Oncology revision Flashcards Preview

Oncology > Oncology revision > Flashcards

Flashcards in Oncology revision Deck (88)
Loading flashcards...
1

Diagnosis and staging of lung cancer

- role of low dose CT scan for screening

- PET scan, CT scan significance

- Staging

- positive prognostic factors

 

  • Low dose CT scan screening - NOT recommended:
    • 20% reduction in mortality for a high risk population ( age 55-74, 30 pack year smoking) 
    • 95% false positive rate 
  • PET scan sensitive (91%) and specificity (86%) for mediastinal LNs.
    • Useful pre-operative to avoid futile thoracotomy
    • Also to exclude distant metastasis
  • CT scan sensitive ( 75%) and specificity ( 66%) for mediastinal LNs.
  • Mediastinal LNs sampling is necessary for all patients with enlarged or abnormal nodes detected by CT or PET scan.
  • Staging 8th Edition: many changes 
    • M1A: pleural effusion, tumor in contra-lateral lung , pleural or pericardial nodule 
  • Positive prognostic factors: stage of disease, performance status (most cancers), lack of substantial weight loss and female sex.

2

Mx of lung cancer by stages

Stage 1: 

  • Surgery if medically fit 
  • Non surgical candidate: Stereotactic surgery effective treatment option (only for T1 or T2, N0)

Stage 2: ​

  • Surgery if medically fit
  • Non surgical candidate: Radiotherapy ( conventional fractionated radiotherapy )
  • *surgery = lobectomy is preferred and draining LNs resection is recommended.
  • Stereotactic radiotherapy effective alternative for node negative non-bulky tumour

Non bulky Stage 3A: 

  • local approach
  • Surgery +/- radiotherapy plus chemotherapy * (neoadjuvant chemo: Durvalumab anti PDL-1 inhibitor )

Bulky Stage 3A & 3B - considered not resectable​

  • NO surgery 
  • Chemo-Radiotherapy (CRT) 

Stage 4: 

  • Confirm absence of actionable mutation (e.g. EGFR, ALK rearrangement, ROS1). squamous cell cancer rarely carry actionable mutation). 
    • ALK rearrangement confirmed by FISH: alectinib, ceritinib. No longer use crizotinib due to low CNS penetration. 
  • If PDL1 high (> 50%, present in 30% of NSLCa): immunotherapy (pembrolizumab; anti PD1 antibody)
  • If low PDL-1: chemotherapy or supportive mx
    • Doublet platinum based chemotherapy
    • Single agent chemo for elderly patient
    • Best supportive care for poor performance patient 
  • PDL-1 high squamous cell + any non squamous cell:  Pembrolizumab in combination with chemotherapy ( better response in squamous cell, then in non squmous NSLCa) improve PFS, OS and RR.
  • Any non-squamous cell NSCLC: Carboplatin with paclitaxel with bevacizumab and atezolizumab (PABC) shows similar benefit 

3

Colon cancer screening & risks

 

  • Screening:
    • FOBT for >50yo. (decrease mortality by 20-30%)
    • Colonoscopy for moderate risk patient every 5 years after age 50.
    • Low dose Aspirin: could be offered after discussing pros and cons ( reduced 20 years risk of colon cancer incidence (HR 0.76 and reduced mortality HR 0.65)
  • HNPCC (NEW); autosomal dominant familial cancer syndrome due to MMR deficiency
    • 3% of CRC, 3% endometrial cancer and other cancers as well
    • Autosomal dominant, associated with MMR (MLH1, MSH2, MSH6, PMS2) -> Germline defect in MMR gene responsible for Lynch syndrome 
    • loss of MMR gene also occurs in 15% of sporadic CRC associated BRAF mutation (i.e. if BRAF mutation; unlikely Lynch syndrome. it also use to exclude germline testing) 
    • Screening for carrier: annually or 2 yearly with colonoscopy around the age 25 or 5 years before youngest family member diagnosed with cancer.
  • NEW: Treatment impact of MMR deficient tumors: ( germline and sporadic)
    • FDA approved immunotherapy (pembrolizumab, nivolumab and combination (ipilimumaband nivolumab)) as class specific agent for any MMR associated tumors 
    • Pembrolizumab improve ORR and PFS (not on pbs)

