Exam 2 Flashcards

Question

What insufficiencies should we be cautious with for morphine, hydromorphone, oxycodone, fentanyl, methadone

Answer 1

Morphine: most common - metabolized in the liver (caution) - excreted renally (caution) Hydromorphone: - metabolized in the liver (caution) - excreted renally (caution) Oxycodone: - metabolized by CYP2D6 (liver) - no IV formulation Fentanyl: most potent - safe in liver and renal dysfunction - very toxic Methadone: - don't use in sever liver dysfunction - no adverse effects in renal failure - t1/2 is very unpredictable

Answer 2

Consider: - true morphine allergy - opioid-induced ADRs - pain refractory to other opioids at high doses - neuropathic pain - in need of long-acting oral dosage form at low cost Avoid: - numerous drug interactions - risk for syncope or arrhythmias - hx of unpredictable adherence - poor cognition

Answer 3

Constipation - always add a bowel regimen (pts never develop tolerance to constipation Sedation - tolerance helps, hold sedatives, consider dose reductions N/V - change opioid, consider adding anti-emetic Pruritus (itching) - decrease dose, change opioid, add anti-histamine Hallucinations/confusion/delirium - decrease dose, change opioid, consider adding neuroleptic medication Myoclonic jerking - consider changing opioid or treating underlying causes Respiratory Depression - hold opioid, give low dose naloxone (give slowly)

Answer 4

- PCA: patient can choose when to administer their doses of pain meds to a certain point (IV) - Celiac plexus block: the celiac plexus is a group of nerves that supply the organs in the abdomen. Here, the pain medications are ineffective. So we deactivate the nerves through a procedure. Used commonly with pancreatic cancer patients. - Intrathecal pain pump: similar to insulin pump. It's implanted into pt spine. Used in pts who are refractory to other opioid therapy or increased toxicities. The meds are way more potent through this route (300:1) - Radiation therapy: Can treat metastases. - Bisphosphonate therapy

Answer 5

The tumor cells can produce procoagulants and fibrinolytic activity. This directly increases blood clotting through thrombin & fibrin formation. Additionally, adhesion receptors are expressed that release cytokines and angiogenic factors. This activates host cell procoagulant and pro-adhesive cells. Both of these processes together result in a hyper-coagulable state.

Answer 6

Patient and Cancer: - Active cancer - Advanced stage cancer - Cancer type - Older age - Poor performance status - Medical co-morbidities Treatment: - Major surgery - Central venous catheter - Chemotherapy - Exogenous hormone therapy - ESAs Modifiable Risks: - Smoking - Obesity - Activity level

Answer 7

Monotherapy: start pt on monotherapy for a minumum of three months, continue indefinitely while cancer is active, or if other risk factors persist. If catheter related, can stop after 3 months - DOACs: preferred in pts w/o gastric or gastroesophageal lesions (low VTE recurrence, but these have higher relevant non-major bleeding) - LMWHs: preferred in pts w/ gastric or gastroesophageal lesions - Factor XA inhibitors: - UFH Combo therapy: minimum of 3 months, stop at 3 months if catheter related - LMWH -> Edoxaban - LMWF/UFH/Fondaparinux -> Warfarin - If cannot have LMWH: LMWH/UFH -> Dabigatran

Answer 8

Breast: breast self exam once 20 years old, annual mammogram from 45-54 (can start at 40), biennial mammograms at 55 years old Prostate: Men at least 50yo, so annual screening if PSA is over 2.5 ng/mL, every 2 years if <2.5 ng/mL +/- digital rectal exam (DRE); High risk pts should start discussion at 45 years old - 1º degree relatives with prostate cancer puts pt at higher risk, AA race, increasing age, abnormal DRE Colon: screen once 25 years old regardless of male/female, colonoscopy every 10 years - detect cancer: annual fecal occult blood test (FOBT) shows many false positives; annual fecal immunohistochemical test (FIT) also test Hb w/o the false +; FIT DNA tests Hb and DNA biomarkers - detect cancer and advanced lesions: endoscopy/colonoscopy every 10 years Lung: low dose CT scans - consider in pts age 55-74 w/ 30 year pack smoking history, still smoking or have quit w/in last 15 years, and willing to have curative lung surgery if detected Cervical: No effective screening tool, just do annual physical and pelvic exam. If high risk, can start pelvic exams/ultrasounds every 6-12months starting at age 25-35. Melanoma: examine your skin, high-risk pts can receive yearly clinical exams

Answer 9

Breast: high risk patients (BRCA mutations) can talk about surgeries (prophylactic mastectomy, bilateral oophorectomy); tamoxifen decreases risk (some bad side effects), raloxifene decreases risk & both FDA approved Prostate: finasteride decreases risk & is FDA approved Colon: diet (high fiber, low fat, calcium rich), NSAIDs/ASA/celecoxib may decrease risk, but increased risk for bleeding, so we don't really use. Lung: Stop smoking Cervical: oral contraceptives, prophylactic oophorectomy, have children Melanoma: sunscreen >SPF 15, avoid tanning beds

Answer 10

- Risk increases with age - family history (& BRCA-1 and 2) - previous breast cancer - radiation from prior treatment for environmental radiation exposure - estrogen exposure endogenously or exogenously - alcohol - prior breast biopses with proliferative histology - last first birth (>30yo) or never having kinds - elevated BMI - Diet *more than 60% of pts will not have any risk factors

Answer 11

*adjuvant = therapy after surgery; neoadjuvant: therapy before surgery Stage I, II, IIIA - our goal is to cure. Surgery is involved. Some II and IIIA patients will do neoadjuvant therapy (larger tumors). Most patients will do adjuvant therapy. Stage IV (metastatic): Goal is no longer to cure. Treatment is palliative and mostly involves chemo, hormonal, +/- biologics, +/- immunotherapy. Surgery only used for symptomatic relief.

