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Danielle S. Graham, Mykola Onyshchenko, Mark A. Eckardt, Benjamin J. DiPardo, Sriram Venigalla, Scott D. Nelson, Bartosz Chmielowski, Arun S. Singh, Jacob E. Shabason, Fritz C. Eilber and Anusha Kalbasi

Background: There is conflicting evidence regarding the role of chemotherapy for high-grade soft tissue sarcoma (STS) in adults. We sought to characterize patterns of chemotherapy use, including multiagent and neoadjuvant chemotherapy, in the United States. Patients and Methods: Using the National Cancer Database, we identified 19,969 adult patients who underwent surgical resection for primary high-grade STS from 2004 to 2016. Using logistic regression, we examined factors associated with overall, multiagent, and neoadjuvant chemotherapy use. Results: Chemotherapy was administered to 22% (n=4,377) of the study population. Among patients treated using chemotherapy, 85% received multiagent treatment and 47% received neoadjuvant treatment. On multivariate analysis, factors associated with chemotherapy use included tumor size, depth, histology, and primary site; receipt of radiation treatment; younger age; higher patient income; and academic treatment facility. Factors associated with multiagent chemotherapy use included tumor histology, tumor primary site, and younger age. Factors associated with neoadjuvant chemotherapy use included tumor size, depth, margin status, and primary site; receipt of radiation treatment; higher patient income; academic treatment facility type; and distance to treatment facility. Treatment at a high-volume facility was the only factor associated with overall, multiagent, and neoadjuvant chemotherapy use. No significant temporal trend was seen in overall, multiagent, or neoadjuvant chemotherapy use. Conclusions: Overall chemotherapy use was low (22%). The variability in chemotherapy use was driven by clinical, patient, demographic, and facility factors. Among patients treated with chemotherapy, the use of multiagent chemotherapy was high (85%), and nearly half received neoadjuvant therapy. There was a discrepancy in the use of chemotherapy—including neoadjuvant and multiagent chemotherapy—between high- and low-volume treatment centers.

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NCCN Guidelines Insights: Survivorship, Version 2.2020

Featured Updates to the NCCN Guidelines

Crystal S. Denlinger, Tara Sanft, Javid J. Moslehi, Linda Overholser, Saro Armenian, K. Scott Baker, Gregory Broderick, Wendy Demark-Wahnefried, Debra L. Friedman, Mindy Goldman, Norah Lynn Henry, Christine Hill-Kayser, Melissa Hudson, Nazanin Khakpour, Divya Koura, Allison L. McDonough, Michelle Melisko, Kathi Mooney, Halle C. F. Moore, Natalie Moryl, Tracey O’Connor, Electra D. Paskett, Chirayu Patel, Lindsay Peterson, William Pirl, M. Alma Rodriguez, Kathryn J. Ruddy, Lillie Shockney, Sophia Smith, Karen L. Syrjala, Amye Tevaarwerk, Phyllis Zee, Nicole R. McMillian and Deborah A. Freedman-Cass

The NCCN Guidelines for Survivorship provide screening, evaluation, and treatment recommendations for consequences of adult-onset cancer and its treatment, with the goal of helping healthcare professionals who work with survivors, including those in primary care. The guidelines also provide recommendations to help clinicians promote physical activity, weight management, and proper immunizations in survivors and facilitate care coordination to ensure that all of the survivors’ needs are addressed. These NCCN Guidelines Insights summarize additions and changes made to the guidelines in 2020 regarding cardiovascular disease risk assessment and screening for subsequent primary malignancies.

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Paul D. Harker-Murray, Lauren Pommert and Matthew J. Barth