4

Mx of colon cancer based on stages

 

Stage 1:  surgery

Stage 2: 

  • Surgery cured most
  • Single agent (5FU or Capecitabine) Chemotherapy for high risk patients (T4, perforation, obstruction, vascular invasion), benefit is <5%
  • No need for adjuvant chemo in stage II microsatellite instability high patients 

Stage 3: ​

  • Surgery with chemotherapy for most patients
  • Single or doublet chemotherapy ( 5FU, Capecitabine+/-Oxaliplatin) for 6 months for high risk. 
  • 3 months treatment: alternate option for low risk category
  • For Rectal cancer:
    • Neoadjuvant chemoradiotherapy + surgery +/- adjuvant chemotherapy  
    • Chemo-Radiation improve local control 

Stage 4. oligometastatic vs. multiple metastatic: chemotherapy is backbone

  • Resectable (oligometastasis)
    • Surgery 
    • Adjuvant chemotherapy in selected patients ( controversial)
  • Partially resectable (oligometasasis) 
    • Treat as below with aggressive treatment to downsize and resect
    • Neoadjuvant treatment
  • Unresectable 
    • Factors to consider: KRAS, NRAS or BRAF mutations, MSI high, Performance status, Organ function, NEW right vs left
    • chemotherapy (5FU/capecitabine) with biologics (EGFR inhibitors panitumumab or VEGF inhibitors bevacizumab)
      • KRAS/NRAS/BRAF wild type (L sided): cetuximab or panitumumab with chemo (FOLFOX, XELOX or FOLFIRI)
      • RAS/RAF mutant and all R) side cancers: bevacizumab + chemo combo (FOLFOX, FOLFIRI, single agent 5FU or capecitabine)
      • MSI high: pembrolizumab, nivolumab, ipilimumab with nivolumab. 
  • on top of backbone chemotherapy, immunotherapies include: 
    • bevacizumab: VEGF inhibitor. only given with chemo. SE: HTN, proteinuria, arterial thrombosis, bleeding, poor wound healing. 1st or 2nd line status depending on RAS status. 
    • EGFR antibodies (cetuximab, panitumumab): restricted use for KRAS, NRAS, BRAF wildtype. KRAS predictive marker. BRAF mutation = aggressive, poor prognostic marker. SE: acneform rash. NOT recommended for R) sided tumours (even if RAS wild type)

 

Peculiar side effects:

  • Oxaliplatin: dose dependent neurotoxicity
  • Irinotecan: cholinergic side effects and diarrohea
  • 5FU/Capecitabine: hand-foot syndorme, diarrohea and coronary spasm

5

SE of oxaliplatin

a platinum based chemo

 dose dependent neurotoxicity

 

6

SE of irinotecan

a topoisomerase I inhibitors

cholinergic side effects and diarrohea

 

7

SE of 5FU/Capecitabine 

 

5FU/fluorouracil: Pyrimidine antimetabolite which, following intracellular conversion to active metabolites, interferes with DNA and RNA synthesis. (antimetabolite)

Capecitabine: Converted to fluorouracil by a 3‑step process in which the final step is more active in malignant than normal cells. (antimetabolite). commonly used with 5FU.

