Cancer treatment, regimens and response

A patient has cT3N1 adenocarcinoma of the rectum; tumor testing shows mismatch repair deficiency (dMMR). The APRN recommends:

1. total neoadjuvant chemoradiation.
   Total neoadjuvant therapy is the standard for pMMR locally advanced rectal cancer; dMMR tumors respond poorly to chemotherapy, and its toxicity can be avoided here.
2. PD-1 blockade with dostarlimab.
   dMMR rectal tumors respond dramatically to PD-1 blockade; in the dostarlimab trial nearly all patients with locally advanced dMMR rectal cancer reached a sustained clinical complete response, sparing chemoradiation and surgery.
3. upfront total mesorectal excision.
   Upfront surgery for a cT3N1 tumor gives up both neoadjuvant treatment and the chance of organ preservation that dMMR status opens.
4. FOLFOX followed by mesorectal excision.
   Neoadjuvant FOLFOX is a pMMR strategy; the mismatch repair result is what redirects this patient to immunotherapy.

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A patient with newly diagnosed metastatic EGFR L858R–mutated lung adenocarcinoma is ECOG 3 because of cancer-related symptoms. The APRN recommends:

1. pembrolizumab monotherapy.
   Immunotherapy alone performs poorly in EGFR-mutant lung cancer and raises pneumonitis risk if a TKI follows.
2. carboplatin-pemetrexed-pembrolizumab.
   Triplet chemoimmunotherapy is poorly tolerated at ECOG 3, and checkpoint inhibitors are ineffective in EGFR-mutant disease.
3. hospice enrollment now.
   Hospice enrollment means forgoing disease-directed treatment, yet an effective, well-tolerated targeted drug can reverse cancer-related decline.
4. osimertinib as first-line therapy.
   Targeted therapy for an EGFR driver often brings rapid responses that restore performance status, so osimertinib is appropriate even at ECOG 3 when the decline comes from the cancer.

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A patient with BRAF V600E–mutated metastatic colorectal cancer progresses after first-line oxaliplatin-based chemotherapy. The APRN recommends:

1. vemurafenib monotherapy.
   BRAF monotherapy is nearly inactive in colorectal cancer because of that EGFR feedback, unlike its activity in melanoma.
2. regorafenib monotherapy.
   Regorafenib is a later-line option with small benefit; using it here skips the targeted regimen this mutation qualifies for.
3. encorafenib plus cetuximab.
   In BRAF V600E colorectal cancer, BRAF inhibition alone triggers feedback EGFR signaling, so encorafenib is paired with cetuximab, the regimen that improved survival after prior therapy in BEACON.
4. dabrafenib-trametinib.
   Dabrafenib-trametinib is the melanoma and lung BRAF regimen; without EGFR blockade its activity in colorectal cancer is modest.

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A patient has borderline resectable pancreatic adenocarcinoma with more than 180° contact with the superior mesenteric vein, which is reconstructible, ECOG 0. The APRN recommends:

1. immediate pancreaticoduodenectomy, then adjuvant therapy.
   Operating first on a tumor encasing the SMV risks a positive margin, and a slow recovery may prevent any systemic therapy afterward.
2. single-agent gemcitabine indefinitely.
   Single-agent gemcitabine without restaging treats the tumor as incurable and abandons the planned resection.
3. palliative biliary bypass.
   Biliary bypass is palliative; it gives up the curative pathway in a fit patient with potentially resectable disease.
4. neoadjuvant FOLFIRINOX, then restaging.
   Borderline resectable tumors get neoadjuvant systemic therapy such as FOLFIRINOX first, which raises margin-negative resection rates, treats micrometastases early, and selects patients whose disease stays localized.

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A patient has newly diagnosed RAS/BRAF wild-type, pMMR metastatic adenocarcinoma of the ascending colon. The APRN recommends first-line:

1. cetuximab monotherapy.
   Single-agent cetuximab is a later-line option and, for a right-sided tumor, the least effective one.
2. FOLFOX plus bevacizumab.
   Right-sided primary tumors gain little from anti-EGFR antibodies even when RAS and BRAF are wild-type, so a chemotherapy doublet with bevacizumab is preferred first-line.
3. FOLFOX plus pembrolizumab.
   Checkpoint inhibitors help dMMR/MSI-high colorectal cancer; this tumor is pMMR, where immunotherapy has little activity.
4. FOLFOX plus panitumumab.
   Anti-EGFR antibodies are the first-line partner for left-sided RAS wild-type tumors; choosing one here ignores primary tumor sidedness.

