Oncology & Palliative Care 2025 PDF - Internal Medicine Review

Oncology & Palliative Care Friday November 29, 2024 Dr. Tian Xiao www.internalmedicinereview.ca © Internal Medicine Review 2025  Overview (RC Objectives)...

Oncology & Palliative Care Friday November 29, 2024 Dr. Tian Xiao www.internalmedicinereview.ca © Internal Medicine Review 2025  Overview (RC Objectives) Marked with ⌘ Oncologic emergencies (1.4.12.3.1.) Screening and prevention (1.4.12.3.2.) Common solid tumour sites (1.4.12.3.4.) o Breast o Lung o Colorectal o Prostate o Cancers almost never tested but on objectives o Other GI (gastroesophageal, HCC, pancreatic) o Genitourinary (testes, bladder, renal cell) o Gynecologic (endometrial, cervical, ovarian) Systemic toxicities (1.4.12.3.3.)- Almost never tested except for immunotherapy toxicity Palliative care (1.4.13.7.) (The Royal College of Physicians and Surgeons of Canada: Internal Medicine Competencies. 2018; Version 1.0:1-28.) 2  Housekeeping Marked with ⌘ 0-5% of Written Exam !!! HIGH Yield for studying Screening, Diagnosis, Oncologic Emergencies, Palliative Care. Recognize certain treatment drugs and their S.E Pearl- Exam Targeted Tips/ Trap Avoidance Common Orals: - Screening NOT on Exam (NOE) - Diagnosing cancer - Oncologic Emergencies can be a common oral scenario! Context- (To help understanding) Recent Changes ✔ Remember: There are “trial” questions on RC each year- ✗ Controversial thus questions with no clear answers will generally not make it to subsequent exams 3  Oncologic Emergencies Feb Neut, Hypercalcemia, TLS SVC, MBO, Spinal Cord Compression, Brain Mets/Leptomeningeal Disease 4  MCQ1. What’s the big deal? Miss Ava Stine is a 38F who presents to ED with a fever of 38.3C. She had chemo 14 days ago for colon cancer and her neutrophil count (ANC) is 0.9. She had bloodwork the day prior with her GP and her ANC was 0.7. She otherwise reports runny nose, but no cough or other symptoms. She runs a daycare. HR 83, BP 120/83, O2 100% RA, RR 12. Lytes, Cr, LFTs unremarkable. COVID –ve. What would be the best course of management? A. Admit to Hospital. Blood cultures x 2 STAT, CXR, urinalysis. Broad-spec Abx. B. Admit to Hospital. Blood cultures x 2 STAT, CXR, urinalysis. Viral Swab. Amox-Clav. C. Discharge from Hospital. Blood cultures x 2 STAT, CXR, urinalysis. Resp Viral Swab. No antibiotics. D. Discharge from Hospital. Blood cultures x 2 STAT, CXR, urinalysis. Resp Viral Swab. Amox-Clav + Cipro. E. Discharge from Hospital. CXR, Resp Viral Swab. Olseltamivir. 5 !!! Febrile Neutropenia1 Definition Temperature Criteria Absolute Neutrophil Count (ANC) Criteria Single temp ≥ 38.3˚C ANC ≤1.0 Both Criteria OR Moderate: 0.5-1.0 Need to be Met ≥ 38.0 ˚C for >1hr Severe: ≤ 0.5 Nadir of neutropenia occurs 7-14 days after chemo Work-up to find the Standard: infection (In addition to Blood culture x2 PIV + CVC (if present) standard CBC, renal, Urine culture liver function) CXR Other: Skin exam, Sputum (if present), Stool sample + C. diff (if diarrhea) Additional imaging as indicated Management Broad spectrum antibiotics IMMEDIATELY after cultures done Ex: Piptazo (Pseudomonas dose) to start, Add Vancomycin if still febrile after 72hrs Most source of Feb Neut is from patient’s own gut G-CSF used when neutropenic does NOT improve outcomes 6 !!! Outpatient management of Febrile Neutropenia in adults1 Risk Stratification System MASCC Score (COMMIT TO MEMORY) Management Administer empiric Antibiotics within 1 hour of triage Ciprofloxacin + amoxicillin/clavulanate* or Clindamycin (if Pen allergic) Bottom Line (Remember this is a safety exam): It’s never wrong to ask Med Onc for help on oral exam. Consider Outpatient Management if all of the following- Picture a simple ED visit. ID: Young Age- < 60 Chief Complaint: Cancer that doesn’t cause super low blood counts: Solid Tumor PMH: No Comorbidities- No COPD/ Active Bronchitis HPI: Fever Only- Minimal to no symptoms Physical Exam: Unremarkable- No hypotension Investigation: Unremarkable. Neutropenia will recover soon (Ex. chemo was 2 weeks ago) Management: Easy. No fluids needed Follow-up: Patient will be reliable in coming back if encounters problem. Neutrophils low beyond “nadir”- may be too much chemo was given/ patient factors 7 !!! Hypercalcemia of Malignancy Etiology 1. Lytic bone destruction Breast Cancer, Myeloma 2. PTHrP production Lung Cancer- Squamous cell - NOT Small Cell 3. 1,25-dihydroxyvit D/calcitriol production Lymphoma Management IV hydration (most effective short-terms) +/- Lasix Calcitonin Bisphosphonates Zoledronic acid IV x 1 Treat underlying malignancy Remember to reduce dose for renal dysfunction Calcitonin IM/sc reserved for severe hypercalcemia – quick onset 4-6h but tachyphylaxis by 48h (use as a bridge to bisphosphonate effect) Bisphosphonates max effect 4-7 days post-infusion (therefore NOT short-term solution) Hypercalcemia can co-exist with active bone mets. Steroids are used to treat bone mets pain/ flare, not useful in lowering calcium. 8  !!! Tumor Lysis Syndrome (TLS) Etiology Rapid Cellular Breakdown Fast Cancer (Leukemia, Lymphoma), Large Cancer Burden – Spontaneous TLS Sensitive to Treatment(Steroids, Chemo for Lymphoma) – Post-treatment TLS Diagnosis Requires ≥ 2 lab abnormalities within 7 days post-chemo 1. Hyper K+ – muscle weakness, ECG Δs, cardiac arrhythmias, sudden death 2. Hyper PO4 – AKI, secondary hypocalcemia, N/V, lethargy, seizures 3. Hyperuricemia – AKI (renal tubule deposition), flank pain (renal stones), N/V, anorexia 4. Hypo Ca2+ – Tetany, parasthesias, mental status changes Management of TLS Treatment Prophylaxis IV fluids (target U/O of 2cc/kg/hr) IV fluids AND Rasburicase Allopurinol OR o Allopurinol if G6PD deficient. Rasburicase (if NOT G6PD deficient) OR Treatment of electrolyte abnormalities (Dialysis PRN) Febuxostat G6PD Deficiency – X linked recessive. If MCQ says a woman, no FamHx, assume no G6PD defic! 9 !!! Malignant Bowel Obstruction (MBO) Etiology 1. Intraluminal Block (Colon CA) 2. Peritoneal disease (Ovarian, Gastric metastases) 3. Extrinsic Compression (Intra-abdominal lymphoma/ Sarcoma) Diagnosis CT abdomen Management Interventional Consult Gen Surg (even if palliative) stent, diverting ileostomy, venting G-tube Non-Pharm IV fluids to supplement losses NG decompress Pharmacologic Octreotide ↓gastric secretions, ↓ motility, ↓ splanchnic blood flow ± Corticosteroids ↓ peritumor edema, ↑ mobility Metoclopramide* *For RC: Can use if partial MBO. NOT for use in complete MBO 10  !!! SVC Syndrome Etiology Malignancy (up to 90% of cases)- Non-small cell lung cancer (~50% of cases) Thrombosis/ Fibrosis Symptoms Facial and arm edema, distended neck and chest veins, Dyspnea, cough, facial plethora, hoarseness, stridor, neurologic (confusion/change in LOC) Diagnosis CT chest, head and neck. Venography if unstable Management of Tumor associated SVC Syndrome Step 1 Be Safe. Call for help: Thoracics and Radiation Oncology Step 2 Life-threatening/ Urgent Stent (Fastest) Grade 4 symptoms* Steroids if not able to stent or steroid-responsive histology (ex. Lymphoma) Radiation to Temporize Non-life threatening Obtain tissue diagnosis to guide treatment. Above options + Tumor-guided treatment (Radiation/ Systemic Therapy) *Grade 4: Life-threatening: confusion/obtunded, stridor, hemodynamic comprise (syncope without precipitant), hypotension 11  !!! Spinal Cord Compression Etiology 1. Path # of spine due to metastasis (Breast, Lung, Prostate, Multiple myeloma) 2. Tumor pushing into thecal sac (Metastasis or primary tumor ex. Lung) Symptoms EARLY CLINICAL RECOGNITION IS KEY Back pain (often 1st sign, occurs in 95% cases) Leg weakness, sensory loss Urinary retention, Bowel incontinence If spinal cord compression = UMN findings* If cauda equina syndrome = LMN findings, Saddle anesthesia* Diagnosis MRI Whole Spine Management of Cord Compression Step 1 Be Safe. Call