CONCEPTUAL SUMMARY
HEAD AND NECK SQUAMOUS CELL CARCINOMA (HNSCC)
Epidemiology and Risk Factors:
- Alcohol is an INDEPENDENT risk factor even without tobacco use.
- HPV status (via p16 IHC) is standard workup for oropharyngeal SCC — has significant prognostic and treatment implications.
- HPV testing is a standard part of the diagnostic workup for oropharyngeal cancer.
- No screening strategy has been shown to reduce mortality in head and neck cancer.
- Isotretinoin is NOT routinely recommended for chemoprevention — toxicity without proven survival benefit.
Adjuvant Treatment After Surgery with Positive Margins:
- Preferred: concurrent chemoradiation with cisplatin 100 mg/m² every 3 weeks × 2–3 doses (Category 1).
- Weekly cisplatin is Category 2B — less preferred.
- Weekly cetuximab is Category 2B — not preferred over chemoradiation.
- Re-resection is a surgical option for positive margins — NOT combined with induction chemotherapy.
- Pembrolizumab/fluorouracil/cisplatin is NOT a recommended induction regimen.
- Weekly carboplatin is NOT a preferred primary systemic therapy option.
Recurrent/Metastatic HNSCC
- First-Line (KEYNOTE-048):
- PD-L1 CPS ≥ 1: single-agent pembrolizumab is Category 1 preferred.
- PD-L1 CPS ≥ 1: pembrolizumab + fluorouracil + platinum (cisplatin or carboplatin) is the preferred combination regimen.
- PD-L1 CPS > 20: pembrolizumab + chemotherapy showed improved OS over cetuximab + chemotherapy.
- Cetuximab + platinum + fluorouracil (EXTREME regimen): Category 1 alternative — NOT preferred when immunotherapy is eligible.
- Cisplatin + paclitaxel: used if pembrolizumab or cetuximab + chemotherapy cannot be used.
- Second-line:
- nivolumab — approved for progression on or after platinum-based therapy (must be > 6 months since prior platinum to be eligible for retreatment distinction).
- Pembrolizumab/fluorouracil/docetaxel is NOT an NCCN regimen.
- Nivolumab + fluorouracil + cisplatin is NOT an NCCN regimen.
Salivary Gland Cancer (Adenoid Cystic Carcinoma):
Standard of care for resectable salivary gland cancer: surgical resection, often followed by adjuvant radiation. Definitive chemoradiation or induction chemotherapy are NOT the initial approach for resectable disease.
MUCOSITIS MANAGEMENT (MASCC Guidelines):
- Prevention — salt and soda solution swish is the only "suggested for use" prevention option.
- Treatment (chemo/radiation-induced) — salt and soda swishes + morphine 0.2% oral rinse are the only "suggested for use" treatment options for mucositis pain.
- Amifostine, doxepin swishes, and dexamethasone swish are NOT recommended for prevention or treatment per MASCC.
- mTOR inhibitor-induced mucositis (everolimus): preferred treatment = dexamethasone mouthwash.
- Sucralfate mouthwash is NOT recommended regardless of cause.
THYROID CANCERS
Papillary Thyroid Carcinoma (PTC):
- Indications for RAI — gross extrathyroid extension (e.g., tracheal involvement), primary tumor > 4 cm, ≥ 5 positive lymph nodes, or combination of 2–4 cm primary + lymph node involvement.
- Lenvatinib: approved for PTC after RAI progression.
- Dabrafenib/trametinib: for advanced PTC with BRAF V600E mutation after RAI — NOT for NRAS mutations. NRAS Q61R mutation does NOT indicate dabrafenib/trametinib.
Follicular Thyroid Carcinoma (FTC):
- Primary tumor > 4 cm OR > 5 positive lymph nodes → RAI preferred.
- Lenvatinib: approved for FTC after RAI progression.
