Systemic Anticancer Therapy and Thromboembolic Outcomes in Hospitalized Patients With Cancer and COVID-19

IMPORTANCE: Systematic data on the association between anticancer therapies and thromboembolic events (TEEs) in patients with COVID-19 are lacking. OBJECTIVE: To assess the association between anticancer therapy exposure within 3 months prior to COVID-19 and TEEs following COVID-19 diagnosis in patients with cancer. DESIGN, SETTING, AND PARTICIPANTS: This registry-based retrospective cohort study included patients who were hospitalized and had active cancer and laboratory-confirmed SARS-CoV-2 infection. Data were accrued from March 2020 to December 2021 and analyzed from December 2021 to October 2022. EXPOSURE: Treatments of interest (TOIs) (endocrine therapy, vascular endothelial growth factor inhibitors/tyrosine kinase inhibitors [VEGFis/TKIs], immunomodulators [IMiDs], immune checkpoint inhibitors [ICIs], chemotherapy) vs reference (no systemic therapy) in 3 months prior to COVID-19. MAIN OUTCOMES AND MEASURES: Main outcomes were (1) venous thromboembolism (VTE) and (2) arterial thromboembolism (ATE). Secondary outcome was severity of COVID-19 (rates of intensive care unit admission, mechanical ventilation, 30-day all-cause mortality following TEEs in TOI vs reference group) at 30-day follow-up. RESULTS: Of 4988 hospitalized patients with cancer (median [IQR] age, 69 [59-78] years; 2608 [52%] male), 1869 had received 1 or more TOIs. Incidence of VTE was higher in all TOI groups: endocrine therapy, 7%; VEGFis/TKIs, 10%; IMiDs, 8%; ICIs, 12%; and chemotherapy, 10%, compared with patients not receiving systemic therapies (6%). In multivariable log-binomial regression analyses, relative risk of VTE (adjusted risk ratio [aRR], 1.33; 95% CI, 1.04-1.69) but not ATE (aRR, 0.81; 95% CI, 0.56-1.16) was significantly higher in those exposed to all TOIs pooled together vs those with no exposure. Among individual drugs, ICIs were significantly associated with VTE (aRR, 1.45; 95% CI, 1.01-2.07). Also noted were significant associations between VTE and active and progressing cancer (aRR, 1.43; 95% CI, 1.01-2.03), history of VTE (aRR, 3.10; 95% CI, 2.38-4.04), and high-risk site of cancer (aRR, 1.42; 95% CI, 1.14-1.75). Black patients had a higher risk of TEEs (aRR, 1.24; 95% CI, 1.03-1.50) than White patients. Patients with TEEs had high intensive care unit admission (46%) and mechanical ventilation (31%) rates. Relative risk of death in patients with TEEs was higher in those exposed to TOIs vs not (aRR, 1.12; 95% CI, 0.91-1.38) and was significantly associated with poor performance status (aRR, 1.77; 95% CI, 1.30-2.40) and active/progressing cancer (aRR, 1.55; 95% CI, 1.13-2.13). CONCLUSIONS AND RELEVANCE: In this cohort study, relative risk of developing VTE was high among patients receiving TOIs and varied by the type of therapy, underlying risk factors, and demographics, such as race and ethnicity. These findings highlight the need for close monitoring and perhaps personalized thromboprophylaxis to prevent morbidity and mortality associated with COVID-19-related thromboembolism in patients with cancer

A Stroke of Bad Luck

Introduction Unusual case of adrenal masses in a normotensive patient Clinical case A 37 year old female, no significant medical history, presented with sudden onset of right sided weakness and dysarthria. On presentation she was normotensive but exhibited expressive aphasia and complete right hemiplegia. Initial CT Head demonstrated a dense left MCA infarct with no hemorrhage. Echo was normal. Abdominal Ultra sonogram and CT revealed large bilateral cystic and solid adrenal masses, right measured 22x12.5x11cm, weighing 2058g and left measured 16x11.5x7.7cm, weighing 672g; highly suspicious for neoplastic disease. A repeat CT head showed increasing edema and brainstem herniation which necessitated emergent decompressive frontotemporoparietal craniectomy and durotomy. 24-hour urine studies were metanephrine 130,896 µg (35-460 µg), normetanephrine 25,938 µg (110-1050 µg) and vanillylmandelic acid 127.2 mg (1.8-6.7 mg). TSH and serum calcitonin were normal. MEN2 screening for RET proto-oncogene mutation was negative. Hypercoagulable work up was negative. Patient was pretreated with phenoxybenzamine and had exploratory laparotomy and bilateral adrenalectomy. Pathology and immunohistochemical staining confirmed the diagnosis of bilateral benign pheochromocytomas. Patient was discharged with daily hydrocortisone and fludrocortisone. 24-hour urinary fractionated metanephrines measured 2 weeks post-surgery were normal. The triad of episodic headache, sweating and tachycardia is infrequent; pheochromocytomas may present as paroxysmal hypertension, acute pulmonary edema, myocardial infarction or stroke. Plasma metanephrines were normal though urinary metanephrines were elevated. Patient was not on medication that might alter catecholamine metabolism. Conclusion Manifestations of catecholamine hypersecretion are common. Though adrenal masses were found incidentally in our patient, pheochromocytoma should be considered in young patients presenting with acute stroke

