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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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To translate the Pediatric Nausea Assessment Tool (PeNAT) into Hindi and validate it in Indian pediatric cancer patients and survivors., Methods: The PeNAT-Hindi was finalized by forward and backward translations, and pilot testing. The PeNAT-Hindi was administered to 200 Hindi-speaking pediatric (4-18 y) cancer patients/survivors, in three groups. These included pediatric cancer patients who had recently received chemotherapy (n = 150); who received no chemotherapy within 5 d (n = 25) and survivors (n = 25). Construct validity was tested by comparing scores among the three groups. Test-retest reliability and criterion validity were estimated by the correlation of the first PeNAT score with the second (taken 1 h later) PeNAT score and the number of vomiting/retching episodes, respectively. Convergent validity and discriminant validity were estimated by correlating PeNAT scores with parent-assessed nausea severity, and pain, respectively. The responsiveness was tested by comparing second PeNAT scores with subsequent divergent PeNAT scores among patients reporting subjective change (improvement and worsening, respectively) in nausea severity., Results: Test-retest reliability of PeNAT-Hindi was good (intraclass correlation = 0.791). The initial PeNAT score had moderate correlation with the number of vomiting/retching episodes (Spearman ρ = 0.401). Median PeNAT scores in group 1 versus groups 2 and 3 were significantly different (p < 0.001). Initial PeNAT scores showed a moderate correlation with parent-assessed nausea (Spearman ρ = 0.657) and a weak correlation with parent-assessed pain (Spearman ρ = 0.319). The responsiveness (standardized response mean) of PeNAT-Hindi to the change in nausea severity was -1.79 (improvement) and 2.19 (worsening), respectively., Conclusion: PeNAT-Hindi showed good reliability and acceptable validity. It may be used among Hindi-speaking children for measuring nausea. The responsiveness of PeNAT-Hindi needs further evaluation., (© 2023. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Purpose: Serial patient-reported outcome (PRO) measurements in clinical practice are associated with a better quality of life and survival. Recording electronic PROs using smartphones is an efficient way to implement this. We aimed to assess the feasibility of the electronically filled Edmonton Symptom Assessment System (e-ESAS) scale in the lower-middle-income country (LMIC) setting., Methods: Baseline clinical features and conventional paper-based ESAS (p-ESAS) were collected in newly diagnosed patients with solid organ tumors. Text message link was sent to these patients for filling e-ESAS. ESAS was categorized into physical, psychological, and total symptom domains. Scores were divided into none to mild (0-3) and moderate to severe (4-10). Intraclass correlation coefficients (ICCs) were used to determine the correlation between p-ESAS and e-ESAS. Multivariable logistic regression was used to identify independent factors affecting symptom burden., Results: Of 1,160 participants who filled out p-ESAS, 595 completed both e-ESAS and p-ESAS questionnaires and were included in the final analysis. Moderate to severe physical, psychological, and total symptom scores were seen in 39.8%, 40%, and 39% of participants. Tiredness and anxiety were the most common physical and psychological symptoms, respectively. ICCs between the p-ESAS and e-ESAS varied between 0.75 and 0.9. Total symptom scores were independently predicted by metastatic disease (odds ratio [OR], 1.83; 95% CI, 1.26 to 2.67; P = .001) and a higher level of education (OR, 0.42; 95% CI, 0.25 to 0.72; P = .001)., Conclusion: Paper-based and electronically filled ESASs have good intraobserver reliability across individual symptoms and domain scores in a representative cohort at a tertiary care institute in the LMIC. This may help us incorporate e-ESAS in routine clinical care in the real-world setting with financial, infrastructural, and manpower limitations.

