Oncology Question Bank

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1. According to the NIH 2014 consensus criteria, which clinical finding is sufficient on its own to establish a diagnosis of chronic graft-versus-host disease?

The NIH 2014 criteria distinguish 'diagnostic' signs, which are sufficient to establish chronic GVHD, from 'distinctive' signs, which require biopsy or other confirmation. Diagnostic features include poikiloderma, lichen planus–like, sclerotic, morphea-like or lichen sclerosus–like skin changes; lichen planus–like oral changes; genital lichen planus–like or vaginal scarring; oesophageal web or stricture; bronchiolitis obliterans diagnosed by lung biopsy; and fasciitis or joint contractures. Maculopapular rash, diarrhoea, anorexia and hyperbilirubinaemia are common to acute and chronic GVHD and cannot establish chronic GVHD alone. The diagnosis is based on clinical features, not on the time since transplantation. Pearl: xerostomia, nail dystrophy and keratoconjunctivitis sicca are distinctive but not diagnostic features.

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2. An 81-year-old man has a 6 cm ulcerated basal cell carcinoma at the medial canthus invading the orbit. Curative surgery would require orbital exenteration, which he declines, and the multidisciplinary team considers radiotherapy inappropriate. There are no distant metastases. What is the most appropriate systemic treatment?

More than 90% of BCCs have activated hedgehog signalling, usually through PTCH1 loss or SMO mutation. Hedgehog pathway inhibitors (vismodegib or sonidegib) inhibit Smoothened and are first-line systemic therapy for locally advanced BCC not amenable to surgery or radiotherapy; in ERIVANCE, vismodegib achieved an objective response rate of about 43–60% in locally advanced disease. Cemiplimab is approved for patients who progress on or are intolerant of hedgehog inhibitors. Platinum-taxane chemotherapy has limited evidence and more toxicity. Imatinib has no established role. Pearl: common hedgehog inhibitor adverse effects are muscle spasms, dysgeusia, alopecia and weight loss; the drugs are teratogenic.

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3. A 63-year-old woman with multiple myeloma has received monthly IV zoledronic acid for 3 years. Ten weeks after a lower molar extraction she has pain and an area of exposed, necrotic bone in the mandible at the extraction site that has not healed. She has never received head and neck radiotherapy. What is the most likely diagnosis?

The AAOMS 2022 definition of medication-related osteonecrosis of the jaw (MRONJ) requires current or previous treatment with an antiresorptive (bisphosphonate or denosumab) or antiangiogenic agent, exposed bone or bone probeable through a fistula in the maxillofacial region persisting for more than 8 weeks, and no history of jaw radiotherapy or obvious metastatic disease of the jaw. High-dose, prolonged IV bisphosphonate therapy and dental extraction are the main risk factors. Osteoradionecrosis requires prior radiotherapy. Dry socket occurs within days of extraction and resolves within weeks. Plasmacytoma presents as a lytic mass rather than exposed necrotic bone. Pearl: management is conservative (antiseptic rinses, antibiotics, limited debridement), and dental work should ideally be completed before antiresorptive therapy.

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4. A 58-year-old woman with bulky chronic lymphocytic leukaemia on day 2 of chemoimmunotherapy develops palpitations. Potassium is 7.1 mmol/L, and the ECG shows peaked T waves and widening of the QRS complex. What is the most appropriate immediate treatment?

Hyperkalaemia with ECG changes is a medical emergency. IV calcium gluconate (e.g., 10 mL of 10% solution over several minutes) stabilises the cardiac membrane within minutes, although it does not lower serum potassium. It should be followed immediately by measures that shift potassium intracellularly (IV insulin with glucose, nebulised salbutamol) and then remove it. Oral sodium polystyrene sulfonate acts over hours and is unsuitable as immediate therapy. Furosemide is slow and ineffective with oliguric TLS-related kidney injury. Haemodialysis may be required for refractory hyperkalaemia in TLS but cannot be arranged quickly enough to be the first measure. Pearl: in TLS, repeat potassium every 4–6 hours.

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5. A 79-year-old immunocompetent man has a recurrent 8 cm cutaneous squamous cell carcinoma of the scalp with skull invasion. He has previously had surgery and radiotherapy to the area, and the tumour board deems further surgery or radiotherapy not feasible with curative intent. He has ECOG 1 and no autoimmune disease. What is the most appropriate systemic treatment?

Cutaneous SCC has one of the highest tumour mutational burdens, driven by UV damage, and is highly responsive to PD-1 blockade. Cemiplimab produced objective responses in about 45–50% of locally advanced or metastatic cSCC not amenable to curative surgery or radiotherapy, with durable responses, and pembrolizumab is also approved; NCCN lists anti-PD-1 therapy as preferred first-line systemic treatment. Cetuximab has lower, shorter responses and is reserved for patients unsuitable for immunotherapy. Vismodegib targets the hedgehog pathway in BCC. BRAF/MEK inhibitors have no role in cSCC. Pearl: in solid-organ transplant recipients, PD-1 inhibitors carry a high risk of allograft rejection.

