Citations

529 Background: Multiple prognostic models exist to predict late relapse risk in early stage hormone receptor-positive (HR+) breast cancer (BC). The CTS5 is one such model that has been validated in HR+ HER2-negative BC. The value of this model in HR+ HER2+ has not been established. Here, we assessed CTS5 in patients (pts) with early stage HER2+ BC treated in the NCCTG N9831 (Alliance) trial. Methods: Pts with stage I-III HER2+ HR+ BC who survived ≥ 5 years were included. The online CTS5 calculator was used to determine CTS5 score and risk group (low, intermediate, and high) based on age, tumor size, grade, and number of involved nodes. Kaplan-Meier (KM) estimates, Cox regression models, and C index were used for analysis. Results: From 3,130 pts, 1,204 pts met the criteria and were included. Median age was 49 (22-79) years and median tumor size was 2.4 (0.1-12) cm. 63.6% had grade 3 tumors, 33.6% grade 2, and 2.8% grade 1. Median follow up was 10.89 (5.01-15.32) years. Based on CTS5, 821 (68.2%) pts were classified as high risk, 289 (24%) as intermediate risk, and 94 (7.8%) as low risk. Overall, using univariate Cox regression analysis, there was no statistically significant difference in recurrence free survival (RFS) among pts with intermediate vs. low (HR 0.47 95%CI 0.18-1.22, p = 0.12) and high vs. low (HR1.23 95%CI0.57-2.67, p = 0.6) with the C index of 0.58. Among pts who received concurrent trastuzumab (H) with HR+ BC, there was also no statistical difference in RFS between high vs. low (HR 0.68 95%CI0.24-1.97, p = 0.48) with the C index of 0.55. Paradoxically, pts with intermediate risk had better RFS than low risk (HR 0.18 95%CI0.03-0.97, p = 0.05). As a continuous variable, there is also no significant improvement in RFS per 1 unit increase in CTS5 score (HR 1.19 95%CI 0.73-1.96, p = 0.49) with the C index of 0.54. After 5 years, 7.06% (n = 30/425) of HR+ pts treated with concurrent H recurred. Conclusions: The CTS5 model is not prognostic in pts with early stage HR+ HER2+ BC receiving adjuvant H. While most HR+ HER2+ pts are classified as high risk by CTS5, the recurrence between years 5-10 was low in pts who received adjuvant H. This study highlights the need to develop a new predictive model for risk of late relapse in this specific group of pts to enable clinicians to determine which pts would benefit from extended adjuvant endocrine therapy. Support: BCRF-19-161, U10CA180821, Genentech. https://acknowledgments.alliancefound.org Clinical trial information: NCT00005970 .

Abstract Wiskott-Aldrich syndrome (WAS) is an X-linked disease caused by mutations in the WAS gene, leading to thrombocytopenia, eczema, recurrent infections, autoimmune disease, and malignancy. Hematopoietic cell transplantation (HCT) is the primary curative approach, with the goal of correcting the underlying immunodeficiency and thrombocytopenia. HCT outcomes have improved over time, particularly for patients with HLA-matched sibling and unrelated donors. We report the outcomes of 129 patients with WAS who underwent HCT at 29 Primary Immune Deficiency Treatment Consortium centers from 2005 through 2015. Median age at HCT was 1.2 years. Most patients (65%) received myeloablative busulfan-based conditioning. With a median follow-up of 4.5 years, the 5-year overall survival (OS) was 91%. Superior 5-year OS was observed in patients <5 vs ≥5 years of age at the time of HCT (94% vs 66%; overall P = .0008). OS was excellent regardless of donor type, even in cord blood recipients (90%). Conditioning intensity did not affect OS, but was associated with donor T-cell and myeloid engraftment after HCT. Specifically, patients who received fludarabine/melphalan-based reduced-intensity regimens were more likely to have donor myeloid chimerism <50% early after HCT. In addition, higher platelet counts were observed among recipients who achieved full (>95%) vs low-level (5%-49%) donor myeloid engraftment. In summary, HCT outcomes for WAS have improved since 2005, compared with prior reports. HCT at a younger age continues to be associated with superior outcomes supporting the recommendation for early HCT. High-level donor myeloid engraftment is important for platelet reconstitution after either myeloablative or busulfan-containing reduced intensity conditioning. (This trial was registered at www.clinicaltrials.gov as #NCT02064933.)