Objective: Health-related quality of life (HRQoL) is an important outcome for paediatric cancer studies. We compared the HRQoL between patients of progressive paediatric solid tumours randomised to metronomic chemotherapy versus placebo., Methods: In this double-blinded, placebo-controlled randomised study of 108 children with progressive malignancies, HRQoL was evaluated using the PedsQOL Cancer module V.3 at baseline (A1), A2 (9 weeks or earlier if progressed) or A3 (18 weeks or earlier if progressed)., Results: There was no statistically significant difference in the change in quality of life produced by each arm from A1 to A2 in either mean total scores or individual domain scores, reported by children or their parents. On analysing the response according to the minimal clinically important difference, defined as an improvement by 4.5 points, we found no significant differences, be it among bone-sarcomas, other tumours, responders (those who received ≥9 weeks of treatment) or non-responders., Conclusions: The present study concludes that there was no significant difference in HRQoL, between the patients in the two arms at second and later assessments. This is consistent with the other survival endpoints in the study., Trial Registration Number: Clinical trial registration: clinicaltrials.gov Identifier: NCT01858571., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Nutritional status is an important aspect of childhood cancer, with a bearing on the disease and subsequent survivorship. We sought to evaluate the long-term anthropometric outcomes in a cohort of pediatric solid tumor survivors treated between 1994 and 2016. Anthropometry was noted at the time of presentation, after completion of therapy, and at the last follow-up. The z -scores for weight-for-age, height-for-age, and BMI-for-age were calculated using WHO growth charts for ages <5 years and the Indian Academy of Pediatrics growth charts for age >/= 5 years. BMI was calculated for adult survivors. We included 317 survivors, comprising 48, 81, and 188 survivors of Hepatoblastoma (HB), Malignant Germ cell Tumor (MGCT), and Wilms Tumor (WT) respectively. The median age at diagnosis was 24.5 (IQR 59-13.2) months, with a follow-up ranging from 5 to 19.54 years. The z -scores of the collective cohort and individual cohorts of HB, MGCT, and WT showed an improving trend from diagnosis to the last follow-up. The difference in the prevalence of malnutrition was found to be statistically significant when any two-time points were compared. Of the 28 adult survivors, 43% were noted to be underweight. Thus, anthropometric measures improve during follow-up, however, up to 15% of children persist in being malnourished.

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., (© 2022 John Wiley & Sons Ltd.)

Background & Aims: Impact of micronutrient deficiency on childhood malignancy is unexplored. We estimated the prevalence of baseline micronutrient deficiency in children with cancer and its impact on event-free survival (EFS) and overall survival (OS)., Methods: A longitudinal cohort study was conducted at a tertiary cancer centre in India. Children (≤18 years) with de novo malignancy were enrolled between October 2012 and May 2014. Baseline levels of vitamin B 12 , folate, zinc, selenium, copper, and iron were measured and values below 150 pmol/L, 6 ng/mL, International Zinc Nutrition Collaborative Group cut-off, 0.5 μmol/L, 10 μmol/L, and 50 μg/dL, respectively, indicated deficiency., Results: Total 535 children [326 (60.9%) haematological and 209 (39.1%) solid malignancies] were enrolled with median follow-up of 66 months. Vitamin B 12 , folate, zinc, selenium, copper and iron deficiencies were found in 209 (39.1%), 89 (16.6%), 173 (32.3%), 39 (7.3%), 12 (2.2%), and 231 (43.2%) children, respectively. Selenium deficiency independently predicted poor EFS (hazard ratio [HR] = 1.56; p = 0.038) and OS (HR = 1.65; p = 0.027) in the cohort. In haematological malignancies, selenium deficiency predicted poor EFS (HR = 1.81; p = 0.023) and OS (HR = 2.12; p = 0.004). In solid malignancies, vitamin B 12 (HR = 1.55; p = 0.028) and zinc (HR = 1.74; p = 0.009) deficiencies predicted poor EFS, and zinc deficiency predicted poor OS (HR = 1.77; p = 0.009). Multiple micronutrient (≥3) deficiencies also predicted poor EFS (HR = 1.69; p = 0.001) and OS (HR = 1.83; p < 0.001) in the whole cohort., Conclusions: Selenium deficiency was independently predictive of adverse outcomes in childhood cancer, particularly in haematological malignancies. Zinc deficiency adversely affected solid tumours. The adjunct use of micronutrient supplementation in paediatric malignancies should be explored., Competing Interests: Conflict of interest The authors declare no potential conflicts of interest., (Copyright © 2022 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background & Objectives: High mortality has been observed in the cancer population affected with COVID-19 during this pandemic. We undertook this study to determine the characteristics and outcomes of cancer patients with COVID-19 and assessed the factors predicting outcome., Methods: Patients of all age groups with a proven history of malignancy and a recent diagnosis of SARS-CoV-2 infection based on nasal/nasopharyngeal reverse transcriptase (RT)-PCR tests were included. Demographic, clinical and laboratory variables were compared between survivors and non-survivors groups, with respect to observed mortality., Results: Between May 11 and August 10, 2020, 134 patients were included from the three centres and observed mortality was 17.1 per cent. The median age was 53 yr (interquartile range 39-61 yr) and thirty four patients (25%) were asymptomatic. Solid tumours accounted for 69.1 per cent and breast cancer was the most common tumour type (20%). One hundred and five patients (70.5%) had received chemotherapy within the past four weeks and 25 patients (19.3%) had neutropenia at presentation. On multivariate analysis, age [odds ratio (OR) 7.99 (95% confidence interval [CI] 1.18-54.00); P=0.033], haemoglobin [OR 6.28 (95% CI 1.07-37.04); P=0.042] neutrophil-lymphocyte ratio [OR 12.02 (95% CI 2.08-69.51); P=0.005] and baseline serum albumin [OR 18.52 (95% CI 2.80-122.27); P=0.002], were associated with higher mortality. Recent chemotherapy, haematological tumours type and baseline neutropenia did not affect the outcome., Interpretation & Conclusions: Higher mortality in moderate and severe infections was associated with baseline organ dysfunction and elderly age. Significant proportion of patients were asymptomatic and might remain undetected.

