Evaluation of Ki-67 expression and large cell content as prognostic markers in MZL: a multicenter cohort study.

Marginal zone lymphoma (MZL) can have varied presentations and pathologic features, including high Ki-67 expression ( > 20%) as well as increased numbers of large B cells (LC). However, there are limited data available demonstrating the prognostic significance of these variables in patients with MZL. In this multi-institutional retrospective cohort study of patients with MZL treated at 10 centers, we evaluated the association between the presence of Ki-67 expression and increased LCs on survival and risk of histologic transformation (HT). A total of 785 patients were included (60% with extranodal MZL, 20% with nodal MZL, and 20% with splenic MZL). Among the 440 patients with Ki-67 staining, 22% had high Ki-67 (Ki-67 >20%). The median progression-free survival (PFS) for patients with high Ki-67 was 5.4 years compared to 7.0 years for patients with low Ki-67 (HR = 1.45, 95%CI = 1.03-2.05). Ki-67 > 20% strongly correlated with high LDH level. The risk of HT was higher in patients with increased Ki-67 than those without (5-year risk, 9.8% vs 3.87%, p = 0.01). Twelve percent of patients had LC reported on biopsy with 6% having >10% LC. The presence of LC was associated with high Ki-67 (p < 0.001), but not associated with shorter PFS or overall survival (OS). The cumulative risk for HT was higher in patients with LC compared to those without LC (5-year risk, 9.4% vs 2.9%, p = 0.04). Receipt of anthracycline-based therapy did not impact PFS or OS in either group. Ki-67 staining >20% was a prognostic factor for worse survival and strongly correlated with elevated LDH. Novel therapies should be investigated for their potential ability to overcome the high-risk features in MZL. Our data reinforce the importance of obtaining biopsies at relapse or progression, particularly in patients with baseline high Ki-67 and increased LCs, given their increased risk for HT.

"A safe, non-judgmental space where I can really challenge myself:" learner experiences in a virtual, case-based diagnostic reasoning conference for students.

Case-based diagnostic reasoning conferences, like morning reports, allow undergraduate medical trainees to practice diagnostic reasoning alongside senior clinicians. However, trainees have reported discomfort doing so. Peer-assisted learning offers an alternative approach. We describe the design, implementation, and evaluation of a virtual, student-only diagnostic reasoning conference that leverages peer-assisted learning. Student virtual morning report's (VMR) design was informed by social and cognitive congruence and experience-based learning. We evaluated participant experiences using a survey focused on participant perceptions of Student VMR's value, their methods for participation, and their preferences for Student VMR compared with VMR with more senior clinicians. 110 participants (28.9%) completed the survey. 90 participants (81.2%) reported that Student VMR was educational. Compared to VMR, participants reported being more likely to participate in Student VMR by turning on their video (50.0%), presenting a case (43.6%), verbally participating (44.5%), or participating in the chat (70.0%). Strengths included a safe learning environment to practice DR and the opportunity to engage with an international learning community. When asked whether they preferred Student VMR or non-Student VMR, most respondents (64.5%, 71/110) identified that they did not have a preference between the two. A student-focused DR conference may offer a valuable complement to, but not a replacement of, apprenticeship-based DR case conferences.

Online description of services provided in adult survivorship programs across U.S. accredited cancer centers.

PURPOSE: The American College of Surgeons Standard 4.8 requires an institution to implement a survivorship program to become a Commission on Cancer (CoC)-accredited cancer center. The online information offered by these cancer centers can help educate patients and their caregivers about available services. We assessed the content of survivorship program websites of CoC-accredited cancer centers in the United States. METHODS: Of the 1245 CoC-accredited centers for adults, we sampled 325 institutions (26%) based proportionately on the 2019 new cancer cases by state. Website pages of the institutions' survivorship programs were assessed for information and services offered using the COC Standard 4.8. We included programs for adult survivors of adult- and childhood-onset cancers. RESULTS: 54.5% of the cancer centers did not have a survivorship program website. Of the 189 included programs, most were aimed at adult survivors in general, rather than those with specific cancer types. On average, five essential CoC-recommended services were described, most commonly nutrition, care plans, and psychology services. The least mentioned services were genetic counseling, fertility, and smoking cessation. Most programs described services offered to patients who had completed treatment, while 7.4% of described services for those with metastatic disease. CONCLUSION: More than half of CoC-accredited programs did have information about cancer survivorship programs on their websites and when included, had variable and limited description of services. IMPLICATIONS FOR CANCER SURVIVORS: Our study provides an overview of online cancer survivorship services and offers a methodology that may be used by cancer centers to review, expand, and improve the information described on their websites.

