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CANCER STUDIES & P ALLIATIVE CARE Samir Waheed • CA125 – Ovarian • CA19-9 – Pancreatic • CA15-3 – Breast Tumour • PSA – Prostate Markers • CEA – Bowel • AFP – NSGCT (Yolk Sac/Teratocarcinoma), Hepatocellular • HCG – Germ Cell Tumours (Seminomas, NSGCT) • Calcitonin – Medullary Thyroid Cancer T erminology TNM Staging • T = tumour size and local invasion (T1-4) • N = lymph node involvement (N0-3) • M = metastatic spread to other parts of the body (M0-M1) Treatment Aim • Radical: curative • Neoadjuvant: given before primary treatment to shrink tumour • Adjuvant:given after primary treatment to destroy remaining cells and reduce likelihood of recurrence • Palliative: aims to extend life and control pain but will not cure Radiotherapy • Ionising radiation damages DNA • Cancer cells have poorer repair mechanisms than healthy cells which results in increased cancer cell death. • Used for radical, adjuvant, neoadjuvant or palliative intent • Gray (Gy) = the DOSE • Fraction = the number of sessions the dose is delivered over • Types • ExternalBeam: traditional radiotherapy • Brachytherapy: radioactive beads placed into tumour e.g. prostate cancer • SABR: Highly focused (CT-guided) therefore gives higher doses in fewer fractions • Compared to Surgery:  No GA  Less staging information  Less painful  Treat tumour margin  Greater risk of secondary malignancy  Less psychological benefitRadiotherapy Side Effects Usually localised to the area of the body receiving treatment EARLY (SHORT-TERM INFLAMMATION) LATE (LONG-TERM FIBROSIS/SCARRING) Fatigue Nausea Fatigue Pain Hair loss Altered bowel habit Hoarseness Urinary discomfort/cystitis Pain/discomfort Dry mouth (xerostomia) Skin reactions: Dry cough (pneumonitis) • Dry desquamation (skin not broken) Infertility • Wet desquamation (skin broken; infection risk) Secondary cancers e.g. sarcomas Mucositis: Cardiac toxicity • Dysphagia Skin reactions: • Weight loss • Pigmentation • Ulceration • Altered bowel habit • Telangiectasia • Permanent hair loss • Urinary symptoms • Atrophy Chemotherapy/Cytotoxic therapy • Combination treatment using chemo with differing MOAs reduces toxicity • Targets rapidly dividing cells therefore the following non-cancer cells are commonly damaged: • Hair follicles Hair loss • GIT cells Altered bowel habit • Bone marrow cells Bone marrow suppression (anaemia, neutropenia, thrombocytopenia, pancytopenia) • Other side effects: • General fatigue • Infertility • Nausea and vomiting • Hypersensitivityreactions (anaphylaxis) • Thrombosis • Organ toxicity • Palmar-plantar erythema (rx with emollients) • Peripheral neuropathy • Extravasation: • Leakage of fluids/medications from vein, can cause tissue damage and necrosis • PICC line reduces this risk Neutropenic Sepsis Thrombocytopenia Spinal Cord Compression Superior Vena Cava Obstruction Oncological Emergencies Hypercalcaemia Pulmonary Embolism Brain Metastases Tumour Lysis Syndrome Sepsis with an absolute neutrophil count (ANC) < 1.0 x10 L 9 -1 Neutropenic Sepsis *HAVE A LOW THRESHOLD* • Neutropenia is caused by bone marrow suppression due to chemotherapy, bone marrow transplant, wide-field radiation or malignant infiltration of bone bone (takes 7-14 days after chemotherapy to become apparent). Symptoms: Immediate Management: o Confusion o Lethargy o SEPSIS 6 o Headache o Local symptoms of infection o BROAD SPECTRUM ANTIBIOTICS o Malaise  Tazocin (+ Gent if severe)  Watch out for penicillin allergy Signs: o Stop chemo if during cycle o Temp ≥38°C or ≤36°C o HR > 90bpm, RR >20, hypotensive Extended