Objectives: To evaluate the presence of developmental dental anomalies, like microdontia, hypodontia, abnormally shaped teeth (AST), and developmental defects of enamel (DDE) in childhood cancer survivors and compare it with the healthy controls., Methods: This cross-sectional analytical study was conducted in 2 groups: childhood cancer survivors (CCS) group including children (> 12 y, m/f) who had undergone anticancer therapy (ACT) before 8 y of age and healthy control group (> 12 y, m/f) without any systemic disease. Pearson chi-square test was used to analyze the difference between the CCS group and the control group for microdontia, hypodontia, AST, DDE and for intragroup analysis in CCS group. Odds ratio was also calculated., Results: A total of 120 and 121 children were included in CCS and control group, respectively. The prevalence of microdontia, hypodontia, abnormally shaped teeth, and DDE was 17.5% (21), 5% (6), 8.33% (10), and 37.5% (45), respectively in CCS group. It was 8.2% (10), 2.5% (3), 1.65% (2), and 22.3% (27), respectively in the control group. A statistically significant difference was seen in microdontia (p = 0.032), abnormally shaped teeth (p = 0.017) and DDE (p = 0.01). Higher prevalence was seen when ACT began at an early age., Conclusion: An association between developmental dental anomalies and anticancer therapy (ACT) exists with significantly higher difference in microdontia, abnormally shaped teeth and DDE among survivors of childhood cancer as compared to healthy population. These known adverse effects of ACT on developing teeth should be considered during treatment planning of the children having cancers., (© 2021. Dr. K C Chaudhuri Foundation.)

Background: The coronavirus disease 2019 (COVID-19) pandemic led the Indian government to announce a nationwide lockdown on March 23, 2020. This study aimed to explore the impact of the pandemic on the accessibility of care for children with cancer and to view strategies adopted by hospitals for service delivery., Methods: Weekly average of childhood cancer (≤18 years) patient registrations during pre-lockdown period (January 1 to March 23, 2020) were compared with post-lockdown period (March 24 to May 31, 2020). The effect on the scheduled treatment was investigated for post-lockdown period. A survey of health care providers was conducted to determine centers' adopted strategies., Results: In 30 participating centers, 1146 patients with childhood cancer (797 pre-lockdown period and 349 post-lockdown period) were registered. The weekly average registration was 67.3 and 35.5 patients during pre-lockdown and post-lockdown respectively (decline of 47.9%). Although most centers experienced this decline, there were 4 that saw an increase in patient registrations. The distribution of patients registered post-lockdown was found significantly different by age (lesser older age, P = .010) and distance (lesser travel distance, P = .001). 36.1% of patients, who were scheduled for any of the treatment modalities (chemotherapy, surgery, radiotherapy, and hematopoietic stem cell transplantation) during the post-lockdown period, experienced delays. Centers adopted several strategies including modifications to treatment protocols, increased use of growth factors, and increased support from social organizations., Conclusions: This multicenter study from India suggests that the COVID-19 pandemic and the lockdown impacted 2 out of 3 children with cancer. The effect of this on survival is yet to be established., (© 2021 American Cancer Society.)

