2024 Medical management DAY 2 2024 FINAL (1).pdf

Oncology Unit March 18 -22, 2024 Day 2: Diagnosis, Staging, and Grading Presented to: Physiology II Presented on: March 20, 2024 Presented by: Ann Marie Flores, PT, MSPT, PhD, Certified Lymphedema Therapist Associate Professor & Director, Cancer Rehabilitation Studies (CARES) Laboratory, PTHMS; Dept...

Oncology Unit March 18 -22, 2024 Day 2: Diagnosis, Staging, and Grading Presented to: Physiology II Presented on: March 20, 2024 Presented by: Ann Marie Flores, PT, MSPT, PhD, Certified Lymphedema Therapist Associate Professor & Director, Cancer Rehabilitation Studies (CARES) Laboratory, PTHMS; Dept. of Medical Social Sciences Director of Cancer Rehabilitation, Cancer Survivorship Institute Robert H. Lurie Comprehensive Cancer Center of Northwestern University [email protected] Cell/text: (615) 364 -2544 Disclosures Financial Disclosures - NCI/NIH 3UM1CA233035-01S1, R01 CA271220 - Lynn Sage Breast Cancer Research Foundation Scholar Award - FDA UG3FD006794 Bias Mitigation - I have used the Feinberg bias checklist to review this lecture to mitigate bias. - I have reviewed this lecture for use of stereotypical or offensive terms, language, etc. - I have, to the best of my abilities, used inclusive language, pronouns, photos and images. - Despite best efforts and intentions, if there is concerning content, please feel free to contact me or report via the bias reporting system. Oncology Unit Overview Day 1 - March 18, 2024: What is cancer? Introduction to cancer epidemiology, pathophysiology, & risk factors for cancer development Day 2 - March 20, 2024: How is cancer treated? Medical management of cancer diagnoses - screening, detection, diagnostic work-up, treatment options Day 3 - March 22, 2024: How does physical therapy help patients with cancer? Principles of oncology physical therapy management 3/20/23 2 Oncology Unit Objectives Appreciate the prevalence, incidence, mortality & survival from cancer Identify & use terminology to describe cancers and its pathophysiology Identify risk factors that contribute to cancer development Identify signs, symptoms, & tests that clarify a cancer diagnosis Discuss & describe medical treatment for cancer, side effects and adverse events that affect tolerance for medical treatment & implications for rehabilitation – including clinical red flags for emergencies, urgencies, and recurrence Discuss & apply the benefits of cancer rehabilitation, exercise, and physical activity on symptoms, side effects and adverse events of cancer survivors – including the use of clinical practice guidelines 3 “What I do not remember signing up for was all the late and longterm side effects of cancer treatment, or maybe I did sign for them in a sort of deal with the devil so that I could finish PT school on time and return to my precancer life of running and being with my friends. We sign on the dotted line to rid the cancer from our bodies, but just like the mortgage, student loans, and back taxes, we end up having to pay in the end. Unfortunately, paying off this debt comes with a high interest rate (a multitude of adverse effects) heaped on top of the principal balance.” Cancer Diagnostic Work-Up 6 7 Warning Signs of Cancer “CAUTION(S)” CAUTION(S) Changes in bowel or bladder habits Long-term constipation, diarrhea; change stool size; urinary pain and blood; change in bladder function (urinary frequency) A sore that does not heal in 6 weeks Skin, mouth (white patches/spots in mouth/tongue, infections, smoking, or other tobacco); genitalia Unusual bleeding or discharge Hemoptysis; blood in the stool (very dark or black), abnormal vaginal bleeding; hematuria; bloody nipple discharge Thickening or lump in breast or elsewhere Any thickened skin (may indicate some breast cancers); lump anywhere (e.g., breast, testicle, lymph nodes (glands), soft tissues Indigestion or difficulty swallowing Persistent, long-term Obvious change in wart or mole Any change in color, size, shape, loses sharp