Answer 12

hormonal therapy: - tamoxifen: SERM, remember DVT and endometrial cancer adverse effects - Leuprolide, Goserelin: LHRH analogs, use in premenopausal women (ovarian suppression) - letrozole, anastrozole, exemestane: use in post-menopausal women (or use ovarian suppression if premenopausal), watch out for osteoporosis chemotherapy: - doxorubicin: anthracyclin (cardiotoxicity) - cyclophosphamide: alkylating agent - paclitaxel: taxane (microtubule inhibitor) biological therapy - trastuzumab (don't use with doxorubicin due to cardiotoxicity) - pertuzumab - CDK4/6i: abemaciclib, palbociclib, ribociclib radiation surgery

Answer 13

If tumor is small (≤0.5cm): hormonal therapy - if HER2 positive, give HER2 targeted therapy if tumor is bigger than 0.5cm or 1-3 pos nodes, do the oncotype dx test: - if low risk (<26), pt needs hormonal therapy only if high risk (≥26), pt needs hormonal and chemo - if HER2 positive, give HER2 targeted therapy if pt is premenopausal at diagnosis, we will likely give aromatase inhibitors + ovarian suppression for 5 years. At the 5 year mark, we may do an additional 5 years. (could also do tamoxifen) if pt is postmenopausal at dx, we will likely give aromatase inhibitor for 5 years, then maybe another 5 years

Answer 14

if tumor is bigger than 0.5cm or 1-3 pos nodes, do the oncotype dx test: - if low risk (<26), pt needs hormonal therapy only if high risk (≥26), pt needs hormonal and chemo - if HER2 positive, give HER2 targeted therapy adjuvant chemo longer than 3-6 months does not improve survival in HER 2 negative disease: - Dose dense AC -> Paclitaxel: doxorubicin, cyclophosphamide, followed by paclitaxel (dose dense gives same amount of chemo in a shorter time, which is good) - If heart disease - TC: docetaxel, cyclophosphamide

Answer 15

- dexamethasone - antihistamine - famotidine give albumin bound paclitaxel to mitigate the hypersensitivity reaction

Answer 16

want to do 1 full year of HER2 targeted therapy APT: (adjuvant) - paclitaxel - trastuzumab w/ first dose of paclitaxel - trastuzumab weekly TCH: - docetaxel - carboplatin - trastuzumab TCH + pertuzumab: - docetaxel - carboplatin - traztuzumab - pertuzumab *if residual disease found after surgery, can switch to ado-trastuzumab, just need HER2 therapy to be 1 year long total

Answer 17

HER2 -, ER - , PR - Immunotherapy - pembrolizumab (PD1 inhibitor) added into chemotherapy regimen AC -> Paclitaxel - doxorubicin - cyclophosphamide - pembrolizumab (for total of 1 year)

Answer 18

Our goal shifts from cure to palliative care. Survival time can vary based on where the cancer is (bone and soft tissue metastases usually have better prognosis). ER/PR+, bone mets, asymptomatic visceral disease: Hormone therapy (aromatase inhibitor + CDK-i) (if bone disease, add bisphosphonate or denosumab) OR clinical trials ER/PR-, symptomatic visceral disease, or hormone refractory: - If HER2+, use anti-HER2 therapy +/- chemo: docetaxel, trastuzumab, and pertuzumab OR paclitaxel, trastuzumab, and pertuzumab - If HER2-, do chemo

Answer 19

*testosterone is a growth signal to the prostate, so if something increases exposure to testosterone, it'll increase risk of prostate cancer - age (typically ≥60 yo) - african-americans - family hx - potentially diet, occupation

Answer 20

- alterations in urinary habits - impotence - lower extremity edema - weight loss - anemia **early stage will likely be asymptomatic

Answer 21

Gleason score (2-10) - 2-4 are slow-growing, well differentiated -8-10 are aggressive, poorly differentiated PSA: >4ng/mL requires evaluation >10ng/mL is highly suspicious for malignancy *also look at velocity, if increase is >0.75 per year, that's suspicious

Answer 22

Observation - Watch and wait. If they start developing symptoms, we can treat palliatively. - Good for an older man (don't want to be too aggressive for no reason) Active surveillance - Watch and wait. If PSA starts to go up, we are going to treat with curative intent. Radiation - external beam (radiation from the outside in) VS. brachytherapy (radiation pellets placed around prostate. This method comes with side effects and complications (ex. rectal symptoms, ED, etc.) Adrogen Deprivation Therapy - Use with radiation if pt is high risk. Use an LHRH agonist +/- antiadrogen (abiraterone, bicalutamide, etc.) Prostatectomy - definitive curative therapy. Very effective, but comes with potential complications.

Answer 23

m1 = metastatic found on scans m0 = PSA is going up, but we can't find it on the scans HSPC = hormone sensitive prostate cancer CRPC = castrate resistant prostate cancer (failed hormone therapy) m1HSPC low volume = 1-2 mets m1HSPC high volume = numerous mets

Answer 24

first line - palliation of disease. We want to suppress testosterone production and determine the PSA doubling time (if it doubles fast, we have progressing disease) m0HSPC - consider ADT if the PSA doubling time is less than 6 months. Can use LHRH agonists (these are reversible and as effective as orchiectomy). Also can do orchiectomy (now we no longer need LHRH agonist). - can do intermittent ADT, where we stop ADT once we lower the PSA, then start again when the PSA rises again. This can decrease side effects & cost, and it's just as effective. This is only if we have increasing PSA but we can't find mets on a scan!!

Answer 25

This is when the PSA is still increasing, but it is not responding to ADT and there's no distant metastasis found. 1. continue ADT (usually LHRH agonist) 2. Add anti-androgen - enzalutamide: unique toxicities like causing falls, decrease seizure threshold, "enzalutamide syndrome" that causes brain fog/confusion - apalutamide: risk for seizures, falls, etc. - darolutamide: structurally different, so it has less adverse effects. Less seizures or falls. **abiraterone is not approved for m0!!!!

