Anti-Emetics in Children Receiving Chemotherapy for Solid Tumors and Leukemia: Pharmacology and Optimization of Therapy for Nausea and Vomiting.

The management of chemotherapy-induced nausea and vomiting (CINV) in children remains challenging due to differences in the chemotherapy regimens, their relative emetogenicity compared to that in adults and differences in drug metabolism and the available formulations. The common four classes of anti-emetics used for the treatment and prophylaxis of CINV in children include dexamethasone, neurokinin-1 receptor antagonists, 5-hydroxytryptamine-3 receptor antagonists (5HT3RAs), and olanzapine. The appropriate dose of dexamethasone for CINV prophylaxis in children is unknown, with a significant variability in dosage ranging between 6 and 32 mg/m2/day. The dose of dexamethasone is decreased by 30% when this drug is combined with (fos)aprepitant in children, in contrast to a decrease of 50% required in adults. The use of aprepitant in younger children (<12 years) is often hampered by the non-availability of oral suspension formulations in many countries; alternatively, 80 mg capsules are administered for 1-3 days in certain institutes to children weighing between 15 and 40 kg. Among the different 5HT3RAs, palonosetron is comparatively metabolized faster in children than in adults, requiring a higher dosage for similar efficacy to that achieved in adults. Olanzapine is a newer agent, used in doses between 0.1 and 0.14 mg/kg/day in children, with good anti-emetic efficacy, but has sedation and hyperglycemia as concerning adverse effects. Drug interactions between anti-emetics and between anti-emetics and chemotherapy/supportive agents (azole antifungals, cyclosporine, arsenic trioxide), especially QTc prolongation, should be considered during prescription.

Management of Extraocular Retinoblastoma: ICMR Consensus Guidelines.

Retinoblastoma (RB) is the most common intraocular malignancy of childhood. Advanced stage presentation of RB is common in low middle-income countries (LMICs) due to lack of awareness, social taboos associated with enucleation, seeking alternative conservative treatment options, and poor accessibility to health care. Over the last few decades, there have been significant advancements in the management of extraocular RB (EORB) which have improved outcomes and helped in minimizing treatment-related toxicities. The incorporation of multimodality approaches including chemotherapy, surgery, and radiotherapy (RT) has shown promising results; however, prognosis remains poor especially in LMICs. In this article, authors have discussed the ICMR consensus guidelines on the management of EORB, including metastatic RB.

Management of Intraocular Retinoblastoma: ICMR Consensus Guidelines.

Retinoblastoma (RB) is the most common childhood intraocular malignancy. Delayed presentation due to a lack of awareness and advanced intraocular tumors are a common scenario in low-middle income countries (LMICs). Remarkable treatment advances have been made in the past few decades allowing globe salvage in advanced intraocular RB (IORB) including systemic chemotherapy with focal consolidation and targeted treatments like intraarterial chemotherapy and intravitreal chemotherapy. However, a lack of availability and affordability limits the use of such advances in LMICs. External beam radiotherapy, despite risk of second cancers in RB with germline mutations, still remains useful for recalcitrant RB not responding to any other treatment. When choosing conservative treatment for advanced IORB, the cost and long duration of treatment, morbidity from multiple evaluation under anesthesias (EUAs), side effects of treatment and risk of treatment failure need to be taken into account and discussed with the parents. In this article, the authors discuss the ICMR consensus guidelines on the management of IORB.

Knowledge and attitude on childhood cancer survivorship among healthcare trainees: a multicentre study from India.

