Homologous Recombination Repair Deficiency and the Immune Response in Breast Cancer: A Literature Review.

The success of cancer immunotherapy with immune checkpoint blockade (ICB) has demonstrated the importance of targeting a preexisting immune response in a broad spectrum of tumors. This is particularly novel and relevant for less immunogenic tumors, such as breast cancer (BC), where the efficacy of ICB was more evident in the triple-negative (TNBC) subtype, in earlier stages, and in association with chemotherapy. Tumors harboring homologous recombination DNA repair (HRR) deficiency (HRD) are supposed to have a higher number of mutations, hence a higher tumor mutational burden, which could potentially make them more sensitive to immunotherapy. However, the mechanisms involved in ICB sensitivity and patient selection are still yet to be defined in BC: whether the innate system could play a role and how the adaptive immunity could be linked with HRR pathways are the two key points of debate that we will discuss in this article. The aim of this review was to close the loop between what was found in clinical trial results so far, go back to laboratory theory and preclinical results and point out what needs to be clarified from now on.

[Agressive fibromatosis: genetic and biological correlations]. / Agresívna fibromatóza: geneticko-biologické korelácie.

Aggressive fibromatosis, also known as desmoid tumor, is specific and relatively rarely occuring disease. It belongs to heterogenous group of soft tissue tumors. Originally, it arises from fibroblasts with monoclonal proliferation derived from fibro-aponeurotic tissue with typical local invasive spreading without metastatic tendency. Increased amount of knowledge about the role of the APC gene and its protein product in FAP play an important role in revealing the molecular nature of desmoid tumors. In general, we can conclude that the ß-catenin dysregulation is the key player of the FAP associated desmoid tumor onset. The Wingless/Wnt cascade plays a crucial role in the pathogenesis of aggressive fibromatosis. However, it has not been definitely proven that the mutations of APC or ß-catenin genes are the trigger mechanisms. The research outcome can pave the way for using target biological therapy in routine practice in patients with aggressive fibromatosis in the future.

[Aggressive fibromatosis: clinical aspects]. / Agresívna fibromatóza: klinické aspekty.

The clinical picture of desmoids is unpredictable, which is a feature of different tumor specific associations. Anatomic location, age, sex, association with FAP as well as other factors determine biological behavior of the tumor. Negative prognosis is linked with the intraabdominal area and as many as 80% of desmoids are associated with FAP. Currently, biological targeting therapy is used in the treatment of many cancer diseases. It is only the question of time when and by which of these therapies we will be able to treat the patients with aggressive fibromatosis as well. A disadvantage is heterogenity and rare occurrence of desmoids. The efficacy of tailoring treatment still depends on knowledge and study of particular disease biological markers, which is currently the most important issue. .

The value of 18-FDG PET/CT imaging in a patient with atypical metastatic colorectal cancer--case report: 18-FDG PET/CT in colorectal cancer.

BACKGROUNDS: Cancer metastasis to skeletal muscle is very rare. Lung cancer, renal cell carcinoma and malignant melanoma have been reported as the most frequent primary tumours. Diagnosis of muscle metastasis from other primary cancer sites is more than problematic. CASE: In this paper we report a case of metastasis of colorectal cancer in a 44-year-old man who underwent left-sided hemicolectomy due to the tumour mass in his left colic flexure followed by liver metastasectomy and cryocautery of the non-resectable metastasis in the VII segment. Subsequently, the patient was treated with two lines of chemotherapy. However, shortly after initiation of the second chemotherapy line he started to suffer from unbearable pain in the lumbosacral region. Neither a whole spinal cord MRI nor abdominal CT scan and scintigraphy explained the origin of the pain. Finally, PET/CT examination clarified the origin of the pain and showed massive hypermetabolic metastatic lesions in the muscles, further confirmed by autopsy. CONCLUSION: Thus, among the different imaging techniques, FDG PET/CT enables the detection of metabolically highly active tumour cells, undetectable by other conventional imaging means.