Answer 26

Leuprolide, Eligard, Goserelin, Triptorelin, Histerelin *no one is better than another, just go based off of what gets paid for by insurance Relugolix - oral agent!! With less cardiovascualr events! Acute toxicities: tumor flare (give with another med (anti-androgen like bicalutamide) to reduce the flare), gynecomastia, hot flashes, ED, edema, injection site reaction Long term: osteoporosis, fracture, increase in fat mass, insulin levels, and cholesterol/triglycerides

Answer 27

Therapy is determined based on the volume of disease. - Low volume: ~1-2 mets - High volume: numerous mets Low volume: 1. ADT 2. Continue ADT and add abiraterone+prednisone, enzalutamide, or apalutamide - abiraterone relatively well tolerated, considered better than enzalutamide. Not the best in adrenal insufficiency High volume: - could do anything that was previousy mentioned (ADT), but now chemo is an option - ADT + abiraterone + prednisone - ADT + enzalutamide - ADT + apalutamide 1. docetaxel + ADT - can do ADT + docetaxel + abiraterone/darolutamide

Answer 28

- continue ADT - want to maintain castrate testosterone concentrations 1. Sipuleucel-T (but $$$, so not used a lot) 2. docetaxel (alone or in combo w/ abiraterone or darolutamide) 3. Cabazitaxel (unlike other taxanes) 4. more options *can do bisphosphonate or radium 223 for bone metastases. causes lots of myelosuppression though. Do radium 223 after trying bisphosphonate

Answer 29

- Smoking - Asbestos exposure - Heavy metals/ionizing radiation - Genetic predisposition Etiology: chronic exposure of epithelial cells to carcinogens, which results in chronic inflammation. This induces genetic and cytologic changes, which eventually leads to carcinogenesis. Mutations: - EGFR: mutation predicts sensitivity to tyrosine kinase inhibitors - K-RAS: mutation predicts resistance to our tyrosine kinase inhibitors - ALK: will likely be less sensitive to EGFR inhibitors and chemo - ROS-1 - BRAF V600E *pts with EGFR mutations or ALK/ROS-1 rearrangements typically don't have PD1 expression

Answer 30

Non-small cell: slower growth fraction. Moderately sensitive to radiation, marginally sensitive to chemo. - adenocarcinoma: (50%) most common in non-smokers - squamous: (30%) clearly related to smoking Small cell: (15%) related to smoking. Fast growing and rapidly progressive. Highly sensitive to radiation and chemotherapy

Answer 31

Limited stage: one small area they can treat with radiation Extensive stage: more than one small area if they were to treat with radiation Limited stage: curative intent - radiation + combo chemotherapy (platinum doublet: cisplatin + etoposide OR carboplatin + etoposide). *carboplatin causes less toxicity compared to cisplatin, but more myelosuppression - If pt responds really well to this treatment, we can do prophylactic cranial radiation, since over 50% of pts will develop brain metastases - After the chemo and radiation, we don't treat any further. Extensive: rarely curable - no radiation - chemo (cis/carboplatin + etoposide/irinotecan) - prophylactic cranial radiation if chemo works - now we include immunotherapy. atezolizumab or durvalumab. also can do pembrolizumab if pt failed the platinum doublet.

Answer 32

- NSCLC is only moderately sensitive to radiation and has low sensitivity to chemotherapy Surgery is most efficacious for NSCLC. If this is not able to be performed, we can do radiation for early stage NSCLC Treatment: - neoadjuvant - surgery - chemotherapy (platinum doublet) followed by immunotherapy (nivolumab (PD1i) or oral agent; if non-squamous, do ciplatin + pemetrexed; if squamous, cisplatin + gemcitabine OR cisplatin + docetaxel; if someone can't tolerate cisplatin, switch to carboplatin - osimertinib is also an option (T790M)

Answer 33

If unrescetable: - chemotherapy AND radiation - if non-squamous, do cisplatin + pemetrexed - if squamous, do cisplatin + gemcitabine OR cisplatin + docetaxel - for late stage III and IV disease, no platinum doublet is better than another - also immunotherapy for up to a year

Answer 34

If a patient has a targetable mutation and is PD-L1+, it is preferred to use the oral therapies first, then move to immunotherapy later. - Osimertinib: 1st line for EGFR mutations - Dabrafenib + Trametinib: 1st line for BRAF therapies - Sotorasib: K-RAS G12C Mutation If no mutation, or if targeted oral chemotherapy options have been exhausted, check the PD-L1 status (use pembrolizumab) - non-squamous mutation negative, do carboplatin + pemetrexed + pembrolizumab - squamous, do platinum doublet + immunotherapy if they can tolerate both: pembrolizumab + carboplatin + paclitaxel (or albumin bound)

Answer 35

New immunotherapies have shown to be effective - atezolizumab - durvalumab - pembrolizumab these can be added to extensive small cell lung cancer

Answer 36

Immunotherapy toxicities: tissue inflammation pretty much anywhere Rare and serious immune mediated toxicities: - pneumonitis - colitis - hepatitis - nephritis - endocrine (thyroid, pituitary)

Answer 37

3rd leading cancer in incidence and death in men and women. - about 100,000 new cases in 2023 with around 50,000 deaths The 5-year survival is around 91% in early disease. More and more young people are getting diagnosed with colon cancer. - This means colon cancer screening is very important

Answer 38

- age (increases after 40 years old, even greater after 50 years old) - family hx of colon cancer - polyps can go onto turn into cancer - dietary factors (high fat, low fiber, reduced folate, reduced calcium) - lifestyle (alcohol, smoking, obesity) - Ulcerative colitis (Crohn's disease) results in 5-10x higher risk - Familial Adenomatous Polyposis (FAP) -> nearly 100% lifetime risk - Hereditary Nonpolyposis Colorectal Cancer -> 80% risk

