Hello, everyone. I am Steve Pastores from Memorial Sloan Kettering Cancer Center in New York City, and I'm going to be talking about oncologic emergencies for this Board Review course. I have no conflict of interest related to this presentation. Nearly 6% of the ABIM blueprint for the critical care medicine examination will be on hematology and oncology emergencies. In this talk, I'm going to be referring to both classic and novel oncologic emergencies. I'm going to discuss the risk factors and treatment approaches for two of the most common metabolic oncological emergencies, and those are tumor lysis syndrome and hypercalcemia. And then finally, I'm going to describe the clinical presentation and management of emergencies related to hematologic malignancies and immunotherapies for cancer. Shown here are the recent cancer statistics in the United States. It is estimated this year that approximately 1.9 million new cancer cases are going to be discovered, and about 610,000 deaths are going to occur from cancer. Cancer patients account for 6 to 20% of ICU patients. I'd like to divide oncologic emergencies into five big categories, metabolic, structural, cardiopulmonary, malignancy related, and immunotherapy related specifically to the immune checkpoint inhibitors, as well as to chimeric antigen receptor T cell therapy or CAR T cell therapy. Let's talk about metabolic emergencies, starting off with tumor lysis syndrome. This is the most common malignancy related emergency. It occurs when tumor cells release contents into the bloodstream, either spontaneously, as one might see with high-grade hematologic malignancies such as Burkitt's lymphoma, anaplastic T cell, or diffuse large B cell lymphoma. Or more commonly, tumor lysis syndrome occurs after cytotoxic chemotherapy. Tumor lysis syndrome can also be seen in solid tumors, particularly of the stomach, lung, and breast cancer, as well as in patients with large tumor burden who are receiving novel immune therapy agents such as PD-1 inhibitors and bruton-pyrosine inhibitors, as well as patients with solid tumors receiving radiotherapy and high-dose corticosteroids. Tumor lysis syndrome is associated with hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia. Risk factors for tumor lysis syndrome include pre-existing hyperuricemia, rapidly growing tumors, high-grade malignancies such as diffuse large B cell lymphoma and Burkitt's lymphoma, pre-existing renal dysfunction, as well as volume depletion. The Cairo-Bishop classification of tumor lysis syndrome classifies TLS into laboratory TLS and clinical TLS. Laboratory TLS has the presence of at least two or more laboratory abnormalities in serum calcium, phosphorus, potassium, and uric acid in one 24-hour period within three days prior or seven days after cytotoxic therapy. Clinical TLS occurs when laboratory TLS is associated by an increase in serum creatinine or presence of seizures, cardiac dysrhythmia, or sudden death. The majority of patients with grade 3 and 4 TLS will require immediate aggressive management in the ICU. Let's start with the first question. A 55-year-old man with diffuse large B cell lymphoma is treated with rituximab and CHOP chemotherapy. At the start of chemotherapy, his hemoglobin is 10.4, white cell count 95,000 with 95% lymphocytes, platelets of 102,000, serum creatinine 1.1, BUN 25, uric acid 7, and LDH of 625. He has massive spondymegaly and bulky intra-abdominal and retroperitoneal adenopathy. Five days after chemotherapy, he presents to the hospital with flank pain, weakness, and nausea. Laboratory data show an increase in serum creatinine to 2.4, BUN of 55, uric acid of 18, LDH of 1,800, and potassium of 5.9. In addition to intravenous fluids, which of the following intervention should be initiated? Is it A, resvericase, B, immediate hemodialysis, C, immediate CBVH dialysis, D, urine alkalinization, or E, intravenous furosemide? The correct answer here is resvericase, and we will go over these answers. Central to the management of tumor lysis syndrome is intravenous fluid hydration. The goal is to maintain a high urine output and correction of underlying electrolyte abnormalities. The simultaneous use of loop diuretics can be considered to increase urine output. However, diuretics have not been shown to improve outcomes. Urine alkalinization is no longer recommended, as it may increase phosphate and xanthine precipitation in the renal tubules. Alipurinol, a xanthine oxidase inhibitor, prevents formation of uric acid. It is commonly administered 48 hours prior to initiation of cytotoxic chemotherapy. Both intravenous and oral preparations of alipurinol are effective. For patients at high risk for TLS, however, alipurinol is not recommended as first-line prophylaxis. The reason being that existing uric acid must still be excreted, and it may take two or more days to decrease, which allows for urinary nephropathy to occur. Rasburicase, which is a recombinant uric oxidase, degrades