|Year : 2020 | Volume
| Issue : 4 | Page : 716-723
First symptom and time to diagnosis in pediatric patients with solid tumors: A cross-sectional study from a regional cancer institute in South India
Saksham Singh, Arun Kumar, Nuthan Kumar, Prakruthi S Kaushik, Veena Akkineni, L Appaji
Department of Pediatric Oncology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India
|Date of Submission||31-May-2020|
|Date of Decision||27-Jul-2020|
|Date of Acceptance||05-Oct-2020|
|Date of Web Publication||25-Dec-2020|
Prakruthi S Kaushik
Department of Pediatric Oncology, Kidwai Memorial Institute of Oncology, Dr M. H. Marigowda Road, Bengaluru - 560 029, Karnataka
Source of Support: None, Conflict of Interest: None
Background: Timely diagnosis and early treatment are essential components of oncology that translate to better outcomes.
Objectives: The primary aim of this study was to determine the time to diagnosis and its associated factors in pediatric patients with solid tumors registered at our tertiary health-care facility in South India.
Materials and Methods: This cross-sectional study was conducted in the Outpatient Department of Pediatric Oncology of the Kidwai Memorial Institute of Oncology (Karnataka, India) from January 2019 to December 2019. Children aged<15 years with newly diagnosed solid tumors were included in the study after obtaining written informed consent from their parents/guardians. The demographic details of the patients were noted, and the relevant time intervals were calculated based on the history and previous medical records. Prediagnostic time intervals were categorized as parent time (TP), time to referral (TR), time to definitive diagnosis (TDD), and total time to diagnosis (TD). The data were analyzed using the Wilcoxon signed-rank test and the independent samples median test.
Results: We enrolled 75 pediatric patients in the study, with an equal distribution of male and female patients. The median TD, TR, TP, and TDD were 76, 43, 7, and 16 days, respectively. The factors associated with a delay in the diagnosis included the maternal educational status, the state of residence, site of lesion, disease stage, and tumor type. The median TD was the shortest in patients with hepatoblastoma and longest in patients with retinoblastoma.
Conclusions: Educating the mothers, raising awareness among the primary care physicians about the symptoms at presentation of childhood cancers, strengthening the screening system, decentralization of cancer care, and increasing the number of pediatric oncology care centers are the need of the hour.
Keywords: Pediatric oncology, prediagnostic intervals, solid tumors, time to diagnosis
|How to cite this article:|
Singh S, Kumar A, Kumar N, Kaushik PS, Akkineni V, Appaji L. First symptom and time to diagnosis in pediatric patients with solid tumors: A cross-sectional study from a regional cancer institute in South India. Cancer Res Stat Treat 2020;3:716-23
|How to cite this URL:|
Singh S, Kumar A, Kumar N, Kaushik PS, Akkineni V, Appaji L. First symptom and time to diagnosis in pediatric patients with solid tumors: A cross-sectional study from a regional cancer institute in South India. Cancer Res Stat Treat [serial online] 2020 [cited 2021 Jan 18];3:716-23. Available from: https://www.crstonline.com/text.asp?2020/3/4/716/304949
| Introduction|| |
Childhood cancers are an important cause of morbidity and mortality around the world., In India, the incidence of childhood cancers ranges from 38 to 124 per 10 lakh children per year. The mortality rate is approximately 14–34 per 60 lakh children per year, making childhood cancers the ninth most common cause of death in pediatric patients aged 5–14 years., Timely diagnosis and early initiation of treatment are essential to the adequate management and outcome of childhood cancers. However, several factors related to the caregivers (parents), health-care workers, and the disease itself cause a delay in the diagnosis. The time interval between the onset of symptoms and the first contact of the patient with the physician is called the patient or parental delay, whereas the time interval between the first health-care visit and the establishment of the final diagnosis is called the physician delay.,
Treatment of diseases with a delayed presentation may require a more extensive local therapy in the form of surgery or radiotherapy. This can result in increased morbidity and long-term side effects. Moreover, some patients who present with disease in the advanced stages may not be amenable to treatment at all. Understanding the factors associated with delayed diagnosis may help formulate policies to achieve early diagnosis, which in turn could improve the survival. Factors associated with delayed diagnosis have been extensively reported from the developed countries. However, owing to the differences in the sociocultural factors, facilities, and outcomes between the developed and developing countries, a study of factors associated with delayed diagnosis and treatment in developing countries like India is warranted. Therefore, in this study, we aimed to determine the time to diagnosis, the parental and physician delay, and the factors associated with them for the purpose of improving patient care and outcomes for childhood cancers.
