Lung autotransplantation combined with postoperative chemotherapy and immunotherapy: a three-year follow-up case report

Abstract

Background

Lung cancer remains a leading cause of cancer-related mortality worldwide. Autotransplantation has emerged as a potential surgical intervention in select cases, with the aim of achieving curative outcomes. This case report describes a novel approach combining lung autotransplantation with postoperative chemotherapy and immunotherapy, delineating the patient's journey over a period of three years.

Case presentation

We report on a 37-year-old patient with stage IIIA non-small cell lung cancer (NSCLC) who underwent lung autotransplantation. Despite the complexity of the procedure, the patient had a favorable postoperative course. Adjuvant therapy included a PD-1 inhibitor and a standard chemotherapy regimen. The patient’s follow-up involved regular clinical assessment, imaging, and functional status evaluation, demonstrating a remarkable disease-free survival at the three-year mark postoperatively.

Conclusion

This case highlights the potential for lung autotransplantation coupled with immunotherapy and chemotherapy to yield significant long-term survival benefits in patients with NSCLC. The favorable outcome suggests that this integrative treatment strategy warrants further investigation and may offer hope to patients with similarly advanced lung cancer.

Introduction

Lung autotransplantation is one of the surgical tools for treating patients with central and advanced lung cancer. Its advantage lies in the complete realization of R0 resection of tumor, while preserving the normal lung lobe and avoiding pneumonectomy. For patients with advanced lung who received lobectomy, postoperative adjuvant chemotherapy combined with immunotherapy can effectively prolong disease-free and overall survival. However, there is a lack of long-term follow-up data for patients who have received lung autotransplantation combined with postoperative chemotherapy and immunotherapy. We describe a three-year follow-up of a patient with lung autotransplantation who received four cycles of pembrolizumab combined with pemetrexed and carboplatin, including regular clinical evaluation, imaging and functional status assessment, and achieved disease-free survival for three years. This report provides a new treatment for patients with advanced lung cancer.

Case presentation

Clinical data

A 37-year-old male, with a history of smoking totaling 75 pack-years, sought medical care for a chronic, irritative cough persisting for three months. The enduring nature and severity of the cough led to comprehensive clinical investigations. A chest CT scan revealed a mass at the left hilar region (Fig. 1A), suggestive of a possible malignancy with potential invasion into the left pulmonary artery trunk (Fig. 1B), but not involving the left lower lobe pulmonary artery (Fig. 1C-D). Further examination through fiberoptic bronchoscopy showed an extrinsic protrusion on the distal membrane of the left main bronchus, with associated mucosal thickening and narrowing in the upper lobe bronchus of the left lung. No abnormalities were detected in the rest of the bronchial tree. Histopathological evaluation confirmed non-small cell lung cancer (NSCLC), adenocarcinoma subtype. Immunohistochemical staining identified adenocarcinoma with micropapillary features and intravascular cancer thrombi. The expression of Programmed Death Ligand-1 (PD-L1) was significantly elevated in 90% of tumor cells and in 10% of immune cells, indicating a likely responsiveness to immune checkpoint inhibitor therapy. These findings offer a potential therapeutic avenue through immunotherapy targeting PD-L1. The Multidisciplinary Team (MDT) developed a treatment protocol involving a left pneumonectomy with ex vivo resection of the left upper lobe and reimplantation of the left lower lobe to preserve lung function. The post-surgical plan includes adjuvant chemotherapy and immunotherapy to optimize treatment outcomes.

Fig. 1.

Imaging of a Tumor in the Left Hilar Region. A Chest CT scan depicting a mass in the left upper lobe. B Imaging showing invasion of the tumor into the trunk of the left pulmonary artery. C-D Imaging indicates no tumor presence in the left lower lobe

Surgical procedure

After induction with general anesthesia and endotracheal intubation using a double-lumen tube, the patient is positioned in a right lateral decubitus position. The surgical approach includes a 25 cm incision along the anterior lateral aspect of the fifth intercostal space. Additionally, a 1.5 cm thoracoscopic port is established in the eighth intercostal space. This setup is commonly used in thoracoscopic surgery, allowing for direct access through the larger incision while the smaller port facilitates minimally invasive techniques for enhanced visualization and instrument handling.

Surgical exploration begins at the pulmonary hilum with an incision into the mediastinal pleura, followed by systematic lymphadenectomy. Subsequently, the left main bronchus is circled posteriorly to the hilum. The pericardium, once incised behind the phrenic nerve, reveals the major vascular structures, specifically the left upper and lower pulmonary veins, along with the left pulmonary artery. The left main bronchus is then sequentially transected (Fig. 2A) and the veins of the upper and lower lobes are sealed with a stapler (Fig. 2B-C). A vascular clamp is applied to occlude the left pulmonary artery trunk (Fig. 2D), enabling its sharp dissection to secure an adequate length for division (Fig. 2E-F).