existing uric acid to allantoin, which is now more soluble than uric acid, and therefore can be excreted in the urine. Rasburicase has been shown to be superior than alipurinol in not only clearing uric acid, but also in prevention of AKI. The recommended dose is 0.1 to 0.2 milligrams per kilogram IV infusion. It is important to recognize that rasburicase can be associated with serious adverse reactions, including anaphylaxis, hemolysis, methemoglobinemia, neutropenia, respiratory distress, sepsis, and mucositis. A G6PD level should be obtained in every patient being considered for rasburicase therapy. Among patients with G6PD deficiency who get rasburicase, they run the risk of developing hemolysis. Patients with a prior history of anaphylaxis or hypersensitivity reaction should also not be administered rasburicase. Hemodialysis, or continuous venohemofiltration, is only recommended in patients with severe TLS who develop life-threatening electrolyte abnormalities, such as severe hyperphosphatemia, and those patients with renal failure, with associated uremia, volume overload, hyperkalemia, and acidosis. The next metabolic oncologic emergency is hyperkalcemia. This is reported in up to 30% of patients with cancer, most commonly with multiple myeloma, Hodgkin's and non-Hodgkin's lymphomas, adult T-cell leukemia lymphoma, as well as breast, renal, and lung cancer. Umeral hyperkalcemia is the most common mechanism in 80% of cases related to the production of PTH-related protein. Less commonly, hyperkalcemia occurs due to bone destruction or osteolysis, as well as to extrarenal PTH-mediated 125-dihydroxyvitamin D, or calcitriol production. Severe hyperkalcemia is usually associated with a calcium level of 14 or greater milligrams per deciliter. Neurologic, renal, and cardiac manifestations can occur with severe hyperkalcemia that can include altered mental status to coma, polyuria, acute kidney injury, bradycardia, and short QT interval. Management of hyperkalcemia is with volume expansion with saline at 250 cc an hour or greater. Loop diuretics are not routinely recommended and are only reserved for patients with volume overload and congestive heart failure. Calcitonin, 4 units per kilogram subcutaneously or intramuscularly administered every 12 hours, can be effective for up to 72 hours. The agents of choice for management of hyperkalcemia are the biphosphonates. Those include soledronic acid as well as pamidronate. Biphosphonates block bone resorption by osteoclasts and they are the standard of care owing to their efficacy and safety profile. Soledronic acid, 4 mg IV over 15 minutes, is preferred over pamidronate in patients with malignancy-associated hyperkalcemia and normal to slightly impaired renal function. Be aware, however, that soledronic acid can be potentially nephrotoxic and can cause acute tubular necrosis and focal segmental glomerulosclerosis. Corticosteroids are the therapy of choice for malignancy-associated hyperkalcemia that is caused by ectopic PTH calcitriol activation. Hydrocortisone, 200-400 mg per day for 5 days, is a common regimen followed by a 7-day taper of oral prednisone. A relatively new agent, denusamab, has also been shown to be very effective in patients with refractory malignancy-associated hypercalcemia and can be a safe alternative to biphosphonates. Denusamab inhibits osteoclast maturation, activation, and function. It is approved for malignancy-associated hypercalcemia in patients with solid tumors and multiple myeloma. Denusamab is not renally excreted and no dose adjustment is required. However, it can be very, very potent and can sometimes lead to symptomatic hypocalcemia. Let's talk about some of the obstructive oncologic emergencies, starting off with malignant spinal cord compression. This can occur in 5-10% of cancer patients with bony metastases. Lung, breast, and prostate cancers are the most common cancers associated with malignant spinal cord compression. The mechanism is associated with compressive indentation, displacement, or encasement of the thecal sac surrounding the spinal cord or the cauda equina. The thoracic vertebrae are the most commonly involved region for spinal cord compression in 60% of cases and less commonly in the lumbar and cervical regions. Symptoms and signs of spinal cord compression from cancer include back pain, tenderness over the affected spinal region. Patients may develop motor weakness as well as sensory deficits and autonomic dysfunction. The diagnosis is made by MRI of the total spine. However, if MRI is not feasible, then a CT myelogram should be requested. The mainstays of treatment include pain control and preservation of neurologic function. Management primarily is with corticosteroids such as dexamethasone. Additionally, surgical decompression may be required with neurosurgical consultation as well as radiation therapy. The next obstructive oncologic emergency is superior vena cava syndrome. Shown on this slide is a patient with very prominent dilated veins on his upper anterior chest. 