border; darkening, yellowing, reddishness, itching, and excessive hair growth Nagging cough or hoarseness Persistent, long-term Supplemental Signs & Symptoms Unexplained weight loss (>= 10 #), fatigue (extreme tiredness; unrelieved from rest), persistent pain (esp. back, abdomen, headache) Cleveland Clinic. Accessed at: https://my.clevelandclinic.org/departments/cancer/patient-education/wellness-prevention/warning-signs; American Cancer Society. Last Revised: November 6, 2020. Available at: https://www.cancer.org/cancer/diagnosis-staging/signs-and2 symptoms-of-cancer.html Cancer Diagnosis Work-Up – Biopsy, Labs, & Imaging Biopsy of suspicious area Needle biopsy Surgical Biopsy Fine needle aspiration (FNA) fluid/cells/tissue w/ thin needle Core - wide needle sample Needle-localized biopsy – Imaging guided wire w/ hook @ end through hollow needle to mark abnormal area; biopsy taken & wire removed) Labs & imaging Blood, sputum, urine, stool, spinal fluid (lumbar puncture) Plain film (X-ray) radiography Colonoscopy, sigmoidoscopy Mammography, ultrasound CT & MRI PET-CT DEXA bone scan Incisional – sample area Excisional – remove entire area (also healthy margin) Ultrasound-guided Stereotactic (CT or MRI guided) 8 Tumor markers Biochemically measured substances produced by tumors Hormones, gene mutations, proteins, enzymes, antigens, antibodies - Indicate the presence of a neoplasm (malignancy or benign) - Can guide diagnosis, prognosis, and treatment - - Sensitivity to various medical (chemotherapy, immunotherapy) options Responsiveness to treatment Determine prognosis Analyzed with blood sample or tumor - 85 common marker tests - 9 Tumor Marker CA Type What’s analyzed? How is it used? Alpha-fetoprotein (AFP) Liver cancer, ovarian cancer, germ cell tumors Blood Diagnosis (stage), prognosis, treatment responsiveness BRCA1 & BRCA2 gene mutations Breast, ovarian, pancreatic, prostate Tumor, blood Determine treatment Carcinoembryonic antigen (CEA) Colorectal, breast, lung Pancreatic, stomach, liver, ovarian Blood Treatment effectiveness, detect recurrence Epidermal growth factor receptor (EGFR) mutation Non-small cell lung cancer and colorectal cancer Tumor Determine treatment & prognosis Estrogen receptor (ER)/progesterone receptor (PR) Breast cancer Tumor Determine treatment HER2/neu (ERBB2) gene amplification, mutations, protein overexpression Breast, ovarian, bladder, pancreatic, non-small cell lung, gastroesophageal, and stomach cancers Tumor Determine treatment Tumor Prognosis, determine treatment (which targeted therapy(ies) will work) PIK3CA (Phosphatidyl Inositol-4,5bisphosphate 3-Kinase Catalytic subunit Alpha) gene mutation Breast, colorectal, non-small cell lung, ovarian Programmed death ligand 1 (PDL1) Non-small cell lung, triple negative breast cancer (TNBC), liver, stomach, gastroesophageal, cervical, bladder, head & neck, Hodgkin lymphoma, aggressive lymphoma subtypes Tumor Determine treatment Prostate-Specific Antigen (PSA) Prostate Blood Diagnosis, assess treatment response, recurrence Tumor Staging Stage - extent of cancer & relies on: - Tumor size - Nodal involvement - Presence of Metastasis - TNM status Clinical & pathological staging - also posttherapy, recurrence, & autopsy staging - Clinical (cTNM) - based on patient history, physical exam, imaging, biopsy - Pathological (pTNM) – combines clinical staging w/ surgical pathology results; before adjuvant radiation or systemic therapy. Staging - Solid Tumors In Situ – pre-invasive - Stage I - Limited to organ of origin & small - Stage II – Larger than Stage I, same anatomic region; local invasion of organ; possible nodal spread Stage III - Larger invasion of organ; regional nodal spread (surrounding primary organ) - Stage IV - Largest; extensive invasion; distant metastasis(es) - Amin M. AJCC Cancer Staging Manual, 8th Edition. American College of Surgeons. 2017. ISBN 10: 3319406175 1 T = tumor size & extent of tumor Amin M. AJCC Cancer Staging Manual, 8th Edition. American College of Surgeons. 