Onc lec 5

what causes spinal cord compression?

cancers that metastasize to spinal column causing injury from edema, hemorrhage, and pressure induced ischemia

Where does spinal cord compression most commonly arise?

thoracic spine

What happens w/ persistent compression of the spinal cord?

irreversible changes to myelin sheaths → neurological impairment

what is often a late sign of spinal cord compression?

bowel and bladder dysfunction that can progress to incontinence

What are signs/sx of spinal cord compression?

back pain at level of tumor aggravated by lying down, weight bearing, and sneezing/ coughing (usually first sx)

progressive weakness

sensory changes

incontinence

ataxia

when dx spinal cord compression, what should you do if you are ever in doubt?

image the entire spine (MRI/Xray/bone scan) - don’t want to miss a tumor

what is the tx for spinal cord compression?

STAT corticosteroids to reduce edema in spinal cord (IV dexamethasone) and consult oncology / surgery

What may be the initial finding of a pt w/ cancer?

malignant effusions

What are malignant effusions?

fluid fills pleural space, pericardial space, or peritoneal space

involves direct contact w/ serous surface OR blockage of lymph drainage

what is a life threatening sx of malignant pericardial effusions?

hypotension → may indicate cardiac tamponade

What are lab findings for malignant effusions?

fluid analysis reveals presence of malignant cells and exudative fluid

What scans can your order for malignant effusion dx?

Xrays, ultrasound, echocardiography

what is the tx for malignant effusions?

tx underlying cancer and drain fluid for relief of sx

How do you drain pleural effusions?

large volume thoracentesis or indwelling pleural catheter

how do you tx pericardial effusions?

needle aspiration or catheter placement

how do you tx malignant ascites?

large volume paracentesis, catheter or port placement, or peritoneovenous shunt placement

what is the most common paraneoplastic endocrine syndrome?

hypercalcemia

what are the most common cancer causes not hypercalcemia?

multiple myeloma, breast cancer, lung cancer (NSCLC), lymphoma

what causes the sx assoc. w/ hypercalcemia?

ionized/free calcium

Why would the total serum calcium concentrations in pt’s w/ low or high serum albumin not accurately reflect the calcium concentration?

Ca in serum is bound to proteins, usually albumin (if albumin is low, free calcium would be higher, etc)

need to calculate the corrected serum ca

what would a corrected serum ca >12 mg/dL indicate?

cardiac arrhythmias, which may lead to sudden death (possible short QT interval)

What are tx for hypercalcemia?

IV hydration w/ 0.9% NS, calcitonin, bisphosphonate, and dialysis (last resort)

What cancers does tumor lysis syndrome (TLS) occur in?

most often during chemo in lymphoma and leukemias

can occur w/ other tumor types that have high proliferative rate (acute lmphyoblastic leukemia and burkitt lymphoma) or high sensitivity to chemo

what causes TLS?

massive relate of cellular material into systemic circulation (nucleic acids/uric acids, proteins, phosphorus, K+)

What abruptly develops with the impaired metabolism/excretion of TLS?

hyperuricemia, hyperkalemia, and hyperphosphatemia (w/ secondary hypocalcemia)

What TLS tx is reserved for high risk scenarios?

rasburicase

How does TLS cause acute kidney injury?

crystallization and deposition of uric acid and calcium phosphate in renal tubules; can exacerbate hyperphosphatemia and hyperkalemia

When is a nephrology referral required in TLS?

dec urinary output, rising Cr levels, persistent hyperphosphatemia

what is a medical emergency in patients w/ neutropenia?

infection / fever

What is neutropenia?

neutrophil count < 1500 / ul (severe is under 500 and profound is under 100)

What does neutropenia result from?

myelosuppresive and immunosuppressive effects of chemo

malignant infiltration of bone marrow inhibiting hematopoiesis

What is considered low risk febrile neutropenia?

expected duration of ANC < 500 cells/ul and is less than 7 days w/ no comorbidities or evidence of hepatic/renal dysfunction

(usually solid tumors)

what is considered high risk febrile neutropenia?

expected duration of ANC < 500 cells/uL is greater than 7 days, ongoing comorbidities, or evidence of hepatic/renal dysfunction

(usually blood cancers)

A pt presents to the ED w/ SIRS and recently received systemic anticancer therapy w/in the past 6 weeks. What should you always assume for the diagnosis until proven otherwise?

neutropenic sepsis syndrome

What is systemic inflammatory response syndrome (SIRS)?

2 or more of the following:

fever >38C or < 36C

HR > 90 BPM

RR > 20 or PaCO2 < 32mmHg

abnormal WBC count (>12,00, <4,00, or >10% immature/band forms)

What should fever >100.4 in a patient w/ neutropenia be considered until proven otherwise?

infection- can be life threatening

How does chemo lead to potential sources of infection?

long term venous access; causes stomatitis, mucositis, N/V/D

What organism is the most common cause of infection in febrile neutropenia?

gram positive organisms

What organism is generally associated w/ more serious febrile neutropenia infections?

gram negative organisms (esp. pseudomonas aeruginosa)

What organisms are more common in high risk (prolonged) neutropenic patients?

fungal

What organisms are more common in high risk febrile neutropenia patients who need prophylactic antivirals like acyclovir?

viral- human herpes virus

Tx for febrile neutropenia

empiric broad spectrum abc begun asap after blood culture obtained - w/in 1 hr of presentation

what should all patients w/ anticipated prolonged neutropenia be placed on?

prophylactic anti-infective

what is transfusion related acute lung injury (TRALI)?

new ALI / ARDS occurring during or within 6 hrs after blood product administration ; docuemented by hypoxemia and abnormal chest imaging

what are DDX of TRALI?

TACO (transfusion-accelerated circulatory overload), ARDS, other transfusion reactions

what is the tx for TRALI?

discontinue transfusion immediately (alert blood bank and initiate transfusion rxn eval) and supportive care

what is hemophagocytic lymphohistiocytosis (HLH)?

aggressive and life threatening syndrome of excessive immune activation

→ excessive inflammation and tissue destruction from persistent activation of macrophages, NK cells, CTLs → excessive cytokine storm/production

what causes HLH?

often follows infx or alteration in immune homeostasis- immune activation or immune deficiency (lymphoid malignancies)

what is the goal of tx in HLH?

suppress life threatening inflammation by destroying immune cells

induction tx- weekly dex and etoposide; intrathecal methotrexate if CNS involvement

no improvement, mutations, or relapse- allogeneic stem cell transplant

What is CAR-T therapy?

chimeric antigen receptor (CAR) genetically modified T cells recognize specific ags on tumor cells → activation and proliferation → significant and durable destruction of malignant cells

considered “living drug” and persists for long time

what are acute toxicities of CAR-T therapy?

cytokine release syndrome, ICANS, cytopenia, acute infusion toxicity, TLS, coagulopathy

what is cytokine release syndrome (CRS)?

systemic inflammatory dz w/ broad range of mediators/clinical indicators (ferritin, CRP, IL6)

caused by CAR-T therapy

what is the hallmark presenting sign of CRS?

fever that occurs after infusion of immune effector cells

what is immune effector cell-associated neurotoxicity syndrome (ICANS)?

pathologic process involving CNS following immune therapy that results in activation of engagement of endogenous or infused T cells/other immune effector cells