Fig. 2.

Left Pneumonectomy Part. A Transection of the left main bronchus. B Closure of the left upper lobe vein. C Closure of the left lower lobe vein. D-E Encirclement and division of the left pulmonary artery trunk. F Complete removal of the left lung from the thoracic cavity

After the ex vivo resection of the upper lobe of the left lung, the lower lobe was immediately immersed in ice-cold low-potassium dextran (LPD) solution. The perfusion method using LPD solution for lung autotransplantation is a sophisticated surgical technique, first reported by Oto et al. (2012), who described its use in basal segmental autotransplantation following pneumonectomy for advanced central lung cancer [1]. In this case, perfusion was performed using both anterograde and retrograde techniques to ensure thorough clearance of blood and preservation of lung tissue. No additional additives were introduced to the LPD solution, which was utilized in its standard form to maintain osmotic balance and microvascular integrity. The perfusion was maintained at 4 °C and continued until the effluent perfusate was clear, indicating that the lung tissue was adequately prepared for reimplantation. Following perfusion, the bronchi (Fig. 3A), artery (Fig. 3B), and vein (Fig. 3C) of the lower left lobe were prepared for anastomosis.

Fig. 3.

Preparation and Reimplantation of the Left Lower Lobe. A Preparation of the bronchus of the left lower lobe. B Preparation of the artery of the left lower lobe. C Preparation of the vein of the left lower lobe. D Anastomosis of the left main bronchus and the bronchus of the left lower lobe. E Anastomosis of the left pulmonary artery trunk and the artery of the left lower lobe. F Anastomosis of the remnant of the left upper lobe vein and the vein of the left lower lobe

Rapid intraoperative pathological examination confirmed a classification of T4N1M0 (stage IIIA) with tumor-free margins noted in the bronchial, arterial, and venous tissues. The surgical procedure entailed anastomosis of the lower bronchus to the main bronchus using 3–0 Prolene sutures (Fig. 3D). This was followed by suturing the stumps of the pulmonary artery with 5–0 Prolene (Fig. 3E) and anastomosis of the lower pulmonary vein to the site of the upper vein using 4–0 Prolene sutures (Fig. 3F). Subsequently, the left lung artery and vein were sequentially released. After air evacuation through the venous anastomosis site, the site was secured with a suture. Perfusion and ventilation of the replanted left lower lobe were satisfactory. The surgical intervention spanned 245 min and entailed a cold ischemia period of 90 min.

Postoperative management

The patient was observed in the ICU for 48 h. Therapeutic measures included the administration of antibiotics, anticoagulants, nebulized treatments, and nutritional support. Bronchoscopic suctioning was utilized to clear pulmonary secretions and evaluate the anastomosis. The lymph nodes of the N1 group were positive for metastasis, confirming a stage IIIA tumor (pT4N1M0). The patient's recovery was uneventful, and they were discharged 2 weeks later with satisfactory pulmonary function and without significant morbidity.

Adjuvant chemotherapy and immunotherapy

The patient underwent a systemic adjuvant therapy regimen that involved four cycles of chemotherapy with pemetrexed and carboplatin, along with intravenous administration of a PD-L1 inhibitor every three weeks for 16 cycles. This treatment was well-tolerated, with no severe immune-related adverse events observed.

Follow-up and outcomes

Postoperative chest CT at one week showed favorable lung re-expansion (Fig. 4A). Subsequent imaging three months later showed reduced pulmonary inflammation (Fig. 4B). Follow-up examinations during the second (Fig. 4C) and third years (Fig. 4D) postoperatively revealed no signs of recurrence or tumor metastasis. Pulmonary function tests have remained stable. The patient reports maintaining a high quality of life with unrestricted physical activity.

Fig. 4.

Longitudinal Follow-Up CT Imaging After Lung Reimplantation. A CT scan obtained one week postoperatively, illustrating the initial status of the implanted lung. B CT scan three months postoperatively, demonstrating diminished pulmonary inflammation. C CT scan at the second postoperative year, with no evidence of tumor recurrence. D CT scan at the third postoperative year, with no signs of tumor recurrence

Discussion

Resectable NSCLC mainly refers to stage I-II and some locally advanced (stage III) tumors. Surgery is the only radical treatment at present [2]. For patients with central lung cancer involving extensive invasion of the pulmonary artery and bronchus, pneumonectomy is a commonly employed approach. This procedure often leads to significant loss of lung function, negatively impacting postoperative quality of life and increasing the risk of perioperative mortality [3–5]. When possible, a conventional double sleeve lobectomy is preferred because it preserves lung function and reduces postoperative complications, thereby leading to an improved quality of life compared to pneumonectomy [6–8]. If the tumor extensively involves central structures such as the bronchus and pulmonary artery, making a tension-free double sleeve lobectomy unfeasible, lung autotransplantation becomes a viable alternative [9, 10].