BACKGROUND: The proportion of childhood cancer survivors (CCS) in low/middle-income countries (LMICs) is rising. CCS often develop several physical and psycho-social long-term adverse effects, with unique healthcare needs. Primary healthcare providers (primary care physicians (PCPs)), especially in LMICs, are often not equipped to handle survivorship care. This study aimed to assess knowledge, and attitude among trainee healthcare providers concerning major issues of paediatric survivorship care. METHODS: A multi-centre, cross-sectional, questionnaire-based study was conducted among nursing and medical undergraduate students, and postgraduate medical residents across three tertiary-care teaching hospitals in India-All India Institute of Medical Sciences, New Delhi; Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry; and Maulana Azad Medical College, New Delhi. A questionnaire with total of 24 questions (14 knowledge-based and 10 attitude-based) was finalised after validation by expert review and piloting. The major domains covered in the questionnaire included knowledge and attitude regarding long-term adverse effects and psychosocial, employment-related issues faced by the survivors. It was administered to the study participants electronically. The knowledge-based questions had true/false responses (scored as 0 or 1 if incorrect or correct, respectively). Attitude-based questions were scored as 5-point Likert scale. RESULTS: Total 898 responses were collected (median age: 21 years, 64% (576/898) female). Among the respondents, 44% were undergraduate medical students, 42% were nursing students and 14% were postgraduate medical residents. The mean (SD) of knowledge score was 8.72 (2.04) (out of 14). On multivariable analysis, only discipline of training predicted knowledge scores regarding survivorship care. Postgraduate medical residents (9.08) as well as undergraduate medical students (8.85), had significantly higher mean knowledge scores than nursing students (8.47) (p=0.004).Two questions were answered incorrectly by the majority; children and siblings of CCS need additional genetic screening (79% incorrectly answered true), and CCS face intimacy issues in relation to normal sexual functioning (59% incorrectly answered false).Nearly half (48%) of respondents believed that their knowledge of cancer survivorship issues was inadequate. Majority of respondents (84%) suggested that oncologists should handle long-term survivorship care rather than PCPs. CONCLUSION: Trainee healthcare providers in India reported inadequate knowledge regarding survivorship care. Improving awareness by incorporating survivorship in teaching curriculum is imperative to equip future PCPs to provide survivorship care across the country.

Epidemiology, Diagnosis and Genetics of Retinoblastoma: ICMR Consensus Guidelines.

Retinoblastoma (RB) is the most common intraocular tumor in childhood. It is mainly caused by mutations in both alleles of the RB1 tumor suppressor gene that is found on chromosome 13 and regulates the cell cycle. Approximately 8000 children are diagnosed with RB globally each year, with an estimated 1500 cases occurring in India. The survival rate of RB has improved to more than 90% in the developed world. Leukocoria and proptosis are the most common presenting features of RB in Asian Indian populations. Most cases of RB are diagnosed by fundus examination followed by ultrasound. The International Classification of Retinoblastoma is the most used scheme for the staging and classification of intraocular RB in India. Prenatal testing and preimplantation genetic testing for RB may be beneficial in high-risk families. Histopathologic risk factors such as massive choroidal invasion and post-laminar optic nerve help in predicting the occurrence of metastasis in children with RB, while presence of microscopic residual disease requires aggressive adjuvant treatment in eyes enucleated for group E RB. The review provides a consensus document on diagnosis and genetics of RB in India.

Humoral and cellular immunity to SARS-CoV-2 following vaccination with non-mRNA vaccines in adolescent/young adults with cancer: A prospective cohort study.

BACKGROUND: Data on SARS-CoV-2 vaccine responsiveness in adolescent/young adult (AYA) cancer patients are sparse. The present study assessed humoral and cellular immune responses post-vaccination in this population. METHODS: In this prospective study, patients aged 12-30 years undergoing cancer therapy ("on therapy") and survivors ("off therapy") were recruited. Anti-receptor binding domain (RBD) protein IgG levels were measured at baseline, four weeks post-first vaccine dose (T1), and six weeks post-second dose (T2). Cellular immunity was assessed using activation-induced markers and intracellular cytokine staining in a patient subset. The primary outcome was to quantify humoral responses in both cohorts at T2 compared to baseline. Clinical predictors of log antibody titres at T2 were identified. RESULTS: Between April-December 2022, 118 patients were recruited of median age 15.4 years. Among them, 77 (65.2 %) were in the "on therapy" group, and 77 (65.2 %) had received the BBV152 vaccine. At baseline, 108 (91.5 %) patients were seropositive for anti-RBD antibody. The log anti-RBD titre rose from baseline to T2 (p-value = 0.001) in the whole cohort; this rise was significant from baseline-T1 (p-value < 0.001), but not from T1 to T2 (p-value = 0.842). A similar pattern was seen in the "on therapy" cohort. BECOV-2 vaccine was independently associated with higher log anti-RBD titres than BBV152 (regression coefficient: 0.41; 95 % CI: 0.10-0.73; p = 0.011). Cellular immune responses were similar in the "on-" and "off therapy" groups at the three time points. CONCLUSION: Among AYA cancer patients, a single non-mRNA vaccine dose confers robust hybrid humoral immunity with limited benefit from a second dose.

