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EBOT practice questions

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Question 1Clinical Assessment and Diagnosis in Oncology

A 58-year-old man with metastatic colorectal cancer has a CT scan showing measurable liver lesions. According to RECIST 1.1, which lesion qualifies as a measurable target lesion?

  1. A bone lesion with a soft-tissue component of 15 mm
  2. A pleural effusion visible on the same scan
  3. A lymph node with a short axis of 12 mm Correct answer.
  4. A liver lesion with a longest diameter of 8 mm

Explanation

RECIST 1.1 defines measurable lymph nodes by short-axis diameter, and a pathological node must reach at least 15 mm in short axis to count as a target lesion, so a 12 mm node is non-target. Non-nodal lesions must measure at least 10 mm in longest diameter on CT.

Question 2Clinical Assessment and Diagnosis in Oncology

A patient on immunotherapy develops new skin lesions and mild diarrhea after two cycles. The clinician suspects immune-related adverse events. Which grading framework is most appropriate for categorizing these toxicities?

  1. Child-Pugh classification
  2. Karnofsky Performance Status
  3. RECIST 1.1
  4. CTCAE (Common Terminology Criteria for Adverse Events) Correct answer.

Explanation

CTCAE provides standardized severity grading (grades 1-5) for adverse events including immune-related toxicities, guiding decisions about holding or discontinuing therapy. RECIST assesses tumor response, while Karnofsky and Child-Pugh measure functional status and hepatic reserve respectively.

Question 3Clinical Assessment and Diagnosis in Oncology

A 45-year-old woman presents with a palpable breast mass. Which imaging modality is generally the first-line study for evaluating the extent of disease in a newly diagnosed breast cancer?

  1. Diagnostic bilateral mammography and breast ultrasound Correct answer.
  2. Bone scintigraphy
  3. Brain MRI
  4. Whole-body PET-CT

Explanation

Diagnostic mammography combined with breast ultrasound is the standard initial imaging to characterize the primary tumor and assess the ipsilateral and contralateral breast. Whole-body staging studies such as PET-CT or bone scan are reserved for patients with clinical suspicion of metastatic disease.

Question 4Clinical Assessment and Diagnosis in Oncology

A tumor is described as T3N1M0 according to the TNM classification. What does the 'N1' designation indicate?

  1. Direct extension into an adjacent structure
  2. Metastasis to a distant organ
  3. No regional lymph node involvement
  4. Involvement of regional lymph nodes Correct answer.

Explanation

In the TNM system, the N category describes regional lymph node status, and N1 indicates involvement of regional nodes (the specific criteria vary by primary site). The M category addresses distant metastasis, and T describes the primary tumor.

Question 5Clinical Assessment and Diagnosis in Oncology

A 62-year-old with lung cancer has a performance status of 2 on the ECOG scale. Which description best matches this score?

  1. Completely disabled and totally confined to bed
  2. Fully active with no restriction
  3. Restricted in physically strenuous activity but ambulatory and able to carry out light work Correct answer.
  4. Capable of only limited self-care, confined to bed more than half the day

Explanation

ECOG performance status 2 means the patient is ambulatory and capable of all self-care but unable to carry out any work activities, up and about more than 50% of waking hours. This differs from ECOG 0 (fully active) and ECOG 3-4 (limited self-care or bedbound).

Question 6Clinical Assessment and Diagnosis in Oncology

During assessment of a patient with suspected malignant bowel obstruction, which finding most strongly supports the diagnosis?

  1. Hyperactive bowel sounds with frequent diarrhea
  2. Absent bowel sounds with abdominal distension and vomiting Correct answer.
  3. Normal abdominal radiograph
  4. Isolated lower abdominal tenderness without distension

Explanation

Malignant bowel obstruction typically presents with colicky abdominal pain, vomiting, distension, and absent or diminished bowel sounds, often with air-fluid levels on imaging. Diarrhea and hyperactive sounds suggest an alternative process such as gastroenteritis.

Question 7Clinical Assessment and Diagnosis in Oncology

A patient with prostate cancer has a markedly elevated serum PSA and bone pain. Which imaging study is most appropriate to evaluate for skeletal metastases?

  1. Chest radiograph
  2. Abdominal ultrasound
  3. Colonoscopy
  4. Technetium-99m bone scintigraphy Correct answer.

Explanation

Technetium-99m bone scintigraphy is a sensitive whole-body survey for osteoblastic skeletal metastases, which are common in prostate cancer. Ultrasound, chest radiograph, and colonoscopy do not evaluate the skeleton.