- Dabrafenib/trametinib: only for BRAF V600E mutations — NOT for NRAS activating alterations.
Medullary Thyroid Carcinoma (MTC):
- Does NOT concentrate iodine → RAI is ineffective and NOT recommended.
- Elevated calcitonin and CEA are surveillance markers.
- RET activating mutation present → selpercatinib preferred (RET-targeted inhibitor).
- RET wild-type / no activating alteration → cabozantinib (multikinase inhibitor) preferred.
- Lenvatinib: preferred for DIFFERENTIATED thyroid carcinoma — NOT MTC.
- Doxorubicin: very limited activity in MTC.
- Vandetanib (ZETA trial): most concerning toxicity = prolonged QTc → risk of Torsades de pointes and sudden death; requires REMS program; QTc prolongation occurred in 8% of patients.
- Selpercatinib key toxicities: hypersensitivity reactions + elevated liver enzymes (most common reasons for discontinuation); hypocalcemia (NOT hypercalcemia); acne-form rash, GI perforation, and hypercalcemia are NOT characteristic.
Anaplastic Thyroid Carcinoma (ATC):
- Unresectable, BRAF wild-type: external beam radiation + radiosensitizing doxorubicin (concurrent chemoradiation).
- Vandetanib is for MTC — NOT ATC.
- Sorafenib is for differentiated thyroid carcinoma — NOT ATC.
CNS TUMORS
Glioblastoma (GBM — WHO Grade IV, IDH Wild-Type):
- Standard of care (ALL patients regardless of MGMT status): temozolomide 75 mg/m² PO daily concurrent with radiation → temozolomide 150–200 mg/m² × 5 days every 28 days × 6 cycles (maintenance). Improves 2-year OS by 16% (Stupp trial). MGMT promoter methylated: improved outcomes vs. unmethylated, but SAME regimen used regardless. EGFR amplification/EGFRvIII: NOT currently a biomarker to direct therapy — clinical trials enrolling.
- PCV regimen: used for low-grade astrocytomas and oligodendrogliomas — NOT glioblastoma.
- IDH mutation → produces oncometabolite 2-hydroxyglutarate (2-HG) → inhibits DNA demethylases → global HYPERMETHYLATION (G-CIMP) → blocks cellular differentiation.
Anaplastic Astrocytoma (IDH-Mutant):
- Standard of care: temozolomide concurrent with radiation → adjuvant temozolomide (same Stupp regimen as GBM). Applies regardless of MGMT methylation status.
- PCV chemotherapy: reserved for anaplastic oligodendroglioma with 1p/19q codeletion — NOT astrocytoma.
Anaplastic Oligodendroglioma (IDH-Mutant, 1p/19q Codeleted):
- Standard of care with high-risk features (subtotal resection, older age): radiation followed by PCV (procarbazine + lomustine/CCNU + vincristine). Observation: NOT appropriate with high-risk features.
- Temozolomide + radiation (Stupp protocol): for glioblastoma — NOT oligodendroglioma.
CANCER CACHEXIA/ANOREXIA SYNDROME (CACS):
- First-line appetite stimulants: corticosteroids (prednisolone, dexamethasone) — appropriate for patients with VTE history.
- Megestrol acetate: effective but CONTRAINDICATED in patients with prior VTE (significantly increases thrombosis risk).
- Megestrol acetate side effects: VTE, lower extremity edema, hypertension. Euphoria is NOT a side effect of megestrol — it is a side effect of dronabinol (marinol).
Smoking Cessation in Patients with Seizure History:
- Varenicline and bupropion are relatively CONTRAINDICATED — both lower seizure threshold.
- Preferred: nicotine replacement therapy (NRT) + behavioral counseling. E-cigarettes are NOT FDA-approved for smoking cessation.