Treatment outcomes in patients with Ewing sarcoma of the spine in a resource-challenged setting: 17-year experience from a single center in India.

Ewing sarcoma (ES) of the spine is a rare childhood cancer with sparse literature on treatment outcomes. We aimed to describe survival outcomes and prognostic factors in patients with spinal ES treated at a single institute in a resource-challenged setting. We conducted a retrospective analysis of patients with spinal ES registered at a tertiary care oncology center between 2003-2019. Clinical patient data was retrieved from hospital records. Cox regression analysis was used to identify the association of baseline clinical parameters with event free survival (EFS) and overall survival (OS). A cohort of 85 patients was analyzed including 38 (45%) patients with metastatic disease. The median age was 15 years with 73% being male. Local therapy was administered in 62 (72.9%) patients with surgery alone in 8 (9.4%), radiotherapy alone in 36 (42.4%) and both in 18 (21.2%) patients. A higher proportion of males received local therapy than females (80.3% versus 59.1%; p = 0.049). The median EFS and OS were 20.1 and 28.6 months, respectively. On univariable analysis, age ≤ 15 years, female sex, serum albumin ≤3.5 g/dL and hemoglobin ≤11 g/dL were associated with inferior EFS while younger age, female sex, hypoalbuminemia and metastatic disease were associated with inferior OS. On multivariable analysis, only hypoalbuminemia was predictive for inferior EFS (HR:2.41; p = 0.005) while hypoalbuminemia (HR:2.06;p = 0.033) and female sex (HR:1.83; p = 0.046) were associated with inferior OS. We concluded that hypoalbuminemia confers poor prognosis in ES spine. Survival outcomes are poorer in females treated in our setting, possibly due to prevailing sex-based biases.

Sex Bias in Treatment Abandonment of Childhood Cancer in India.

OBJECTIVES: To explore the magnitude of sex bias and determinants of treatment abandonment (TA) in childhood cancer in India. METHODS: Individual data of children (0-19 y) registered between January 1, 2017 and July 31, 2022, was compiled. TA was defined as defaulting curative intent treatment ≥4 wk. Defaulting treatment irrespective of intent ≥4 wk was defined as Treatment Default (TD). The primary outcome was the proportion of male-to-female children with TA. Secondary outcomes included the proportion of male-to-female children with upfront TA, TA at relapse, TD, TD-p (TD only in the palliative setting). The impact of clinico-demographic factors on TA was analysed using multivariable regression and propensity score matching (PSM). RESULTS: Three thousand two hundred eighty four patients were analysed. The overall male-to-female ratio (MFR) was 2.08 (95% CI 1.94-2.24). Of 2906 patients treated with curative intent, 415 (14·3%) abandoned treatment. TA was higher in females than males (16·4% vs. 13·3%; p = 0·022) with adjusted MFR of 0·81 (0·66-0·98). The adjusted MFR of TA for treatment-naïve and relapsed patients and TD were 0·73 (0·59-0·91), 1·13 (0·65-1·96) and 0·84 (0·71-1·00) respectively. Sex independently predicted TA on multivariable analysis. However, on PSM analysis including socio-economic variables, lower maternal education predicted higher TA in children with cancer (10·1% vs. 6%, p = 0·015). CONCLUSIONS: Child sex predicted TA in childhood cancer in India with more females abandoning treatment. Maternal education is a more crucial factor predicting TA over child sex, when socio-economic factors were considered. Hence, policies promoting female education and gender equality may mitigate sex-based gaps in childhood cancer care.

Olanzapine cost-effectiveness in vomiting and nausea from highly emetogenic chemotherapy in children and adolescents.

