Cancer: Concept Checklist

Concepts covered across the module lectures, grouped by lecture. Tick each once you can explain it from memory.

L1 Clinical biology and treatment of cancer (14 Jul) L1 Cancer Clinical biology and treatment of cancer

• Four pillars of cancer diagnosis: clinical, radiology, tissue, biomarkers
• Symptoms and examination findings suggestive of cancer, including a spinal cord sensory level
• Screening vs diagnostic mammography, NZ breast screening eligibility, and the imaging-to-biopsy pathway
• Histology vs cytology; ductal vs lobular breast carcinoma
• Tumour grading systems and the modified Bloom-Richardson score
• Four modes of cancer spread
• Breast lymphatic drainage and axillary node levels
• TNM staging: prefixes, T, N and M categories for breast cancer, sentinel node biopsy vs axillary dissection, clinical vs pathological prognostic stage
• Breast cancer biomarkers (ER, PR, HER2 by IHC and FISH, Ki-67) and molecular subtypes with prognosis
• Genomic tools and risk prediction: NGS/liquid biopsy, Oncotype DX recurrence score and TAILORx, NHS Predict
• Treatment intent: neoadjuvant, adjuvant and palliative, and acceptable toxicity for each
• Cancer multidisciplinary meeting and palliative treatment modalities
• PET tracers used in oncology
• Monitoring response: pain scores, bloods, tumour markers by cancer type, imaging; lead-time bias

L2 Oncological emergencies and late effects (14 Jul) L2 Cancer Oncological emergencies and late effects

• Metastatic spinal cord compression: associated cancers, early radicular pain vs late neurological signs, MRI whole spine, immediate dexamethasone, surgery and radiotherapy, time-critical prognosis
• Superior vena cava obstruction: causes, clinical features, acute management and therapeutic options
• Neutropenic fever: definition and door-to-antibiotics target
• Tumour lysis syndrome: mechanism, electrolyte derangements, timing, Cairo-Bishop criteria, high-risk patients
• Prevention and acute management of tumour lysis syndrome: hydration, allopurinol, rasburicase, handling hyperkalaemia, acidosis and hypocalcaemia
• Malignant hypercalcaemia: clinical picture, PTHrP mechanism, prognosis, and management with fluids and bisphosphonates
• Cancer-associated VTE: DVT and PE presentation, investigations and anticoagulation options; DIC as clotting with bleeding
• Late complications of cancer treatment, including secondary malignancies from specific therapies
• Immune-related adverse events of immunotherapy by organ system, including endocrinopathies requiring lifelong replacement
• EGFR inhibitor skin and nail toxicity
• Managing effects of oestrogen withdrawal in breast cancer therapy: pelvic symptoms, arthralgias, vasomotor symptoms (CYP2D6 caution with tamoxifen), bone health

L3 Transition from anti-cancer to palliative care (3 Aug) L3 Cancer Transition from anti-cancer to palliative care

• Define curable, incurable, palliative and terminal; palliative care as everyone’s role and broader than cancer
• Median survival of common metastatic cancers and three illness trajectories in modern treatment
• Common communication mistakes in incurable disease and a structured approach, including SPIKES for breaking bad news
• Prognostication: broad time bands, acknowledging uncertainty, and why patients need prognostic information
• Kübler-Ross stages as a psychological response to incurable illness
• Introducing hospice, the NZ hospice model, and whole-person care including Te Whare Tapa Whā
• Establishing goals of care, ceiling of care and resuscitation status, with attention to cultural values
• Temel trial evidence for early palliative care and reasons early referral helps
• Recognising the last year and last days of life
• Balancing hope with honesty and benefit with burden; features of a good death

L4 Principles of chemotherapy and pharmacology of cancer drugs (12 Aug) L4 Cancer Principles of chemotherapy and pharmacology of cancer drugs

• Uses of chemotherapy (curative, life-extending, palliative), combination with surgery and radiation, and measuring response (PFS, overall survival)
• The cell cycle as the target of cytotoxic drugs and the rationale for combination therapy
• Cell cycle-independent vs cell cycle-dependent agents and dose-response implications
• Alkylating agents: cyclophosphamide mechanism, uses, adverse effects including haemorrhagic cystitis, AML and infertility
• Platinum agents: guanine crosslinking, uses (testicular cancer cure), neurotoxicity, nephrotoxicity, radiosensitisation
• Antimetabolites: methotrexate (DHFR inhibition) and 5-FU (thymidylate synthase inhibition), uses, adverse effects, narrow therapeutic index of 5-FU
• Microtubule agents: taxanes (stabilising) vs vinca alkaloids (destabilising); uses, myelosuppression, hypersensitivity, CYP3A4 interactions, vesicant properties
• Topoisomerase inhibitors: doxorubicin mechanism, uses, cardiomyopathy and dexrazoxane
• Targeted, immune and hormonal therapies compared with chemotherapy, and why chemotherapy remains the mainstay

