The COVID-19 pandemic has inspired us, as medical students, to reflect upon the communication training we have received in medical school and the obstacles we have faced in the clinic due to COVID-19. We hold the view that our communication training is inadequate; this view is driven by our limited exposure to patients, a situation that is currently being exacerbated by the pandemic. The medical curriculum must be inclusive of all groups and take into account the new challenges arising during the COVID-19 pandemic.
Background: Bendamustine rituximab (BR) is a frequently used chemoimmunotherapy for indolent lymphomas, including Waldenström macroglobulinemia (WM), a rare B-cell malignancy. The promising results of a small subset analysis (n= 41) of the Study group indolent Lymphomas (StiL) trial, demonstrating a median progression-free survival (PFS) of 69.5 months in the frontline setting served as the basis for widespread adoption of BR. Whether the more recently identified somatic mutations within the MYD88 and CXCR4 genes impact the outcomes of patients (pts) treated with BR remains less clear. Aims: To study a large cohort of BR-treated pts with active WM through an international, multicenter collaborative effort. Methods: Records of pts with newly diagnosed active WM who received BR between January 2012 and July 2021, in the US and Europe, were reviewed. The MYD88L265P and CXCR4 mutation status were captured, if available. All time-to-event analyses were performed from the frontline therapy initiation, using the Kaplan-Meier method. Results: Among 248 pts who were treated with BR, 208 pts received BR induction without rituximab maintenance, and were included in the primary analysis. The median age at treatment initiation was 65 (range 40-86) years; 64 % were males. The baseline characteristics are outlined in Table 1. The median follow-up was 4 (95% CI: 3.6-4.6) years. The estimated median PFS was 5.9 years [95% CI: 5.3-not reached (NR)]. The estimated 5-year overall survival (OS) rate was 90%. Among 174 pts evaluable for response, the overall response rate (ORR), major response rate (MRR) and very good partial response (VGPR) rates were 95%, 93% and 31%, respectively, per the modified IWWM-6 criteria based on serum IgM level alone. Pts with progression of disease (POD) within 24 months of BR therapy (11%) had an inferior subsequent survival compared to those without POD within 24 months, the reference group [5-year subsequent survival rate, 71 % versus (vs) 86%, p=0.02]. Among 131 (63%) pts with a known MYD88L265P status, 88% (n=116) had MYD88L265P genotype. The 4-year PFS was 71% for both pts with MYD88L265P and MYD88WT genotypes (p=0.44), Figure 1A. The VGPR rates were also comparable between the two groups (41% for MYD88L265P and 50% for MYD88WT genotypes, p=0.55). Among 42 (20%) pts with a known CXCR4 mutation status, 28% harbored a CXCR4 mutation. The ≥VGPR rate for pts with CXCR4MUT genotype was numerically lower; 33% vs 57% for those with CXCR4WT genotype, p=0.3. A trend towards shorter PFS among pts with CXCR4MUT genotype [estimated median PFS for 3.9 years (95% CI: 0.8-NR) vs 5.5 years (95% CI 5.3-NR) for pts with CXCR4WT genotype, p=0.05, Figure 1B] was observed. The PFS rates for pts without a known MYD88 or CXCR4 mutational status was comparable to their counterparts with known genotypes, respectively. Among 40 (16%) pts who had received rituximab maintenance following BR, the median age at initiation of therapy was 67 years (range 44-88). After 1:1 matching for age, the 4-year PFS for the rituximab maintenance group was 89% vs 73% for pts who did not receive rituximab maintenance (p=0.09); OS was comparable (5-year OS rate, 85% for both groups, p=0.99). Image:Summary/Conclusion: Fixed-duration BR is a highly effective regimen for pts with previously untreated symptomatic WM, irrespective of the MYD88L265P mutation status, although early POD, within 2 years of initiation of BR, is associated with inferior subsequent survival. Our preliminary analysis, suggesting that the presence of CXCR4 mutation confers resistance to BR, warrants confirmation in prospective studies.
