Citations

Certain cancer treatments have been linked to specific cardiovascular toxicities, including (but not limited to) cardiomyopathy, atrial fibrillation, arterial hypertension, and myocarditis. Radiation, anthracyclines, human epidermal growth factor receptor 2 (Her2)-directed therapies, fluoropyrimidines, platinums, tyrosine kinase inhibitors and proteasome inhibitors, immune checkpoint inhibitors, and chimeric antigen-presenting (CAR)-T cell therapy can all cause cardiovascular side effects. Management of cardiovascular dysfunction that occurs during cancer therapy often requires temporary or permanent cessation of the risk-potentiating anti-neoplastic drug as well as optimization of medical management from a cardiovascular standpoint. Stem cell or bone marrow transplant recipients face unique cardiovascular challenges, as do patients at extremes of age.

OBJECTIVE Investigations of the combined effects of neoadjuvant Onyx embolization and stereotactic radiosurgery (SRS) on brain arteriovenous malformations (AVMs) have not accounted for initial angioarchitectural features prior to neuroendovascular intervention. The aim of this retrospective, multicenter matched cohort study is to compare the outcomes of SRS with versus without upfront Onyx embolization for AVMs using de novo characteristics of the preembolized nidus. METHODS The International Radiosurgery Research Foundation AVM databases from 1987 to 2018 were retrospectively reviewed. Patients were categorized based on AVM treatment approach into Onyx embolization (OE) and SRS (OE+SRS) or SRS alone (SRS-only) cohorts and then propensity score matched in a 1:1 ratio. The primary outcome was AVM obliteration. Secondary outcomes were post-SRS hemorrhage, all-cause mortality, radiological and symptomatic radiation-induced changes (RICs), and cyst formation. Comparisons were analyzed using crude rates and cumulative probabilities adjusted for competing risk of death. RESULTS The matched OE+SRS and SRS-only cohorts each comprised 53 patients. Crude rates (37.7% vs 47.2% for the OE+SRS vs SRS-only cohorts, respectively; OR 0.679, p = 0.327) and cumulative probabilities at 3, 4, 5, and 6 years (33.7%, 44.1%, 57.5%, and 65.7% for the OE+SRS cohort vs 34.8%, 45.5%, 59.0%, and 67.1% for the SRS-only cohort, respectively; subhazard ratio 0.961, p = 0.896) of AVM obliteration were similar between the matched cohorts. The secondary outcomes of the matched cohorts were also similar. Asymptomatic and symptomatic embolization-related complication rates in the matched OE+SRS cohort were 18.9% and 9.4%, respectively. CONCLUSIONS Pre-SRS AVM embolization with Onyx does not appear to negatively influence outcomes after SRS. These analyses, based on de novo nidal characteristics, thereby refute previous studies that found detrimental effects of Onyx embolization on SRS-induced AVM obliteration. However, given the risks incurred by nidal embolization using Onyx, this neoadjuvant intervention should be used judiciously in multimodal treatment strategies involving SRS for appropriately selected large-volume or angioarchitecturally high-risk AVMs.