SE: hand-foot syndorme, diarrohea and coronary spasm

8

SE of Lonsurf

Trifluridine/tipiricil.

trifluridine is a thymidine analogue which is incorporated into DNA, interfering with its function and preventing cellular proliferation; see also Antimetabolites

tipiracil inhibits the first‑pass degradation of trifluridine by thymidine phosphorylase, increasing its oral bioavailability

very new medication approved 2020 as last line mx for metastatic CRC

given orally

shown to improve OS in refractory setting

key SE: cytopaenia 

9

Mx of Prostate cancer

- genomics

- localised disease

- biochemical recurrent disease (M0)

- risk stratification

- main line of treatment

- castrate sensitive metastatic disease 

- castrate resistant metastatic disease 

 

  • Genomics: DNA-repair anomalies up to 20% of cases, germline repair BRCA1, BRCA2 and Lynch Syndrome -> PARP inhibitor in refractory setting 
  • Localised disease: low risk could be observed. radical prostatectomy or radical radiotherapy (with or without ADT) is reasonable
  • Biochemical recurrence (M0) disease: recurrence of PSA without evident disease on imaging. 24 months of adjuvant ADT with salvage radiotherapy improve overall survival in surgical candidate
    • now rare biochemical recurrence with PSMA scan; PET scan with prostate specific membrane antigen (present on cell surface of prostate cancer) enabling earlier and better identification of metastases, with high sensitivity & specificity. 
  • Risk stratification: 
    • Gleason score ( higher the score = aggressive cancer )
    • PSA doubling time, PSA nadir after ADT
  • Androgen Deprivation Therapy (ADT) as 1st line treatment for non-localised disease: (continuous or intermittent) gold standard for many years 
    • Agonist like Goserelin (has flare response), antagonist like Firmagon (Degaralix) (rapid onset of action, no any oral ADT require to prevent flare response )
    • SE: CVS risks, osteoporosis,↓ libido, psychological and fatigue, hot flushes
    • All newer agents shown benefit with ADT (i.e. ADT continued as backbone even in metastatic disease)
  • Castrate sensitive metastatic cancer: upfront aggressive mx
    • Upfront chemotherapy ( Docetaxel X 6 cycles) improve OS in high risk patients ( high Gleason score , 4 or more metastasis) compare to ADT alone. standard practice
    • Upfront Abiraterone improve overall survival compare with ADT alone. on access program only.
    • Denosumab and Zoledronic acid reduce skeletal related event
  • Castrate resistant prostate cancer
    • 1st line:
      • Docetaxel for good performance status and chemo Naïve 
      • Abiraterone or Enzalutamide if unfit & previous chemo (both improve OS compare to placebo)
    • 2nd/3rd line:
      • Abiraterone (Inhibits CYP17, reducing androgen synthesis in testicular, adrenal and prostate tumour tissues) or Enzalutamide (antiandrogen; Competitively inhibit the binding of androgen at androgen receptors) in patients post progression of chemotheapy
      • Cabazitaxel (improve overall survival compare with Mitoxantrone)
      • Radium 223 for symptomatic bone metastasis only (not on pbs, uncommon ) ALSYMPCA study
      • Sipuleucel-T, vaccine based, improve OS in CRPC. ( not on pbs, uncommon)
    • NEW: 
      • Olaparib (PARP inhibitor) improve RR in patients with DNA repair anomalies 
      • Apalutamide improve metastasis free survival and symptomatic progression in patient with M0 castrate resistance disease compare with placebo
      • Experimental Lutetium ( radioactive treatment ) based on similar principle as PSMA scan to deliver targeted radioactive treatment

 

SE of medications:

  • Abiraterone
    • Irreversible inhibits CYP17 (in adrenals and possibly intratumoral)
    • Increase accumulation of steroid precursors can cause Hypokalemia and hypertension
    • Need to be give with Prednisolone 10mg to mitigate side effects
    • Less preferred when steroid is contra-indicated 
    • Role in castrate sensitive and in resistance setting
    • Multiple interactions 
    • NEED to watch for LFTs
  • Enzalutamide: 
    • Novel potent androgen receptor antagonist 
    • Also cause intranuclear inhibition of androgen receptor dependent DNA transcription 
    • ADT like side effects 
    • contraindicated in patients with history of seizures
  • Docetaxel & cabazitazel: 
    • Taxane based chemotherapy
    • Neuropathy, infusion reaction, aches and pain

 