2017. ISBN 10: 3319406175 - assessed differently based on involved anatomic structures Example: Gastric (stomach) cancer T4 invasion to adjacent organ w/ distant mets T3 invasion in serosa T2 invasion in muscle T1 invasion in submucosa Tis in situ (mucosal layer) T0 no evidence of tumor TX No info. about T category for primary tumor, or it is unknown, or cannot be assessed Wu HQ, Wang HY, Xie WM, et al. Scanning photoacoustic imaging of submucosal gastric tumor based on a long-focused transducer in phantom and in vitro experiments. Journal of Innovative Optical Health Sciences. 2019; Vol. 12, No. 03, 1950011. https://doi.org/10.1142/S1793545819500111 N = Nodal involvement/spread N0 - no regional nodal spread N1-N3 - degree of nodal spread w/ progressively distal spread Varies by tumor type # of nodes Nodal location Sub-categories & micrometastasis Example: Colorectal Cancer N0 - No nodal involvement N1 - 1-3 regional nodes N2 - 4-6 regional nodes N3 - 7+ regional nodes Nx - unable to be assessed Amin M. AJCC Cancer Staging Manual, 8th Edition. American College of Surgeons. 2017. ISBN 10: 3319406175 1 M = Distant Metastasis MX: Metastasis cannot be measured M0: Cancer has not spread to other parts of the body M1: Cancer has spread to other parts of the body Amin M. AJCC Cancer Staging Manual, 8th Edition. American College of Surgeons. 2017. ISBN 10: 3319406175 1 Tumor Grading - How “aggressive” is the cancer? In general, most tumors are graded as: Based on - Microscopic appearance of cells - Rate of growth (undetermined grade) - Degree of differentiation - Mitotic activity/phase of mitosis - Angiogenesis - Irregular borders Grade X: Grade cannot be assessed Grade 1: Well differentiated (low grade); cells look close to normal Grade 2: Moderately differentiated (intermediate grade) Grade 3: Poorly differentiated (high grade) Grade 4: Undifferentiated (high grade); cells most abnormal Amin M. AJCC Cancer Staging Manual, 8th Edition. American College of Surgeons. 2017. ISBN 10: 3319406175 https://www.cancer.gov/about-cancer/diagnosis-staging/diagnosis/tumor-grade 10 https://www.cancer.gov/about-cancer/diagnosis-staging/diagnosis/tumor-grade General Relationship Between Tumor Grade & Survival 100% Low grade Patient Survival Rate High grade 0% 1 3 2 Years 4 5 11 Additional Tumor Classification Systems Gleason score - Prostate CA - Two samples of highest grade are added Score can be 2, or up to 10. Score 8-10 = ↑ mortality FAB type - Leukemia FAB (French, American, British) system Classification for Acute myeloid leukemia (AML) 8 subtypes - MO-M7 based on cell type Clark Levels – Malignant Melanoma Levels I - V - Depth of lesion in mm FIGO Staging System – Cervical, - Level I - epidermis only Endometrial/Uterine, Ovarian - Level II – spread into upper layer of dermis Endometrial example: - Level III – spread into lower layer of dermis Stage I (1) - confined to the uterus - Level IV – spread into reticular dermis - Level V – spread into subcutaneous tissue Stage II (2) - spread to the cervix Stage III (3) - spread to vagina, ovaries, and/or lymph nodes Stage IV (4) spread to bladder, rectum, or organs distant from uterus (e.g., lungs, bones) 18 Paraneoplastic Syndromes Symptom complexes triggered but not caused by tumor mass Effects remote from neoplastic site Hormone secretions or metabolic abnormalities that can be measured Early sign of cancer (10 – 20%) Causes altered immune system Tumor cells make autoantibodies, cytokines, hormones, or peptides affecting multiple organ systems (e.g., neuro, derm, GI, endo, heme, cardio) Happens before or after diagnosis Monitor to diagnose the occult malignancy and improve patient clinical outcomes. Hapa B, Mahendraker N, Ramphul K. Paraneoplastic Syndromes. [Updated 2023 Mar 31]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK507890/# 19 Paraneoplastic Syndromes – caused by CA treatment Cushing Syndrome - from small cell lung cancer Hormonal disorder, high levels of cortisol. upper body obesity, easily bruise