No abstract

Background Historically, the treatment of choice for anal cancer had been abdominoperineal resection (APR). Radical radiotherapy with concurrent 5-fluorouracil plus mitomycin C chemotherapy was later established as standard therapy, although with a failure rate of 20–30%. The aim of this study was to evaluate the outcomes after radical chemoradiotherapy (CRT), prognostic and predictive factors and patterns of failure. Patients and methods This study included 47 patients treated with radical CRT for patohistologicaly confirmed anal squamous cell carcinoma. Analysed haematological parameters included: neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and haemoglobin level. The final logistic regression model included treatment break period. Tumour response was assessed at 24 weeks from CRT completion. Follow-up was performed every 3 months during the first two years, and every 6 months thereafter. Results A complete clinical response (CR) was detected in 30 patients (63.8%). Patients who did not achieve a 6-months CR and those who had a CR after 6 months but then relapsed were referred to surgical treatment. With combined CRT and surgical salvage treatment the CR rate was 80.9%. Patients with CR after 6 months had significantly longer disease-free survival (DFS), progression-free survival (PFS), and overall survival (OS). A significant effect on the 6-month response was confirmed for PLR (p = 0.03). Conclusions Important prognostic factors associated with CR were baseline haemoglobin level and period of treatment interruptions. Potential haematological prognostic factors could be PLR and NLR, which can be routinely determined by low-cost and minimally invasive methods.

Background: Understanding the molecular features associated with response to neoadjuvant chemoradiotherapy is an unmet clinical need in locally advanced rectal cancer (LARC). The aim of the study was to apply a high-sensitivity proteomic approach for in-depth characterization of the LARC proteome in search of patients who might have a good response to preoperative treatment and potentially be followed by a watch-and-wait strategy, rather than having immediate surgery, maximizing the therapeutic effect and quality of life. Methods: A total of 97 LARC patients treated at the Institute for Oncology and Radiology of Serbia in the period of 2018-2019 were included in the study. Patients were treated with long-course chemoradiotherapy (CRT): Radiotherapy (RT) was delivered with a total dose of 50.4 Gy in 28 fractions; concomitant chemotherapy (5-FU, 350 mg/m2 daily) and Leucovorin (25 mg/m2 daily) was administered during the first and the fifth week of RT. Patients were evaluated in week 6-8 after treatment completion with pelvic MRI scan and rigid proctoscopy. Pathohistological response after surgery was assessed according to tumor regression grading (TRG) categories by Mandard. Twenty biopsy samples taken at diagnosis were used for proteomic analysis, 9 responders (R, TRG 1-2), and 11 non-responders (NR, TRG 3-5), to achieve the maximum range of different molecular features potentially associated with response. Formalin-fixed paraffin-embedded (FFPE) biopsies were processed, and isolated proteins were digested with trypsin. The resulting peptides were analyzed by liquid chromatography coupled to a Q Exactive HF-X mass spectrometer operated in data independent mode (DIA-MS). Data analysis was performed with DIA-NN and Perseus. Data are available via ProteomeXchange with the identifier PXD040451. Results: The use of DIA-MS allowed the identification and quantification of more than 3,000 proteins per sample in general, a significant increase when compared to the 1,000 proteins previously identified by Data Dependent Acquisition-MS (DDA-MS) in LARC FFPE samples. In total, 4,849 proteins were identified in 20 rectal cancer FFPE samples. Principal Component Analysis (PCA) indicated that responders had a significantly different proteomic profile than non-responders. Statistical analysis of the two groups resulted in the identification of 915 differentially expressed proteins (DEPs) (215 in responders and 700 in non-responders, p<0.05), and 384 with more stringent criteria (p<0.01). Results indicate that some of the leading signaling pathways that correlate with response include the metabolism of RNA, MYC targets, neutrophil degranulation, cellular transport, and response to stimuli. Conclusions: The DIA-MS approach offered unprecedented proteome coverage for FFPE samples. The differentially expressed proteins and biological processes constitute interesting findings that hold the potential for improving LARC patient management.

Background The aim of this research was to evaluate clinical and low-cost genetic determinants of treatment outcome in EGFR mutation positive advanced lung adenocarcinoma patients. Material and Methods EGFR mutation testing and EGFR 181946C>T genotyping were performed in 101 advanced lung adenocarcinoma patients using qRT-PCR and PCR-RFLP, respectively. Progression-free survival was defined as the time from the start of TKI therapy to date of progression, and overall survival as the time from diagnosis to death from any cause. Pain level was evaluated using a Numerical Rating Scale and the Verbal Descriptor Scale. Statistical significance was considered for P < .05. Results Patients were treated with EGFR-TKIs for a period of 1–39months (median 9), with a median PFS of 12.0 months (10.4-13.6, CI 95%), and a median OS of 19.0 months (15.1-22.7, CI 95%). The presence of pain was significantly correlated with the existence of bone ( P < .001) and adrenal glands metastases ( P = .029). Genetic factors did not have a direct impact on pain management but had a significant effect on the response to TKIs leading to pain alleviation. Conclusions EGFR mutation subtype and the EGFR 181946 C>T SNP had a significant effect on the response to TKI inducing an indirect anti-dolorous effect.

nema