70% of SVC syndrome is due to malignancy, especially from the lung as well as lymphomas. The mechanism for SVC syndrome is related to obstruction of blood flow in the SVC due to either extrinsic compression by tumor or by enlarged mediastinal lymph nodes, but also can be caused by direct tumor invasion or device-related thrombosis such as with central venous cateters and pacemakers. Manifestations include facial and upper extremity swelling, neck and superficial chest vein distension as I shown in the previous slide. Patients may also have difficulty breathing, stridor, cough and hoarseness. As shown on the chest x-ray on the top right of the slide, a widened mediastinum may be an important clue to the presence of superior vena cava syndrome. A contrast CT or MRI will reveal this diagnosis. The management of SVC syndrome is to keep the head of the bed elevated, stabilization of the airway if compromised, administration of steroids in patients with stridor, mechanical and pharmacologic thrombolysis may be indicated, SVC stenting in the appropriate setting, systemic anticoagulation in the presence of a thrombus, it's important to avoid over hydration, cautiously use diuretics, and in select cases radiotherapy and chemotherapy will be indicated. Shifting over to cardiopulmonary emergencies, let's talk about cardiac tamponade. This is commonly associated with metastatic lung, breast cancer as well as lymphomas. Manifestations and symptoms include chest pain and dyspnea, hypotension, elevated jugular venous pressure and distant heart sounds or what we call the bec triad may be present as well as pulses paradoxes. On ECG, one may appreciate low voltages, PR depression, and as shown in the ECG below, electrical alternates. A chest radiograph may reveal an enlarged cardiac silhouette, the imaging modality of choice is trans thoracic echo. The classic signs on echo include right atrial collapse, early diastolic collapse of the right ventricle, as well as IVC dilation with absent normal inspiratory collapse. The management of cardiac tamponade includes echo guided pericardial synthesis, pericardial cateter drainage. In some patients, this may require creation of a pericardial window, as well as the administration of sclerosing agents such as Diotiba. Shown here are echo images of pericardial tamponade. On the left is the parasternal long axis view of the heart at the end of systole surrounded by a large pericardial effusion. On the right, the arrow is pointing to the invagination of the right ventricular free wall in early diastole. The next structural oncologic emergency is malignant airway obstruction. Most common cause of this is primary bronchogenic carcinoma. Mechanism of airway obstruction is related to external compression of the trachea or the bronchi by a tumor or lymph node. Classically, patients with malignant airway obstruction will have dyspnea that is worse at night and while lying supine. They may have a productive cough, wheezing, and stridor, especially if the obstruction is located in the trachea or carina. As you can see from the CT image on the right, there is a significant tumor that is located and compressing the trachea and the main central bronchi. The treatment of malignant airway obstruction includes rigid bronchoscopy with stenting as well as radiotherapy or chemotherapy in selected cases. Let's talk about some of the unique hematologic malignancy-related emergencies, starting off with blast crises. This is defined as the presence of greater than 20% peripheral or bone marrow blast cells of either myeloid or lymphoid lineage. Approximately 10% of patients with CML will progress to accelerated phase and ultimately to blast crises. The clinical features include night sweats, fever, weight loss, bone pain, symptoms of anemia, infection, and bleeding. Fortunately, with the advent of imatinib and other novel agents for the treatment of CML, the incidence of blast crises has significantly decreased. Definitive management of blast crises will depend on whether the patient has a myeloid or lymphoid leukemia. Most importantly is to recognize that the most common cause of death in patients with CML blast crises is sepsis due to functional neutropenia. This is hyperleukocytosis and leukostasis. Hyperleukocytosis is defined as greater than 100,000 white blood cells. Leukostasis is symptomatic hyperleukocytosis. It develops when leukemic blast cells aggregate in the microvasculature, causing tissue hypoxia, disseminated intravascular coagulation that can result in organ dysfunction and or failure. Leukostasis occurs in 6 to 20% of patients with adult acute myelogenous leukemia. The pathogenesis involves the abnormal interaction between leukemic blast cells and the endothelium with resulting release of pro-inflammatory cytokines such as TNF-alpha and interleukin-1-beta. The lung and the central nervous system are most commonly involved