(P 23) METASTATIC ALVEOLAR SOFT PART SARCOMA: PREGNANCY-RELATED WORSENING AND SPONTANEOUS EXCEPTIONAL REMISSION POSTPARTUM- A CASE REPORT.

Objective: Documented evidence on the influence of pregnancy on sarcoma progression is limited. While a few cases of Ewing's sarcoma and synovial sarcoma potentially influenced by pregnancy have been reported, there are even fewer cases suggesting a possible relationship between pregnancy and alveolar soft part sarcoma (ASPS). This case report examines a rare instance where ASPS, initially diagnosed before pregnancy, worsened during pregnancy and then experienced spontaneous resolution after delivery. The report highlights potential mechanisms and implications for management and treatment during this critical period.

Methods: We present a 35-year-old female who was referred to our early-phase clinical research facility at UCLH for potential enrolment in one of our clinical trials during the last quarter of 2023.

Her oncology history began in 2006 when she was diagnosed with ASPS in the right lower limb. She underwent surgical resection followed by adjuvant radiotherapy, achieving disease-free status. Regular chest x-rays were conducted until 2016, with no identified lesions during this period. Subsequently, she was discharged from follow-ups.

In 2016, an incidental discovery of Chiari malformation led to conservative management, with annual MRI brain/spine follow-ups. In early 2021, three suspicious lung lesions were incidentally detected on annual brain/spine MRIs, prompting consent for a lung lesion biopsy. Unfortunately, the lung biopsy confirmed metastatic ASPS.

A follow-up scan a few months later showed mild reduction in lung nodules. Considering these results, a conservative approach (watchful waiting) was adopted.

Notably, the patient experienced a miscarriage in July 2022, coinciding with an increase in the size of lung lesions on a chest CT performed shortly after the miscarriage. Subsequent CT chest scans in July 2022 showed the first lesion measuring 3.6cm (from 3.2cm), the second lesion 2.8cm (from 2.4cm), and the last lesion 2.5cm (from 1.5cm).

She became pregnant again in September 2022. In December 2022, a chest ultrasound was requested to assess lung disease, but it was unable to evaluate lung lesions. No MRI chest was requested at this point. The delivery took place in June 2023.

In August 2023, a CT chest revealed multifocal progressive disease with the first lung lesion measuring 5.6cm (from 3.5cm), the second lesion 2.7cm (from 1.6cm), and the third lesion 2.4cm (from 1.6cm).

In September 2023, she was referred to our early-phase clinical trials clinic. Consent was obtained for her to receive a combination of a tyrosine kinase inhibitor and immunotherapy. The protocol mandated a new baseline whole-body CT (head/chest/abdomen/pelvis). The CT conducted in October 2023 showed a single lung lesion with a diameter of 3.3cm, with the other two lesions having resolved. The CT findings were re-reviewed during a multidisciplinary team meeting the following week, confirming the above results.

Consequently, she was deemed ineligible for the trial due to the requirement for recent progression as per the trial protocol. She was discharged to the care of her primary oncologist.

Results: The rapid progression and subsequent spontaneous resolution of lung metastasis observed in this case are hypothesized to be influenced by hormonal factors such as progesterone, estrogen, and/or β-HCG. However, immunohistochemistry results from a 2021 lung metastasis sample showed negative oestrogen receptor (ER) and progesterone receptor (PR). MLH1, MSH2, and MSH6 were intact, but further markers such as β-HCG or NGS were not assessed due to limited tissue availability.

Additionally, low levels of oestrogen, progesterone, LH, and FSH observed in December 2023 and May 2024, five and nine months post-delivery respectively, coincide with ongoing improvement of lung metastasis. Hormonal dynamics during or before pregnancy were not assessed. Repeated CT scans in January and April 2024 confirmed sustained spontaneous resolution of the lung lesions.

Had this patient been enrolled in our clinical trial earlier or received cancer treatment immediately after delivery, the observed improvement might have been attributed to treatment, potentially prolonging treatment duration with associated side effects.

Conclusion: Hormonal factors likely played a role in the observed rapid progression and resolution of ASPS in this patient. However, further studies are necessary to confirm this association. A retrospective analysis of a larger cohort of ASPS patients, specifically assessing significant progression during pregnancy, could provide valuable insights. Additionally, a follow-up study focusing on patients with ASPS who become pregnant would be insightful.

At present, careful evaluation of disease progression in ASPS patients post-delivery before initiating cancer treatment is crucial. This approach aims to avoid unnecessary exposure to treatment side effects when the disease may be undergoing spontaneous improvement.