Question 8Clinical Assessment and Diagnosis in Oncology

Which laboratory abnormality most directly suggests tumor lysis syndrome in a patient recently started on cytotoxic chemotherapy?

  1. Isolated hyperbilirubinemia
  2. Hypernatremia with hyperchloremia
  3. Hypokalemia with hypophosphatemia
  4. Hyperkalemia with hyperphosphatemia and hypocalcemia Correct answer.

Explanation

Tumor lysis syndrome results from rapid breakdown of malignant cells, releasing potassium and phosphate and causing secondary hypocalcemia, often with acute kidney injury and hyperuricemia. The characteristic constellation is hyperkalemia, hyperphosphatemia, hyperuricemia, and hypocalcemia.

Question 9Clinical Assessment and Diagnosis in Oncology

A 70-year-old with known lung cancer presents with facial swelling, distended neck veins, and dyspnea. Which diagnosis should be considered first?

  1. Superior vena cava syndrome Correct answer.
  2. Hypercalcemia of malignancy
  3. Spinal cord compression
  4. Febrile neutropenia

Explanation

Facial plethora, distended neck veins, and dyspnea in a patient with lung cancer suggest superior vena cava syndrome from tumor compression or thrombosis. Cord compression presents with neurologic deficits, hypercalcemia with confusion and polyuria, and neutropenia with fever.

Question 10Clinical Assessment and Diagnosis in Oncology

A patient with lymphoma has a staging PET-CT showing a single hypermetabolic node. According to the Lugano classification, which parameter is used to assess response on PET-CT?

  1. Number of circulating tumor cells
  2. Serum lactate dehydrogenase level
  3. Deauville score based on uptake relative to reference regions Correct answer.
  4. Absolute tumor diameter only

Explanation

The Lugano classification uses the five-point Deauville scale, which grades FDG uptake relative to the mediastinal blood pool and liver, to define metabolic response in FDG-avid lymphomas. Diameter alone is insufficient for metabolic response assessment.

Question 11Clinical Assessment and Diagnosis in Oncology

A patient with advanced pancreatic cancer reports severe epigastric pain radiating to the back. Which assessment finding would most suggest celiac plexus involvement requiring intervention?

  1. Pain reproduced by superficial palpation only
  2. Pain poorly controlled by escalating opioids with a visceral pattern Correct answer.
  3. Pain localized to the right lower quadrant
  4. Pain relief with upright posture

Explanation

Celiac plexus-mediated pain from upper abdominal malignancy is typically visceral, poorly localized, and often refractory to opioids, making it a candidate for neurolytic celiac plexus block. Postural relief suggests musculoskeletal causes, and right lower quadrant pain suggests another process.

Question 12Clinical Assessment and Diagnosis in Oncology

Which finding on a complete blood count most strongly supports a diagnosis of febrile neutropenia in a patient receiving chemotherapy?

  1. Platelet count of 150,000/µL with mild fatigue
  2. Hemoglobin of 10 g/dL with normal temperature
  3. White blood cell count of 12,000/µL with fever
  4. Absolute neutrophil count below 500 cells/µL with temperature of 38.3°C Correct answer.

Explanation

Febrile neutropenia is defined by an absolute neutrophil count below 500 cells/µL (or expected to fall below that) combined with a single oral temperature of at least 38.3°C or sustained fever of 38.0°C. Leukocytosis with fever suggests infection without neutropenia.

Question 13Clinical Assessment and Diagnosis in Oncology

A patient with a solitary pulmonary nodule undergoes CT. Which feature most increases the likelihood that the nodule is malignant?

  1. Stable size over five years
  2. Spiculated margins with growth on serial imaging Correct answer.
  3. Smooth margins with diffuse calcification
  4. Uniform fat attenuation

Explanation

Spiculated margins and documented growth are high-risk features for malignancy in a pulmonary nodule. Benign patterns include diffuse or central calcification, fat attenuation, and stability over two years or more.

Question 14Clinical Assessment and Diagnosis in Oncology

A 55-year-old with colorectal cancer has an elevated CEA level before surgery. What is the most appropriate use of CEA during follow-up?