with leukocytosis and leukostasis syndrome. Because of the extremely high white blood cell count, there can be associated leukocyte larceny causing spuriously low PaO2 or pseudohypoxemia. In these patients, a pulse oximeter may be a more accurate reflection of oxygen saturation rather than the PaO2 from the arterial blood gas. The management of patients with hyperleukocytosis and leukostasis is primarily leukophoresis in AML patients who have greater than 50,000 white cells and in ALL patients whose white cell count is over 250,000. Cytoreduction therapy with hydroxyurea or intensive chemotherapy may also be required. And in one study by Azoulay, the use of dexamethasone resulted in improvement in acute lung injury due to leukostasis from AML. Next oncological emergency related to heme cancers is hyperviscosity syndrome. This is present in 15% of patients with Waldenstrom macroglobulinemia due to very high levels of monoclonal IgM protein. Hyperviscosity syndrome can occur in up to 6% of patients with multiple myeloma of the IgA subtype. And the clinical presentation of hyperviscosity can include neurologic signs and symptoms such as headache, ataxia, seizures and stroke, blurry vision and retinal hemorrhages, mucosal bleeding and constitutional symptoms. The management of hyperviscosity syndrome is plasmapheresis. In these patients, one should avoid transfusions until the hyperviscosity is reduced. And treatment of the underlying malignancy with chemotherapy as well as plobotomy to reduce the hyperviscosity will also be necessary. The next unique hematologic malignancy associated emergency is hemophagocytic lymphohistiocytosis or HLH. This is a life-threatening hyperinflammatory syndrome that can be seen with malignancies as well as with severe viral infections, autoimmune diseases and after CAR T cell therapy. It can also occur after autologous and allogeneic hematopoietic stem cell transplant associated with graft-versus-host disease. HLH is associated with high mortality and involves the release and activation of several pro-inflammatory cytokines such as TNF, IL-1 and IL-6. The diagnostic criteria of HLH requires the presence of at least five of the eight following criteria. Fever, splenomegaly, at least two lines of cytopenias, hemophagocytosis in the bone marrow spleen, lymph node or liver as shown up on that slide which is showing hemophagocytosis in the bone marrow, elevations in triglycerides, low fibrinogen, low or absent natural killer cell activity, high ferritin levels and elevation in soluble IL-2 receptor. The management of HLH includes supportive transfusions of red blood cells, platelets, plasma and cryoprecipitate, infectious disease workup and management, blood pressure control, the use of etoposide and steroids, and in selected patients, the use of emapalumab, which is an interferon gamma monoclonal antibody has been shown to be effective. Other treatment modalities include the JAK inhibitor roxalutinib, alantuzumab, cyclosporine, IVIG, anakinra, vincristine, paracetamide and siltuximab, an IL-6 inhibitor have also been tried as well as extracorporeal removal of cytokines with the use of the cytosol technology. Here is my next case for the Q&A. A 55-year-old male with history of hypertension and 20-pack year of smoking was diagnosed with metastatic renal cell carcinoma. He starts treatment with nivolumab and ipilimumab every two weeks for the first four cycles and then continues on single drug nivolumab every two weeks after. He comes to the hospital with fatigue, altered mental status, refractory hypotension requiring ICU admission. Laboratory data reveal a low serum sodium of 116, potassium 4.9, hemoglobin 7.8, white count of 12,000 with 90% PMNs, platelets of 102, creatinine 1.5, BUN50. In addition to IV fluids and vasopressors, which of the following intervention should be initiated? Is it A, ceftazidime and vancomycin, B, red blood cell transfusion, C, continuous venovenous hemofiltration, D, hydrocortisone or E, obtain a CT scan of the abdomen? Correct answer is D, hydrocortisone. And we'll go over the answers. In this final section of the talk, I'm going to talk about the immunotherapy-related toxicity, specifically related to the immune checkpoint inhibitors and CAR T cell therapy. Over the last 10 years, there have been at least close to a dozen checkpoint inhibitors that have already been approved. These are generally inhibitors that target cytotoxic delymphocyte antigen 4, or CTLA-4, as well as program death 1, PD-1, and program death ligand 1, or PD-L1. These checkpoint inhibitors have been shown to be efficacious in the treatment of patients with metastatic melanoma, non-small cell lung cancer, renal cell carcinoma, as well as other urethral cancers. The main toxicities from checkpoint inhibitors are neurotoxicity, pulmonary toxicity, and other organ toxicities, such as endocrine toxicity, hypophysitis, which was the case that I gave you the question. It relates to a patient