| Materials and Methods|| |
General study details
This cross-sectional study was conducted in the Outpatient Department of Pediatric Oncology of the Kidwai Memorial Institute of Oncology, a tertiary cancer referral center in Bengaluru, India, from January 2019 to December 2019. The data were collected over a period of 10 months. Our Institutional Ethics Committee permitted the analysis and publication of the patient data without obtaining a formal approval. Patients were enrolled after obtaining written informed consent from their parents/guardians. The study was conducted according to the ethical guidelines of the Indian Council of Medical Research and the Declaration of Helsinki.
Patients aged 15 years or less who had been diagnosed with malignant solid tumors and were undergoing treatment were included in the study. Those diagnosed with benign tumors, those who refused to take treatment, those lost to follow-up after registration, and those who died before a definitive diagnosis were excluded from the study.
The primary aim of the study was to determine the time to diagnosis and the factors associated with it in pediatric patients with solid tumors registered at our tertiary health-care facility in South India.
The time to diagnosis was calculated based on the history and previous medical records. The prediagnostic time intervals were categorized as parent time (TP), time to referral (TR), time to definitive diagnosis (TDD), and total time to diagnosis (TD). The factors associated with the prediagnostic time intervals were analyzed and broadly classified as patient- or tumor-related factors.
The definitions of the prediagnostic time intervals are depicted in [Figure 1].
|Figure 1: The various time intervals between disease onset and diagnosis|
Click here to view
- TP: It was defined as the duration between the onset of symptoms and the first contact with any physician or a member of the health-care system, in addition to the duration between the final referral and registration at our institute. This denoted the time taken by the parent to approach the health-care facilities
- TR: It was defined as the time interval between the first health-care visit and the final referral to our institute with the suspicion of a malignancy. This denoted the time taken by the physician to suspect a malignancy and finally refer the patient to our cancer institute
- TDD: It referred to the duration between the date of registration at our institute and the date of definitive diagnosis (determining the type and stage of the tumor). This denoted the total time taken to establish the diagnosis and the stage of the tumor after registration at our institute
- TD: It was defined as the duration between the first appearance of symptoms and the establishment of a definitive diagnosis based on the type (histopathologically in most cases and by imaging in some patients with brain tumors and retinoblastoma) and the stage of the tumor. This denoted the time taken to make the final diagnosis of cancer.
The clinico-demographic data were collected by the principal investigator as per the pro forma [Supplementary Appendix 1] from the clinical and treatment history taken at the time of registration from the hospital documents retrieved by the patients.
The Surveillance, Epidemiology, and End Results staging was done to clinically stage the disease. Specifically, a localized tumor was one that was limited to the organ of origin, with no spread beyond the organ of origin; locally advanced tumors were those that extended beyond the limits of the organ of origin but with no evidence of distant metastasis; metastatic (distant) tumors were those that had spread to distant areas of the body or were remote from the primary tumor.
Since this was a cross-sectional study, we enrolled all the patients in the decided time frame of the study, and hence, no formal sample size calculation was done.