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A patient with B-cell ALL relapses after CD19-directed CAR T-cell therapy; flow cytometry shows CD19-negative, CD22-positive blasts. The APRN recommends:

1. blinatumomab.
   Blinatumomab is a CD19-directed T-cell engager, so it targets the antigen the leukemia has just lost.
2. inotuzumab ozogamicin.
   Relapse with CD19-negative blasts after CAR-T is antigen escape, so therapy switches to another target; inotuzumab is a CD22-directed antibody-drug conjugate, with hepatic sinusoidal obstruction monitored.
3. rituximab monotherapy.
   Rituximab targets CD20, which is variably expressed in B-ALL and is not active alone against relapsed disease.
4. repeat CD19 CAR-T infusion.
   Reinfusing a CD19-directed product cannot work against CD19-negative blasts.

Item 733107 · Flag an error

After two cycles of ABVD for advanced-stage classic Hodgkin lymphoma, interim PET shows a Deauville score of 2. The APRN anticipates the next step is to:

1. continue AVD without bleomycin.
   A Deauville score of 2 is a complete metabolic response, and in RATHL bleomycin could then be dropped for the remaining cycles without losing efficacy, sparing lung toxicity.
2. escalate to BEACOPP.
   Escalation is the response-adapted step for a positive interim PET (Deauville 4–5), not for a complete metabolic response.
3. proceed to autologous transplant.
   Autologous transplant is for relapsed or refractory Hodgkin lymphoma, not for a patient responding to first-line therapy.
4. add consolidative radiation now.
   Consolidative radiation is not routinely added in advanced-stage disease that is PET-negative after two cycles.

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A patient with metastatic KIT exon 11–mutated GIST has progression on imatinib 800 mg daily. The APRN anticipates which next-line therapy?

1. Regorafenib
   Regorafenib is effective but approved as third-line therapy after both imatinib and sunitinib.
2. Avapritinib
   Avapritinib is used for PDGFRA exon 18 (D842V) GIST, which resists imatinib; it is not the next step for a KIT exon 11 tumor.
3. Sunitinib
   After progression on imatinib, including escalation to 800 mg, sunitinib is the standard second-line agent for KIT-mutant GIST.
4. Ripretinib
   Ripretinib is approved for fourth-line therapy after three prior kinase inhibitors, so it comes too early here.

Item 1009536 · Flag an error

A CMV-seropositive 58-year-old is undergoing matched unrelated allogeneic HSCT for AML. The APRN's CMV prevention plan is:

1. letermovir prophylaxis with weekly CMV PCR
   Letermovir prophylaxis through about day 100 reduces clinically significant CMV infection in seropositive allogeneic recipients, but breakthrough viremia still occurs, so weekly PCR monitoring continues.
2. no prophylaxis; treat CMV end-organ disease
   Waiting for end-organ disease is outdated; CMV is prevented, or treated preemptively at the viremia stage.
3. letermovir prophylaxis with no further CMV PCR
   Stopping PCR monitoring treats prophylaxis as complete protection; breakthrough and resistance occur, and missed viremia can progress to disease.
4. valganciclovir prophylaxis from day 0
   Valganciclovir is myelosuppressive and would threaten engraftment, which is why it is not used for early prophylaxis after allogeneic transplant.

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A woman undergoing interval cytoreductive surgery for stage III ovarian cancer will receive HIPEC with cisplatin 100 mg/m², as in the OVHIPEC-1 trial. To protect her kidneys, the APRN anticipates IV:

1. dexrazoxane
   Dexrazoxane protects the heart from anthracyclines and treats anthracycline extravasation, not cisplatin kidney injury.
2. mesna
   Mesna is also a sulfur-containing protectant, but it neutralizes acrolein in the bladder after ifosfamide or cyclophosphamide.
3. leucovorin calcium
   Leucovorin rescues normal cells from methotrexate; it does not bind platinum.
4. sodium thiosulfate
   With hyperthermic intraperitoneal cisplatin at 100 mg/m², OVHIPEC-1 gave IV sodium thiosulfate, which binds free platinum and reduces nephrotoxicity.