Background: Although the monitoring of a pitcher’s throwing arm workload has become a hot topic in both research and the pitching world, the impact of mound height and distance still remains unclear. Purpose: To compare the kinetics and kinematics between pitches from a mound and flat ground at 2 different distances. Study Design: Descriptive laboratory study. Methods: A total of 21 healthy high school varsity baseball pitchers (age, 16.2 ± 1.3 years; weight, 73.6 ± 11.0 kg; height, 181.3 ± 6.4 cm) participated in this study. Players were fitted with a motusBASEBALL sensor and sleeve. Each pitcher was instructed to pitch 5 fastballs under 4 conditions: mound at 60.5 ft (regulation distance), flat ground at 60.5 ft, mound at 50.5 ft, and flat ground at 50.5 ft. Linear mixed-effects models were used to account for both intra- and interplayer variability. A multivariable model was used to evaluate the association of mound pitching, flat-ground pitching, and their distances (50.5 ft and 60.5 ft), and their interaction to arm speed, arm slot, arm rotation, elbow varus torque, and ball velocity. Results: There were no statistically significant effects of mound, flat-ground, or distance variation on arm speed or shoulder rotation. Arm slot was significantly higher (+3.0°; P = .02) on pitches from the mound at 60.5 ft compared with 50.5 ft. Elbow varus torque was lower (–1.5 N·m; P = .02) on mound pitches at 60.5 ft compared with 50.5 ft. Pitches thrown from the mound displayed significantly faster ball velocity compared with flat-ground pitches at both distances ( P < .01 for both), with pitches at 60.5 ft having higher velocity (+0.7 m/s; P < .01). Conclusion: Contrary to long-standing notions, the study results suggest that pitching from the mound does not significantly increase stress on the elbow compared with flat-ground pitching. Lower elbow varus torque and faster ball velocity at the regulation distance compared with the reduced distance indicate that elbow stress and ball velocity may not correlate perfectly, and radar guns may not be an appropriate surrogate measure of elbow varus torque. Clinical Relevance: A better understanding of the kinetic and kinematic implications of various throwing programs will allow for the designing of programs that are driven by objective data with aims directed toward injury prevention and rehabilitation in baseball pitchers.

Abstract Hereditary angioedema (HAE) is a disease manifested by repeated episodes of localized submucosal or subcutaneous edematous episodes, potentially triggered by emotional stress, mechanical trauma, or intake of estrogens. We present our experience managing two parturients with HAE. Multidisciplinary care is essential for planning and executing the specialized care of these patients, and management included extensive planning among obstetric, anesthesiology, and allergy and immunology teams. Pregnancy has been shown to have a variable effect on triggering HAE episodes. First-line treatment includes C1 esterase inhibitor concentrate, which can also be used for prophylaxis in high-risk patients. Neuraxial analgesia is recommended to avoid general anesthesia and was established early in both individuals. Vaginal delivery was well tolerated without need for emergent treatment for angioedema symptoms.

This report presents the American Society of Clinical Oncology’s (ASCO’s) evaluation of the adaptations in care delivery, research operations, and regulatory oversight made in response to the coronavirus pandemic and presents recommendations for moving forward as the pandemic recedes. ASCO organized its recommendations for clinical research around five goals to ensure lessons learned from the COVID-19 experience are used to craft a more equitable, accessible, and efficient clinical research system that protects patient safety, ensures scientific integrity, and maintains data quality. The specific goals are: (1) ensure that clinical research is accessible, affordable, and equitable; (2) design more pragmatic and efficient clinical trials; (3) minimize administrative and regulatory burdens on research sites; (4) recruit, retain, and support a well-trained clinical research workforce; and (5) promote appropriate oversight and review of clinical trial conduct and results. Similarly, ASCO also organized its recommendations regarding cancer care delivery around five goals: (1) promote and protect equitable access to high-quality cancer care; (2) support safe delivery of high-quality cancer care; (3) advance policies to ensure oncology providers have sufficient resources to provide high-quality patient care; (4) recognize and address threats to clinician, provider, and patient well-being; and (5) improve patient access to high-quality cancer care via telemedicine. ASCO will work at all levels to advance the recommendations made in this report.

Abstract Background Recurrent pleomorphic adenoma (PA) can be a lifelong disease, and rates of subsequent recurrence are high. Methods Patients between 2000 and 2015 were identified. Primary outcome was subsequent recurrence after surgical salvage. Results Twenty‐seven of 84 patients developed a subsequent recurrence. Risk factors for subsequent recurrence included a higher number of previous recurrences ( P < .01), worse preoperative facial nerve function ( P < .01), and deep parotid lesion(s) ( P < .01). Interval since last surgery was protective ( P < .01), specifically >10 years since last surgery ( P < .01). For patients with a >10‐year interval since their last surgery, the subsequent recurrence‐free rate at 10 years follow‐up was 80.2% vs 31.8%. Conclusions For patients presenting with a >10‐year interval since their last surgery, subsequent recurrence rates are low, which may allow for as needed surveillance recommendations. For patients presenting with recurrent PA and ≤10 years since their last surgery, a closer surveillance is warranted.

