The Impact of Sidedness on the Efficacy of Anti-EGFR-Based First-Line Chemotherapy in Advanced Colorectal Cancer Patients in Real-Life Setting-A Nation-Wide Retrospective Analysis (RACER).

Anti-EGFR antibodies combined with chemotherapy doublets are a cornerstone of the upfront treatment of colorectal cancer. RAS and BRAF mutations are established negative predictive factors for such therapy. The primary tumour located in the proximal colon has recently emerged as another negative predictive factor. We have conducted a retrospective multicentre study to collect data on real-world population characteristics, practice patterns, and outcomes in patients with metastatic colorectal cancer treated in a first-line setting with either cetuximab or panitumumab in combination with either FOLFOX or FOLFIRI chemotherapy. The presented analysis focuses on the impact of the primary tumour location. 126 of 842 patients analysed (15.0%) had proximal primary. It was associated with a lower BMI at diagnosis, mucinous histology, and peritoneal metastases. It was also associated with inferior treatment outcomes in terms of response ratio: 59.4% vs. 74.22% (odds ratio [OR] 0.51, 95% CI 0.33-0.78, p = 0.010), and median depth of response: -36.7% vs. -50.0% (p = 0.038). There was only a borderline non-significant trend for inferior PFS in patients with proximal tumours. OS data was incomplete. The presented analysis confirms the negative impact of tumour sidedness on the efficacy of an upfront anti-EGFR-chemotherapy combination and provides valuable data on real-world population characteristics.

Association of dietary intake of polyphenols, lignans, and phytosterols with immune-stimulating microbiota and COVID-19 risk in a group of Polish men and women.

Objectives: Devastating consequences of COVID-19 disease enhanced the role of promoting prevention-focused practices. Among targeted efforts, diet is regarded as one of the potential factors which can affect immune function and optimal nutrition is postulated as the method of augmentation of people's viral resistance. As epidemiological evidence is scarce, the present study aimed to explore the association between dietary intake of total polyphenols, lignans and plant sterols and the abundance of immunomodulatory gut microbiota such as Enterococcus spp. and Escherichia coli and the risk of developing COVID-19 disease. Methods: Demographic data, dietary habits, physical activity as well as the composition of body and gut microbiota were analyzed in a sample of 95 young healthy individuals. Dietary polyphenol, lignan and plant sterol intakes have been retrieved based on the amount of food consumed by the participants, the phytochemical content was assessed in laboratory analysis and using available databases. Results: For all investigated polyphenols and phytosterols, except campesterol, every unit increase in the tertile of intake category was associated with a decrease in the odds of contracting COVID-19. The risk reduction ranged from several dozen percent to 70 %, depending on the individual plant-based chemical, and after controlling for basic covariates it was statistically significant for secoisolariciresinol (OR = 0.28, 95% CI: 0.11-0.61), total phytosterols (OR = 0.47, 95% CI: 0.22-0.95) and for stigmasterols (OR = 0.34, 95% CI: 0.14-0.72). We found an inverse association between increased ß-sitosterol intake and phytosterols in total and the occurrence of Escherichia coli in stool samples outside reference values, with 72% (OR = 0.28, 95% CI: 0.08-0.86) and 66% (OR = 0.34, 95% CI: 0.10-1.08) reduced odds of abnormal level of bacteria for the highest compared with the lowest tertile of phytochemical consumption. Additionally, there was a trend of more frequent presence of Enterococcus spp. at relevant level in people with a higher intake of lariciresinol. Conclusion: The beneficial effects of polyphenols and phytosterols should be emphasized and these plant-based compounds should be regarded in the context of their utility as antiviral agents preventing influenza-type infections.

Clinical Characterization of Targetable Mutations (BRAF V600E and KRAS G12C) in Advanced Colorectal Cancer-A Nation-Wide Study.

BRAF V600E and KRAS mutations that occur in colorectal cancer (CRC) define a subpopulation of patients with an inferior prognosis. Recently, the first BRAF V600E-targeting therapy has been approved and novel agents targeting KRAS G12C are being evaluated in CRC. A better understanding of the clinical characteristics of the populations defined by those mutations is needed. We created a retrospective database that collects clinical characteristics of patients with metastatic CRC evaluated for RAS and BRAF mutations in a single laboratory. A total of 7604 patients tested between October 2017 and December 2019 were included in the analysis. The prevalence of BRAF V600E was 6.77%. Female sex, primary in the right colon, high-grade, mucinous, signet cell, partially neuroendocrine histology, perineural and vascular invasion, and surgical tissue sample were factors associated with increased mutation rates. The prevalence of KRAS G12C was 3.11%. Cancer of primary origin in the left colon and in samples from brain metastases were associated with increased mutation rates. The high prevalence of the BRAF V600E mutation in cancers with a neuroendocrine component identifies a potential candidate population for BRAF inhibition. The association of KRAS G12C with the left part of the intestine and brain metastases of CRC are new findings and require further investigation.