for help: Spine Surgery AND Radiation Oncology (Rad Onc first if you have to pick one) Step 2 Steroids – Dexamethasone IV (Reduce Swelling/ Inflammation)** Pain control Have low threshold for scanning, even if neurological exam not definitive **Typical dose: 10mg IV x1 à 4mg PO/IV QID ongoing until definitive management (NOE) 12  !!! Brain Mass/ Leptomeningeal Disease Etiology Intra-parenchymal lesions causing vasogenic edema, or meningeal disease block CSF flow Most common implicated malignancies – Breast, Lung, Melanoma metastases, Glioblastomas. Symptoms EARLY CLINICAL RECOGNITION IS KEY Vertigo, Ataxia, Headache, Vision changes, Neurologic deficits Diagnosis Brain Mass: URGENT MRI Brain Leptomeningeal disease: URGENT MRI Brain + Full Spine. Consider LP depending on clinical status Management of Brain Malignancy/ Leptomeningeal disease Step 1 Be Safe. Consult Neurosurgical service AND Rad Onc* Step 2 Steroids– Dexamethasone IV (Reduce Swelling/ Inflammation)** Further management (including mannitol or acetozolamide)- discuss with specialists Q: UNRELENTING HEADACHE x days-weeks in a patient with active/ recent cancer within 5 years (even if hx of prior similar headaches) A: MRI brain ideally, CT head w contrast if MRI not available, contrast preferred w CT to r/o CVT *Both services can treat brain mets definitively. (NOE) *Leptomeningeal disease- Limited role for any service except treat underlying disease (NOE) 13  MCQ 1. What’s the big deal? Miss Ava Stine is a 38F who presents to ED with a fever of 38.3C. She had chemo 14 days ago for colon cancer and her neutrophil count (ANC) is 0.9. She had bloodwork the day prior with her GP and her ANC was 0.7. She otherwise reports runny nose, but no cough or other symptoms. She runs a daycare. HR 83, BP 120/83, O2 100% RA, RR 12. Lytes, Cr, LFTs unremarkable. COVID –ve. What would be the best course of management? A. Admit to Hospital. Blood cultures x 2 STAT, CXR, urinalysis. Broad-spec Abx. B. Admit to Hospital. Blood cultures x 2 STAT, CXR, urinalysis. Viral Swab. Amox-Clav. C. Discharge from Hospital. Blood cultures x 2 STAT, CXR, urinalysis. Resp Viral Swab. No antibiotics. D. Discharge from Hospital. Blood cultures x 2 STAT, CXR, urinalysis. Resp Viral Swab. Amox-Clav + Cipro. E. Discharge from Hospital. CXR, Resp Viral Swab. Olseltamivir. Wrong answers: A, B- Not necessary as she is so well. Assuming she’s reliable in coming back. C- Would send home with Abx (whether she should take it is a different question in real life) E- NEED blood cultures. The most dangerous = bacterial for which we should prescribe empiric. 14  Screening and Prevention Screening for Breast, Lung, Colon, HCC, Cervical Cancer Prevention 15  Approach to the solid tumor oncology section Prevention Relevant Recognition Early Stage Metastatic Surveillance and Screening Biology and Diagnosis Management Management Treatment-Related Side Effects Disclaimer: Early Stage + Metastatic Treatment Sequence/ Regimen: Very complicated. Will only cover selected topics. Don’t ROUTINELY order cancer-characterizing (ie. Staging) work-up without confirmation of cancer Examples: Tumor markers or full body CT/ PET without pathologic evidence of cancer (Caveat: unknown primary) Screening (Asymptomatic) is DIFFERENT than Diagnosis. Ex. If there’s a problem (ex. Membranous nephropathy)- Diagnosis with appropriate work-up. DO NOT follow screening guidelines (ie. Don’t do FIT test when you see rectal bleed, NEED TO SCOPE) 16  MCQ 2. To screen or not to screen… Miss Liv Inwell is a 45F from Cote d’Ivoire who presents for routine cancer screening. She reports a recent diagnosis of HBV (Sag+), family history of colon cancer in her father at age 70, She smoked 1 ppd from age 18 onward. She loves to tan. No family history of breast cancer. What cancer screening do you recommend? a) Mammogram, FIT testing, Abdo U/S, AFP, annual skin exam. b) FIT testing, AFP, low dose CT Thorax, PSA c) Mammogram, Abdo U/S, AFP, colonoscopy, low dose CT Thorax d) Mammogram, FIT testing, AFP, low dose CT Thorax e) Colonoscopy, Abdo U/S, AFP 17 Screening for Breast Cancer (UPDATE 2024)2 Average Risk (No Prior Breast CA, amongst other factors) Age Groups 40-49* No screening 50-74 Screen 75+ No screening Method of Mammogram q2-3 yrs Screening *Caveat: Provide info to all. If wants to screen- can screen. Source CTFPHC 2024 Draft Recommendation2 Bottom Line: Women Age 50-74, screen with Mammogram q2-3 years ✔✗ For Age 40-49: NOE Canadian Cancer Society: Mammo q2years. CTFPHC DRAFT: Don’t systematically screen, but if patient wants mammo, q2-3y. CTFPHC – Canadian Task Force Preventative Health Care 18  Breast Cancer Screening age 40-49 [As CTFPHC guidelines are still in draft and the practice varies WIDELY across Canada this is not MCQ material] CTFPHC: “We suggest not to systematically screen with mammography” ALSO CTFPHC: “Breast cancer screening is a personal choice.” Women aged 40 to 74 should be provided information about the benefits and harms of screening to make a screening decision that aligns with their values and preferences. If someone in this age range is aware of this information and wants to be screened, they should be offered mammography screening every 2 to 3 years.” Ontario + Nova Scotia + New Brunswick + Women 40-49 can self-refer for screening, Q2Y Yukon Breast Screening Program PEI + Nunavut: Women 40-49 can self-refer for screening Q1Y (yup, 1y) BC Breast Cancer Screening Women 40-49 encouraged to speak to healthcare provider and if they decide to screen, do so every 2 yrs Alberta + Northwest Territories Breast Cancer 40-44 = talk to healthcare provider Screening 45-74 = every 2 years, may self refer Quebec, Manitoba, Saskatchewan, Newfoundland 50-74 19  Breast Cancer Screening for 2S/Transgender/nonbinary/Gender Diverse Patients History of Chest Surgery? No Chest surgery or simple Mastectomy bilateral reduction mammoplasty? Screening mammo not Screen per usual guidelines recommended, ‘discuss w/ Healthcare provider’ if concern re risk. Chest (breast) Tissue present If taking Estrogen >5yrs – screen per Provincial Guidelines due to gender-affirming hormone therapy? (e.g in Ontario –eligible to self-refer for screening mammo q2y 40-74) (Transfeminine patients) 20  Screening for Lung cancer3 Risk Criteria (Need to meet all 3) 1) Age 55 to 74 2) Smoking History ≥ 30 pack-year* 3) Smoking Status Current smoker OR Quit within the past 15 years Method of Screening Annual low dose CT every year up to 3 consecutive years Source CTFPHC 20163 Bottom Line: Anyone 55-74 AND 30+py, AND current/ quit within 15 years, screen with annual CT x 3 CTFPHC Review Comment (Similar Choosing Wisely comment) Screen if patient has reasonable life expectancy. (ie. Don’t screen in most stage 4 CAs, endstage organ disease, etc) 21  Screening for Colorectal Cancer (CRC) 4,5 Average Risk4 Increased Risk5 Applicable People age 50+ ≥ 1 First-degree relative with colon cancer OR Population No previous CRC or polyps, no IBD, no FHx CRC advanced adenoma Age Groups 50-74 Screen 2 options: Whichever youngest 75+ No Screening Age 40 10 yrs before earliest age of relative’s diagnosis Method of 2 Options Colonoscopy q5-10 yrs Screening FIT q2 yrs Flex sigmoidoscopy q10 yrs FIT q1-2 yrs can be considered as 2nd-line/ DO NOT USE colonoscopy alternative Source CTFPHC 20164 CAG 20185 Bottom Line Colon CA average risk- FIT q2 or Colon CA high risk- Colonoscopy q5-10 either Sigmoidoscopy q10 from 50 to 74 from either 40 or 10 years prior to earliest dx FDA approved circulating tumor DNA (blood test) for colon CA screening 2024 (SHIELD) (NOE) 22  Screening for Hepatocellular Carcinoma (HCC) 6,7 Cirrhosis No Cirrhosis but is Hep B carrier (sAg+) Setting AGE of Screening Childs Pugh A-B Any Age Setting AGE of Screening Endemic Countries (male 40+, female 50+) 40+ Childs Pugh C Screen ONLY if FHx of HCC in 1st degree relative