OBJECTIVES: To assess the cost-effectiveness of addition of olanzapine to a prophylactic antiemetic regimen containing aprepitant, dexamethasone and ondansetron among children receiving highly emetogenic chemotherapy (HEC) in India, Bangladesh, Indonesia, the UK and the USA. METHODS: Health states were estimated using individual patient-level outcome data from a randomised trial. The incremental cost-utility ratio (ICUR), incremental cost-effectiveness ratio and net monetary benefit (NMB) were calculated from the patient perspective for India, Bangladesh, Indonesia, the UK and the USA. One-way sensitivity analysis was done by varying the cost of olanzapine, cost of hospitalisation and utility values by ±25%. RESULTS: The olanzapine arm had an increment of 0.0018 quality-adjusted life-years (QALY) over the control arm. The mean total expenditure in the olanzapine arm was greater by US$0.51, US$0.43, US$6.73, US$11.05 and US$12.35 in India, Bangladesh, Indonesia, the UK and the USA, respectively. The ICUR($/QALY) was US$282.60 in India, US$241.42 in Bangladesh, US$3755.93 in Indonesia, US$6161.83 in the UK and US$6887.41 in the USA. The NMB was US$9.86, US$10.12, US$14.08, US$44.74 and US$98.79 for India, Bangladesh, Indonesia, the UK and the USA, respectively. The ICUR estimates of the base case and sensitivity analysis were below the willingness-to-pay threshold in all scenarios. CONCLUSION: The addition of olanzapine as a fourth agent for antiemetic prophylaxis is cost-effective despite an increase in overall expenditure. Olanzapine should be uniformly considered for children receiving HEC.

Philadelphia Chromosome Positive and Philadelphia-Like Acute Lymphoblastic Leukemia in Children and Adolescents: Current Management, Controversies and Emerging Concepts.

Philadelphia chromosome positive (Ph+) acute lymphoblastic lymphoma (ALL) is an uncommon subtype of ALL in children, seen in 2-5% cases. Diagnostic evaluation includes conventional karyotyping and detection of BCR-ABL1 translocation by fluorescence in-situ hybridization (FISH) or reverse transcriptase polymerase chain reaction (RT-PCR). For children, the frontline management includes combination of intensive chemotherapy along with imatinib (300-340 mg/m2/d) or dasatinib (60-80 mg/m2/d). Imatinib/dasatinib should be introduced in induction as soon as results for BCR-ABL are available. Minimal residual disease (MRD) monitoring is essential; multi-parametric flowcytometry and immunoglobulin/T-cell receptor rearrangement PCR are the preferred methods. Intrathecal therapy with at least 12 doses of methotrexate is adequate for central nervous system (CNS) prophylaxis, but cranial radiation is necessary for CNS3 involvement. Allogeneic hematopoietic stem cell transplantation (HSCT) in first remission may be considered in high-risk cases (persistent MRD positivity/induction failure). Maintenance therapy with tyrosine kinase inhibitors (TKI) in children is debatable, with potential concerns for long term adverse effects. At relapse, the choice of TKI is guided by the presence of BCR-ABL tyrosine kinase domain resistance mutations, although the frequency of resistance mutations in children are lower. Allogeneic HSCT is essential for consolidation in second remission, if not done. Ph-like ALL is a newly recognized molecular entity, with gene expression profile similar to Ph+ALL and poor survival outcomes. In resource-constrained settings, a stepwise cost-effective diagnostic evaluation should be considered among high-risk patients without recurrent genetic abnormalities. Current treatment strategies remain similar to Ph-negative ALL. Enrolment in clinical trials is encouraged for such children to evaluate potential targeted agents in this subtype.

Fully automatic deep learning-based lung parenchyma segmentation and boundary correction in thoracic CT scans.

