Long-Term Tumor Control After Carbon Ion Radiation Therapy Boost in Locally Advanced Cervical Clear Cell Adenocarcinoma

Abstract

Clear cell adenocarcinoma of the uterine cervix is a rare and aggressive subtype of cervical cancer, typically resistant to conventional radiation therapy and lacking dedicated treatment guidelines. We present the case of a young patient with an ataxia telangiectasia mutation and locally advanced disease, who was unfit for brachytherapy following standard chemoradiotherapy and subsequently received a carbon ion radiation therapy boost. This mixed-beam strategy was well tolerated and led to durable local control along with a nodal response, which is suggestive of a possible abscopal effect. These findings underscore the potential of carbon ion radiation therapy in overcoming radioresistance and suggest a contributory role of genetic background in mediating systemic immune effects.

Keywords: Abscopal effect; Carbon ion radiation therapy; Cervix; Clear cell adenocarcinoma.

Figure 1

Schematic summary of the patient's therapeutic pathway.

Figure 2

Magnetic resonance imaging (MRI) of the pelvic lesion before and after carbon ion radiation therapy (CIRT) boost. (A) and (B) Pretreatment MRI in the sagittal (A) and axial (B) planes shows a pathological mass centered at the level of the uterine cervix, infiltrating the posterior vaginal fornix and the posterior wall of the upper third of the vagina. The lesion demonstrates multilobulated margins with nodular extensions, including an anterior nodule invading 15 mm into the right parametrium. Posteriorly, the mass infiltrates the anterior perirectal fat tissue with a distance of 2 mm from the rectum. An exception is noted for a pseudo-nodular extension that comes into close contact with the anterior wall of the proximal rectum, with no clearly discernible intervening fat plane. (C) and (D) Post-treatment MRI in the sagittal (C) and axial (D) planes obtained 6 months after the CIRT boost demonstrates a complete response.

Figure 3

Summed dose distribution of the 2 treatment plans (dose from external beam photon radiation therapy and carbon ion radiation therapy - CIRT), expressed in EQD2. The photon beam plan was prescribed at 95% of the volume, while CIRT was at 50% of the volume. The nominal prescribed median total dose to the clinical target volume (CTV) exceeded 94.8 Gy(RBE). Due to the proximity of critical organs at risk, the dose was reduced in the cranial portion of the CTV. Note that the two planning CT scans were registered using different patient setup conditions.

Figure 4

Pedigree of the family. The arrow points to the proband. + = carrier of the ATM gene variant; - = non-carrier of the ATM gene variant; CML = Chronic myeloid leukemia; PDAC= pancreatic ductal adenocarcinoma

Figure 5

18F-FDG PET/CT images showing metabolic response of para-aortic lymphadenopathy. (A) Pathological hypermetabolic uptake (outlined in red) involving the para-aortic lymphadenopathy, which was progressing after conventional chemoradiotherapy and was not included in the carbon ion boost treatment plan. (B) A complete metabolic response at this site on the first PET scan performed 6 months after the boost.