that developed severe hypophysitis, causing adrenal insufficiency and refractory hypotension. The neurotoxicity associated with checkpoint inhibitors may present with aseptic meningitis, as well as peripheral neurotoxicities, such as Guillain-Barre syndrome, myasthenia gravis. Patients may also develop seizures, encephalitis, and cerebral edema. Pulmonary toxicity is usually in the form of pneumonitis, although cases of alveolar hemorrhage have also been reported. Other toxicities with checkpoint inhibitors include pericarditis and myocarditis, liver, renal, as well as hepatotoxicities. The management of severe checkpoint inhibitor toxicities, such as severe colitis, hypophysitis, pneumonitis, aseptic meningitis, and myocarditis will generally require consideration for ICU admission. It is important to rule out infection and cancer progression in these patients. Corticosteroids are the mainstay of treatment for these patients. Because some of these toxicities can be reversed, these patients should be considered for mechanical ventilation, use of vasopressors, renal replacement therapy, and even extra corporeal life support for those with severe refractory hypoxemia. In patients that fail to respond to steroids, consideration of other immunosuppressive agents or steroid sparing agents, such as infliximab, as well as chemotherapeutic agents, cyclophosphamide and mycophenolate may be useful. IVIG can also be tried, as well as plasma exchange. Let's talk about CAR T-cell therapy. Chimeric antigen receptor T-cells Chimeric antigen receptor T-cells are T-cells that are genetically engineered to produce an artificial T-cell receptor that targets specific tumor antigens on cancer cells. CAR T-cell therapy has revolutionized the care of many patients with advanced hematologic malignancies. CAR T-cells are considered a living drug against cancer cells. Panel A on this slide shows the general steps in CAR T-cell therapy, in which first the white cells are isolated from the patient through leukophoresis. They're then taken to a manufacturing practice production facility where the T-cells are activated, genetically engineered with a retrovirus encoding the CAR. The CAR T-cells are further expanded in vitro, harvested, and then finally re-infused into the patient who has undergone a preparative limpodepletion regimen, most commonly with cyclophosphamide and glutarabine before the CAR T-cells are infused. Panel B shows the differences in design of the anti-CD CARs, which are the CARs that have been approved to date. They're largely of the second-generation variety that have the co-stimulatory domains such as CD28 or 4-1BB. The two most common toxicities associated with CAR T-cell therapy are cytokine release syndrome and neurotoxicity, or now called immune effector cell-associated neurotoxicity syndrome, or ICANS. Other toxicities are secondary HLH, grade 3 or 4 cytopenias persisting beyond 30 days, uncommonly tumor lysis syndrome, and B-cell aplasia and hypogammaglobulinemia, which may require the administration monthly of intravenous gamma globulin in many of these patients. Cytokine release syndrome is the most common toxicity associated with CAR T-cell therapy. This is a hyperinflammatory syndrome that is mediated by IL-6 and IL-1 that is released from activated macrophages and monocytes. It occurs in 10% to 30% of patients that receive CAR T-cell therapy, and most commonly occurs in patients with high disease burden, those who receive hard CAR T doses, and those that receive glutarabine-based lymphodepleting chemotherapy. Cytokine release syndrome, or CRS, can have many signs and symptoms, which can be gradual in onset. They typically start two to three days after CAR T-cell infusion. Constitutional symptoms, including very high fevers, rigors, malaise, anorexia, and arthritis are very common, but every organ in the body from head to toe can be affected. Laboratory findings in CRS are variable. Typically, we'll have elevations in C-reactive protein, ferritin, and IL-6, and occasionally derangements similar to that that we see in patients with tumor lysis syndrome, such as electrolyte abnormalities. The grading of CRS has been standardized by the American Society of Transplantation and Cellular Therapeutics into grades one to four. The three domains are fever, hypotension, and hypoxia. Patients with grade three or four CRS are patients that will have hypotension or shock requiring one or more vasopressor. They will have evidence of cardiomyopathy and even unstable or life-threatening arrhythmias. Grade three patients are also going to be hypoxemic, requiring high flow oxygen. And patients with grade four are generally those with severe hypoxemia requiring non-invasive positive pressure or mechanical ventilation. The management of CRS has also been standardized by the ASCSD. And for most patients with grade one, these are usually patients that will require supportive treatment with antipyretics, hydration, infectious