Stereotactic Body Radiotherapy in a Transplanted Lung for a Primary Lung Cancer: Case Report

Abstract

Introduction

Lung cancer in the transplanted organ is an extremely rare occurrence with very few cases reported. The use of stereotactic body radiotherapy (SBRT) for medically inoperable early stage non-small cell lung cancer is an option to treat an early stage lung adenocarcinoma on a transplanted lung.

Case Presentation

We report the case of a 63-year-old woman with a history of hypersensitivity pneumonitis, who underwent a right lung transplant in 2010 and developed pulmonary adenocarcinoma, stage IA2, in 2023. The patient was ineligible for surgical management and was referred for SBRT. The treatment was administered with a total dose of 48 Gy in 4 fractions in December 2023. The nodule remained stable at 9-month follow-up, with post-radiogenic pneumonitis observed. Pulmonary function remained stable after treatment.

Conclusions

This case shows that SBRT on a transplanted lung cancer seems to be safe, even maintaining a standard SBRT fractionation, with good early local control. Careful consideration of dose, fractionation, and potential toxicities is essential in managing these complex cases, always in close cooperation with the transplant medical team.

Introduction

The need for lung transplant is a life-saving treatment for patients with end-stage lung disease [1]. The incidence of cancers in transplanted patients is known to be higher, a risk that is also present for primary lung cancer [2]. However, lung cancer in the transplanted organ is an extremely rare occurrence with very few cases reported in the literature. In parallel, the use of stereotactic body radiotherapy (SBRT) for medically inoperable early stage non-small cell lung cancer is now standard practice for patients without surgical conditions [3]. Here, we present a case where SBRT was used safely to treat an early stage lung adenocarcinoma (ADC) on a transplanted lung.

Case Presentation

We report the case of a 63-year-old Caucasian woman with a personal history of hypersensitivity pneumonitis treated with a right lung transplant in November 2010. Other significant comorbidities are renal chronic failure in the context of insulin-dependent diabetes mellitus and chronic immunosuppression with tacrolimus + azathioprine + prednisolone, for which she initiated hemodialysis in June 2023.

In a follow-up thoracic scan in September 2022, a pulmonary nodule appeared in the right superior lobe with a size of 16 × 11 mm (shown in Fig. 1). At the next follow-up, in April 2023, the pulmonary nodule increased in size presenting with an axial diameter of 18 × 18 mm.

Fig. 1.

Axial slice of chest CT at initial diagnosis showing the nodule in right superior lobe.

The nodule was subject to a transthoracic biopsy which proved a pulmonary ADC with 40% PD-L1 expression and EGFR mutation in exon 20. The patient was staged by ¹⁸F-FDG PET/CT and brain MRI, without other sites of disease. Therefore, a cT1bN0M0 – stage IA2 was determined.

Pulmonary function tests since 2016 showed stable forced expiratory volume in 1 s (FEV1), within the 1,410 and the 1,670 mL range. The FEV1/forced vital capacity varied between 55% and 77%. The most recent evaluation was from October 2023 and showed a FEV1 of 1,510 mL (67% of the predicted value).

The patient, due to its comorbidities, was referred for SBRT to the ADC lung tumor. Prior to treatment, the immunosuppression was discussed with the transplant medical team and decided to discontinue azathioprine, maintaining the remaining immunosuppression, tacrolimus, and prednisolone, at the lowest possible doses.

For the radiotherapy simulation, a 4D-CT with 2-mm-thick slices was performed with vacuum cushion immobilization and both arms raised above the head using an arm rest. The treatment volumes were defined as follows: the gross tumor volume was contoured on five different respiratory phases, namely the end-inspiratory, the end-expiratory phases and 3 intermediate phases, no margin for microscopic disease extension was used; the internal target volume was generated by merging gross tumor volumes from all phases; the planning target volume was generated by a geometrical margin of 0.5 cm around the internal target volume. The treatment was delivered with free breathing and daily megavoltage cone beam CT – based guidance to verify the treatment position.

A total dose of 48 Gy was prescribed, in 4 fractions of 12 Gy (biological effective dose, BED10 = 105.6 Gy). The planning target volume was covered by the 48 Gy isodose level in 95.5% of the volume with a good conformity of the isodose distribution (shown in Fig. 2). In terms of organs at risk, due to the rarity of the clinical situation, there were no specific constraints that warranted safety. Therefore, usual SBRT constraints were respected with special attention to minimize dose to the lung. The mean dose for the lungs was 3.05 Gy and the volume of lung receiving ≥20 Gy or more (V20) was 2.72% (shown in Table 1).

Fig. 2.

Axial and coronal slices representing SBRT isodose distribution of 95% and 50% prescription dose.

Table 1.