The data were recorded in an Excel sheet and analyzed statistically using the Statistical Program for the Social Sciences (IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp). Descriptive statistics, namely median and range, were evaluated. Different categorical variables were analyzed using the independent samples median test. The TP and TR were compared using the Wilcoxon signed-rank test. All durations were calculated in days. P ≤ 0.05 was considered statistically significant.
| Results|| |
Of the 570 pediatric patients registered at our tertiary care center between January 2019 and December 2019, 75 patients who fulfilled the eligibility criteria were recruited in the study [Figure 2]. There were 38 male and 37 female patients in the cohort, and 54 (72%) of them were in the age group of 0–5 years. The median TP, TR, TD, and TDD of the entire cohort were 7, 43, 76, and 16 days respectively [Figure 3]. The turnaround time for histopathological reports at our institute was 7–10 days. TR was found to be significantly longer than TP (Wilcoxon signed-rank test, P < 0.001).
The time to diagnosis was studied with respect to both patient characteristics (age, sex, place of residence, education of parents, and first health-care visit) and tumor-related characteristics (site, stage, and type of tumor). The relationship of the various patient and tumor-related characteristics with the time intervals TP, TR, and TD is provided in [Table 1], [Table 2], [Table 3], respectively. The time to diagnosis was not affected by age, sex, or the place of residence (rural or urban). TD was longer for children staying more than 1000 km away from the institute (P = 0.044) and for those from outside the state of Karnataka (P = 0.025). However, the distance from our center did not significantly affect the TP and TR. The maternal educational status significantly affected the TP (P = 0.014).
|Table 1: Sociodemographic and tumor characteristics affecting time to presentation|
Click here to view
|Table 2: Sociodemographic and tumor characteristics affecting time to referral|
Click here to view
|Table 3: Sociodemographic and tumor characteristics affecting time to diagnosis|
Click here to view
TR and TD were 51 and 100 days, respectively, if the first health-care facility (HCF) was a primary health center (PHC). In cases where the first HCF was either a secondary or tertiary health center, the TR and TD were 35 and 74 days, respectively. However, this difference was not statistically significant, with P value for TR and TD being 0.271 and 0.465, respectively. With respect to the site of the tumor, TP was maximum for tumors involving the orbit followed by lymph node masses and tumors involving the upper and lower limbs. TP was the lowest for malignancies arising in the brain, head-and-neck, and chest. This difference was statistically significant (P = 0.007).
With respect to the stage of the disease, physician delay was found to significantly contribute to the delay in referral (P = 0.04). Patients with locally advanced disease were referred later (57.5 days) as compared to those with localized or metastatic disease. The disease-wise distribution according to the stage is described in [Supplementary Table 1].
With respect to the type of tumor, there was a significant parental delay (P = 0.003) which was maximum for retinoblastoma (40.5 days) and osteosarcoma (40.5 days) and minimum for brain tumors (4 days) and Wilms' tumor (4.5 days). TD and TP were not significantly different with respect to tumor types.
The reasons for delay as stated by the parents are listed in [Supplementary Table 2]. The most common reasons were a misdiagnosis and treatment for the wrong diagnosis (39%).
| Discussion|| |
In our study, the various time intervals related to diagnosis were longer than those reported from the developed countries. Moreover, we observed that physician delay was significantly longer than parental delay. The mothers' education helped in the early presentation of children with cancer. In addition, a longer distance from the pediatric cancer center was associated with longer time to diagnosis. Among the various cancer-related factors, the site and type of tumor affected the TP, whereas the stage of the disease affected the TR. Moreover, the TR was found to be significantly longer for patients with locally advanced disease than for those with metastatic and localized tumors.