  1. Confirming the histologic subtype of the tumor
  2. Serial monitoring for recurrence after curative resection Correct answer.
  3. Screening for colorectal cancer in the general population
  4. Determining the TNM stage at diagnosis

Explanation

CEA is not a screening test because of limited sensitivity and specificity, but a preoperative elevation that normalizes after resection makes serial CEA useful for detecting recurrence. CEA does not establish histology or independently determine TNM stage.

Question 15Clinical Assessment and Diagnosis in Oncology

A patient with breast cancer is being assessed for HER2 status. Which assay result is generally required before initiating HER2-targeted therapy?

  1. Immunohistochemistry score of 3+ or gene amplification by in situ hybridization Correct answer.
  2. Immunohistochemistry score of 1+
  3. Serum HER2 extracellular domain elevation
  4. Normal serum CA 15-3 level

Explanation

HER2 positivity is defined by immunohistochemistry 3+ or by in situ hybridization demonstrating gene amplification; equivocal 2+ results require reflex ISH testing. Serum HER2 and CA 15-3 are not used to determine eligibility for HER2-directed therapy.

Question 16Clinical Assessment and Diagnosis in Oncology

A patient with non-small cell lung cancer is being considered for immune checkpoint inhibitor therapy. Which biomarker is most commonly used to guide first-line single-agent pembrolizumab eligibility?

  1. PD-L1 tumor proportion score Correct answer.
  2. Serum carcinoembryonic antigen
  3. ALK rearrangement
  4. Absolute lymphocyte count

Explanation

PD-L1 expression measured as a tumor proportion score guides selection of single-agent checkpoint inhibition in advanced non-small cell lung cancer without driver mutations. CEA and lymphocyte counts are not validated selection biomarkers, and ALK rearrangement instead directs ALK inhibitor therapy.

Question 17Clinical Assessment and Diagnosis in Oncology

During a diagnostic workup, a patient with a neck mass undergoes fine-needle aspiration. Which result most reliably distinguishes a benign from a malignant thyroid nodule?

  1. Thyroid ultrasound echogenicity alone
  2. Serum thyroid-stimulating hormone level
  3. Patient age at presentation
  4. Cytologic classification according to the Bethesda System Correct answer.

Explanation

Fine-needle aspiration cytology reported using the Bethesda System for Reporting Thyroid Cytopathology provides standardized diagnostic categories with associated malignancy risk, guiding management. TSH, echogenicity, and age inform risk but do not establish a cytologic diagnosis.

Question 18Clinical Assessment and Diagnosis in Oncology

A patient with multiple myeloma reports new back pain and leg weakness. Which imaging study is most appropriate to evaluate for spinal cord compression?

  1. Bone scan
  2. Abdominal CT
  3. Emergent MRI of the whole spine Correct answer.
  4. Plain radiograph of the lumbar spine only

Explanation

MRI of the entire spine is the study of choice for suspected spinal cord compression because it identifies multifocal disease and soft-tissue cord compromise. Plain radiographs and bone scans cannot reliably assess the spinal cord or epidural space.

Question 19Clinical Assessment and Diagnosis in Oncology

A patient with known malignancy develops confusion, polyuria, and constipation. Serum calcium is 13.5 mg/dL. Which mechanism most commonly underlies this presentation?

  1. Renal failure causing phosphate retention
  2. Vitamin D intoxication
  3. Primary hyperparathyroidism
  4. Parathyroid hormone-related peptide secretion by the tumor Correct answer.

Explanation

Hypercalcemia of malignancy most often results from tumor secretion of parathyroid hormone-related peptide, which increases bone resorption and renal calcium reabsorption. Primary hyperparathyroidism and vitamin D excess are non-malignant causes, and renal failure typically lowers calcium.

Question 20Clinical Assessment and Diagnosis in Oncology

A patient with melanoma is being evaluated for response after targeted therapy. Which pattern on imaging would be considered progressive disease by RECIST 1.1?

  1. A 10% decrease in the sum of target lesion diameters
  2. A 25% increase in the sum of target lesion diameters from nadir with a new lesion Correct answer.
  3. Stable disease with no change in any lesion
  4. A 15% increase in the sum of diameters without new lesions

Explanation

RECIST 1.1 defines progressive disease as at least a 20% increase in the sum of target lesion diameters from nadir (with an absolute increase of at least 5 mm) or the appearance of new lesions. A 15% increase and stable disease do not meet progression criteria.

Question 21Clinical Assessment and Diagnosis in Oncology

A 60-year-old with cirrhosis and a liver mass undergoes evaluation. Which finding on multiphasic CT most strongly suggests hepatocellular carcinoma?

