High-dose chemotherapy with autologous stem-cell transplantation for relapsed metastatic germ cell tumors The Alberta experience.

INTRODUCTION: High-dose chemotherapy with autologous stem-cell transplantation (HDC-ASCT) is standard therapy for metastatic germ cell tumors (mGCTs) in patients whose disease progresses during or after conventional chemotherapy. We conducted a retrospective review of HDC-ASCT in relapsed mGCT patients in the province of Alberta, Canada, over the past two decades. METHODS: Patients with mGCTs who received HDC-ASCT at two provincial cancer referral centers from 2000-2018 were identified from institutional databases. Baseline clinical and treatment characteristics were collected, as well as overall survival (OS ) and disease-free survival (DFS). Relevant prognostic variables were analyzed. RESULTS: Forty-three patients were identified. The median age was 28 years (range 19-56). A majority (95%) had non-seminoma histology and testis/retroperitoneal primary (84%). Twenty patients (47%) had poor-risk disease, as per The International Germ Cell Consensus Classification (IGCCC), at start of first-line chemotherapy. HDC-ASCT was used as second-line therapy in 65% of patients, and 58% of ASCT patients received tandem transplants. Median followup after ASCT was 22 months (range 2-181). At last followup, 42% of patients were alive without disease, including 3/7 (43%) of patients with primary mediastinal disease. Two-year and five-year DFS/OS ratios were 44%/65% and 38%/45%, respectively. Median OS and DFS for all patients were 30.0 months (13.3-46.6) and 8.0 months (0.9-15.1), respectively. CONCLUSIONS: We found that HDC-ASCT is an effective salvage therapy in mGCT, consistent with existing literature. Patients appeared to benefit regardless of primary site. Although limited by small sample size, we found a numerical difference in DFS and OS between second- and third-line HDC-ASCT and single vs. tandem ASCT.

Cardio-oncology and Cancer Rehabilitation: Is an Integrated Approach Possible?

With significant improvements in the understanding of cancer biology, improved detection, and the use of novel adjuvant therapies, each year more Canadians are surviving a cancer diagnosis. Despite their effectiveness these therapies often result in short- and long-term deleterious effects to major organ systems, particularly cardiovascular. Cardio-oncology is an emerging field of study with the aim to improve cardiovascular health across the oncology disease spectrum. International guidelines distinguish "cardio-oncology" rehabilitation from "cancer" rehabilitation, but how this is navigated is currently unknown. How such care should be assessed and integrated acutely or in the longer term remains unknown. Accordingly, the aim of this article is to consider the cancer patient's needs beyond the scope of cardio-oncology rehabilitation to holistically integrate cancer rehabilitation across the disease trajectory.

An approach to anxiety during watch-and-wait for Chronic Lymphocytic Leukemia: Monitor and move on.

Chronic Lymphocytic Leukemia (CLL) is the most frequently diagnosed hematologic malignancy with the majority of patients at diagnosis in the "watch and wait" stage of treatment - language that gives the perception of an axe waiting to fall, belying the fact that up to 30% of patients will never need treatment in their lifetime. While receiving active surveillance, patients report anxiety, distress, and depression, yet there is little research capturing the experience of this patient population, nor describing interventions to improve their experience (Damen, 2022). In an effort to "do something," patients may turn to often expensive and unproven alternative therapies. At each clinic visit, there is an opportunity to provide relevant and understandable information, resources to address anxiety, and response to unmet needs to increase the patient's experience of shared decision making. Reframing the experience to a more proactive perspective such as 'Monitor and Move On' versus "Watch and Wait' may empower patients with CLL along their trajectory.

Expanded antigen-experienced CD160+CD8+effector T cells exhibit impaired effector functions in chronic lymphocytic leukemia.

BACKGROUND: T cell exhaustion compromises antitumor immunity, and a sustained elevation of co-inhibitory receptors is a hallmark of T cell exhaustion in solid tumors. Similarly, upregulation of co-inhibitory receptors has been reported in T cells in hematological cancers such as chronic lymphocytic leukemia (CLL). However, the role of CD160, a glycosylphosphatidylinositol-anchored protein, as one of these co-inhibitory receptors has been contradictory in T cell function. Therefore, we decided to elucidate how CD160 expression and/or co-expression with other co-inhibitory receptors influence T cell effector functions in patients with CLL. METHODS: We studied 56 patients with CLL and 25 age-matched and sex-matched healthy controls in this study. The expression of different co-inhibitory receptors was analyzed in T cells obtained from the peripheral blood or the bone marrow. Also, we quantified the properties of extracellular vesicles (EVs) in the plasma of patients with CLL versus healthy controls. Finally, we measured 29 different cytokines, chemokines or other biomarkers in the plasma specimens of patients with CLL and healthy controls. RESULTS: We found that CD160 was the most upregulated co-inhibitory receptor in patients with CLL. Its expression was associated with an exhausted T cell phenotype. CD160+CD8+ T cells were highly antigen-experienced/effector T cells, while CD160+CD4+ T cells were more heterogeneous. In particular, we identified EVs as a source of CD160 in the plasma of patients with CLL that can be taken up by T cells. Moreover, we observed a dominantly proinflammatory cytokine profile in the plasma of patients with CLL. In particular, interleukin-16 (IL-16) was highly elevated and correlated with the advanced clinical stage (Rai). Furthermore, we observed that the incubation of T cells with IL-16 results in the upregulation of CD160. CONCLUSIONS: Our study provides a novel insight into the influence of CD160 expression/co-expression with other co-inhibitory receptors in T cell effector functions in patients with CLL. Besides, IL-16-mediated upregulation of CD160 expression in T cells highlights the importance of IL-16/CD160 as potential immunotherapy targets in patients with CLL. Therefore, our findings propose a significant role for CD160 in T cell exhaustion in patients with CLL.

