Background Randomized controlled trials (RCT) of scalp cooling (SC) to prevent chemotherapy induced alopecia (CIA) did not evaluate its effect on hair regrowth (HR) and was conducted in a predominantly taxane (T) treated population. We conducted an RCT of SC in a setting of anthracycline (A) and taxane chemotherapy (CT) and assessed its effect on CIA and HR. Methods Non-metastatic breast cancer women undergoing (neo) adjuvant CT were randomized to receive SC using the Paxman scalp cooling system during every cycle of CT, or no SC. The primary end point (PEP) was successful hair preservation (HP) assessed clinically and by review of photographs after CT. HR was assessed at 6 and 12 weeks. Results 51 patients were randomized to SC (34) or control arm (17) in a 2:1 ratio. Twenty-five (49%) patients received A followed by T and the two arms were balanced with respect to this factor. HP rate was significantly higher in SC arm compared to control arm (56.3% vs 0%, P = 0.000004). HR was higher in SC arm compared to control at 6 weeks (89% vs 12%; P < 0.001) and 12 weeks (100% vs 59%, P = 0.0003). Loss of hair at PEP evaluation, which was a quality of life measure, was significantly lower in SC versus control arm (45% vs 82%, P = 0.016). There were no grade 3–4 cold related adverse effects. Conclusions Women with breast cancer receiving A or T chemotherapy receiving SC were significantly more likely to have less than 50% hair loss after CT, superior hair regrowth and improvement in patient reported outcomes, with acceptable tolerance. It merits wider usage.

Background: Pregnancy associated breast cancer (PABC) is a rare entity and defined as breast cancer diagnosed during pregnancy or one-year post-partum. There is sparse data especially from low and middle-income countries (LMIC) and merits exploration. Methods: The study (2013e2020) evaluated demographics, treatment patterns and outcomes of PABC. Results: There were 104 patients, median age of 31 years; 43 (41%) had triple-negative disease, 31(29.8%) had hormone-receptor (HR) positive and HER2 negative, 14 (13.5%) had HER2-positive and HR negative and 16(15.4%) had triple positive disease. 101(97%) had IDC grade III tumors and 74% had delayed diagnosis. 72% presented with early stage (24, EBC) or locally advanced breast cancer (53, LABC) and received either neoadjuvant (n ¼ 49) or adjuvant (n ¼ 26) chemotherapy and surgery. Trastuzumab, tamoxifen, and radiotherapy were administered post-delivery. At a median follow up of 27 (IQR:19e35) months, the estimated 3-year event-free survival (EFS) for EBC and LABC was 82% (95% CI: 65.2e100) and 56% (95% CI: 42e75.6%) and for metastatic 24% (95% CI: 10.1%e58.5%) respectively. Of the 104 patients, 34 were diagnosed antepartum (AP) and 15 had termination, 2 had preterm and 16 had full-term deliveries(FTDs). Among postpartum cohort (n ¼ 70), 2 had termination, 1 had preterm, 67 had FTDs. 83(including 17 from AP) children from both cohorts were experiencing normal milestones. Conclusion: Data from the first Indian PABC registry showed that the majority had delayed diagnosis and aggressive features(TNBC, higher grade). Treatment was feasible in majority and stage matched outcomes were comparable to non-PABCs.

Inhibitors are an impediment to the effective management of haemophilia B (HB), but there is limited understanding of the underlying genetic risk factors. In this study we aim to understand the role of F9 gene mutations on inhibitor development in patients with HB. Mutations in the F9 gene were identified and HLA typing performed for five boys with severe HB. Data from the CDC Haemophilia B Mutation Project (CHBMP) database were used to assess association between F9 gene mutation type and inhibitor development. Analysis of the CHBMP database showed that larger disruptions in the F9 gene are associated with a higher life-time prevalence of inhibitors. We detected the following mutations in the five subjects, including four novel mutations: Nonsense in three patients (c.223 C>T; p.Arg75* in two siblings, c.553 C>T; p.Glu185*); Splice site in two patients (c.723 + 1 G>A, c.278-27 A>G); Missense in one patient (c.580 A>G, p.Thr194Ala; c.723 G>T; p.Gln241His). Of the two siblings only one responded to immune tolerance induction (ITI). These siblings have identical F9 gene mutations but differ with respect to the HLA alleles. Interestingly, an analysis of peptide-MHC binding affinities shows a significantly higher (one-sided unpaired t-test, P = 0.0018) median affinity for FIX-derived peptides in the sibling that responded to ITI. We conclude that the nature of the F9 gene mutation may be an important risk factor for the development of inhibitors. In addition, the HLA alleles of the individual patients, in conjunction with the mutation type, could be a predictor for the development of inhibitors as well as the response to ITI.

Background: Outcome and toxicity data in adolescent-adult Ewing sarcoma (AA-ES) patients are sparse and merits exploration. Methods: Histopathologically confirmed, nonmetastatic AA-ES patients, who received standard institutional combination chemotherapy regimen (Ewing's family of tumors-2001 [EFT-2001]) comprising of ifosfamide plus etoposide and vincristine, doxorubicin plus cyclophosphamide, lasting a total of 12 months between 2013 and 2018, were analyzed for treatment-related toxicities, event-free survival (EFS), and overall survival (OS). Results: There were 235 patients (primary safety cohort [PSC]) with median age of 23 (15-61) years; 159 (67.7%) were males, 155 (65.9%) had skeletal primary and 114(48.5%) had extremity tumors. One hundred ninety-six (83.4%) were treatment naïve (primary efficacy cohort [PEC]) and of these 119 (60.7%) had surgery. In PEC, at a median follow-up of 36.4 (interquartile range [IQR] 20-55) months, estimated 3-year EFS and OS were 67.3% (95% CI 60.3-75.1%) and 91.1% (95% CI 86.7-95.7%), respectively. Of these, 158 (80.6%) complying with intended treatment, at a median followup of 39 (IQR 26-57) months had an estimated 3-year EFS of 68.2% (95% CI 60.3-76.1%). In multivariable analysis, good prognostic factors included longer symptom(s) duration (HR 0.93, 95% CI 0.86-0.994), ≥99% necrosis (HR 0.30, 95% CI 0.11-0.77), and treatment completion (HR 0.32, 95% CI 0.14-0.74). Among PSC, grade 3-4 toxicities were febrile neutropenia (119, 50.6%), anemia (130, 55.3%), peripheral neuropathy (37, 15.7%), with three (1.3%) chemo-toxic deaths. Conclusions:The outcomes of AA nonmetastatic ES patients treated with EFT-2001 regimen were comparable to those reported by others, with acceptable toxicity. This regimen can be considered a standard of care in AA-ES.