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6. A 58-year-old man with metastatic colorectal cancer receiving FOLFOX reports that during his last 2-hour oxaliplatin infusion he developed jaw tightness, a sensation of difficulty swallowing and breathing, and tingling fingers, worsened by drinking cold water. During the episode SpO₂ was 98%, with no stridor, wheeze, rash or hypotension, and symptoms resolved within hours. What is the most appropriate modification for the next cycle?

This is acute oxaliplatin neurotoxicity with pharyngolaryngeal dysaesthesia: transient, cold-triggered paraesthesias and a subjective feeling of throat tightness without objective airway compromise, affecting most patients to some degree. It reflects oxalate-related prolongation of voltage-gated sodium channel opening in peripheral nerves. Management is reassurance, avoiding cold exposure, and prolonging the infusion to 6 hours, which lowers peak concentration and reduces recurrence. Normal saturation and the absence of stridor, rash or hypotension distinguish it from hypersensitivity, so discontinuation or desensitisation is not warranted. Calcium–magnesium infusions failed to reduce oxaliplatin neurotoxicity in the phase III N08CB trial and are not recommended by ASCO. Pearl: this acute syndrome is distinct from cumulative sensory neuropathy.

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7. Which measure is recommended by MASCC/ISOO guidelines to prevent oral mucositis in patients receiving bolus 5-fluorouracil chemotherapy?

Oral cryotherapy (holding ice chips in the mouth starting shortly before and continuing for about 30 minutes during bolus 5-FU administration) causes local vasoconstriction, reducing delivery of the short half-life drug to the oral mucosa. MASCC/ISOO 2020 guidelines recommend it for bolus 5-FU and for high-dose melphalan conditioning. The guidelines recommend against chlorhexidine and sucralfate mouthwashes for mucositis prevention because of lack of efficacy. Palifermin, a keratinocyte growth factor, is recommended for patients with haematological malignancies receiving high-dose chemotherapy and total body irradiation before autologous stem cell transplantation, not for standard 5-FU regimens. Pearl: avoid cryotherapy with oxaliplatin because it triggers cold-induced dysaesthesia.

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8. A 24-year-old man presents with cough and chest pain. CT shows a 9-cm anterior mediastinal mass and enlarged retroperitoneal lymph nodes. Serum beta-hCG is 2,500 IU/L and AFP is 350 ng/mL. Testicular ultrasound is normal. Biopsy shows poorly differentiated carcinoma, and FISH demonstrates isochromosome 12p. What is the most appropriate treatment?

A young man with midline (mediastinal and retroperitoneal) disease, markedly raised AFP and hCG, and isochromosome 12p, the genetic hallmark of germ cell tumors, has an extragonadal nonseminomatous germ cell tumor, a favourable subset of carcinoma of unknown primary that is potentially curable. Primary mediastinal nonseminomatous germ cell tumors are classified as poor risk by IGCCCG and are treated with four cycles of cisplatin-based chemotherapy (BEP or VIP; VIP is often preferred to avoid bleomycin lung toxicity before thoracic surgery), followed by resection of residual masses. Empirical carboplatin-paclitaxel is inferior for this chemosensitive tumor. Radiotherapy is not curative for nonseminomatous disease, and upfront surgery is inappropriate with elevated markers and metastatic spread. Pearl: mediastinal NSGCT is associated with Klinefelter syndrome and hematological malignancies.

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9. According to WHO CNS5 (2021), which molecular combination defines oligodendroglioma?

Oligodendroglioma is defined by the combination of an IDH1 or IDH2 mutation and whole-arm codeletion of chromosomes 1p and 19q; these tumours also typically have TERT promoter mutations and retain nuclear ATRX. They are graded as CNS WHO grade 2 or 3 and carry the most favourable prognosis among diffuse gliomas, with high chemosensitivity. IDH mutation with ATRX loss and TP53 mutation characterises astrocytoma, IDH-mutant. IDH-wildtype tumours with EGFR amplification are glioblastoma in adults. H3 K27M mutation defines diffuse midline glioma, H3 K27-altered. Pearl: ATRX loss and 1p/19q codeletion are mutually exclusive, so ATRX loss makes oligodendroglioma unlikely.

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10. A 55-year-old woman who has never smoked undergoes CT of the chest after a road traffic accident. There is an incidental solitary 4-mm smooth solid nodule in the right lower lobe. She has no history of malignancy or immunosuppression. According to the Fleischner Society 2017 guidelines, what is the most appropriate management of the nodule?

For an incidental single solid nodule smaller than 6 mm in a low-risk patient, the Fleischner Society 2017 guidelines recommend no routine follow-up, because the malignancy risk is below 1%. In high-risk patients an optional CT at 12 months may be considered. PET-CT is unreliable below about 8 mm owing to limited spatial resolution, and biopsy of a 4-mm nodule is neither feasible nor justified. Short-interval CT at 3 months is reserved for larger (>8 mm) nodules. Pearl: Fleischner guidelines do not apply to lung cancer screening (use Lung-RADS), patients younger than 35 years, or patients with known cancer or immunosuppression.