PRACTICE QUESTIONS — HEAD AND NECK CANCERS, THYROID CANCERS, AND CNS TUMORS
AG is a 50-year-old man with locally advanced squamous carcinoma of the tonsil, p16 IHC negative (HPV-negative), and cN2 lymphadenopathy. He underwent resection and pathology showed positive margins. Which of the following is most appropriate for AG at this time?
A. Concurrent radiation and weekly cisplatin
B. Concurrent radiation and every-3-week cisplatin
C. Concurrent radiation with weekly cetuximab
D. Docetaxel/fluorouracil/cisplatin then re-resection
Answer: B. Concurrent radiation and every-3-week cisplatin
Explanation: Since AG had positive margins after surgery, re-resection is an option but NOT combined with induction chemotherapy.
- Cisplatin 100 mg/m² every 3 weeks × 2–3 doses is the PREFERRED chemotherapy combination with concurrent radiation — it is the Category 1 standard for positive margins.
- Weekly cisplatin (option A) is Category 2B — less preferred.
- Weekly cetuximab (option C) is also Category 2B — not preferred over concurrent chemoradiation.
- Docetaxel/fluorouracil/cisplatin then re-resection (option D) is not a recommended approach — induction chemotherapy before re-resection is not endorsed by guidelines.
AG returns at 12 months with a new right lung lesion confirmed as recurrent SCC. PD-L1 CPS = 50. What is the most appropriate therapy for AG at this time?
A. Cetuximab + fluorouracil + cisplatin
B. Pembrolizumab + fluorouracil + cisplatin
C. Cisplatin + paclitaxel
D. Nivolumab
Explanation: AG has recurrent/metastatic HNSCC with PD-L1 CPS = 50 — this strongly favors pembrolizumab-based therapy per KEYNOTE-048. For CPS ≥ 20 (and especially CPS ≥ 50), pembrolizumab + chemotherapy demonstrated improved OS over the EXTREME regimen (cetuximab + chemotherapy). The cetuximab + fluorouracil + cisplatin regimen (EXTREME, option A) is a Category 1 alternative but is NOT preferred over pembrolizumab-containing therapy when the patient is eligible. Cisplatin + paclitaxel (option C) is used if pembrolizumab or cetuximab + chemo cannot be administered. Nivolumab (option D) is approved for SECOND-LINE therapy after progression on platinum — it is not the first-line preferred option for recurrent/metastatic HNSCC.
[/expand]AK is a 66-year-old man starting cisplatin and radiation for locally advanced oropharyngeal cancer. He is a current smoker. What would you counsel him on regarding mucositis prevention?
A. He will receive amifostine prior to each cisplatin, so he won't need to do anything at home
B. He will need to swish and spit with doxepin solution before each radiation treatment
C. He will need to swish and spit with a salt and soda solution
D. He will receive dexamethasone swish and spit prior to each cisplatin, so he won't need to do anything at home
Answer: C. He will need to swish and spit with a salt and soda solution
Explanation:
For AK, you would counsel him that he will need to swish and spit with a salt and soda solution (Option C) regarding mucositis prevention.
According to the sources, this selection is based on the following:
- Basic Oral Care Protocols: Clinical guidelines recommend that basic oral care (BOC) protocols should be utilized for all cancer patients regardless of their treatment modality to prevent mucositis. These protocols specifically include the use of bland saline and/or sodium bicarbonate (salt and soda) mouth rinses.
- Guideline Support: One source explicitly identifies a salt and soda solution as the only "suggested for use" option for the prevention of mucositis based on MASCC guidelines.
- Addressing Other Options:
- Amifostine (Option A): Guidelines explicitly recommend against the use of amifostine to prevent oral mucositis associated with radiation therapy for head and neck cancer.
- Doxepin (Option B): Doxepin rinses are used for the treatment of acute pain associated with existing mucositis, rather than as a preventive measure.
- Dexamethasone (Option D): While dexamethasone rinses have shown benefit in preventing stomatitis caused by targeted agents (specifically mTOR inhibitors like everolimus), they are not the standard preventive measure for patients receiving traditional cisplatin and radiation.
