Search

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/m2 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/m2 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.

Objective To explore the efficacy of primary chemoradiation with cisplatin versus cetuximab with respect to HPV/p16 and smoking statuses. Methods We retrospectively reviewed patients from our center with locally advanced non-nasopharyngeal head and neck squamous cell carcinoma (HNSCC) who received primary chemoradiation with cisplatin or cetuximab between 2006 and 2018. Results The median OS for cisplatin (n = 66) was not reached versus 132 months when treated with cetuximab (n = 55) (p = 0.03). For HPV/p16-positive patients, we found the median OS for cisplatin (n = 34) was not reached versus 60 months with cetuximab (n = 21) (p = 0.036). In the smoking group, the median OS was not reached in the cisplatin group (n = 44) versus 60 months when treated with cetuximab (n = 32) (p = 0.03). Conclusion HPV/p16-positive and smoking cohorts treated with cisplatin-based chemoradiotherapy had a significantly better OS versus cetuximab.

Background While 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. Methods Retrospective cohort study of 454 patients undergoing total thyroidectomy between 2003 and 2015. All patients had surgery for hyperthyroidism, benign euthyroid disease, or thyroid malignancy. Results Total 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. Conclusion This study affirms safety and efficacy of total thyroidectomy as standard treatment for hyperthyroidism.

Pineoblastoma is a rare, primitive, and malignant tumor arising from the parenchyma of the pineal gland. It typically metastasizes along the cerebral neural axis, with rare extraneural metastasis and even more rare intraosseous extraneural metastasis. A patient with pineoblastoma, initially treated with chemotherapy, presented 10 years after initial diagnosis with multiple osseous metastases including his pelvis, femur, and vertebrae, and is currently undergoing chemotherapy.

Cutaneous metastasis of breast cancer carries a poor prognosis, invokes a poor quality of life, and increases mortality by raising one’s risk of bleeding and infection. Currently, options for treatment are systemic chemotherapy, surgical resection and radiation. These treatments are invasive and can have toxic side effects. A 50-year-old African-American woman with stage IV breast cancer with cutaneous metastasis to the left anterior chest and left supraclavicular area was successfully treated with topical imiquimod. She experienced improvement in appearance and symptoms within several months of starting treatment, resulting in near resolution of her cutaneous metastasis. Imiquimod is currently approved for several cutaneous conditions and has the potential to treat cutaneous metastasis of breast cancer.

Introduction: In order to assess hematopoietic precursor cells, bone marrow biopsies are routinely conducted, which is painful for the patient and is not applicable for frequent testing. However, precursor, maturating, and matured cells are known to produce exosomes, which are released into peripheral blood. By analyzing these exosomes in plasma, bone marrow condition may be assessed noninvasively. Myeloid precursor cells express different surface markers than when they have matured. It is reasonable to speculate that these markers would be incorporated into exosomes. In this study, we developed a novel sandwich enzyme-linked immunosorbent assay (ELISA) by using a combination of monoclonal antibodies against 2 different leukocyte antigens, to account for the number of exosomes in plasma. Methods In 6 patients undergoing chemotherapy, venous blood was drawn at regular intervals before, during, and after respective chemotherapies was given. Various clones of monoclonal antibodies against CD11b, CD33, CD34, CD35, CD81, and CD117 were obtained, and antibodies were biotinylated by EZ link Sulfo-NHS-LC-Biotin. Anti-brain antibodies were switched with anti-leukocyte antibodies, and exosome activity was trended. Results CD11b+ and CD 117+ plates showed small changes during chemotherapy (within +/- 50% of the initial value), while plasma WBC count showed a dramatic decrease during chemotherapy. In the recovery phase of WBC after chemotherapy, CD11b+ and CD16+showed a greater than 2-fold increase, with the up-trend taking place earlier than its plasma WBC counterparts. CD 117+ CD33+ also showed an up-trend, but was slower than their CD11b+ and CD16+ counterpart. Finally, each exosome value was divided by other markers to calculate the ratio, and compared between pre and post chemotherapy blood. In half of the cases, there was not a difference, versus an almost double premature/mature ratio in post-chemotherapy blood in the other half of patients. Conclusion From data collected from pre-chemotherapy studies, the lack of correlation between ELISA data compared to plasma WBC data, indicates that plasma exosome analysis might not be suitable for the monitoring of acute bone marrow suppression. Additionally, in the recovery phase, surface markers correlation with WBC was present in only some of the markers, indicating that the assay sensitivity is dependent on the marker combinations. Overall, both myeloid precursor- and mature granulocyte-derived exosomes were increased during the recovery from chemotherapy in 3 out of 5 patients, and exosome profiles were different after chemotherapy in 2 out of 5 patients. Disclosures Mitsuhash: NanoSomiX:Current Employment.

