Background: Cisplatin-based chemotherapy remains a key treatment option for advanced non-small cell lung cancer (NSCLC), particularly in patients with squamous histology or those who develop histologic transformation after resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Squamous transformation represents an uncommon but clinically challenging resistance mechanism, often associated with limited therapeutic options and continued reliance on platinum-based regimens. However, prior platinum-associated acute tubular necrosis (ATN), particularly when histologically confirmed, frequently precludes further use of platinum in clinical practice. This creates a critical therapeutic dilemma in which effective treatment options are limited; however, re-administration of platinum agents is considered high-risk. Evidence regarding the safety of cisplatin re-challenge after recovery from biopsy-proven ATN is extremely limited, leaving clinicians without clear guidance Case Description: We describe the case of a 57-year-old Japanese man who developed squamous transformation after osimertinib treatment and subsequently experienced carboplatin-induced biopsy-proven ATN following the first cycle of chemoimmunotherapy. Serum creatinine increased from 0.76 to 1.55 mg/dL, with a decline in estimated glomerular filtration rate (eGFR) from 83.82 to 37.83 mL/min/1.73 m². Renal function recovered within 1 month after the ATN episode, and cisplatin-based therapy was initiated 3 months after creatinine recovered to 0.91 mg/dL with an eGFR of 67.40 mL/min/1.73 m² and creatinine clearance of 83.60 mL/min/1.73 m², exceeding the predefined eligibility threshold of 80 mL/min/1.73 m². During the first cycle, severe gastrointestinal toxicity led to dehydration-associated acute kidney injury (AKI), with creatinine peaking at 2.46 mg/dL and eGFR declining to 22.71 mL/min/1.73 m², but renal function improved after prompt hydration, electrolyte replacement, and treatment modification. Conclusions: This case suggests that cisplatin re-challenge should be considered in carefully selected patients after recovery from biopsy-proven platinum-associated ATN, when clinically necessary. Importantly, our findings highlight that even in the setting of recurrent AKI, treatment continuation may be feasible under strict multidisciplinary management, including intensive hydration, electrolyte correction, and close nephrology involvement. Rather than demonstrating general safety, this case provides a clinically relevant framework for risk assessment and management in situations where therapeutic options are limited. However, these observations were derived from a single case and should be interpreted with caution.

Radiotherapy (RT) has traditionally been considered a local treatment modality; however, accumulating evidence suggests that it can induce systemic antitumor responses outside the irradiated field. The classical abscopal effect, defined as the regression of non-irradiated tumor lesions following localized RT, has gained renewed attention in the era of immune checkpoint inhibitors (ICIs). Preclinical and clinical studies have demonstrated that RT can promote immunogenic cell death, antigen presentation, cytokine release, and adaptive immune activation, processes that may contribute to systemic antitumor immunity, particularly when combined with ICIs. Clinically apparent abscopal responses remain rare and heterogeneous, and the biological mechanisms underlying these phenomena are not completely understood. Systemic tumor regression has occasionally been observed in clinical settings that do not involve checkpoint blockade, including RT alone, chemotherapy-containing regimens, and central nervous system-directed therapies. These findings suggest that radiation-associated systemic antitumor responses may arise through overlapping immunologic mechanisms involving both innate and adaptive immunity, tumor microenvironment remodeling, and treatment-associated cellular stress. This review summarizes the current clinical evidence and biological mechanisms underlying radiation-associated systemic antitumor responses and discusses emerging concepts extending beyond the conventional RT–immunotherapy paradigm. We further examined unresolved challenges, including treatment heterogeneity, biomarker limitations, pseudoprogression, and difficulties in mechanistic confirmation. Finally, we propose that the broader “beyond-abscopal” framework may serve as a hypothesis-generating conceptual model for investigating systemic tumor responses across diverse treatment contexts while emphasizing the need for cautious interpretation and prospective translational validation.

