Oncology Syllabus

Name three common serum tumor markers and the cancers they are associated with.

PSA — prostate cancer; CA-125 — ovarian cancer; CEA — colorectal (and other GI) cancers; AFP — hepatocellular carcinoma and germ cell tumors; CA 19-9 — pancreatic cancer.

What is the difference between tumor grade and tumor stage?

Grade describes how abnormal (differentiated) the cancer cells look under the microscope, indicating aggressiveness. Stage describes the anatomic extent of spread (size, nodes, metastases). Grade is microscopic; stage is anatomic.

Explain the TNM staging system.

T = size/extent of the primary Tumor; N = regional lymph Node involvement; M = distant Metastasis (M0 absent, M1 present). Categories combine into an overall stage grouping (I–IV).

Define "surgical margin" and the terms R0, R1, R2.

The margin is the rim of normal tissue around the excised tumor. R0 = no residual tumor (margins clear), R1 = microscopic residual tumor at margin, R2 = macroscopic (visible) residual tumor left behind.

Distinguish neoadjuvant from adjuvant therapy.

Neoadjuvant therapy is given before the primary (usually surgical) treatment to shrink the tumor. Adjuvant therapy is given after primary treatment to eliminate residual micrometastatic disease and reduce recurrence.

What is the biological rationale for fractionation of radiation therapy (the "4 R's")?

Splitting the total dose into fractions exploits differences between tumor and normal tissue via the 4 R's: Repair of sublethal damage, Reassortment (redistribution) into radiosensitive cell-cycle phases, Repopulation, and Reoxygenation of hypoxic tumor cells.

What is the SI unit of absorbed radiation dose, and how is it defined?

The gray (Gy), defined as one joule of energy absorbed per kilogram of tissue: $$1\ \text{Gy} = 1\ \frac{\text{J}}{\text{kg}}$$

Differentiate external beam radiotherapy from brachytherapy.

External beam radiotherapy delivers radiation from a machine (e.g., linear accelerator) outside the body. Brachytherapy places radioactive sources directly within or adjacent to the tumor (e.g., prostate seeds), delivering high local dose with rapid falloff.

How does the primary mechanism of most cytotoxic chemotherapy relate to the cell cycle?

Most cytotoxic agents target rapidly dividing cells by damaging DNA or disrupting mitosis. This explains toxicity to normal fast-dividing tissues (bone marrow, GI mucosa, hair follicles), causing myelosuppression, mucositis, and alopecia.

Match these chemotherapy classes to their mechanism: alkylating agents, antimetabolites, taxanes, vinca alkaloids.

Alkylating agents (e.g., cyclophosphamide) crosslink DNA. Antimetabolites (e.g., methotrexate, 5-FU) mimic nucleotides to block DNA synthesis. Taxanes (e.g., paclitaxel) stabilize microtubules. Vinca alkaloids (e.g., vincristine) inhibit microtubule assembly.

State the log-kill hypothesis of chemotherapy.

A given dose of chemotherapy kills a constant fraction (not a constant number) of tumor cells, regardless of tumor size. Thus repeated cycles are needed because each reduces the cell population by a fixed logarithmic fraction (e.g., 99% = 2 logs).

What is the dose-limiting toxicity most commonly seen with cytotoxic chemotherapy, and its most dangerous consequence?

Myelosuppression (bone marrow suppression). The most dangerous consequence is neutropenia leading to febrile neutropenia and life-threatening infection; also anemia and thrombocytopenia.

How do targeted therapies differ fundamentally from conventional chemotherapy?

Targeted therapies act on specific molecules (mutated proteins, receptors, or pathways) driving a particular cancer, sparing most normal cells. Chemotherapy broadly kills all rapidly dividing cells, so targeted agents generally have more specific, distinct toxicity profiles.

What is the naming convention difference between "-mab" and "-nib" drugs?

"-mab" denotes a monoclonal antibody (large protein, e.g., trastuzumab, rituximab), usually targeting extracellular/surface molecules. "-nib" denotes a small-molecule inhibitor (e.g., imatinib, erlotinib), usually targeting intracellular kinases.

What genetic abnormality does imatinib target, and in which cancer?

Imatinib inhibits the BCR-ABL fusion tyrosine kinase produced by the Philadelphia chromosome, t(9;22), in chronic myeloid leukemia (CML). It also targets c-KIT in GIST.

How do immune checkpoint inhibitors work, and name two checkpoint targets.

They block inhibitory signals that tumors use to evade T cells, "releasing the brakes" on the immune response. Targets include CTLA-4 (e.g., ipilimumab) and the PD-1/PD-L1 axis (e.g., pembrolizumab, nivolumab; atezolizumab for PD-L1).