  1. Fat attenuation without enhancement
  2. Peripheral nodular enhancement with delayed filling
  3. Homogeneous hypoenhancement in all phases
  4. Arterial phase hyperenhancement with venous washout Correct answer.

Explanation

Hepatocellular carcinoma classically shows arterial phase hyperenhancement followed by washout in the portal venous or delayed phase, which can be diagnostic in a cirrhotic liver. Peripheral nodular enhancement with delayed filling is characteristic of hemangioma.

Question 22Clinical Assessment and Diagnosis in Oncology

A patient with advanced cancer and a history of smoking presents with hyponatremia and concentrated urine. Which paraneoplastic syndrome should be considered?

  1. Carcinoid syndrome
  2. Lambert-Eaton syndrome
  3. Cushing syndrome from ectopic ACTH
  4. Syndrome of inappropriate antidiuretic hormone secretion Correct answer.

Explanation

SIADH from ectopic antidiuretic hormone production causes euvolemic hyponatremia with inappropriately concentrated urine, commonly associated with small cell lung cancer. Ectopic ACTH causes hypercortisolism and hypokalemia, while carcinoid and Lambert-Eaton produce distinct clinical pictures.

Question 23Clinical Assessment and Diagnosis in Oncology

A 68-year-old with pancreatic cancer has a Karnofsky Performance Status of 40. What does this score most likely indicate about the patient's functional ability?

  1. Moribund, fatal processes progressing rapidly
  2. Requires considerable assistance and frequent medical care, disabled Correct answer.
  3. Able to carry on normal activity with effort and some symptoms
  4. Able to carry on normal activity with no special care needed

Explanation

A Karnofsky score of 40 corresponds to disability requiring considerable assistance and frequent medical care. Normal activity without care is 90-100, activity with effort is 70-80, and moribund status is 10.

Question 24Clinical Assessment and Diagnosis in Oncology

A patient with a suspected malignant pleural effusion undergoes thoracentesis. Which finding most strongly suggests the effusion is malignant rather than parapneumonic?

  1. Elevated pleural fluid neutrophil count
  2. Pleural fluid pH below 7.20
  3. Glucose above 60 mg/dL
  4. Positive cytology for malignant cells Correct answer.

Explanation

Demonstration of malignant cells on pleural fluid cytology is the most specific finding for a malignant effusion. Low pH, neutrophilia, and low glucose are features of complicated parapneumonic effusions or empyema rather than proof of malignancy.

Question 25Clinical Assessment and Diagnosis in Oncology

A patient with neuroblastoma is being staged. Which biomarker combination is most useful for diagnosis and monitoring of disease burden?

  1. Urinary catecholamine metabolites (VMA and HVA) with serum neuron-specific enolase Correct answer.
  2. Serum CA 19-9 and CEA
  3. Serum alpha-fetoprotein and beta-hCG
  4. Serum calcitonin and carcinoembryonic antigen

Explanation

Neuroblastoma characteristically secretes catecholamine metabolites measured as urinary VMA and HVA, and neuron-specific enolase supports monitoring of disease burden. AFP and beta-hCG are germ cell tumor markers, CA 19-9 and CEA relate to gastrointestinal cancers, and calcitonin is used in medullary thyroid carcinoma.

Question 26Clinical Assessment and Diagnosis in Oncology

A patient with a newly diagnosed solid tumor is being assessed for performance status using the ECOG scale. The patient is ambulatory and able to carry out light work but is restricted in physically strenuous activity. Which ECOG performance status score does this correspond to?

  1. 2
  2. 3
  3. 0
  4. 1 Correct answer.

Explanation

The ECOG scale ranges from 0 (fully active) to 4 (completely disabled). A score of 1 indicates restriction in physically strenuous activity but ambulatory and able to carry out light or sedentary work. A score of 2 indicates ambulatory and capable of all self-care but unable to carry out any work activities, while 3 indicates limited self-care and confined to bed or chair more than 50% of waking hours.

Question 27Clinical Assessment and Diagnosis in Oncology

A 62-year-old man with a 40-pack-year smoking history presents with a 3-cm right upper lobe lung mass and enlarged ipsilateral mediastinal lymph nodes. There is no evidence of distant metastasis. According to the TNM staging system for non-small cell lung cancer, what is the most appropriate stage grouping?