Burkitt lymphoma, diffuse large B-cell lymphoma (DLBCL), and primary mediastinal B-cell lymphoma are the most common aggressive pediatric mature B-cell non-Hodgkin lymphomas (B-NHLs). Despite excellent survival with current chemotherapy regimens, therapy for Burkitt lymphoma and DLBCL has a high incidence of short- and long-term toxicities. Patients who experience relapse generally have a very poor prognosis. Therefore, novel approaches using targeted therapies to reduce toxicities and improve outcomes in the relapse setting are needed. The addition of rituximab, a monoclonal antibody against CD20, to upfront therapy has improved survival outcomes for high-risk patients and may allow decreased total chemotherapy in those with low-risk disease. Antibody–drug conjugates have been combined with chemotherapy in relapsed/refractory (R/R) NHL, and multiple antibody–drug conjugates are in development. Additionally, bispecific T-cell–engaging antibody constructs and autologous CAR T-cells have been successful in the treatment of R/R acute leukemias and are now being applied to R/R B-NHL with some successes. PD-L1 and PD-L2 on tumor cells can be targeted with checkpoint inhibitors, which restore T-cell–mediated immunity and antitumor responses and can be added to conventional chemotherapy and immune-directed therapies to augment responses. Lastly, trials of small molecule inhibitors targeting cell signaling pathways in NHL subtypes are underway. This article reviews many of the targeted therapies under development that could be considered for future trials in R/R pediatric mature B-NHL.

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Kimberly Davies, Matthew Barth, Saro Armenian, Anthony N. Audino, Phillip Barnette, Branko Cuglievan, Hilda Ding, James B. Ford, Paul J. Galardy, Rebecca Gardner, Rabi Hanna, Robert Hayashi, Alexandra E. Kovach, Andrea Judit Machnitz, Kelly W. Maloney, Lianna Marks, Kristin Page, Anne F. Reilly, Joanna L. Weinstein, Ana C. Xavier, Nicole R. McMillian and Deborah A. Freedman-Cass

Pediatric aggressive mature B-cell lymphomas are the most common types of non-Hodgkin lymphoma in children, and they include Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL). These diseases are highly aggressive but curable, the treatment is complex, and patients may have many complicated supportive care issues. The NCCN Guidelines for Pediatric Aggressive Mature B-Cell Lymphomas provide guidance regarding pathology and diagnosis, staging, initial treatment, disease reassessment, surveillance, therapy for relapsed/refractory disease, and supportive care for clinicians who treat sporadic pediatric BL and DLBCL.

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Michelle Guan, Gillian Gresham, Arvind Shinde, Isaac Lapite, Jun Gong, Veronica R. Placencio-Hickok, Christopher B. Forrest and Andrew E. Hendifar

Background: Pancreatic ductal adenocarcinoma (PDAC) is associated with high symptom burden. However, treatment decisions currently depend heavily on physician interpretation of clinical parameters and may not consider patients’ health preferences. The NIH Patient-Reported Outcomes Measurement Information System (PROMIS) initiative standardized a set of patient-reported outcomes for use in chronic diseases. This study identifies preference rankings among patients with PDAC and physicians for PROMIS domains and compares the priorities of patients and their providers. Methods: We condensed the 96 NIH PROMIS adult domains into 31 domains and created a Maximum Difference Scaling questionnaire. Domain preference scores were generated from the responses of patients with PDAC and physicians, which were compared using Maximum Difference Scaling software across demographic and clinical variables. Results: Participants included 135 patients with PDAC (53% male; median age, 68 years) and 54 physicians (76% male; median years of experience, 10). Patients selected physical functioning (PF) as their top priority, whereas physicians identified pain as most important. PF, ability to perform activities of daily living, and symptom management were within the top 5 domains for both patients and physicians, and varied only slightly across age, sex, and ethnicity. However, several domains were ranked significantly higher by patients than by physicians, including but not limited to PF; ability to do things for yourself, family, and friends; ability to interact with others to obtain help; and sleep quality. Physicians ranked pain, anxiety, and depression higher than patients did. Conclusions: Our findings suggest that patients with PDAC value PF and engaging in daily and social activities the most, whereas physicians prioritize symptoms such as pain. Patient-reported outcomes need to become more integrated into PDAC care and research to better identify unmet patient needs, inform treatment decisions, and develop therapies that address outcomes valued by patients.

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Christina Signorelli, Claire E. Wakefield, Karen A. Johnston, Joanna E. Fardell, Jordana K McLoone, Mary-Ellen E. Brierley, Maria Schaffer, Elysia Thornton-Benko, Afaf Girgis, W. Hamish Wallace, Richard J. Cohn and on behalf of the BSU Implementation Group