Presence of AR-V7 mutation in circulating tumour cell associated with poor response to abiraterone or enzalutamide (marker of resistance, not routine to check )

10

SE of abiraterone

 

  • Irreversible inhibits CYP17 (in adrenals and possibly intratumoral)
  • Increase accumulation of steroid precursors can cause Hypokalemia and hypertension
  • Need to be give with Prednisolone 10mg to mitigate side effects
  • Less preferred when steroid is contra-indicated 
  • Role in castrate sensitive and in resistance setting
  • Multiple interactions 
  • NEED to watch for LFTs

11

SE of enzalutamide

  • Novel potent androgen receptor antagonist 
  • Also cause intranuclear inhibition of androgen receptor dependent DNA transcription 
  • ADT like side effects 
  • contraindicated in patients with history of seizures

12

SE of docetaxel & cabazitaxel 

 

•Taxane based chemotherapy

•Neuropathy, infusion reaction, aches and pain

 

13

Mx of advanced melanoma

- factors needed for ax to guide mx

- 1st line

- 2nd line

- CNS metastasis

 

  • Assessment: 
    • Surgical resectability (metastasectomy), FDG PET scan recommended
    • Presence of driver mutation BRAF mutation
    • CNS involvement is common
    • LDH (independent prognostic marker)
  • not resectable, metastatic disease. 1st line: 
    • BRAF mutation +ve: BRAF & MEK kinase inhibitor. e.g. dabrafenib & trametinib, or vemurafenib & cobimetinib. SE: fever, photosensitivity, rash, cutaneous SCC
    • BRAF -ve & fit: combo immunotherapy with ipilimumab (CTLA4 inhibitor) & nivolumab (anti-PD1). SE: ipilimumab most toxic. 60% grade 3/4 autoimmune toxicity including colitis, pneumonitis 
    • BRAF -ve & unfit: mono immunotherapy. nivolumab (anti PD1), pembrolizumab (anti-PD1, less toxic than ipilimumab), or ipilimumab (anti CTLA4, not preferred as first line) 
  • not resectable, metastatic disease. 2nd line: 
    • BRAF mutation: BRAF & MEK kinase inhibitor, then immunotherapy
    • Nivo/pembrolizumab followed by ipilimumab
    • chemotherapy 
    • trials
  • CNS metastasis
    • isolated: targeted radiotherapy (SBRT) or surgery
    • low volume can be mx with systemic disease mx
    • symptomatic & multiple brain mets; whole brain radiotherapy  
  • new routine practice to give adjuvant treatment
    • resected stage III: pembrolizumab (anti PD1)
    • resected stage III & IV: nivolumab (anti PD1)
    • resected stage III + BRAF mutation: dabrafenib & trametinib (BRAF & MEK kinase inhibitor)

14

Why is BRAF inhibitor used with MEK inhibitor as a combination in melanoma with BRAF V600 mutation?

 

While BRAF inhibitors are effective, resistance eventually occurs

 

Dual BRAF-MEK inhibition is the standard of care

15

Mx of metastatic renal cell carcinoma

- characteristics of RCC

- risk stratification

- indication for adjuvant treatment

- 1st line

- 2nd line

 

  • clear-cell renal-cell carcinoma most common (70% of all RCC)
    • associated with mutations in VHL, an essential component of the cellular oxygen-sensing pathway (involving HIF factor)
    • usual indication for systemic treatment 
  • No chemotherapy works in RCC
  • RISK stratification: There are prognostic calculators available (IMDC) 
    • Karnofsky Performance Status (KPS) <80 
    • Time from original diagnosis to initiation of targeted therapy <1 year
    • Hemoglobin less than the lower limit of normal 
    • Serum calcium greater than the upper limit of normal
    • Neutrophil count greater than the upper limit of normal
    • Platelet count greater than the upper limit of normal
  • Adjuvant sunitinib treatment for 1 year for high risk local RCC post resection, however significant SE. Not routine. 
  • Nephrectomy in stage IV setting: only in selected patient. Not in high risk/intermediate risk category 
  • 1st line: sunitinib, pazopanib
  • 2nd line: everolimus (mTOR inhibitor), cabozantinib (TKI), axitinib (TKI), nivolumab (anti-PD1)
  • No well defined sequence: bevacizumab (anti VEGF)