Abstract Purpose: Low-dose tamoxifen reduces breast cancer risk, but remains untested in chest-irradiated cancer survivors—a population with breast cancer risk comparable with BRCA mutation carriers. We hypothesized that low-dose tamoxifen would be safe and efficacious in reducing radiation-related breast cancer risk. Patients and Methods: We conducted an investigator-initiated, randomized, phase IIb, double-blinded, placebo-controlled trial (FDA IND107367) between 2010 and 2016 at 15 U.S. sites. Eligibility included ≥12 Gy of chest radiation by age 40 years and age at enrollment ≥25 years. Patients were randomized 1:1 to low-dose tamoxifen (5 mg/day) or identical placebo tablets for 2 years. The primary endpoint was mammographic dense area at baseline, 1 and 2 years. IGF-1 plays a role in breast carcinogenesis; circulating IGF-1 and IGF-BP3 levels at baseline, 1 and 2 years served as secondary endpoints. Results: Seventy-two participants (low-dose tamoxifen: n = 34, placebo: n = 38) enrolled at a median age of 43.8 years (35–49) were evaluable. They had received chest radiation at a median dose of 30.3 Gy. Compared with the placebo arm, the low-dose tamoxifen arm participants had significantly lower mammographic dense area (P = 0.02) and IGF1 levels (P &lt; 0.0001), and higher IGFBP-3 levels (P = 0.02). There was no difference in toxicity biomarkers (serum bone-specific alkaline phosphatase, lipids, and antithrombin III; urine N-telopeptide cross-links) between the treatment arms. We did not identify any grade 3–4 adverse events related to low-dose tamoxifen. Conclusions: In this randomized trial in chest-irradiated cancer survivors, we find that low-dose tamoxifen is effective in reducing established biomarkers of breast cancer risk and could serve as a risk-reduction strategy.

Abstract Purpose Chemotherapy-induced nausea and vomiting (CINV) contributes to avoidable acute care, a metric now tracked in Medicare's oncology outcome measure. CINV is preventable, yet guidelines are often not followed. We sought to quantify acute care involving CINV and other avoidable toxicities after highly emetogenic chemotherapy (HEC) to identify excess risk and assess clinician adherence to antiemesis guidelines for HEC. Materials and Methods We retrospectively evaluated U.S. electronic health records (2012-2018) using Medicare's OP-35 outcome measure to identify avoidable acute care involving any of 10 toxicities, including CINV, after HEC regimens relative to non-HEC. Antiemetic guideline adherence was defined as use ofneurokinin-1 (NKl) receptor antagonists Q5 (RAs) plus 5-hydroxytryptamine type 3 RA+ dexamethasone at HEC initiation. Results Among 17,609 patients receiving HEC, acute care rates associated with HEC chemotherapy included 32% cisplatin, 31% carboplatin, and 21% anthracycline/cyclosphospharnide (AC), with 76% meeting the criteria as avoidable events. Oxaliplatin rates were 29%. Avoidable acute care occurred 1.83 times (95% confidence interval, 1.76-1.91, p &lt; .0001) as often after HEC versus non-HEC excluding oxaliplatin; CINV-related acute care occurred 2.29 times as often. Nonadherence to antiemesis guidelines occurred in 34% and 24% of cisplatin and AC courses, respectively, because of omission of a NKl RA. Conclusions Patients treated with HEC regimens experienced high avoidable acute care use, 1.8 times the risk seen for other chemotherapy. Nonadherence to guideline-directed antiemetic prophylaxis highlights the need to ensure adherence to antiemetic guidelines, including the use of NKl RA in HEC. Implications for Practice After survival, perhaps the most important goal in oncology is limiting avoidable acute care, a goal now used by Medicare to impact cancer reimbursement. This study found that patients treated with highly emetogenic chemotherapy (HEC) regimens had high rates of avoidable acute care use, 1.8 times the risk seen for other chemotherapy. A substantial proportion of the avoidable acute care involved chemotherapy-induced nausea and vomiting. Results showed that incomplete adherence to national antiemetic guidelines for HEC regimens primarily driven by omission of upfront neurokinin-1 receptor antagonist use, suggesting that improved adherence can meaningfully resolve this gap in quality and cost of care.