Paclitaxel, bleomycin, etoposide, and cisplatin (T-BEP) as initial treatment in patients with poor-prognosis germ cell tumors (GCT): a phase II study.

First line treatment of patients pts with poor-prognosis GCT, using BEP, is unsatisfactory. T-BEP (paclitaxel followed by BEP) demonstrated promising efficacy in the group of pts with intermediate and poor prognosis GCT. We present the results achieved with 1st line T-BEP in pts with poor-prognosis CGT. Twenty-four pts received T-BEP as initial therapy. Three pts (12.5%) had primary mediastinal GCT. Four cycles of T-BEP were given 21 days apart. Paclitaxel 175 mg/m2 was administered on day 1 before administration of BEP. The administration of G-CSF was not scheduled. Surgical resection of all radiographic residua was considered. All pts were assessable for response. Complete or partial response with negative tumor markers was achieved in 13 pts (54.2%; CI 95%: 34.3-74.1%). Median follow-up is 35.6 months. Median survival was not achieved and median time-to-progression is 9.5 months. Myelosuppression was the major toxicity with Gr3-4 granulocytopenia experienced in 52.1% of all courses. There were two treatment-related deaths due to sepsis. Patients treated with 1st line T-BEP didn't achieve higher response rate or time to progression. However, the overall survival observed in our study is surprisingly long. We do not recommend using this regimen without G-CSF support due to substantial toxicity.

Paclitaxel plus ifosfamide and cisplatin in second-line treatment of germ cell tumors: a phase II study.

The aim of this study was to determine efficacy and toxicity of TIP combination (paclitaxel, ifosfamid, cisplatin) as first salvage treatment in patients with relapsed germ cell tumours (GCTs). Excellent results were achieved from TIP combination with a dose 250 mg/m(2) of paclitaxel [5]. Our hypothesis was that comparable efficacy with less toxicity could be achieved even with a lower dose of 175 mg/m(2) paclitaxel in TIP. In 17 consecutive patients with failed standard 1st line treatment, we used four to six courses of paclitaxel 175 mg/m(2) on day 1 and ifosfamide 1,200 mg/m(2) plus cisplatin 20 mg/m(2), both on day 1 through 5, every 3 weeks. Eleven patients achieved favorable response (65%; 95% confidence interval, 42 to 87%) with 7 complete responses (41%). Estimated 2-year disease free survival is 47% (95% CI, 23-71%). Treatment combination was well tolerated and myelosupression was major toxicity. Granulocytopenia Gr3-4 was observed in 8% and febrile neutropenia in 7% of the courses. No case of severe neurotoxicity or treatment-related death was observed. In our study, TIP combination had good toxicity profile. The results however, did not show expected treatment efficacy and we raise the idea of paclitaxel dosage relevance in TIP.

Gemcitabine plus cisplatine and paclitaxel (GCP) in second-line treatment of germ cell tumors (GCT): a phase II study.

The aim of the study was to determine the efficacy and toxicity of gemcitabine, cisplatin and paclitaxel (GCP) combination as a first salvage treatment of patients with relapsed GCT. Four courses of paclitaxel 175 mg/m(2) and cisplatin 50 mg/m(2), both on day 1, and gemcitabine 1000 mg/m(2), on days 1 and 8, every 3 weeks, were given to 12 consecutive patients who had failed standard 1st line treatment. Six patients (50%; 95% CI 21-79%) achieved favourable response and two of them are maintained 38+ and 29+ months. Median survival time was 16 months (range, 0.77-38+). All, but two patients had hematological toxicity Gr3-4 with infectious complication seen only in 6 courses of therapy. GCP is an active second-line combination regimen for relapsed GCTs with acceptable toxicity profile. However the results of this study did not show expected treatment efficacy and we raise the idea of cisplatin dosage relevance in this combination.