transplant candidate7 All HIV co-infected patients African or North American blacks 20+ Hep D Co-infected Any Age Method of Ultrasound q6 months (CASL) 6 / Ultrasound + AFP q6 months (AASLD) 7 Screening Source CASL 2018 + AASLD 2023 CASL 2018 does not recommend AFP where US is available (Insufficient evidence in 2018) (NOE) 23  Screening for Cervical Cancer8 CTFPHC releasing update 2025 (NOE) Applicable Anyone 25+ with a cervix Population Age Groups 25-69 Screen 70+ No/ STOP Screening IF ALSO ≥ 3 negative tests in the last 10 yrs Population Excluded Never sexually active, Previous abnormal Pap tests, Immunocompromised (eg. HIV, organ transplant, chemo, chronic corticosteroid use), Symptomatic of cervical cancer (eg. abnormal vaginal bleeding), limited life expectancy Method of Screening Cervical cytology q3 years (Pap Smears) Source CTFPHC 20138 Bottom Line Age 25-69 with cervix- Pap smear q3yrs until age 70 + 3 negative tests over last 1yrs ✔✗ ACS (American Cancer Society Recommendation 2020): HPV test q5 years age 25-65. (NOE) 24  DO NOT SCREEN for These Cancers Touch me and I’ll turn you into PESTO Nothing up my rear end Prostate CTFPHC releasing update 2026 (NOE) Nothing down my throat Esophagus even if chronic GERD* Don’t touch me Skin (Melanoma) Don’t fondle my family jewels Testes and Ovaries *Exclusion: Pertains to ‘average risk’ patients – exceptions if Known familial cancer Syndrome (e.g. Peutz-Jeughers (routine endoscopy), BRCA (PSA prostate), many more) Previously diagnosed Barrett’s Alarm symptoms (dysphagia, odynophagia, weight loss, anemia, bleed, loss of appetite) (Technically not screening) 25 Cancer Prevention- ETOH (Jan 2023)9 WHO- World Health Organization CCSA- Canadian Centre on Substance Abuse and Addictions 26  Cancer Prevention- Smoking (Jul 2024) 10 What we know Cigarettes or Non-Cigarette = Harmful Pharmacologic 1. Varenicline 2. Bupropion 3. Nicotine Replacement Therapy (NRT) 4. Cytisine Non-Pharmacologic Behavioural interventions (Brief health-worker counselling 30 seconds to 3 minutes) More intensive behavioural support for those interested SSRIs are NOT effective in smoking cessation WHO- World Health Organization 27  MCQ 2. To screen or not to screen… Miss Liv Inwell is a 45F African-descent presents for routine cancer screening. She reports a recent diagnosis of HBV (Sag+), family history of colon cancer in her father at age 70, She smoked 1 ppd from age 18 onward. She loves to tan. No family history of breast cancer. What cancer screening do you recommend? a) Mammogram, FIT testing, Abdo U/S, AFP, annual skin exam. b) FIT testing, AFP, low dose CT Thorax, PSA c) Mammogram, Abdo U/S, AFP, colonoscopy, low dose CT Thorax d) Mammogram, FIT testing, AFP, low dose CT Thorax e) Colonoscopy, Abdo U/S, AFP Wrong answers: A, B, C – Colonoscopy for high risk. She has no prostate. Melanoma screening not routinely recommended. D – No need for CT given young age 28  Key Knowledge around Common Solid Tumour Sites 29  MCQ 3: I’m so wise… Mr. Classic is a 46m with history of reflux, admitted to your service with abdominal pain and new onset brown plaques over his chest. CT C/A/P shows omental thickening, suspicious for peritoneal metastases. Hb 100, Plt 200, WBC 9. CRP is normal. What is the best next step? A. Upper Endoscopy B. Prednisone 1mg/kg daily C. Colonoscopy, CEA D. PET scan, CA 19-9, CEA, CA 125 E. DRE, PSA F. Call Medical Oncology 30 !!! Breast Cancer: Biology + Confirm Cancer Relevant Biology Diagnostic Workup (NEED ALL) ESTROGEN (Hormone-driven) vs HER2 Imaging 1. Diagnostic bilateral mammogram ER/ PR pos (+) ER/ PR neg (-) 2. Ultrasound of breast + axilla* HER2 + Triple + HER2 + Biopsy Method Core needle biopsy (US-guided) HER2 - Hormone + Triple - Markers 1. ER (estrogen hormone receptor) 2. PR (progesterone hormone receptor) 3. HER-2 (human epidermal growth factor receptor) Mastitis not responding to antibiotics à BIOPSY to rule out Paget’s/ Inflammatory Breast CA) Post COVID vaccine- Mammogram/U/S prior or 4-6 weeks later to avoid reactive lymph nodes In real world: U/S + Mammogram TOGETHER with Biopsy (NOE) Once Confirmed Localized Breast Cancer- Move on to Surgery! (Before completion of staging) 31  Breast Cancer: Localized Management + Staging Tumor (2 options) Lymph Nodes (LN) (2 options) Surgery 1. Mastectomy 1. Sentinel LN Biopsy (SLNB)** 2. Lumpectomy (Breast Conserving Surgery)* 2. Axillary LN Dissection (ALND) Bottom Line For early stage Breast CA: Tumor treatment (Mastectomy / Lumpectomy) + Lymph node treatment ( SLNB/ ALND) Staging: Decision based on Surgical pathology results Stage 1 No Staging Stage 2 Stage only if symptoms Stage 3 STAGE - Bone scan + CT C/A/P PET now funded in Ontario for early stage breast CA (Stage 2B and 3) and oligometastatic breast CA 32  Breast Cancer: Systemic Therapy Hormone + HER2 + Triple negative 1. Endocrine therapy 1. Chemo AND 1. Chemo 2. CDK 4/6 2. Anti-HER2~ 2. Immunotherapy Post-menopause: TAM or AI Pre-menopause : TAM* KEY DRUGS TO BE AWARE OF FOR EXAM Endocrine Chemo CDK4/6 Anti-HER2 Immunotherapy Anti-Resportive Agents Tamoxifen Anthracycline - Ciclibs Trastuzumab Other -mabs excluding Zoledronic Acid Aromatase (-rubicin) (ex. Ribociclib) the 2 Anti-HER2s Inhibitor Pertuzumab (ex. Pembrolizumab) Denosumab *Pre-menopausal adjuvant occasionally use AI + GnRH agonist ~Many new drugs now. One of which is Antibody Drug Conjugate = Antibody Tagged with Chemo 33  Breast Cancer: Surveillance11 Method of Surveillance* Lifestyle Modification post Breast Cancer (CMAJ 2017) 11 Annual Clinical (History and Physical) Live healthy- Just know cardiac guidelines** Annual Mammogram ** Examples: Prevent weight gain Exercise (150 mins/wk = reduces breast cancer mortality) No smoking. Minimal Alcohol Limit saturated fats and high-fat dairy products *Recommend AGAINST surveillance blood work, bone scan, CT scans (Choosing Wisely ASCO) 34 !!! Breast Cancer Treatment Side Effects Endocrine Therapy Cardiomyopathy Side Effect Tamoxifen Aromatase Anthracyclines Anti-Her2 Inhibitor (ex. Doxorubicin) (ex. Trastuzumab) Endometrial cancer ↑ None Irreversible Reversible Thrombosis ↑ None Late in course/ delayed During treatment Osteoporosis ↓ (relative) ↑ CV Risk ↓ (relative) ↑ Side Effects of TAM vs AI plagues RC takers every year. I would stick to the top 3. The CV risk option is always tricky. Pick TAM > AI in reducing CV risk. 35  Lung Cancer: Biology Non-Small Cell Small Cell Squamous Cell Central lesions Central lesions Strong link with smoking Strong link with smoking Non-EGFR/ALK mutated Unlikely EGFR/ALK mutated Rapidly growing Adenocarcinoma Peripheral lesions Bottom Line Has driver mutations (EGFR) The 4 S’s of Lung Ca: Smokers get Squamous and the Speedy Small cell Rare(ish) tumor types Adeno: “I Don’t Know why I got cancer…” – Lots of targetable mutation Neuroendocrine Adenosquamous Neuroendocrine tumor of lung (RARE- know workup for carcinoid): Sarcomatoid PREOP do an Echo if suspicious Large cell Serum Chromogranin A Urine 24-HR Urine 5-HIAA. Gallium-PET scan (NOT Regular PET) 36 !!! Lung Cancer: Paraneoplastic Syndromes Cancer Type Paraneoplastic Syndromes Highlights SCLC SIADH Lambert-Eaton Myasthenic Syndrome (LEMS) o Anti-VGCC Ab* : reduced presynaptic ACh release o Similarities to myasthenia gravis, but notably absent/decreased reflexes Encephalomyelitis & sensory neuropathy o Anti-Hu Ab* cross reacts w/ both SCLC antigens and neuron-specific RNA-binding nuclear proteins Cushing’s syndrome o Ectopic ACTH production. NOT suppressed by dexamethasone supp test Adeno Hypertrophic osteoarthropathy o Clubbing + periosteal new bone formation of tubular bones NSCLC o Symmetrical, painful arthropathy (ankles, knees, wrists, elbows) Squamous Hypercalcemia o PTHrP production (NOT measured in modern assays for PTH) NSCLC *Only order antibodies (serum + CSF) if suspecting the clinical syndrome. NOT used