  1. Stage IIIB
  2. Stage IV
  3. Stage IIB
  4. Stage IIIA Correct answer.

Explanation

In the TNM classification for NSCLC, a tumor larger than 3 cm but not exceeding 5 cm is T2, and ipsilateral mediastinal lymph node involvement is N2. The combination of T2 N2 M0 is stage IIIA. Stage IIB would require N1 disease or a larger tumor without mediastinal nodes, and stage IV requires distant metastasis.

Question 28Clinical Assessment and Diagnosis in Oncology

A 58-year-old woman with metastatic breast cancer has been on an aromatase inhibitor for 18 months. She now reports new right hip pain. Which assessment finding would most strongly suggest a pathologic fracture rather than a flare response?

  1. Increased uptake on a bone scan without corresponding symptoms
  2. New lytic lesion on plain radiograph at the site of pain Correct answer.
  3. Transient increase in tumor markers
  4. Resolution of pain after starting an NSAID

Explanation

A new lytic lesion on plain radiograph indicates cortical bone destruction, which is a hallmark of an impending or actual pathologic fracture and warrants urgent orthopedic evaluation. Tumor flare and isolated bone scan uptake are less specific and do not directly demonstrate structural compromise.

Question 29Clinical Assessment and Diagnosis in Oncology

A 45-year-old man with a history of treated Hodgkin lymphoma presents with fatigue and early satiety. Physical examination reveals a palpable left upper quadrant mass. Which finding on contrast-enhanced CT would most strongly support the diagnosis of a secondary malignancy rather than recurrent lymphoma?

  1. Multiple enlarged para-aortic lymph nodes with homogeneous enhancement
  2. Splenomegaly with homogeneous parenchyma
  3. A well-defined cystic lesion in the liver
  4. A solitary gastric mass with irregular margins and central necrosis Correct answer.

Explanation

A solitary gastric mass with irregular margins and central necrosis is highly suspicious for gastric adenocarcinoma, a known secondary malignancy after Hodgkin lymphoma treatment. Recurrent lymphoma typically presents with lymphadenopathy or splenic involvement, not an isolated necrotic gastric mass.

Question 30Clinical Assessment and Diagnosis in Oncology

A 70-year-old woman with advanced ovarian cancer has a CA-125 level of 850 U/mL. She completes three cycles of platinum-based chemotherapy. Which change in CA-125 is most indicative of a favorable response according to GCIG criteria?

  1. A 25% decrease from baseline
  2. A stable level with no increase
  3. A 50% decrease from baseline Correct answer.
  4. A transient increase followed by a return to baseline

Explanation

According to GCIG criteria for ovarian cancer, a 50% reduction in CA-125 from the pretreatment sample is considered a response, provided it is confirmed and maintained for at least 28 days. A 25% decrease is not sufficient, and stable disease or transient increases do not meet response criteria.

Question 31Systemic Therapy: Chemotherapy, Targeted Agents and Immunotherapy

A patient with metastatic colorectal cancer is starting FOLFOX. Which component of this regimen acts by inhibiting thymidylate synthase?

  1. Leucovorin
  2. 5-Fluorouracil Correct answer.
  3. Irinotecan
  4. Oxaliplatin

Explanation

5-Fluorouracil is an antimetabolite whose active metabolite FdUMP forms a ternary complex with thymidylate synthase and folate, blocking pyrimidine synthesis. Oxaliplatin is a platinum alkylator and leucovorin is a folinic acid modulator rather than the cytotoxic antimetabolite itself. Irinotecan inhibits topoisomerase I and belongs to a different regimen (FOLFIRI).

Question 32Systemic Therapy: Chemotherapy, Targeted Agents and Immunotherapy

Before administering trastuzumab to a patient with HER2-positive breast cancer, which baseline assessment is most important to obtain?

  1. Pulmonary function tests
  2. Serum amylase
  3. Audiology testing
  4. Left ventricular ejection fraction Correct answer.

Explanation

Trastuzumab carries a boxed warning for cardiomyopathy and congestive heart failure, so a baseline cardiac evaluation including LVEF is required before and during therapy. Amylase, audiometry, and pulmonary function are not standard baseline monitoring for this agent. Recognizing cardiotoxicity risk guides serial ejection fraction monitoring.

Question 33Systemic Therapy: Chemotherapy, Targeted Agents and Immunotherapy

Which immune checkpoint inhibitor mechanism describes pembrolizumab?