Answer 39

Malignant polyps grow from inner basement membrane of the bowel wall outward into the mucosa, submucosa, muscularis, and serosa. It can/will spread via lymphatic and hematogenous routes to the lymph nodes, lungs, liver, and bone *testing for MSI (microsatellite instability) can tell us whether or not to use chemo. dMMR (DNA mismatch repair) means immunotherapy will work well

Answer 40

For stage I-III, curing is the goal. Stage I: surgery & that's probably it. Stage II: no chemo (unless certain high risk people), yes surgery. If a patient has MSI high disease, chemo will not be a benefit!! No chemo for these people. - must test for MSI!!!! - IF we give chemo, it'll be FOLFOX (5-FU, Leucovorin, and Oxaliplatin) OR CapeOX (capecitabine and oxaliplatin) Stage III: surgery & give chemo - FOLFOX or CapeOX - for low-risk people, CapeOx for 3 months was just as or more effective than FOLFOX for 6 months (can still do FOLFOX for 6 months if needed) - for high-risk people, FOLFOX for 6 months was more effective than CapeOx for 3 months (can still do CapeOx for 6 months if needed)

Answer 41

Goal is now palliation. Chemotherapy is the mainstay of therapy. (surgery or radiation not really common, but maybe if it would help their pain) - FOLFOX: 5-FU, Leucovorin, Oxaliplatin - CapeOx: Capecitabine, Oxaliplatin - FOLFIRI: 5-FU, Leucovorin, Irinotecan (don't give if UGT1A1 mutation) - If pt fails FOLFOX, try FOLFIRI next. If patient first failed FOLFIRI, try FOLFOX. You can add other Abs like (EGFR inhibitors for VEGF inhibitors as long as no KRAS mutation) MIGHT use immunotherapy, but usually will only give this after they've failed our other treatments. - K-RAS is important in metastatic setting. If they have this mutation, we know they will not respond to cetuximab and panitumumab. We should test for this in metastatic disease every time! - Test for BRAF too!!

Answer 42

5-FU: binds to thymidylate synthase; extensively metabolized by DPD; causes diarrhea, mucositis, fatigue Leucovorin: used with 5-FU to increase efficacy Irinotecan: Diarrhea huge problem (can be acute). Make sure to get OTC imodium & give atropine during. Oxaliplatin: Neuropathy and cold intolerances Capecitabine: hand-foot syndrome and diarrhea Cetuximab & Panitumumab: mAb, EGFR inhibitor, only use in KRAS wild type patients. Can cause acneform rash (really severe) and hypomagnesemia Bevacizumab: HTN, proteinuria

Answer 43

Melanocytes are dendritic pigmented cells that arise from neural-crest tissue during early fetal development and migrate to sites within the body. These are located in the skin, uveal tract, meninges, and ectodermal mucosa. Melanocytes synthesize melanin to protect tissues from UV radiation induced damage. Melanoma results from the malignant transformation of skin melanocytes. There are many growth factors, immune factors, and tumor antigens that are identified in the progression of melanoma (ex. BRAF!!!, MEK, PI3K, etc.)

Answer 44

- Genetic factors (familial atypical multiple mole syndrome (FAMMs) or hereditary dysplastic nevus syndrome (HDNS)) - Exposure to sunlight (esp. UV B) - People who sunburn easily - Immunosuppression

Answer 45

Superficial spreading melanoma: - most common, 70% of cases - initially is flat, but becomes irregular and symmetrical Nodular melanoma: - 15% of cases - strictly vertical growth, more aggressive tumors - appear blue/black, usually raised and symmetrical - more common in men, usually appear on head, neck, and trunk Lentigo maligna melanoma: - in frequent - on elderly patients - tan lesion Acral lentiginous melanoma: - on palms, soles, under nails Uveal: - In the eye

Answer 46

Asymmetric Have irregular borders Wide variety of colors Diameter of >6mm Evolution of a mole

Answer 47

If you can remove it, remove it!! IB or IIA: - clinical trial or observation IIB or IIC: - clinical trial, observation, maybe pembrolizumab

Answer 48

Remove it, then use these: - Nivolumab (PD-1i) - Pembrolizumab (PD-1i) - If BRAF mutant: dabrafenib/trametinib - +/- radiation

Answer 49

- talimogene laherparepvec (T-VEC) - topical imiquimod - radiation - isolated limb perfusion

Answer 50

First line treatment options: - Anti-PD-1 monotherapy: nivolumab or pembrolizumab - combo BRAF therapy: dabrafenib/trametinib, vemurafenib/cobimetinib, encorafenib/binimetinib - certian circumstances: nivolumab/ipilimumab (if the pt is young and willing to go through all of the side effects Start with targeted therapy first if the pt tests positive. - chemo rarely cures patient, so we don't usually use it. Immunotherapy is MUCH more effective.

Answer 51

The exact cause is unknown, but the risk increases with # of ovulations. It is thought that the repairing of the epithelial lining of the ovaries after ovulation is one of the origins of cervical cancer.

Answer 52

If experiencing any of these symptoms for more than 12 days of the month for 2 months, pt should go see provider. - Increased abdominal size - Abdominal bloating - Fatigue - Abdominal pain - Indigestion Advanced disease symptoms: - Ascites - Pleural effusion - Constipation - Small bowel obstruction - Nausea or vomiting

Answer 53

Goal: cure!! - Surgery + adjuvant chemotherapy - Relapse may occur (70-90% of patients recur in first 3 years). In this case, therapy is palliative. - Want to test for mutations so we can use that to determine therapy. About 50% of pts have defects in genes due to homologous recombination deficiency.

