Retrospective study of the incidence and outcomes from lung cancer in solid organ transplant recipients

doi:10.1016/j.lungcan.2020.07.020

Lung Cancer

Volume 147, September 2020, Pages 214-220

https://doi.org/10.1016/j.lungcan.2020.07.020 Get rights and content

Highlights

•
Survival of organ transplant recipients with lung cancer is reduced compared to historical norms in non-transplant patients.
•
Those treated with definitive therapy instage III and chemotherapy in stage IV NSCLC had survivals matching historic norms.
•
Adverse events from chemotherapy appear higher in transplant recipients and appear lessened with dose reductions.
•
Treated SCLC patients had survivals slightly lower than historic norms.

Abstract

Objective

Organ transplant recipients (OTR) have an increased risk of developing post-transplant malignancies with lung cancer being one of the most common. In this retrospective study, we investigated incidence, use of systemic therapy and outcomes from lung cancer in OTR.

Materials and Methods: Patients diagnosed with lung cancer following a solid organ transplant at the University Health Network, Toronto, ON, CA, from January 1, 1980 to June 30, 2016 were included. Data for the study population, patient characteristics, treatments and outcomes were abstracted from solid OTR databases, our cancer registry and patient charts. Univariate Kaplan-Meier curves estimated median overall survival (OS) by histology, stage and systemic therapy.

Results

Amongst 7944 OTR (heart [N = 765], lung [n = 1668], liver [n = 2238], kidney [n = 3273]), 101 (1.3 %) developed lung cancer which were included in our analyses. Of these, 81 % were non-small cell lung cancer (NSCLC), 11 % small cell lung cancer (SCLC) and 8% neuroendocrine tumor (NET). Median OS (months) was 25 in those that presented with Stage I/II NSCLC (44 %); 25 for Stage III NSCLC (7%); 3 for Stage IV NCLC (31 %); 10 for Limited stage SCLC (6%); 2 for Extensive stage (ES) SCLC (5%). NSCLC patients that received palliative chemotherapy had an OS of 8 months; ES-SCLC patients that received chemotherapy had an OS of 6 months. Of all patients who received platinum doublets (n = 16), 10 (62.5 %) required dose reductions at some point. Five patients experienced febrile neutropenia (31 %); two (12 %) had other toxicities leading to discontinuation.

Conclusion

Patients with stage I/II NSCLC and NET had poorer survival compared to historical norms in non-transplant patients. Patients who had stage III NSCLC or received palliative systemic therapy had survivals at or slightly below historic norms, although numbers were small. Chemotherapy can be administered in selected OTR patients though dose reductions and febrile neutropenia were common.

Introduction

Solid organ transplant recipients (OTR) have an increased incidence of developing a malignancy post-transplant, which is the 2nd leading cause of mortality in transplant patients [1,2]. The increased risk is thought to be largely due to immunosuppression in transplant patients, allowing more cancers to escape immune surveillance, similar to other immunosuppressed populations (e.g. patients with HIV) [3]. Other theories include local immune reactions against the transplanted organ, carcinogenicity of immunosuppressants, increased surveillance, and risk from the underlying conditions that led to the need for an organ transplant [[4], [5], [6], [7]] Lung cancer is one of the most common malignancies seen in OTR’s after hematological and skin cancers. However, there is a paucity of studies evaluating treatment and outcomes from lung cancer in patients with an organ transplant [1,2].

The University Health Network (UHN) has one of the largest transplant centres in North America. In this retrospective study, we investigated the incidence, treatment and survival outcomes of patients with post-transplant lung cancers in UHN from 1980 to 2016.

Section snippets

Study population

This was a retrospective study, which included all patients who received a solid organ (heart, liver, lung or kidney) transplant at the University Health Network, Toronto, CA from January 1, 1980 to June 30, 2016 and diagnosed with a post-transplant non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC) or lung neuroendocrine tumor (NET) (Fig. 1). Patients with insufficient available data critical for our analyses, due to follow up at another institution, were excluded from the

Results

Of the 7944 patients who underwent a solid organ transplant, 123 patients (1.5 %) were diagnosed with a primary lung malignancy of which 101 (1.3 %) were included in our analysis (Fig. 1). Patient baseline characteristics are described in Table 1. The median time from transplant to cancer diagnosis was 60 months (excluding those diagnosed in the removed/explanted lung. The majority of the lung cancers were NSCLC (82 cases); with 11 cases of SCLC and 8 cases of NETs (typical carcinoid).

