Modern practice is shifting away from routine Prophylactic Cranial Irradiation (PCI) for extensive-stage small cell lung cancer. This change is driven by a key Japanese study where patients, screened with baseline MRI, showed a survival trend favoring observation with serial MRIs over PCI, challenging a long-standing treatment paradigm.

While Trastuzumab deruxtecan (TDXD) is effective in HER2-low breast cancer, there is no evidence that it benefits patients with HER2-low or HER2-intermediate (IHC 2+/FISH negative) gastric cancer. Its use should be strictly limited to truly HER2-positive cases in this disease.

Immediate therapy is not always required for mesothelioma. For older patients with incidentally discovered, asymptomatic, and slow-growing disease, active observation is a reasonable clinical strategy. This approach avoids treatment-related toxicity while keeping a close watch on disease progression.

With new CNS-active drugs dramatically improving survival after a brain metastasis diagnosis, some experts are now advocating for routine screening brain MRIs in high-risk patients. The goal is to detect asymptomatic lesions early, potentially preventing catastrophic neurologic events like seizures.

The SANO trial's 'watch-and-wait' approach for esophageal cancer avoids initial surgical risks, showing superior survival for the first two years. However, the survival curves cross after that point, suggesting that surgery, despite its initial toll, may offer better long-term outcomes for patients who can tolerate the procedure.

For frail elderly patients with HER2+ gastric cancer, starting with targeted therapy and immunotherapy alone can gauge response and tolerance. Cytotoxic chemotherapy can be added later if the patient's performance status improves, distinguishing disease-related frailty from baseline comorbidities.

For patients with otherwise well-controlled disease who develop isolated oligoprogression in the brain, evidence suggests a better survival outcome from adding local therapy (like SRS) and continuing the current effective systemic therapy, rather than switching the systemic regimen entirely.

When a patient becomes ctDNA positive during surveillance after completing adjuvant therapy, the optimal next step is not immediate systemic chemotherapy. Clinicians should instead initiate intensive imaging (e.g., CT, PET) to identify a potential radiographic recurrence, which may be isolated and resectable.

In the increasingly common scenario of a patient with multiple positive biomarkers, a clear hierarchy exists for treatment decisions. Based on the robustness and maturity of clinical trial data, HER2-directed therapy is the top priority, followed by PD-L1 immunotherapy, with Claudin-18.2 targeting considered third.