PURPOSE: The proposed work aims to develop an algorithm to precisely segment the lung parenchyma in thoracic CT scans. To achieve this goal, the proposed technique utilized a combination of deep learning and traditional image processing algorithms. The initial step utilized a trained convolutional neural network (CNN) to generate preliminary lung masks, followed by the proposed post-processing algorithm for lung boundary correction. METHODS: First, the proposed method trained an improved 2D U-Net CNN model with Inception-ResNet-v2 as its backbone. The model was trained on 32 CT scans from two different sources: one from the VESSEL12 grand challenge and the other from AIIMS Delhi. Further, the model's performance was evaluated on a test dataset of 16 CT scans with juxta-pleural nodules obtained from AIIMS Delhi and the LUNA16 challenge. The model's performance was assessed using evaluation metrics such as average volumetric dice coefficient (DSCavg), average IoU score (IoUavg), and average F1 score (F1avg). Finally, the proposed post-processing algorithm was implemented to eliminate false positives from the model's prediction and to include juxta-pleural nodules in the final lung masks. RESULTS: The trained model reported a DSCavg of 0.9791 ± 0.008, IoUavg of 0.9624 ± 0.007, and F1avg of 0.9792 ± 0.004 on the test dataset. Applying the post-processing algorithm to the predicted lung masks obtained a DSCavg of 0.9713 ± 0.007, IoUavg of 0.9486 ± 0.007, and F1avg of 0.9701 ± 0.008. The post-processing algorithm successfully included juxta-pleural nodules in the final lung mask. CONCLUSIONS: Using a CNN model, the proposed method for lung parenchyma segmentation produced precise segmentation results. Furthermore, the post-processing algorithm addressed false positives and negatives in the model's predictions. Overall, the proposed approach demonstrated promising results for lung parenchyma segmentation. The method has the potential to be valuable in the advancement of computer-aided diagnosis (CAD) systems for automatic nodule detection.

Current stand on systemic therapy in localized soft tissue sarcomas: a clinician's perspective.

Soft tissue sarcomas (STS) are rare heterogenous tumors derived from mesenchymal tissue. While surgery represents the primary treatment modality, the high recurrence rates following surgery alone necessitate consideration for systemic therapy in high-risk sarcomas. Despite multiple trials and meta-analyses over the last 3 decades, the role of chemotherapy remains controversial. It is crucial to accurately identify patients with high-risk diseases who may benefit the most from adjuvant and/or neoadjuvant chemotherapy. There is renewed interest in the potential to improve outcomes in localized resectable STSs with the addition of targeted and immunotherapeutic strategies. The review presented here is a summary of current evidence on systemic therapy in resectable localized STSs of the trunk and extremities to facilitate clinician decision-making.

A proposed methodology for detecting the malignant potential of pulmonary nodules in sarcoma using computed tomographic imaging and artificial intelligence-based models.

The presence of lung metastases in patients with primary malignancies is an important criterion for treatment management and prognostication. Computed tomography (CT) of the chest is the preferred method to detect lung metastasis. However, CT has limited efficacy in differentiating metastatic nodules from benign nodules (e.g., granulomas due to tuberculosis) especially at early stages (<5 mm). There is also a significant subjectivity associated in making this distinction, leading to frequent CT follow-ups and additional radiation exposure along with financial and emotional burden to the patients and family. Even 18F-fluoro-deoxyglucose positron emission technology-computed tomography (18F-FDG PET-CT) is not always confirmatory for this clinical problem. While pathological biopsy is the gold standard to demonstrate malignancy, invasive sampling of small lung nodules is often not clinically feasible. Currently, there is no non-invasive imaging technique that can reliably characterize lung metastases. The lung is one of the favored sites of metastasis in sarcomas. Hence, patients with sarcomas, especially from tuberculosis prevalent developing countries, can provide an ideal platform to develop a model to differentiate lung metastases from benign nodules. To overcome the lack of optimal specificity of CT scan in detecting pulmonary metastasis, a novel artificial intelligence (AI)-based protocol is proposed utilizing a combination of radiological and clinical biomarkers to identify lung nodules and characterize it as benign or metastasis. This protocol includes a retrospective cohort of nearly 2,000-2,250 sample nodules (from at least 450 patients) for training and testing and an ambispective cohort of nearly 500 nodules (from 100 patients; 50 patients each from the retrospective and prospective cohort) for validation. Ground-truth annotation of lung nodules will be performed using an in-house-built segmentation tool. Ground-truth labeling of lung nodules (metastatic/benign) will be performed based on histopathological results or baseline and/or follow-up radiological findings along with clinical outcome of the patient. Optimal methods for data handling and statistical analysis are included to develop a robust protocol for early detection and classification of pulmonary metastasis at baseline and at follow-up and identification of associated potential clinical and radiological markers.