as a screening test for paraneoplastic syndromes 37  Lung Cancer: Workup Diagnosis of Cancer Staging once diagnosis is confirmed 1. CT guided biopsy (Interventional Rad) 1. CT Chest Abdomen Pelvis** OR AND 1. EBUS (Endobronchial ultrasound) biopsy (Thoracics/ Resp)* 2. MRI brain 3. ± Bone scan if symptomatic Molecular Testing- Genetic alterations/ signs of immune system attacking cancer using the tumor sample Adenocarcinoma Squamous Small Cell Biomarkers 1. EGFR (amongst many others) PD-L1 None 2. PD-L1 Bottom line: Having molecular profile is crucial to treating non-small cell lung cancer “Typical” EGFR+ profile – Elderly, Female, Asian, Non-smoker, Adenocarcinoma * Bx of metastases okay too but pleural effusion alone not enough (Not enough cells for more testing) (NOE) **PET/CT scan and mediastinal staging is done prior to curative treatment- Job of the oncologists (NOE) 38  NSCLC: Staging Malignant Pleural Effusion = Stage 4 Q: Symptomatic Pleural Effusion NYD for malignancy (Exudative doesn’t count)? A: Thoracics referral first (drain + diagnostic) In real life may refer to both medical oncology and thoracics Primary tumor Hilar LN Mediastinal LN Distant mets Pleural effusion (NOE) Stage 1 Stage 2 Stage 3 Stage 4 Lymph node (LN) terminology in Lung Cancer: Malignant effusion Hilar -> Mediastinal -> Supraclav/ Scalene Distant metastases Ipsilateral vs Contralateral AJCC 8th edition TNM staging 39  Non-Small Cell Lung Cancer: Early Stage Management Stage 1 Stage 2 and 3 (Resectable) Stage 3 (Unresectable) Definitive Fit for surgery: Surgery Complicated** Concurrent Treatment Unfit: Radiation (SBRT*) 12 chemoradiation Adjuvant None Immunotherapy x 1 yr Treatment Bottom Line: For any lung nodule NYD OR diagnosed lung cancer with stage NYD (PRESUMED EARLY STAGE)… Q: Next best service to consult? A: Thoracics- Need to determine resectability (or Rad Onc if question says stage 1 and frail) Q: One other service to consult aside from thoracics for stage 2 or 3? A: Medical Oncology (See red context box below) *SBRT = Stereotactic Body Radiation Treatment **2024 Update: Definition of resectability is changing. Resectable stage 2 and 3 can be treated many ways Most commonly: neoadjuvant chemo + Immuno then surgery. EGFR+: surgery + adjuvant Osimertinib. (NOE) 40 Non-Small Cell Lung Cancer: Metastatic Management EGFR mutation positive Driver mutation negative First Line Treatment EGFR inhibitor* Immunotherapy +/- Chemo14 Bottom Line Always refer to Medical Oncology first *Adenocarcinoma + EGFR? = Osimertinib (regardless of stage 2+ or late stage) (As long as no mention of extreme frailty and refusing treatment) 2024 Update (NOE) Osimertinib + Chemo for EGFR. Other EGFR inhibitors may be better Double Immuno for lung CA Many targeted therapy for many mutations other than EGFR 41  Small Cell Lung Cancer: Workup & Management Limited Stage Extensive Stage Definition Confined to 1 radiation field 1. Beyond 1 radiation field (i.e. mets) 2. Malignant Effusion Treatment Concurrent chemoradiation* + Brain Radiation Chemotherapy + Immunotherapy** Bottom Line Small Cell Lung Cancer can kill in short weeks to months. Refer to Medical Oncology and Radiation Oncology ASAP. Medical Oncology First 2024 Update: Immunotherapy coming to curative intent small cell lung cancer (NOE) Highly chemo/radio-sensitive, but frequently relapse Surgery is generally NOT a part of SCLC treatment unless very early stage (NOE) ** Prophylactic brain radiation is no longer routinely recommended in extensive stage (No survival benefit) 42  Lung Cancer: Note on Radiation Pneumonitis Timing Delayed. 4-12 weeks (1-3 months post radiation). Way after immunosuppression with chemo Location Radiation field Mimickers 1. Pneumonia (Ground glass opacities) 2. ILD (Interstitial changes) 3. Immunotherapy Pneumonitis (Diffuse + bilateral) Treatment Steroids (Prednisone) (Also treats Immuno Pneumonitis) Bottom 1-3 months post radiation with Line unilateral pneumonia where radiation was done previously? Written: Steroids Source: Dr McKenna – used with Oral: Empiric CAP abx + Steroids permission of patient (who did very well on steroids!) 43  Colorectal Cancer: Workup Diagnostic Method Full Colonoscopy + Biopsy !!! Staging CT Chest Abdomen and Pelvis Markers Carcinoembryonic antigen (CEA) (NOE) bowelcanceruk.org.uk 44  Colorectal Cancer: Management Stage 1 and 2 (No LNs) Stage 3 (Has LNs) Stage 4 Treatment Surgery Surgery + Adjuvant Chemo Sytemic Therapy* (Adjuvant Chemo for some stage 2) Bottom Line: Upfront surgery for colon cancer Stage 4 potentially curable (RARE in Solid Tumor Cancers) *Curable Stage 4 Oligometastatic (stage 4): isolated liver or lung lesions, generally < 4 mets o Metastectomy + chemotherapy (May be curable) Chemotherapy alone, Chemotherapy + VEGF antibody, Chemotherapy + EGFR antibody, Immunotherapy. Radiation limited role in all settings of colon cancer 2024 Updates: Double Immunotherapy for colon cancer (NOE) 2024 Updates: Full liver transplant for liver-only metastases for colon cancer 45  Colorectal Cancer: Stage 1-3 Surveillance Marked with ⌘ CCO potential update 2025 Timeline Year 1-3 Year 4-5 History and Physical Q6 months At discretion CEA At discretion At discretion CT CAP CT CAP Year 1 and 3 At discretion Colonoscopy 1 year post-resection. Subsequent colonoscopies based on findings of previous scope (not annually), if negative, every 5 years. ⌘ Bottom Line: Clinic visits q6 months for 3 years. CT year 1 and 3. C-scope at year 1 then go from there. Recurrence risk highest first 2-3 years. True Practice varies: Visits q6months x 3 years, annual at year 4-5. CEA each visit. (NOE) CT CAP q6months x 2 years then annual to year 5. Follow-ups different for stage 1 vs stage 3 2021 Cancer Care Ontario guideline 46  Gastroesophageal Cancer: Biology Squamous cell Adenocarcinoma Common location: Upper-mid esophagus Distal esophagus Risk factors: EtOH Barrett’s esophagus Caustic injury GERD Smoking Obesity Smoking Leser-Trelat sign- sudden eruption of seborrheic keratosis. Think gastric or breast Kilickap et al. NEJM 2007 47 !!! Prostate Cancer: Biology + Workup Biology Depends on Androgen Metastasize to bone Diagnosis Digital rectal examination Prostate biopsy + Gleason Score (Calculated on biopsy specimen) Markers PSA Staging* Bone scan** CT chest/abdomen/pelvis Paraneoplastic coagulopathy. DIC most common in metastatic setting/ post-op **Sclerotic Bone Lesion ONLY – Think Prostate Cancer Metastases *For High risk prostate CA only. Remember many prostate CA requires no treatment but needs to be watched 48  Prostate Cancer: Management Marked with ⌘ Castrate Sensitive- Responds to lowering Androgen Castrate Resistant Early/ 1. Active surveillance (PSA monitoring, intervene if progression)⌘ NoE Localized 2. Radical prostatectomy 3. Radiation (Brachytherapy or External Beam) Metastatic 1. Androgen Deprivation Therapy (ADT) NoE AND 2. Other Agents CYP17 inhibitor (shuts down androgen production) Anti-androgen pill +/- Chemotherapy *ADT = Monthly injections to shut down androgen production. 2024 Update: Anti-androgen pill and CYP17 inhibitor moved into Early/Localized setting. PARP inhibitors (Used to be only for BRCA patients) may be used as front-line treatment for metastatic disease 49  BONUS Read on own Testicular Cancer Biology Many types. Primarily would be tumor from germ cells (Germ cell tumors) 2 types of Germ Cell Tumors: Seminoma vs Non-Seminoma Diagnosis Scrotal ultrasound to find mass with radical orchiectomy Markers (Need all 3) 1. β-hCG 2. AFP (NEVER elevated in seminoma. ONLY in Non-seminoma) 3. LDH Staging CT chest/abdomen/pelvis Management Localized: Surgery Metastatic: Chemotherapy (Bleomycin) 1. NEVER needle biopsy testicular mass- risk of tumor seeding 2. If AFP elevated. non-seminoma will ALWAYS be present (worse survival, higher recurrence) 3. Patient with Pulmonary Fibrosis and any history of Testicular Cancer? A: Bleomycin toxicity 4. Testicular Cancer- Another rare solid tumor cancer that can be cured when metastasized. 