Metronomic Chemotherapy Based on Topotecan or Topotecan and Cyclophosphamide Combination (CyTo) in Advanced, Pretreated Ovarian Cancer.

Patients with advanced ovarian cancer (OC) have a detrimental prognosis. The options for systemic treatment of advanced OC in later lines of treatment are limited by the availability of active therapies and their applicability to often fragile, exhausted patients with poor performance status. Metronomic chemotherapy (MC) is a concept of a continuous administration of cytotoxic drugs, which is characterized by multidirectional activity (anti-proliferative, anti-angiogenic, and anti-immunosuppressive) and low toxicity. We have performed a retrospective analysis of consecutive, advanced, chemo-refractory OC patients treated with MC based on single-agent topotecan (1 mg p.o. q2d) or on a topotecan (1 mg q2d) and cyclophosphamide (50 mg p.o. qd) combination (CyTo). Metronomic chemotherapy demonstrated promising activity, with 72% and 86% of patients achieving biochemical or objective disease control and 18% and 27% of patients achieving a biochemical or objective response, respectively. The median PFS in the whole population was 3.65 months, but the median PFS in patients with a biochemical response to MC (18.2% of patients) reached 10.7 months. The study also suggested that overweight or obese patients had significantly better outcomes on MC than patients with BMI <25 kg/m2. This article is the first report in the literature on metronomic chemotherapy based on a topotecan + cyclophosphamide combination (CyTo). The CyTo regimen demonstrated safety, clinical activity, and potential broad clinical applicability in advanced OC patients and will be evaluated in a forthcoming clinical trial.

Metronomic Chemo-Endocrine Therapy (FulVEC) as a Salvage Treatment for Patients with Advanced, Treatment-Refractory ER+/HER2-Breast Cancer-A Retrospective Analysis of Consecutive Patients Data.

BACKGROUND: Breast cancer, with 2.3 million new cases and 0.7 million deaths every year, represents a great medical challenge worldwide. These numbers confirm that approx. 30% of BC patients will develop an incurable disease requiring life-long, palliative systemic treatment. Endocrine treatment and chemotherapy administered in a sequential fashion are the basic treatment options in advanced ER+/HER2- BC, which is the most common BC type. The palliative, long-term treatment of advanced BC should not only be highly active but also minimally toxic to allow long-term survival with the optimal quality of life. A combination of metronomic chemotherapy (MC) with endocrine treatment (ET) in patients who failed earlier lines of ET represents an interesting and promising option. METHODS: The methodology includes retrospective data analyses of pretreated, metastatic ER+/HER2- BC (mBC) patients who were treated with the FulVEC regimen combining fulvestrant and MC (cyclophosphamide, vinorelbine, and capecitabine). RESULTS: Thirty-nine previously treated (median 2 lines 1-9) mBC patients received FulVEC. The median PFS and OS were 8.4 and 21.5 months, respectively. Biochemical responses (CA-15.3 serum marker decline ≥50%) were observed in 48.7%, and any increase in CA-15.3 was observed in 23.1% of patients. The activity of FulVEC was independent of previous treatments with fulvestrant of cytotoxic components of the FulVEC regimen. The treatment was safe and well tolerated. CONCLUSIONS: Metronomic chemo-endocrine therapy with FulVEC regimen represents an interesting option and compares favorably with other approaches in patients' refractory to endocrine treatments. A phase II randomized trial is warranted.

Polish Consensus on Gastric Cancer Diagnosis and Treatment - Update 2022.

This document - "Polish Consensus on Gastric Cancer Diagnosis and Treatment - Update 2022" - represents an expert consensus following a year's worth of dedicated effort by a team of specialists throughout 2021, put forward in a conference in December 2021 in Krakow, and finalized below for publication in 2022. The effective date of this document is June 14th 2022. The work that went into updating this consensus was made under auspices of the Polish Society of Surgical Oncology and the Association of Polish Surgeons.

