.4. The role functioning score from 2 months to 3 years after treatment, the QOL in the enucleation group decreased (P = 0.012), and that in the fractionated stereotactic radiation therapy group increased (P = 0.005), 4 years after treatment, there was no significant difference in QOL scores between the two treatment groups. Patients with metastases were more anxious than those without. Subjective pain in patients with metastases compared with those without metastases at baseline (P = 0.037). Increases in overall pain (P = 0.023) and emotional functioning (P < 0.001) were observed after 1 year of treatment. Decreased physical functioning (P = 0.035), insomnia (P < 0.001) and anxiety (P < 0.001) from pre-treatment to 2 years post-treatment. Patients with enucleation had worse peripheral vision observed up to 3 years after treatment (P = 0.026).

Barker et al. (2019) [17]

Radiotherapy

(n = 201)

a) 201

b) 111/90

a) QOL

b) EORTC QLQ-C30, QLQ-OPT30

After diagnosis and prior to treatment with radiotherapy.

No

Overall QOL was good, with the most common severe QOL concern being worry about disease recurrence (41%). The most common ophthalmic symptoms were visual impairment (81%) and eye irritation (66%). Overall QOL was related to demographics, but not strongly (P < 0.01, r = 0.14), and patients with advanced disease had poorer QOL after initial diagnosis.

Damato et al. (2019) [41]

Enucleation (n = 442) , radiotherapy (n = 1154, ruthenium plaque brachytherapy (n = 730), proton beam radiotherapy (n = 424))

a) 1596

b) 825/771

a) QOL, anxiety and depression, HRQOL

b) EORTC QLQ-OPT30, HADS, FACT-G

6 months, 1 year, and 2 years after treatment.

Yes

Self-reported QOL decreased with both groups. Treatment modality is not related to QOL level. Overall anxiety tended to decrease and depression increased, especially after enucleation. Emotional health improved after treatment, while functional and physical health decreased after enucleation but improved after radiotherapy. The overall FACT-G score increased in the radiotherapy group and decreased in the enucleation group. Depression had nothing to do with treatment, but was related to unemployment, which occurred more among enucleation treatment. Over time, visual difficulties decreased after enucleation but increased in patients who received radiation therapy, and concerns about metastasis, health loss, and tumor recurrence decreased in both groups.

Hope-Stone et al. (2019) [28]

Enucleation (n = 66) , proton beam radiotherapy(n = 49)

a) 115

b) 56/59

a) QOL

b) EORTC QLQ OPT30

6-, 12-, and 24-months following diagnosis.

Yes

Patients treated with enucleation having more functional problems at 6 months, which were resolved at 12 and 24 months (P = 0.020). Central and peripheral visual impairment (P = 0.009) and dyslexia (P = 0.002) were more severe in proton beam radiotherapy patients within 24 months. But treatment did not affect driving (P = 0.694), eye irritation (P = 0.281), headache (P = 0.640), cosmetic problems (P = 0.187) or fear of recurrence (P = 0.899).

Scannell et al. (2019) [5]

PR (n = 103) , enucleation (n = 35)

a) 138

b) 78/60

a) QOL

b) EORTC QLQ-C30, QLQ-OPT30

/

No

There was no significant difference in QOL score between the treatment groups. 32% of the patients were worried about tumour recurrence in other parts of the body. The role functioning score of the brachytherapy group was significantly higher (P = 0.030). Patients with enucleation are more prone to appearance problems (P < 0.0005). Younger patients (12–54 years old) are more likely to report headaches (P < 0.0005) and dyslexia (P = 0.042), and the cognitive function score (P = 0.003) is lower than patients ≥ 55 years of age.