Integrative analysis of clinicopathological features defines novel prognostic models for mantle cell lymphoma in the immunochemotherapy era: a report from The North American Mantle Cell Lymphoma Consortium.

BACKGROUND: Patients with mantle cell lymphoma (MCL) exhibit a wide variation in clinical presentation and outcome. However, the commonly used prognostic models are outdated and inadequate to address the needs of the current multidisciplinary management of this disease. This study aims to investigate the clinical and pathological features of MCL in the immunochemotherapy era and improve the prognostic models for a more accurate prediction of patient outcomes. METHODS: The North American Mantle Cell Lymphoma Project is a multi-institutional collaboration of 23 institutions across North America to evaluate and refine prognosticators for front-line therapy. A total of 586 MCL cases diagnosed between 2000 and 2012 are included in this study. A comprehensive retrospective analysis was performed on the clinicopathological features, treatment approaches, and outcomes of these cases. The establishment of novel prognostic models was based on in-depth examination of baseline parameters, and subsequent validation in an independent cohort of MCL cases. RESULTS: In front-line strategies, the use of hematopoietic stem cell transplantation was the most significant parameter affecting outcomes, for both overall survival (OS, p < 0.0001) and progression-free survival (PFS, p < 0.0001). P53 positive expression was the most significant pathological parameter correlating with inferior outcomes (p < 0.0001 for OS and p = 0.0021 for PFS). Based on the baseline risk factor profile, we developed a set of prognostic models incorporating clinical, laboratory, and pathological parameters that are specifically tailored for various applications. These models, when tested in the validation cohort, exhibited strong predictive power for survival and showed a stratification resembling the training cohort. CONCLUSIONS: The outcome of patients with MCL has markedly improved over the past two decades, and further enhancement is anticipated with the evolution of clinical management. The innovative prognostic models developed in this study would serve as a valuable tool to guide the selection of more suitable treatment strategies for patients with MCL.

The Democratization of Hematology-Oncology Medical Education during the COVID-19 Pandemic.

Like many other aspects of hematology-oncology training, medical education experienced rapid changes throughout the COVID-19 pandemic that continue until today. We discuss some of the most transformative areas within medical education, including, but not limited to, educational philosophy; use of virtual resources; inter-institutional connections, shifts in clinical training; changes in recruitment practice; and attention to equity and diversity. Moreover, we add our own experiences to complement the limited literature addressing these topics. We conclude by highlighting some of the benefits of this unprecedented transformation in democratizing medical education that we hope endure beyond the pandemic.

Impact of detectable monoclonal protein at diagnosis on outcomes in marginal zone lymphoma: a multicenter cohort study.

Given the paucity of data surrounding the prognostic relevance of monoclonal paraprotein (M-protein) in marginal zone lymphoma (MZL), we sought to evaluate the impact of detecting M-protein at diagnosis on outcomes in patients with MZL in a large retrospective cohort. The study included 547 patients receiving first-line therapy for MZL. M-protein was detectable at diagnosis in 173 (32%) patients. There was no significant difference in the time from diagnosis to initiation of any therapy (systemic and local) between the M-protein and no M-protein groups. Patients with M-protein at diagnosis had significantly inferior progression-free survival (PFS) compared with those without M-protein at diagnosis. After adjusting for factors associated with inferior PFS in univariate models, presence of M-protein remained significantly associated with inferior PFS (hazard ratio, 1.74; 95% confidence interval, 1.20-2.54; P = .004). We observed no significant difference in the PFS based on the type or quantity of M-protein at diagnosis. There were differential outcomes in PFS based on the first-line therapy in patients with M-protein at diagnosis, in that, those receiving immunochemotherapy had better outcomes compared with those receiving rituximab monotherapy. The cumulative incidence of relapse in stage 1 disease among the recipients of local therapy was higher in the presence of M-protein; however, this did not reach statistical significance. We found that M-protein at diagnosis was associated with a higher risk of histologic transformation. Because the PFS difference related to presence of M-protein was not observed in patients receiving bendamustine and rituximab, immunochemotherapy may be a preferred approach over rituximab monotherapy in this group and needs to be explored further.

Impact of early relapse within 24 months after first-line systemic therapy (POD24) on outcomes in patients with marginal zone lymphoma: A US multisite study.