Objectives: To investigate the patterns and temporal trends of childhood cancer incidence (0-14 years) in Delhi from 1990 to 2014., Methods: The new childhood cancer cases diagnosed between 1990 and 2014 were extracted from the Delhi population-based cancer registry (PBCR). Joinpoint regression analysis was performed to assess the temporal behaviour of new childhood cancer. The magnitude of temporal trend was assessed by estimated annual percentage changes (EAPCs)., Results: The Delhi PBCR registered 12,637 cases (8484 boys and 4153 girls) during 1990-2014. The overall childhood cancer was twice in boys than girls (5.62% vs. 2.78%). The age-standardised incidence rates (ASIRs) of childhood cancer adjusted to the WHO World standard population distribution (year 2000) was 163 per one million in boys and 92 per one million in girls; median age at diagnosis being 6 and 7 years, respectively. Five-top childhood cancer sites was leukaemia, lymphoma, central nervous system (CNS), bone and retinoblastoma. A decreasing linear trend in proportion of new childhood cancer cases to total all age-group cancer was observed in both sexes during this period. The percentage increase in childhood cancer is similar in both sexes from 1990-94 to 2010-14 (97% vs. 93%). Increasing trend in ASIRs of childhood cancer was observed., Conclusions: The new childhood cancer cases observed increasing trend during 1990 to 2014. Boys had nearly double the number of childhood cancer cases than girls while population ratio of boys and girls during the same period was 1.14:1.

India has made significant improvement in childhood cancer services in last few decades. However, the outcome still remains modest as compared to global standards due to significant barriers in recognition, diagnosis and cure. Data regarding comprehensive childhood cancer burden in country is lacking due to low and urban predominant coverage of population-based cancer registry programs. The available data shows lower incidence of childhood cancer incidence especially in leukaemia and CNS tumours which may suggest poor awareness of caregivers and delayed diagnosis with many "missed cases". Incidence data are also skewed towards male preponderance which suggests gender bias in seeking healthcare. The childhood cancer services in India are predominantly restricted to few tertiary care centres in major cities. The outcome in major groups of cancer is complicated by delayed and more advanced stage of presentation and poor supportive care during intensive treatment. Treatment refusal and abandonment remains major hurdles. Last few decades saw development of dedicated paediatric oncology services and training programs in the country. The development of InPOG (Indian Paediatric Oncology group) for conducting collaborative trials will lead to adoption of uniform treatment protocols suited for the country. Financial support through the government promoted health insurance and holistic support through philanthropic organizations have improved treatment adherence and outcome. Moving forward, the focus should be on strengthening the cancer registries for capturing nationwide data, improving awareness of childhood cancer among caregivers and healthcare workers for early recognition and improving accessibility of childhood cancer care services beyond major cities., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: To determine if early discontinuation of antimicrobials in pediatric patients with low risk febrile neutropenia is as effective as continuing therapy before recovery of counts, in an outpatient setting., Methods: In an open label, non-inferiority, randomized controlled phase 3 trial at a tertiary cancer center, patients aged 3-18 y, with low risk febrile neutropenia were started on empirical intra-venous antibiotics in an outpatient setting. Randomization was done when the patients became afebrile for at least 24 h; standard arm consisted of oral antibiotics, while antibiotics were stopped in the experimental arm. Enrolled patients were followed for re-appearance of fever and rate of re-admission, until ANC ≥ 500. A pilot feasibility randomized study with similar design preceded this trial., Results: From Jan 2017-Dec 2018, 75 patients were randomized: 38 to stoppage arm while 37 patients received oral antibiotics. Baseline characteristics were equally matched. Success rates were 94.6% in the continuation arm vs. 94.7% in the stoppage arm; absolute risk difference was 0.1% (95% CI: -10.0% to +10.3%), thus suggesting that the experimental arm is non-inferior to the standard arm. There was no re-admission on failure in any arm., Conclusions: Antimicrobial therapy in low risk afebrile neutropenic patients can be stopped early. This approach can lead to significant cost and resource benefits.

