Background Chemotherapy related mucosal toxicity is a major hindrance to successful therapy in pediatric cancers. The role of gut dysbiosis in modulation of chemotherapy related gastrointestinal toxicity is poorly understood. Methods Pediatric cancer patients with neutropenia and gastrointestinal symptoms were evaluated for neutropenic enterocolitis (NEC) with CECT abdomen. Clinical features, fecal calprotectin and microbiological data were analysed. Fecal Gut microbiota was evaluated in children with NEC and compared with children where NEC was excluded and healthy controls using conventional culture method. Results Of 590 children receiving chemotherapy during study period, 44 were diagnosed with NEC. Significantly higher frequency of isolation of Bacteroides was observed in children with NEC (42%) as compared to non- NEC group (14%) and healthy controls (13%). Isolation of Lactobacilli was infrequent in NEC group (26%) than non- NEC group (74%) and healthy controls (80%). There was nonsignificant trend towards higher isolation of Clostridium in children with NEC. Clostridiodes difficle or Clostridium septicum were not identified in any group. Isolation of other bacterial flora was similar in the sub groups. No significant association of survival with gut dysbiosis could be established. Isolation of Lactobacilli was associated with reduction in duration of intravenous alimentation by 2.4 days, whereas isolation of Bacteroides prolonged the requirement of bowel rest by 2.2 days. Conclusion Gut dysbiosis was significantly higher in NEC group and associated with higher morbidity suggesting its role in pathogenesis. This highlights role of interventions towards gut dysbiosis like prebiotics and probiotics in pediatric cancer patients.

The second wave of COVID 19, far outnumbered the first, in cases and deaths. We report outcome of pediatric cancer patients with COVID-19 during the second wave, from a tertiary center in India. Out of 41 patients who tested positive; 51% were asymptomatic, 36% had mild symptoms, 12 required admissions in ward and 4 in intensive care. Mechanical ventilation, systemic steroids, Remdesivir and IVIG were required in those admitted to intensive care unit. Out of 4 deaths (9.7%), 3 occurred in adolescent age and 2 had superimposed bacterial/viral infections. Other contributors to mortality were: cachexia, airway obstruction, disease relapse.

Background Neutropenic enterocolitis (NEC) is a dreaded complication of chemotherapy. There is scant literature regarding incidence, clinical features, and determinants. The understanding of gut dysbiosis in NEC and pediatric cancer is evolving. Methods Pediatric cancer patients with neutropenia and gastrointestinal symptoms were evaluated for NEC with CECT abdomen. Clinical, imaging, and laboratory features were analysed. Fecal samples were analysed for fecal calprotectin by sandwich ELISA and gut microbiota by conventional culture and compared with healthy controls and children without NEC. Results NEC was diagnosed in 44 children based on clinical and imaging features with incidence of 7.4% (Four had recurrent episodes). Common manifestations included fever(98%), pain abdomen(88%), and diarrhoea(83%). Hypoalbuminemia was observed in 78% patients. Large bowel involvement(94%) with diffuse bowel involvement(63%) and pancolitis(64%) were common. Fecal calprotectin was significantly elevated in NEC group than non-NEC group and healthy controls (median 87, 53, and 42 µg/g respectively). Higher degree of gut dysbiosis was observed in children with NEC with higher isolation of Bacteroides and infrequent isolation of Lactobacilli.. Mortality rate of 23% was observed. Only presence of free fluid predicted higher mortality. Though levels of fecal calprotectin and gut dysbiosis were higher in NEC, they didn’t increase mortality. Isolation of Bacteroides and absence of Lactobacilli predicted longer duration of intravenous alimentation. Conclusion NEC caused significant morbidity and mortality in pediatric cancer patients. Gut dysbiosis was significantly higher in NEC group suggesting role in pathogenesis and influencing outcome. This highlights role of targeted interventions towards gut dysbiosis like prebiotics and probiotics.