Discussion

This retrospective, single institution study evaluated the outcome and treatments administered in a cohort of 101 patients diagnosed with lung cancer after a solid organ transplant. Overall outcomes were poor for patients with stage I-II NSCLC, having a median OS of 25 months and for patients with stage IV disease, 3 months. Patients with SCLC similarly had a poorer OS. Systemic therapy was administered to a minority of patients, however some patients included in this analysis were treated

Conclusions

In patients diagnosed with lung cancer after a prior organ transplant, we found shorter survival in general compared to historical norms for patients with particularly early stage NSCLC despite surgical resection or radiation. Patients with stage III disease, and in the selected patients that received palliative chemotherapy for NSCLC and SCLC, outcomes were similar (for stage III), or on the lower range of what may be expected at the time for non-OTR patients, however, only a minority of NSCLC

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

CRediT authorship contribution statement

Kelvin Young: Conceptualization, Visualization, Methodology, Investigation, Writing - original draft, Writing - review & editing. Haiyan Jiang: Formal analysis, Writing - review & editing. Max Marquez: Data curation, Writing - review & editing. Jonathan Yeung: Writing - review & editing. Frances A. Shepherd: Writing - review & editing. Eberhard Renner: Writing - review & editing. Shaf Keshavjee: Writing - review & editing. Joseph Kim: Writing - review & editing. Heather Ross: Writing - review &

Declaration of Competing Interest

None.

References (33)

P. Villeneuve et al.
Cancer incidence among canadian kidney transplant recipients
Am. J. Transplant.
(2007)
J. Dantal
Effect of long-term immunosuppression in kidney-graft recipients on cancer incidence: randomised comparison of two cyclosporin regimens
Lancet
(1998)
G. Opelz et al.
Incidence of non-Hodgkin lymphoma in kidney and heart transplant recipients
Lancet
(1993)
S.K. Vinod et al.
Stage III non-small-Cell lung Cancer: population-Based patterns of treatment in British Columbia, Canada
J. Thorac. Oncol.
(2012)
D.J. Goldstein et al.
De novo solid malignancies after cardiac transplantation
Ann. Thorac. Surg.
(1995)
A.B. Olland et al.
Primary lung cancer in lung transplant recipients
Ann. Thorac. Surg.
(2014)
O.A. Minai et al.
Bronchogenic carcinoma after lung transplantation: characteristics and outcomes
J. Thorac. Oncol.
(2008)
B. Kiberd et al.
Cancer mortality in kidney transplantation
Am. J. Transplant.
(2009)
F. Kocher et al.
Liver transplantation-associated lung cancer: comparison of clinical parameters and outcomes
Clin. Lung Cancer
(2015)
J. Fisher et al.
Immune checkpoint inhibitor therapy in solid organ transplant recipients: a patient-centered systematic review
J. Am. Acad. Dermatol.
(2020)

B. Krynitz et al.

Risk of skin cancer and other malignancies in kidney, liver, heart and lung transplant recipients 1970 to 2008—a Swedish population-based study

Int. J. Cancer

(2013)

Tracy Hampton

Skin Cancer’s ranks rise

JAMA

(2005)

C. Vajdic et al.

Cancer incidence before and after kidney transplantation

JAMA

(2006)

M. Hojo et al.

Cyclosporine induces cancer progression by a cell-autonomous mechanism

Nature

(1999)

Ya-Ping Xu et al.

Is there a survival benefit in patients with stage IIIA (N2) non-small cell lung Cancer Receiving neoadjuvant chemotherapy and/or radiotherapy prior to surgical resection

Medicine

(2015)

K. Hotta et al.

Meta-analysis of randomized clinical trials comparing cisplatin to carboplatin in patients with advanced non–Small-Cell lung Cancer

J. Clin. Oncol.

(2004)

Cited by (3)