Background and Aims: Oral mucositis (OM) is a common and distressing toxicity in children on chemotherapy. There are a limited number of safe and effective therapeutic options available for OM. Ketamine oral rinse has shown promising results in a few studies in adults. This randomized, double-blind placebo-controlled trial aimed to test the efficacy of ketamine mouthwash in reducing chemotherapy-induced severe OM pain in children., Methods: Children aged 8-18 years with severe OM were randomized to a single dose of ketamine mouthwash (4 mg/mL solution; dose 1 mg/kg) or a placebo. A sample size of 44 patients was determined. Pain score (6-point faces scale) was noted at baseline and 15, 30, 45, 60, 120, 180, and 240 min. The outcome variables were a reduction in pain score, need for rescue medications, and adverse events., Results: The baseline characteristics were comparable in the two groups. The mean OM pain at 60 min decreased by 1.64 points (CI 1.13-2.14) in the ketamine group and 1.32 points (CI 0.76-1.87) in the placebo group (P = 0.425), with a group difference of 0.32 points. Rescue pain medication (at 60 min) was required in 13.6% in the ketamine group and 18.2% in the placebo group (P = 1.000). No significant adverse events were observed., Conclusions: Among children on cancer chemotherapy with severe OM, ketamine mouthwash at a dose of 1 mg/kg did not significantly reduce OM pain. It did not decrease the need for rescue pain medications. Further research is warranted to test higher doses of ketamine for a clinically significant effect., (© 2020 Wiley Periodicals LLC.)

Objective: We compared Vascular Endothelial Growth factor (VEGF) and Thrombospondin-1 between patients with progressive paediatric malignancies randomized to metronomic chemotherapy versus placebo to determine their role as biomarker., Methods: In this double-blinded, placebo-controlled randomized study of 108 progressive pediatric malignancies, serum VEGF and thrombospondin-1 levels were evaluated using ELISA at baseline, A2 (week-9 or earlier if progressed) and A3 (week-18 or earlier if progressed)., Results: Mean VEGF and thrombospondin-1 at baseline, A2 and A3 and the change from baseline to A2 were not different between two groups. In metronomic arm, responders (those completing 3 cycles) had significantly lower mean (SD) baseline VEGF levels [659.7(362.1) vs 1143.9 (622.0) µg/mL] (P=0.002) and significant decrease in thrombospondin-1 from baseline to A2 [-4.43(8.0) µg/mL vs 1.7(11.3) µg/mL] (P=0.04), as compared to non-responders. Similar changes were not observed in responders on placebo arm. No consistent trend of these biomarkers was observed., Conclusions: VEGF and thrombospondin-1 are not reliable biomarkers for response to metronomic chemotherapy.

Background: Cure rates for children with cancer in India lag behind that of high-income countries. Various disease, treatment and socio-economic related factors contribute to this gap including barriers in timely access of diagnostic and therapeutic care. This study investigated barriers to accessing care from symptom onset to beginning of treatment, from perspectives of caregivers of children with cancer in India., Methods: Semi-structured in-depth interviews were conducted with caregivers of children (< 18 years) diagnosed with cancer in seven tertiary care hospitals across New Delhi and Hyderabad. Purposive sampling to saturation was used to ensure adequate representation of the child's gender, age, cancer type, geographical location and socioeconomic status. Interviews were audio recorded after obtaining informed consent. Thematic content analysis was conducted and organised using NVivo 11., Results: Thirty-nine caregivers were interviewed, where three key themes emerged from the narratives: time intervals to definitive diagnosis and treatment, the importance of social supportive care and the overall accumulative impacts of the journey. There were two phases encapsulating the experiences of the family: referral pathways taken to reach the hospital and after reaching the hospital. Most caregivers, especially those from distant geographical areas had variable and inconsistent referral pathways partly due to poor availability of specialist doctors and diagnostic facilities outside major cities, influence from family or friends, and long travel times. Upon reaching the hospital, families mostly from public hospitals faced challenges navigating the hospital facilities, finding accommodation, and comprehending the diagnosis and treatment pathway. Throughout both phases, financial constraint was a recurring issue amongst low-income families. The caregiver's knowledge and awareness of the disease and health system, religious and social factors were also common barriers., Conclusion: This qualitative study highlights and explores some of the barriers to childhood cancer care in India. Our findings show that referral pathways are intrinsically linked to the treatment experience and there should be better recognition of the financial and emotional challenges faced by the family that occur prior to definitive diagnosis and treatment. This information would help inform various stakeholders and contribute to improved interventions addressing these barriers.