Although several studies have been conducted in the developed countries about the factors contributing to a delay in the diagnosis of cancer in pediatric patients, only a few have been reported from India. The longer time intervals observed in our study as compared to those observed in studies reported from the developed countries may be due to the difference in the awareness about pediatric cancers, socioeconomic factors, basic health infrastructure, and access to oncology care. Haimi et al. and Saha et al. found a positive association between the geographical distance and diagnostic delay,, similar to our study. Moreover, similar to other studies, the sex did not affect the time to diagnosis in our study., We also assessed the various time intervals during the diagnosis of pediatric solid tumors and the factors associated with them. The TP was found to be significantly associated with the mother's educational status and the site and type of tumor. Dang-Tan et al. in their systematic review reported that the site of the tumor also affected the TD. This could be because sites such as the abdomen and the brain present with more severe and appreciable symptoms than sites such as the eyes, lymph nodes, and limbs. Similar findings were reported by Pollock et al. and Haimi et al. The longer TP observed in the patients with retinoblastoma as compared to hepatoblastoma and renal tumors in our study suggested the ignorance of the parents regarding slow-growing tumors. Moreover, the denial of the possibility of cancer and reluctance to undergo morbid surgeries (enucleation or amputation) also prompted the parents to consult multiple physicians or seek alternative therapies. Factors associated with parental delay emphasize the need to educate the general public and create awareness among parents regarding childhood cancers. Haimi et al. found physician delay to be significantly longer than parental delay in their study from Israel. The factors associated with physician delay were treatment for non-malignant conditions such as tuberculosis, multiple and delayed referrals due to the unavailability of specific tests, and the lack of awareness of the physician at the primary health-care facilities. This suggests the need for the decentralization of cancer care with an increasing need for dedicated pediatric oncology centers across the country.
Halperin and Friedman found that the stage of the tumor can affect the time to diagnosis. In our study, patients with locally advanced tumors had a longer TR than those with localized or metastatic disease. Patients with metastatic disease presented early due to the aggressive biology of the tumor. Similarly, patients with localized disease were referred to us earlier, probably because of the presence of a noticeable tumor in an external location, such as rhabdomyosarcoma and Ewing sarcoma, and easily available investigations such as ultrasound and X-rays to detect Wilms' tumor and Ewing sarcoma. The delay in the diagnosis of locally advanced tumors, especially retinoblastoma [Supplementary Table 2], could be due to the lack of awareness among physicians or the indolent nature of the tumor. Although the biology of the tumor plays a role, the physician's knowledge of the signs and symptoms of childhood cancers is important for the early diagnosis and referral of these cases. The delay in diagnosing retinoblastoma, which can otherwise be detected early by screening, prompts us to consider and strengthen our cancer screening system.
Age significantly affected the delay in 19 out of 23 studies in a review by Jean Francois Brasme et al. Older children were found to present late. Although it does not significantly affect the time to diagnosis, it is interesting to note that the tumors are diagnosed earlier in infants and toddlers than in adolescents. This may be attributed to the vigilance of parents with younger children and to adolescents being reluctant to approach parents with complaints.
The limitations of our study include the heterogeneity of the study sample and the small numbers of specific tumor types. Hence, an association of the delay in diagnosis with outcomes could not be assessed. In addition to the education of the mother, the socioeconomic status may have affected the delay in diagnosis due to the hesitancy in seeking medical care; therefore, a scale such as the Kuppuswamy scale should have been included. However, most of the patients were below the poverty line, and the socioeconomic status was not assessed as a part of the study. Another limitation was that the onset of cancer symptoms could have occurred much before the symptoms were noticed by the patients or their families, as some symptoms could be subtle and not alarming.