 

SE of medications

  • VEGF ligand antibody (bevacizumab): Hypertension, proteinuria, impaired wound healing, gastrointestinal perforation, arterial thrombosis
  • Tyrosine kinase inhibitors (axitinib, cabozantinib, lenvatinib, pazopanib, sorafenib, sunitinib): Fatigue, hypertension, oral and GI toxicity (mucositis, dysphonia, nausea, vomiting, stomatitis, dysgeusia, diarrhea), skin problems (rash, hand–foot skin reactions), hair loss and changes in hair color, weight loss, cytopenias, hypothyroidism, elevated liver-function values
  • mTOR inhibitors (Mechanistic target of rapamycin inhibitor, e.g. everolimus, temsirolimus for poor risk category): Fatigue, nausea, rash, pulmonary side effects (cough, dyspnea, pneumonitis), diarrhea, infections, peripheral edema, anemia, hyper-lipidemia, hyperglycemia
  • Nivolumab or Ipilimumab (anti-CTLA4) and nivolumab (anti-PD1): autoimmune SE 

16

SE of bevacizumab

VEGF ligand antibody

SE: Hypertension, proteinuria, impaired wound healing, gastrointestinal perforation, arterial thrombosis

17

SE of tyrosine kinase inhibitors

e.g. axitinib, cabozantinib, lenvatinib, pazopanib, sorafenib, sunitinib

 

SE: Fatigue, hypertension, oral and GI toxicity (mucositis, dysphonia, nausea, vomiting, stomatitis, dysgeusia, diarrhea), skin problems (rash, hand–foot skin reactions), hair loss and changes in hair color, weight loss, cytopenias, hypothyroidism, elevated liver-function values

18

SE of mTOR inhibitors

Mechanistic target of rapamycin inhibitor

e.g. everolimus, temsirolimus for RCC poor risk category 

SE: Fatigue, nausea, rash, pulmonary side effects (cough, dyspnea, pneumonitis), diarrhea, infections, peripheral edema, anemia, hyper-lipidemia, hyperglycemia

19

Summary of Mx of breast cancer

  • Early stage disease
  • Her2-positive disease
  • Triple negative disease
  • Hormone positive disease -metastatic
  • Poor prognostic markers
  • BRCA & hereditary breast cancer

 

1. Early stage disease

  • Surgery:
    • Breast conservation surgery preferred in most (wide-local excision) + post op RT. WLE + RT outcomes equivalent to mastectomy
    • Mastectomy +/-reconstruction if > 4cm, multifocal, previous chest RT, central tumour
    • Axillary dissection/clearance (AC): if +ve sentinel node biopsy, or clinically nodes are involved at diagnosis. 
  • Chemotherapy
    • Anthracyclines (doxorubicin, epirubicin) +/- Taxanes (paclitaxel, docetaxel)
      • SE of Anthracyclines: cardiomyopathy (dose dependent), secondary leukaemias
      • SE of taxanes: peripheral neuropathy
    • Indications: 
      • Node +ve cancer
      • Node -ve with High risk features (Grade 3, extensive LVI, size > 4cm, weak ER/PR expression)
      • New genomic essay help to avoid chemotherapy based on risk score (like Oncotype DX) , not on pbs
    • Chemotherapy induced ovarian failure: may resolve. Age = strongest risk factor (>40yo). mx fertility preservation 
  • Radiotherapy: 
    • post ALL breast conserving surgery (↓ local recurrence).
    • Post mastectomy –larger tumour >5cm, nodes +ve
  • Endocrine therapy
    • Premenopausal: tamoxifen. SE: joint aches, hot flushes, VTE , secondary uterine ca
    • Post menopausal: aromatase inhibitor e.g. Anastrazole, letrozole. SE: osteoporosis, joint ache, hot flushes
    • Treatment for 5-10 years (new data ~10 years)

