Clin Shonc Flashcards
Tumour Lysis
1) Pathophys including sequalae:
2) Broadly differentiated into? Key blood results?
Large volume tumour cell death eith spontaneouly or in response to treatment -> Release of intracellular ions, nucleic acids, proteins and their metabolites into the systemic circulation.
Leads to: metabolic abnormalities such as hyperuricaemia, hyperK, hyperphosphataemia, secondary hypoCa and uraemia, can in turn lead to renal failure, arrhythmias, seizures, neurological sx.
2) Laboratory TLS, Clinical TLS
The presence of 2 or more of: HyperUric acid, HyperK, HyperP04-, HYPO Ca (adjusted)
For clinical note the Cairo-Bishop grading of clinical tumour lysis syndrome
Prophylaxis/Mx of tumour Lysis syndrome?
1) Evaluate risk:
High proliferation rate, rapid response to Tx anticipated (chemo or radio sensitive), large volume, HR Cancer (lymphoma e.g Burkitts, SCLC), pre-existing metabolic disturbance.
2) Aggressive Hydration, ideally begin 24Hrs prior to Tx. Aim UO >100ml/msqr/Hr.
3) Allopurinol TDS
4)Consider Rasburicase (converts uric acid to excretable)
5) Close monitoring
Describe Child-Pugh class.
Rad onc relevance?
Assesses the severity of liver disease, particularly cirrhosis, using 5clinical and lab factors:
Serum bilirubin,
Serum albumin,
Prothrombin time/INR,
Ascites,
Encephalopathy.
Factors scored (1-3) based on severity, and the total score determines Child-Pugh class (A, B, or C)
Liver SABR if <=7 points = A or very low B
In DVT Mx (prophylaxis or haem stable) give the two main classes of drug, a brand name for each, MOA.
What drug if patient has HITs?
Haemodynamically stable.
1) Preferred - Rivaroxaban (e.g Xaralto) - Factor Xa inhibitor. Factor Xa promotes coagulation by binding to factor Va to form the prothrombinase.
More kidney friendly (GFR>15), high caution if previous haemorrhagic stroke - prefer LMWH.
2) LMWH - e.g Enoxaparin: Activates Antithrombin which inhibits FactorXa.
Not if GFR<30, Hyper K or thrombocytopenia.
Prophylaxis low risk = 20mg/day
HR = 40mg/day
If patient has HITS:
Selective Factor Xa inhibitor Fondoparinux.
Medication Mx of PE.
If Haemstable:
Intervention being considered (thrombolysis or pulmonary embolectomy): LMWH, or UFH until intervention.
No Thrombolysis: Rivaroxaban 15 mg BD for 3 weeks
then 20 mg XARELTO once daily.
Unstable:
High bleeding risk: consider pulmonary embolectomy.
Low bleeding risk: Alteplase.
Duration of medicaal Mx PE/DVT
- DVT Provoked limited and distal - do 6 weeks
- PE or Unprovoked = 3 months
- Cancer Related!!! 6 months, consider with LMWH then oral Rivaroxaban,
List the late toxicities (Mx where applicable) after definitive Chemo RT for stage 3B cervix cancer:
1) Infertility: preTx counseling ect
2) Gynae: Dryness (estrogen cream), stenosis - dilators/reg intercourse
3) Ovarian failure: Address oseoporotic RFs (smoking, lack of weight bearing exercise), vit D, encourage exercise, consider dxa scan. HRT an option with risks.
4) Proctitis: Improve diet, avoid triggers, lopermide PRN.
5) Cystitis.
6) Pelvic insufficiency #s: vit D, analgesia, physio, consider bone denisty
7) Lymphoedema: stay active, weight loss/avoid obesity, lymphoedema practitioner - compression garmets.
8) 2nd maligancy - increased surveillance, lower threshold for Ix.
Give grades for urinary toxicity (e.g. after bladder RT):
Grade 0: No toxicity.
Grade 1: Mild symptoms, no intervention needed.
Grade 2: Moderate symptoms, requiring minor or local intervention.
Grade 3: Severe symptoms, requiring hospitalization or significant intervention.
Grade 4: Life-threatening toxicity, requiring urgent intervention.