Item 1970971 · Flag an error

Minutes after an Ommaya reservoir injection, staff discover that vincristine, not methotrexate, was given intraventricularly. The APRN's priority is:

1. immediate CSF removal and irrigation
   Intrathecal vincristine causes an ascending myeloencephalopathy that is nearly always fatal; immediate CSF removal and neurosurgical irrigation are the only measures associated with survival.
2. intraventricular leucovorin rescue
   Leucovorin is the rescue for methotrexate, the drug that was supposed to be given, and has no effect on vincristine.
3. IV dexamethasone and close observation
   Steroids and observation waste the short window in which removing the drug can change the outcome.
4. IV glucarpidase as an antidote
   Glucarpidase cleaves methotrexate; reaching for the antidote of the intended drug is the error here.

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A 68-year-old with very high-risk MDS (IPSS-R), ECOG 0, and an HCT-CI score of 1 has a matched donor. The APRN anticipates:

1. allogeneic HCT, reduced-intensity
   Allogeneic transplant is the only curative therapy for higher-risk MDS and improved survival over hypomethylating agents alone in fit older adults (BMT CTN 1102); reduced-intensity conditioning keeps transplant mortality acceptable at 68.
2. azacitidine without transplant
   Hypomethylating therapy alone is the plan for transplant-ineligible patients; it controls but does not cure higher-risk MDS.
3. allogeneic HCT, myeloablative
   Myeloablative conditioning lowers relapse, but at 68 its toxicity outweighs that gain, so fit older adults get reduced-intensity regimens.
4. autologous HCT after azacitidine therapy
   Autologous transplant reinfuses the patient's own diseased marrow and has no role in MDS.

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Six weeks after chemoradiation for stage III NSCLC, a patient on durvalumab consolidation has new dyspnea and ground-glass opacities limited to the radiation field; oxygen saturation is normal (grade 2). The APRN:

1. continues durvalumab and gives antibiotics.
   Antibiotics treat infection, not inflammatory pneumonitis, and continuing durvalumab lets the pneumonitis progress.
2. continues durvalumab and starts prednisone.
   Steroids while the checkpoint inhibitor continues keep driving the inflammation; the label and ASCO guidance withhold the drug at grade 2.
3. holds durvalumab and starts prednisone.
   Grade 2 pneumonitis, whether radiation- or immune-related, is managed by withholding durvalumab and giving prednisone 1–2 mg/kg/day, with rechallenge possible after recovery to grade 1 or less.
4. permanently discontinues durvalumab.
   Permanent discontinuation is for grade 3–4 pneumonitis; at grade 2 the drug is held and may be restarted.

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A patient on adjuvant trastuzumab has an LVEF drop from 62% to 48% (lower limit of normal 50%) with no symptoms. The APRN:

1. Reduces the trastuzumab dose by 25%
   Trastuzumab is not dose-reduced for cardiotoxicity; the dose is either given or held.
2. Continues trastuzumab; echo in 3 months
   Routine 3-month monitoring is for patients whose LVEF stays above the hold thresholds; this decline already meets one.
3. Holds trastuzumab; repeats echo in 4 weeks
   An absolute LVEF fall of 10 points or more to below the lower limit of normal is a labeled reason to hold trastuzumab and repeat LVEF in about 4 weeks; the dysfunction is usually reversible and the drug can often be resumed.
4. Permanently discontinues trastuzumab
   Trastuzumab cardiotoxicity is usually reversible, so permanent discontinuation is reserved for persistent decline or repeated holds, not a first asymptomatic drop.

Item 1971224 · Flag an error

Next-generation sequencing of metastatic colon adenocarcinoma shows KRAS G13D (VAF 42%) and a BRAF missense variant of uncertain significance (VAF 3%). The APRN plans treatment as for:

1. G13D disease for cetuximab
   Early retrospective data suggested G13D tumors might benefit from cetuximab, but prospective trials did not confirm it, and anti-EGFR antibodies are not given for RAS-mutant colorectal cancer.
2. RAS-mutant disease with no BRAF target
   KRAS G13D at a high allele fraction is the clonal driver, so the tumor is treated as RAS-mutant, while a low-fraction BRAF variant of uncertain significance is not a basis for targeted therapy.
3. dual-driver disease needing MEK inhibition
   Treating both variants as drivers over-reads the report, and MEK inhibitor monotherapy is inactive in colorectal cancer.
4. BRAF-mutant disease needing a BRAF inhibitor
   BRAF-directed therapy requires a pathogenic V600E mutation; a 3% variant of uncertain significance is neither a known driver nor a validated target.

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