Reasons for missed chemotherapy appointments in retinoblastoma patients undergoing chemotherapy: A report from a Tertiary Care Hospital from India

Abstract Background Delays in chemotherapy due to missed‐appointments can lead to sub‐optimal outcomes in any cancer. Missed appointments or delayed follow up are an important concern in the treatment of pediatric cancers as it compromises the patient's health and overall outcomes. Aim This study was conducted to understand the reasons responsible for missed‐appointments in Retinoblastoma (RB) patients scheduled for daycare based chemotherapy. Methods We prospectively recorded the causes for missed‐appointments in RB patients from February 2018 to September 2018. A delay of more than 48‐hours from the pre‐scheduled date of chemotherapy was categorized as a “missed‐appointment.” Results Out of 870 scheduled visits of patients with RB for chemotherapy to our center, there were 122 (14%) instances of missed‐appointments during the study period. There were 40 instances (4.6%) where the patient had missed‐appointments (possibly avoidable reasons). These 40 instances occurred in 33 patients who had a median age of 29 months (IQR 22.5‐51.5 m) with 22 males. Six patients lived within 100 km of the treating center, 12 lived between 100 and 500 km, and 15 patients lived beyond 500 km. The median length of delay was 13.75 days (IQR‐7‐20.75 days). Twenty‐seven patients used a train as a means of transport, and 10 used the state‐bus. The main cause of delay was the illness of other family members (52.5%) followed by financial issues (27.5%), transport‐related problems (10%), and absence of an adult to accompany (10%). Conclusion Causes for missed‐appointments for chemotherapy in RB patients were multifactorial and included the illness of other family members, financial issues, distance/transport‐related problems, and no caregiver to accompany. The future study with a large sample size with a multicenter design is needed to confirm the results of the current study and to know the deficiency in the improvement of the follow‐up RB patients.

to RB patients in the country. We enrolled children age <18 years on chemotherapy for RB who had missed appointment and delayed for follow up >48 hours. Both the treatment appointments and routine follow-ups missed by these patients were recorded. The exclusion criteria were: missed appointments due to infection or illness after the previous chemotherapy cycle or surgery; missed appointment due to delayed count recovery or derangement in pre-chemotherapy investigations; missed appointment due to delay in getting the investigations done in the hospital. Children were included if the parent/legally authorized representative (LAR) signed informed consent.

| Objectives
The objective of the study was to determine the factors that contribute to missed appointments and delayed follow-up in RB patients on chemotherapy. The outcome variables were: median delays of chemotherapy (days); reasons for missed appointments and delays after which phase of chemotherapy.

| Missed-appointment
A delay of more than 48-hours from the pre-scheduled date of chemotherapy was categorized as a "missed-appointment."

| Statistical analysis
The categorical variables were presented as frequency (percentage).
The continuous data were presented as mean ± SD for normally distributed data, and as median with interquartile range (IQR) for skewed data. Statistical analysis was carried out using the STATA software (STATA version 14, for Windows 10).

| RESULTS
Out of a total of 870 scheduled visits during the study period to the Pediatric Oncology daycare for RB chemotherapy, there were 122 instances (14%) where the patient was delayed by more than 48 hours. Of these, 52 instances (6%) were due to the patient being neutropenic or due to having an infection or with delayed counts recovery that precluded chemotherapy. In 30 cases (3.4%), the patient would have come on time, but there was a delay in getting the prechemotherapy laboratory tests done ( Figure 1). The remaining instances of delays (n = 40, 4.6%) were unanticipated and these 40 instances of delay happened in 33 patients.
The median age of these 33 patients was 29 months (IOR 22.5-51.5 months). Sixteen patients had an extraocular disease and in 11 patients, the disease was bilateral. Thirteen patients were on standard doses of chemotherapy, whereas in 20, the doses were higher for either an extraocular presentation or sub-optimal response to previous chemotherapy cycles (Table 1).
Six patients lived within 100 km of the treating center, 12 lived between 100 and 500 km, and 15 patients lived beyond 500 km.
Twenty-five patients lived in ill-constructed (thatched house/hut). In 11 cases, both parents had never been to school, whereas for the rest, Out of the 33 patients, 7 patients had the previous radiotherapy, and 13 patients had an enucleation. Thirteen patients had been previous defaulters, even before the first enrolment in the study. After the first enrolment in the study, six patients missed appointments again during the study period. Three patients had co-morbidities [twodevelopmental delay, one-chronic suppurative otitis media (CSOM)].
Twenty-seven families used trains as a means of transport, and 10 used the state-bus.
The median number of days of the delay of chemotherapy was 13.75 days (IQR 7-20.75 days). The main cause of delay was an illness of other family members (52.5%) followed by financial issues (27.5%), transport-related problems (10%), and absence of an adult to accompany (10%). More than 50% of patients had missed appointments during the first 4 cycles of chemotherapy (Table 2).

| DISCUSSION
In the treatment of any malignancy, it is crucial to adhere to schedules and dates of chemotherapy. Delays in chemotherapy in adult cancers such as colon cancers are known to be associated with poor outcomes. 8 The RB involves multi-modality super-specialty care for the best outcomes.
The primary purposes of the application of systemic therapy are to reduce the tumor size for local treatment (chemo reduction) or to reduce the risk of metastasis after enucleation surgery (adjuvant therapy). 9 In the present study, we found that in 14% of instances, there was a delay of more than 48 hours for reporting for chemotherapy. The implications of increasing travel distance can be profound. It has been reported that even a small increase in distance can result in a substantial barrier for optimal cancer treatment. 11 In our study, about half of these patients had to travel more than 500 km to get the chemotherapy administered.
The main cause of delayed chemotherapy administration was the illness of the other family members (52.5%), followed by financial issues in this study. In about 20% of the families, another family member was suffering from a chronic illness.
In a country like India where the burden of RB is high, it is important to establish a grid of multi-specialty cancer centers so that facilities for early diagnosis and optimal treatment are accessible to the majority of the population. to return home after the 2 days of chemotherapy. This could be risky because it leads to the patient becoming more distant from the primary treating center, and in case of an emergency resulting from the chemotherapy, the patient may only be left with sub-optimal health care access.
In our cohort, most of them had a non-cemented accommodation, also called a "kaccha house" in India. Whereas in 11 families, both parents had no exposure to education, in the case of two, at least one parent was a graduate. Even in the ones where either parent has some form of schooling, it was below the level of matriculation. The average income of the household was approx. INR 9560 (approx. 135 USD) per month. The socioeconomic and educational lag of these families is a major hindrance to health-seeking behavior.
Poor accommodation may result in the patient with RB becoming vulnerable to infections and malnutrition. Poor education is a deterrent in the family's understanding of the complexities associated with the care of a RB child. Financial insecurity in the absence of social security schemes can make the RB child vulnerable to delays and abandonment of treatment. Lower socioeconomic status is known to be associated with poor overall survival in cancers. 12 Socioeconomic differences in cancer survival are well known.
Apart from the fact that patient with poor socioeconomic status have a delayed presentation and diagnosis, evidence of differential treatment between social groups. 13 The average number of family members per household was eight in our cohort. A large family may be a boon in certain situations where it leads to a better economic and social support system. In cases where the family's socioeconomic and educational backbone is fragile, more-family members would mean more liability for the head of the household. It carries the risk of the income being divided, and the time and attention that the child with RB is entitled to are often distributed amongst others. approximately 1% of the GDP. Out of pocket expenditures pose the