Grade 5: Death
Treatment for paraneoplastic cushings syndrome and most common cause.
SCLC followed by other carcinoid tumours.
1) Treat the tumour
2) Ketoconazole to inhibit cortisol production
3) Octreotide to inhibit ACTH
4) Monitor treat HTN, keep an eye on electrolytes.
Give the complete list of Sx and signs associated with an anterior or superior mediastinum mass
Respiratory:
Cough
Dyspnea
Stridor
Orthopnea
Esophageal:
Dysphagia
Nervous:
Hoarseness: due to pressure on recurrent laryngeal nerve.
Pain
Systemic:
Facial and arm oedema due to SVC obstruction
Hypotension
If lymphoma then +/- B Sx
Signs:
Pemberton’s sign
Hamman’s sign = mediastinal crunch or during auscultation over the cardiac apex and left sternal border, synchronous with the heartbeat.
Diagnostic criteria for delerium:
The CAM diagnostic algorithm evaluates four key features of delirium:
1) Acute Change in Mental Status with Fluctuating Course,
2) Inattention,
3) Disorganized Thinking
4) Altered Level of Consciousness.
Rationale and possible MOA for the concurrent use of immunotherapy with radiation
- Radiation-induced immunogenicity:
a. Radiation damages cancer cells, leading to the release of tumor-associated antigens stimulating immune system not just at tumour site (abscopal effect).
b. Increase the expression of surface antigens on tumor cells, making them more targetable by immune cells.
c. Alter tumour immune microenvironment (TIME) through local release of inflammatory mediators. Can increase number of tumour inflitrating lymphocytes,
- Immune checkpoint blockade:
ICIs, like PD-1/PD-L1 inhibitors, prevent immune cells from being inhibited by tumor-induced signals, allowing T cells to attack cancer cells more effectively.
- Synergistic immune response:
Radiation-induced immunogenicity and ICIs working together can enhance T-cell recruitment to the tumor site.
More activated T-cell + less inhibition of cell kill via (PD-L1/CTLA) = enhanced cell kill both at the site of radiation but also distally due to pro-inflammatory systemic response post radiation.
Side effects of Bevicuzumab?
Benefit in GBM
Improves PFS, no OS benefit, increased tox including grade III events. Controversy around sponsorship by pharmaceutical company.
MOst consequential (due to binding/inactivating VEGF):
GI haemorrhage
GI perforation.
Common:
HTN
Protein urea
Gi Upset
What is the CODEL study? What has it found so far?
CODEL: phase III RCT: RT, RT + TMZ, or TMZ for newly diagnosed 1p/19q codeleted oligodendroglioma.(useful for rembering the options for oligo).
Early data shows much less PFS in TMZ alone group
Criteria for a test to be used as a screening test:
1) Disease is a significant health problem: Burden to patient/health system/society. WHERE early detection caries benefit.
2) Accuracy - sens/spec
3) efficiency: Cost, accessible
4) Acceptable
5) Treatment available
6) Evidence of screening effectiveness = favourable benefit harm ratio, reduced morbidity/mortality
7) Practical considerations: Can be delivered in health system, ethical (informed consent).
Toxicities of immune-checkpoint inhibitors
Most common:
Skin reactions most common: rash, puritis.
GI: diarrhoea, colitis
Endocrine: Thyroid most common - hypothyroidism in particular.
Other:
Auto-immune:
1) Anti-CTLA-4 inhibitors (e.g., ipilimumab): Rash, pruritus, colitis, and endocrinopathies are frequently reported.
2) Anti-PD-1/PD-L1 inhibitors (e.g., pembrolizumab, nivolumab, atezolizumab): Hypothyroidism, hyperthyroidism, pneumonitis, and colitis are common
Reactivating radiation pneumonitis
Infusion reaction.
Auto immune reactions associated with each class of checkpoint inhibitor:
Anti-CTLA-4 inhibitors (e.g., ipilimumab):
Rash, pruritus, colitis, and endocrinopathies are frequently reported.
Anti-PD-1/PD-L1 inhibitors (e.g., pembrolizumab, nivolumab, atezolizumab):
Hypothyroidism, hyperthyroidism, pneumonitis, and colitis are common