Progression of disease within 24 months (POD24) from diagnosis in marginal zone lymphoma (MZL) was shown to portend poor outcomes in prior studies. However, many patients with MZL do not require immediate therapy, and the time from diagnosis-to-treatment interval can be highly variable with no universal criteria to initiate systemic therapy. Hence, we sought to evaluate the prognostic relevance of early relapse or progression within 24 months from systemic therapy initiation in a large US cohort. The primary objective was to evaluate the overall survival (OS) in the two groups. The secondary objective included the evaluation of factors predictive of POD24 and the assessment of cumulative incidence of histologic transformation (HT) in POD24 versus non-POD24 groups. The study included 524 patients with 143 (27%) in POD24 and 381 (73%) in non-POD24 groups. Patients with POD24 had inferior OS compared to those without POD24, regardless of the type of systemic therapy received (rituximab monotherapy or immunochemotherapy) at diagnosis. After adjusting for factors associated with inferior OS in the univariate Cox model, POD24 remained associated with significantly inferior OS (HR = 2.50, 95% CI = 1.53-4.09, p = 0.0003) in multivariable analysis. The presence of monoclonal protein at diagnosis and those who received first-line rituximab monotherapy had higher odds of POD24 on logistic regression analysis. Patients with POD24 had a significantly higher risk for HT compared to those without POD24. POD24 in MZL might be associated with adverse biology and could be used as an additional information point in clinical trials and investigated as a marker for worse prognosis.

Health Disparities Experienced by Hispanic Americans with Multiple Myeloma: A Systematic Review.

Health disparities in multiple myeloma (MM) disproportionately affect minorities. Characterization of health disparities encountered by Hispanic Americans with MM is necessary to identify gaps and inform future strategies to eliminate them. We performed a systematic review of publications that described health disparities relevant to Hispanic Americans with MM through December 2021. We included all original studies which compared incidence, treatment, and/or outcomes of Hispanic Americans with other ethnic groups. Eight hundred and sixty-eight articles were identified of which 22 original study articles were included in our systematic review. The number of publications varied over time with the highest number of studies (32%) published in 2021. Most of the published studies (59%) reported worse outcomes for Hispanic Americans with MM compared to other ethnic groups. There is growing evidence that Hispanic Americans with MM are facing a multitude of disparities that require immediate attention and solutions.

Carfilzomib combined with rituximab, ifosfamide, carboplatin, and etoposide for relapsed or refractory DLBCL.

The CORAL study highlighted the need to develop novel salvage regimens in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) previously treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. Carfilzomib (CFZ) can overcome rituximab chemotherapy resistance in lymphoma preclinical models by targeting the ubiquitin-proteasome system. We conducted an investigator initiated, single-center, open-label, prospective phase 1 study evaluating the safety and efficacy of CFZ in combination with rituximab, ifosfamide, carboplatin, and etoposide (C-R-ICE) in high-dose chemotherapy with autologous stem cell transplant (HDC-ASCT) eligible patients with R/R DLBCL (NCT01959698). In the dose-escalation phase, 18 patients were enrolled at 6 dose levels with no dose-limiting toxicities noted. CFZ 45 mg/m2 was selected as the recommended dose for expansion. Eleven additional patients were enrolled in the dose-expansion phase. Overall response rate (ORR) was 66% (48% CR; 17% PR); 52% patients underwent HDC-ASCT. An ORR of 85% was observed in patients with nongerminal center B-cell-like (non-GCB) DLBCL compared with only 13% in those with GCB DLBCL. Median progression-free survival (PFS) was 15.2 months (5.1 months, not reached [NR]), and median overall survival (OS) was 22.6 months (6.8 months, NR). Patients with non-GCB subtype had a significantly longer PFS (NR vs 6.6 months; P = .0001) and OS (NR vs 6.6 months; P = .001) than those with GCB subtype. C-R-ICE is well tolerated in patients with R/R DLBCL with toxicities comparable to rituximab, ifosfamide, carboplatin, and etoposide therapy. Our data show that patients with non-GCB DLBCL benefit significantly from incorporating CFZ into second-line therapy and HDC-ASCT.

The Rise of the Expert Patient in Cancer: From Backseat Passenger to Co-navigator.