Changes over time in the causes of death with a functioning graft in kidney transplantation recipients
2023, Nefrologia
Death with a functioning graft (DWFG) is the most frequent cause of loss of kidney transplantation (KT).
To analyze the evolution of the causes of DWFG and the frequency of the types of cancer causing DWFG.
Retrospective study of KT in Andalusia from 1984 to 2018. We analyzed the evolution according to eras (1984–1995; 1996–2007; 2008–2018) and according to post-transplant period (early death: first year post-KT; late death: after first year post-KT).
A total of 9905 KT were performed, registering 1861 DWFG. The most frequent causes were cardiovascular disease (25.1%), infections (21.5%) and cancer (19.9%).
In early death we did not observe changes, and infections were always the main cause. In late death, cardiovascular death decreased (1984−1995: 35.2%, 1996−2007: 22.6%, 2008−2018: 23.9%), but infections (1984−1995: 12.5%, 1996−2007: 18.3%, 2008−2018: 19.9%) and, above all, cancer-related deaths increased (1984−1995: 21.8%, 1996–2007: 29%, 2008−2018: 26.8%) (P < .001). In the multivariable analysis for late death due to cardiovascular disease, recipient age, retransplantation, diabetes, and the first period were risk factors, while the risk of late death due to cancer and infections was associated with recent eras.
In the first year after transplantation, the most frequent neoplasia causing DWFG was post-transplant lymphoproliferative disease, and after the first year, it was lung cancer, without differences when it was analyzed by eras.
Despite the greater comorbidity of the recipients, cardiovascular deaths have decreased. Cancer has been the main cause of late death in recent years. Lung cancer is the most frequent malignancy that causes DWFG in our transplant patients.
La muerte con injerto funcionante (MCIF) es la causa más frecuente de pérdida del trasplante renal (TR).
Analizar la evolución de las etiologías de MCIF y la frecuencia de los tipos de neoplasia causantes.
Estudio retrospectivo de los TR en Andalucía desde 1984 hasta 2018. Analizamos la evolución de las MCIF según etapas (1984–1995; 1996–2007; 2008–2018) y según período post-TR (muerte precoz: primer año post-TR; muerte tardía: tras el primer año post-TR).
Se realizaron 9.905 TR; se produjeron 1.861 MCIF. Las causas más frecuentes fueron enfermedad cardiovascular (25,1%), infecciones (21,5%) y neoplasias (19,9%).
En las muertes precoces no observamos cambios en el tiempo; las infecciones siempre fueron la causa principal. En las tardías, desciende la muerte cardiovascular (1984−1995: 35,2%; 1996−2007: 22,6%; 2008−2018: 23,9%) y aumentan las muertes por infecciones (1984−1995: 12,5%; 1996−2007: 18,3%; 2008−2018: 19,9%) y, sobre todo, por cáncer (1984−1995: 21,8%; 1996−2007: 29%; 2008−2018: 26,8%) (P < ,001). En el análisis multivariante para muerte tardía cardiovascular, edad del receptor, retrasplante, diabetes y primera etapa fueron factores de riesgo, mientras que el riesgo de muerte tardía por cáncer e infecciones se asoció con las etapas recientes.
La neoplasia más frecuente en el primer año post-TR fue la enfermedad linfoproliferativa post-TR y tras el primer año el cáncer de pulmón, sin diferencias entre etapas.
A pesar de la mayor comorbilidad del receptor, las muertes cardiovasculares han descendido. Las neoplasias son la principal causa de muerte tardía en los últimos años. El cáncer de pulmón es la neoplasia más frecuente causante de MCIF en TR.
Cancer mortality after kidney transplantation: A multicenter cohort study in Italy
2024, International Journal of Cancer
Percutaneous diagnosis of an atypical presentation of pulmonary aspergillosis mimicking lung cancer in a renal transplant patient
2023, Transplant Infectious Disease

View full text

Retrospective study of the incidence and outcomes from lung cancer in solid organ transplant recipients

Highlights

Abstract

Objective

Results

Conclusion

Introduction

Section snippets

Study population

Results

Discussion

Conclusions

Funding

CRediT authorship contribution statement

Declaration of Competing Interest

Am. J. Transplant.

Lancet

Lancet

J. Thorac. Oncol.

Ann. Thorac. Surg.

Ann. Thorac. Surg.

J. Thorac. Oncol.

Am. J. Transplant.

Clin. Lung Cancer

J. Am. Acad. Dermatol.

Risk of skin cancer and other malignancies in kidney, liver, heart and lung transplant recipients 1970 to 2008—a Swedish population-based study

Int. J. Cancer

Skin Cancer’s ranks rise

JAMA

Cancer incidence before and after kidney transplantation

JAMA

Cyclosporine induces cancer progression by a cell-autonomous mechanism

Nature

Is there a survival benefit in patients with stage IIIA (N2) non-small cell lung Cancer Receiving neoadjuvant chemotherapy and/or radiotherapy prior to surgical resection

Medicine

Meta-analysis of randomized clinical trials comparing cisplatin to carboplatin in patients with advanced non–Small-Cell lung Cancer

J. Clin. Oncol.