Krebswissenschaft und -therapie

Objective: Chondroblastic osteosarcoma is an aggressive bone cancer with poor outcome accounting for 25% of cases of conventional osteosarcoma. The aim of our study was to assess the clinico-epidemiological profile, prognostic factors, and treatment outcome of chondroblastic osteosarcoma.

Methods: A monocentric retrospective study was conducted between 1982 and 2020. Data of chondroblastic osteosarcoma patients treated in Salah Azaïz Institute were collected. Patient's treatment variables, prognostic factors and and treatment outcome were assessed.

Results: Thirty patients were included. Most of them (n=24) were younger than 25 years. Femur (n=15) and tibia (n=8) were the most common sites involved. Twenty patients had localized disease and 10 patients had metastatic disease on presentation. Neoadjuvant chemotherapy was performed in 23 patients. They received combination regimen of methotrexate, adrimaycin and cisplatin (MAP) (44%), methotrexate, etoposide and ifosfamide (30%), combined doxorubicin-ifosfamide-cisplatin (API) and doxorubicinifosfamide (AI) (22%), etoposide, ifosfamide and cisplatin (VIP) (4%). 16% of patients had partial response, 63% a clinical progression and 21% patients a stable disease. Surgery was performed in 22 patients. Of 16 patients operated, 4 (25%) were good responders while 12 (75%) were poor responders. For patients with metastatic disease, only one achieved complete remission. Six patients progressed after treatment and two died. For patients with localized osteosarcoma, 6 patients had local recurrence and 6 patients had distant metastases. Median overall survival was 35 months. Overall survival at 2 years was 43%. Median disease free survival was 12 months. Disease free survival at 2 years was 21%. The absence of clinical response after neoadjuvant chemotherapy and age> 25 years were prognostic factor influencing disease-free-survival (p=0.025 and p=0.012, respectively).

Conclusion: Chondroblastic osteosarcoma is an aggressive tumor with a tendency for local recurrence and distant metastasis. Younger onset age and response to neoadjuvant chemotherapy can predict better disease free survival.

Introduction: The most common sites for distant nasopharyngeal carcinoma metastases are the bone, lung, and liver. Leptomeningeal metastases LM in undifferentiated nasopharyngeal carcinoma are rare.

Case and outcomes: We present a case report of a 36 years old patient treated initially for undifferentiated nasopharyngeal carcinoma (T2N3M0, stage III of AJCC 7th edition) by association of chemotherapy and radiotherapy. Two years and half later, the patient developed a frontal leptomeningeal metastasis in association with subcutaneous and left parotid relapses on MRI. The patient was treated by resection of the leptomeningeal and subcutaneous lesions. These masses turned out to be an undifferentiated carcinoma consistent with nasopharyngeal carcinoma metastasis. The patient refused parotidectomy and adjuvant radiotherapy of leptomeningeal metastasis was performed. She is now being treated with chemotherapy.

Discussion: Leptomeningeal metastases from nasopharyngeal carcinoma are rare and occur in almost 3% of patients. Multifocal neurologic signs are common and indicate multilevel involvement. The treatment of LM is based on chemotherapy and radiation therapy. Even with chemotherapeutic agents active on central neurologic system, the median survival was up to four months.

Conclusion: Leptomeningeal metastases from NPC are rare. The prognosis of patients with LM is poor. However a small subset of patients with low tumor burden and good performance status could be treated more aggressively with multimodal strategy.

Introduction: diagnostic and therapeutic difficulties for cancer are emerging in COVID-19 pandemic. In addition to interstitial pneumonia, disseminated intravascular coagulation and sepsis, liver injury (LI) is a fairly frequent occurrence, with significant weight on evolution and prognosis of COVID-19. Its involvement is linked to cholangiocytes ACE2. Excluded other pathogenesis, LI could represent prodromal phase of COVID-19, if initial diagnostic negativity will be followed by COVID-19 positivity.

Clinical case: A 59-year-old male patient has diagnosis of metastatic papillary non-clear cell renal cell carcinoma (nccRCC). After neoadjuvant Sunitinib he was submitted to right nephrectomy with caval-atrial thrombectomy in extra-corporeal circulation. Thereafter he continues Sunitinib until disease progression (PD) to bone followed by Axitinib from December 2015 to December 2015 and left femoral radiotherapy (RT) with disease control (DC). After lung and liver PD he was treated with Nivolumab from December 2015 to June 2016 with liver response and overall DC. After liver and caval thrombosis PD, Sorafenib, administered from June 2016 to December 2017, quarterly Zoledronic acid and bone RT obtained DC. Subsequent RT and Cabozantinib from February 2018 to September 2019, during which he reported pathological fracture of left femur, he underwent a surgical reduction and synthesis. From January 2020 to September 2020 Everolimus was administered with DC.

Subsequently, in light of PD related to immunosuppression, after proven COVID-19 negativity, he started therapy with intravenous low doses Cyclophosphamide, Fluorouracil and subcutaneous Interleukin-2 with moderate toxicity. Following the onset of dyspnea, confirmation of COVID-19 negativity, he was hospitalized and chest CT scan demonstrated size reduction of largest lung lesion. After antibiotic and steroid therapy with clinical improvement and discharge, patient complained symptoms worsening and biochemistry showed cholestatic hepatitis signs and INR lengthening. During subsequent hospitalization, he experienced rectorrhagia and biohumoral tests shown negativity for COVID-19, hypo-albumin, and persistence of coagulative and hepatic disorders. Change of immunological parameters, from which lymphocyte immunophenotype with initial increase of Treg counts followed by decrease during chemo-immunotherapy were observed. Despite support care, patient died with nasopharyngeal swab COVID-19 positivity.

Conclusion: This prodromal hepatic picture in heavy treated nccRCC could be an expression of increase of T lymphocytes and Treg counts, stimulated by IL-2, with negative feedback on hyper-inflammation, linked to hyper-cytokinemia, with attempt to control viral infection. It result in the delaying of the disease course whereas failure with lymphocyte and Treg reduction count culminates with final worsening until COVID-19 positivity.