Treatment of Anaphylaxis unmasks another Life-Treatening condition-Pheochromocytoma

Introduction We report an unusual case of pheochromocytoma unmasked by anaphylaxis. Clinical case A 65 year old male with a history of hypertension, non-insulin dependent diabetes mellitus presented after multiple wasp stings. He was hypertensive with swelling of his tongue, face and neck. He was treated with epinephrine, diphenhydramine, methylprednisolone and famotidine. After few hours, he had acute onset of dyspnea with hypoxia and profound hypertension. Examination revealed acute pulmonary edema with a blood pressure of 265/140.He was treated with 100% oxygen, IV furosemide, IV enalapril and a nitroglycerin infusion. Troponin I was elevated at 1.77 ng/mL (0.00-1.5) and EKG showed acute T wave inversions in V4-6. Echocardiogram showed mild concentric left ventricular hypertrophy, ejection fraction 35%, and moderate global hypokinesis with moderate aortic stenosis. Left heart catheterization revealed mild luminal irregularities and moderate aortic stenosis. Given his severe hypertension with acute pulmonary edema after two doses of epinephrine, pheochromocytoma was suspected. 24-hr urine fractionated metanephrine was 20605 ug( 35-460) and normetanephrine was 5895 ug (110-1050).24-hr urine vanillylmandelic acid was 61.5mg (1.8-6.7).Serum aldosterone ,renin and calcitonin were 22.5ng/dL (1.0-16.0) ,37.22ng/ml/hr and 22.3 pg/ml(0.0-11.5) respectively. TSH was normal. CT and MRI of the abdomen showed a large left adrenal gland measuring 4.4 cm x 4.7 cm with central areas of necrosis and heterogeneous enhancement pattern suggesting pheochromocytoma. Patient was pretreated with phenoxybenzamine, labetalol and metyrosine and had elective left transabdominal radical adrenalectomy. Screening for MEN2 mutation in the RET proto-oncogene was negative. He was continued on labetalol, furosemide and insulin and subsequent echocardiogram showed improved left ventricular function. Conclusion Pheochromocytoma is a great masquerader that may present atypically with acute myocardial infarction, pulmonary edema, dilated cardiomyopathy or cardiogenic shock. In our case, the patient became profoundly hypertensive with acute pulmonary edema after receiving two doses of epinephrine for treatment of anaphylaxis likely due to already high amounts of epinephrine in the circulatory system. Given effective treatment options that significantly improve survival, it is essential to entertain the diagnosis with atypical presentations such as unexplained acute pulmonary edema

Systemic Anticancer Therapy and Thromboembolic Outcomes in Hospitalized Patients With Cancer and COVID-19