PURPOSE: Patients who have cancer have leveraged the Internet to gain a better understanding of their disease and connect across geographic boundaries with others facing the same challenges. Online cancer communities have developed into resources that highlight new research and evolving care pathways. Combined with increasing health literacy and social media, they have enabled some patients to become experts in their cancer. This combination of empowerment and expertise describes the new "e-patients." METHODS: We reviewed the literature to identify key areas where expert e-patients have directly participated in advancing cancer medicine, as well as opportunities available to those who wish to become more involved in research advocacy. RESULTS: E-patients are widely acknowledged as key stakeholders in oncology by clinicians, researchers, cancer centers, government agencies, and nonprofits. Their input is vital for informing cancer care delivery, developing and launching research initiatives, creating care guidelines and pathways, and formulating policy. CONCLUSION: Expert e-patients play an expanded role in their own care and in larger conversations regarding practice, research, and policy. Clinicians can engage e-patients as partners in cancer care as we work together towards improving health care access and outcomes for people with cancer.

ASCO-Sponsored Oncology Student Interest Groups in the World.

PURPOSE: In 2015, ASCO established a program designed to support medical interest in cancer-related careers: Oncology Student Interest Groups (OSIGs). The purpose of this study was to describe the characteristics of current student leaders of ASCO-sponsored OSIGs and their perceptions of cancer-related careers. METHODS: We reviewed the list of all ASCO-sponsored OSIGs between 2015 and 2021. For this study, we focused on OSIGs that were sponsored during the 2019-2020 academic year. All student leaders of the 89 OSIGs active in that academic year were invited to participate. RESULTS: The number of groups has more than tripled in the 6 years since the program's inception. The number of international groups has increased to become almost one fifth of all OSIGs; however, the range of countries represented remains limited. The majority of OSIG leaders were female. Eighty two percent of OSIGs were returning members, with most of their leaders being registered ASCO student members. Almost all participants reported an interest in pursuing a cancer-related specialty. Only a minority (14.8%) reported having a family member working in a cancer-related career. However, 85% reported having experience with a cancer diagnosis in their family. The majority of the respondents had a favorable perception of medical oncology as a specialty. Participants reported the highest levels of interest in medical oncology and pediatric oncology. CONCLUSION: The number of ASCO-sponsored OSIGs has steadily increased since the creation of the program. Most participants reported an interest in pursuing a cancer-related career. To our knowledge, this study is the first to provide insights into the makeup of this program around the world. Additional efforts are needed to increase the global reach of the program, particularly in low-income countries.

Cancer Survivorship in Latin America: Current Status and Opportunities.

PURPOSE: The number of cancer survivors is increasing globally although the status of cancer survivorship care provision and research in developing countries is limited. This study aimed to review published literature and available guidelines and/or recommendations to inform cancer survivorship care in Latin America. METHODS: Embase, Web of Science, Scopus, PubMed, and SciELO were systematically searched for articles and guidelines and/or recommendations published through December 31, 2020. Our search terms included cancer, survivors, neoplasm, cancer, survivorship, survivor, follow-up studies, and the name of the countries. We categorized the articles by country, year, cancer type(s), language, and domain of cancer survivorship care. We also searched governmental health agencies websites in all Latin American countries. RESULTS: Our literature review found 664 articles for inclusion. The number of publications increased over time. Brazil had most of the survivorship research (n = 483, 72.7%). The most common topics included surveillance and management of psychosocial effects (n = 237, 35.7%) and physical effects (n = 230, 34.6%). Prevention and surveillance for recurrences and health promotion and disease prevention were each addressed by about 10% (n = 71) of the publications. Although close to half of the publications included more than one cancer, 28.9% (n = 192) focused solely on breast cancer. We found no guidelines and/or recommendations explicitly focusing on Latin America in the reviews of the literature or the national governmental institutions' websites. CONCLUSION: We found a growing body of cancer survivorship publications, mainly focusing on psychosocial and physical effects, although no cancer survivorship guidance and/or recommendations focused on Latin America were identified. Expanding research across Latin American countries and covering a broader spectrum of cancer survivorship care is needed. Development of guidelines may further promote provision of quality care for this growing population of cancer survivors.

The Matilda Effect: Underrecognition of Women in Hematology and Oncology Awards.