Metronomic chemotherapy transitioned from the bench to bedside in the early 2000s and since then has carved a niche for itself in pediatric oncology. It has been used solely or in combination with other modalities such as radiotherapy, maximum tolerated dose chemotherapy, and targeted agents in adjuvant, palliative, as well as maintenance settings. No wonder, the resulting medical literature is extremely heterogeneous. In this review, the authors review and synthesize the published literature in pediatric metronomics giving a glimpse of its history, varied applications, and evolution of this genre of chemotherapy in pediatric cancers. Limitations, future prospects, and grey areas are also highlighted., (© 2019 Wiley Periodicals, Inc.)

Purpose: To determine the prevalence of poor food knowledge and food restrictions among families of children with cancer and assess their impact on nutritional outcomes., Methods: In this cross-sectional study of 700 families of children with cancer who attended a referral cancer clinic, parents were asked 9 questions about nutritional knowledge ("Knowledge score") and 12 questions about food restrictions ("Restriction score"). Secondary outcomes included the nutritional status of children and possible socio-demographic associations of poor food knowledge., Findings: Commercial foods were considered more nutritious than homemade foods. Restriction of protein and energy-rich foods was frequent. Low knowledge scores were associated with rural background, poverty, and illiteracy. Low parental knowledge scores were associated with low weight and low height of the child. High restriction scores were associated with low weight but not low height., Conclusions and Implications: Harmful perceptions are widely prevalent in parents of children with cancer and targeted educational interventions may have a role in improving malnutrition in these children.

Context: Evidence-based research on psycho-oncology in last three decades lays emphasis upon the critical role of psychological services for better illness adjustment, improved quality of life, reduced distress and cognitive problems among the rapidly increasing pediatric cancer population., Justification: This review aims to summarize the evidence-based psychological interventions in childhood cancer over the two decades and addresses the wide gap that existed between intervention studies worldwide and India, thus highlighting the need for research and appropriate services., Evidence Acquisition: We searched electronic databases such as MedLine, PubMed, PsycINFO, and Google Scholar. Key search terms were pediatric cancer, psycho-oncology, children with cancer + psychological intervention, or multimodal treatment, psychotherapy, cognitive training, behavioral, social skills+ feasibility study, pilot, randomized controlled trial, case study, systematic reviews., Results: 28 full papers published between 1996 to 2016, including survivors and under-treatment children below 18 years, were reviewed. Various types of key interventions were psychosocial, physical, cognitive behavioral, cognitive, music art therapy and play therapy. Generally, intervention settings were either hospital or home, and were designed to promote psychological well-being. Psychological interventions were more in customised formats in these studies. A generic intervention module was not available for replication., Conclusion: Development of culture-specific generic intervention module and using the same in randomized control studies with larger effect size are needed in India for larger coverage of patients.

