ABSTRACTS

Urethral carcinoma: A rare disease but yet no clear guideline for treatment

Female urethral carcinoma is among the rarest types of neoplasia of the genitourinary tract and corresponds to 0.003% of all malignant neoplasias occurring in the female urogenital tract. Of the urethral cancers, 70% are squamous cell, 20% are transitional cell, and 10% are adenocarcinoma. Primary urethral adenocarcinoma in women is a rare malignancy of unclear origin.

We present the case of a 69-year-old woman diagnosed in 2015 with an adenocarcinoma of the urethra (pT4N0R1L0Pn1), treated by cystectomy and hysterectomy, adnexectomy and lymphadenectomy followed by radiotherapy. One year later, a PET-CT scan showed micro-nodules in the lungs and a biopsy confirmed the diagnosis of disseminated adenocarcinoma from the urethra. The patient was discussed by our multidisciplinary oncology treatment team and we decided to treat the patient with carboplatin and taxol. A CT scan after three courses of treatment revealed a partial response. It is not clear whether the patient would have benefited from adjuvant chemotherapy since the tumour extent was large.

This is an extremely rare case with no clear guidelines regarding treatment. Options for treatment of female urethral carcinoma include surgery, radiation therapy and chemotherapy, alone or in combination. Treatment has tended toward a multimodality approach in recent years. For advanced female urethral cancer, a combination of chemotherapy, radiation therapy and surgery is recommended for optimal local and distant disease control.

Autoimmune Thrombocytopenia: Another Toxicity Induced by Immunotherapy

Metastatic urothelial bladder carcinoma is an incurable disease. For years, the therapeutic options were limited to platinum based chemotherapy with modest efficacy. Considering the large mutational burden in bladder cancer, immunotherapy became a standard of care in the second line and in the front line when patients are unfit for platinum based regimen. Thus, oncologists are dealing with new side effects and toxicities.

We report the case of a 66-year-old male patient, smoker, diagnosed with urothelial bladder cancer, with initial metastases to the lungs, retroperitoneal and mediastinal lymphadenopathies. He received a first-line chemotherapy consisting of cisplatin and gemcitabine. After 3 cycles, the evaluation showed a partial response. The response was maintained after 6 cycles and a decision of therapeutic pause was taken. Three months later, the follow-up imaging revealed pulmonary and nodal progression. Immunotherapy was initiated with a checkpoint inhibitor. Partial response was obtained after 3 cycles with good clinical and biological tolerance. After the fourth cycle, he developed an isolated grade I thrombocytopenia that worsened to grade III, before the administration of the sixth cycle. CT-scan confirmed the persistence of partial response. Immunotherapy was put on hold. A bone scan excluded bone metastases. Bone marrow aspirate and biopsy were in favor of a peripheral origin of thrombocytopenia without any dysplasia or infiltration by metastatic cells. After completing the viral and autoimmune work-up, the diagnosis of autoimmunethrombocytopenia secondary to immunotherapy was made. The patient received the same regimen administered for idiopathic thrombocytopenic purpura based on dexamethasone 40 mg daily for 4 days. Platelet count began to recover with normalization after one week. Immunotherapy was discontinued. Six months later, the disease progressed with interval appearance of new liver metastases. A third line chemotherapy was administered without any response. The patient’s clinical condition deteriorated and he died as a result of progression of the metastatic disease. Autoimmune thrombocytopenia has been rarely reported as an autoimmune disorder related to immunotherapy. Clinicians must exclude all other causes of thrombocytopenia before validating this diagnosis. Its management is extrapolated from that of idiopathic thrombocytopenic purpura.

From breast implants to squamous cell carcinoma

Squamous cell carcinoma is a malignant neoplasm of squamous cell of the epidermis, it has the potential for rapid growth and a low but significant risk of metsastasis and death. Chronically injured skin is one of the risk factors for the development of cutaneous Squamous cell carcinoma.

Hereby, we describe the case of a 44-year old woman who had a right breast prosthesis with many surgical re-interventions for aesthetic reasons, at least eight operations were done over nine years complicated each time by superimposed infections at the site of the interventions.

