Principles of Cancer Immunobiology and Immunotherapy of Solid Tumors

The immune system and cancer coexist in close relationship which is an indispensable part of the processes of tumorigenesis, tumor growth, and metastatic spread. The elucidation and understanding of this continuous process could provide opportunities to develop strategies to impact the prognosis, and eventually to improve the cancer treatment process. Such strategies have been already implicated and proven efficient in the treatment of several tumor localizations such as malignant melanoma, lung and renal cancer. The present publication reviews the principles of cancer-related immune response, types and mechanisms of immune response and suppression, immunotherapy of solid tumors. We also discuss the pathways and the signaling molecules, participating in those immune response/suppression processes, turning them into potential targets and their actual and potential future role in the management of solid tumors. We focus on potential role and rationale for combination of immunotherapeutic and chemotherapeutic/targeted agents and radiotherapy in one treatment strategy

Diagnostic value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography over conventional imaging studies to detect malignant lesions in staging and restaging after radically treated primary and recurrent locoregional cutaneous melanoma

Introduction. Cutaneous melanoma (CM) has a high metastasizing potential and requires many imaging tests for accurate staging and restaging. As a hybrid imaging method, 18F-FDG PET/CT has the power to diagnose clinically undetected regional and distant metastatic disease with a better detection rate than conventional imaging. The aim of our study was to assess the value of 18F-FDG PET/CT in detecting different types of malignant lesions – local recurrences, regional lymph nodes (RLN), in-transit (ITM) and distant metastases (DM) after radical excision of the primary lesion or regional recurrence.  Materials and methods. A retrospective analysis was performed of all patients with CM referred for 18F-FDG PET/CT for staging or after resection of locoregional recurrent disease. All patients had a combination of pre-PET/CT conventional imaging studies (CIS), including a whole body computed tomography (CT) and ultrasonography (US) of the RLN basin/s. The results from 18F-FDG PET/CT were compared with the CIS results.  Results. 246 consecutive patients, aged 10-87 years were included with identification of 71 malignant lymph nodes, 4 local recurrences, 28 ITM, and 65 DM in total. The detection rate of 18F-FDG PET/CT for RLN was 84.5%, and in the diagnosis of ITM and DM, it reached a sensitivity of 100.0% with 0.7% of false positive results.  Conclusions. 18F-FDG PET/CT has an invaluable role in the detection of small, clinically silent ITM and DM and has a smaller value in RLN detection. It may guide the process of selection of suspicious lesions, suitable for biopsy or further ultrasound follow-up

2-year single center clinical experience in patients with colon cancer stage II and III receiving adjuvant chemotherapy

Introduction: Colorectal cancer is the most commonly diagnosed gastrointestinal cancer worldwide. For patients without metastatic disease, surgery is the first option used with curative intention, for stage I disease the adequate treatment consists only of surgical excision. In stage III additional adjuvant chemotherapy post-surgery is recommended. In stage II colon cancer, adjuvant treatment remains controversial.We aim to stratify patients according to different criteria, identify those with recurrence within the first year post last cycle of adjuvant chemotherapy and discuss those primary results.Materials and methods: a total of 52 patients who were subject to curative resection of stage II and III colon adenocarcinoma and who were administrated 5 FU based adjuvant chemotherapy were included and were followed for a period of two years. Data analysis was performed.Result: After a mean of 2 years of follow-up, recurrence was identified in 16 patients. None of stage II patients (n=6) and 3 patients in stage III (n=6) experienced recurrence. Patients with Nx cancer (n=30) were detached in separate group. Thirteen of them experienced recurrence (9 patients had relapse within 6 months after surgery - defined as synchronous metastatic disease).Conclusion: Surgery remains the cornerstone of treatment for the majority of colon patients. The selection of optimal chemotherapy for each patient is a complex process and there is a practice evidence gap which remains a significant problem. Our results for relapse are comparable with the reported ones worldwide. The reports suggest that there is still lack of evidence in the adjuvant colon cancer chemotherapy worldwide

Diagnostic and clinical value of [18F]FDG PET/CT in the follow-up regimen in IIA–IIID stage cutaneous malignant melanoma after first regional recurrence

