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. 2022 Jun 1;14(11):2748.
doi: 10.3390/cancers14112748.

Reducing Immunosuppression in Patients with De Novo Lung Carcinoma after Liver Transplantation Could Significantly Prolong Survival

Sina Pesthy  1 , Elisa Wegener  1 , Ramin Raul Ossami Saidy  1 , Lea Timmermann  1 , Deniz Uluk  1 , Mustafa Aydin  1 , Tomasz Dziodzio  1   2 , Wenzel Schoening  1 , Georg Lurje  1 , Robert Öllinger  1 , Nikolaj Frost  3 , Uli Fehrenbach  4 , Jens-Carsten Rückert  1 , Jens Neudecker  1 , Johann Pratschke  1 , Dennis Eurich  1
Affiliations

Reducing Immunosuppression in Patients with De Novo Lung Carcinoma after Liver Transplantation Could Significantly Prolong Survival

Sina Pesthy et al. Cancers (Basel). .

Abstract

(1) Background: Liver transplantation (LT) is an established treatment for selected patients with end-stage liver disease resulting in a subsequent need for long-term immunosuppressive therapy. With cumulative exposure to immunosuppression (IS), the risk for the development of de novo lung carcinoma increases. Due to limited therapy options and prognosis after diagnosis of lung cancer, the question of the mode and extent of IS in this particular situation is raised. (2) Methods: All patients diagnosed with de novo lung cancer in the follow-up after LT were identified from the institution's register of liver allograft recipients (Charité-Universitätsmedizin Berlin, Germany) transplanted between 1988 and 2021. Survival analysis was performed based on the IS therapy following diagnosis of lung cancer and the oncological treatment approach. (3) Results: Among 3207 adult LTs performed in 2644 patients at our institution, 62 patients (2.3%) developed de novo lung carcinoma following LT. Lung cancer was diagnosed at a median interval of 9.7 years after LT (range 0.7-27.0 years). Median survival after diagnosis of lung carcinoma was 13.2 months (range 0-196 months). Surgical approach with curative intent significantly prolonged survival rates compared to palliative treatment (median 67.4 months vs. 6.4 months). Reduction of IS facilitated a significant improvement in survival (median 38.6 months vs. 6.7 months). In six patients (9.7%) complete IS weaning was achieved with unimpaired liver allograft function. (4) Conclusion: Reduction of IS therapy after the diagnosis of de novo lung cancer in LT patients is associated with prolonged survival. The risk of acute rejection does not appear to be increased with restrictive IS management. Therefore, strict reduction of IS should be an early intervention following diagnosis. In addition, surgical resection should be attempted, if technically feasible and oncologically meaningful.

Keywords: de novo lung cancer; immunosuppression; liver transplantation; lung carcinoma; surgical tumor resection.

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Conflict of interest statement

All authors declare no conflict of interest related to the presented work.

Figures

Figure 1
Figure 1
Time of diagnosis of de novo lung carcinoma after liver transplantation. LT—liver transplantation.
Figure 2
Figure 2
Impact of therapeutical strategies on survival diagnosis of de novo lung carcinoma after liver transplantation. BSC—best supportive care.
Figure 3
Figure 3
Comparison of patients with or without surgical approach after diagnosis of de novo lung carcinoma after liver transplantation.
Figure 4
Figure 4
Comparison of patients with or without restrictive immunosuppressive management after diagnosis of de novo lung carcinoma after liver transplantation. RIM—restrictive immunosuppressive management.
Figure 5
Figure 5
Impact on modification of immunosuppressive therapy after diagnosis of de novo lung carcinoma after liver transplantation. CNI—calcineurin inhibitors.
Figure 6
Figure 6
Impact on modification of immunosuppressive therapy in patients with palliative treatment after diagnosis of de novo lung carcinoma after liver transplantation. CNI—calcineurin inhibitors.
Figure 7
Figure 7
Impact on conversion to mTOR after diagnosis of de novo lung carcinoma after liver transplantation. mTORi—mammalian target of rapamycin inhibitors.
Figure 8
Figure 8
Impact on MMF-based IS after diagnosis of de novo lung carcinoma after liver transplantation. IS—immunosuppression; MMF—mycophenolate mofetil.
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Grants and funding

We acknowledge financial support from the Open Access Publication Fund of Charité—Universitätsmedizin Berlin and the German Research Foundation (DFG). This research received no external funding.

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