Background The COVID-19 pandemic had led the Indian government to announce a nationwide lockdown on the 23rd of March 2020. This study (InPOG-ACC-20-04) aimed to explore the impact of this on the accessibility of care of children with cancer in India and to see strategies adopted by hospitals for service delivery during the lockdown. Procedure Weekly average childhood cancer (<18 years) patient registrations during pre-lockdown period (Jan 1st, 2020 to March 23rd 2020) were compared with the post-lockdown period (Mar 24th, 2020 to May 31st, 2020). The effect on the scheduled treatment was investigated for the post-lockdown period. A survey of health care providers was conducted to determine centres’ strategies to deal with the effect of COVID-19. Results In 30 centres participating in this study, 1146 childhood cancer patients were registered from Jan 1st, 2020 to May 31st 2020. The weekly average patient registration was 67.3 pre-lockdown and 35.5 post-lockdown which was a decline of 47.3% with travel distance being a factor. While most centres experience this decline, there were a few who saw an increase in patient registrations. Of those patients scheduled for treatment during the post-lockdown period, 36.1% experience delays in one or more modalities. Centres adopted several strategies to including modifications to treatment protocols, increased use of growth factors, and increased support from social organisations. Conclusion Our multicentre study from India suggests that the COVID19 pandemic and the lockdown impacted two out of three children with cancer. The effect of this on survival remains to be established.

Xeroderma pigmentosum (XP) is a rare genodermatosis characterized by defective DNA repair, leading to hypersensitivity to ultraviolet (UV) sunlight and predisposes to various cutaneous and non-cutaneous malignancies. Platinum compounds are used against cutaneous cancers as concurrent chemoradiotherapy. But the XP gene polymorphism has a potential role in metabolism of these agents and their susceptibility. Here, we report a case of cutaneous squamous cell carcinoma in a patient with XP who had severe toxicity to chemotherapy. We also discuss other similar cases reported in literature of this entity, to highlight this potentially lethal pharmacogenomic association.

Paraneoplastic neurologic syndromes (PNS) are rare in pediatrics and are understood to be consequences of cross-reactivity against various neuroendocrine antigens expressed on cancer cells. Here, we report a case of autoimmune encephalitis, a type of paraneoplastic neurologic syndrome that was associated with a case of adrenocortical carcinoma and had some clinical response to immunosuppressive therapy. Adrenocortical carcinoma is a rare tumor with controversial tissue of origin but expresses various neuroendocrine antigens that could be the possible mechanism for this rare yet interesting association.

Introduction: The InPOG-HL-15-01, a multi-centric prospective study used a risk-stratified and response-based approach with a doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) backbone to treat children with newly diagnosed Hodgkin Lymphoma (HL) and reduce the use of radiation therapy (RT). Children/adolescents with bulky disease or inadequate response at early response assessment (ERA) after 2 cycles of chemotherapy were assigned to receive RT. For ERA, positron emission tomography computed tomography (PET-CT) was recommended but not mandatory in view of limited access. This study aimed to compare the impact of using contrast enhanced computed tomography (CECT) vs PET-CT on treatment decisions and outcomes. Methodology: 396 patients were enrolled and 382 had an ERA at the assigned time point. Results: At ERA, satisfactory response was documented in 277/382 (72.5%) participants and this was significantly higher in PET-CT (151/186, 81.2%) as compared to CECT (126/196, 64.3%) respectively (p value<0.001). Amongst the 203 patients with non-bulky disease (wherein the indication for RT was entirely dependent on ERA), 96/114 (84.2%) and 61/89 (68.5%) patients achieved a satisfactory response according to the PET-CT and CECT (p value=0.008) respectively and hence a lesser proportion of patients in the PET-CT arm received RT. Despite a lower usage of RT the 5 year overall survival (OS) of both groups- ERA based on CECT (91.8%) vs PET-CT (94.1%) was comparable (p value=0.391) and so was the 5 year event free survival (EFS) (86.7 vs 85.5%, p value=0.724). Conclusion: Use of PET-CT as the modality for ERA is more likely to indicate a satisfactory response as compared to CECT and thereby decreases the need for RT in response-based treatment algorithm for HL afflicted children. The reduction in the application of RT did not impact the overall outcome and plausibly would lower the risk of delayed toxic effects.

