Branching cross-examination

This is a MedVellum formative viva. It is not an official RACP, MRCPCH, ABP, ACGME or RCPSC station, mark scheme, duration or pass standard. Release each update only after the candidate states the mechanism, the dose principle, and the safeguard. [1] [4]

Candidate brief

You are the paediatric registrar in an oncology shared-care clinic. Speak as you would when building a supportive pharmacology plan around a child on doxorubicin and cisplatin. State the toxicity, the matched antidote, and the surveillance at each step. This is one continuous case. Each escalation branch leads to the next update. [1]

Question 1 — The dexrazoxane cardioprotection decision

Stimulus update. An eight-year-old on doxorubicin for a solid tumour has a cumulative anthracycline dose approaching the high-risk threshold, and the oncology team is considering dexrazoxane. Question: Explain the mechanism of anthracycline cardiotoxicity, how dexrazoxane protects the heart, and the dose principle. [1]

Consultant-level model answer. "Doxorubicin injures the cardiomyocyte through an iron-catalysed free-radical cascade that the slowly regenerating cardiac cell cannot repair. Dexrazoxane is an intracellular iron chelator — given before the anthracycline it binds the iron before the radical cascade begins, protecting the heart without shielding the tumour. The cardioprotection ratio is about ten parts dexrazoxane to one part doxorubicin, given ahead of each dose, and it is reserved for the child crossing a high cumulative threshold — classically above about 300 milligrams per square metre of doxorubicin equivalent." [1]

Probing follow-up. "Some teams worry dexrazoxane causes secondary malignancy. How do you respond?" A strong answer is: "The Barry study in high-risk acute lymphoblastic leukaemia found no excess secondary neoplasms with dexrazoxane, so withholding it from a high-cumulative-dose child on the basis of that outdated fear denies a proven cardioprotection." [1]

Common weak answer. "Dexrazoxane is too risky and I would not use it." This denies a proven cardioprotection on the basis of a concern the evidence did not bear out. [1]

Escalation branch. If the candidate states the mechanism and the dose principle, release the cisplatin antiemetic question. If they cannot name the mechanism, re-teach the iron-free-radical cascade before proceeding. [1]

Question 2 — The antiemetic ladder for cisplatin

Stimulus update. The regimen also includes cisplatin, which sits at the top of the emetogenic ladder. Question: Describe the antiemetic combination and the window to warn the family about. [2]

Consultant-level model answer. "For cisplatin I use the triple combination — ondansetron for the 5-HT3 receptor, aprepitant for the NK1 receptor that carries substance P, and dexamethasone for the inflammatory arm. Together they cover the acute phase in the first twenty-four hours and the delayed phase from forty-eight to ninety-six hours, and I warn the family specifically about the delayed window because the vomiting recurs when they expect it to have settled. I keep dose-related ondansetron QT prolongation in mind at higher intravenous doses." [2] [3]

Probing follow-up. "What evidence supports adding aprepitant in children?" A strong answer is: "The Kang phase three randomised trial showed aprepitant added to ondansetron and dexamethasone is effective and tolerable in children, and the MASCC/ESMO paediatric consensus builds the antiemetic strength to the emetogenic challenge." [2] [3]

Common weak answer. "Ondansetron alone is enough for any regimen." This under-covers a highly emetogenic course and risks dehydration and non-adherence. [2]

Escalation branch. If the candidate names the triple combination and the delayed window, release the febrile neutropenia question. [4]

Question 3 — Febrile neutropenia prophylaxis and the front door

Stimulus update. The regimen is myelosuppressive and the child is at high risk of febrile neutropenia. Question: State the colony-stimulating factor prophylaxis options and the immediate management if the child arrives febrile and neutropenic. [4]