Answer 54

- Maybe neoadjuvant, platinum based chemo - Surgery: take out everything. Depending on how much disease is left after surgery, we know prognosis (<1cm of disease left is optimal) - Adjuvant platinum based chemo: 90%+ we will do chemo, since they will likely present with stage III. Do paclitaxel + carboplatin q3weeks!!! *carboplatin is dosed using the Calvert equation, which reflects renal function and uses AUC* - Frontline maintenance therapy (PARP inhibitors) - Relapse - Recurrence therapy - Maintenance therapy of recurrence (PARP inhibitors again)

Answer 55

Platinum sensitive: greater than 6 months since platinum containing treatment - Give same agents again (ex. paclitaxel/carboplatin) Platinum resistant: less than 6 months since platinum containing treatment - Single agent therapy (ex. doxorubicin) so we have less toxicities Platinum progressive: no response during primary platinum containing therapy. - did not mention

Answer 56

Type I - immediate; experience anaphylaxis, itching, rash, and chest tightness Type 4 - seen when there's repeated exposure to the agent; experience erythema, induration - Allergic to drug itself: These patients need desensitization. Symptoms persist after stopping - Infusion related reaction: Paclitaxel (cremophor), Taxane (liposome) Decrease infusion rate. Symptoms resolve quickly after stopping infusion - Carboplatin can cause type 4 reaction (usually around cycle 7-8) Pre-medications for paclitaxel: - Dexamethasone - Famotidine - Diphenhydramine *for docetaxel, just do dexamethasone*

Answer 57

These inhibit PARP, which prevents DNA repair, leading to cell death. Olaparib: use for 1st line maintenance if BCRA mutation present, use for maintenance after relapse regardless of BRCA variant Niraparib: use for 1st line maintenance regardless of BRCA variant, use for maintenance after relapse if BCRA mutation Rucaparib: use for maintence after relapse if BCRA mutation *monitor CBCs (anemia, thrombocytopenia side effects)

Answer 58

hypercalcemia of malignancy - elevated calcium level in a patient with cancer (most common with lung and breast cancer) mild: (<12mg/dL) may not be able to tell at this stage moderate: (12-14mg/dL) start to see more symptoms like lethargy, confusion, and muscle weakness severe: (>14mg/dL) seizures, stupor, coma corrected calcium: serum calcium + 0.8 (4 - serum albumin)

Answer 59

Risks: - osteonecrosis - hypocalcemia (give supplemental calcium and vit D if using agents for prevention)

Answer 60

Women: breast cancer - age/post-menopausal - use of aromatase inhibitor - smoking - BMI less than 20 Men: prostate cancer - smoking - androgen deprivation therapy

Answer 61

Mild w/ no or mild symptoms: - encourage hydration - d/c medications that increase serum calcium (ex. calcium supplements) - repeat calcium level in 4 weeks Mild with symptoms: - hydration (200-400mL/hr of NS) - maybe IV bisphosphonate (ex. zoledronic acid, pamidronate)

Answer 62

Moderate: - Hydration: IV fluids - no loop diuretic - IV bisphosphonate (zoledronic acid, pamidronate): these inhibit osteoclast activity, decrease bone resorption, and increase mineralization. They concentrate at active bone remodeling sites Severe: - HYDRATION 200mL/hr - IV bisphosphonate - calcitonin (if nothing else is working)

Answer 63

Refractory: - phosphate binders - drives calcium into tissues. Not used that often - gallium nitrate - Inhibits bone resorption. Not used that often. - denosumab - RANK-L inhibitor. This inhibits osteoclast activity. It's approved and used. Chronic: - Zoledronic acid monthly - Pamidronate monthly

Answer 64

Skeletal related events: pathologic fracture, need for bone radiation, need for bone surgery, spinal cord compression, hypercalcemia Symptoms: bony pain or tenderness Diagnosis: scans Goal: help with pain and stop further destruction of the bone - radiation (only do radiation to the area one time) - chemo to treat the cancer - bisphosphonates (delays time to first SRE by 50%): pamidronate, zoledronic acid *renal adjustment dosing is needed (CrCL) - denosumab: use in refractory, SQ (not IV), no renal adjustment needed Adverse effect: osteonecrosis of the jaw

Answer 65

(140-age) (body weight in kg) / (Scr) (72) *multiply by 0.85 if female

Answer 66

Tumor Lysis Syndrome (TLS) - constellation of metabolic derangements resulting from the death of malignant cells. It's a massive release of intracellular contents into the bloodstream that overwhelms the body's homeostasis. - Mostly occurs 1-5 days after treatment, but can also happen spontaneously - Will see hyperkalemia, hyperuricemia, hyperphospahtemia, and HYPOcalcemia High risk: associated with aggressive hematologic malignancies, but also seen in solid tumors - high tumor burden - high tumor grade with rapid cell turnover - treatment sensitive tumors - old age - pre-existing renal impairment - concomitant use of drugs known to increase uric acid (ex. aspirin, alcohol, thiazide diuretics, caffeine)

Answer 67

*prevention and immediate management is key 1. Identify high risk patients - proactively implement aggressive prophylactic strategies to prevent and/or reduce severity of TLS 2. Monitor electrolytes before and during cytoreductive regimens 3. Aggressive hydration - this enhances urine flow, which promotes uric acid and phosphate excretion. Want to maintain a urine output of 80-100 mL/m2/hr 4. Control hyperuricemia with uric acid lowering drugs (allopurinol for low-intermediate risk, since it can't break down uric acid that's already formed, & rasburicase for high risk, since it breaks down uric acid that's already been formed) *manage hyperkalemia w/ fluids/loop diurectics, hyperphosphatemia w/ phosphate binder, do not treat asymptomatic hypocalcemia

Answer 68

*early diagnosis and treatment are essential to prevent permanent neurologic damage and possible paralysis - Start steroids immediately (dexamethasone) - Surgery and radiotherapy (if pt is not a surgical candidate) are the only treatments that leads to immediate relief of MSCC - Bisphosphonates

Answer 69

- facial and arm edema - distention of the superficial neck and chest wall veins - hypotension - dyspnea at rest - cough - stridor - dysphagia - headaches -syncope - dizziness Treatment: - elevation of the head - steroids (if tumor is steroid sensitive & if pt undergoing radiation therapy) - diuretics

Answer 70

Thoracentesis: needle aspiration of fluid from a pleural effusion. The fluid usually comes back within 30 days, but it's useful for pts who have a lifespan of 1-3 months. Pleural Fluid Analysis: send fluid to get tested in order to distinguish the type of pleural effusion Pleurodesis: This activates the inflammatory cascade, leading to adhesion of pleural layers. This is useful for pts who have a lifespan of longer than 1-3 months. Pleural Catheter: Drains the pleural space frequently. Pleurectomy: Removal of part or all of the pleura. This is beneficial for patients with prolonged life expectancy or patients with uncontrolled pleural effusions.