Background: Survivors of childhood cancer often experience treatment-related chronic health conditions. Survivorship care improves survivors’ physical and mental health, yet many are disengaged from care. Innovative models of care are necessary to overcome patient-reported barriers to accessing survivorship care and to maximize survivors’ health. Methods: We piloted a novel survivorship program, called “Re-engage,” a distance-delivered, nurse-led intervention aiming to engage, educate, and empower survivors not receiving any cancer-related care. Re-engage involves a nurse-led consultation delivered via telephone/online to establish survivors’ medical history and needs. Participants completed questionnaires at baseline, 1 month postintervention, and 6-month follow-up. Results: A total of 27 survivors who had not accessed survivorship care in the last 2 years participated (median age, 31 years; interquartile range [IQR], 27–39 years); of which, 82% were at high-risk for treatment-related complications. Participation in Re-engage was high (75%) and there was no attrition once survivors enrolled. At 1 month postintervention, 92% of survivors reported that Re-engage was “beneficial,” which all survivors reported at 6-month follow-up. Survivors’ overall satisfaction with their care increased from 52% before Re-engage to 84% at 1 month postintervention. Survivors’ mean self-efficacy scores remained similar from baseline to 1 month postintervention (b = −0.33, 95% CI, −1.31 to 0.65), but increased significantly from baseline to 6-month follow-up (b = 1.64, 95% CI, 0.28–3.00). At 6-month follow-up, 73% of survivors showed an increase in health-related self-efficacy compared with baseline. Conclusions: Re-engage is a highly acceptable and feasible intervention and promotes health-related self-efficacy, which is integral to survivors being advocates for their own health. Further empirical work is needed to evaluate the long-term efficacy of Re-engage.

Trial registration: ACTRN12618000194268

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Katherine Cotangco, Mary Meram and M. Patrick Lowe

The estimated 5-year survival rate for patients with stage IV uterine leiomyosarcoma is 29%, with a median survival of <1 year. This report describes a patient with stage IVB leiomyosarcoma who experienced stable disease for 15 months on pembrolizumab. A woman aged 62 years, gravida 2 para 2, with postmenopausal bleeding and a necrotic uterine fibroid underwent a dilation and curettage and was diagnosed with uterine leiomyosarcoma. CT imaging showed pulmonary and bony metastasis. She underwent surgical staging with biopsy-proved stage IVB disease. A mixed partial response was noted using first- and second-line chemotherapy. Molecular tumor profiling confirmed PD-L1 expression. The patient was started on pembrolizumab, and at the time of writing she is status post 23 cycles with stable disease. Pembrolizumab was well tolerated and aided prolonged disease stabilization.

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Alexandra K. Zaleta, Melissa F. Miller, Julie S. Olson, Eva Y.N. Yuen, Thomas W. LeBlanc, Craig E. Cole, Shauna McManus and Joanne S. Buzaglo

Background: New therapies for multiple myeloma (MM) have improved survival rates but often expose patients to heightened toxicities and prolonged treatment, leading to increasing complications and side effects. We evaluated the association between symptom burden, perceived control over illness, and quality of life (QoL) among a national sample of patients with MM. Methods: For this observational, cross-sectional study, we used data from the Cancer Experience Registry research initiative to examine symptom- and functioning-related concerns among 289 patients with MM across the illness trajectory. We applied hierarchical multiple linear regression analyses to explore associations between symptom burden and perceived control over illness with QoL indicators: depression, anxiety, and social satisfaction. Results: In our sample, 73% of participants with MM reported currently receiving treatment; 39% experienced relapse; 56% received 1 to 2 autologous transplants, 10% received ≥3 autologous transplants, and 4% received allogeneic and autologous transplants; 30% had not received a stem cell transplant. Average time since diagnosis was 4.4 years. The most highly endorsed concerns included eating and nutrition (61%), physical activity (59%), moving around (56%), fatigue (55%), pain (52%), and sleep (46%). Only 27% believed they had control over their disease, whereas 48% perceived having control over the physical side effects of MM. Approximately one-third of the variance in anxiety and depression and nearly two-thirds of variance in social satisfaction were explained by sociodemographic, clinical, and symptom burden variables. Perceived control over illness significantly predicted depression and anxiety, but not social satisfaction. Our results highlight substantial concern among patients with MM about physical symptoms and function. Additionally, greater symptom burden significantly accounted for poorer QoL, and lower perceived control over illness was linked to depression and anxiety. Conclusions: Patients with MM and survivors experience substantive long-term QoL issues. Together, these findings point to the critical need for comprehensive symptom management, integrated palliative care, and enhancement of social and emotional support for individuals with MM.