Lung Cancer Surgery Succeeds After Near-Fatal Immunotherapy Heart Complication

A 53-year-old man with lung cancer survived a near-fatal heart inflammation triggered by his immunotherapy, recovered his cardiac function, and then underwent curative-intent lung surgery that appears to have kept him free of disease for more than six years, according to a case report published in General Thoracic and Cardiovascular Surgery Cases. The report describes one of the few documented pathways in which fulminant immune checkpoint inhibitor-associated myocarditis did not permanently end a patient’s chance of definitive cancer surgery.

The patient had left upper lobe adenocarcinoma with ipsilateral hilar nodal disease, classified as cT2aN1M0, stage IIB. Testing showed a programmed death-ligand 1 tumor proportion score below 1%, and Oncomine testing found no actionable alterations in EGFR, ALK, ROS1, or other tested genes. He received four cycles of neoadjuvant cisplatin, pemetrexed, and pembrolizumab following the KEYNOTE-671 protocol. The treatment worked well against the tumor: the primary lesion shrank from 38 mm to 14 mm in longest diameter, and the short-axis diameter of the hilar node fell from 38 mm to 5 mm, a partial response under the Response Evaluation Criteria in Solid Tumors.

Eighty-six days after chemoimmunotherapy began, roughly three weeks after his final cycle, the man developed dyspnea and cough and was admitted for preoperative evaluation. Initial echocardiography measured a left ventricular ejection fraction of 51%. His condition then deteriorated rapidly, with blood pressure of 87/60 mmHg, a heart rate of 120 beats per minute, and oxygen saturation of 89% on room air. Repeat echocardiography revealed diffuse severe left ventricular hypokinesis with a visually estimated ejection fraction of about 20%, which dropped to approximately 10% during the early critical phase. Electrocardiography showed low voltage in the limb leads, Q waves in V1 through V4, and ST-segment elevation in leads I, aVL, and V1 through V4. Chest radiography revealed bilateral pulmonary congestion.

Laboratory findings confirmed severe cardiac injury. His initial creatine kinase level was 966 U/L, creatine kinase-MB was 90 U/L, N-terminal pro-B-type natriuretic peptide was 9,388 pg/mL, and troponin T was 5.84 ng/mL. Coronary angiography showed no significant coronary stenosis, ruling out a blocked artery as the cause. Endomyocardial biopsy showed active lymphocytic myocarditis without significant fibrosis, with focal infiltrates composed predominantly of CD3-positive T lymphocytes, with CD8 cells exceeding CD4 cells, and macrophages. During evaluation, ventricular fibrillation led to cardiac arrest requiring intubation, percutaneous cardiopulmonary support, intra-aortic balloon pumping, continuous hemodiafiltration, and intensive care. Because the event was life-threatening and demanded urgent mechanical circulatory and respiratory support, it was classified as grade 4 myocarditis under the Common Terminology Criteria for Adverse Events.

Treatment centered on high-dose corticosteroids. Methylprednisolone was given at 1,000 mg/day for three days and 500 mg/day for the next three days, followed by oral prednisolone starting at 120 mg/day and tapered gradually according to his clinical course and cardiac recovery. Percutaneous cardiopulmonary support was discontinued four days after myocarditis onset, and intra-aortic balloon pumping and mechanical ventilation were withdrawn the following day. The course was complicated by transient renal failure, deep venous thrombosis, and lower-extremity neurologic deficits requiring rehabilitation. Spinal cord infarction was suspected, but the final cause of the neurologic deficits remained undetermined. By the time of surgery, prednisolone had been reduced to 10 mg/day.

Cardiac function recovered steadily. Left ventricular ejection fraction improved to 67%, 69%, and 71% on days 107, 132, and 224 after chemoimmunotherapy initiation, respectively. No recurrent malignant arrhythmia was documented after withdrawal of circulatory support. Follow-up computed tomography obtained 205 days after treatment initiation showed tumor regrowth without distant metastasis. At preoperative reassessment, the maximum diameter of the primary lesion was 2.1 cm, including a 1.8-cm solid component, and hilar nodal disease persisted at station 12u. Despite impaired activities of daily living, preoperative electrocardiography and echocardiography were unremarkable, and lower-extremity venous ultrasonography showed no residual thrombosis.