  1. Anti-PD-1 monoclonal antibody Correct answer.
  2. Anti-PD-L1 monoclonal antibody
  3. Anti-CTLA-4 monoclonal antibody
  4. Anti-VEGF monoclonal antibody

Explanation

Pembrolizumab is a humanized IgG4 monoclonal antibody that binds PD-1 on T cells, blocking interaction with PD-L1 and PD-L2 and restoring antitumor T-cell activity. Ipilimumab is the anti-CTLA-4 agent, while atezolizumab and durvalumab target PD-L1. Bevacizumab targets VEGF and is antiangiogenic rather than immunomodulatory.

Question 34Systemic Therapy: Chemotherapy, Targeted Agents and Immunotherapy

A patient receiving cisplatin develops delayed nausea and vomiting 48 hours after infusion. Which agent is most appropriate for this delayed phase?

  1. Dexamethasone alone at low dose
  2. Metoclopramide
  3. Ondansetron
  4. Aprepitant Correct answer.

Explanation

The delayed emesis phase after highly emetogenic cisplatin is mediated largely by substance P acting at NK1 receptors, so an NK1 antagonist such as aprepitant (or a similar agent) is a cornerstone of delayed prophylaxis. 5-HT3 antagonists like ondansetron are most effective in the acute phase. Guidelines combine an NK1 antagonist with dexamethasone for delayed prevention.

Question 35Systemic Therapy: Chemotherapy, Targeted Agents and Immunotherapy

Which chemotherapy agent class is most characteristically associated with dose-limiting cumulative cardiomyopathy?

  1. Vinca alkaloids
  2. Anthracyclines Correct answer.
  3. Antimetabolites
  4. Taxanes

Explanation

Anthracyclines such as doxorubicin generate reactive oxygen species and topoisomerase II-mediated DNA damage in cardiomyocytes, producing cumulative dose-related cardiomyopathy. Taxanes and vinca alkaloids are primarily neurotoxic and myelosuppressive, and antimetabolites do not characteristically cause cumulative cardiomyopathy. Cumulative dose limits exist specifically for anthracyclines.

Question 36Systemic Therapy: Chemotherapy, Targeted Agents and Immunotherapy

A patient on oxaliplatin reports numbness and tingling in a stocking-glove distribution that worsens with cold exposure. Which toxicity is this?

  1. Hemolytic anemia
  2. Febrile neutropenia
  3. Chemotherapy-induced nausea
  4. Cumulative sensory neuropathy Correct answer.

Explanation

Oxaliplatin causes a characteristic acute cold-triggered dysesthesia and a cumulative sensory peripheral neuropathy that can limit treatment duration. Nausea, febrile neutropenia, and hemolytic anemia are not the described cold-sensitive stocking-glove syndrome. Dose modification may be needed if function is impaired.

Question 37Systemic Therapy: Chemotherapy, Targeted Agents and Immunotherapy

Which oral targeted agent is used in chronic myeloid leukemia by inhibiting BCR-ABL tyrosine kinase?

  1. Erlotinib
  2. Vemurafenib
  3. Imatinib Correct answer.
  4. Ruxolitinib

Explanation

Imatinib inhibits the BCR-ABL fusion tyrosine kinase that drives chronic myeloid leukemia, and it is a landmark example of molecularly targeted therapy. Erlotinib targets EGFR in lung cancer, ruxolitinib inhibits JAK1/2 in myelofibrosis, and vemurafenib targets BRAF V600E. Each agent is matched to its oncogenic driver.

Question 38Systemic Therapy: Chemotherapy, Targeted Agents and Immunotherapy

Which immune-related adverse event is most characteristic of CTLA-4 blockade with ipilimumab?

  1. Interstitial nephritis
  2. Peripheral neuropathy
  3. Hypophysitis Correct answer.
  4. Alopecia

Explanation

CTLA-4 blockade is associated with a distinctive pattern of immune-related toxicity that includes hypophysitis, colitis, and hepatitis. Hypophysitis is notably more frequent with anti-CTLA-4 therapy than with anti-PD-1 agents. Interstitial nephritis, neuropathy, and alopecia are not the hallmark CTLA-4 events.

Question 39Systemic Therapy: Chemotherapy, Targeted Agents and Immunotherapy

A patient with non-small cell lung cancer has an activating EGFR exon 19 deletion. Which targeted approach is most appropriate first-line?