Management: o Local signs of infection e.g. chest crackles o Modify abx using sensitivities o 2 line abx if pt deteriorating/fever doesn’t resolve after 48hrs o Consult micro if no response after 5 days Investigations: o A-E assessment and look for source • Granulocyte Colony Stimulating Factor (GCSF) o Blood cultures (peripheral and central if in place) o Prophylactic measure for those continuing treatment o Infection screen:  Urinalysis and culture o Helps to increase ANC – DOES NOT treat neutropenic sepsis  CXR  Sputum culture  Throat swabs  LP if meningism o Used with RADICAL treatment only + reduce chemo dose  Palliative chemo will be stopped following neutropenia Thrombocytopenia • Commonly caused by chemotherapy due to bone marrow suppression • Spontaneous bleeding becomes more likely when platelets <20 x10 L 9 -1 • Symptoms: o Malaise o General weakness o Fatigue o Unexplained bleeding e.g. epistaxis, gum bleeding • Signs: o Bruising – purpura, petechial rash • Investigations: o FBC (low plt, may be anaemic) o LFTs, U+Es (high urea ?upper GI bleed), coag screen o Vit B12, folic acid • Management: o Group and crossmatch o Arrange platelet transfusion if: 9 -1  Plt <10 x109 -1  Plt <20 x10 L with active sepsis/bleeding Hypercalcaemia Symptoms (uncommon <3.0mmol): • Metabolic complication of cancer • Dehydration most common finding • Indication of poor prognosis • Bones, stones, abdominal groans and psychiatric moans • Normal serum calcium = 2.2 – 2.6 • Confusion, drowsiness, death • Most common with: Investigations: o Breast o Renal o Lung o Lymphoma • Routine bloods, PTH, bone profile (ALP) o Head and neck o Multiple Myeloma • ECG – shortened QT • Caused by: • CXR if cause unknown o Bone mets (20%) o PTHrP secretion from tumour (80%) Management: o Calcitriol secretion from tumour • Immediate rehydration: 4-6L 0.9% NaCl over 24hrs • IV bisphosphonate: zolendronic acid 4mg IV after 24hrs • Check Kardex and stop meds that raise calcium Tumour Lysis Syndrome • Caused by destruction of a large number of cancer cells, resulting in electrolyte abnormalities and renal failure (similar to rhabdomyolysis) • Most common in leukaemia and lymphoma Management: Clinically: • A-E assessment, IV fluids • Fatigue Investigations: • Rasburicase • N+V • Hyperphosphatemia (causes low calcium) o Clears uric acid from blood • SOB • Hyperkalaemia kit • Myalgia • Hyperkalaemia (tall tented T waves) • Haemodialysis if required • Syncope • Hyperuricaemia • Tetany • Hypocalcaemia Prophylaxis: • Seizures • Lactic acidosis • Raised serum LDH • Allopurinol • Dark urine • Adequate hydration • Arrythmias • HF Spinal mets but no SCC: • RT if just pain Spinal Cord Compression (SCC) • Surgery if instability • Caused by vertebral bone mets (think breast, prostate, lung, MM, renal, thyroid) st • 1 presentation of cancer for 10% of patients • 70% affect thoracic spine Immediate Management Clinically: • Dexamethasone 8mg PO/IV BD + PPI • Localised back pain and tenderness • Analgesia • Bladder/bowel dysfunction Definitive Management • Limb weakness • Surgical decompression • Hypoesthesia o Contraindications: • Cauda equina syndrome (below L1/L2) • Unfit • Bilateral motor neurone signs = SCC until proven otherwise • Complete paraplegia for >24hrs + pain well controlled • Gibbus (swelling) may be visible • RT if unsuitable for surgery o Unless complete paraplegia >24hrs + pain well controlled) o Can make symptoms worse before they improve Investigations:  Prophylactic dexamethasone for oedema • Neurological exam o Melanoma + clear cell carcinoma are radioresistant • MRI whole spine • Bisphosphonates if myeloma, breast or prostate cancer Superior Vena Cava Obstruction (SVCO) Tumour obstructs flow of blood from head, neck and upper limbs o Lung cancer (SCLC most common) o Lymphoma (2 most common) Investigations • CT chest is ix of choice o CVCs can cause thrombus to form in SVC Clinically: • Gradual onset Immediate Management • Dyspnoea • A-E if acutely unwell, high flow O2 • Plethora • Dexamethasone 8mg BD + PPI • Swelling of face/neck/arms • Headache • Visual disturbance Definitive Management • Syncope/dizziness • Tissue diagnosis informs management • Haemoptysis/epitaxis • Stenting - emergency and need bridge to chemo/RT • Increased venous pressure • Chemo – chemosensitive (SCLC, germ cell, lymphoma) • Raised JVP • RT – Poor ECOG, previous chemo, relapse • Prominent veins over neck/chest wall PEMBERTON SIGN Brain Metastases 80-90% of intracranial tumours are mets • The rest are primaries (mainly gliomas) Investigations: • Routine bloods, tumour markers if unknown • Contrast-enhanced CT brain • MRI if more detail needed/diagnostic doubt Clinically: • Headache o Worse in morning/lying down, straining/coughing Immediate Management: • N+V • Dexamethasone8mg PO/IV BD + PPI • Confusion • Seizures Further Management: • Drowsiness • Whole brain RT • Focal neurological deficit • Personality changes • Surgery/SRS if few mets and disease well controlled • Papilloedema (50%) • Tissue diagnosis may be required CANNOT DRIVEPulmonary Embolism Can result from local invasion or clotting dysfunction Management: • A-E Clinically: • Anticoagulation: • Triad: SOB, chest pain (pleuritic), haemoptysis o DOAC o LMWH if on chemo • Tachycardia – most common • Thrombolysisif SBP <90mmHg • Cough • Raised JVP • Cyanosis • Check for DVT Complications: • Development of chronic Investigations: thromboembolic HTN can lead to • 2-level Wells score right-sided HF • Routine bloods, D-dimer, ABG, troponin, BNP • CTPA • CXR, ECG SCREENING: • 3 yearly mammogram from 50-70 Breast Cancer • Younger if strong Family hx RISK FACTORS TRIPLE ASSESSMENT • Lifestyle – sedentary, alcohol, high fat diet, smoking • Examination • Genetic – BRCA1/2 mutation, fhx of breast/ovarian ca • Imaging (mammogram +/- USS) • Hormonal – nulliparity, early menarche, late menopause, HRT • Biopsy (FNA / core biopsy) • Ionising radiation Mammogram not as useful in younger women REFERRAL CRITERIA TNM STAGING RED FLAG (2 weeks): T Stage: N Stage • ≥30 with unexplained breast lump T1: <2cm N0: no nodes • ≥50 with unilateral nipple discharge or retraction T2: 2-5cm N1: 1-3 nodes CONSIDER RED FLAG: N2: 4-9 nodes • Skin changes suggesting breast cancer T3: >5cm N3: >10 nodes T4a: Chest wall • ≥30 with unexplained axillary lump T4b: skin M Stage NON-URGENT REFERRAL: T4c: both M0: no mets • <30 with unexplained breast lump T4d: inflammatory M1: mets Staging scans (≥T3/≥T2) = isotope bone scan and CT abdo/thorax Follow-up: Annual mammogram for 5 years Breast Cancer CHEMOTHERAPY PRIMARY SURGICAL MANAGEMENT • CI’d in M1 and T4, and those unfit for surgery • Neoadjuvant: can be used to shrink tumour • WLE or Mastectomy • Adjuvant: • WLE: solitary, peripheral, small lesion • Node –ve, 2-5% risk: Oncotype DX analysis • Mastectomy: multifocal, central, large lesion • Node –ve, >5% risk: FEC chemo • Node +ve: FEC-docetaxel (FEC-D) chemo • AxillaryNode Clearance • Palpable/USS +VE, SLNB indicated • If >1 node +ve on SLNB or N1-3 clinically ADJUVANT SACT • SE: lymphadenopathy (15%) and functional arm impairment • Hormonal used in ER or PR +ve for 5-10 years • Pre-/Perimenopausal = Tamoxifen ADJUVANT RADIOTHERAPY • Postmenopausal = Anastrozole (risk of OP) • Targeted used in HER2 +ve for 1 year • Almost always done unless extremely low risk • Node -ve = Trastuzumab (Herceptin) • Node +ve = Trastuzumab and Pertuzumab • Whole Breast RT after WLE • Tumour bed boost: ≥50, triple –ve, high grade, close margins • Chest Wall RT after mastectomy and ≥T3 or ≥N2 PRIMARY SACT • Only if surgery CI’d • Supraclavicular fossa ≥N2 • Hormonal/Targeted/Chemotherapy Palliative radiotherapyonly if symptomatic breast tumour SCREENING Colorectal Cancer • FOB home kit sent out every 2 years from 60-74 RISK FACTORS • Age • Lifestyle: • Large polyp • Genetics/FH: o Obesity, diet • Pelvic RT o Lynch Syndrome (HNPCC) o Smoking/Alcohol o FAP o Sedentary REFERRAL CRITERIA INVESTIGATIONS RED FLAG (2 weeks): • 1 line: Colonoscopy • ≥40 with weight loss + abdo pain • CT Colonogram if frail/intolerant/co-morbidities • ≥50 with rectal bleeding • ≥60 with iron-deficiency anaemia or altered bowel habit • CEA: NOT for screening, only used after diagnosis • Positive FOB/QFIT • After diagnosis, look for metastases: CONSIDER RED FLAG: abdo pain • CT • Rectal or abdominal mass altered bowel habit • PET CT • <50 with rectal bleeding and: weight loss • If rectal: MRI rectum and endo-anal USS iron-deficiency anaemia OFFER QFIT: • ≥50 abdominal pain or weight loss • <60 with changes in bowel habit or iron-deficiency anaemia • ≥60 with anaemia but no iron deficiency Colorectal Cancer STAGING Stage 1: ≤T2 + N0 + M0 Stage 2: T3 or T4 + N0 + M0 TNM STAGING Stage 3: Any T + N1 or N2 + M0 T Stage: T1: through mucosa into submucosa Stage 4: M1 T2: through submucosa into muscularis propria T3: through muscularis propria into subserosa T4: through intestinal wall, extending into adjacent organ N Stage M Stage MANAGEMENT N0: no nodes M0: no mets N1: 1-3 nodes M1: mets Stage 1: Surgery alone N2: ≥4 nodes Stage 2: Surgery and clinical trial Stage 3: Surgery and chemotherapy Stage 4: Palliative surgery/chemo Prostate Cancer No routine screening REFERRAL CRITERIA GLEASON SCORE • Raised PSA (>4) • 1 = differentiated cells (not cancerous) • Abnormal prostate on DRE • 3 = cells turn cancerous • 5 = undifferentiated cells GLEASON GROUP INVESTIGATIONS • 2 numbers are used (most dominant comes first) 1. Multiparametric MRI • A total of 6 is benign and 10 is highly malignant • Results reported using 5-point LIKERT scale Group 1: ≤6 influence decision to biopsy Group 2: 3 + 4 = 7 2. Biopsy (for Gleason Score) Group 3: 4 + 3 = 7 • LIKERT score ≥3 = TRUS or transperineal biopsy Group 4: 8 • 1 or 2 (low risk) = discuss pros and cons of biopsy Group 5: ≥9 3. Isotope Bone Scan Prostate Cancer PROGNOSTIC GROUPING CLINICAL T STAGE RISK PSA GLEASON GROUP CLINICAL T STAGE T1: invisible Low < 10 ng/mL 1 (score ≤6) T1 – T2a T2: confined to prostate (a:<½ lobe, b:>1/2 lobe, c: both) Intermediate 10-20 ng/mL 2 or 3 (score = 7) T2b – T2c T3: extends through capsule High > 20 4 or 5 score (8-10) T3 – T4 T4: extends to other structures (excluding seminal vesicles) NON-METASTATIC MANAGEMENT METASTATIC MANAGEMENT Active Surveillancegery BrachytherapyExternal RT • Hormonal Therapy: Risk • LHRH (GnRH agonists) Low • e.g. goserelin, deslorelin Intermediate • Anti-androgens • e.g. abiraterone, bicalutamide High • Chemo – docetaxel Choice of treatment is decided by effect profile suitable to the patient  Psych benefit, histolo Fast recovery, further rx, less ED • Bone targeted therapy  GA, incontinence, ED, bowel Urinary obstruction, GA No GA, less ED/urinary SE • e.g. zolendronic acid/radium perf  Proctitis, 2* malignancy • RT/SABR for