Answer 71

Malignant transformation of lymphocytes that form solid tumors of the immune system. - Lymphatic system is in the lymph nodes & lymph vessels - Most commonly it's the B cells that become malignant (T cells and NK cells are also lymph cells) Major types: 1. Hodgkin lymphoma: Reed-Sternberg cells 2. Non-Hodgkin Lymphoma (anything else) *Chemotherapy is the backbone of treatment. *Many subtypes are curable.

Answer 72

B symptoms - Fever (over 38º C) - Drenching night sweats - Unintentional weight loss of greater than 10% in less than 6 months Painless, rubbery, enlarged lymph node Itchiness

Answer 73

Goal: Cure while minimizing toxicities and long-term complications Options: - Combination Chemo: ABVD & AAVD - Radiation - Autologous stem cell transplant IA, IIA Favorable: - RT alone - ABVD + RT - ABVD Stage I-II Unfavorable: - ABVD + RT Stage III/IV: - ABVD +/- RT - AAVD (maybe more efficacious, but also more cautious) preferred in younger patients After relapse, we do autologous stem cell transplant. After transplant for high risk patients, we can do maintenance brentuximab vedotin.

Answer 74

A - Doxorubicin B - Bleomycin V - Vinblastine D - Dacarbazine *pulmonary toxicity A - Doxorubicin A - Brentuximab vendotin (antibody drug conjugate) V - Vinblastine D - Dacarbazine *increased risk of peripheral neuropathies Both ABVD and AAVD have cardiotoxicity, myelosuppression, and N/V YES, even if counts are low, we will give chemo!!! (rates of infection are low)

Answer 75

Presentation depends on tumor location: - B Cell: (85%) lymph nodes, spleen, bone marrow - T Cell: (15%) extra nodal sites (skin and lungs) Lymphadenopathy (can lead to organ dysfunction) B symptoms (40%) Extranodal involvement in 10-35% of patients (GI tract/skin most common, testes, and bone)

Answer 76

Hodgkin: - often localized to single group of nodes - orderly spread - Waldeyer ring rarely involved (tonsils) - extranodal presentation is rare Non-Hodgkin: - more frequent involvement of multiple peripheral nodes - noncontinuous spread - Waldeyer ring commonly involved - Extranodal presentation is common 5-year overall survival is over 70%!

Answer 77

Indolent: grade 1 and 2; only treat if the pt is symptomatic (increasing adenopathy, organ compromise, bone marrow failure) Aggressive: 1st line: Bendamustine + Rituximab, R-CHOP, R-CVP, or Rituximab + lenalidomide 1st line for elderly: rituximab is preferred

Answer 78

Richter's Transformation: When a follicular lymphoma switches to a DLBCL. - It takes about 5 years for a low-grade NHL to switch. - Once it switched, median survival is about 2 years. Chemo can cure the DLBCL, but they still have the follicular lymphoma, so we have to cure that. - Treat the same as aggressive lymphomas

Answer 79

- MYC, BCL2, and BCL6 translocations can be double/triple hit cancers, which are more aggressive and do not respond well to chemo. R-CHOP: rituximab (CD20), cyclophosphamide, doxorubicin, vincristine, prednisone Pola+R+CHP: polatuzumab vedotin (targets B cells specifically), rituximab, cyclophosphamide, doxorubicin, prednisone - $$$, but improves progression free survival. May be better for high IPI score pts. Stage I-II: can do 3 cycles of R-CHOP + RT or 6 cycles of R-CHOP Stage III-IV: 6 cycles of either R-CHOP or 6 cycles of Pola+R+CHP if IPI at or over 2

Answer 80

Rituximab is an anti-CD20 antibody. Hep B viral reactivation is seen in patients who receive anti-CD20 monoclonal antibody-based therapy, which can cause liver failure and death. Need to test for Hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (HBcAb) before anti-CD20 directed therapy If positive, we should treat with entecavir 0.5mg daily

Answer 81

Still have curative intent! - Salvage chemotherapy followed by autologous stem cell rescue. We need to prove that chemo can still be efficacious in these patients. If the disease shrinks by at least 50%, then they can do autologous stem cell treatment. - If they don't respond to chemo, we can do CAR T-cell therapy (genetically engineer T cells to target the tumor) - Also can do BiTEs (3rd line option after at least 2 lines of systemic therapy) - for palliative (not curative), we could do bendamustine + rituximab + polatuzumab

Answer 82

Burkitt's Lymphoma is the highly aggressive form of DLBCL. It always has a MYC gene translocation. - It has a 2 year survival of 70-80% - Treated by intensive multi-agent chemotherapy AIDS Related Lymphoma - You have a 100x increased risk of NHL compared to general population when you have AIDS. It occurs late in the HIV course. - 95% are B cell lymphomas - Treatment is HAART (normal HIV treatment) + chemotherapy

Answer 83

Plasma cells become malignant, called M-protein. Multiple myeloma cells are long-lived and slowly proliferate (normal plasma cells die off after a few days). These M-proteins secrete immunoglobulins (60% IgG) that do nothing helpful, only wreak havoc. - MM is a progressive disease Presentation: CRAB symptoms! C - hypercalcemia (>11.5mg/dL) R - renal dysfunction (SCr >2 or CrCL <40) A - anemia (<10g/dL or 2g/dL below normal) B - bone (one or more osteolytic lesions or pathologic fracture

Answer 84

This is chronic and incurable, so our ultimate goal is to give them high doses of chemo to get them into remission for as long as possible, also hoping to get them an autologous transplant. - 3 drug chemo regimen - steroids (dexamethasone), immunomodulatory drugs (lenalidomide), proteasome inhibitors (bortezomib)

Answer 85

Unregulated myeloid proliferation that results in mature neutrophil production. So these cells accumulate but they don't die. In 95% of cases, the Philadelphia chromosome is present (BCR-Abl or chromosome 22 translocation), which results in constitutively active tyrosine kinase. Presentation: - Just found during routine examination or CBC - Will be extremely high white blood cell count (300-500k) Leukostasis - blood is super thick due to all the white cells, which causes a thrombosis effect. These pts can present with stroke like, arthritis, and PE symptoms. This is medical emergency!