5. Stage 1-3 only. There is no stage 4 (Metastatic disease is still stage 3) 50  MCQ 3: I’m so wise… Mr. Classic is a 46m with history of reflux, admitted to your service with abdominal pain and new onset brown plaques over his chest. CT C/A/P shows omental thickening, suspicious for peritoneal metastases. Hb 100, Plt 200, WBC 9. CRP is normal. What is the best next step? A. Upper Endoscopy B. Prednisone 1mg/kg daily Wrong answers: C. Colonoscopy, CEA B – Steroids won’t help with diagnosis D. PET scan, CA 19-9, CEA, CA 125 C – Colon doesn’t typically metastasize to omentum. With hx of reflux and Leser Trelat sign, this is most likely upper GI. E. DRE, PSA D – PET not indicated prior to cancer-specific tests F. Call Medical Oncology E – Prostate doesn’t typically metastasize to omentum. This hx is suggestive of upper GI Correct answer: A – Most likely gastric cancer with peritoneal metastases F – Last resort on oral exam which is still acceptable 51 Systemic Therapy and their Side Effects Chemotherapy (Common, Life-Threatening) Immunotherapy 52  Systemic Therapy Toxicities Disclaimer The unprecedented advancements in oncology are likely to render a general medical oncologist less adept at managing certain cancers within a span of 2 years. Thus expecting internists to thoroughly understand and reliably differentiate all toxicities associated with traditional and emerging therapies would be Impractical and arguably Unfair. In real life, when in doubt, these 2 actions are NEVER wrong 1. Stop the Treatment 2. Ask the Oncologist - Some Medical Oncologist in the Greater Toronto Region, 2024… 53  BONUS Chemotherapy Toxicities – REFERENCE ONLY, not comprehensive Read on own list of all treatments! See bonus slides for some other toxicity tips. Drug Toxicity Common Use Anthracyclines Irreversible cardiomyopathy Breast CA (FEC-D, ddAC-T) **GIM relevant** Doxorubicin (Adriamycin), Epirubicin Secondary leukemias Lymphoma (R-CHOP) Antimetabolite Diarrhea, mucositis, hand-foot syndrome, coronary Colon CA (FOLFOX/FOLFIRI) 5-Fluourouracil, Capecitabine vasospasm Breast CA (FEC-D) Topoisomerase inhibitors myelosuppression, diarrhea, nausea, vomiting, Colon CA (FOLFIRI) Irinotecan cholinergic reactions (Irinotecan) Testicular (BEP) Etoposide Etoposide: Hypersensitivity reactions Lung (small cell Cis + Etop) Platinums All – Peripheral neuropathy Cisplatin – Lung CA, H & N Cisplatin Cisplatin-specific – Highly emetogenic, nephrotoxic, Carboplatin – Ovarian CA Carboplatin ototoxic, hypoMg/Ca/K Oxaliplatin – Colon CA Oxaliplatin Oxaliplatin-specific – Cold-induced neuropathy Taxanes Peripheral neuropathy, myalgias, hypersensitivity Breast CA (FEC-D, ddAC-T) Paclitaxel reaction (SOB, flushing, hypotension), fluid retention Ovarian CA Docetaxel (docetaxel) Prostate CA Vinca alkaloids Peripheral neuropathy Lung CA, Breast CA Vincristine, Vinorelbine CHOP (“O”) Cyclophosphamide Emetogenic Breast CA (FEC-D, ddAC-T) Hemorrhagic cystitis, bladder CA CHOP (“C”) **GIM relevant** Secondary malignancies (MDS, AML, bladder Ca) Connective tissue diseases Infertility 54  BONUS Other Systemic Therapy Toxicities – Read on own REFERENCE ONLY Drug Toxicity Common Use Immunotherapy (not comprehensive) Autoimmune phenomena Melanoma, Lung Cancer Pembrolizumab, Nivolumab Most common are dermatitis, hypothyroidism. Bladder Cancer, Renal Ipilimumab Rare: hypophysitis, pneumonitis, colitis Cell, Gastroesophageal Atezolizumab, Durvalumab Anti-angiogenesis/VEGF inhibitors HTN, bleeding, bowel perforation, delayed wound healing, Metastatic colon CA Bevacizumab (Avastin) arterial thrombo-embolism (MI, CVA) Gynecologic CA EGFR Tyrosine-kinase inhibitors Acneiform rash TIP: EGFR lives on mucosa (oral, Metastatic lung CA Osimertinib Diarrhea skin, GI)- Hence the side effects (NSCLC) ILD Trastuzumab (Herceptin) Cardiomyopathy (reversible) HER2+ breast CA Infusion-rxn (flu-like) **HIGH YIELD ** Rituximab Infusion rxn (flushing, hypotension, tachycardia, allergic) Lymphoma (R-CHOP) Tyrosine-kinase inhibitors (TKIs) HTN, bleeding, hand-food skin reaction, diarrhea, RCC, HCC Sunitinib, Sorafenib mucositis, hypothyroidism (sunitinib) PARP inhibitor Cytopenias BRCA + Ovarian cancer, Olaparib, Niraparib GI symptoms Pancreatic cancer 55  !!! The Terrible 2’s: Heart and Lung Organ Heart Lung Anthracyclines (-rubicins) Trastuzumab Bleomycin Ex. Doxorubicin Reversibility Irreversible Reversible* Irreversible Onset Delayed/ Early onset/ Delayed/ Cumulative with dose Cumulative with dose During treatment Symptoms Typical HF symptoms Pneumonitis symptoms (Fatigue, cough, SOB) Diagnosis TTE CT chest * Real Life: Trastuzumab MAY be restarted after recovery of heart function 56 !!! Immunotherapy Toxicity Management12 Role as general internist- Recognize as a differential. Not expected to be well-versed in treatment Mild (Vitals/ Function ok) Moderate/Severe (Sick. Needs Hospital) Admission: No Supportive Admission: Yes Consider Steroid (Prednisone) Steroids (Pred or Methylpred) Infliximab if refractory to steroids (72 hours) +/- Empiric Antibiotics Consult Subspecialty of Inflamed Organ Unpredictable ORGAN Unpredictable TIMING (Up to 2 years post-treatment) Always Hold Immunotherapy (Discontinue if severe) Always Rule Out infection. C.diff + ICI colitis – YES or No Steroids? Short answer: YES. No matter how dire of situation, Don’t forget steroids 57 https://www.cancercareontario.ca/sites/ccocancercare/files/guidelines/full/ImmuneCheckpointInhibitor.pdf  Common Chemo Side Effects: Nausea Chemo induced nausea (Starts 2-3 days post-chemo) Anti-Emetic Mild Moderate Highly NK1-receptor antagonist (-pitant) ✔ Ex. Neuprepitant, aprepitant 5-HT3 antagonists (-setron) ✔ OR ✔ ✔ Ex. Ondansetron, granisetron Steroid (dexamethasone) ✔ ✔ ✔ 5-HT2/D2 antagonist (olanzapine) ✔ ✔ Remember: Treat Nausea SOON! (Steroid, Ondans, Olanz, NK1) Anticipatory nausea (Vomiting before/during chemo) o Refer to Psychiatry (behavioural therapy) o May use Benzodiazepines (Lorazepam) 58  “Higher Yield Systemic Therapy Names to recognize” (Scattered throughout the lecture) Type of therapy Drug Name (Drug Class) Exam-Relevant Importance Chemo Doxorubicin (Anthracyclines) Cardiomyopathy Bleomycin Pneumonitis Antibody (Anti-HER2) Trastuzumab Cardiomyopathy Anti-Hormone (Estrogen) Tamoxifen Pre-menopausal uses VTE. Endometrial CA (Aromatase Inhibitor) Post-menopausal uses Osteoporosis Androgen Deprivation Therapy (ADT) Menopause for men symptoms Anti-Androgen Abiraterone Hyperaldosteronism Enzalutamide / Apalutamide Falls, seizures Immunotherapy Pembrolizumab Immuotherapy toxicities Nivolumab Targeted therapy (EGFR) Osimertinib Very good drug for lung cancer with EGFR mutations. Select population 59  MCQ 4: Immuno is a box of chocolate… Mrs. Celinne Dionne is a 30F on pembrolizumab for colon cancer x 1 year presents to office with progressive fatigue, dyspnea, feeling cold and clammy. You note bilateral pitting edema 3+. HR is 115, BP is 100/50, SPO2 90%RA, Afebrile. TSH 20. CXR shows non-specific intersitial changes. What would be the best NEXT investigation? A. Echocardiogram B. Free T3 and T4 C. Blood gas D. Blood culture x 2 60  MCQ 4: Immuno is a box of chocolate… Mrs. Celinne Dionne is a 30F on pembrolizumab for colon cancer x 1 year presents to office with progressive fatigue, dyspnea, feeling cold and clammy. You note bilateral pitting edema 3+. HR is 115, BP is 100/50, SPO2 90%RA, Afebrile. TSH 20. CXR shows non-specific intersitial changes. What would be the best investigation to identify the etiology? A. Echocardiogram Wrong answers: B – While technically correct, wouldn’t be the BEST test. Myxedema generally would be with B. Free T3 and T4 much higher TSH C – While this would provide you with oxygenation information, wouldn’t