Background: Malignant melanoma stands out as a disease with highly aggressive behavior and frequent recurrences. It is crucial to find a non-invasive method for early recurrence detection which allows early and radical treatment. Our aim was to assess the diagnostic and clinical value of [18F]FDG PET/CT in the follow-up regimen of patients after radically treated first regional recurrence and for early detection of operable disease progression.Material and methods: We performed [18F]FDG PET/CT in 96 consecutive patients who had a histologically proven regional recurrent disease that was radically treated. In 46 patients [18F]FDG PET/CT was used in the follow-up regimen and in the other 50 it was used for clarification of suspicious lesions seen in conventional studies. We explored the diagnostic performance of [18F]FDG PET/CT. We also compared the results with conventional studies and explored the clinical impact of [18F]FDG PET/CT by its ability to find localized disease progression in those groups.Results: [18F]FDG PET/CT had better sensitivity, specificity, PPV and NPV, and accuracy in patients with symptoms. This good results in the second group had a high price for the patients, as there was a prevalence of distant metastatic disease in the second group — 64.0% vs. 28.3% in the surveillance group (p = 0.001). [18F]FDG PET/CT revealed more of the distant and in-transit lesions and assisted in lymph node detection by guiding the ultrasonography. Owing to the [18F]FDG PET/CT surveillance, 64.5% of all operable lesions were found in the surveillance group vs. only 35.5% in the second group, where the distant metastatic disease was prevalent.Conclusions: [18F]FDG PET/CT used as a follow-up tool in the surveillance regimen of patients after the first recurrence showed excellent performance in timely and accurate recognition of operable lesions. It had significantly better performance than conventional studies in the follow-up regimen of the patients in this high risk of progression group

Adjuvant Treatment in Colon Cancer

Worldwide, more than 1 million people develop colorectal cancer (CRC) annually. CRC is a major health problem in the Western world and the second most common cause of cancer mortality. To improve performance, the role of chemotherapy for CRC has increased dramatically over the last decade. The vast majority of CRC patients now receive chemotherapy with multiple agents that are currently approved for the treatment in the appropriate setting [1]. However, it is a complex process to select the optimal chemotherapy for each patient and practice evidence gap is still a problem. Some guidelines for the treatment of CRC have been developed to promote the standardization of CRC treatment. Postoperative, or “adjuvant,” systemic therapy has become standard for stage III colon cancer. Adjuvant therapy should also be strongly considered in stage II patients. It is generally recommended for any medically fit patient with stage II cancer with unfavorable factors. The hypothesis that the antitumor activity of the combination agent, including oxaliplatin, irinotecan, bevacizumab, cetuximab in metastatic cure rates, would result in increased adjuvant proved to be often wrong. Although new drug development takes years, targeted drug use can occur more quickly with advanced tests and will be a focus of future work. In addition, efforts will focus on identifying biomarkers that predict response to systemic therapy so that tailored therapy can be initiated. The future of oncology will come with the better understanding of the biology and genetics of the tumor and its host. This will help to develop tailored approach to the patients, including more specific systemic therapy, aimed at molecular targets of the malignant tumor, thus reducing the negative effects. At that time, the treatment of oncological diseases will experience a new era, comparable to the introduction of antibiotics

First line 5-FU-based chemotherapy with/without bevacizumab for metastatic colorectal cancer: one center experience results

Purpose: Colorectal cancer is the second leading cause of cancer mortality in the United States. According to the National Institute of Statistics in Bulgaria for 2012 there have been 2370 newly diagnosed colon cancer and 1664 rectal cancer cases and the total number of registered patients is 29995. Adding Bevacizumab to chemotherapy in patients with metastatic colorectal cancer improves progression-free survival but yet no predictive markers for patient selection have been described and proved in the clinical practice. In our study we examined two plasma biomarkers that may correlate with response to first line Bevacizumab containing chemotherapy in patients with metastatic colorectal cancer.Patients and Methods: 54 patients with metastatic colorectal cancer were assigned to first line 5-Fubased chemotherapy with/without Bevacizumab. The primary end point was progression-free survival, with additional determination of response and toxicity. Blood samples were collected at baseline from all 54 patients prior to initiation of chemotherapy and Bevacizumab. Plasma samples were stored at -80º C until analysis at the Immunology Laboratory at the University Hospital `St. Marina` (Varna, Bulgaria) by a multiple-step sandwich immunoassay Human ELISA VEGF121 and VEGF165 kits.Results: The median progression-free survival for the group treated with CT/Bev was 8.8 months, compared with 5.4 months for the group treated with chemotherapy alone (95% CI, log-rank test P =0.003). The corresponding overall response rates were 19.3% and 10.2% respectively (P < 0.05 for CT/Bev vs CT).Conclusion: The addition of Bevacizumab to 5-Fu based chemotherapy improves progression-free survival duration for patients with metastatic colorectal cancer. We could not find any association between pretreatment plasma levels of VEGF 121 and 165 and worse PFS

Comparative analysis of main clinical features in melanoma patients with and without sentinel lymph node biopsy