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 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.

12037 Background: Metastatic melanoma carries poor prognosis and traditional chemotherapy has limited efficacy. Immune checkpoint inhibitors (ICI) have drastically improved disease outcomes since first approved in 2011. Elderly patients were underrepresented in landmark early trials of ICI leading to limited clinical trial data on efficacy and treatment patterns in this population. We aimed to examine the real-world IO outcomes and demographics of elderly patients in the National Cancer Database. Methods: We queried the database for patients with stage IV melanoma diagnosed between 2011-2015 with survival data available. Patients were divided into receipt of immunotherapy (IO) or no receipt of IO; those without documentation were excluded. Cases were separated into 3 cohorts of age at diagnosis (60 years-old or younger, 61-74 years-old, and 75 years-old and greater). Descriptive variables were compared by Chi-squared analysis and survival analyses were performed by Kaplan-Meier method and log-rank test. Results: 11,265 cases met inclusion criteria: 4,117 aged 60 or less, 3,940 aged 61-74, and 3,208 aged 75 or older. Those receiving immuno-oncologic agents (IO) in all age groups showed a longer median OS (mOS) than those who did not receive IO (mOS overall 17.28 v 7.49; p

e14513 Background: Brain metastases (BM) are a major cause of morbidity and mortality in metastatic melanoma. Radiotherapy (RT) and/or surgery are the standard of care for treating brain metastases. The introduction of immune checkpoint inhibitors has drastically improved disease outcomes since approved in 2011 and recent trials have exhibited intracranial activity. We aim to assess the added survival benefit of immuno-oncologic agents (IO) for melanoma with BM in National Cancer Database. Methods: We queried the database from 2011 to 2015 for Stage IV melanoma with BM. RT treatments were divided into stereotactic radiosurgery (SRS), whole brain radiotherapy (WBRT), or no brain radiation; those with insufficient documentation were excluded. Patients were further divided into receipt of IO or no receipt of IO; those without documentation were excluded. Concurrent (CC) treatment was defined as IO begun before or during RT treatment; sequential (SQ) therapy was defined as IO begun after RT. Survival analyses were performed by Kaplan-Meier method and log-rank test. Results: Among 8,561 metastatic melanoma patients with documentation of metastatic sites, 3,008 (35.1%) had documented BM. Median overall survival (mOS) for all stage IV melanoma was 10.5 months with worse survival for those with BM compared to those without (mOS 6.0 v 14.7 m; p < 0.01). Among 3,008 cases with survival data available, 2,762 met criteria for survival analysis of BM treatments. Table summarizes treatment outcomes between cohorts by RT and IO treatment categories. IO + SRS had improved survival compared to all other treatment groups (mOS 19.9 m; p < 0.01). No difference in survival between SRS and IO alone was observed (mOS 10.9 v 11.5 m; p = 0.56). WBRT as single modality did not appear to improve survival over no therapy (mOS 4.2 v 3.3 m; p = 0.35). 436 cases had documented time course between IO and RT. IO was given SQ with RT in 69% of SRS (n = 158/230) and 67% of WBRT (n = 137/206) treated patients. In SRS + IO cohort, survival was longer for SQ compared to CC treatment (23.5 v 13.1 m; p < 0.01). Survival was similar in WBRT for SQ v CC groups (6.8 v 7.9 m; p = 0.62). Conclusions: Superior survival is realized for those who receive IO in addition to SRS for BM. IO and SRS as single modality have similar outcomes, while WBRT seems to add little survival benefit to IO or no therapy. [Table: see text]