Introduction Immunotherapy (IT) and radiotherapy (RT) have improved overall survival in patients with melanoma with brain metastasis (MBM). We examined the real‐world survival impact of IT and RT combination and timing strategies. Materials and Methods From the facility‐based National Cancer Database (NCDB) data set, 3008 cases of MBM were identified between 2011 and 2015. Six treatment cohorts were identified: stereotactic radiosurgery (SRS) + IT, SRS alone, whole brain radiotherapy (WBRT) + IT, WBRT alone, IT alone, and none. Concurrent therapy was defined as IT given within 28 days before or after RT; nonconcurrent defined as IT administered within 28–90 days of RT. The co‐primary outcomes were propensity score‐adjusted overall survival by treatment regimen and overall survival by RT and IT timing. Results Median overall survival (mOS) was performed for each treatment category; SRS +IT 15.77 m; (95%CI 12.13–21.29), SRS alone (9.33 m; 95%CI: 8.0–11.3), IT alone (7.29 m; 95%CI: 5.35–12.91), WBRT +IT (4.89 m; 95%CI: 3.65–5.92), No RT or IT (3.29 m; 95%CI: 2.96–3.75), and WBRT alone (3.12 m; 95%CI 2.79–3.52). By propensity score matching, mOS for SRS +IT (15.5 m; 95%CI: 11.5–20.2) was greater than SRS alone (10.1 m; 95%CI: 8.4–11.8) (p = 0.010), and median survival for WBRT +IT (4.6 m; 95%CI: 3.4–5.6) was greater than WBRT alone (2.9 m; 95%CI: 2.5–3.5) (p < 0.001). In the SRS +IT group, 24‐month landmark survival was 47% (95%CI; 42–52) for concurrent versus 37% (95%CI; 30–44) for nonconcurrent (p = 0.40). Conclusion Those who received IT in addition to WBRT and SRS experienced longer survival compared to RT modalities alone, while those receiving concurrent SRS and IT trended toward improved survival versus nonconcurrent therapy.
BackgroundWhile use of total thyroidectomy has increased in management of hyperthyroidism, concerns exist about increased surgical complication rates; most notably, hematoma, recurrent laryngeal nerve (RLN) injury, and hypocalcemia.MethodsRetrospective cohort study of 454 patients undergoing total thyroidectomy between 2003 and 2015. All patients had surgery for hyperthyroidism, benign euthyroid disease, or thyroid malignancy.ResultsTotal thyroidectomy for hyperthyroidism was not associated with an increased risk for any postoperative complication. Transient hypocalcemia, temporary dysphonia, and postoperative hematoma rates were not significantly different for patients with hyperthyroid (n = 91), euthyroid benign (n = 237), and malignant (n = 126) disease. Permanent hypocalcemia and recurrent laryngeal nerve injury were not noted in any hyperthyroid patients. Complication rates were similar for hyperthyroid patients with Graves' disease vs toxic multinodular goiter.ConclusionThis study affirms safety and efficacy of total thyroidectomy as standard treatment for hyperthyroidism.
The tumor microenvironment (TME) plays an essential role in the development, proliferation, and survival of leukemic blasts in acute myeloid leukemia (AML). Within the bone marrow and peripheral blood, various phenotypically and functionally altered cells in the TME provide critical signals to suppress the anti-tumor immune response, allowing tumor cells to evade elimination. Thus, unraveling the complex interplay between AML and its microenvironment may have important clinical implications and are essential to directing the development of novel targeted therapies. This review summarizes recent advancements in our understanding of the AML TME and its ramifications on current immunotherapeutic strategies. We further review the role of natural products in modulating the TME to enhance response to immunotherapy.