mets Targeted lung cancer screening only Lung Cancer (high risk patients) RISK FACTORS INVESTIGATIONS • Smoking • Lung disease e.g. TB • CXR • FH • Radon Gas Central lesion = Bronchoscopy with biopsy • Asbestos/silicosis exposure • RT • CTCAP Peripheral lesion = CT-guided biopsy • Biopsy Mediastinal lymphadenopathy/parabronchial mass = • PET CT endobronchial USS and transbronchial needle biopsy REFERRAL CRITERIA • CT brain RED FLAG (2 weeks): • CXR findings suggest lung cancer • >40 with unexplained haemoptysis TNM STAGING Urgent CXR (2 weeks) if smoker/ex-smoker with 1 of the following or >40 with 2 of the following, for at least 3 weeks: T Stage • Cough • Chest pain T1: ≤3cm • Fatigue • Weight loss T2: >3cm ≤7cm • Appetite loss T3/T4: >7cm or another separate tumour present or invading local • SOB structures Consider Urgent CXR if >40 and any of: N Stage • Persistent/recurrent chest infection M Stage • Finger clubbing N1: ipsilateral bronchopulmonary/hilar nodes M0: no mets • Supraclavicular/cervical lymphadenopathy N2: Ipsilateral mediastinal or subcarinal nodes M1: mets • Thrombocytosis N3: Contralateral mediastinal nodes Lung Cancer TYPE FEATURES MANAGEMENT NSCLC Squamous cell (SCC): T1/T2 + N0/1 = RADICAL • Radical Surgery o Smokers o Pneumonectomy o Central tumour o PTHrP secretion – HYPERCALCAEMIA o Lobectomy/bilobectomy Adenocarcinoma: o Wedge resection (not recommended) • Radical RT (SABR if localised stage 1/2) o Non-smokers o Peripheral tumour • May have concurrent or adjuvant chemoRT Large cell (rarer) PALLIATIVE (majority) • RT • Chemo • Targeted e.g. TKIs in EGFR positive adenocarcinomas SCLC Paraneoplastic syndromes Chemosensitive (80% response rate), surgery not appropriate o ACTH secretion - CUSHINGS Concurrent chemoRT and prophylactic cranial RT Metastatic Cancer Brain Cannonball Bone mets mets mets • Lung • Renal • Prostate (sclerotic) • Breast (lytic) • Breast • Endometrial • Lung (both) • Melanoma • Prostate • Multiple Myeloma (lytic) • Testicular • Thyroid (lytic) • Renal (lytic)5 things to treat at the End of Life Pain Breathlessness Anxiety, Delirium and Agitation Secretions Nausea & VomitingPain Management 1 2 3 4 5 Undertake an Categorize pain Apply the WHO Adjuvant analgesics Adjuvant therapies assessment(history syndromes Ladder in selecting for the management for the management and examination)of an appropriate of neuropathicpain. of malignant bone a patient with pain, analgesic regimen pain and devise an effective managementplan amitriptyline, pregabalin, ketamine bisphosphonates, radiotherapy • Look out for contraindications • Beware renal impairment • Always co-prescribe a Analgesia laxative and naloxone with opiates • Breakthrough dose= total daily dose / 6 (short acting prep.)Analgesia Ladder Pain Relief 1. Morphine 2. Oxycodone 3. Alfentanil 4. FentanylOpiates in Renal FailureOpioid Toxicity CAUSES= dehydration, sepsis, recent dose,deteriorating renal/liver function - Pinpoint pupils - Myoclonus - Confusion/ ABCDE approach – secure airway and - Hallucinations/ give oxygen, call senior - vivid dreams - Resp. Depression STOP offending drug (often PCA or syringe driver needs to be stopped) Give NALOXONE (but not STAT bolus and titrate) Treat cause eg. IV fluids, reduce dose, switch opioid not filtered via kidney / liverNausea and VomitingNausea and VomitingSecretions • Glycopyrronium • Hyoscine hydrobromide, hyoscine butylbromide (Also used for cramping) • Generally given every 4 hours when required • Ce.g. regular mouth wetting, chewing gum, sucking iceBreathlessnessAnxiety, Delirium and AgitationMwaheed01@qub.ac.uk