Anti-cancer treatments

Question 1

Surgery:

• Types (3)
• SE

Answer 1

Surgery:

• Types:
  Curative: mastectomy, whipples, anterior resection
  Biopsy: lobectomy, mediastinoscopy
  Palliative: defunctioning stoma, gastrojejunostomy
• SE: bleeding, infection, anaesthetic risks, recovery time, pre/post op fitness, specific complications/risks

Question 2

Radiotherapy:

• Definition
• Types
• Intent
• SE: acute vs chronic toxicity
• Radiosensitisers

Answer 2

Radiotherapy:

• Definition: high energy ionising radiation to treat malignant disease. The radiation damages DNA which causes cell death. Indirectly also causes free radicals which in turn cause DNA damage hence death. The aim is to deliver highest dose to tumour and minimise to surrounding normal tissue
  You can have radiotherapy alone, with surgery, with SACT, with hormonal treatment
• Types: external beam, brachytherapy (as a primary or boost treatment in prostate/cervical cancers), systemic treatments (radioactive substance injected/swallowed)
• Intent: radical radiother used as part of a curative strategy (neoadjuvant, adjuvant, definitive) or to improve symptoms in palliation
• SE:

Acute (is before 3 months and is reversible if tissues have high cell turnover) (depends on site treated): hair loss, fatigue, N+V, skin erythema, lymphoedema, dyaphagia/sore throat/oral mucositis, diarrhea, low blood counts, dysuria/cystitis

Chronic: lung (fibrosis), heart (cardiomyopathy/ pericardial fibrosis), skin (pigmentation, ulceration, telangiectasia), bone (necrosis/fracture/ impaired growth), gonads (infert/ menopause), eyes (cataracts, sight loss), mouth (ulceration, xerostomia), lymphoedema, bowel (strictures), secondary malignancy

• Radiosensitisers: agent which makes tumour cells more sensitive to radiation therapy

Question 3

Cytotoxic chemotherapy:

• Definition
• Intent
• Combination chemo
• Acute toxicities
• Late toxicities
• Classes of drugs (7)

Answer 3

Cytotoxic chemotherapy:

• Definition: cytotoxic drugs to destroy cancer cells directly (apoptosis) or indirectly (by inhibiting proliferation of rapidly dividing cells) via single or combination of agents. Is part of systemic anti cancer treatment (SACT). As they target rapidly dividing cells can’t distinguish between cancer and normal cells so lots SE.
• Intent: curative (neo/adjuvant), palliative
  Fraction cell kill hypothesis: a given dose kills a constant proportion of tumour cells so give repeated doses and freq/duration limited by toxicities. Drugs have narrow therapeutic index and alter dose for BMI, liver/renal function, performance status
• Combination chemo: Aim is to circumvent multiple resistance mechanisms and maximises therapeutic effect without undue toxicity. Involves drugs which have different modes of action, and minimises toxicity overlap e.g. folfirinox
• Acute SE: alopecia, mucositis, dry mouth, N+V, pneumonitis, dyspnoea, VTE, hearing loss/tinnitus, renal/liver insufficiency, tumour lysis syndrome, colitis, cystitis, myelosuppression (leading to neutropenia), febrile neutropenia, infection, anaemia
  N+V: acute (within few hours), delayed (>24), anticipatory. Advise small light meals, BRAT, behavioural therapy, sleep. Or ondanestron, aprepitant, dexamethasone (for delayed)
• Late SE: chemobrain, mental health, insommnia, fatigue, pleuritis, pericarditis, cvs complications, arthritis, myalgia
• Classes of drugs:

1. Alkylating agents: e.g. cyclophosphamide. Causes methylation of DNA bases which causes cross-linking leading to stopping of DNA replication. Used in breast/sarcoma
2. Taxanes: e.g. paclitaxel. Binds and stabilises tubulin in microtubules which inhibits anaphase in DNA cycle. Used in breast, lung, prostate. Known to cause alopecia/peripheral neuropathy
3. Vinka alkaloids: e.g. vinorelbine. Prevents polymerisation of tubulin so can’t form microtubules for a mitotic spindle. Used in lung, mesothelioma, sarcoma. Known to cause peripheral toxicity
4. Platinums: e.g. cisplatin. Causes crosslinking DNA stands. Used in breast, lung, colon, HPB, H&N. Known to cause A LOT of N+V, senor hearing loss (ototoxicity), nephrotoxic, peripheral nephropathy
5. Antimetabolites: e.g. methotrexate, 5 fluorouracil. Various mechanisms where they interfere with DNA synthesis. Used in colon, HPB, breast, sarcoma, lung. Known to cause palmar erythema, diarrhea, mucositis
6. Topoisomerase 1 inhibitors: e.g. irinotecan. Used in colon, HPB, lung. Known to cause alopecia, diarrhoea
7. Topoisomerase 2 inhibitors: e.g. Anthracyclines (doxorubicin). Generates free radicals hence causes DNA damage. Used in breast, sarcoma. Known to cause cardiomyopathy, alopecia, vesicant