2. Her2-positive disease

  • HERCEPTIN (Trastuzumab): Monoclonal antibody against Her-2. Needs Her2-ISH amplification (FISH/SISH)
  • Herceptin as adjuvant mx given with chemo for 12 months if:
    • No CSF penetration. cerebral mets frequent sanctuary site on recurrene
    • Key side effect = reversible cardiotoxicity (unlike anthracyclines). RFs: age > 50, post-anthracycline, pre-existing LVF impairment. 
  • Metastatic mx; 
    • 1st line: Given with chemotherapy + pertuzumab (anti-HER2) + trastuzumab. Dual HER 2 action (↑ OS)
    • 2nd line – Kadcyla (TDM1; ado –emtansine trastuzumab) Antibody drug conjugate 

3. Triple negative disease (ER/PR/HER2 -ve)

  • Consider BRCA testing if <50yo
  • Neoadjuvant chemotherapy; aim for pathological complete response (pCR–important prognostication)
  • BRCA1: sensitive to Carboplatin + anthracycline/taxane regimen 
  • Consider clinical trials e.g. PARP inhibitors for BRCA breast ca & Immunotherapy 

4. Hormone positive disease -metastatic

  • Typically elderly woman, bone only disease
  • Respond well to endocrine therapy (anastrazole, letrozole, tamoxifen, exemestane + everolimus); consider chemo if visceral crisis
  • 1st line treatment: CDK4/6 inhibitor (arrest cell cycle at G1) + aromatase inhibitor e.g. ribociclib+ letrozole (PFS 25 mthsvs 16mths) on PBS. SE: QT prolongation (Needs ECG monitoring), hepatotoxicity, diarrhoea, neutropenia

5. BRCA & hereditary breast cancer

  • BRCA 1 and BRCA 2
    • DNA repair genes (tumour suppressor genes)
    • Several hundred mutations
    • autosomal dominant inheritance with variable penetrance (50-80%)
  • Risk reducing strategies
    • Bilateral prophylactic mastectomy
    • Screening available (MRI) for those declining surgery from age 25
    • Bilateral salpingo-oophorectomy 
      • At ~40 or on completion of child-bearing
      • Improves survival
      • Greatly reduces risk of ovarian/fallopian tube ca
    • PARP inhibitors. great senstivity to BRCA tumours. e.g. Olaparib improved PFS for HER2 -ve mBC and a germline BRCA mutation

 

Poor prognostic markers

  • +ve axillary LN (strongest predictor of long-term prognosis)
  • Negative hormone markers
    • Triple negative = ↑ short-term mortality
    • ER +/-PR +ve= better prognosis, but chance of late relapse
  • ↑ size
  • Higher grade (higher KI 67%)
  • Untreated Her-2 +ve
  • Younger age
  • Lymphovascular invasion (LVI)

20

Poor prognostic markers of breast cancer

 

  • +ve axillary LN (strongest predictor of long-term prognosis)
  • Negative hormone markers
  • Triple negative = ↑ short-term mortality
  • ER +/-PR +ve= better prognosis, but chance of late relapse
  • ↑ size
  • Higher grade (higher KI 67%)
  • Untreated Her-2 +ve
  • Younger age
  • Lymphovascular invasion (LVI)

21

Indications for chemotherapy in early stage breast cancer

 

•Node +ve cancer

•Node negative High risk features (Grade 3, extensive LVI, size > 4cm, weak ER/PR expression)

•New genomic essay help to avoid chemotherapy based on risk score (like OncotypeDX), not on pbs

 

22

Discuss differences how immunotherapy SE differs from chemotherapy SE

 

  • Minimal infusion related reaction 
  • Patients stay on these treatment longer
  • SE:
    • Fewer than chemotherapy and different 
    • Not predictable
    • Not dose dependent (no dose reduction)
    • Can arise at any time (even after stopping)
    • Any system of body get involved
    • Could be life threatening
    • Need a team to manage side effects
    • Steroid is key treatment( to supress immune system) 
  • NOTE: active auto-immune disease or transplant is contra-indication for immunotherapy
  • Examples
    • anti-CTLA4: ipilimumab for melanoma
    • anti-PD1: nivolumab, pembrolizumab for various cancers including melanoma, NSCLC, renal cell cancer
    • anti-PDL1: atezolizumab (for NSCLC), avelumab, durvalumab.

