Unusual lung tumors in clinical practice.

Targeted antibody therapy for metastatic NSCLC with NRG1 fusion.

A 50-year-old female patient was diagnosed with non-small cell lung cancer (NSCLC) in the left lower lobe of the lung in mid-2019 (TNM: T2b, N3, M1c (LYM, OSS), St. IVb according to UICC 8th version 2017). Histologically, it was an acinar adenocarcinoma without driver mutation in molecular pathology NGS-based analysis. First-line therapy was 4 cycles of CT (cisplatin/carboplatin, pemetrexed, pembrolizumab), followed by 5 cycles of maintenance therapy with pemetrexed/pembrolizumab or pembrolizumab monotherapy (07/2019 to 01/2020). Local tumor progression was detected on CT during maintenance therapy. In the case of nonsmoker status, a renewed this time Archer-based molecular diagnosis by videothoracoscopy with wedge resection was initiated, write Felix Maria Schönhofer and Dr. Claas Wesseler, Asklepios Klinikum Harburg, Hamburg (D).

A gene fusion in the NRG1 gene was detected. Due to the pandemic lockdown in March 2020, the patient was unable to participate in a randomized trial abroad, so targeted tumor therapy with zenocutuzumab was administered via early access program in 3-week cycles from April to November 2020. The carcinoma responded to antibody therapy in the form of partial remission. In addition to cough and radiological monitoring, the effect could be shown by the tumor marker CA19-9.

This was followed by PET-CT in November 2020 and evidence of “slow progress” with increasing CA19-9. Following the ESMO recommendation, the treatment providers switched to third-line therapy with afatinib by August 2021, which resulted in tumor stabilization at an increased dose of 50mg/d, but also resulted in relevant side effects such as chronic diarrhea. Chemotherapy (carboplatin/gemcitabine) could also only be applied with 2 cycles due to side effects. In addition, symptomatic brain filiae stood out in the diagnostic workup.

From this case report with lung carcinomas without evidence of driver mutations in the initial diagnosis, never-smoker status, and lack of response to first-line therapy, it can be deduced that tissue sampling and molecular biology diagnostics should be repeated in order to possibly be able to perform individualized pharmacotherapy after all, the authors conclude. In this case, he said, it was the first patient in Germany to receive the targeted NRG-1 fusion therapy.

DGP Congress 2022, Poster Po 271.

Monstrous endobronchial lipoma

Endobronchial lipomas are rare benign tumors. Mohamed Garhy, Dr. Edgar Haasler, and Prof. Dr. Bernd Schönhofer of the Evangelisches Klinikum Bethel in Bielefeld, Germany, Department of Internal Medicine, Pneumology, and Intensive Care Medicine, describe a case with unusual widespread findings, significant disease symptoms, and ultimately successful interventional endoscopic therapy:

A 60-year-old man complained of increasing exertional dyspnea, cough, and recurrent febrile infections for several months. In addition, there was a general decrease in performance and a weight loss of 10 kilograms. Computed tomography of the chest revealed a severely volume-depleted left lung with consolidated infiltrates. There was a fluid level in the left main bronchus and occlusion behind it by a soft tissue mass of fat-equivalent density, which also filled large portions of the central bronchi of the left upper and lower lobes.

Bronchoscopy confirmed these findings. The tumor spreading intraluminally in the central bronchial system was ablated fractionally by diathermy snare (with a flexible bronchoscope using a spiral tracheal tube) during the same session. A large amount of purulent secretion emptied from the periphery. The base of the pedunculated tumor was located at the outlet of segmental bronchus 3, and here the remaining tissue was removed by cryotherapy and argon plasma coagulation. Histopathologic examination revealed a lipoma.

Due to poststenotic pneumonia, physicians initiated antibiotic therapy. Follow-up visits in the following months showed extensive re-aeration of the left lung with residual minor scarring and bronchiectasis.

DGP Congress 2022, Poster Po 254.

ECMO for acute respiratory failure due to advanced lung CA.

A 57-year-old male patient was admitted to the hospital with acute respiratory failure and CT morphology of diffuse bipulmonary nodular condensations and enlarged mediastinal lymph nodes. Endosonographic puncture of mediastinal lymph nodes revealed papillary adenocarcinoma of the lung. Thus, clinically, pulmonary diffuse metastatic lung carcinoma was present, writes a group of authors led by Dr. Peggy Balting and Johannes Purschwitz of Fachkrankenhaus Coswig (D), Lung Center; Internal Medicine and Pneumology.

Before receiving the molecular pathology results, physicians had to intubate and invasively ventilate their patient due to respiratory exhaustion. When an exon 19 deletion was detected as an activating mutation in the EGF receptor, therapy with osimertinib (80 mg/d) was started by gavage. Finally, due to refractory hypoxemia, veno-venous extra-corporeal membrane oxygenation (vvECMO) was initiated.

A clinically relevant therapeutic response was seen after 21 days of ECMO therapy. The patient could be completely weaned from ECMO on day 21 and from ventilation on day 27. Discharge occurred on day 42 with an oxygen requirement of 3 l/min. Three months after discharge, the patient was in good general condition (ECOG 0) and without further oxygen requirements.

In principle, vvECMO therapy is recommended in patients with severe ARDS – mostly due to pulmonary infection – and refractory hypoxemia as a so-called “rescue therapy”. As reported by the team from Coswig, this was the first successful use of vvECMO therapy in severe respiratory failure in the setting of an initial diagnosis of advanced pulmonary metastatic lung cancer.

This casuistry shows that in rare cases, intensive medical therapy including mechanical ventilation and even ECMO therapy is warranted for acute respiratory failure in the setting of an initial diagnosis of advanced lung cancer, the pulmonologists concluded. In particular, the possibility of targeted therapy in the presence of an activating mutation and associated good response to therapy must be considered.

DGP Congress 2022, Poster Po 72.