Additionally, because AK is a current smoker, he should be counseled on smoking cessation, as smoking during radiation therapy more than doubles the risk of disease progression or death and increases the risk of treatment-associated complications.
[/expand]HK is a 63-year-old woman receiving cisplatin and radiation for locally advanced oropharyngeal cancer, HPV-negative. She presents with terrible mucositis — able to swallow water but not food. Based on MASCC Guidelines, in addition to salt and soda swishes, what would you counsel her on regarding mucositis treatment?
A. Add amifostine prior to each cisplatin
B. Add morphine swishes for pain
C. Add doxepin swishes for pain
D. Add dexamethasone swish and spit
Explanation: Per MASCC guidelines, salt and soda swishes + morphine 0.2% oral rinse are the ONLY "suggested for use" options for TREATMENT of chemoradiation-induced mucositis pain. Amifostine (option A) is not recommended by MASCC for mucositis treatment. Doxepin swishes (option C) are NOT recommended per MASCC guidelines in this setting. Dexamethasone swish (option D) is appropriate for mTOR inhibitor-induced mucositis specifically — NOT for chemoradiation-induced mucositis treatment.
[/expand]HN is a 62-year-old woman on exemestane + everolimus for metastatic ER+ breast cancer who developed oral mucositis despite regular saline-based oral rinses. Which is most appropriate for HN to manage her mucositis at this time?
A. Dexamethasone mouthwash
B. 2% viscous lidocaine oral rinse
C. Sucralfate oral rinse
D. Morphine 0.2% oral rinse
Answer: A. Dexamethasone mouthwash
Explanation: HN's mucositis is caused by everolimus — an mTOR inhibitor. For mTOR inhibitor-induced mucositis, dexamethasone mouthwash is the PREFERRED treatment. Viscous lidocaine (option B) and morphine rinses (option D) have shown benefit in chemotherapy/radiation-induced mucositis but dexamethasone is specifically preferred for mTOR inhibitor-related mucositis. Sucralfate mouthwash (option C) is NOT recommended for oral mucositis management regardless of the cause — this is a consistent MASCC guideline statement.
[/expand]CA is a 65-year-old woman who underwent total thyroidectomy for papillary thyroid carcinoma. Pathology: 6 of 33 lymph nodes positive, left tracheal resection showed PTC (gross extrathyroid extension). What is the most appropriate therapy for CA at this time?
A. Observation
B. Lenvatinib
C. Radioactive iodine
D. Dabrafenib/trametinib
Explanation: RAI is the preferred next step because CA has gross extrathyroid extension (tracheal involvement) — a strong indication for RAI. Additionally, she has ≥ 5 positive lymph nodes (6 positive) and a primary tumor in the 2–4 cm range — both additional factors favoring RAI recommendation. Lenvatinib (option B) is approved for PTC but only after progression on RAI — not as initial therapy. Dabrafenib/trametinib (option D) can be considered for BRAF V600E-mutated advanced PTC after RAI — but mutational status is not confirmed, and RAI should come first. Observation (option A) is not appropriate given the high-risk features.
[/expand]JA is a 67-year-old man with medullary thyroid carcinoma. He has metastatic lung disease with elevated calcitonin. Germline RET testing was negative. Tumor NGS shows a RET M918T alteration. He was previously started on vandetanib.
Which treatment option is most appropriate for JA at this time?
A. Cabozantinib
B. Lenvatinib
C. Selpercatinib
D. Radioactive iodine
Explanation: JA has an activating RET alteration (RET M918T) identified on tumor NGS. The RET-targeted inhibitor selpercatinib is the preferred therapy for patients with a RET activating mutation in MTC. Cabozantinib (option A) is preferred for RET wild-type MTC or in the absence of a RET activating alteration — not the preferred choice when a RET-targeted agent is available. Lenvatinib (option B) is preferred for differentiated thyroid carcinoma — NOT medullary thyroid carcinoma. Radioactive iodine (option D) is not effective in MTC because MTC does not concentrate iodine.