Myasthenia gravis - Lung cancer, thymoma Autoimmune neuromuscular disorder, muscle weakness Scleroderma - Carcinoid syndrome Autoimmune connective tissue disease, stiffening of skin, blood vessels, muscles, & nternal organs Nephrotic syndrome - Hodgkin’s lymphoma Group of symptoms: protein in urine, high cholesterol, swelling Vasculitis - Leukemia Inflammation in the blood vessels 20 Cancer Treatment: Medical Interventions 15 Cancer Prevention & Control Primary – Eliminating or mitigating cancer risk by: - Adopting healthy behaviors & lifestyles Avoiding tobacco & alcohol use Exercising & physical activity Healthy diet Applying sunscreen to protect against UV exposure Secondary - Cancer screening for early detection Prevent disease progression to malignancy. Examples: Breast - self exam, mammography Colorectal – colonoscopy, fecal occult blood test, colonoscopy Prostate - PSA blood test Cervical cancer - Pap smear Tertiary – Reducing/controlling symptoms & morbidity of cancer Gu KJ, Li G. An Overview of Cancer Prevention: Chemoprevention and Immunoprevention. J Cancer Prev. 2020 Sep 30;25(3):127-135. doi: 10.15430/JCP.2020.25.3.127. PMID: 33033707; PMCID: PMC7523034. Managing symptoms Limiting complications Preventing disability 16 Cancer Treatment Strategies Surgery Systemic chemotherapy Endocrine (hormone) therapy Immunotherapy (biologic, targeted) Radiation Stem Cell Transplant Palliative Care 17 Cancer Surgery - Surgical Oncology 24 Surgery Curative excision - Whole lesion Lymph node dissection: removal of an area of lymph nodes Sentinel lymph node biopsy Amputation Palliative - Relieve pressure or blockage - Control bleeding - Reduce infection risk 25 Surgery Prophylactic Cryosurgery Cryotherapy, liquid nitrogen or cold probe Electrosurgery Laser surgery Mohs surgery 1 layer at a time until cells look normal under microscope Typically used for skin cancers Reconstruction 26 Side Effects of Surgery – PT Scope of Practice Amputation Bowel & Bladder Incontinence Chemotherapy induced neuropathy Fatigue Function loss Infection Lymphocele & seroma Lymphedema & axillary web syndrome Muscle weakness, paralysis Non-healing wounds Pain Postural malalignment Scar tissue adhesions Skin ulceration Chemotherapy - Medical Oncology 28 Chemotherapy Most effective during DNA synthesis & mitosis Most organ cells take 19-33 days to complete one full cycle Chemotherapy is given in cycles to “catch” cells in the most effective stage www.chemocare.com 29 Chemotherapy Combinations of drugs often used Used more frequently when more than one mass present or when a mass cannot be removed surgically Different purposes for use at different times: Induction chemotherapy - Shrinks tumor, improves symptoms, may or may not result in a cure Neoadjuvant chemotherapy – also type of induction chemotherapy - Shrinks tumor prior to surgery or radiation Adjuvant chemotherapy - Micro-metastases after surgery 24 Side Effects of Chemotherapy Alopecia Arthralgias Cardiomyopathy Cognitive changes Fatigue GI reactions Hepatotoxicity Metabolic alterations - Ca, glucose, K Myelosuppression Neurotoxicity Pulmonary Toxicity Renal Toxicity Reproductive Dysfunction Skin reactions Chemotherapyinduced neuropathy AKA chemotherapy induced peripheral neuropathy Was H, Borkowska A, Bagues A, Tu L, Liu JYH, Lu Z, Rudd JA, Nurgali K, Abalo R. Mechanisms of Chemotherapy-Induced Neurotoxicity. Front Pharmacol. 2022 Mar 28;13:750507. Chemotherapy-Induced Neuropathy (CIN) Caused by cancer chemotherapy agents – most notably Platinum-based (oxaliplatin, carboplatin, cisplatin) Taxanes (paclitaxel, docetaxel and cabazitaxel) Vinca alkaloids (vincristine, vinblastine, vindesine, vinorelbine) Burgess et al. Oncol Ther. 2021; 9:385–450. Neurotoxic adverse event Generally, interferes w/ axonal transport, causes DNA &/or mitochondrial damage, & alters ion channel activity. Burgess et al. Oncol Ther. 2021; 9:385–450; Zajaczkowska R et al. Int J Mol Sci. 2019;20(6):1451 ‘P’ in CIPN = damage to the peripheral nervous system However, central neurotoxicity also occurs – MORE LATER Burgess et al. Oncol Ther. 2021; 9:385–450 Housley SN et al. Exp Neurol. 