Answer 86

Chronic Phase (CP) - 90% of patients are in CP at diagnosis - <10% blasts (healthy/normal people are 1-5%) Accelerated Phase (AP) - 10-19% blasts Blast Crisis (BC) - terminal phase - 20% blasts - Sometimes disease can switch to lymphoid here

Answer 87

Goal: eradicate leukemic clone with minimal toxicity. The only way to cure is to do an allogenic hematopoietic stem cell transplant (HSCT). - We use tyrosine kinase inhibitors (TKIs) now (pill, now it's treated like a chronic disease) Imatinib - nasuea dasatinib - fluid retention (pleural effusion), avoid OTC acid reducers nilotinib - QTc interval prolonged, metabolic syndrome bosutinib - diarrhea (she uses this last) ponatinib - dose-limiting cardiac toxic side effects, use in resistant pts (T315I mutation causes resistance to 1st and 2nd gen agents) asciminib - used in T315I resistant CML & other refractory pts, binds to different area of transmembrane protein *these are all metabolized by CYP3A4, so we will NEED to dose reduce with antifungals (and paxlovid) If pt doesn't have BCR-Abl mutation, we can only do allogenic transplant.

Answer 88

Hematologic Response: CBC. Want return of normal blood counts Cytogenic response: Using FISH test to see how many Ph cells we see. - Complete = 0% - Partial = 1-35% Molecular Response: Use PCR test every 3 months to assess how quick and deep of a response we get from the TKI. - True gold standard is to get less than 0.01% BCR-Abl prevalence - This is what we really care about!

Answer 89

TKI discontinuation: - No history of AP or BP - On TKI therapy for at least 3 years - Stable, deep molecular response for at least 2 years - BCR-ABL ≤0.01% Monitor: - Quantifiable PCR (monthly for months 1-6, qom months 7-12, q3m after that) - must remain in major molecular response - loss of MMR means they have to restart TKI w/in 4 weeks

Answer 90

Monoclonal B lymphocyte transformation that results in clonal expansion and lymphocyte accumulation (can convert to aggressive lymphoma: Richter's transformation) Incidental finding usually (or recurrent sinus infections that aren't resolved with antibiotics) Del(11q) - associated with extensive lymphadenopathy, disease progression, and shorter survival Del(17p) - associated with the worst outcomes. This reflects the loss of key tumor suppressor TP53 gene. With this, chemos aren't going to work & the cell will keep dividing :(

Answer 91

We do NOT treat a number! - Treatment is reserved for Stage III or IV disease, clinical symptoms, and end organ dysfunction First line option for everyone is BTK inhibitors as a single agent or chemoimmunotherapy - acalabrutinib (BTKi) +/- obinutuzumab (CD20) - venetoclax (BCL2i) + obinutuzumab - zanubrutinib (BTKi) *we don't use ibrutinib anymore bc the newer agents don't have as much toxicity and they have better efficacy Treatment for relapse or refractory disease is based on patient factors, we just want to palliate symptoms.

Answer 92

BTK inhibitors: acalabrutinib, zanubrutinib - BTK inhibitors inhibit the phosphorylation of the TK pathway, which prevents downstream protein synthesis Venetoclax: - Venetoclax is a BCL-2 inhibitor (BCL-2 is pro-survival), which induces apoptosis - Drug interactions to watch out for: CYP3A4 and Pgp inhibitors/inducers

Answer 93

With acalabrutinib and zanubrutinib, we can see transient lymphocytosis. This is when the WBC goes up, but it should come down after 4-6 months. Do not d/c treatment in this case. This may occur with BTK inhibitors and idelalisib (PI3K inhibitor).

Answer 94

Pathophysiology depends on what cell line is effected. It results in proliferation in monoclonal population of leukemia cells (myeloid lineage). These cells won't be differentiated and they will out crowd the normal cells. Presentation: - Anemia - Neutropenia (infections) - Thrombocytopenia (bleeding) - Bone pain (from hyperactive marrow) - Gum hypertrophy Diagnose: bone marrow biopsy (need 20% to diagnose)

Answer 95

Favorable: t(15;17), NPM1, Double CEBPA - responds better to chemo Intermediate: NPM1 + FLT3-ITD Unfavorable: FLT3-ITD & complex (over 3) deletions - poor overall survival FLT3 is present in 30% of cases. We have midostaurin, gilteritinib, and quizartinib to target this.

Answer 96

Goal: induction to induce a remission. Then we do consolidation to prevent relapse. *no cure here* Induction: Intensive: continuous infusion cytarabine (7+3) + anthracycline (either idarubicin or daunorubicin, NOT doxorubicin). - Only 60% of pts can tolerate intensive. Goal is complete remission. Low to Moderate: Venetoclax + hypo-methylating agent (azacitidine) - Goal is complete remission. Low-intensity: hypo-methylating agents; low dose chemo - Will not result in complete remission. Supportive care: blood products, prophylactic anti-infectives, hydroxyurea - Goal is symptomatic management. *for FLT3+, add in midostaurin on top of cytarabine 7+3. these patients will need stem cell transplant For consolidation: Favorable risk - chemo (cytarabine 7+3) If low-to-moderate venetoclax + hypo-methylating agent, continue this for consolidation, as well. Unfavorable risk - allo stem cell transplant (but must be in remission for the transplant)

Answer 97

These pts have the t(15;17) translocation. - this one is very curable Induction: - give ATRA & arsenic to these patients Differentiation syndrome: all WBCs differentiate to their mature form, which is cause a bunch of inflammation. So we need to keep an eye out for this.