Organs at risk dose statistics

OAR	Volume of interest	Maximum dose
Total lung	D1500cc = 0.2 Gy
	D1000cc = 0.4 Gy
Heart	D15cc = 1.2 Gy	4 Gy
Skin	D10cc = 8.1 Gy	16.2 Gy
Esophagus	D5cc = 3.6 Gy	7.7 Gy
Proximal bronchial tree	D4cc = 4.5 Gy	7.1 Gy
Ribs	D1cc = 48.7 Gy	51.3 Gy
Spinal cord	D1.2cc = 6.7 Gy	9.9 Gy
	D0.35cc = 8.2 Gy

The patient was planned with volumetric modulated arc therapy using 3 arcs with energy of 6 MV flattening filter free. The patient was treated between December 20, 2023, and December 29, 2023, in a Varian Novalis Tx equipment. Treatment was well tolerated with no adverse acute events or measurable toxicity.

On her first reevaluation by CT in February 2024 the nodule remained stable with 21 × 17 mm (shown in Fig. 3a), without evidence of regional disease. On her second evaluation by CT in May 2024, half year after treatment, the lesion remained stable with 21 × 14 mm and peripheral signs of post-radiogenic pneumonitis (shown in Fig. 3b). Her pulmonary function test remained stable after the treatment, evaluated in June 2024, with a FEV1 of 1,550 mL and a FEV1/forced vital capacity of 70%. In July 2024, the patient reported cough and worsening fatigue and subsequently was diagnosed with COVID-19, prompting an increase in daily prednisolone to 10 mg. In her most recent reevaluation, in September 2024, 9 months after the treatment, the TC showed partial remission of the radiogenic pneumonitis while the nodule remained table without other signs of disease (shown in Fig. 3c). The treatment was overall well tolerated, and the disease remained stable without other significant toxicity.

Fig. 3.

a Axial slice of chest CT at first evaluation after treatment showing a stable nodule in right superior lobe. b Axial slice of chest CT 6 months after treatment showing a stable nodule in right superior lobe with associated post-radiogenic pneumonitis. c Axial slice of chest CT 9 months after treatment showing a stable nodule in right superior lobe with partial response of the post-radiogenic pneumonitis.

Discussion

The clinical context of this case report, a primary tumor on a transplanted organ, and the specific intervention decided and described here, a stereotactic treatment on a transplanted lung, is a very rare occurrence. It has been rarely described in the literature and almost always in single case reports [4, 5]. Therefore, various uncertainties need to be addressed in order to establish a therapeutic plan, in what is a challenging clinical scenario without a well-established care algorithm.

First, in an early stage pulmonary tumor, standard of care treatment would be surgical resection. In this patient, with significant comorbidities, poor pulmonary function, and multiple chronic medications, including immunosuppressants, it was deemed nonviable to pursue this treatment option. That being the case, SBRT is a clear and established alternative for patients without surgical conditions, as the best possible option [3].

Second, transplanted patients on immunosuppression not only have an increased risk for certain tumors, including lung cancer, but also raise numerous doubts concerning the cancer natural history [6, 7]. While some reports suggest no difference in overall survival, progression-free survival, and local control rates compared to immunocompetent patients, concerns remain regarding the risk of distant metastasis and response to SBRT under immunosuppressive conditions [8].

Finally, the risk of adverse events and potential toxicities in a transplanted organ with impaired function influenced the choice of SBRT dose and fractionation. A standard SBRT dose of 48 Gy in 4 fractions was selected, balancing the need for effective local control with the risk of toxicity. This decision considered the tumor’s location and dosimetric constraints, despite the lack of specific data for transplanted organs. It is also important to state a limitation of this case report as no specific genetic or biological analyses were performed to understand whether the lung cancer in this patient originated from the donor or the recipient.

Posttreatment evaluation showed successful local tumor control at an early 9 months follow-up which needs to be reevaluated at short term and closely followed. Most importantly, in terms of toxicities, even though radiologic findings of post-radiogenic pneumonitis and the patient complaints of subtle fatigue associated with cough, overall, this case reassures the safety of the approach.

Conclusion

This case shows that SBRT on a transplanted lung cancer seems to be safe, even maintaining a standard SBRT fractionation, with good early local control and showing promising prospect of overall disease control. Careful consideration of dose, fractionation, and potential toxicities is essential in managing these complex cases, always in close cooperation with the transplant medical team.

Statement of Ethics

Written informed consent was obtained from the patient for the publication of this case report and any accompanying images. Ethical approval is not required for this case report in accordance with local or national guidelines. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000542713).

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

This study was not supported by any sponsor or funder.

Author Contributions

P.F.: manuscript preparation, data collection, and literature search; D.M. and M.A.: manuscript revision. All authors read and approved the final manuscript.

Funding Statement

This study was not supported by any sponsor or funder.

Data Availability Statement

All data generated or analyzed during this study are included in this article and its online supplementary material files. Further inquiries can be directed to the corresponding author.