[/expand]JA is started on selpercatinib. Which of the following side effects should be discussed with JA prior to starting therapy?
A. Acne-form rash
B. Hypersensitivity
C. GI perforation
D. Hypercalcemia
Explanation: Though rare, hypersensitivity reactions have been reported with selpercatinib and were the most common treatment-related toxicity leading to discontinuation, along with elevated liver enzymes (hepatotoxicity). Acne-form rash (option A) is characteristic of EGFR inhibitors — not selpercatinib. GI perforation (option C) is not a characteristic of selpercatinib toxicity. Hypocalcemia (not hypercalcemia) has been reported with selpercatinib.
[/expand]JA was started on vandetanib for MTC. According to the main trial (ZETA) supporting vandetanib use, what was the most concerning side effect requiring a REMS program? A. Fetal harm B. Prolonged QTc C. GI perforation D. Stevens-Johnson syndrome
[expand] Answer: B. Prolonged QTcExplanation: In the ZETA trial, 19 patients (8%) experienced QTc prolongation. Because of this risk for Torsades de pointes and sudden death, vandetanib is only available from certified REMS program providers. This is the primary safety concern that distinguishes vandetanib from other agents and requires special prescribing authorization. Fetal harm, GI perforation, and Stevens-Johnson syndrome are not the defining REMS-triggering toxicity for vandetanib.
[/expand]GG is a 42-year-old man with newly diagnosed anaplastic oligodendroglioma of the right temporal lobe after sub-total resection. Mutational analysis: 1p19q codeleted, IDH-mutant, MGMT methylated.
What is the most appropriate therapy for GG at this time?
A. Observation
B. Radiation followed by procarbazine, lomustine (CCNU), and vincristine
C. Temozolomide with concurrent radiation
D. Temozolomide with concurrent radiation followed by temozolomide maintenance
Explanation: GG has anaplastic oligodendroglioma with 1p/19q codeletion and IDH mutation — the defining molecular features of oligodendroglioma. He also has high-risk features (sub-total resection, age 42). Per NCCN guidelines, radiation followed by PCV is the preferred standard of care for anaplastic oligodendroglioma with 1p/19q codeletion. Observation (option A) is not appropriate given high-risk features. Temozolomide + radiation (options C and D) — the Stupp protocol — is the standard for GLIOBLASTOMA, not oligodendroglioma. PCV is specifically the correct chemotherapy for IDH-mutant 1p/19q codeleted oligodendroglioma.
[/expand]CS is a 60-year-old man with locally advanced squamous cell carcinoma of the oral cavity, 20-pack year smoking history. He underwent resection with positive margins. Which is most appropriate first-line treatment at this time?
A. Pembrolizumab + fluorouracil + cisplatin
B. Concurrent radiation and weekly cetuximab
C. Concurrent radiation and every-3-week cisplatin
D. Concurrent radiation with weekly carboplatin
Explanation: For positive margins after surgical resection of locally advanced HNSCC, the NCCN preferred adjuvant treatment is concurrent chemoradiation with cisplatin 100 mg/m² every 3 weeks × 2–3 doses. Pembrolizumab/fluorouracil/cisplatin (option A) is not a recommended induction regimen for locally advanced disease with positive margins. Weekly cetuximab (option B) is Category 2B — less preferred over high-dose cisplatin every 3 weeks. Weekly carboplatin (option D) is NOT a preferred primary systemic therapy option in this setting.
[/expand]CS returns at 6 months with recurrent HNSCC (new right lung lesion). PD-L1 CPS = 10. What is the most appropriate therapy for CS at this time?