L5 Principles of non-chemotherapy systemic anti-cancer treatments (12 Aug) L5 Cancer Principles of non-chemotherapy systemic anti-cancer treatments

• Burden of cancer in NZ: leading causes, commonest types, rising deaths but falling death rate; tumour heterogeneity
• Five categories of systemic anti-cancer therapy and the cellular level at which each acts
• Architecture of targeted therapy: ligand, receptor extracellular domain and intracellular tyrosine kinase as drug targets; VEGF, EGF and HER2 pathways
• Hormonal therapy as the original targeted therapy: historical breast cancer treatment, identification of the oestrogen receptor, tamoxifen
• Monoclonal antibody nomenclature by degree of humanisation, and examples with their targets and indications
• Antibody-drug conjugates: composition and mechanism (T-DM1)
• Toxicities of targeted therapies: on-target vs off-target; mechanisms of anti-VEGF hypertension; skin toxicity
• KRAS as a predictive rather than prognostic biomarker for cetuximab (CRYSTAL)
• Why the same targeted drug can harm in another setting (New EPOC, REAL3), and general lessons from EGFR targeting
• Immune checkpoints: co-inhibitory and co-stimulatory pairs; mechanisms of anti-CTLA-4 and anti-PD-1/PD-L1
• Immune-related adverse events by organ system
• Patterns and mechanisms of primary, adaptive and acquired resistance to immunotherapy
• Melanoma as multiple molecular diseases: BRAF V600E and vemurafenib response and toxicity; checkpoint blockade evidence; brain metastases and problems with steroids

L6 Principles of cancer surgery (14 Aug) L6 Cancer Principles of cancer surgery

• Aims of diagnosis and staging, and the role of imaging and TNM in surgical planning
• Assessing the patient rather than only the tumour: physiological reserve, frailty scoring, goals and support
• Local vs systemic treatment, and the role and benefits of the multidisciplinary meeting
• Curative vs palliative intent in cancer surgery
• Resection margins: R0, R1 and R2, and how an adequate margin is achieved
• Anatomical basis of oncological resection, including total mesorectal excision
• Reconstruction after resection: organ reconstruction, pedicled flaps and free flaps
• Palliative surgery: aims and the altered risk-benefit calculation
• Principles of surgical practice: teamwork, humility, outcome monitoring, patient-centred decision making

L8 Principles of radiation treatment of cancer (changed 7_7) (18 Aug) L8 Cancer Principles of radiation treatment of cancer (changed 7_7)

• Role of radiotherapy in cancer care: proportion of patients treated, contribution to cure, cost-effectiveness
• History of radiation discovery and evidence of biological harm (radium dial painters, atomic bomb survivors); dose-related attributable cancer risk and comparative exposures
• Radiation dose units, curative vs palliative dose and fractionation schedules, and stereotactic ablative radiotherapy
• Aims of radiotherapy treatment and when each applies
• How a linear accelerator produces a therapeutic beam
• Ionising vs non-ionising radiation, and direct vs indirect (free radical) DNA damage
• Cellular response to radiation: double- and single-strand breaks, repair, and differential killing of tumour vs normal cells
• Radiotherapy patient pathway: planning CT, immobilisation, contouring of targets and organs at risk, delivery
• Mechanisms and patterns of acute and late radiotherapy side effects

L9 Pharmacology of analgesia (18 Aug) L9 Cancer Pharmacology of analgesia

• Definition of opioids and the structural difference between endogenous peptides and clinical opioids
• Pharmacological actions of opioids, and which effects are desirable vs undesirable depending on context
• Place of opioids on the WHO pain ladder and the range of pain severity covered by different agents
• Mechanism of opioid analgesia: inhibitory G protein-coupled receptors acting presynaptically (reduced cAMP and Ca2+ influx) and postsynaptically (K+ hyperpolarisation)
• Distribution of opioid receptors along pain and reward pathways, including descending inhibition
• Roles of mu, delta and kappa receptor subtypes in analgesia, respiratory depression, euphoria, dysphoria, GI motility and dependence
• Receptor selectivity of common opioids and the central role of the mu receptor
• Morphine pharmacokinetics: onset, duration, first-pass metabolism, hepatic metabolism
• Pharmacokinetic differences between fentanyl, methadone and heroin
• Opioid tolerance: which effects show it, which do not, and its mechanisms including cross-tolerance
• Clinically important opioids and their characteristic uses and risks
• Codeine and heroin as pro-drugs for morphine, and active metabolites including morphine-6-glucuronide
• Tramadol and tapentadol: mixed opioid and noradrenergic mechanism and reduced respiratory depression
• Cannabinoids in pain: THC vs CBD evidence, individual variation, and trial results in cancer pain