Formulation and validation of a baseline prognostic score for osteosarcoma treated uniformly with a non-high dose methotrexate-based protocol from a low middle income healthcare setting: a single centre analysis of 594 patients.

Introduction: The outcomes of osteosarcoma in low middle income countries (LMICs) are different due to patients presenting in advanced stages, resource constraints and the use of non-high-dose-methotrexate (HDMTX)-based regimens. This study derived and validated a prognostic score for osteosarcoma that integrates biologic and social factors and is tailored for patients from an LMIC setting using a non-HDMTX-based protocol. Materials and methods: A retrospective study including osteosarcoma patients enrolled for treatment at a single tertiary care centre in India between 2003-19 was conducted. Baseline biologic and social characteristics were extracted from medical records and survival outcomes were noted. The cohort was randomised into a derivation and validation cohort. Multivariable Cox regression was used to identify baseline characteristics that were independently prognostic for survival outcomes in the derivation cohort. A score was derived from the prognostic factors identified in the derivation cohort and further validated in the validation cohort with estimation of its predictive ability. Results: 594 patients with osteosarcoma were eligible for inclusion in the study. Around one-third of the cohort had metastatic disease with 59% of the patients residing in rural areas. The presence of metastases at baseline (HR 3.39; p<0.001; score=3), elevated serum alkaline phosphatase (SAP) >450 IU/L (HR 1.57; p=0.001; score=1) and baseline tumour size > 10 cm (HR 1.68; p<0.001; score=1) were identified to be independent factors predicting inferior event free survival (EFS) and were included in development of the prognostic score. Patients were categorized as low risk (score 0), intermediate risk (score 1-3) and high risk (4-5). Harrell's c-indices for the score were 0.682, 0.608 and 0.657 respectively for EFS in the derivation, validation and whole cohort respectively. The timed AUC of ROC was 0.67 for predicting 18-month EFS in the derivation, validation and whole cohorts while that for 36-month EFS were 0.68, 0.66 and 0.68 respectively. Conclusions: The study describes the outcomes among osteosarcoma patients from an LMIC treated uniformly with a non-HDMTX-based protocol. Tumor size, baseline metastases and SAP were prognostic factors used to derive a score with good predictive value for survival outcomes. Social factors did not emerge as determinants of survival.

Sex disparity in childhood cancer in India: a multi-centre, individual patient data analysis.