During the last procedure, skin biopsies revealed keratinizing, well-differentiated squamous cell carcinoma, tumor was infiltrating the lower quadrants of the breast, and deeply infiltrating the 3^rd, 4^th and 5^th ribs along with lymph nodes involvement (axillary and internal mammary chain).

Six cycles of Carboplatine with Paclitaxel were received as neoadjuvant chemotherapy but unfortunately the fluorodeoxyglucose (FDG)-positron emission tomography (PET) showed a disease progression; subsequently we decided to go for surgical resection planned in the upcoming two weeks.

A rare tumor of the parotid gland

Epithelial-myoepithelial carcinoma (EMC) is a rare type of malignant tumor, accounting for about 1% of all salivary gland tumors arising most commonly in the parotid gland, but it has also been described in the submandibular gland as well as in minor salivary glands and palate. A biphasic cell arrangement formed by an inner layer of duct-forming epithelial cells and an outer layer of myoepithelial cells is the histological hallmark

Herein, we describe the case of a 44 year old patient diagnosed with an epithelial-myoepithelial carcinoma of the right parotid treated surgically with positive margins, followed by adjuvant radiotherapy; a next generation sequencing showed a HRAS Q61R mutation; three years and a half later he relapsed with lung metastasis treated by surgical excisions along with a platinum based therapy coupled with 5-FU but two years later new lung lesions were seen and the platinum based therapy coupled with 5-FU was adopted again with a stable disease; hence he was started on oral cyclophosphamide for one year; once again, those lung lesions kept on increasing in size and number and once again the platinum based therapy coupled with 5-FU was prescribed but stopped after 6 months for intolerance and major asthenia, and a we decided to stop the treatment . After a median follow up of three years, the disease is always stable and there’s no evidence of loco-regional recurrence.

Genomic profiling of patients with metastatic castration-resistant prostate cancer (mCRPC) for the evaluation of rucaparib: next-generation sequencing (NGS) of tumour tissue and cell-free DNA (cfDNA)

Background

The phase 2 TRITON2 (NCT02952534) and phase 3 TRITON3 (NCT02975934) studies are evaluating the poly(ADP-ribose) polymerase inhibitor rucaparib in patients with mCRPC who have a deleterious germline or somatic mutation in BRCA1, BRCA2, ATM, or other DNA damage repair (DDR) gene. Here we present interim results of central genomic screening of tissue samples and plasma cfDNA in TRITON2 and TRITON3.

Methods

Formalin-fixed paraffin-embedded (FFPE) tumour tissue samples were profiled for genomic alterations in 395 genes, and plasma samples were profiled for genomic alterations in 70 genes, using Foundation Medicine, Inc., NGS assays.

Results

As of 2 July 2018, 1311 tumour tissue blocks (73%) and slides (27%) from primary prostate cancer tumours (84%) and metastases (16%) of 1214 patients with mCRPC were processed. The median sample age was 2.8 years (range, 4 days to 21 years). The NGS tissue test failure rate was 32%, mainly (18%) due to insufficient tumour content or DNA. In total, samples from 872 patients were sequenced successfully. Deleterious genomic alterations in BRCA1, BRCA2, and/or ATM were observed in 15% of patients with successfully sequenced samples: BRCA1 (2%), BRCA2 (7%), and ATM (6%).

In parallel, a total of 638 plasma samples from 606 patients with mCRPC progressing on prior therapy were sequenced. The median sample age was 2 days (range, 1-10 days). NGS was successful for 97% of the plasma samples, and in 93% of those, a genomic alteration was detected in at least 1 assayed gene. Deleterious genomic alterations in BRCA1, BRCA2, and/or ATM were observed in 19% of patients with successfully sequenced samples: BRCA1 (2%), BRCA2 (9%), and ATM (12%).

Conclusions

Genomic profiling of both FFPE tumour tissue samples and cfDNA using NGS successfully identified patients with a genomic alteration in a DDR gene for the evaluation of rucaparib in mCRPC. Additional genomic analyses will be presented.

O.01 IDENTIFICATION, CLINICAL CHARACTERISTICS AND TREATMENT OUTCOMES OF SOMATIC HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 (HER2) MUTATIONS IN METASTATIC BREAST CANCER PATIENTS

O.02 REAL-LIFE TREATMENT PRACTICE FOR MALIGNANT PLEURAL MESOTHELIOMA IN BELGIUM