| Conclusion|| |
We found that mothers' educational status and the site and type of tumor affected the parental time to presentation, the stage of the tumor affected the time to referral, and the geographical distance affected the time to diagnosis. Thus, the educational status of the parents, decentralization of cancer care, increasing the number of pediatric oncology care centers, awareness among primary care physicians and pediatricians about the signs and symptoms of malignancy, and strengthening the screening system can help in avoiding an undue delay in the diagnosis of childhood cancers. Increasing the awareness about childhood cancers may help in achieving an early diagnosis and providing early treatment, thereby improving the outcomes in our country.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| Supplementary Appendix|| |
Supplementary Appendix 1 Pro forma for the study
Name –––––––– Age ––––––––– Sex ––––––––
Registration no: –––––––– Contact number: –––––––
Date of registration: –––––
Address (rural/urban): ––––––
Presenting complaints: ––––––
Duration of symptoms: –––––
First health-care facility contact Type (government [primary/secondary/tertiary]/private):––––
Date of contacting first health-care facility (approximately): –––––
Date of referral to our institute: ––––––
Any history of receiving alternative care medicine: –––––
No of health-care facility visits before KMIO: –––––
Initial diagnosis and treatment: –––––
Date of registration to our institute: –––––
Date of tissue diagnosis: ––––––
Date of imaging: –––––
Date of final metastatic investigation (bone marrow aspiration, CECT chest, bone scan, etc.): –––––
Date of definitive diagnosis (nature, stage, risk): –––––
Final diagnosis: –––––
Father's education: –––––
Mother's education: –––––
Cause of delay by parents: –––––
Cause of delay by physician: –––––
| References|| |
Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al
. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359-86.
World Health Organization. International Childhood Cancer Day: Much remains to be Done to Fight Childhood Cancer. WHO Press Release No. 241. Lyon, France: World Health Organization; 2016. Available online at https://www.iarc.fr/wp-content/uploads/2018/07/pr241_E.pdf
. [Last accessed 2020 May 30]
Arora RS, Eden TO, Kapoor G. Epidemiology of childhood cancer in India. Indian J Cancer 2009;46:264-73.
] [Full text]
Brown BJ, Bamgboye EA, Sodeinde O. Causes of death in childhood cancer at the departmentof paediatrics, University College Hospital, Ibadan, Nigeria. Afr J Med MedSci 2008;37:7-13.
Klein-Geltink JE, Pogany LM, Barr RD, Greenberg ML, Mery LS. Waiting times for African Health Sciences Vol 9 No 4 December 2009 253 cancer care in Canadian children: Impact of distance, clinical, and demographic factors. Pediatr Blood Cancer 2005;44:318-27.
Haimi M, Peretz Nahum M, Ben Arush MW. Delay in diagnosis of children with cancer: A retrospective study of 315 children. Pediatr Hematol Oncol 2004;21:37-48.
Dang-Tan T, Franco EL. Diagnosis delays in childhood cancer: A review. Cancer 2007;110:703-13.
Young JL Jr., Roffers SD, Ries LA, Fritz AG, Hurlbut AA, editors. SEER Summary Staging Manual-2000: Codes and Coding Instructions. Bethesda MD: National Cancer Institute; 2001. Available online at: https://seer.cancer.gov/tools/ssm/ssm2000/
. [Last accessed on 2020 May 30].
Saha V, Love S, Eden T, Micallef-Eynaud P, MacKinlay G. Determinants of symptom interval in childhood cancer. Arch Dis Child 1993;68:771-4.
Dang-Tan T, Trottier H, Mery LS, Morrison HI, Barr RD, Greenberg ML, et al
. Delays in diagnosis and treatment among children and adolescents with cancer in Canada. Pediatr Blood Cancer 2008;51:468-74.
Pollock BH, Krischer JP, Vietti TJ. Interval between symptom onset and diagnosis of pediatric solid tumors. J Pediatr 1991;119:725-32.
Halperin EC, Friedman HS. Is there a correlation between duration of presenting symptoms and stage of medulloblastoma at the time of diagnosis? Cancer 1996;78:874-80.
Brasme JF, Morfouace M, Grill J, Martinot A, Amalberti R, Bons-Letouzey C, et al
. Delays in diagnosis of paediatric cancers: A systematic review and comparison with expert testimony in lawsuits. Lancet Oncol 2012;13:e445-59.
Fajardo-Gutiérrez A, Sandoval-Mex AM, Mejía-Aranguré JM, Rendón-Macías ME, Martínez-García Mdel C. Clinical and social factors that affect the time to diagnosis of Mexican children with cancer. Med Pediatr Oncol 2002;39:25-31.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3]