BACKGROUND: Sex disparity and its determinants in childhood cancer in India remain unexplored, with scarce information available through summary statistics of cancer registries. This study analysed the degree of sex bias in childhood cancer in India and its clinical and demographical associations. METHODS: In this retrospective, multicentre cohort study, we collected individual data of children (aged 0-19 years) with cancer extracted from the hospital-based records of three cancer centres in India between Jan 1, 2005, and Dec 31, 2019, and two population-based cancer registries (PBCRs; Delhi [between Jan 1, 2005, and Dec 31, 2014] and Madras Metropolitan Tumour Registry [between Jan 1, 2005, and Dec 31, 2017]). We extracted data on age, sex, and confirmed diagnosis of malignancy (according to the International Classification of Diseases-10 coding),and excluded participants if they were without a recorded diagnosis, had a benign diagnosis, had missing sex information, resided outside of India, or were a donor for haematopoietic stem cell transplantation (HSCT). The primary outcome was the male-to-female incidence rate ratio (MF-IRR) in the two PBCRs and the male-to-female ratios (MFR) from the hospital-based and the HSCT data. For PBCR data, MF-IRR was estimated by dividing the MFR by the total population at risk. MFR was analysed for patients seeking treatment at the cancer centres and for those undergoing HSCT. Logistic regression analyses were done to explore the association of clinical and demographical variables with sex of the patients seeking treatment and those undergoing HSCT in hospital-based data and multivariable analyses were done to determine independent sociodemographic predictors of sex bias. Annual time trends of MFR and MF-IRR during the 15-year study period were ascertained by time series regression analyses. FINDINGS: We included 11 375 children from PBCRs in the study. 26 891 children from hospital-based records were screened, and data from 22 893 (85·1%) were included (including 514 who underwent HSCT). Residence details were missing for 257 (1·1%) of 22 893 patients from hospital-based records. The crude MFR of children at diagnosis was in favour of boys: 2·00 (95% CI 1·92-2·09) in the Delhi PBCR and 1·44 (1·32-1·57) in Madras Metropolitan Tumour Registry. The MF-IRRs for cancer diagnosis were also skewed in favour of boys in both PBCRs (Delhi 1·69 [95% CI 1·61-1·76]; Madras Metropolitan Tumour Registry 1·37 [1·26-1·49]). The MFR for children seeking treatment from hospital-based records was 2·06 (95% CI 2·00-2·12) in favour of boys. In subgroup analyses, the proportion of boys seeking treatment was higher in northern India than southern India (p<0·0001); in private centres than in centres providing subsidised treatment (p<0·0001); in patients with haematological malignancies than those with solid malignancies (p<0·0001); in those residing 100 km or further from the hospital than those within 100 km of a hospital (p<0·0001); and those living in rural areas than those living in urban areas (p=0·0006). The MFR of 514 children who underwent HSCT was 2·81 (95% CI 2·32-3·43) in favour of boys. Time trend analysis showed that MFR did not show any significant annual change in either the overall cohort or in any of the individual centres for hospital-based data; however, the analysis did show a declining MF-IRR in the Delhi PBCR from 2005 to 2014 (p=0·031). INTERPRETATION: The sex ratio for childhood cancer in India has a bias towards boys at the level of diagnosis, which is more pronounced in northern India and in situations demanding greater financial commitment. Addressing societal sex bias and enhancing affordable health care for girls should be pursued simultaneously in India. FUNDING: None. TRANSLATION: For the Hindi translation of the abstract see Supplementary Materials section.

Determinants and impact of diagnostic interval in bone sarcomas: A retrospective cohort study.

BACKGROUND: Diagnostic delays in cancers are frequent in developing countries due to poor health infrastructure. Existing literature from developed countries suggests that diagnostic interval in bone sarcomas is primarily dictated by tumour biology with no impact on survival. This study evaluates the social and biological determinants of the diagnostic interval in bone sarcomas in a resource-challenged setting and assesses its impact on treatment outcomes. METHODS: A retrospective single-institutional study was conducted on patients with high-grade bone sarcomas recorded in the sarcoma clinic database between 2003 and 2018. Baseline clinical characteristics and treatment outcomes were recorded. Logistic regression was performed to assess the impact of baseline clinical and social characteristics (distance from treating centre and rural vs. urban residence) on the diagnostic interval. Further, the impact of diagnostic interval on histologic response to neoadjuvant chemotherapy, amputation requirement in extremity sarcomas and survival was evaluated. RESULTS: A total of 1227 patients were included for analysis. The median diagnostic interval was 4 months (3-7 months). Age above 18 years, Ewing sarcoma (ES) diagnosis, absence of fever at presentation and tumour size above 7.5 cm were predictors of a longer diagnostic interval (>4 months). The length of the diagnostic interval did not impact amputation requirement or survival outcomes. However, the proportion of patients with good necrosis post-neoadjuvant chemotherapy was lower among patients with longer diagnostic intervals (25% vs. 34·16%; p-value = .04). CONCLUSION: Tumour characteristics rather than social factors determined the diagnostic interval. Diagnostic interval did not impact survival outcomes even in a resource-constrained setting.

Adaptation of the Patient Reported Outcome Measurement Information System (PROMIS) tool for childhood cancer in India: A qualitative study.