contribute much to C. Blood gas the diagnosis D. Blood culture x 2 D – There’s no evidence sepsis is the most likely clinical picture here. Correct answer: A – Safety exam- Rule out most dangerous thing which would be immunotherapy-related myocarditis 61  Palliative Care Early Involvement Performance Status Pain Management + Opioid Rotation Symptom Management MAID 62  MCQ 5. Pain Management Mr. T Pain, a 68yM with metastatic lung CA presents with an acute pathological T8 fracture. He rates his pain as 10/10. He is nauseous and vomiting. AKI with Cr 220. He was taking M-Eslon 120 mg po BID for pain plus 30 mg morphine IR for breakthrough, 7 doses per day before the fracture occurred. In addition to dexamethasone, what treatment will you initiate for his pain control? a) Morphine IV 30mg q4h prn b) Fentanyl patch 40 mcg q 72h + hydromorphone 2mg sc q1h PRN c) Hydromorphone Contin 42mg po BID + 5 mg IR q1h prn d) Hydromorphone 8mg sc q4h + 2 mg sc q1h prn e) Hydromorphone 6mg sc q4h + 4 mg sc q1h prn 63  !!! Involving Palliative Care Marked with ⌘ Palliative-Intent Treatment Palliative Care* Oncology Term: (Think Diabetes) Symptomatic management that often coincides Treatment that will control the cancer but can not cure it with oncological care. Stopped when patient too frail Used until the end of life Bottom Line: Don’t delay or avoid palliative care for a patient with metastatic cancer just because they are pursuing disease-directed treatment.**⌘ *Palliative vs Med Onc- Who to consult first in advanced cancer on Royal College? A: Med Onc Choose Palliative ONLY if VERY frail and/or refuse treatment. (On O2, ECOG 3-4, life span < 3-6 months independent of cancer) ** Benefits include: better mood, quality of life. Less aggressive interventions near end of life. Improved survival However… Big difference in survival vs Med Onc: Early Palliative Care (3 months) vs Med Onc (1.5 years to years)13 (NOE) 64  !!! Performance Status Marked with ⌘ ECOG score Palliative Performance Scale 100% (perfectly well) – 0% (death) Score Description Measure of physical status in palliative care 0 Asymptomatic PPS 50% (sit/lie throughout day) = only 10% of pts expected to survive >6mo 1 Symptomatic Completely ambulatory Able to do light house work 2 50% day spent in bed/chair (patients ECOG 3-4) ⌘ Only limited self-care 4 Bedbound 5 Dead 65  Pain Control Options Non-opioids – Acetaminophen, NSAIDs Nociceptive pain Opioids – Morphine, Hydromorphone, Fentanyl, etc. Adjuvants – Pregabalin, Gabapentin, TCAs Neuropathic pain Opioid titration Goal to address most of the baseline pain with long-acting formulations 1. Start with immediate release (IR) formulation Q1-Q4H PRN (q4h PRN for opioid naïve) 2. Low dose à increase to effect/side effects 3. Allow for steady state (~24hrs = 5 half lives) 4. Once steady state achieved, calculate total use in past 24 h 5. Divide 24hr dose into distributed doses of long acting formula 6. Order breakthroughs (= 10% of total daily dose in IR tabs) Cannabinoids Nabilone > placebo, but benefits compared to other analgesics not proven (CADTH 2011) 66  !!! Pain Control Picking an opioid No comorbidities – No one right answer. Usually based on physician comfort Renal dysfunction – Hydromorphone, Methadone, Fentanyl o Do NOT use: Morphine, Codeine, Tramadol, Demerol ”No Morphine with No Urine” Hepatic dysfunction – Hydromorphone, Morphine, Fentanyl o Do NOT use: Codeine, Methadone “No Meth with Failing Heps” Excess opioid-induced itching/urticaria – Fentanyl Opioid side effects Common: Constipation, Nausea, Vomiting, Sedation Rare: Confusion, hallucination, Myoclonus **Important, lesser-known side effect Methadone specific: QT prolongation, Drug-drug interactions (CYP3A4 metabolism) If treatment addresses source of pain, need to decrease opioids to prevent toxicity 67 !!! Opioid Rotation 1. Calculate total daily dose (TDD) of drug 2. Convert TDD to ORAL MORPHINE EQUIVALENT using equianalgesic table19 below 3. Convert TDD to drug of choice 4. Calculate regular/interval dosing – long-acting (BID) or short-acting (q4h) 5. Calculate PRN dose (q1h) based on 10% of TDD or 50% of q4h dose Equivalence to 30 To convert to PO PO : IV/SC Effect Duration mg oral morphine morphine, multiply by Morphine 30 mg 1 2:1 2-4 hrs Oxycodone 20 mg 1.5 N/A 3-4 hrs Hydromorphone 6 mg 5 2:1 2-4 hrs Transdermal 60-90 mg morphine = 25 mcg/hr 48-72 hrs Fentanyl 120-180 mg morphine = 50 mcg/hr Clinical Pearl: If switching meds due to toxicity (i.e. myoclonus), consider 25-50% dose reduction to allow for cross tolerance à 50% for well controlled pain, 25% for uncontrolled pain. 68  Symptom Management Marked with ⌘ Dyspnea Stepwise approach: Non-pharmacologic therapies (i.e. fan, open window, walker) à oxygen (if hypoxic) à Opioids20 Oxygen ineffective for non-hypoxemic dyspnea⌘ Nausea and Vomiting Direct treatment towards etiology Unknown etiology – Dopamine antagonist favored (haloperidol, olanzapine) or agents used for chemotherapy-induced nausea and vomiting Delirium Risperidone/haloperidol do not alleviate distress at end of life and tend towards harm (JAMA 2017) o May slightly worsen delirium symptoms (low quality evidence, Cochrane Review 2020) o May increase adverse side effects (EPS symptoms) (low-mod quality) Cachexia: Refer for counseling + assessment re: high protein, nutrient dense food, advise against extreme diets/fad diets Do NOT offer enteral tube feeding or parenteral nutrition to manage cancer cachexia Olanzapine now recommended at low dose. 69  Medical Assistance In Dying – Legal since 2017 Criteria- Need to meet ALL FIVE Personal Attributes 1. Eligible for health services funded by the province/ country 2. 18+ years old and is capable* 3. Make a voluntary request for MAID (free from outside pressure or influence) 4. Provide informed consent for MAID Disease Attribute 5. Grievous and Irremediable Physical, NOT mental illness*~ 1. Serious and Incurable illness 2. Advanced decline that CAN’T be reversed 3. Suffering but ways of improvement are not acceptable to patient * Can’t be in state of delirium/ dementia/ encephalopathic (ex. From organ failure from cancer) ** Mental Health- Eligibility date moved to 2027. ~ It used to be “death is reasonably foreseeable”. This was repealed in 2021. (ex. ALS patients would previously be excluded but now are not) 70  Stream 1: Death is reasonably Stream 2: Death is NOT foreseeable Foreseeable * Request in writing, signed by 1. Request in writing, signed by independent witness independent witness 2 independent MD/NPs must 2 independent MD/NPs must confirm all eligibility criteria met confirm all eligibility criteria met AND consult with expert in the Person must be given opportunity medical condition (if MD/NP is to withdraw consent, and confirm unfamiliar with it) consent expressly before receiving MAID The person must be informed of means to alleviate suffering and be offered consults with experts in this (incl. counselling, pall care…) *MAID can happen as quickly as The eligibility assessments must 1-2 days depending on logistics. take at least 90d, but this period 10 day reflection was removed can be shortened if pt about to lose capacity Person must be given opportunity to withdraw consent, and confirm consent expressly before receiving MAID MAID  MAID: Final Consent Requirement Pt does not have to provide consent immediately before provision of MAID if : 1. Pt has been assessed and approved for MAID 2. Pt was at risk of losing decision making capability prior to receiving MAID and was made aware of that risk 3. Person makes arrangement in writing with their practitioner to waive final consent, and according to which their practitioner will provide MAID on their preferred date if they have lost capacity (“Audrey’s amendment” ) 72  MAID legislation… more confusion in 2024 Advanced Request Legislation = Not Legal Yet Scenario: A physician has early dementia and requests, when capable, that when she is dependent for an ADL like toileting or cannot recognize her family she would like to have MAID. Under current Canadian Criminal Code legislation, this is not allowed as patient would not be capable at time of MAID and cannot give an ‘advanced date’ as time from decision to incapacity could be months or years in this scenario, depending on cause of dementia. As of October 30, 2024 – Quebec (only Quebec) has new legislations that will allow Quebec physicians to provide MAID in Quebec (only Quebec) under an advanced request This is technically still “not legal” in that the federal Criminal Code does not allow advanced requests. – However Health Minister (federal) has indicated they will not challenge Quebec in their legislation This is an area of ongoing debate and legislation – You being a Quebec doctor asked about future MAID for a patient with dementia WILL NOT BE A SCENARIO on the Royal College. If it is, you should call the CMPA as part of your exam response! 