disease workup, and management with broad-spectrum antimicrobials, because these patients can certainly have manifestations of sepsis and could be infected. For patients with grade two, in addition to supportive measures, consideration for ICU admission if it's a high-risk patient, and administration of tocilizumab, which is an IL-6 receptor antagonist, or siltuximab, which is a direct IL-6 inhibitor. For patients with grade three or four with associated hypotension requiring vasopressors or requiring high flow oxygen or even invasive mechanical ventilation, these patients will require treatment with corticosteroids, such as dexamethasone, 10 to 20 milligrams, IVQ6 hours. And in some patients with very severe CRS, the use of pulse-dosed steroids will also be indicated. Tocilizumab is the IL-6 receptor antagonist that is used at a dose of 8 milligrams per kilogram, not to exceed 800 milligram total dose. In patients who are refractory to the use of tocilizumab, siltuximab, which is a direct IL-6 inhibitor, as well as pulse-dosed steroids, and anakinra, which is an anti-IL-1 receptor antagonist, may also be required. Neurotoxicity, or ICANS, is another major toxicity from CAR T-cell therapy. This is felt to be related to impairment of the blood-brain barrier integrity, resulting in leukocyte and cytokine infiltration into the CSF. This will typically occur 45 days after CAR T-cell therapy, and antecedent or previous severe CRS is the primary risk factor for neurotoxicity. Other risk factors for ICANS include a history of neurologic disease, high tumor burden, receipt of high CAR T-cell dose, CD28 co-stimulated CAR T products, and having an abnormal MRI of the brain. The clinical symptoms can include encephalopathy, headache, obtundation, word-finding difficulty, aphasia, as well as coma and seizures. Laboratory markers of neurotoxicity include elevations in cytokines, IL-6, IL-10, IR-12, interferon gamma, GM-CSF, as well as elevations in C-reactive protein. Shown here are brain MRI images in patients with ICANS following CD19 CAR T-cell therapy. On the top left, you can see symmetric edema of the deep structures. On the top right, you can see global cerebral edema with blurring of the gray-white junction and slit-like ventricles. Lower left panel, you'll see diffuse leptomeningeal involvement. And on the lower right, you'll see focal white matter hyperintensities. In many patients, however, neuroimaging may be completely normal, particularly in those with milder forms of neurotoxicity. The grading has also been standardized for ICANS, and they range from grade 1 to 4. Patients' domains include the ICE score or the encephalopathy score, level of consciousness, seizures, cerebral edema, and more findings of the other domains. Patients with grade 3 or 4 will require admission to intensive care. These are patients that will only awaken to tactile stimuli or may be actually stuporous or comatose. They may have partial or status epilepticus, focal, local, or diffuse cerebral edema, and may also have severe focal motor deficits if they have grade 4 neurotoxicity. This is the ICE score where patients are asked about their orientation, the ability to name three objects, follow simple commands, write a sentence, and ability to count backwards. Management of grade 1 and 2 ICANS is supportive. We do EEGs to rule out seizures and brain imaging to rule out cerebral edema. Prophylactic antiepileptic agents such as Lavera teracitam or Keppra is started on day of CAR T cell infusion in those patients with high incidence of ICANS. Tocilizumab should only be used if there is concurrent CRS with the neurotoxicity. For patients with grade 3 or 4, corticosteroids, dexamethasone 10 to 20 milligrams, Q6, and supportive care is needed, and impulse-dose steroids may be indicated in those with more severe grade 4 toxicity. These patients require ICU admission, mechanical ventilation for airway protection, seizure management, as well as management of cerebral edema with high-dose steroids and measures to lower ICP such as hyperventilation, osmolar therapy with mannitol and or hypertonic saline. And in some patients, VP shunting may be required with neurosurgical consultation. In summary, oncologic emergencies can be divided into metabolic, structural, cardiopulmonary, malignancy-related, and immunotherapy-related. It is important to promptly recognize and institute appropriate therapy for oncologic emergencies because they can be lifesaving. And it is crucial for intensivists and ICU clinicians to have a working knowledge of diagnosis and management of not only the classic oncologic emergencies, but also the toxicities related with checkpoint inhibitors and CAR T-cell therapy. Thank you very much for your attention.

oncologic emergencies

metabolic emergencies

structural emergencies

cardiopulmonary emergencies

hematologic malignancy-related emergencies

toxicities associated with immunotherapy

CAR T-cell therapy

case scenarios