Liquid biopsy in the detection of tumor relapse in primary peritoneal serous papillary carcinoma

Díaz Vico, Tamara; Turienzo Santos, Estrella O.; Ruiz Fernández, María Luisa

doi:10.1016/j.medcle.2021.01.022

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Turienzo Santos, María Luisa Ruiz Fernández" "autores" => array:3 [ 0 => array:4 [ "nombre" => "Tamara" "apellidos" => "Díaz Vico" "email" => array:1 [ 0 => "tamara.diaz.vico@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Estrella O." "apellidos" => "Turienzo Santos" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "María Luisa" "apellidos" => "Ruiz Fernández" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Unidad de Cirugía Oncológica Peritoneal (UCOP), Servicio de Cirugía General y del Aparato Digestivo, Hospital Universitario Central de Asturias (HUCA), Oviedo, Asturias, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Centro Médico de Asturias, Oviedo, Asturias, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Biopsia líquida en la detección de recidiva tumoral en el carcinoma papilar seroso primario de peritoneo" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1244 "Ancho" => 2925 "Tamanyo" => 195087 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Parameterization of cfDNA levels (ng/mL, plasma) (large circles) and TP53 variant allele frequency in cfDNA (%) in targeted PCR (small circles) and FoundationOne® Liquid panel (triangle)." ] ] ] "textoCompleto" => "Primary peritoneal serous papillary carcinoma (PPSPC) is a rare tumour that affects the peritoneal surface diffusely.<a class="elsevierStyleCrossRef" href="#bib0005">1</a> It has similar clinical and histological features to ovarian serous papillary carcinoma in the absence of a detectable primary ovarian tumor.<a class="elsevierStyleCrossRef" href="#bib0010">2</a> Following the latest update of the FIGO classification for the staging of ovarian tumours, the concept of mesothelial surface as the origin of ovarian epithelial tumours is discarded and the discussion of tubal carcinogenesis is introduced.<a class="elsevierStyleCrossRef" href="#bib0015">3</a>The patient is a 52-year-old female who presents with a 4-month history of diffuse abdominal pain. A chest-abdominal computed tomography (CT) scan was performed, which described multiple pericapsular hepatic lesions indicative of tumour deposits, nodular lesions in the greater omentum, right diaphragmatic and supravesical pelvic peritoneum, and capsular thickening of the right ovary, compatible with peritoneal carcinomatosis (PC). Exploratory laparoscopy was performed along with biopsy and right adnexectomy. The pathological study showed a high-grade PPSPC with absence of malignancy in the right adnexa. The patient was referred to the Peritoneal Cancer Surgery Unit of our centre in May 2015, undergoing complementary studies that showed elevated levels of CA 125: 1,145.2 U/mL. Debulking surgery was scheduled, with removal of tumour deposits in hepatic segments 6–8, cholecystectomy, omentectomy, hysterectomy and left adnexectomy, pelvic peritonectomy, appendectomy, and peritonectomy of the right hemidiaphragm, with an initial PC index of 11, final of 0 and complete debulking of 0. Hyperthermic intraperitoneal chemotherapy (HIPEC) was combined with paclitaxel 90 mg. The pathological analysis revealed PPSPC involvement in all samples submitted. He subsequently received 6 cycles of adjuvant carboplatin and paclitaxel-based chemotherapy.After a disease-free interval of 2 years, the patient presented with peritoneal recurrence confirmed by CT scan in the form of tumour deposits in the left diaphragm with spleen infiltration. Debulking surgery was scheduled again, completing peritonectomy of the remaining areas: left hemidiaphragm, mesocolon, and both leaves of the small bowel mesentery, as well as splenectomy, atypical gastrectomy of the greater gastric curvature, and removal of tumour deposits on the body and tail of the pancreas (initial PC index of 10, final of 0; complete debulking of 0). i-HIPEC (second-look surgery or repeat HIPEC) was performed, combined with adjuvant treatment, repeating the previous regimen. The pathological findings showed tumour involvement not only in the specimens with known tumour deposits, but also in the macroscopically seemingly healthy peritoneal specimens. After completing chemotherapy, Olaparib was prescribed as maintenance treatment.Throughout the entire cancer process, tumour marker monitoring and thoracoabdominal CT scan was carried out every 3–4 months, incorporating serial plasma liquid biopsies (LB) with bio-TM parametrisation for the early detection of tumour recurrence. At the time of diagnosis, the patient had elevated levels of CA 125 and circulating tumour DNA (ctDNA) (p.Cys242fs * 5 TP53). PCys242fs*5 levels TP53 remained high after the first debulking surgery, becoming negative only after i-HIPEC was performed, once the peritonectomy was completed (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). To date, no tumour relapse or elevation of tumour markers has been observed, neither in serum nor in LB, with a disease-free interval of 30 months.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Patients with early-stage disease or at risk of developing PC may benefit from increasing diagnostic alternatives. The concept of LB has evolved into a highly active field of research in search of plasma bio-TMs and is recommended as an alternative to tumour tissue analysis in some malignancies.<a class="elsevierStyleCrossRef" href="#bib0020">4</a> It encompasses the analysis of ctDNA, circulating free DNA (cfDNA), circulating tumour cells, circulating miRNAs, and exosomes. In general, cfDNA can be identified in plasma, detecting genetic and dynamic changes. Regarding PPSPC, mutation in the TP53 gene, whether or not associated with mutations in BRCA1/BRCA2, is believed to be driving the carcinogenic process.<a class="elsevierStyleCrossRef" href="#bib0025">5</a> Accordingly, we established a parameterisation by serial LB of cfDNA and ctDNA levels. Interestingly, ctDNA levels, elevated at baseline and after surgery, decreased to undetectable levels after complete peritonectomy and HIPEC, performed after confirmation of tumour relapse. The fact that plasma levels of ctDNA remained elevated after the initial surgery, despite the removal of all macroscopically visible tumour burden, leads us to consider complete peritonectomy and HIPEC as the optimal therapeutic approach for PPSPC with peritoneal extension.AuthorshipTamara Díaz Vico and Estrella O. Turienzo Santos: design and writing of the article. María Luisa Ruiz Fernández: critical review and final approval of the article. All authors have read and approved the final manuscript." 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Swerdlow" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/0002-9378(59)90287-x" "Revista" => array:6 [ "tituloSerie" => "Am J Obstet Gynecol" "fecha" => "1959" "volumen" => "77" "paginaInicial" => "197" "paginaFinal" => "200" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/13606191" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Serous ovarian and primary peritoneal cancers: a comparative analysis of clinico-pathological features, molecular subtypes and treatment outcome" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "B. Gao" 1 => "K. Lindemann" 2 => "L. Anderson" 3 => "S. Fereday" 4 => "J. Hung" 5 => "K. 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Vol. 158. Issue 1.

Pages 36-37 (January 2022)

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