BACKGROUND: To fill the gap in patient-reported outcome (PRO) assessment in children with cancer in India, we planned to adapt domains from the HealthMeasures Patient Reported Outcomes Measurement Information System (PROMIS) tool. This study attempted to identify and pool outcomes relevant to children with cancer and their caregivers in Northern India. METHODS: The study was qualitative and conducted through focussed group discussions (FGDs) and in-depth interviews of children with cancer and their caregivers. Content analysis of transcripts from the sessions was done. The collected themes were collated with existing item banks of the PROMIS tool and new concepts unique to our population were compiled. RESULTS: A set of three FGDs and 14 interviews each for children and their caregivers were conducted. Following content analysis, 121 themes were identified including 10 new concepts. Themes pertaining to the physical domain were cited most. The theme distribution across the three domains was similar among children and caregivers. In the survivor cohort, the relative frequency of mention of psychological and social themes was higher compared to the whole cohort. Themes pertaining to mobility, cognitive dysfunction and peer relationships were more common among survivors. CONCLUSIONS: This qualitative study in children with cancer and their caregivers in India has facilitated a better understanding of the issues pertaining to cancer care that are of most importance to its stake holders. The themes collected may be used to formulate a PRO tool uniquely tailored for use in this population.

A study on the effect of mobile phone use on sleep.

Background & objectives: Several studies have been conducted globally to assess the impact of usage of mobile phones on quality and duration of sleep as also on day time sleepiness. The objective of the present study was to assess the effect of mobile phone usage on the quality and composition of sleep in a sample from Indian population. Methods: The study was conducted at two tertiary care hospitals in north India from July 2014 to September 2019. A total of 566 participants were recruited in this study from both the centres. Sleep quality was assessed with the help of the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Subsequently, actigraphy was done in 96 participants and polysomnography in 95 participants. Results: Of the 566 participants, 128 (22.61%) had PSQI ≥5, reflecting poor sleep quality. A higher use of mobile phone was significantly associated with a poor sleep quality as a component of PSQI questionnaire (P=0.01) and higher overall PSQI score (P=0.01). The latency from sleep onset to N2 and N3 sleep stages was significantly shorter in participants having a higher mobile phone usage as compared to those with a lower usage [Median (range): 13.5 min (1.5-109) vs. 6.5 min (0-89); P=0.02] and [Median (range): 49 min (8.5-220.5) vs. 28.75 min (0-141); P=0.03], respectively. Interpretation & conclusions: This study focused on the maladaptive changes brought on by mobile phone usage on sleep. More studies with larger sample sizes need to be done that may serve to confirm the hypothesis generating findings of our study.

Cost-effectiveness analysis of aprepitant-based anti-emetic regimen for children receiving highly emetogenic chemotherapy: Individual patient data analysis of a randomized trial.

BACKGROUND: Aprepitant has been shown to reduce chemotherapy-induced nausea and vomiting in children receiving highly emetogenic chemotherapy (HEC). In this study, we assessed the cost-effectiveness of aprepitant for children receiving HEC in India, United Kingdom, and the United States. PROCEDURE: We utilized individual patient-level outcome data from a pediatric randomized trial, which demonstrated the superiority of an aprepitant-based anti-emetic prophylaxis over standard ondansetron and dexamethasone for HEC. Health state for each day of follow-up was analyzed and quality-adjusted life years (QALYs) were estimated. The incremental cost-utility ratio (ICUR), incremental cost-effectiveness ratio (ICER), and net monetary benefit (NMB) for each country were estimated. Sensitivity analyses by varying cost of aprepitant, hospitalization, and health state utility values by ±25% were conducted. RESULTS: Use of the aprepitant-based regimen resulted in gain of 0.0019 QALY per chemotherapy cycle along with cost savings of $22.25, $1335.52, and $6612.10 for India, United Kingdom, and the United States, respectively. The cost savings per QALY was estimated to be $12,355.84 for India, $734,282.90 for the United Kingdom, and $3,567,564.11 for the United States. The cost savings for 50% gain in the percentage of days without grade 3 vomiting was $124.18 for India, $7451.63 for the United Kingdom, and $36,892.76 for the United States. The NMB for gain in QALY was $33.62, $1418.60, and $6727.01 for India, United Kingdom, and the United States, respectively. The estimates remained cost-effective across all scenarios of the sensitivity analyses. CONCLUSION: Aprepitant-based anti-emetic regimen is cost-effective for children receiving HEC. It results in overall cost savings and reduced healthcare-resource utilization.