2020;331:113354; Sioka C, Kyritsis AP..Cancer Chemother Pharmacol.. 2009;63(5):761–7.. Incidence & Prevalence of Chemotherapy-Induced Neuropathy Overall prevalence of CI(P)N: - 19% - 85% Incidence of OX-based CIPN (OIPN) Acute OIPN: 4–98% Platinum-based: 70–100% Gebremedhn et al. BMC Cancer. 2018;18(1):410 Oxaliplatin most detrimental 3-day peak acute OIPN presents w/ Taxanes: 11–87% Vinca alkaloids: up to 20% Cold-induced hypersensitivity (71%), Sensitivity to swallowing cold food/drink (71%) Throat discomfort (63%) Muscle cramps (42%) Acute OIPN can result in: Prolonged infusion times: 22% Chemo dose reduction: 15–43% Discontinued chemo: 6–21.4% Pachman DR et al. J Clin Oncol. 2015;33(30):3416–22. Initial severity of acute OIPN predicts chronic OIPN in 84% of patients after 25 months Gebremedhn EG et al. BMC Cancer. 2018;18(1):410; Park SB et al. Oncologist. 2011;16(5):708–16.; Lehky TJ, et al. Muscle Nerve. 2004;29(3):387–92.; Land SR et al. J Clin Oncol. 2007;25(16):2205–11.; de Gramont A,et al. J Clin Oncol. 2000;18(16):2938–47. Pachman DR et al. J Clin Oncol. 2015;33(30):3416–22; Briani C et al. Peripher Nerv Syst. 2014;19(4):299–306. Oxaliplatin-induced neuropathy as most common example... Acute No coasting Severity When does it happen & how is acute different than chronic? Chronic Coasting – severity increases & persists after OX-based chemo Sereno M et al. Oxaliplatin induced neuropathy in digestive tumors. Review Crit Rev Oncol Hematol. 2014. Jan;89(1):166-78. Other chemotherapy induced neurotoxicity Chemotherapy-Induced Cognitive Impairment aka Post-chemotherapy Cognitive Impairment (PCCI) “Chemo brain” Memory, problem solving, concentration, dizziness, etc. ~25% who have had chemotherapy Most return to full cognitive function within 1-2 years Ototoxicity 36% of adult cancer survivors; 40%-60% survivors of pediatric cancers Vestibular or cochlear (tinnitus, ear pain, hearing loss) Vincristine Paralytic Ileus Constipation or paralytic ileus. 32% in patients receiving vincristine + concomitant itraconazole (p = 0.04) Chattaraj, A, Syed MP, Low CA, Owonikoko TK. Cisplatin-Induced Ototoxicity: A Concise Review of the Burden, Prevention, and Interception Strategies. JCO Oncology Practice. Vol 19, Number 5. Endocrine Therapy - Hormone Therapy by Medical Oncology 37 Endocrine Therapy Depends on hormone-sensitivity of cancer cells & reduces recurrence risk 2 types that: How it works 1. Block production of hormones anastrozle (Arimidex), letrozole (Femara), exemestane (Aromasin) Blocks aromatase enzyme from converting androgens into estrogen Block production of hormones Interfere with effects of hormones on cancer cells Hormone receptor tests - +/-? Treatment options? Are hormones increasing tumor growth? Breast cancer - ER+, PR+ Prostate cancer – androgen (testosterone) dependent Breast cancer: Aromatase inhibitors e.g., Prostate cancer: Androgen Deprivation Therapy (ADT) 2. Interfere with hormone effects on CA cells Decrease receptors or block receptors on cancer cells 3. Used in combination w: Resection of hormone-producing gland Ovaries, testes Targeted therapy, radiation Dosage can be over several years 38 Side effects of endocrine therapy Breast Cancer Common Hot flashes & night sweats Vaginal dryness Early menopause Less Common Blood clots, CVA Cataracts Constipation New primary CAs – endometrial, uterine Osteopenia, osteoporosis Muscle weakness, fatigue Mood swings, depression, loss of libido Pain w/ breathing, shortness of breath, and cough In men: headaches, nausea, vomiting, skin rash, Pain (e.g., bone, back, musculoskeletal pain, joint pain, in extremities, headache) Prostate Cancer Karzai FH, Madan RA, Dahut WL. Metabolic syndrome in prostate cancer: impact on risk and outcomes. Future Oncol. 