Proptosis is a frequent presenting symptom/ sign of many pediatric malignancies. Acute onset proptosis is an oncological emergency that can endanger vision if not treated promptly. Appropriate treatment must be instituted only after investigating for the underlying etiology. Here we report a 6-year-old developmentally delayed boy who presented with recent onset bilateral proptosis. Clinical examination followed by radiological evaluation suggested scurvy to be the underlying cause and vitamin C supplementation lead to prompt reversal of proptosis. The relevant literature has been reviewed and presented here to apprise the pediatric oncologists about this rare but easily treatable cause of proptosis.

Background: Childhood cancer survivors are 8.8 times more likely to die of pulmonary causes when compared to general population: an aspect of concern. Pulmonary dysfunction is the third leading cause of non recurrence related cause of death among Hodgkin lymphoma survivors. Methods: A cross section study on Hodgkin lymphoma survivors in complete remission, who completed treatment within last 5 years was done. All children were subjected to detail history including drugs, past history of respiratory illnesses, physical and respiratory system examination followed by spirometry and three minute step test under supervision. Pulmonary dysfunction was determined as presence of obstructive, restrictive or mixed pattern on spirometry or abnormality in three minute step test. Subclinical pulmonary dysfunction was determined as patients who were clinically asymptomatic but had pulmonary dysfunction Results: A total of 60 children were enrolled (Mean age of 11.3 years and 53 were boys) Abnormal pulmonary function tests were documented in 11 (18.3%) of HL survivors at a median time of 2 years (IQR 1,3) from treatment completion. Restrictive pattern was documented in 10 (16.67%) and obstructive pattern in only one patient (1.67%), mostly mild in severity. Older age at start of chemotherapy and radiotherapy and past history of respiratory illness were found to be significantly associated with pulmonary dysfunction. Conclusion: Majority of Hodgkin lymphoma survivors had subclinical pulmonary dysfunction at median follow up of 2 years from treatment completion. Hodgkin lymphoma survivors require long term follow up for timely detection of pulmonary dysfunction and improve quality of life.

BACKGROUND: Neurocognitive deficits are an important late effect in survivors of acute lymphoblastic Leukemia(ALL). Data from low middle income countries is scarce and highly influenced by biological and cultural variations. Such data would be useful for highlighting the importance of early intervention in an already disadvantaged population. PROCEDURE: 70 consecutive survivors of childhood ALL were evaluated for neurocognitive deficits by the Indian adaptation of Wechsler Intelligence Scale for Children-Fourth Edition(WISC-INDIA). Prevalence of neurocognitive deficits was calculated based on Full Scale Intelligence Quotient(FSIQ) and scores in discrete domains like Verbal Comprehension, Perceptual Reasoning, Working Memory and Processing Speed were calculated and compared to baseline characteristics, chemotherapy and radiation dose received. RESULTS: The mean FSIQ was 86.1 ± 20.5, with significant neurocognitive deficit(FSIQ <90) being prevalent in 50%(95% CI 38% to 62%) of the cohort. The proportion of survivors with deficits in individual domains of verbal comprehension, perceptual reasoning, working memory and processing speed were 49%, 50%, 47% and 44% respectively. The odds of having deficits in neurocognitive function was higher when a child belonged to lower socioeconomic strata, had parents with less than primary school education and whose birth order was higher(All p<0.05). Age at diagnosis, current age at assessment, receiving lower or higher dose of radiotherapy, high dose methotrexate or cytarabine did not have a direct impact on neurocognitive function. CONCLUSIONS AND RELEVANCE: The current need is to develop country specific neurocognition assessment tools to initiate early screening and develop culturally appropriate preventive and rehabilitative interventions.

Data on the prevalence and outcomes of coronavirus disease (COVID-19) in children with cancer is limited, more so from developing countries. We aimed to evaluate the prevalence, severity and outcome of COVID-19 in pediatric oncology patients by implementing a screening and testing plan. Among 104 children tested, the rate of COVID-19 positivity was 15% and 3% in symptomatic and asymptomatic respectively. Majority had mild illness with uneventful recovery, whereas neutropenia increased the risk of serious illness. Prolonged virus shedding with a median time to negativity of 21 days was observed.

A document by Anupama Ivaturi. Click on the document to view its contents.