The Arrow is pointing the cervix tumoral mass There was no argument on PET/CT for distant disease, and clinical benefit was reported

The Arrow is pointing the cervix tumoral mass There was no argument on PET/CT for distant disease, and clinical benefit was reported. The multidisciplinary meeting Mericitabine (multidisciplinary tumor board) discussed the option of surgery at that time. is reported. Clinical trials using poly(ADP-ribose) polymerase inhibitors for advanced cervical cancer are warranted. mutated woman diagnosed with advanced CC treated by chemoradiation, followed by the combination olaparib/bevacizumab with complete pathological response. Case presentation A Caucasian 49-year-old patient was referred to our center in January 2016 with a uterine mass of 6?cm discovered during an ultrasound examination performed for lumbar pain. Clinical examination showed a friable suspect cervix with bilateral parametrial involvement. Pelvic magnetic resonance imaging (MRI) revealed a 91-mm cervical and uterine mass, with involvement of the uterine serosa, left distal parametrium, left pelvic wall, and left hydronephrosis. Imaging revealed close contact with the rectal wall and bladder trigone without transmural invasion and a suspicious left external iliac adenomegaly. Positron emission tomography/computed tomography (PET/CT) showed no evidence of paraaortic lymph node involvement or distant metastasis. Cervical biopsy found a poorly differentiated cervical carcinoma human papilloma virus (HPV) 16 positive. A laparoscopic extraperitoneal paraaortic lymphadenectomy was performed in February 2016. Pathological report showed two nonmetastatic left external iliac nodes (2N-/2) and 23 paraaortic lymph nodes including five metastatic nodes (5N+/23): International Federation of Obstetricians and Gynecologists (FIGO) 2018 stage IIIC2. The patient received two cycles of capecitabine/cisplatin and subsequent concurrent chemoradiation (64,8 Gy in 36 fractions in the pelvic area, 45 Gy in 25 fractions in iliac and paraaortic area, and 8 concurrent cycles Erg of cisplatin). The treatment was completed in June 2016. At 3?months follow-up (September 2016), MRI showed partial response. The decision of the multidisciplinary meeting was to propose carboplatin, paclitaxel, plus bevacizumab adjuvant chemotherapy with partial response at 3?months. Patient received genetic counseling because of family history of cancers, and results returned positive in April 2017 showing a deleterious germline mutation (p.His1006Glnfs*17.c.3018_3021delTTCA) that motivated the use of PARPi. Olaparib was started (800?mg twice daily) in maintenance associated with bevacizumab. Somatic tumor testing showed that the BRCA1 germline mutation was associated with loss Mericitabine of heterozygosity and with a TP53 mutation p.Arg248Gln; c.743 G A validating homologous recombination deficiency (HRD) in this tumor. The treatment was well tolerated, despite nausea, grade 1 asthenia, and grade 4 anemia leading to dose reduction (400?mg twice daily). In January 2019, pelvis MRI showed a decrease of nearly 50% in size of the tumor residue compared with previous examinations, with persistence of a left proximal infiltration of the parametrium and fibrous retraction of the left ureter. A timeline of treatment received and Mericitabine corresponding pelvic magnetic resonance imaging is shown in Fig. ?Fig.11. Open in a separate window Fig. 1 Timeline of treatment received and corresponding pelvic magnetic resonance imaging. The Arrow is pointing the cervix tumoral mass There was no argument on PET/CT for distant disease, and clinical benefit was reported. The multidisciplinary meeting (multidisciplinary tumor board) discussed the option of surgery at that time. After reevaluation of patients medical record, we proposed surgery. A simple hysterectomy was performed in March 2019 without ureteral resection as parametrium appeared normal. No intra- or postoperative complications were noticed. Histological results showed no residual malignancy. After 1?year follow-up, clinical and radiological examinations do not show any recurrence without maintenance therapy. Discussion Mericitabine and conclusions We report the first case of a mutated patient with persistent advanced CC following chemoradiation and chemotherapy showing a complete tumor response after olaparib/bevacizumab adjuvant treatment and 12?months disease-free survival after surgery. The understanding of the molecular changes involved in the development of cancer led to the development of a new anticancer therapy known as targeted therapy and to a more personalized management of patients. In CC, therapies targeting different molecular pathways are investigated, including epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), mammalian target of rapamycin (mTOR), and poly(ADP-ribose) polymerase (PARP). An analysis of 592 samples of cervical cancer in a tumor library in the US using a combination of sequencing (that is, next-generation sequencing), gene amplification (that is, hybridization), and protein expression (that is, immunohistochemistry) identified mutations in 224 specimens (BRCA1 in 10%). These biomarkers could help guide therapy in clinical trials for patients with PARPi; mitogen-activated protein kinase, cell cycle checkpoint, and PI3K/AKT/mTOR pathway inhibitors; EGFR- and HER2-directed therapy; immunotherapy; and hormonal.