2016 Aug;12(16):1947-55. doi: 10.2217/fon-2016-0061. Epub 2016 Apr 12. PMID: 27067408; PMCID: PMC5551937. Common Low libido & erectile dysfunction Hot flashes, gynecomastia Loss of bone density & risk for bone fractures Muscle loss & reduced physical strength Hyperlipidemia & insulin resistance Weight gain/obesity Mood swings & fatigue Liver damage Bone loss Diarrhea Seizures & falls Itching, rash Myocardial infarction, CVA Mimicking metabolic syndrome Less Common Major long term & late effects of endocrine therapy Peripheral neuropathy Chemotherapy – mostly OX Sensory or sensorimotor balance, coordination, pain Cardiotoxicity CHF, MI, HTN, blood clots, thromboembolism, QT prolongation, bradycardia Joint pain/arthralgias Osteopenia - hormone therapy, chemotherapy, surgery Cancer-Related Fatigue Yeh, 2009 44 Therapeutic Radiation - Radiation Oncology 41 Radiation Therapy Destroys hydrogen bonds between DNA strands in cancer cells Standard external beam - 35-37 txs: 5x/week x 5-6 weeks Fractionated doses: to catch all cells at end of G2 Proton beam - More specific - Higher dose possible - Less tissue injury 42 Radiation Therapy Intensity-modulated radiation therapy (IMRT) Sculpts the beam Minimizes damage to normal healthy tissue Internal radiation – AKA brachytherapy Sealed implant Pellets/seeds, ribbons, wires, needles, capsules, balloons, tubes Prostate, breast, head & neck, cervical, ovarian Systemic - Total Body Irradiation (TBI) Leukemia/lymphoma - given before stem cell transplant Eradicate cancer cells Immunosuppression - given so donor stem cells can engraft Lungs & heart often blocked to protect from radiation fibrosis From: http://www.seedos.co.uk/prostate_brachytherapy1.htm 43 Side Effects of Therapeutic Radiation Cardiac toxicity Bowel/bladder changes Diarrhea Fatigue Hair loss Lymphedema Mouth problems Nausea/vomiting Pulmonary dysfunction Radiation fibrosis Skin reactions - Skin color changes Burns Desquamation Swelling Trouble swallowing Ventkatramani et al, 2014; Stubblefield M & Harris. 2011; Gross et al, 2018.. Radiation Therapy Autoimmunity Diabetes Infection Irritant dust Hypertension Trauma Chemicals TISSUE INJURY Radiation induced tissue fibrosis Activation of monocytes/macrophages/platelets Release of cytokines & growth factors Fibroblasts Recruitment Proliferation Increased synthesis of ECM* Degradation of ECM *ECM = Extracellular Matrix FIBROSIS Adapted from Figure 2: Generalized sequence of events leading from tissue injury to fibrosis.: O'Sullivan B, Levin W. Late radiation-related fibrosis: pathogenesis, manifestations and current management. Seminars in Radiation Oncology 2003 Radiation induced tissue fibrosis Straub JM, New J, Hamilton CD, Lominska C, Shnayder Y, Thomas SM. Radiation-induced fibrosis: mechanisms and implications for therapy. J Cancer Res Clin Oncol. 2015 Nov;141(11):1985-94. doi: 10.1007/s00432-0151974-6. Epub 2015 Apr 25. PMID: 25910988; PMCID: PMC4573901. Radiation induced tissue fibrosis Stubblefield, 2011; Purkayastha et al, 2019; DiFrancesco T et al, 2020 31 Stem Cell Transplant - Medical Oncology 48 Stem Cell Transplantation (SCT) AKA hematopoietic cell or bone marrow stem cell transplantation In addition to certain non-malignant conditions, it is used to treat some malignancies Solid tumors Testicular germ cell Non-solid tumors Multiple myeloma, Hodgkin & non-Hodgkin lymphoma, leukemias (acute myeloid, chronic myeloid, acute lymphocytic, chronic lymphocytic, myelodysplastic syndrome) Autologous & allogenic Khaddour K, Hana C, Mewawalla P. Hematopoietic stem cell transplantation. StatPearls. May 2023. National Library of Medicine. Purpose of SCT Curative or provide longer period of disease-free survival Used to treat bone marrow or stem cells that are diseased (malignant) or destroyed by chemotherapy &/or radiation Without stem cells, the immune system cannot be supported SCT infuses healthy stem cells that grow & support immune system Stem cells collected from: Bloodstream (peripheral blood) Umbilical cord blood Bone marrow Gulbis AM, Wallis WD. Chapter 10: Preparative Regimens Used in Hematopoietic Cell Transplantation and Chimeric Antigen Receptor T-Cell Therapies. Manual of Hematopoietic Cell Transplantation and Cellular Therapies. 