Long-term Disease Control in Lung Adenocarcinoma with Recurrent Oligometastases: PET-guided Management

Introduction

Nonsmall cell lung cancer is one of the most common malignancies worldwide and a leading cause of cancer-related death. The number of new cases worldwide in 2020 achieved 2,206,771 (11.4% of cases of all cancers, second place), and the number of new deaths was 1,796,144 (18.0% of all deaths due to cancer, first place).[1] Intramedullary cauda equina metastases (ICEM) are rare lesions in patients with malignant tumors, accounting for <1% of all metastatic sites.[2] We present a history of a 65-year-old female diagnosed with lung adenocarcinoma who achieved unusually long disease-free survival after local treatment of ICEM in the course of oligometastatic disease.

Case Report

The patient initially underwent pneumonectomy with mediastinal lymphadenectomy due to adenocarcinoma of the left lung [Figure 1], with postoperative staging pT2aN0 [Figure 1a], (November 2015). No adjuvant chemotherapy was administered. After 24 months of follow-up, ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) revealed a single lesion in the right lung, highly consistent with the recurrence of the disease (March 2018) [Figure 1b]. The patient underwent stereotactic body radiation therapy (SBRT), achieving a complete metabolic response in the control FDG PET/CT (August 2021) [Figure 1c].

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Figure 1 A series of fused ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography scans of a 65-year-old female demonstrating adenocarcinoma of the left lung, with hilar localization (a, November 2015, SUVmax 14.6, arrow); FDG-avid focal lesion in the right lung, highly consistent with recurrent tumor (b, March 2018, SUVmax 12.9, arrow); complete metabolic response of the recurrent tumor in the right lung after stereotactic body radiation therapy (completed in May 2018) (c, August 2021, arrow)

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At the same time, she was diagnosed with hypopituitarism. Based on the head magnetic resonance imaging (MRI) and FDG PET/CT, which revealed the presence of a focal lesion in the sella turcica – an adenocarcinoma metastasis of the pituitary gland was suspected (March 2018) [Figure 2a and b, respectively]. The patient received hormone replacement therapy and underwent SBRT of the pituitary gland region, with a complete radiographic and metabolic response in the follow-up MRI and FDG PET/CT, respectively (August 2021) [Figure 2c and d, respectively].

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Figure 2 A follow-up magnetic resonance imaging (MRI) (a, arrow, T1-weighted, TFE, January 2018) and ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) (b, circle, SUVmax 9.7, March 2018) demonstrating a focal, FDG-avid lesion of the pituitary gland – highly suspected for a lung adenocarcinoma metastasis. A follow-up magnetic resonance imaging (c, arrow, Dual TSE, November 2020) and FDG PET/CT (d, circle, August 2021) showing the complete radiographic and metabolic response of the pituitary gland lesion after stereotactic body radiation therapy, respectively

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After another 12 months, the patient developed low back pain radiating to the gluteal region and pudendum, waking the patient up at night. She also suffered from urine incontinence. The MRI scan revealed a lesion in the S2 region, initially interpreted as neurofibroma [Figure 3a]. During the operation, two lesions were found, from which the proximal one was bonded to the roots of the cauda equina. Postoperative histopathological examination confirmed the presence of adenocarcinoma metastaticum e pulmone, phenotype AE1 / 3+, p40−, TTF1+, p16−, WT1−, CDX2−, and SYN− and termed as ICEM [Figure 4]. The following FDG PET/CT revealed residual focal uptake in the S1/S2 region (August 2021) [Figure 3b], interpreted as incomplete resection of the lesion. Moreover, the patient still suffered from urodysfunction and pain in the sacral region, nonresponding to painkillers. Hence, she was referred to adjuvant radiotherapy (November 2021) [Figure 3c]. After 7 months, a follow-up MRI scan revealed no pathological lesions in the sacral region [Figure 3e], whereas FDG PET/CT showed only diffuse, mild residual uptake consistent with postradiotherapeutic changes and no other metastases (June 2022) [Figure 3d].

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Figure 3 A follow-up magnetic resonance imaging (MRI) (a, arrow, T2-weighted, SPC, June 2021) and ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) (b, SUVmax 14.2, arrow, August 2021) showing residual, focal, FDG-avid lesion in the S1/S2 region, interpreted as incomplete surgical resection of intramedullary cauda equina metastases. Radiation therapy planning dose distribution is shown in panel c (November 2021). Another follow-up FDG PET/CT (d, June 2022) showed diffuse, mild residual uptake in the S1/S2 region (arrow) consistent with postradiotherapeutic changes, with no signs of recurrence in MRI (e, arrow, T2-weighted, TSE, January 2023)

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Figure 4 Postoperative histopathological evaluation of the lesion resected from cauda equina, demonstrating the presence of metastatic cells (a and b, H and E staining), with pan-cytokeratin positive staining (c) and TTF1 positive staining (d) at immunistochemistry – confirming their pulmonary origin

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Discussion

Specific low back pain is very rare and requires a proper diagnostic process. Their frequency is estimated at around 10% of all back pains. Among specific low back pains, only 0.7% occur as a result of cancer and malignancies. In most cases, malignancy-induced back pain is a result of the spinal stenosis due to external compression of the neoplastic lesion, whereas ICEM is a rare entity resulting from direct compression and damage of the nerve root of cauda equina by the metastatic lesion.[23]

The lung cancer is known as the most common origin of metastases to the cauda equina (18.7%). Other significant malignancies metastasizing to cauda equina are: breast cancer (13%), renal cancer (11.4%), and prostate cancer (10.6%). On the other hand, the most characteristic metastatic sites for lung adenocarcinoma involve nervous system, skeleton, liver, contralateral lung, and adrenal glands.[4]

The most common symptom of ICEM is low back pain, present in 74% of patients. Other symptoms include motor weakness, radiculalgia, and sphincter dysfunction. If the neuronal roots are not decompressed in time, it may make the radicular pain worsen and lead to mioparalysis. A lack of medical intervention can make the symptoms irreversible.

ICEM is a late complication – it occurs after about 36 months after the diagnosis of a primary tumor.[5] In our patient, ICEM was stated after 67 months from the cancer diagnosis, although the pain had started before and slowly exacerbated.

The lesion eventually recognized as ICEM in our patient was first noticed in MRI; however, it was the FDG PET/CT which played a key role in the following diagnostic and therapeutic process. It allowed us to determine the precise staging of the cancer, confirm the presence of residual malignant process, determine its extent, and finally confirm the remission. In some cases, PET may prevent from performing unnecessary invasive procedures.[6]

The standard therapy in case of ICEM remains surgical resection with adjuvant radiotherapy. Even a subtotal resection leads to significant pain alleviation.[7] Despite a good local response to the therapy, most patients die within a few months after the diagnosis, not because of the ICEM itself but as a result of the advanced malignant process in their body. In those cases, surgical resection of the tumor in the spinal canal is a part of palliative therapy.[78] In our case, there were no other metastases at the time of the ICEM treatment; therefore, the patient was treated with radical intent due to oligometastatic disease.

More than 24 months after the completion of the local treatment of ICEM, there have been no clinical or radiological signs of recurrence of the malignant process.