A. Pembrolizumab + fluorouracil + docetaxel
B. Pembrolizumab + fluorouracil + carboplatin
C. Cisplatin + paclitaxel
D. Nivolumab + fluorouracil + cisplatin
Explanation: CS has recurrent/metastatic HNSCC with PD-L1 CPS = 10 (≥ 1), supporting pembrolizumab-containing therapy per KEYNOTE-048. Pembrolizumab + fluorouracil + platinum (cisplatin or carboplatin) is the guideline-preferred combination regimen. Pembrolizumab + fluorouracil + docetaxel (option A) is NOT an NCCN regimen. Cisplatin + paclitaxel (option C) is a backup when pembrolizumab or cetuximab-based regimens cannot be used. Nivolumab + fluorouracil + cisplatin (option D) is NOT an NCCN regimen — nivolumab is a second-line single-agent option, not a combination first-line option.
[/expand]LH is a 52-year-old woman with an 8 cm predominantly thyroid mass, 8 of 33 positive lymph nodes — follicular thyroid carcinoma. NGS shows NRAS Q61R alteration. No distant metastases. What is the most appropriate therapy for LH at this time?
A. Observation
B. Radioactive iodine
C. Dabrafenib/trametinib
D. Lenvatinib
Explanation: RAI is the appropriate next step because LH has both a primary tumor > 4 cm (8 cm) AND > 5 positive lymph nodes (8 positive) — both are indications for RAI in follicular thyroid carcinoma. Lenvatinib (option D) is approved for FTC but only AFTER RAI progression — not upfront. Dabrafenib/trametinib (option C) can be considered for BRAF V600E-mutated advanced thyroid cancer after RAI — but LH has an NRAS Q61R mutation, NOT a BRAF V600E mutation; dabrafenib/trametinib is NOT indicated for NRAS mutations. Observation (option A) is not appropriate given the tumor size and lymph node involvement.
[/expand]LM is a 62-year-old woman with glioblastoma, IDH wild-type, WHO Grade 4, MGMT promoter methylated. She also has EGFR amplification and EGFRvIII mutation. ECOG 0 after gross total resection. What is the most appropriate therapy for LM at this time?
A. Observation
B. Temozolomide with concurrent radiation followed by temozolomide maintenance
C. Osimertinib with concurrent radiation followed by osimertinib maintenance
D. Radiation followed by procarbazine, lomustine (CCNU), and vincristine
Explanation: The standard of care for glioblastoma is the Stupp protocol: temozolomide 75 mg/m² PO daily concurrent with radiation → temozolomide 150–200 mg/m² × 5 days every 28 days × 6 cycles. This improves 2-year OS by 16%. Although MGMT methylation predicts improved outcomes, the SAME regimen is used regardless of MGMT status — unmethylated patients still derive benefit. EGFR amplification and EGFRvIII (option C) are present in this patient — however, EGFR amplification is NOT currently a biomarker to direct therapy for GBM; anti-EGFR therapies have lower responses and clinical trials are still enrolling. Osimertinib is an EGFR TKI for NSCLC — not GBM. PCV (option D) is reserved for anaplastic oligodendrogliomas with 1p/19q codeletion — not GBM.
[/expand]PL is a 40-year-old man with newly diagnosed IDH-mutant, MGMT-unmethylated anaplastic astrocytoma after gross total resection. What therapy should PL receive?
A. Radiation alone
B. Radiation followed by PCV
C. Temozolomide with concurrent radiation
D. Temozolomide with concurrent radiation followed by temozolomide maintenance
Explanation: The standard of care for anaplastic astrocytoma (IDH-mutant) is temozolomide concurrent with radiation followed by adjuvant temozolomide cycles — the same Stupp regimen as GBM. This applies regardless of MGMT methylation status. Radiation alone (option A) is insufficient for anaplastic astrocytoma. PCV chemotherapy (option B) is reserved for anaplastic oligodendrogliomas with 1p/19q codeletion — NOT astrocytoma. PL has an astrocytoma without 1p/19q codeletion — PCV is not appropriate.