Question 4

Describe these following terms:

• Radical/curative
• Life extending
• Palliative
• Adjuvant
• Neo-adjuvant
• Maintenance

Answer 4

Describe these following terms:

• Radical/curative: to fully restore health and cure disease. Sometime’s when a persons cancer has not returned for at least 5 years
• Life extending: a palliative term where end goal is to prolong life but not prevent recurrence and not curative
• Palliative: form of treatment that concentrates on reducing a patients symptoms or treatment side effects rather than cure to improve qol and support families
• Adjuvant: treatment (usually chemo/radio/hormone/immuno) given after main treatment/surgery to reduce chance of cancer coming back by destroying any remaining cancer cells
• Neo-adjuvant: treatment such as chemo/radio/hormone therapy given before main treatment/surgery to shrink tumour so easier to remove
• Maintenance: ongoing treatment of cancer after cancer has responded to first treatments to prevent return or delay growth of advanced cancer

Question 5

Immunotherapy:

• Definition
• SE
• Types

Answer 5

Immunotherapy:

• Definition: block tumour cells from deactivating T cells so immune system can target cells. Can be passive where cells activated ex vivo and compensate for missing once in body, or active where stimulates effector functions in vivo but immune system needs to be able to respond
• SE: can cause autoimmune conditions. Encephalitis, meningitis, sjogrens, uveitis, thyroiditis, myocarditis, pneumonitis, hepatitis, pancreatitis, glomerulonephritis, psoriasis, arthritis, neutropenia, anaemia, vasculitis
  Treatment is to without treatment/ cessation and high dose steroids
• Types:
  1. Checkpoint inhibitors (active): In bladder, cervical, colon, kidney, triple - breast. PD1 is a checkpoint protein on T cells which switches them off and stops them attacking own body. Cancer cells have the receptor PDL1 so when they bind T cell leaves them alone and they’re not destroyed.
  2. Monoclonal ab (passive): In bladder, breast, colorectal, lymphoma, leukaemia, melanoma, NSCLC, ovarian. They bind to ag on cancer cell blocking downstream signalling
  3. T cell transfer therapy (passive): leukaemia, lymphoma, breast, brain
  4. Immune system modulators: lymphoma, myeloma
  5. Vaccines (active): prostate

Question 6

Hormone manipulation + biologically targeted therapy:

• Definition
• Types

Answer 6

Hormone manipulation:

• Definition: newer systemic treatment for hormone dependant cancers such as breast and prostate where molecular diagnostics required to deliver target therapy
• Types:
  1. Small molecule drugs: tamoxifen which targets oestrogen receptor in ER+ breast cancer causing blocking of signalling
  2. Monoclonal ab: trastuzumab targets HER2 receptors in HER2+ breast cancers blocking downstream signalling

Question 7

Factors influencing treatment options (4)

Answer 7

• Treatment intent: curative involves small degree of risk of significant SE but curative when risks of SE outweigh benefit of cure. Cure intent depends on if treatment is available, comorbs are low and disease progression is localised. This includes physical characteristics of the tumour/mets
• Co-morbidities
• Performance status: just because same age doesn’t mean same prognosis. ECOG is asked during history
  0 = full active without restriction
  1 = restricted only in physical strenuous activity
  2 = capable of self care but unable to carry out any work activities
  3 = only limited selfcare, confined to chair >50% waking hours
  4 = completely disabled
  5 = dead :/
• Patient choices

Question 8

Immunophenotyping (flow cytometry)

Answer 8

Identifies markers on cells (specific ag are present on cells unique to specific cell types/stage of maturation) + also specific patterns are present on abnormal cells in leukaemias/lymphomas. Therefore flow cytometry immunophenotyping useful to help diagnosis, classify type, determine type of treatment and determine prognosis

Via blood sample/ bm biopsy/ lymph node biopsy
Abnormal white blood cell immunophenotype profiles present in AML, ALL, CLL, non hodgkin lymphomas, myeloma

e.g. CLL: CD38, CD19, CD23, CD20, kappa, lambda markers needed to be looked for. CD38, D49D are also prognostic markers, ZAP70 associated with more aggressive