IMPORTANCE: Systematic data on the association between anticancer therapies and thromboembolic events (TEEs) in patients with COVID-19 are lacking. OBJECTIVE: To assess the association between anticancer therapy exposure within 3 months prior to COVID-19 and TEEs following COVID-19 diagnosis in patients with cancer. DESIGN, SETTING, AND PARTICIPANTS: This registry-based retrospective cohort study included patients who were hospitalized and had active cancer and laboratory-confirmed SARS-CoV-2 infection. Data were accrued from March 2020 to December 2021 and analyzed from December 2021 to October 2022. EXPOSURE: Treatments of interest (TOIs) (endocrine therapy, vascular endothelial growth factor inhibitors/tyrosine kinase inhibitors [VEGFis/TKIs], immunomodulators [IMiDs], immune checkpoint inhibitors [ICIs], chemotherapy) vs reference (no systemic therapy) in 3 months prior to COVID-19. MAIN OUTCOMES AND MEASURES: Main outcomes were (1) venous thromboembolism (VTE) and (2) arterial thromboembolism (ATE). Secondary outcome was severity of COVID-19 (rates of intensive care unit admission, mechanical ventilation, 30-day all-cause mortality following TEEs in TOI vs reference group) at 30-day follow-up. RESULTS: Of 4988 hospitalized patients with cancer (median [IQR] age, 69 [59-78] years; 2608 [52%] male), 1869 had received 1 or more TOIs. Incidence of VTE was higher in all TOI groups: endocrine therapy, 7%; VEGFis/TKIs, 10%; IMiDs, 8%; ICIs, 12%; and chemotherapy, 10%, compared with patients not receiving systemic therapies (6%). In multivariable log-binomial regression analyses, relative risk of VTE (adjusted risk ratio [aRR], 1.33; 95% CI, 1.04-1.69) but not ATE (aRR, 0.81; 95% CI, 0.56-1.16) was significantly higher in those exposed to all TOIs pooled together vs those with no exposure. Among individual drugs, ICIs were significantly associated with VTE (aRR, 1.45; 95% CI, 1.01-2.07). Also noted were significant associations between VTE and active and progressing cancer (aRR, 1.43; 95% CI, 1.01-2.03), history of VTE (aRR, 3.10; 95% CI, 2.38-4.04), and high-risk site of cancer (aRR, 1.42; 95% CI, 1.14-1.75). Black patients had a higher risk of TEEs (aRR, 1.24; 95% CI, 1.03-1.50) than White patients. Patients with TEEs had high intensive care unit admission (46%) and mechanical ventilation (31%) rates. Relative risk of death in patients with TEEs was higher in those exposed to TOIs vs not (aRR, 1.12; 95% CI, 0.91-1.38) and was significantly associated with poor performance status (aRR, 1.77; 95% CI, 1.30-2.40) and active/progressing cancer (aRR, 1.55; 95% CI, 1.13-2.13). CONCLUSIONS AND RELEVANCE: In this cohort study, relative risk of developing VTE was high among patients receiving TOIs and varied by the type of therapy, underlying risk factors, and demographics, such as race and ethnicity. These findings highlight the need for close monitoring and perhaps personalized thromboprophylaxis to prevent morbidity and mortality associated with COVID-19-related thromboembolism in patients with cancer

Patients recently treated for B-lymphoid malignancies show increased risk of severe COVID-19: a CCC19 registry analysis

Patients with B-lymphoid malignancies have been consistently identified as a population at high risk of severe COVID-19. Whether this is exclusively due to cancer-related deficits in humoral and cellular immunity, or whether risk of severe COVID-19 is increased by anti-cancer therapy, is uncertain. Using data derived from the COVID-19 and Cancer Consortium (CCC19), we show that patients treated for B-lymphoid malignancies have an increased risk of severe COVID-19 compared to control populations of patients with non-B-lymphoid hematologic malignancies. Among patients with B-lymphoid malignancies, those who received anti-cancer therapy within 12 months of COVID-19 diagnosis experienced increased COVID-19 severity compared to patients with B-lymphoid malignancies off therapy, after adjustment for cancer status and several other prognostic factors. Our findings suggest that patients recently treated for a B-lymphoid malignancy are at uniquely high risk for severe COVID-19

Patients recently treated for B-lymphoid malignancies show increased risk of severe COVID-19: a CCC19 registry analysisImpact of B-cell malignancy therapy on COVID-19 outcomes

Patients with B-lymphoid malignancies have been consistently identified as a population at high risk of severe COVID-19. Whether this is exclusively due to cancer-related deficits in humoral and cellular immunity, or whether risk of severe COVID-19 is increased by anticancer therapy, is uncertain. Using data derived from the COVID-19 and Cancer Consortium (CCC19), we show that patients treated for B-lymphoid malignancies have an increased risk of severe COVID-19 compared with control populations of patients with non-B-lymphoid malignancies. Among patients with B-lymphoid malignancies, those who received anticancer therapy within 12 months of COVID-19 diagnosis experienced increased COVID-19 severity compared with patients with non-recently treated B-lymphoid malignancies, after adjustment for cancer status and several other prognostic factors. Our findings suggest that patients recently treated for a B-lymphoid malignancy are at uniquely high risk for severe COVID-19.SignificanceOur study suggests that recent therapy for a B-lymphoid malignancy is an independent risk factor for COVID-19 severity. These findings provide rationale to develop mitigation strategies targeted at the uniquely high-risk population of patients with recently treated B-lymphoid malignancies. This article is highlighted in the In This Issue feature, p. 171