[/expand]Which of the following is correct regarding head and neck cancer?
A. Screening was shown to decrease mortality
B. Isotretinoin is recommended as chemoprevention
C. HPV testing is part of oropharyngeal cancer diagnosis
D. Alcohol alone is not a risk factor
Explanation: HPV status, determined by p16 immunohistochemistry (IHC), is a standard part of the diagnostic workup for oropharyngeal squamous cell carcinoma — it has significant prognostic implications (HPV-positive disease has much better prognosis) and treatment implications. Option A is incorrect — no screening strategy has been shown to reduce mortality in head and neck cancer. Option B is incorrect — isotretinoin is NOT routinely recommended for chemoprevention due to toxicity and no proven survival benefit. Option D is incorrect — alcohol is a well-established INDEPENDENT risk factor for head and neck cancer, even without tobacco use.
[/expand]A 67-year-old woman has a 2.2 × 3.1 cm mass within the right parotid gland (Stage II). Core needle biopsy shows moderately differentiated adenoid cystic carcinoma. What is the most appropriate next step?
A. Stereotactic beam radiation therapy to the mass
B. Definitive chemoradiation utilizing cetuximab
C. Docetaxel, cisplatin, and infusional 5-FU × 3 cycles followed by definitive radiation
D. Resection
Explanation: The standard of care for resectable salivary gland cancers, including adenoid cystic carcinoma, is surgical resection. This is often followed by adjuvant radiation due to the high risk of local recurrence, but the definitive next step for a resectable primary tumor is surgery. Stereotactic radiation (option A), definitive chemoradiation (option B), and induction chemotherapy followed by radiation (option C) are not the standard initial approaches for resectable salivary gland tumors.
[/expand]A 73-year-old male has metastatic p16-positive squamous cell carcinoma (base of tongue primary with innumerable FDG-avid lung nodules). PD-L1 CPS = 25%. What is the most appropriate recommendation?
A. Cisplatin + 5-FU + cetuximab
B. Pembrolizumab
C. Cisplatin + 5-FU + cetuximab
D. Cisplatin + 5-FU
Explanation: This patient has metastatic (Stage IVC) p16-positive HNSCC with PD-L1 CPS = 25 (≥ 1). Per KEYNOTE-048, single-agent pembrolizumab is a Category 1 first-line recommendation for patients with CPS ≥ 1. The EXTREME regimen (cetuximab + platinum + 5-FU) is a Category 1 alternative but is NOT preferred over pembrolizumab-based therapy in immunotherapy-eligible patients. For patients with CPS ≥ 20, pembrolizumab-containing therapy showed improved OS over the EXTREME regimen.
[/expand]NM is a 34-year-old woman treated for stage III tongue cancer. Her weight dropped from 80 kg to 40 kg after chemoradiation. She has a history of VTE and is diagnosed with cancer anorexia-cachexia syndrome (CACS). What treatment should be initiated?
A. Nutrition supplements plus prednisolone 10 mg BID
B. Nutrition supplements plus megestrol 400 mg BID
C. Nutrition supplements plus omega-3 fatty acid capsule once daily
D. Nutrition supplements plus methylphenidate 20 mg once daily
Explanation: For cancer cachexia, corticosteroids (prednisolone, dexamethasone) are first-line options to improve appetite and well-being. Megestrol acetate (option B) is also effective for appetite stimulation, but it is CONTRAINDICATED in this patient due to her history of VTE — megestrol significantly increases the risk of thrombosis. Omega-3 fatty acids (option C) have insufficient evidence to be recommended as primary treatment for CACS. Methylphenidate (option D) addresses fatigue but is not an appetite stimulant.
[/expand]JK is a 50-year-old man with stage III oral cancer and a history of seizures (related to brain metastases) who wants to quit smoking. Which smoking cessation approach is recommended for JK?