After multidisciplinary review of oncologic need, resectability, alternatives, and perioperative risk, the cardiology team judged surgery feasible but recommended close monitoring for recurrent ventricular arrhythmia. The patient elected surgery after the risks were explained. Thoracoscopic-assisted thoracotomy was performed 144 days after myocarditis onset, corresponding to 230 days after chemoimmunotherapy began. The operation included left upper lobe sleeve resection, pulmonary artery reconstruction, and hilar and mediastinal lymph node dissection. Operative time was 6 hours and 3 minutes, blood loss was 590 mL, and a minor air leak resolved with conservative management. No perioperative cardiovascular events occurred.

Pathology showed ypT3N1M0 adenocarcinoma with negative margins, an R0 resection, and minor treatment effect graded Ef 1a. T3 classification was assigned because multiple separate tumor nodules, measuring up to 8 mm, were present in the same lobe. Pembrolizumab was permanently discontinued after the grade 4 myocarditis, and no adjuvant systemic therapy was administered. Surveillance computed tomography showed no evidence of recurrence through 3.5 years after surgery, and the patient was alive at the last follow-up 6.3 years after the operation.

The authors place this case in context with published data on the frequency and severity of the complication. In a systematic review and meta-analysis of 589 clinical trials including 83,315 patients, reported all-grade myocarditis rates were 0.24% with PD-1 monotherapy, 0.33% with PD-L1 monotherapy, 0.15% with ipilimumab, and 0.72% with dual immune checkpoint inhibitor therapy. A real-world cohort monitored with serial biomarkers identified the condition in 27 of 2,606 patients, or 1.0%. Severity is substantial: a multicenter registry recorded major adverse cardiac events in 46% of patients with the condition, and a recent systematic review reported myocarditis-associated mortality in 37.7% of published cases.

The authors caution that this course should not be regarded as a standard implementation of the KEYNOTE-671 perioperative strategy, since fulminant myocarditis caused prolonged interruption of the intended schedule and surgery came 144 days after myocarditis onset; the case is best interpreted as an individualized, nonstandard pathway. Evidence on surgery after preoperative immune-related adverse events remains limited. A multicenter retrospective analysis of resectable non-small-cell lung cancer treated with neoadjuvant nivolumab plus chemotherapy found preoperative adverse events in approximately 20% of patients, associated with treatment discontinuation and surgery cancellation, though myocarditis-specific outcomes were not separately defined. A separate perioperative case report described fatal, unrecognized myocarditis in a patient with metastatic disease presenting for mediport placement. In this case, by contrast, myocarditis was diagnosed, treated, and objectively reassessed before curative-intent resection. The authors conclude that fulminant myocarditis does not necessarily preclude subsequent curative-intent lung resection, that surgery may remain feasible in highly selected patients after objective cardiac recovery, multidisciplinary reassessment, and shared decision-making, and that life-threatening cardiovascular immune-related events should be managed at centers with continuous on-site cardiology support, multidisciplinary care, and access to emergency mechanical circulatory support, with perioperative planning that includes continuous electrocardiographic monitoring, immediate defibrillation capability, and prompt cardiology support.

Subject of Research: A case report of curative-intent lung resection after recovery from fulminant immune checkpoint inhibitor-associated myocarditis during neoadjuvant therapy for non-small-cell lung cancer.

Article Title: Curative-intent lung resection after recovery from fulminant immune checkpoint inhibitor-associated myocarditis during neoadjuvant therapy: a case report

Article References: Kaburaki, Y., Ito, H., Isaka, T., Tsunematsu, T., Tsukahara, K., Hayakawa, A., Takada, I., Matsuyama, R., Kanno, C., & Nagashima, T. (2026). Curative-intent lung resection after recovery from fulminant immune checkpoint inhibitor-associated myocarditis during neoadjuvant therapy: a case report. General Thoracic and Cardiovascular Surgery Cases, 5(1), Article 45. https://doi.org/10.1186/s44215-026-00278-x

Image Credits: AI Generated

DOI: 10.1186/s44215-026-00278-x

Keywords: immune checkpoint inhibitor, myocarditis, lung cancer, non-small-cell lung cancer, neoadjuvant chemoimmunotherapy, pembrolizumab, case report, cardiac arrest, ventricular fibrillation, lung resection, immune-related adverse event, left ventricular ejection fraction