Background: Intraoperative cardiac arrest (ICA) has a reported frequency of 1 in 10,000 anesthetics but has a much higher estimated incidence in orthotopic liver transplantation (OLT). Single-center studies of ICA in OLT are limited by small sample size that prohibits multivariable regression analysis of risks. METHODS: Utilizing data from 7 academic medical centers, we performed a retrospective, observational study of 5296 adult liver transplant recipients (18–80 years old) between 2000 and 2017 to identify the rate of ICA, associated risk factors, and outcomes. RESULTS: ICA occurred in 196 cases (3.7% 95% confidence interval [CI], 3.2–4.2) and mortality occurred in 62 patients (1.2%). The intraoperative mortality rate was 31.6% in patients who experienced ICA. In a multivariable generalized linear mixed model, ICA was associated with body mass index (BMI) <20 (odds ratio [OR]: 2.04, 95% CI, 1.05–3.98; P = .0386), BMI ≥40 (2.16 [1.12–4.19]; P = .022), Model for End-Stage Liver Disease (MELD) score: (MELD 30–39: 1.75 [1.09–2.79], P = .02; MELD ≥40: 2.73 [1.53–4.85], P = .001), postreperfusion syndrome (PRS) (3.83 [2.75–5.34], P < .001), living donors (2.13 [1.16–3.89], P = .014), and reoperation (1.87 [1.13–3.11], P = .015). Overall 30-day and 1-year mortality were 4.18% and 11.0%, respectively. After ICA, 30-day and 1-year mortality were 43.9% and 52%, respectively, compared to 2.6% and 9.3% without ICA. CONCLUSIONS: We established a 3.7% incidence of ICA and a 1.2% incidence of intraoperative mortality in liver transplantation and confirmed previously identified risk factors for ICA including BMI, MELD score, PRS, and reoperation and identified new risk factors including living donor and length of surgery in this multicenter retrospective cohort. ICA, while rare, is associated with high intraoperative mortality, and future research must focus on therapy to reduce the incidence of ICA.

Hepatocellular carcinoma (HCC) is among the leading causes of worldwide cancer‐related morbidity and mortality. Poor prognosis of HCC is attributed primarily to tumor presentation at an advanced stage when there is no effective treatment to achieve the long term survival of patients. Currently available tests such as alpha‐fetoprotein have limited accuracy as a diagnostic or prognostic biomarker for HCC. Liver biopsy provides tissue that can reveal tumor biology but it is not used routinely due to its invasiveness and risk of tumor seeding, especially in early‐stage patients. Liver biopsy is also limited in revealing comprehensive tumor biology due to intratumoral heterogeneity. There is a clear need for new biomarkers to improve HCC detection, prognostication, prediction of treatment response, and disease monitoring with treatment. Liquid biopsy could be an effective method of early detection and management of HCC. Circulating tumor cells (CTCs) are cancer cells in circulation derived from the original tumor or metastatic foci, and their measurement by liquid biopsy represents a great potential in facilitating the implementation of precision medicine in patients with HCC. CTCs can be detected by a simple peripheral blood draw and potentially show global features of tumor characteristics. Various CTC detection platforms using immunoaffinity and biophysical properties have been developed to identify and capture CTCs with high efficiency. Quantitative abundance of CTCs, as well as biological characteristics and genomic heterogeneity among the CTCs, can predict disease prognosis and response to therapy in patients with HCC. This review article will discuss the currently available technologies for CTC detection and isolation, their utility in the clinical management of HCC patients, their limitations, and future directions of research.

LINKED CONTENTThis article is linked to Cushing et al and Cushing and Ananthakrishnan papers. To view these articles, visit https://doi.org/10.1111/apt.15568 and https://doi.org/10.1111/apt.15621.

Background Quality measures are important because they can help improve and standardize the delivery of cancer care among healthcare providers and across tumor types. In an environment characterized by a rapidly shifting immunotherapeutic landscape and lack of associated long-term outcome data, defining quality measures for cancer immunotherapy is a high priority yet fraught with many challenges. Methods Thus, the Society for Immunotherapy of Cancer convened a multistakeholder expert panel to, first, identify the current gaps in measures of quality cancer care delivery as it relates to immunotherapy and to, second, advance priority concepts surrounding quality measures that could be developed and broadly adopted by the field. Results After reviewing the existing quality measure landscape employed for immunotherapeutic-based cancer care, the expert panel identified four relevant National Quality Strategy domains (patient safety, person and family-centered care, care coordination and communication, appropriate treatment selection) with significant gaps in immunotherapy-based quality cancer care delivery. Furthermore, these domains offer opportunities for the development of quality measures as they relate to cancer immunotherapy. These four quality measure concepts are presented in this consensus statement. Conclusions This work represents a first step toward defining and standardizing quality delivery of cancer immunotherapy in order to realize its optimal application and benefit for patients.