CTLA-4: cytotoxic T lymphocyte antigen 4

PD-1: programmed cell death 1

PD-L1: programmed cell death ligand 1

23

Mx of GI irAE

1. mild (<4/day): observe. symptomatic mx with oral fluids, loperamide, avoid high fibre/lactose diet. 

2. moderate (<4/day for >14 days, or 4-6/day for >3 days): oral pred 0.5-1mg/kg. If not better in 72h, IV methylpred 1-2mg/kg for 3 days.

3. severe (>=7/day or ilfe threatening): hospitalisation, isolation. withhold immune check point inhibitors. IV methylpred 1-2mg/kg for 3 days.  

4. If not better, infliximab 5mg/kg once off post flexigmoidoscopy/ colonoscopy, and can repeat 2 weeks later. Can consider other immunosuppressive options e.g. MMF or tacrolimus 

 

Must also investigate for:

  • infections (stool MCS, OCP, viral PCR, C.diff, crystospoiridia. culture for drug resistant organisms.
  • baseline bloods including TFTs & LFTs. 
  • AXR for colitis
  • sigmoidoscopy/colonoscopy 

 

Steroid wean duration: 

  • moderate: 2-4 weeks
  • severe: 4-8 weeks
  • if steroids >4 weeks, consider PJP prophylaxis, regular random blood glucose, VitD level, start calcium/vitD supplement 

24

Steroid wean duration for GI irAE

- concurrent mx if on steroids longterm

  • moderate: 2-4 weeks
  • severe: 4-8 weeks
  • if steroids >4 weeks, consider PJP prophylaxis, regular random blood glucose, VitD level, start calcium/vitD supplement 

25

Mx of hypophysitis irAE

  • Mild
    • vague symptoms e.g. mild fatigue, anorexia. no headache. 
    • assess pituitary axis to confirm dx
    • continue ICPi with appropriate hormone replacement therapy
    • replace cortisol +/- thyroxine. MRI pituitary protocol. refer to endo
  • moderate
    • headache, no visual disturbance. fatigue/mood alterations but HD stable. no electrolyte disturbance
    • oral pred 0.5-1mg/kg daily after sending pituitary axis Ax. if not better in 48h, treat as severe with IV methylpred. withhold ICPi
    • MRI pituitary protocol (also exclude brain mets), visual field Ax. wean steroids based on sx over 2-4 weeks to 5mg pred. do NOT stop steroids. refer to endo. monitor TFTs
  • Severe mass effect symptoms or hypoadrenalism
    • severe headache, any visual disturbance
    • hypotension, severe electrolyte disturbance
    • IV methylpred 1mg/kg after bloods for pituitary axis Ax. analgesia PRN for headache. withhold ICPi
    • MRI pituitary protocol (also exclude brain mets)
    • consider formal visual field Ax
    • convert to pred & wean over 4 weeks to 5mg daily. do NOT stop steroids
    • refer to endo. monitor TFTs

26

Discuss cancer related emergencies; spinal cord compression 

- prevalence. which cancers more common

- which spine most commonly affected

- Px

- Ix

- Mx

 