BACKGROUND: The proportion of women in the field of hematology and oncology (H&O) has increased over recent decades, but the representation of women in leadership positions remains poor. In an effort to close the gender gap in academia, it is important to report on such inequities in hopes to close these gaps and improve career development. MATERIALS AND METHODS: We conducted a retrospective, observational study of published award recipients from 1994 to 2019 from the seven major H&O societies in the world. Gender was determined based on publicly available data. The χ2 and Cochran-Armitage tests were used for data analysis. RESULTS: Of the 1,642 awardees over the past 26 years, 915 met inclusion criteria. Award recipients were overwhelmingly men (77.9%) and non-Hispanic White (84.7%). Women awardees received 30.3% of the humanistic and education-related awards, whereas only receiving 16.0% of basic science awards (p < .01). Women represent 35.6% of all hematologists and oncologists but only received 24.0% of awards given to these physicians (p = .004). Black, Hispanic, and Asian awardees represented 3.7%, 3.3%, and 6.8% of the total awardees, respectively. CONCLUSION: From 1994 to 2019, women were less likely to receive recognition awards from the seven major H&O societies studied compared with men. We also observed a considerably low proportion of minority awardees across all oncology subspecialties. Further studies examining how selection criteria favor either gender would be warranted in order to achieve equal representation in academic awards. IMPLICATIONS FOR PRACTICE: In this study, women and minority groups were found to be underrepresented amongst award recipients. Significant disparities were seen in disciplines that have been historically male predominant, such as basic sciences. As awards on an international level enhance academic resumes and assist with career advancement, it is important that awards are being given in an equitable manner. First steps to promote diversity and inclusion in academic medicine is reporting of gender and racial disparities in various areas of academia.

American Society of Clinical Oncology-Sponsored Oncology Student Interest Groups in Latin America.

PURPOSE: To describe the characteristics of the members of the ASCO-sponsored Oncology Student Interest Groups (OSIGs) in Latin America. METHODS: This was a multicenter cross-sectional study. We surveyed 97 OSIG members from three medical schools in Peru and Mexico. We administered a 60-question survey covering topics including personal background, oncology training experience, and professional practice expectations and preferences. RESULTS: A little more than one half of the surveyed OSIG members were female. More than one half had a visa to visit the United States and had an advanced level of English. One half of the OSIG members were also ASCO members. Most participants agreed or strongly agreed that participation in their OSIG increased their interest in cancer-related specialties (94%) and provided professional networking opportunities (94%) and that it was accessible to all students (91%). Most participants believed that their OSIG had sufficient resources to carry out its activities. Students were asked to rate their interest when they entered medical school versus at the time of the survey. Most of the members were strongly interested in pursuing surgical oncology. The majority of members were somewhat interested or very interested in palliative care and medical oncology. CONCLUSION: To our knowledge, this is the first study that provides data on medical student perceptions of the Latin American OSIGs sponsored by ASCO. Student perceptions of medical oncology and the impact of OSIGs were generally positive. Given the shortages of oncology specialists in Latin American and elsewhere, strategies to engage medical students in the pursuit of cancer-related careers are becoming increasingly essential.

Epstein-Barr Virus Infection-associated Hemophagocytic Lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening syndrome characterized by uncontrolled immune activation. There is an aberrant activation of lym-phocytes and macrophages that results in hypercytokinemia. We aim to describe a case of secondary HLH due to primary Epstein-Barr virus (EBV) infection. A Hispanic 28-year-old man presented with sore throat and fatigue for one week. He was diagnosed with mononucleosis and discharged and was treated according to the currently available treatment. HLH is treated by diminishing the inflammation by myelosuppressive and immunosuppressive therapy. EBV infection-associated HLH is a rare disease with high mortality. It is crucial to think about it when facing a patient with fever, cytopenia, hepatosplenomegaly, and high levels of ferritin. Despite medical treatment, the patient died from multiorgan failure.

Erdheim-Chester Disease With Extensive Pericardial Involvement: A Case Report and Systematic Review.

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis characterized by systemic xanthogranulomatous infiltration. We described the case of a female adult presenting with pericardial effusion. Pericardial infiltration is the most frequent cardiac manifestation of ECD and is the one discussed in this article. We found that the majority of patients with pericardial infiltration needed a cardiovascular procedure.

Aorto-cavitary fistula to the left ventricle with severe aortic regurgitation as a complication of prosthetic valve infective endocarditis: a novel report.

Infective endocarditis can present in different clinical forms and lead to a variety of complications depending on the affected valvular and perivalvular structures. We describe a case of a 74-year-old male who developed an aortic-cavitary fistulous tract as a complication of prosthetic aortic valve infective endocarditis. Transesophageal echocardiography (TEE) revealed an aorto-cavitary fistula (ACF) connecting the aortic root with the left ventricle, creating an intracardiac shunt, which resulted in severe aortic regurgitation physiology. The patient underwent surgery with successful exclusion of the ACF. ACF is an unusual complication of infective endocarditis that creates an abnormal communication between the aortic root and the heart chambers, establishing an intracardiac shunt. This case highlights that physicians should be aware of the possibility of rare cardiac complications in infective endocarditis. TEE is a valid diagnostic test for ACF.