Feng et al. (2020) [49]

Enucleation (n = 66) , healthy adults(n = 66)

a) 132 b) 53/79

a) HRQOL, anxiety and depression, fear, facial appearance dissatisfaction

b) Chinese version of the SF-36, HADS, FoP-Q-SF, NPSS-F

/

No

Adult RB survivors did not have significantly higher rates of depression and anxiety compared with the control group, and they experienced a relatively good QOL. RB survivors were more likely to worry about their facial appearance (P < 0.001). Radiotherapy was not the factor affecting satisfaction with facial appearance (P = 0.214). Females were more likely to be influenced by the disease (P = 0.031) and worry about their appearance (P = 0.041).

Brown et al. (2021) [42]

Enucleation(n = 177), plaque radiotherapy (n = 304), resection (n = 35), proton beam radiotherapy (n = 155) other (n = 22)

a) 824

b) 435/389

a) QOL, anxiety and depression, HRQOL

b) EORTC QLQ-OPT 30, HADS, FACT-G

6, 12 and 24 months after diagnosis

No

Overall QOL was good, with anxiety and depression similar to the UK population, and QOL similar to the Australian population. Single predictor analyses showed 6-month depression and poorer functional QOL predicting mortality, as did 6–12 month increases in anxiety and decreases in physical and functional QOL. Multivariate analyses showed independent prediction by 6-month depression and decreasing QOL over 6–12 months and 12–24 months.

Gollrad et al. (2021) [46]

Surgery + Radiotherapy

(n = 131)

a) 131 b) 66/65

a) QOL, anxiety

b) EORTC QLQ-C30, QLQ-OPT30, GAD-7

Before clip-surgery, between clip-surgery and proton therapy, after proton therapy, and three months after treatment

Yes at short-term, no at long-term

Global QOL was similar to that in Germany before treatment, and returned to baseline levels three months after treatment. Compared with clip-surgery and three months after treatment, there was no change, but three months after treatment had more eye-specific symptoms than clip-surgery (P < 0.001). Compared with before treatment, physical functioning and role functioning still deteriorated significantly (P < 0.001), social functioning and emotional functioning improved over time. QOL and an increase in eye-related symptoms, because of the clip surgery (clip-surgery-between clip-surgery and proton therapy). After treatment completion, global QOL improved gradually, and none of the eye-related symptoms significantly deteriorated over the course of proton therapy.

Gollrad et al. (2022) [48]

PBT (n = 108), observation (n = 61), intravitreal injections (n = 17), intraocular surgical procedure (n = 30).

a) 108

b) 52/56

a) QOL

b) EORTC QLQ-C30, QLQ-OPT30

At baseline, and at 3 and 12 months

Yes at short-term, no at long-term

All have a stable global health scores in the short term. In the latter group, several QOL items significantly declined after the 3-month adjuvant interval, but they partially recovered at the 12-month follow-up. In all adjuvant-intervention groups, global QOL scores returned to baseline levels at 12 months. Visual acuity correlates with QOL.

RB = retinoblastoma; UM = uveal melanoma; QOL = Quality of life; HRQOL = health related quality of life; SF-12 = 12-Item Short Form Survey; SF-36 = 36-Item Short Form Survey; EORTC = the European Organization for Research and Treatment of Cancer; QLQ-OPT30 = Quality of Life Questionnaire Ophthalmic Module; QLQ-C30 = The Core Quality of Life questionnaire; CNQ-SF = the Cancer Needs Questionnaire-Short Form;NEI-VFQ-25 = 25-item National Eye Institute Visual Function Questionnaire; CES-D = The Center for Epidemiologic Studies Depression scale; CARS = The Concern about Recurrence scale;BSI-18 = The Brief Symptom Inventory-18; IES = The Impact of Events Scale; PTGI = The Post-Traumatic Growth Inventory; HADS = Hospital Anxiety and Depression Scale; FACT-G = the Functional Assessment of Cancer Therapy-General; VFQ = Visual Function Questionnaire; STAI = The State-Trait Anxiety Inventory; FOP-Q-SF = Fear of Progression Questionnaire-Short Form; NPSS-F = the Negative Physical Self Scale-Facial Appearance Concern; GAD-7 = General Anxiety Disorder-7.