73  MCQ 5. Pain Management Mr. T Pain, a 68yM with metastatic lung CA presents with an acute pathological T8 fracture. He rates his pain as 10/10. He is nauseous and vomiting. AKI with Cr 220. He was taking M-Eslon 120 mg po BID for pain plus 30 mg morphine IR for breakthrough, 7 doses per day before the fracture occurred. In addition Opioid Rotation Calculation to dexamethasone, what treatment will you initiate1)forTDD his= pain 450 mgcontrol? morphine po 2) Divide by 2 to get sc/IV equiv: 225 mg a) Morphine IV 3) 30mg q4htoxicity, Due to renal prn convert to non-morphine (eg) hydromorphone – divide by 5 b) Fentanyl patch= 40 mcg 45 mg totalqdaily 72h + dose iv/sc hydromorphone 2mg sc q1h PRN 4) When converting dose reduce to avoid toxicity w AKI = 6mg q4 (36 mg per day) c) Hydromorphone Contin 5) Calculate PRN =42mg 10% TDDpo BID + 5 mg IR q1h prn d) Hydromorphone Answer E:8mg sc q4h +6mg Hydromorphone 2 mg sc q4hsc+ 3mg q1hscprn q1h prn Wrong Answers: Morphine shouldn’t be used in AKI. Patient is vomiting so po e) Hydromorphone 6mg not hydromorphone sc good. q4h Fentanyl + 3 mgpatch sc q1h prnto ‘kick in’ so not ideal in this takes 12h setting of severe acute pain 74  Questions? Many practice MCQs available in your BONUS materials for self-study and on FLEXIQUIZ online 75  REFERENCES 1. Zimmer AJ, Freifeld AG. Optimal Management of Neutropenic Fever in Patients With Cancer. J Oncol Pract 2019;15(1):19-24. DOI: 10.1200/JOP.18.00269. 2. Canadian Task Force on Preventive Health Care. Breast Cancer (Update) – Draft Recommendations (2024). 3. Canadian Task Force on Preventive Health Care. Recommendations on screening for lung cancer. CMAJ 2016;188(6):425-432. DOI: 10.1503/cmaj.151421. 4. Canadian Task Force on Preventive Health C. Recommendations on screening for colorectal cancer in primary care. Canadian Medical Association Journal 2016;188(5):340-348. DOI: 10.1503/cmaj.151125. 5. Leddin D, Lieberman DA, Tse F, et al. Clinical Practice Guideline on Screening for Colorectal Cancer in Individuals With a Family History of Nonhereditary Colorectal Cancer or Adenoma: The Canadian Association of Gastroenterology Banff Consensus. Gastroenterology 2018;155(5):1325-1347.e3. DOI: 10.1053/j.gastro.2018.08.017. 6. Coffin CS, Fung SK, Alvarez F, et al. Management of Hepatitis B Virus Infection: 2018 Guidelines from the Canadian Association for the Study of Liver Disease and Association of Medical Microbiology and Infectious Disease Canada. Canadian Liver Journal 2018;1(4):156-217. DOI: 10.3138/canlivj.2018-0008. 7. Singal AG, Llovet JM, Yarchoan M, et al. AASLD Practice Guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma. Hepatology 2023;78(6):1922-1965. DOI: 10.1097/HEP.0000000000000466. 8. Dickinson J, Tsakonas E, Conner Gorber S, et al. Recommendations on screening for cervical cancer. CMAJ 2013;185(1):35-45. DOI: 10.1503/cmaj.121505. 76  REFERENCES 9. Anderson BO, Berdzuli N, Ilbawi A, et al. Health and cancer risks associated with low levels of alcohol consumption. The Lancet Public Health 2023;8(1):e6-e7. DOI: 10.1016/S2468-2667(22)00317-6. 10. WHO clinical treatment guideline for tobacco cessation in adults [Internet]. Geneva: World Health Organization; 2024. Executive summary. Available from: https://www.ncbi.nlm.nih.gov/books/NBK604667/ 11. Hamer J, Warner E. Lifestyle modifications for patients with breast cancer to improve prognosis and optimize overall health. CMAJ 2017;189(7):E268-E274. DOI: 10.1503/cmaj.160464. 12. Schneider BJ, Naidoo J, Santomasso BD, et al. Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update. J Clin Oncol 2021;39(36):4073-4126. DOI: 10.1200/JCO.21.01440. 13. Temel JS, Greer JA, Muzikansky A, et al. Early palliative care for patients with metastatic non-small-cell lung cancer. N Engl J Med 2010;363(8):733-42. DOI: 10.1056/NEJMoa1000678. 77  BONUS Read on own Self study: Metastases Trivia Lymph Node Metastases Right supraclavicular nodes o Lung, Esophageal Left supraclavicular nodes (“Virchow’s node”) o Abdominal malignancies (via the thoracic duct) – Gastric, gallbladder, pancreas, kidneys, testicles, ovaries, prostate o Ipsilateral breast & lung Umbilical nodes (“Sister Mary Joseph Node”) = Intra-abdominal/pelvic metastases o GI – Gastric, colon, pancreas o Gynecologic – Ovarian, endometrial o Unknown primary 78  BONUS Read on own Self study: Metastases Trivia Bone metastases Osteoblastic (ie. Sclerotic) o Prostate, SCLC, Carcinoid, Hodgkin lymphoma Osteolytic o Multiple myeloma, NSCLC, RCC, Melanoma, Thyroid, Non-Hodgkin lymphoma Mixed o Breast, GI, Squamous cell carcinomas (NSCLC, H&N, Cervical ca) 79  BONUS Read on own Self study: Stage IV Consolidation Lung Cancer o Pleural effusion in lung cancer = Stage IV (i.e. incurable) Colorectal Cancer o “Few” liver or lung metastases = Stage IV, but may be curable with metastatectomy Testicular Cancer o Metastatic testicular cancer (Technically stage 3C as there’s no stage 4) still potentially curable 80  BONUS Read on own Self-Study: Cancer of Unknown Primary !! Histology Clinical Features Work-Up Suggested treatment “Adenocarcinoma” Woman, Axillary Mammo, MRI breast Treat as breast ca adenopathy Woman, Peritoneal CA-125, TVUS Treat as ovarian ca carcinomatosis Man, Elevated PSA, Bone PSA, Bone scan Treat as prostate ca metastases “Squamous cell Cervical adenopathy Pan-endoscopy, PET Treat as H&N ca carcinoma” Man, Inguinal adenopathy Lower endoscopy Treat as anal cancer Woman, Inguinal Pap smear, TVUS, Treat as cervical cancer or adenopathy endoscopy anal cancer “Poorly- Young man, Midline Scrotal ultrasound Treat as testicular primary differentiated tumour, Elevated hCG/AFP carcinoma” 81 Adapted from UpToDate  !! BONUS Read on own Self Study: Renal Cell Carcinoma RCC once called “The Internist’s Tumor” due to variety of paraneoplastic phenomenons. Remember to consider as a ddx if you see any or constellation of the following: Hypercalcemia Hypertension Polycythemia Cushing’s Classic Triad (occurs in less than 15% of patients) Galactorrhea palpable mass Hematuria Amyloidosis Flank pain Coagulopathy/ Thrombosis Stauffer’s Syndrome 82  BONUS Read on own Chemo Side Effects: Diarrhea and Mucositis Side Effects TOP Differential Clinical Presentation Management Diarrhea* 1. Systemic Therapy (Chemo) Watery diarrhea 1. Rule out C.Diff… then 2. Immunotherapy Can be bloody 2. Loperamide** 3. Infection (C.diff) Abdo pain (Enteritis) 3. Lomotil Often large volume 4. Overflow diarrhea (except for number 4) 4. Octreotide Mucositis 1. Thrush Oral ulcers 1. Baking soda rinses 2. HSV mouth sores burning tongue/ mouth 2. Viscous lidocaine Odynophagia 3. Magic Mouthwash (nystatin + lidocaine) *Sometimes Chemotherapy Diarrhea balances out the hydromorphone constipation which is nice… **Aggressive Loperamide regimen: – 2 tabs (4mg) with 1st loose stool, 1 tab with EVERY loose stool until no more x 12 hours. – Max 8 tabs / 24 hours. 