Rehabilitation Needs in Cancer Treatment-Related Cardiotoxicity.

OBJECTIVES: To examine and summarize current international guidelines regarding cardiovascular risk reduction before and during cancer therapy, and to discuss the emerging role of cardio-oncology as a subspecialty in cancer care and the role of cardio-oncology rehabilitation. DATA SOURCES: Published articles and guidelines. CONCLUSION: With improvements in cancer detection and the use of novel adjuvant therapies, an increasing number of individuals now survive a cancer diagnosis. However, for some the cost is high - many survivors are now at higher risk of death from cardiovascular disease than from recurrent cancer. Cardiovascular morbidity and mortality are common and associated with common cancer therapies serially administered in adult oncology care. IMPLICATIONS FOR NURSING PRACTICE: Timely risk-reduction interventions hold promise in reducing cardiovascular morbidity and mortality. Oncology nurses are the key providers to identify baseline risks, perform necessary referrals, provide individualized teaching, and support the patient within the family and community.

Personalized Care in the Prevention of Treatment-Related Cardiac Dysfunction in Female Cancer Survivors.

Background: The American Cancer Society projects the number of U.S. cancer survivors to exceed 20 million individuals by 2026. However, approximately one in four cancer survivors report decreased quality of life due to physical dysfunction and disabling symptoms. Many effective anticancer treatments are now understood to be associated with cardiotoxicity, such that, for many survivors, the risk of death from cardiovascular disease now exceeds that of recurrent cancer. Materials and Methods: We undertook a Clinical Review of cancer treatment-related cardiac dysfunction (CTRCD) associated with standard treatment regimens with attention to risks experienced by female cancer patients and survivors. Results: Risks of standard (chemotherapy, radiotherapy) and targeted (antibodies, kinase inhibitors) in development of CTCRD in females are discussed. Multidisciplinary approaches in prevention are reviewed. Conclusions: Female cancer survivors with CTRCD represent an entirely new population at high risk of morbidity and mortality. Increased awareness of the short- and long-term effects of anti-cancer treatments is necessary for the community health care provider for early detection and CTRCD risk reduction.

Cardiac Rehabilitation in Patients With Lymphoma Undergoing Autologous Hematopoietic Stem Cell Transplantation: A Cardio-oncology Pilot Project.

BACKGROUND: Worldwide > 50,000 hematopoietic stem cell transplants (HSCTs) are performed annually. HSCT patients receive multiple cardiotoxic therapies (chemotherapy and radiation therapy) in addition to severe physical deconditioning during hospital admission. We hypothesized that guided exercise in a cardiac rehabilitation (CR) program following autologous HSCT is a safe and feasible intervention. METHODS: Pilot project to assess for safety, feasibility and impact of 8 weeks of CR in HSCT patients following transplant. Consecutive patients with lymphoma underwent standard activity protocol testing before HSCT, at 6 weeks following HSCT (prior to CR), and at 14 weeks following HSCT (at completion of CR), consisting of grip strength (GS), gait speed (GtS), timed up-and-go (TUG), and 6-minute walk test (6MWT). CR consisted of 8 weekly visits for guided exercise. RESULTS: Activity tolerance protocol data of 30 patients (24 male, 6 female) from December 2014 to December 2016 were analyzed using repeated measures (analysis of variance [ANOVA]) to observe for changes in GS, GtS, TUG, and 6MWT. Statistically significant improvements were found in GS (P < 0.005), GtS (P = 0.02), and 6MWT (P = 0.001). These improvements show that guided CR-based exercise may assist HSCT survivors to meet or even surpass baseline exercise levels and improve physical functioning. There were no adverse events (ie, death or injury) during the study period. Fifty-seven percent of referred patients participated in CR, exceeding documented CR adherence in cardiac populations. CONCLUSIONS: The addition of CR-based exercise programming in HSCT survivorship care of patients with lymphoma is a safe and feasible intervention to assist in recovery following transplant.

The Role of Cardio-Oncology in the Interprofessional Care of Adult Patients Receiving Cancer Therapy.

OBJECTIVE: To discuss the toxic effects of therapy to the structure and function of the cardiovascular system and the role of the cardio-oncology team in the interprofessional care of adult patients, including current approaches, research findings, and future endeavors DATA SOURCE: Published articles and international cardiology and oncology association guidance documents. CONCLUSION: Although a new field of study, cardio-oncology is a rapidly expanding area of great clinical need. Evidence is only now accumulating, with most guidelines based on opinion or extrapolated from cardiovascular literature. Oncology care providers face complex decisions on a daily basis, whether before, during, or following definitive cancer treatments. IMPLICATIONS FOR NURSING PRACTICE: In the era of both traditional and targeted cancer therapies, the long-term side effects to the cardiovascular system and, consequently, the needs of cancer survivors are increasingly complex. Accordingly, oncology nurses must not only be aware of such potential effects, but should conduct careful serial symptom review and consider risk-reduction and cancer rehabilitation strategies across the disease trajectory.