A. Varenicline + NRT
B. Varenicline + bupropion
C. NRT + behavioral therapy
D. E-cigarettes + behavioral therapy
Explanation: Both varenicline (option A, B) and bupropion lower the seizure threshold and are RELATIVELY CONTRAINDICATED in patients with a history of seizures. The safest effective pharmacotherapy option is nicotine replacement therapy (NRT) combined with behavioral counseling. E-cigarettes (option D) are NOT FDA-approved for smoking cessation and are not recommended as a cessation strategy.
[/expand]A 69-year-old man has a 5.2 cm anaplastic thyroid carcinoma encasing the larynx and esophagus, deemed unresectable. BRAF V600E mutation is negative. What is the most appropriate next step?
A. External beam radiation therapy to the mass with radiosensitizing doxorubicin
B. Total thyroidectomy
C. Vandetanib
D. Sorafenib
Explanation: For unresectable, BRAF wild-type anaplastic thyroid cancer (ATC), the standard approach is aggressive local therapy with concurrent chemoradiation — external beam radiation + radiosensitizing doxorubicin. Total thyroidectomy (option B) is not possible since the tumor is unresectable. Vandetanib (option C) is used for medullary thyroid carcinoma — NOT ATC. Sorafenib (option D) is used for differentiated thyroid carcinoma (RAI-refractory) — NOT ATC. For BRAF V600E-mutated unresectable ATC, dabrafenib + trametinib would be the targeted option, but BRAF is wild-type here.
[/expand]A 52-year-old woman with RET-negative medullary thyroid cancer presents with progressive metastatic disease (pulmonary nodules, severe diarrhea, rising calcitonin/CEA) one year after radiation. What is the most appropriate next step?
A. Supportive care and hospice referral
B. Doxorubicin
C. Radionuclide scan followed by radioactive iodine therapy
D. Cabozantinib
Explanation: For progressive metastatic RET-negative (no activating RET alteration) MTC, cabozantinib (a multikinase inhibitor) is the FDA-approved and preferred treatment option — it provides disease control in this setting. Supportive care alone (option A) is premature, given that active systemic treatment is available and the patient is likely functional. Doxorubicin (option B) has very limited activity in MTC. Radioactive iodine (option C) is INEFFECTIVE in MTC because medullary thyroid carcinoma does NOT concentrate iodine — RAI should never be used for MTC.
[/expand]Which of the following is correct regarding IDH mutation?
A. Is associated with hypomethylation of DNA and prevention of differentiation
B. Is associated with hypermethylation of DNA and prevention of differentiation
C. Is associated with hypomethylation of DNA and increasing of differentiation
D. Is associated with hypermethylation of DNA and increasing of differentiation
Explanation: IDH mutations produce the oncometabolite 2-hydroxyglutarate (2-HG), which inhibits alpha-ketoglutarate-dependent DNA demethylases. This results in GLOBAL HYPERMETHYLATION of DNA — the CpG island methylator phenotype (G-CIMP). This hypermethylation disrupts normal gene expression patterns and BLOCKS cellular differentiation. Options A and C are incorrect — the effect is HYPERmethylation, not hypomethylation. Option D is incorrect — hypermethylation is correct but it PREVENTS (not increases) differentiation.
[/expand]TG has lost 20 pounds on chemotherapy. The oncologist wants to start megestrol acetate.
Which is NOT a side effect to counsel TG on?
A. Venous thromboembolism
B. Lower extremity edema
C. Euphoria
D. Hypertension
Explanation: Common side effects of megestrol acetate include venous thromboembolism (VTE), fluid retention/lower extremity edema, and hypertension. Euphoria is NOT a side effect of megestrol acetate — it is a known side effect of dronabinol (THC-based cannabinoid), another appetite stimulant. This distinction is high-yield: megestrol = VTE risk; dronabinol = euphoria/CNS effects.
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