83  BONUS Read on own Infamous Chemo Side Effects Drug Management Implicated Chemo Drugs Alopecia No great therapy. Small risk of permanent hair loss -rubicins (Breast, Lymphoma) Cold Capping (Preventative)- Mixed results -tecans (Lung, Gyne) -taxels (Breast, Lung, Gyne) Rash 1. Body: Betaderm. Face: Hydrocort. Widespread: Systemic - 5FU / Cape (GI, Breast) steroid 2. Moisturizer 3. Sunscreen/ Sun protection/ Sun avoidance Neuropathy No great therapy. Risk of permanent neuropathy. -taxels (Breast, Lung, Gyne, (Glove and Stocking) Esophagus) -platins (Lung, Gyne) Myelosuppression Feb Neut Any chemotherapy Platelet issues rare. Transfuse Hb PRN. Secondary No great preventative options aside from changing -fosfamide (Breast, Lymphoma) Malignancies chemotherapy - rubicins (Breast, Lymphoma) (Generally haem) 84  BONUS Read on own End-of-Life Tidbits Marked with ⌘ For patients with limited life-expectancy begin end-of-life discussion and advanced care planning early ⌘ o Involve Palliative Care early, even if patient is pursuing disease-directed treatment (i.e. chemo) Discontinue statins (JAMA Int Med 2015: safe, improves QOL and saves money) Do not transfuse RBC at arbitrary cut-off w/o symptoms ⌘ 85  BONUS Q1 2025 40F nonsmoker presents with stage IV lung cancer, she has shaved her hair in preparation for chemotherapy. You are getting her cancer worked up so she can go see her oncologist. Which of the following statement is correct? A. She will need molecular testing as she may not need chemotherapy as treatment. B. The presence of pleural effusion means there’s definite metastatic lung cancer. C. Palliative care referral is only required near the last 3 months of life D. Stage IV lung cancer is one of the few cancers that are curable at stage IV setting. 86  BONUS Q2 2025 50M, obese, with history of hypertension, dyslipidemia, presents with right axillary lymph node enlargement, mixed sclerotic and lytic bone metastases. Biopsy of the lymph node reveals adenocarcinoma. What is the best NEXT investigation? A. PSA and DRE B. Mammogram C. Colonoscopy D. PET scan 87  BONUS Q3 2025 18M with end-stage metastatic colon cancer. He is clearly in distress and his family is begging you to assess him for MAID. You find him at the bedside but he remains delirious, same as he was over the last month. What is the best management? A. Consent is obtained from patient and MAID is performed. B. Consent is obtained from power of attorney/ substitute decision maker and MAID is performed. C. Consent is not possible and thus MAID is not allowed. D. Consent is assumed given his situation and thus MAID is performed. 88  BONUS Q4 2025 65F with advanced colon cancer undergoing treatment. She is quite fatigued for multitude of reasons but she tells you part of the reason is because her hemoglobin is 80. You do note that more recently her hemoglobin was 100 around 3 months ago. Outside of investigation of the cause of anemia, what is the next BEST step? A. Do not transfuse PRC as hemoglobin is not yet at threshold of 70 and there’s no active bleeding. B. Transfuse 1 unit PRC as patient is symptomatic. C. Do not transfuse PRC based on arbitrary cut-off as per Choosing Wisely. D. Transfuse 1 unit PRC as to avoid legal repercussions. 89  BONUS Q5 2025 Per most recent WHO guideline, what is the recommended amount of alcohol use per day? A. None- There is no safe limit B. Less than 2 standard drinks per day C. Less than 4 standard drinks per day D. Party like it’s 1999. 90  BONUS Q6 2025 74F, ultramarathon runner otherwise healthy, presents to the emergency department with acute onset dyspnea. On exam her HR was 120, BP 110/53, spO2 83% RA, JVP elevated, 2+ peripheral edema. CXR showed bilateral interstitial changes. You note that she had a mastectomy scar over her left chest and was notified she had breast cancer 10 years ago. What’s the likely cause of her current symptoms? A. Herceptin B. Myocardial infarction C. Doxorubicin D. Pneumonia 91  BONUS Q7 2025 38F presents to clinic with new onset hypertension, abdominal pain, constipation. Her history and physical exam were otherwise unremarkable. On investigations her Hb was found to be 165, calcium 3.1, albumin 38, ALT 230, AST 200, ALP 300, Bilirubin 18. CT chest abdo pelvis shows one 2-cm lesion in the chest wall, 3- cm lesion in the lung, one 1-cm lesion in the bone, and one 4-cm lesion on the kidney. What is the likely malignancy? A. Multiple myeloma B. Lung cancer C. Breast cancer D. Renal cell carcinoma 92  BONUS Q8 2025 68F presents to clinic with 1 day of fever, confusion, diplopia, and subsequently seizure that resolved with levetiracetam. On reviewing the chart you see that she has metastatic melanoma and is currently on immunotherapy with Nivolumab. MRI head is performed which showed no intracranial abnormalities. Rest of vitals all normal. CBC, lytes, extended lytes, Cr, LFTs all normal. What is the best next step? A. LP to rule out meningitis / encephalitis B. Order serum anti-Hu antibody C. Start pulse steroids D. EEG 93  BONUS 2025 MCQ ANSWERS 1. A- Lung cancer management has evolved and thus some mutations like EGFR can be targeted by oral pills like Osimertinib- significantly prolonging their survival. Pleural effusion needs to prove malignant. Early palliative care is critical. Stage 4 lung cancer is NOT curable. 2. B- Male can have breast cancer too. This history suggests ++ estrogen due to high adiposity. Prostate shouldn’t have lytic bone metastases. Colon CA doesn’t generally give axillary LN. PET scan not indicated upfront when there can be more specific investigation. 3. C- Consent for MAID HAS TO be from patient, POA and SDM not allowed. 4. B- While this is in the gray zone depending on clinical judgment, RC questions can be gray as well. Generally if there’s a reasonable chance this is a contributing factor, we will transfuse (if Hb is 110 then we wouldn’t of course). Choosing Wisely mentions no arbitrary cut-off “in the absence of symptoms”. 5. A- See slides. No safe limit. 6. C- She likely had chemotherapy for her breast cancer, which can cause delayed and permanent cardiotoxicity. Herceptin heart failure occurs on treatment, doesn’t lead to problems years donw the line. Myocardial infarction on ddx but there’s a much more compelling answer and she is an ultramarathon runner with no significant cardiac risk. 7. D- RCC- the classic internist’s tumour: Polycythemia, hypercalcemia, Stauffer’s syndrome. Myeloma can produce similar picture but not the transaminitis and polycythemia, same with lung cancer. 8. A- She likely has immune-related encephalitis. LP is needed. Anti-Hu is part of SCLC paraneoplastic antibody. No dx yet so no steroids. EEG would not lead to the diagnosis. 94  2024 LECTURE MCQ1. Screening Miss Liv Well is a 42F presents for routine cancer screening. She reports a recent diagnosis of MASH (metabolic dysfunction associated steatohepatitis) Childs Pugh A cirrhosis, family history of colon cancer in her father at age 70, She smoked 1 ppd from age 18 onward. Her cervical cancer screening is up to date. What cancer screening do you recommend? a) FIT testing, AFP, low dose CT Thorax, b) Colonoscopy, Abdo U/S, AFP c) Mammogram, Abdo U/S, AFP, colonoscopy, low dose CT Thorax d) Mammogram, FIT testing, AFP, low dose CT Thorax e) Mammogram, FIT testing, Abdo U/S, AFP, low dose CT Thorax 95  2024 LECTURE MCQ 2 Mr. Remy Kade is a 35M with history of uncontrolled Crohn’s disease is admitted to your service with RLQ abdominal pain. CT C/A/P shows small lesions throughout his lungs and liver, suspicious for metastases. Hb 100, Plt 200, WBC 9. CRP is normal. What is the best next step? A. Colonoscopy, CEA B. Prednisone 1mg/kg daily C. Abdo U/S for liver biopsy, AFP D. PET scan, CA 19-9, CEA, CA 125 E. DRE, PSA F. Call Medical Oncology 96  2024 LECTURE MCQ 3 Ms. Sega Rett is a 55F with LU