Consultant-level model answer. "For prophylaxis I would use filgrastim at about five micrograms per kilogram per day subcutaneous after the chemotherapy, or pegfilgrastim at about a hundred micrograms per kilogram subcutaneous as a single dose per cycle, with primary prophylaxis justified at about the twenty per cent febrile neutropenia risk threshold per the ASCO guideline. If the child arrives febrile and neutropenic, I treat it as a medical emergency: cultures from every lumen of the central line and a peripheral site, a full blood count and CRP, and empirical broad-spectrum antipseudomonal antibiotics within the hour — never as a routine viral illness." [4]

Probing follow-up. "Why within the hour, rather than after the cultures grow?" A strong answer is: "Because the depleted neutrophil pool cannot contain mucosal translocation, and the source is bacterial sepsis until proven otherwise; the empirical antibiotic principle is non-negotiable and narrows once the organism returns." [4]

Common weak answer. "Send the child home with a thermometer and review in clinic tomorrow." This loses the hour the sepsis needs. [4]

Escalation branch. If the candidate gives the prophylaxis and the empirical-antibiotic principle, release the vincristine route question. [5]

Question 4 — The vincristine-intravenous-only route rule

Stimulus update. The child is also on vincristine, which appears on the same prescription list as an intrathecal procedure for another patient on the ward round. Question: State the route rule, the consequence of error, and the prevention system. [5]

Consultant-level model answer. "Vincristine is given by the intravenous route only, and into the cerebrospinal fluid it is uniformly fatal — the microtubule blockade ascends the neuraxis and the child dies of ascending paralysis and brainstem failure within days. The prevention is a system, not a memory: vincristine is diluted in a minibag rather than a syringe so it cannot be confused with the small-volume intrathecal drugs, intrathecal drugs are prepared and delivered at a separate time, and two clinicians check the drug, the route and the patient independently." [5]

Probing follow-up. "Why a minibag rather than a syringe for vincristine?" A strong answer is: "Because the small-volume intrathecal drugs are prepared in syringes, and a syringe of vincristine can be physically confused with them; a minibag makes the two routes physically distinct, which is the engineering control that breaks the error chain." [5]

Common weak answer. "I would double-check the dose." A dose check does not prevent a route error; the system is route-specific. [5]

Escalation branch. If the candidate states the route rule and the minibag-plus-independent-check system, move to the extravasation question. [1]

Question 5 — Anthracycline extravasation

Stimulus update. A doxorubicin infusion extravasates at the central line on the ward. Question: What is the immediate pharmacological management, the time window, and the thermal-management principle? [5]

Consultant-level model answer. "An anthracycline extravasation is managed with dexrazoxane intravenously within six hours of the spill, daily for three days, body-surface-area banded — the Mouridsen regimen. Cold compresses are contraindicated for anthracycline extravasation; cold is the management for vinca injury and worsens the anthracycline outcome. I would arrange surgical review for the necrosis that a delayed rescue allows." [5]

Probing follow-up. "Why is cold right for vinca extravasation but wrong for anthracycline?" A strong answer is: "Because the two injuries spread by different mechanisms — vinca injury is reduced by cooling the tissue, while anthracycline tissue injury is neutralised by the dexrazoxane chelation and cold offers no benefit and may worsen perfusion." [5]

Common weak answer. "Apply a cold compress and observe." This is the wrong thermal management and delays the dexrazoxane rescue. [5]

Escalation branch. If the candidate gives the dexrazoxane-within-six-hours regimen and the no-cold principle, close the viva by asking the one principle they most want to carry forward. [6]

Closing principle

Consultant-level model answer. "Chemotherapy and supportive pharmacology rests on pairing each cytotoxic harm with its antidote and protecting the route. Dexrazoxane chelates the iron for the anthracycline heart — and rescues the extravasation within six hours with no cold. The antiemetic ladder matches the emetogenic challenge. The colony-stimulating factors prevent febrile neutropenia, and the febrile-neutropenic child gets antibiotics within the hour. And vincristine is intravenous only, never intrathecal — the single rule the minibag and independent-check culture exists to enforce." [1] [4] [6]