Background: Amivantamab, a bispecific antibody against epidermal growth factor receptor and mesenchymal-epithelial transition receptors, has been approved for certain types of non-small cell lung cancer; however, it is known to cause severe adverse events. The management of such adverse events is necessary for maintaining the therapeutic efficacy of amivantamab. The frequency of cardiotoxicity caused by amivantamab is low, despite its association with a high incidence of severe adverse events. Most of the adverse events are cardiovascular events caused by thrombosis. No reports of amivantamab-induced myocardial injury have been published. Case presentation: We present the first case of drug-induced myocardial injury, detected with tachycardia but not associated with any cardiovascular events, immediately after initiating amivantamab. Echocardiography revealed a decrease in left ventricular ejection fraction and global longitudinal strain, while contrast-enhanced cardiac magnetic resonance imaging showed shortened T1 values, leading to a diagnosis of amivantamab-induced myocardial injury. Furthermore, with early detection and therapeutic interventions, we were able to continue treatment with amivantamab without interruption. Conclusions: When treating patients with amivantamab, oncologists should screen for cardiac disease-related symptoms, even in the absence of elevated cardiac serum biomarkers. Furthermore, when amivantamab-induced myocardial injury is suspected, a cardiologist should be consulted promptly, as the dysfunction may be reversible.

Treatment-associated regression of tumors outside the irradiated field has occasionally been reported, but the underlying mechanisms remain unclear, particularly in the context of central nervous system (CNS)–directed therapy. Glioblastoma (GBM) is commonly treated with radiotherapy and temozolomide, both of which may influence tumor biology and the systemic environment. We report a patient with synchronous primary GBM and early-stage lung adenocarcinoma who underwent craniotomy followed by intensity-modulated radiotherapy with concurrent temozolomide for GBM. During GBM-directed chemoradiotherapy, the untreated pulmonary lesion demonstrated progressive regression without any lung-specific therapy, temporally coinciding with CNS-targeted treatment. Although comprehensive immunophenotyping was not feasible, longitudinal changes in the proportion of peripheral blood lymphocytes were observed during therapy. These findings represent a clinical observation characterized by a temporal association between CNS-directed treatment and regression of a distant, non-irradiated tumor. However, the underlying mechanism remains uncertain, and a contribution from systemic temozolomide exposure cannot be excluded. While treatment-related systemic effects may be considered, no specific causal mechanism can be established based on this single case. This case highlights an unusual clinical observation that may warrant further investigation. Further studies are needed to clarify the relationship between CNS-directed therapies and systemic tumor behavior.

Targeting heterogeneity in atypical epidermal growth factor receptor-mutated non-small cell lung cancer: insights from CHRYSALIS-2

Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a rare inflammatory subtype of cerebral amyloid angiopathy that may present with leptomeningeal enhancement on magnetic resonance imaging (MRI), thereby mimicking leptomeningeal metastasis (LM) in patients with cancer. We report the case of an 82-year-old woman with a recently resected lung adenocarcinoma who underwent brain MRI following a fall. MRI revealed bilateral asymmetric white matter hyperintensities and multifocal leptomeningeal enhancement, which initially suggested LM. However, preserved neurological function, negative cerebrospinal fluid cytology, and the subsequent identification of numerous cortical and subcortical microbleeds on targeted reassessment with susceptibility-weighted MRI prompted diagnostic reassessment. Brain biopsy demonstrated vascular amyloid deposition with perivascular inflammatory infiltrates, confirming CAA-ri. Because the patient remained neurologically stable, she was managed conservatively, and spontaneous radiological improvement was observed during follow-up. This case highlights the fact that leptomeningeal abnormalities in patients with lung cancer do not invariably represent leptomeningeal metastasis. When clinicoradiological findings are discordant, prompt reassessment using appropriately selected MRI sequences should be integrated with cerebrospinal fluid analysis and multidisciplinary evaluation, with pathological confirmation considered when clinically consequential alternative diagnoses cannot be excluded. This approach may help avoid inappropriate LM-directed therapy.