Abscopal Effect: A Very Rare Case Report

Abscopal Effect: A Very Rare Case Report

S.Mhirech1, N.Kanouni1 , M.Wassi 1,  H. Medyouni² , J.Chouef ² FZ.Farhane1, Z. Alami1, T.Bouhafa1

1.  Radiotherapy Department, Oncology Hospital, CHU HASSAN II de Fès.

2. Medical Oncology Department, Oncology Hospital, CHU HASSAN II de Fès.

 

*Correspondence to: S. Mhirech, Radiotherapy Department, Oncology Hospital, CHU HASSAN II de Fès.

 

Copyright.

© 2024 S. Mhirech. This is an open access article distributed under the Creative Commons Attribution   License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Received: 01 April 2024

Published: 26 April 2024

DOI; https://doi.org/10.5281/zenodo.11105142

 

Abstract

We report the case of a 48-year-old woman, admitted for the management of a well-differentiated squamous cell carcinoma of low keratinization infiltrating the uterine cervix classified IIb according to the FIGO classification. The patient underwent 3D external radiotherapy concomitantly with 2 courses of cisplatin chemotherapy and 1 course of carboplatin and four sessions of HDR brachytherapy. The clinical and radiological evolution after the end of treatment was marked by the appearance of local tumour progression with the development of metastatic peritoneal carcinosis, prompting the decision to start palliative chemotherapy, which the patient refused. Two years later, the patient had received no further treatment, and returned with a pelvic MRI showing complete disappearance of the cervical tumour process and peritoneal carcinosis.

This case represents a rare instance of abscopal resolution of metastatic cancer after concomitant radiotherapy and chemotherapy. A literature review of the history of the abscopal effect of radiotherapy was discussed.

Abscopal Effect: A Very Rare Case Report

Introduction

The abscopal effect is defined as the effect induced by radiotherapy on tissues far from the irradiation field. This phenomenon was first described in 1953 by Mole (1). 70 years after Mole's definition, there is still no clear definition of the extent of the abscopal effect, and abscopal effects remain a minority and unpredictable.

 

Observation

We report the case of Mrs. Y.S, 48 years old, with no particular pathological history, who developed spontaneous metrorrhagia 9 months prior to her consultation, in a context of apyrexia and altered general condition, prompting her consultation at the obstetric gynecology department of the Hassan II University Hospital in Fez.

On physical examination, the patient was conscious, hemodynamically and respiratorily stable, with normo-color conjunctiva.

  • -> Vaginal touch: Perception of an irregular 6 cm mass with endocervical development and hard consistency, with invasion of the cul-de-sacs, especially anterolateral on the left, as well as the upper 1/3 of the vagina.
  • -> Rectal examination: perception of a hard, irregular mass, bilateral involvement of parameters.
  • -> Bidigital touch: recto-vaginal septum intact.

 

The patient underwent biopsy of the cervical lesion described above, the results of which were consistent with a well-differentiated squamous cell carcinoma of low keratinization infiltrating the uterine cervix.

Pelvic MRI revealed a 6x4 cm tumoral process of the uterine cervix with the following relationships:

  • Top: Invades the uterine isthmus.
  • Bottom: extends to the posterior vaginal cul de sac and invades the upper 1/3 of the vagina on the posterior wall.
  • Anterior: comes into contact with the bladder with no sign of invasion.
  • Posteriorly, it contacts the recto-sigmoid hinge without parietal thickening.
  • Laterally: it infiltrates the parametrium bilaterally, with restriction to the anterior part of the right parametrium and extension of the tumour to the surface of the uterine body on the left.
  • Peri-lesional and bilateral external iliac lymph node formation of 6.5mm short axis for the largest external iliac.
  • There were no lombo-aortic adenopathies.
  • Both ovaries were follicular, measuring 39x20mm on the left and 44x23mm on the right.
  • No peritoneal effusion.
  • Conclusion: Tumoral process of the uterine cervix classified FIGO IIb.

 

A CAT scan in the absence of a pet scan showed no secondary distant localization.

The patient's case was discussed at a multidisciplinary consultation meeting, with the decision to carry out concomitant chemoradiotherapy.

The therapeutic strategy, the course of radiotherapy sessions and concomitant chemotherapy, as well as any possible side effects of the treatment, were explained to the patient.

The patient underwent a centring CT scan, positioned in a comfortable and reproducible supine position, with hands on the chest and knee and callus supports, aligned with anatomical landmarks using 2 lateral and 2 transverse wall lasers, then acquired 3 mm sections from the D11-D12 joint line to the upper two-thirds of the femur in two C- and C+ steps, and the images transferred to the TPS.

The patient underwent 3D external radiotherapy with photons of 10 to 18 Mev energy, using 4 beams with a total dose of 46 Gy over the pelvic lymph nodes in 23 fractions of 2 Gy/fraction, with a boost on the parameters of 9 Gy in 3 fractions of 3Gy/fraction spread over 42 days, concomitantly with 2 courses of cisplatin-type chemotherapy and 1 course of carboplatin.

During concomitant radiochemotherapy, the patient had developed renal failure and neutropenia.

The patient underwent 4 sessions of HDR brachytherapy at a dose of 7Gy/session after the end of concomitant radiochemotherapy.

A TAP CT scan was performed 1 month after the end of treatment, as bilateral lumbar pain persisted, showing partial regression of the locally advanced cervical tumour process, with the appearance of bilateral ovarian tumour masses associated with trans-tubal implantation metastases, including the one on the left responsible for homolateral uretero-hydro-nephrosis. Diffuse micronodular mesenteric infiltration, with intraperitoneal effusion in the 2 parietocolic gutters bilaterally.