  1. Pembrolizumab monotherapy
  2. Crizotinib
  3. Osimertinib Correct answer.
  4. Bevacizumab plus chemotherapy

Explanation

Activating EGFR exon 19 deletions and L858R mutations predict sensitivity to EGFR tyrosine kinase inhibitors, and third-generation osimertinib is a preferred first-line option with strong intracranial activity. Pembrolizumab monotherapy is less effective in EGFR-mutant tumors and can carry added toxicity. Crizotinib targets ALK or ROS1, not EGFR.

Question 40Systemic Therapy: Chemotherapy, Targeted Agents and Immunotherapy

Which toxicity requires immediate discontinuation and urgent evaluation in a patient receiving high-dose methotrexate?

  1. Mild transaminase elevation
  2. Alopecia
  3. Transient nausea
  4. Acute kidney injury with rising creatinine Correct answer.

Explanation

High-dose methotrexate is cleared renally, so acute kidney injury impairs drug elimination and can precipitate severe systemic toxicity including myelosuppression and mucositis. Rising creatinine therefore demands urgent intervention such as leucovorin rescue, hydration, and possibly glucarpidase. Mild transaminase rises, nausea, and alopecia are common and generally manageable.

Question 41Systemic Therapy: Chemotherapy, Targeted Agents and Immunotherapy

Which laboratory abnormality is the most important to identify before starting a patient on a checkpoint inhibitor to avoid a flare of autoimmune disease?

  1. Vitamin D deficiency
  2. Active autoimmune condition requiring systemic immunosuppression Correct answer.
  3. Mild iron deficiency
  4. Elevated alkaline phosphatase of unclear cause

Explanation

Checkpoint inhibitors can exacerbate pre-existing autoimmune disease, so a history of active autoimmune conditions requiring systemic immunosuppression is a key consideration that may contraindicate or delay therapy. Iron deficiency, isolated alkaline phosphatase elevation, and vitamin D deficiency are not the primary determinants of checkpoint inhibitor safety. Careful baseline autoimmune assessment guides risk stratification.

Question 42Systemic Therapy: Chemotherapy, Targeted Agents and Immunotherapy

A patient on paclitaxel develops acute severe hypersensitivity with hypotension and bronchospasm during the infusion. What is the most appropriate immediate action?

  1. Stop the infusion and treat with epinephrine and supportive care Correct answer.
  2. Increase the infusion rate to finish faster
  3. Slow the infusion and continue
  4. Give oral diphenhydramine and continue at the same rate

Explanation

Paclitaxel can cause acute hypersensitivity reactions, sometimes related to the Cremophor vehicle, and management requires immediately stopping the infusion and treating anaphylaxis with epinephrine, oxygen, and fluids. Continuing the infusion or merely slowing it risks worsening the reaction. Premedication reduces but does not eliminate this risk.

Question 43Systemic Therapy: Chemotherapy, Targeted Agents and Immunotherapy

Which statement best describes the mechanism of action of immune checkpoint inhibitors?

  1. They directly lyse tumor cells by crosslinking DNA
  2. They inhibit angiogenesis by binding VEGF
  3. They deplete regulatory T cells through antibody-dependent cellular cytotoxicity only
  4. They block inhibitory receptors or ligands that restrain T-cell activity Correct answer.

Explanation

Checkpoint inhibitors bind inhibitory receptors such as PD-1 or CTLA-4, or their ligands, releasing brakes on T-cell activation and enabling antitumor immunity. They do not directly crosslink DNA or act primarily through antiangiogenesis. This mechanism explains both delayed responses and immune-related toxicities.

Question 44Systemic Therapy: Chemotherapy, Targeted Agents and Immunotherapy

Which adverse effect is most characteristic of the proteasome inhibitor bortezomib used in multiple myeloma?

  1. Hemorrhagic cystitis
  2. QT prolongation
  3. Interstitial lung disease
  4. Painful peripheral sensory neuropathy Correct answer.

Explanation

Bortezomib frequently causes a dose-limiting painful peripheral sensory neuropathy, which may require dose reduction or a switch to subcutaneous administration. Interstitial lung disease is more typical of agents like bleomycin or EGFR TKIs, hemorrhagic cystitis of cyclophosphamide or ifosfamide, and QT prolongation of certain TKIs. Monitoring for neuropathy is central to bortezomib therapy.

Question 45Systemic Therapy: Chemotherapy, Targeted Agents and Immunotherapy

A patient with BRAF V600E-mutant melanoma is started on dabrafenib plus trametinib. What is the rationale for combining these agents?