  • 5% of all cancer patient but common problem in prostate, lung, breast and RCC. Other includes hodgkin’slymphoma, myeloma as well.
  • Thoracic: 60%, lumber: 25% and cervical 15%
  • Px:
    • Muscle weakness (60-86%). sensory loss less common. 
    • 2/3 not ambulatory at time of diagnosis
    • Bladder and bowel dysfunction: late
    • Functional capacity is the single most predictor of outcome 
  • Ix: 
    • whole spine MRI as 1/3 of the cases have multi-level metastasis with spinal cord compression -> poor prognosis. px with pain 
  • Mx: 
    • multidisciplinary evaluation
    • urgent IV glucocorticoids
    • decompressive surgery
    • + radiotherapy post op if: 
      • radioresistant tumour
      • displacement of spinal cord on MRI
      • single area of spinal cord compression
      • <48h of sx interval
      • >3 mo expected survival
    • Radiotherapy if not surgical candidate as above
    • chemotherapy if highly sensitive (i.e. lymphoma, germ cell tumour, SCLC

27

Mx of cancer related emergencies; superior vena cava syndrome

 

1. investigate for brain metastasis, airway or cardiac compression

2. if grade 1-3 symptoms: 

  • tissue biopsy, staging evaluation
  • develop stage and tumour specific definitive treatment plan as below

3. If grade 4 symptoms: venogram, urgent stent. direct thrombolytics if thrombus 

  • develop stage and tumour specific definitive treatment plan
    • surgically managed tumour (e.g. thymoma, residual germ cell mass): preop chemo -> surgery 
    • chemo/radiosensitive tumour (e.g. SCLC, lymphoma, germ cell) -> definiive treamtent (same as without SVC syndrome)
    • intermediate tumour (e.g. NSCLC) -> definitive treatment (same as without SVC syndrome), or consider stent, early radiotherapy
    • poor treatment options (e.g. malignant pleural mesothelioma), poor performance status -> radiotherapy, supportive care. If recurrent/persistent, stent (rarely surgical bypass)

28

Discuss tumour lysis syndrome

- which tumour types

- risk factors

- effects on electrolytes

- mx

 

  • Common in with hematological malignancy and sensitive solid tumour like germ cell, small cell Lung
  • Risk factors
    • High grade tumour and large burden
    • Sensitive to treatment
    • High LDH
    • Hypovolumia
    • Kidney impairement
    • Nephrotoxic drugs
    • Increased age
  • Breakdown of cancer cells -> release of cell contents to the blood
    • hyperkalaemia, hyperuricaemia, hyperphosphataemia, hypocalcaemia
    • AKI, arrhythmia, muscle cramps, weakness, seizures 
  • Treatment: 
    • Aggressive hydration 
    • allopurinol/ rasburicase prophylaxis 
    • Urine output goals listed 
    • Monitor for signs and symptoms of TLS
    • Frequent blood test 
    • Avoid nephrotoxic drug 
    • Correct electrolytes 
    • Renal replacement therapy 

29

Key SE of each:

anthracyclines (doxorubicin, epirubicin)

taxanes (paclitaxel, docetaxel)

transtuzumab

bleomycin

cisplatin

5-FU/capecitabine

oxaliplatin

bevacizumab

cetuximab

denosumab

 

 

  • Anthracyclines  (doxorubicin, epirubicin): Cardiomyopathy
  • Taxanes (paclitaxel, docetaxel): Peripheral neuropathy
  • Trastuzumab: Cardiomyopathy
  • Bleomycin: Pneumonitis
  • Cisplatin: Nephrotoxicity, neuropathy, hearing loss
  • 5-FU / capecitabine: Diarrhoea, mucositis, hand-foot, vasospasm
  • Oxaliplatin: Peripheral neuropathy
  • Bevacizumab: Hypertension, poor wound healing, thrombosis/bleeding
  • Cetuximab: Acneiform rash
  • Denosumab: Hypocalcemia, osteonecrosis of the jaw

30

Describe staging system for solid tumours

  • Most solid tumors are staged using the TNM cancer staging system
  • T represents the size or extent of local invasion of the primary tumor (T1-T4)
  • N indicates locoregional lymph node involvement (N0-N3),
  • M indicates the absence (M0) or presence (M1) of distant metastases.