2024; pp. 125-143. Elsevier. Autologous SCT Patient’s own stem cells are removed, diseased cells removed Healthy cells infused into body after conditioning regimen NO risk of graft rejection Lower risk of infection Engraftment happens quicker than allograft Elevated risk of recurrence Some reintroduced stem cells may have disease 51 Allogenic SCT DONOR cells Stem cells replaced with healthy stem cells from donor Best donor by: Matching Human leukocyte antigen (HLA) matched donor Possibly a relative Anti-rejection meds (cyclosporine or tacrolimus) given to help prevent graft-versus-host disease (GVHD) & transplant rejection 52 Process of SCT For Allograft - Donor matching Human leukocyte antigen (HLA) typing Mobilization & Collection Growth factor stimulates production of blood cells & release into bloodstream Collect stem cells from bone marrow aspiration (ant. or post. Iliac crest) Gulbis AM, Wallis WD. Chapter 10: Preparative Regimens Used in Hematopoietic Cell Transplantation and Chimeric Antigen Receptor T-Cell Therapies. Manual of Hematopoietic Cell Transplantation and Cellular Therapies. 2024; pp. 125-143. Elsevier. Timeline of SCT 1. Preparative (conditioning) regimen Inpatient admin chemo w/ or w/o whole body irradiation Destroy cancer cells & suppress immune system to reduce rejection of stem cells Day of hospital admission to Day 0 (transplant day) 2. Transplantation day to engraftment - Infusion fresh or frozen stem cells via IV infusion - low blood counts, side effects, may need blood transfusions - Day 0 to engraftment (blood count recovery) - Engraftment happens b/t Day +10 to +30 - Still immunosuppressed 3. Engraftment Blood counts recover and increase Takes 2 – 6 weeks to forms new white & red blood cells & platelets & immunosuppressed w/ hi risk for infection - 100 days 4. Early convalescence Labs recovering Still immunosuppressed & high risk of infection. High dose steroids. Continual monitoring. Hospital discharge to 1 year after transplant (or longer) 5. Late convalescence immune system almost fully recovered Return to normal activites May develop late complications (e.g., organ dysfunction or recurrence of the original disease). Vaccination - like a child. 1 year after transplant and onward https://www.mskcc.org/cancer-care/patient-education/autologous-stemcell-transplant-guide-patients-caregivers Side Effects of Stem Cell Transplant Infection Fatigue, Malaise GI & CNS Symptoms Graft vs Host Disease (Allogenic only) ~50% of patients with allogenic stem cell transplant New immune system sees host body as “foreign” Treated w/ chemotherapy, steroids, targeted therapy Ferrara JL, Levine JE, Reddy P, Holler E. Graft-versus-host disease. Lancet. 2009 May 02;373(9674):1550-61 Justiz Vaillant AA, Modi P, Mohammadi O. Graft-Versus-Host Disease. StatPearls. NIH. 2022 Graft vs Host Disease (GVHD) RISK after ALLOGENIC SCT Acute (~2 weeks) Skin rash, liver & GI irritations Burning, color alterations, hands & feet Chronic (3-15 months) 5-year survival rate varies b/t 5% – 25% Extensive skin involvement, diarrhea, thrombocytopenia, elevated liver enzymes, Involvement of lung or liver are poor prognostic factors Ferrara JL, Levine JE, Reddy P, Holler E. Graft-versus-host disease. Lancet. 2009 May 02;373(9674):1550-61 Justiz Vaillant AA, Modi P, Mohammadi O. Graft-Versus-Host Disease. StatPearls. NIH. 2022 Stubblefield MD, Schmitz KH, Ness KK. Physical functioning and rehabilitation for the cancer survivor. Semin Oncol. 2013 Dec;40(6):784-95. 36 Oncologic Emergencies 57 Oncologic Emergencies Type of Emergency Spinal Cord Compression Superior Vena Cava Syndrome (SVCS) Malignant Pericardial Effusion Signs/symptoms Pain, neurological deficits Initial: Facial/UE redness & edema, SOB Late: Cardio/respiratory/GI symptoms Tumor Lysis Syndrome (TLS) Dyspnea, orthopnea, palpitations, fatigue ↓ absolute neutrophil count (ANC), temp