Introduction. Sentinel lymph node biopsy is fundamental in the treatment and prognosis of cutaneous malignant melanoma. This study aims to identify differences in baseline clinical characteristics and survival of patients with melanoma with and without a sentinel lymph node biopsy (SLNB) performed.  Material and methods. In 2018, a retrospective study of 151 patients with malignant melanoma (MM) was conducted. The patients were hospitalized at the Second Clinic of University Hospital — Pleven, from 2012 to 2017. The patients were divided into two groups: Group A included 58 (38.4%) patients with SLNB performed; Group B included 93 (61.6%) patients who did not undergo SLNB. A double-detection method was used while performing SLNB.  Results. The incidence of achromatic malignant melanoma is significantly higher in patients without SLNB (12 or 12.9%) than in patients with SLNB (2 or 3.4%) — c2 = 3.796, df = 1, p = 0.051. Of all 151 patients in the study, 46 died, representing 30.5% of patients with melanoma. The mortality rate was higher in the patients without SLNB (32.3% vs. 27.6% in Group A). However, the differences in the two groups are not statistically significant.  Conclusions. Patients with achromatic melanoma have significantly fewer sentinel lymph node (SLN) biopsies performed because of a late diagnosis. Most of our patients are diagnosed at a later stage when lymphatic metastases are already present, which leads to a significant increase in lymph node dissections performed. There is no significant difference in mortality and survival in the SLNB and non-SLNB groups

Adenosquamous carcinoma of the uterine cervix – impact of histology on clinical management

Introduction: Historically, the incidence rate of cervical cancer (CC) in Eastern Europe and particularly in Bulgaria has constantly been higher than that in the other European countries. Adenosquamous carcinoma (ASC) is a rare histological subtype of CC with incidence rate of less than 6 per 100,000. We aimed to analyze the epidemiology and prognosis of all Bulgarian patients with ASC, registered at the Bulgarian National Cancer Registry (BNCR), and to compare patients’ characteristics and outcomes with those of patients, treated at a large specialized institution – the Department of Gynecologic Oncology, University Hospital in Pleven, Bulgaria. Materials and Methods: This is a retrospective study of all cases of ASC, registered at the BNCR for a 10-year period of time. The Kaplan–Meier analysis with Log rank test was used to estimate the significant differences. Results: The incidence rate of ASC was calculated as 3.2% of all CC registered in BNCR and 4.97% of all stage I patients, treated in our department. The 5-year overall survival (OS) rate of all patients with ASC tumors from the registry was 50.5%. A total of 171 (48.4%) of the patients had T1 tumors and a 5-year OS of 67.1%. Lymph node status was a significant prognostic factor for OS (p=0.001). Thirty-one patients with T1 tumors and ASC histology were treated in our department for the same period of time. Lymph node metastases were found in 10 of them (32.2%). The 5-year observed OS in ASC group was 74.19%. Conclusion: The histological subtype of cancer of the uterine cervix has an impact on prognosis and should not be simply considered as a descriptive characteristic but a poor prognostic feature and should be an integral part of the decision-making in clinical management of patients.peer-reviewe

Migration von /sw vom AFS ins DCE/DFS

/sw ist eine verteilte Softwarebereitstellung mit dem Ziel, jedem Benutzer Software zentral zur Verfügung zu stellen, ohne daß er sich darum kümmern muß, woher er seine Software bekommt. Für eine Außenstehenden ergibt sich somit das Bild eines großen Softwarepools, aus dem er sich fertig installierte Software für seine Plattform herunterladen kann. Voraussetzung dafür ist, daß ein Benuzter an seiner Workstation über AFS (Andrew File System), DFS (Distributed File System) oder ftp verfügt. Zur Zeit werden vom /sw für 18 verschiedenen Unix-Plattformen 594 Programme in 1024 verschiedenen Installationen angeboten. Die meisten Architekturen vom /sw liegen im AFS, bis auf die Architekturen DEC ALPHA, IRIX 4.0 und Linux, die im NFS liegen. In Zukunft wird es für die gesamte /sw Software nur noch eine Quelle geben, das DFS. Mit der Migration von /sw aus dem AFS ins DFS entfällt dann die Trennung von /sw in einen AFS-Teil und einem NFS-Teil und damit auch der AFS/NFS-Translators, der recht unstabil läuft. Die gesamte Software von /sw wurde aus dem AFS bzw. NFS ins DFS migriert, so daß für alle vom /sw unterstützten Architekturen nur noch eine Quelle zur Verfügung steht, die Stuttgarter DCE-Zelle. Jeder AFS-Klient hat über den AFS/DFS-Translator Zugriff auf /sw und für die NFS-Klienten wird das /sw-Fi-lesystem exportiert, so daß jeder NFS-Klient die Möglichkeit hat das DFS-Filesystem /sw zu mounten. Eine Workstation kann sowohl AFS- als auch DCE/DFS-Klient sein