7566 Background: Parenteral limited-duration BR chemoimmunotherapy and continuous orally administered Ibr, a Bruton tyrosine kinase inhibitor, dominate the treatment landscape of WM, a rare B cell lymphoma. No trials have assessed the comparative effectiveness of these 2 vastly different approaches. We conducted a multiinstitutional, international, collaborative study to compare BR and single-agent Ibr in patients (pts) with treatment naïve (TN) WM. Methods: Data from 347 pts with active TN WM, seen between 2011 and 2021 in the US and Europe, were analyzed. The pts on rituximab maintenance were excluded. The modified IWWM-6 criteria (based on IgM alone) were used for response assessment. All time-to-event analyses were performed from the frontline therapy initiation, using the Kaplan-Meier method. Results: The median age of the pts treated with BR (n=208) and Ibr (n=139) was 66 (range 40-86) years (y) and 69 (39-97) y, respectively, (p=0.005). With a median follow up of 4.2 y (95% CI 3.8-4.5), the 4-y progression free survival (PFS) was 73% in each group, p=0.6, and 4-y overall survival (OS) was 94% (95% CI 91-98) in the BR group versus ( v) 82% (95% CI 75-90) in the Ibr group, p=0.01. In a bivariate analysis adjusting for age and the treatment type, only age emerged as a predictor for OS (HR 7.2, p=0.0001). Therefore, a 1:1 age-matched analysis of 246 pts who received Ibr (n=123) or BR (n=123) was performed. Pts with a known MYD88 WT status who had received Ibr and their age matched controls on BR were excluded. The international prognostic scoring system (IPSS) WM was comparable between the 2 groups (Table). A higher proportion of pts on BR attained very good partial or deeper response (≥VGPR) as the best response in comparison to the pts on Ibr (Table). The 4-y PFS for the BR and Ibr groups was similar [72% (95% CI 63-82) v 78% (95% CI 70-87), p=0.14] and 4-y OS was 95% (95% CI 91-99) with BR v 86% (95% CI 80-93) with Ibr (p=0.3). Premature discontinuation, during active treatment, due to adverse effects (AEs) or lack of response was noted in 13% and 33% of pts on BR and Ibr, respectively. A detailed assessment of the AEs will be presented at the meeting. Conclusions: Both BR and Ibr lead to comparable outcomes in pts with TN WM, although deeper responses are attained with BR. These findings require confirmation in prospective studies. For pts who harbor MYD 88 L265P mutation, selection between the 2 approaches should be dictated by their potential toxicities, pt comorbidities, pt/clinician preference (parenteral fixed-duration v continuous oral) and access to therapies. [Table: see text]
Neuroblastoma-associated renal cell carcinoma (RCC) is a very rare subtype of renal neoplasia and only a handful of cases have been reported. Here we present a 15-year-old boy with metastatic RCC with a previous history of advanced stage neuroblastoma and germline mutation in the TP53 tumor suppressor gene. The probability of the RCC and indeed, the neuroblastoma itself being related to a cancer predisposition syndrome rather than a therapy induced second malignancy, is discussed.
The number of patients desiring fertility-preserving treatment for endometrial cancer rather than standard surgical management continues to increase.We aimed to evaluate the efficacies of fertility-preserving treatments on the live birth rate, remission and relapse rates for women with stage 1a grade 1 endometrial carcinoma to support patient counselling.We performed a meta-analysis for our primary outcomes of overall remission and relapse rate, and for secondary analysis, we divided papers into treatment type: systemic progestins, intrauterine progestins or hysteroscopic resection and adjuvant hormonal treatment.Thirty-five observational studies met inclusion criteria, with a total of 624 patients. Overall, conservative treatment of endometrial cancer showed a remission rate of 77% (95% CI: 70-84%), a relapse rate of 20% (95% CI: 13-27%) and a live birth rate of 20% (95% CI: 15-25%) with more favourable outcomes for the hysteroscopic resection group.Hysteroscopic resection and adjuvant hormonal treatment had the most favourable fertility and oncological outcomes. Further high-quality prospective multi-centre trials are warranted to determine the optimal treatment regimen and dosage and risk stratification for these patients.The number of women diagnosed with womb cancer who want to preserve their fertility is increasing. Traditional treatment involves surgery to remove the womb and ovaries, rendering women infertile. Fertility-preserving treatments (e.g. hormone therapy, removing only affected areas) exist but their impact on remission, relapse and fertility is not certain. Our team discovered that for women who underwent fertility-preserving treatment: three in four had cancer remission, one in five had cancer relapse and one in five had a successful birth. More research is needed to work out the best fertility-preserving treatment and identify which women are more likely to have successful pregnancies.Overall, our research will help to counsel women diagnosed with womb cancer who want to preserve their fertility or are unsuitable for major surgery more effectively.
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