BACKGROUND Doxorubicin and other anthracycline derivatives inhibit topoisomerase II and is an important class of cytotoxic chemotherapy in cancer treatment. The use of anthracycline is limited by dose-dependent cardiotoxicity, which may manifest initially as asymptomatic cardiac dysfunction with subsequent progression to congestive heart failure. Despite baseline assessment and periodic monitoring of cardiac function for patients receiving anthracycline agents, there are unmet needs in prediction and prevention of anthracycline-induced cardiotoxicity (AIC). CASE SUMMARY A 35-year-old African American female was found to have a 9-cm high-grade osteosarcoma of right femur and normal baseline cardiac function with left ventricular ejection fraction of approximately 60%-70% determined by transthoracic and dobutamine stress echocardiogram. She underwent perioperative doxorubicin and cisplatin chemotherapy with 3 cycles before surgery and 3 cycles after surgery, and received a total of 450 mg/m 2 doxorubicin at the end of her treatment course. She was evaluated regularly during chemotherapy without any cardiac or respiratory symptoms. Approximately two months after her last chemotherapy, the patient presented to the emergency department with dyspnea for one week and was intubated for acute hypoxic respiratory failure. Echocardiogram showed an ejection fraction of 5%-10% with severe biventricular failure. Despite attempts to optimize cardiac function, the patient’s hemodynamic status continued to decline, and resuscitation was not successful on the seventh day of hospitalization. The autopsy showed no evidence of osteosarcoma, and the likely cause of death was cardiac failure with the evidence of pulmonary congestion, liver congestion, and multiple body cavity effusions. CONCLUSION We present a case of 35-year-old African American female developing cardiogenic shock shortly after receiving a cumulative dose of 450 mg/m 2 doxorubicin over 9 mo. Cardiac monitoring and management of patients receiving anthracycline chemotherapy have been an area of intense research since introduction of these agents in clinical practice. We have reviewed literature and recent advances in the prediction and prevention of AIC. Although risk factors currently identified can help stratify patients who need closer monitoring, there are limitations to our current understanding and further research is needed in this field.
Introduction: Even after curative intent resection, stage III melanoma carries poor prognosis and traditional chemotherapy has limited efficacy. Adjuvant immune checkpoint inhibitor (ICI) therapy utilizing the anti-CTLA-4 agent, ipilimumab, was shown to improve survival following resection in Stage III disease. Ipilimumab was FDA approved for adjuvant therapy in 2015. The National Cancer Database (NCDB) is a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society and is the largest clinical cancer registry in the world covering 72% of new cancer diagnoses in the US. We aimed to assess the real-world survival data along with sociodemographic factors associated with receipt of adjuvant immunotherapy using the NCDB. Methods: We queried the NCDB for stage III patients since 2015. The most recent dataset available includes treatment data from 2015 and 2016 and survival data from 2015. Patients were included who had documented surgery to primary site; those with systemic therapy before surgery were excluded. Patients were divided into receipt of immunotherapy or no receipt of immunotherapy after surgery; those without documentation of either were excluded. Those who received chemotherapy as their systemic therapy were excluded. Factors compared between the two groups included age, sex, diagnosis year, pathologic stage group, Charlson-Deyo score, primary payer and state Medicaid expansion status, income, treatment region, and facility type. Survival analyses were performed by Kaplan-Meier method. Logistic Regression was used to examine factors associated with immunotherapy receipt. Results: 4,093 patients met criteria to be analyzed for survival with 25% (n=1,014) receiving immunotherapy. Median overall survival has yet to be reached for either treatment group; whereas, the 30-month survival was rate was 78% (95%CI; 74-82%) for those receiving adjuvant immunotherapy versus 73% (95% CI; 72-74%) when immunotherapy was not given (p=0.051). However, adjuvant immunotherapy given to resected stage IIIC patients improved survival 32.8 versus 28.0 months (p<0.01). 8,160 patients met inclusion criteria for treatment pattern analysis of which 28% (n=2,260) received immunotherapy after surgery. Charlson-Deyo Scores of 1-3, 2015 as year of diagnosis, and Medicare as primary payer had lower percentage of patients receiving immunotherapy. Conclusion: We provide the first early analysis of the NCDB in the era of adjuvant ICI. Adjuvant immunotherapy in resected stage IIIC melanoma yielded a superior survival advantage. Additionally, sociodemographic factors appear to play a role in receiving adjuvant immunotherapy. Citation Format: Justin T. Moyers, Esther G. Chong, Jasmine Mitchell, Amie Patel, Il Seok Daniel Jeong, Gayathri Nagaraj. Immunotherapy in resected stage III melanoma: An analysis of the National Cancer Database [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4338.
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