 

GO examination two months after completion of treatment:

  • ->Speculum: post-therapeutic vaginal symphysis in the upper 1/3 of the vagina with presence of a 1-cm defect surrounded by superficial erosions of the vaginal mucosa with emergence of fetid hydrorrhea.
  • ->Vaginal touch: supple vaginal walls.
  • ->Rectal touch: Perception of a 3 cm hard mass at cervical level, the 2 parameters were indurated, related to either fibrosis or invasion.

Pelvic ultrasound performed on the same day as the gynaecological examination showed an anteverted anteflexed uterus measuring 7 cm x 4.9 cm: heterogeneous appearance of the cervix, presence bilaterally of 2 ovarian masses taking up Doppler in places measuring 5 cm x 4 cm on the left and 4 cm x 3 cm on the right, suggestive of ovarian metastases.

Pelvic MRI showed a tumour-like tissue infiltrate circumscribing the entire cervix and measuring 65 mm long, enveloping the 2 ureters with ureteropyelo-caliceal dilatation and coming into intimate contact with the floor. Both ovaries showed some cystic formations whose semiological appearance was suggestive of haemorrhagic cysts.

GO examination four months after completion of treatment:

  • -> Speculum: foul-smelling pyorrhoea, orifice impossible to visualize, with infiltration of the collapsed cul de sacs and induration of the anterior vaginal wall extending to the lower 1/3.
  • -> Vaginal examination: tumoral neck with 7 cm loss of substance in its center, reaching as far as the lateral vaginal wall, which is immobile.

The decision of the PCR was to perform 3 courses of Carboplatin AUC5 + pacli chemotherapy, followed by assessment of the feasibility of surgery.

The patient refused chemotherapy and disappeared from view for 2 years after completion of concomitant radiochemotherapy + brachytherapy.

Pelvic MRI evaluation:

  • ->No evidence of local tumour recurrence.
  • -> Bilateral latero-uterine fibrous remnants still in the inflammatory stage, including a chronic minimal hydrosalpinx on the left.
  • ->Adherent pelvis.

 

Discussion

The abscopal effect is defined as a phenomenon of regression of a lesion located at a distance from the beams of radiotherapy, and was first described in 1953 by Mole (1): the abscopal effect comes from the Latin "ab scopus" and means "at a distance from the target". A recent review is provided by Siva et al. who analyzed 10 cases from 1973 to 2011, in whom no systemic treatment had been given during or after radiotherapy (2). For example, MacManus et al. reported the case of a kidney cancer patient with mediastinal and pulmonary metastases. These secondary lesions had completely regressed on a CT scan carried out at 6 months, after antalgic irradiation of the primary tumour (20 Gy in ten fractions) (3). In this review, anti-tumor response was delayed by an average of six months, and the median duration of effect was 21 months. Five of the ten tumors subsequently recurred or progressed (2). A number of studies have examined the effects of radiotherapy on the immune system, both locally and at a distance from irradiation. Indeed, in mouse models, several arguments indicated that partial irradiation of the lungs could induce effects in the adjacent hidden lung volume outside the irradiated field, through the induction of inflammatory cytokines (4).

However, the mechanisms involved remain uncertain, but in-depth study of the cellular and molecular mechanisms involved in the abscopal effect have described that radiotherapy triggers, among other things, an immunogenic death that induces the release of tumor antigens, the secretion of numerous cytokines and "danger signals" (5). The latter lead to phagocytosis of tumour cells and debris by antigen-presenting cells (APCs), which present tumour antigens to CD8+ T lymphocytes (LTCD8+) via Major Histocompatibility Complex (MHC) 1, whose expression is increased by radiotherapy (6). LTCD8+ then migrate to tumor sites, initially irradiated or outside treatment fields, where they interact with tumor cells presenting tumor antigen via MHC 1. LTCD8+ will then release cytotoxic molecules (perforin, granzyme B) and kill the tumor cell (for review (7)). However, radiotherapy also induces immunosuppressive mechanisms. This is why the abscopal effect is not systematic! Immunosuppressive mechanisms include infiltration of immunosuppressive cells (T regulatory cells (Treg), Myeloid-derived suppressor cells (MDSCs), etc.), induction of Programmed death-ligand 1 (PD-L1) expression, and secretion of Transforming Growth Factor (TGF ) (8). Thus, the factors that modulate this immunoactivation/immunosuppression balance play a central role in triggering the abscopal effect.

 

Conclusion

Radiotherapy can induce an immune response, giving it a new dimension; transforming it from a targeted local treatment to one with systemic activity that can lead to an abscopal effect. This opens up new prospects for curative radiotherapy of metastatic disease.

 

References

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3. MacManus MP, Harte RJ, Stranex S. Spontaneous regression of metastatic renal cell carcinoma following palliative irradiation of the primary tumour. Ir J Med Sci 1994;163:461–3.

4. Khan MA, Van Dyk J, Yeung IWT, Hill RP. Partial volume rat lung irradiation; assessment of early DNA damage in different lung regions and effect of radical scavengers. Radiother Oncol 2003;66:95–102.

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8. Wennerberg E, Lhuillier C, Vanpouille-Box C, Pilones KA, Garcia-Martinez E, Rudqvist NP, et al. Barriers to radiation-induced in situ tumor vaccination. Front Immunol 2017;8:229.