Answer 98

Disease arises form a single leukemic cell (in lymph system) that expands and acquires additional mutations. This results in monoclonal population of leukemic cells (failure to maintain balance between proliferation and differentiation). The leukemic cells have the growth advantage and crowd out the normal cells. These pts present similarly to AML - anemia, neutropenia, thrombocytopenia - lymphadenopathies, splenomegaly, etc. - can go to the brain (confusion, off-balance, etc)

Answer 99

Low - low WBC (<30k) and less than 35yo Intermediate - WBC ≥30k OR ≥35yo High - WBC ≥30k AND ≥35yo Cytogenic characteristics: Standard: absence of all abnormalities High: unfavorable cytogenetics *BCR-ABL will be present in 25% of patients. BUT if they can tolerate their TKI, their survival is about the same Risk stratification can help look at prognosis, but doesn't decide treatment

Answer 100

Induction: goal is remission HyperCVAD: hyper-fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone AND THEN Methotrexate & cytarabine If over 65, do blinatumumab - If Ph+, do TKI Consolidation: goal is to eradicate residual disease Maintenance: 2-3 years 6-MP, methotrexate, prednisone, vincristine *if BCR-ACL+, do TKI+vincristine+prednisone *all patients should receive CNS prophylaxis or treatment. Most protocols include intrathecal chemo!!

Answer 101

Engraftment - hematopoietic stem cell recovery after the transplant Conditioning regimen - chemotherapy or radiation prior to stem cell transplant. The goal is to cause immunosuppression so the host is ready to receive donor cell, create marrow space for stem cell graft, and eliminate as many tumor cells as possible Stem cell mobilization - process of collecting hematopoietic stem cells. We stimulate stem cell production for peripheral blood SC collection (use chemo &/or growth factors)

Answer 102

- Allows for administration of very high doses of chemotherapy (decreases myelosuppression since we are supplementing cells) - Graft vs. malignancy effect in allogeneic transplants

Answer 103

Autologous: recovery takes ~1 week 1. mobilization of peripheral blood stem cells, store and freeze cells 2. select conditioning regimen 3. proceed with transplant 4. manage complications Allogeneic: recovery takes 2-4 weeks 1. Select a donor 2. Donor source: peripheral blood or bone marrow harvest 3. Select conditioning regimen and GVHD prophylaxis 4. Proceed with transplant 5. Await engraftment, manage pre and post transplant complications For high-risk acute leukemia, going straight to stem cell transplant after first chemo/remission gives them the best chance. For good-risk acute leukemias, we can wait for pt to relapse and go into remission #2.

Answer 104

Look at HLA genes on chromosome 6. We want to make sure that Class I and II are matched. - Lower match = higher risk of GVHD

Answer 105

Bone marrow - invasive (requires anesthesia) - most pure (decreased risk of GVHD) - not common Peripheral blood - most common - takes 3 hours Umbilical cord blood - not seen often - small volume - blood collected after childbirth *between bone marrow and peripheral blood, bone marrow has higher chance of 5 year relapse, but the overall survival is the same

Answer 106

Filgrastim (Neupogen) - bone pain is biggest complaint Sargramostim Plerixafor (mozobil) combined with filgrastim - GI/diarrhea biggest complaint need 2-5 million cells in order to infuse into a patient we need to make sure the pts get enough cells

Answer 107

Melphalan - mucositis Carboplatin - Hepatic and renal

Answer 108

neutrophils - ANC over 500 for 3 days (probs takes 10-14 days) platelets - count over 20,000 for 3 days w/o transfusions (begins a few days after neutrophil engraftment) Lymphocyte - may take up to 1 year to recover lymphocyte function in alloSCT Erythrocyte - pt may eventually convert to donor blood type

Answer 109

- Caused by immunocompetent allogeneic donor T-cells reacting against recipient/host antigens. - The donor T cells recognize unmatched histocompatibility antigens. They activate, proliferative, and attack the recipient's tissue. Prevention: Use at least 2 agents with different MOAs - Calcineurin inhibitors: decrease IL-2 function (tacrolimus, cyclosporine) - mTOR inhibitor: decrease IL-2 function (sirolimus) - Antimetabolite: suppress active donor T-cells (methotrexate) Acute: less than 100 days post SCT - Steroids Chronic: more than 100 days post SCT - Steroids

Answer 110

1. Leukapheresis 2. T-cell activation/transduction 3. modified T-cell expansion 4. chemotherapy 5. modified T cell infusion

Answer 111

tisagenlecleucel (Kymriah) - ALL (children and young adult refractory/relapse), follicular lymphoma (relapsed or refractory), NHL (after 2 or more lines of therapy) axicabtagene (Yescarta) - Follicular lymphoma (relapsed/refractory), NHL (refractory to first line therapy or relapsed w/in 12 months, or after 2 or more lines of therapy) brexucabtagene autoleucel (Tacartus) - ALL (relapsed or refractory B cell precursor ALL) lisocabtagene maraleucel (Breyanzi) - NHL (relapsed or refractory after first line therapy)

Answer 112

idecabtagene vicleucel (Abecma) & ciltacabtagene autoleucel (Carvykti) are both indicated for relapsed or refractory multiple myeloma (MM) after 4 or more lines of therapy.

Answer 113

Cytokine release syndrome - treated by tocilizumab (anti IL-6) & steroids Neurologic toxicity (CAR-T cell related encephalopathy syndrome) - steroids *REMS requirements - must have minimum of 2 doses of tocilizumab readily available per patient