Indeed, cases of lung autotransplantation are quite rare, Table 1 presents the postoperative follow-up data for patients who have undergone lung autotransplantation. These studies reported that patients remained free of tumor recurrence for extended periods, ranging from several months to a few years [11–17]. The successful outcomes reported in these rare instances demonstrate the potential of lung autotransplantation to preserve lung function and improve survival in patients.

Table 1.

Clinical outcomes in studies of lung autotransplantation for central and locally advanced lung cancer

Study	Disease	Follow-up Duration	Outcome
Jiang et al. (2008) [11]	Central lung cancer of upper lobe	2–73 months	5 patients disease-free (2–73 months); 1 death due to relapse at 15 months; 1 death due to brain metastasis at 31 months
Mao et al. (2013) [12]	NSCLC, intolerant to pneumonectomy or sleeve lobectomy	12 months	Cancer-free at 12 months
Watanabe et al. (2015) [13]	Locally advanced central lung cancer	6 months	No recurrence at 6 months
Oto et al. (2019) [14]	Advanced central NSCLC (Oto procedure)	43–84 months	4 patients alive without local recurrence; 1-, 3-, and 5-year survival rates were 100%, 100%, and 80%, respectively
Nakajima et al. (2020) [15]	Lung cancer	11–24 months	1 patient recurrence-free at 11 months; 1 patient with no signs of recurrence at 24 months
He et al. (2021) [16]	Central NSCLC (novel technique)	9 months	2 cases, no evidence of recurrence at 9 months
Taira et al. (2022) [17]	Superior sulcus tumor with hilar involvement	18 months	Disease-free at 18 months

Dehiscence of bronchial anastomosis remains a primary concern in lung autotransplantation and other procedures involving bronchial anastomosis [18, 19]. In lung autotransplantation, although traditional graft rejection is not an issue, the use of immunotherapy presents potential risks, particularly related to bronchial anastomotic healing. The heightened immune activity induced by checkpoint inhibitors could potentially lead to increased inflammation at the anastomosis site, raising the risk of dehiscence. There have been isolated case reports suggesting an association between immunotherapy and the development of bronchopleural fistula. However, the evidence remains limited and further investigation is warranted [20–22]. Although this complication did not occur in the present case, it underscores the importance of vigilant postoperative monitoring. Further research is needed to fully understand these risks and to develop strategies that can mitigate them while maintaining the therapeutic benefits of immunotherapy.

In this case, adjuvant immunochemotherapy was successfully implemented, leading to a favorable outcome. However, neoadjuvant immunotherapy, when combined with chemotherapy, is emerging as a cutting-edge treatment for resectable non-small cell lung cancer (NSCLC). Groundbreaking studies, such as CheckMate-816 and NADIM, have played a pivotal role in shaping this innovative therapeutic approach. Notably, neoadjuvant therapy has been shown to significantly improve survival outcomes, including overall survival and event-free survival, in patients with resectable NSCLC. Additionally, it is associated with higher rates of pathological complete response, major pathological response, and successful surgical resection [23, 24]. However, this approach raises several critical concerns. The risk of immune-related adverse events (irAEs) can significantly affect surgical timing and readiness, often necessitating adjustments to the treatment plan. Furthermore, the variability in patient responses to neoadjuvant immunotherapy complicates outcome predictions, with some initially resectable tumors becoming unresectable, underscoring the importance of personalized treatment strategies [25].

There have been limited reports on adjuvant immunochemotherapy for patients undergoing lung autotransplantation. This study presents the 3-year follow-up results of a patient who received postoperative chemotherapy combined with immunotherapy after lung autotransplantation. The successful outcome suggests that this approach may become a new paradigm for treating central lung cancer in lung autotransplant patients, but further research is needed to confirm these findings.

Conclusion

This case highlights the potential for lung autotransplantation coupled with immunotherapy and chemotherapy to yield significant long-term survival benefits in patients with NSCLC. The favorable outcome suggests that this integrative treatment strategy warrants further investigation and may offer hope to patients with similarly advanced lung cancer.

Authors’ contributions

Jiang Wang, Hengxiao Lu and Qiang Zhao wrote the main manuscript text and prepared Figs. 1-4. Tong Li prepared Figs. 2 and 3. All authors reviewed the manuscript.

Funding

This research was supported by the Weifang Municipal Health and Health Committee Fund, with the project number WFWSJK-2023–321.

Availability of data and materials

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

The study was approved by the ethics committee of Weifang People's Hospital. Written informed consent was obtained from the participant for the publication of the details of the medical case and any accompanying images.

Consent for publication

Informed consent has been obtained from the patient included in this study.

Competing interests

The authors declare no competing interests.