  1. The combination reduces the risk of immune-related colitis
  2. Combined BRAF and MEK inhibition delays resistance and reduces paradoxical MAPK activation Correct answer.
  3. Trametinib reverses dabrafenib-induced neuropathy
  4. The combination eliminates the need for baseline cardiac monitoring

Explanation

Combining a BRAF inhibitor with a MEK inhibitor targets two nodes of the MAPK pathway, improving response durability and reducing cutaneous hyperproliferative effects from paradoxical pathway activation. The combination does not eliminate cardiac or other monitoring needs. It is not designed to prevent immune-related colitis, which is a checkpoint inhibitor toxicity.

Question 46Systemic Therapy: Chemotherapy, Targeted Agents and Immunotherapy

Which monitoring is most important during treatment with the antiangiogenic agent bevacizumab?

  1. Thyroid-stimulating hormone only
  2. Blood pressure and urine protein Correct answer.
  3. Serial audiometry
  4. Pulmonary function testing

Explanation

Bevacizumab, a VEGF-directed antibody, causes hypertension and proteinuria through its effects on vascular and glomerular endothelium, so blood pressure and urinary protein monitoring are essential. Audiometry relates to platinum agents, and thyroid and pulmonary testing are not the primary monitoring for bevacizumab. Recognizing these effects guides dose holds and management.

Question 47Systemic Therapy: Chemotherapy, Targeted Agents and Immunotherapy

A patient receiving irinotecan develops severe diarrhea and neutropenia. Which pharmacogenetic factor is most relevant to irinotecan toxicity?

  1. G6PD deficiency
  2. TPMT deficiency
  3. UGT1A1 poor metabolizer status Correct answer.
  4. CYP2D6 ultrarapid metabolizer status

Explanation

Irinotecan's active metabolite SN-38 is glucuronidated by UGT1A1, and reduced UGT1A1 activity (as in *28 homozygosity) increases SN-38 exposure and the risk of severe neutropenia and diarrhea. CYP2D6 relates to tamoxifen and codeine, TPMT to thiopurines, and G6PD to oxidative hemolysis risk. This pharmacogenetic link supports dose consideration in at-risk patients.

Question 48Systemic Therapy: Chemotherapy, Targeted Agents and Immunotherapy

Which statement about leucovorin in 5-fluorouracil-based regimens is correct?

  1. It is a rescue agent that reduces 5-FU efficacy
  2. It stabilizes the 5-FU-thymidylate synthase complex and enhances cytotoxicity Correct answer.
  3. It prevents 5-FU-induced peripheral neuropathy
  4. It directly inhibits topoisomerase I

Explanation

Leucovorin increases intracellular reduced folate pools that stabilize the ternary complex of FdUMP with thymidylate synthase, enhancing 5-FU inhibition of pyrimidine synthesis. It is not a topoisomerase inhibitor, and in this context it is a biochemical modulator rather than a rescue agent. It does not prevent 5-FU neuropathy, which is not a typical 5-FU toxicity.

Question 49Systemic Therapy: Chemotherapy, Targeted Agents and Immunotherapy

Which agent is a monoclonal antibody targeting the PD-L1 ligand and is used in extensive-stage small cell lung cancer in combination with chemotherapy?

  1. Ipilimumab
  2. Pembrolizumab
  3. Atezolizumab Correct answer.
  4. Nivolumab

Explanation

Atezolizumab binds PD-L1 and has been used with platinum-based chemotherapy as first-line therapy in extensive-stage small cell lung cancer. Nivolumab and pembrolizumab target PD-1, and ipilimumab targets CTLA-4. Knowing the specific molecular target distinguishes these agents.

Question 50Systemic Therapy: Chemotherapy, Targeted Agents and Immunotherapy

A patient on tamoxifen for hormone receptor-positive breast cancer asks about drug interactions. Which co-medication most reduces tamoxifen efficacy by inhibiting CYP2D6 conversion to endoxifen?

  1. Atorvastatin
  2. Omeprazole
  3. Paroxetine Correct answer.
  4. Amoxicillin

Explanation

Tamoxifen is converted by CYP2D6 to the more potent metabolite endoxifen, and strong CYP2D6 inhibitors such as paroxetine can lower endoxifen concentrations. Amoxicillin, atorvastatin, and omeprazole are not strong CYP2D6 inhibitors and are not the classic interaction of concern. Clinicians often select alternative antidepressants when possible.