Importance: Although oral metronomic chemotherapy is often used in progressive pediatric solid malignant tumors, a literature review reveals that only small single-arm retrospective or phase 1 and 2 studies have been performed. Skepticism abounds because of the lack of level 1 evidence., Objectives: To compare the effect of metronomic chemotherapy on progression-free survival (PFS) with that of placebo in pediatric patients with primary extracranial, nonhematopoietic solid malignant tumors that progress after at least 2 lines of chemotherapy., Design, Setting, and Participants: A double-blinded, placebo-controlled randomized clinical trial was conducted from October 1, 2013, through December 31, 2015, at the cancer center at All India Institute of Medical Sciences in children aged 5 to 18 years with primary extracranial, nonhematopoietic solid malignant tumors that progressed after at least 2 lines of chemotherapy and had no further curative options., Interventions: One arm received a 4-drug oral metronomic regimen of daily celecoxib and thalidomide with alternating periods of etoposide and cyclophosphamide, whereas the other arm received placebo. Disease status was assessed at baseline, 9 weeks, 18 weeks, and 27 weeks or at clinical progression., Main Outcomes and Measures: The primary end point was PFS as defined by the proportion of patients without disease progression at 6 months, and PFS duration and overall survival (OS) were secondary end points., Results: A total of 108 of the 123 patients screened were enrolled, with 52 randomized to the placebo group (median age, 15 years; 40 male [76.9%]) and 56 to the metronomic chemotherapy group (median age, 13 years; 42 male [75.0%]). At a median follow-up of 2.9 months, 100% of the patients had disease progression by 6 months in the placebo group vs 96.4% in the metronomic chemotherapy group (P = .24). Median PFS and OS in the 2 groups was similar (hazard ratio [HR], 0.69; 95% CI, 0.47-1.03 [P = .07] for PFS; and HR, 0.74; 95% CI, 0.50-1.09 [P = .13] for OS). In post hoc subgroup analysis, cohorts receiving more than 3 cycles (HR for PFS, 0.46; 95% CI, 0.23-0.93; P = .03) and those without a bone sarcoma (ie, neither primitive neuroectodermal tumor nor osteosarcoma) (HR for PFS, 0.39; 95% CI, 0.18-0.81; P = .01) appeared to benefit from metronomic chemotherapy., Conclusions and Relevance: Metronomic chemotherapy does not improve 6-month PFS, compared with placebo, among pediatric patients with extracranial progressive solid malignant tumors . However, patients without bone sarcoma and those able to tolerate therapy for more than 3 cycles (9 weeks) benefit., Trial Registration: clinicaltrials.gov Identifier: NCT01858571.

Despite intensive research in the field of cancer, many pediatric cancers are still incurable with current treatment protocols. Repetitive administration of conventional chemotherapy at maximal tolerated dose imposes many side effects that further limits the dosing and therefore decreases the anticancer effects. Usually limited options remain when a malignancy progresses after one or two lines of standard chemotherapy protocol. The goal of an oncologist at this point of time remains mainly palliative with an effort to halt the progression of cancer and improve quality of life. Metronomic chemotherapy is defined as the chronic administration of chemotherapeutic agents at relatively low, minimally toxic doses, and with no prolonged drug-free breaks. It is thought this type of chemotherapy inhibits tumor growth primarily through anti-angiogenic mechanisms, promoting apoptosis and immune- surveillance.

Background: Little is known about mortality statistics of hospitalised cancer patients from developing countries. This paper describes the distribution of causes of death in various malignancies, status of malignancy at the time of death, type and intent of therapy received by the cancer patient prior to death and nature of infections in terminal cancer patients who died in hospital. We also aimed to study discrepancies in mortality reporting in terms of death certificate at our center and tried to analyse possible causes., Results: Data for 259 consecutive deaths in hospitalized cancer patients in a calendar year were analysed. Of all these, 147 (57%) were cases of solid tumors, 107 (41%) were cases of hematological malignancies and 5 (2%) were other or undiagnosed cases. Median duration of hospital stay prior to death was 7 (1-106) days. Sepsis/multi organ dysfunction syndrome (MODS) was commonest immediate cause of death 118/259 (45.2%) followed by progressive malignancy in 64/259 (24.7%) cases. Only 13/267 (5%) patients died with controlled cancer. Some 184 (71.3%) deaths occurred within 90 days of any form of anticancer treatment of which more than three fourths (77.2%) occurred after chemotherapy. Among these chemotherapy related deaths, 63 were febrile neutropenic deaths, with the commonest site of infection in the lungs, and positive blood culture was found in 18 (28%) cases. There were discrepancies in information derived from death certificates and from case records in 84 (32%) cases. Most of these were due to the use of ambiguous terms like cardio-respiratory arrest as a cause of death in the death certificate., Conclusion: It is important to audit mortality data on a regular basis as this can provide valuable insight into hospital practice and may help to identify preventable causes of mortality. Mortality record keeping is another important aspect as variable practices in this area may have implications for cancer mortality reporting and this may ultimately lead to erroneous cancer epidemiology.