Search

• Adolescent/young adults with cancer are at risk of severe COVID-19 infection. • In this group, humoral responses occurred with single non-mRNA COVID-19 vaccine dose. • No further increase in humoral response was seen with the second vaccine dose. • Survivors had higher antibody levels than those on active cancer therapy. • Cellular immune responses were similar in survivors and those on active therapy. 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. 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. 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. Among AYA cancer patients, a single non-mRNA vaccine dose confers robust hybrid humoral immunity with limited benefit from a second dose. [ABSTRACT FROM AUTHOR]

[Display omitted] • Early surgery is associated with favourable necrosis. • Small tumors predict favourable necrosis. • Low Alkaline phosphatase predicts likelihood of favourable necrosis. • Favourable necrosis is associated with higher survival rates. • Response-adapted treatment escalation does not improve outcome in non-HDMTx based regimens. Response to neoadjuvant chemotherapy in form of tumor necrosis predicts outcome in osteosarcoma; although response-adapted treatment escalation failed to improve outcome among patients treated with high-dose methotrexate-based (HDMTx) chemotherapy. This study aimed to identify factors predicting tumor necrosis and its impact on survival among patients with non-metastatic osteosarcoma treated with a response-adapted non-HDMTx regimen. A retrospective single-institutional study was conducted among non-metastatic osteosarcoma patients treated with neoadjuvant therapy between 2004–2019. Patients were treated uniformly with three cycles of neoadjuvant cisplatin/doxorubicin. Post-operatively, patients with favourable necrosis (≥90 %) received 3 cycles of cisplatin/doxorubicin, while patients with poor necrosis (<90 %) received escalated treatment with alternating six cycles of cisplatin/doxorubicin and ifosfamide/etoposide. Propensity score matching (PSM) analyses were conducted to ascertain independent impact of necrosis on event-free survival (EFS) and overall survival (OS). Of 594 registered osteosarcoma patients, 280 patients (median age 17 years; male 67.1 %) were included for analysis. 73 patients (26.1 %) achieved favourable necrosis. Patients with smaller tumor size (≤10 cm) (aOR = 2.28; p = 0.030), lower serum alkaline phosphatase (≤450 IU/L) (aOR = 2.10; p = 0.035), and who had surgery earlier (<115 days) (aOR = 2.28; p = 0.016) were more likely to have favourable necrosis. On 1:2 PSM analysis, patients not achieving favourable necrosis demonstrated inferior EFS (HR = 2.68; p = 0.003) and OS (HR = 3.42; p = 0.003). Patients of osteosarcoma with smaller tumor, lower serum alkaline phosphatase and earlier surgery are more likely to achieve favourable necrosis. Tumor necrosis independently predicts outcome in osteosarcoma, and response-adapted treatment escalation fails to overcome the adverse impact of poor necrosis in non-HDMTx based regimen. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]