What is CAR-T cell therapy?

Chimeric Antigen Receptor T-cell therapy: a patient's T cells are genetically engineered to express a receptor recognizing a tumor antigen (e.g., CD19 in B-cell malignancies), expanded, and reinfused to kill cancer cells. Used in refractory ALL and lymphomas.

Explain the rationale of hormone (endocrine) therapy and give one example each for breast and prostate cancer.

It blocks hormones that fuel hormone-dependent tumor growth. Breast cancer (ER-positive): tamoxifen (SERM) or aromatase inhibitors (e.g., anastrozole). Prostate cancer: androgen deprivation via GnRH agonists (e.g., leuprolide) or anti-androgens.

Contrast tamoxifen with aromatase inhibitors in mechanism and patient population.

Tamoxifen is a selective estrogen receptor modulator that competitively blocks the estrogen receptor; used in pre- and post-menopausal women. Aromatase inhibitors block peripheral conversion of androgens to estrogen and are effective mainly in postmenopausal women.

Name the three key receptors tested in breast cancer and their therapeutic significance.

Estrogen receptor (ER) and progesterone receptor (PR) — predict response to hormone therapy; HER2 — if overexpressed/amplified, predicts response to anti-HER2 agents (trastuzumab). "Triple-negative" (ER-, PR-, HER2-) lacks these targets and has poorer prognosis.

Which gene mutations markedly raise hereditary breast and ovarian cancer risk, and what is their normal function?

BRCA1 and BRCA2. They are tumor suppressor genes involved in homologous recombination DNA repair; loss impairs double-strand break repair, and such tumors are sensitive to PARP inhibitors.

Distinguish small cell lung cancer (SCLC) from non-small cell lung cancer (NSCLC) in behavior and treatment.

SCLC (~15%) is highly aggressive, central, strongly smoking-related, spreads early, and is usually treated with chemotherapy plus radiation (rarely surgery). NSCLC (~85%; adenocarcinoma, squamous, large cell) is more amenable to surgery and targeted/immunotherapy.

Which lung cancer type is most common in nonsmokers and most likely to harbor targetable EGFR/ALK mutations?

Adenocarcinoma (a subtype of NSCLC), typically peripheral. It most often carries actionable driver mutations such as EGFR mutations (treated with erlotinib/osimertinib) and ALK rearrangements (treated with crizotinib).

What is the recommended lung cancer screening modality and target population?

Low-dose CT (LDCT) annually, for high-risk adults roughly aged 50–80 with a significant smoking history (e.g., $\geq 20$ pack-years) who currently smoke or quit within 15 years.

What is the primary screening test for colorectal cancer and the precursor lesion it targets?

Colonoscopy (also FIT/FOBT stool tests). It detects and removes adenomatous polyps, the precursor lesions, interrupting the adenoma-to-carcinoma sequence.

Outline the classic adenoma-carcinoma sequence of colorectal cancer with key genes.

Normal epithelium → (APC loss) → adenoma → (KRAS activation) → (DCC/SMAD loss) → (TP53 loss) → carcinoma. Progressive accumulation of mutations drives the transition from benign polyp to invasive cancer.

What tumor marker is used to monitor colorectal cancer, and is it useful for screening?

CEA (carcinoembryonic antigen). It is used to monitor treatment response and detect recurrence, but is NOT recommended for screening due to low sensitivity/specificity for early disease.

What screening test is used for prostate cancer, and what score grades its aggressiveness?

Serum PSA (prostate-specific antigen), often with digital rectal exam. Aggressiveness is graded by the Gleason score, which sums the two most prevalent histologic grade patterns (each 1–5), ranging from 6 to 10.

Classify the four main types of leukemia by cell lineage and acuity.

By lineage (myeloid vs lymphoid) and acuity (acute vs chronic): AML (acute myeloid), ALL (acute lymphoblastic), CML (chronic myeloid), CLL (chronic lymphocytic). Acute forms have immature blasts and rapid onset; chronic forms are more indolent with mature cells.

Which leukemia is most common in young children, and which is most common in older adults?

ALL (acute lymphoblastic leukemia) is the most common childhood cancer/leukemia. CLL (chronic lymphocytic leukemia) is the most common leukemia in older adults in the Western world.

Distinguish Hodgkin from non-Hodgkin lymphoma, including the hallmark cell.

Hodgkin lymphoma has Reed-Sternberg cells, spreads contiguously node-to-node, and has a bimodal age distribution with generally good prognosis. Non-Hodgkin lymphoma is a diverse group lacking Reed-Sternberg cells, spreads non-contiguously, and is far more common.