Reduction of Cancer-Induced Thrombocytosis as a Biomarker of Improved Outcomes in Advanced Gastric Cancer.

BACKGROUND: Interplay between non-specific inflammatory reaction and tumor microenvironment in gastric cancer (GC) can be measured indirectly by assessing fluctuations in concentration of platelets. Cytotoxic chemotherapy affects these morphotic elements directly by inducing myelosuppression. It was hypothesized that chemotherapy not only directly affects malignant cells, but also through immunomodulation related to myelosuppression. METHODS: Metastatic GC patients (N: 155) treated with chemotherapy +/- trastuzumab were enrolled in this retrospective study. Platelet pretreatment concentration (PLT-count) and the deepest level of platelet reduction, as well as other inflammatory and general confounders were collected in the first 12 weeks of treatment (PLT-red). Martingale residuals were used to visualize the relationship between PLT-count, PLT-red, and overall survival (OS). Multiple multivariate Cox regression models were built to assess the impact of platelet reduction on OS and progression-free survival (PFS). RESULTS: Reduction of PLT (PLT-red) to 60% of baseline concentration was associated with improved survival rates (HR = 0.60, p = 0.026 for OS and HR 0.56, p = 0.015 for PFS). Cross-classification into four groups based on PLT-count (high vs low) and PLT-red (high vs low) showed significantly worse survival rates in both high PLT-count (HR = 3.60, p = 0.007 for OS and HR = 2.97, p = 0.024 for PFS) and low PLT-count (HR = 1.75, p = 0.035 for OS and HR = 1.80, p = 0.028 for PFS) patients with insufficient platelets reduction. CONCLUSION: Thrombocytosis reduction represents a novel, clinically important, prognostic factor for OS and PFS in patients with stage IV GC.

Combined Neutrophil-to-Lymphocyte and Platelet-Volume-to-Platelet Ratio (NLR and PVPR Score) Represents a Novel Prognostic Factor in Advanced Gastric Cancer Patients.

BACKGROUND: Chemotherapy is a cornerstone of treatment in advanced gastric cancer (GC) with a proven impact on overall survival, however, reliable predictive markers are missing. The role of various inflammatory markers has been tested in gastric cancer patients, but there is still no general consensus on their true clinical applicability. High neutrophil-to-lymphocyte (NLR) and low (medium)-platelets-volume-to-platelet ratio (PVPR) are known markers of unspecific immune system activation, correlating significantly with outcomes in advanced GC patients. METHODS: Metastatic GC patients (N:155) treated with chemotherapy +/- trastuzumab were enrolled in this retrospective study. Pre-treatment NLR and PVPR, as well as other inflammatory markers were measured in peripheral blood. Univariate Cox regression was conducted to find markers with a significant impact on overall survival (OS) and progression-free survival (PFS). Spearman correlation and Cohen's kappa was used to analyze multicollinearity. Multiple multivariable Cox regression models were built to study the combined impact of NLR and PVPR, as well as other known prognostic factors on OS. RESULTS: Elevated NLR was significantly associated with increased risk of death (HR = 1.95; 95% CI: 1.17-3.24), and lower PVPR was significantly associated with improved outcomes (HR = 0.53; 95% CI: 0.32-0.90). A novel inflammatory marker, based on a combination of NLR and PVPR, allows for the classification of GC patients into three prognostic groups, characterized by median OS of 8.4 months (95% CI 5.8-11.1), 10.5 months (95% CI 8.8-12.1), and 15.9 months (95% CI 13.5-18.3). CONCLUSION: The NLR and PVPR score (elevated NLR and decreased PVPR) is a marker of detrimental outcome of advanced GC patients treated with chemotherapy.

Clinical effectiveness and toxicity of second-line irinotecan in advanced gastric and gastroesophageal junction adenocarcinoma: a single-center observational study.

BACKGROUND: Randomized clinical trials showed improved overall survival (OS) of advanced gastroesophageal adenocarcinoma (GEA) patients treated with second-line taxane or irinotecan. However, most data on irinotecan efficacy in this setting come from large Asian trials. We retrospectively analyzed clinical effectiveness and toxicity of irinotecan in a cohort of patients with advanced GEA treated in our department. METHODS: Advanced GEA patients who received at least one cycle of second-line irinotecan were eligible for inclusion. Irinotecan was administered every 3 weeks at an initial dose of 250 mg/m2 of body surface area with subsequent gradual (every 50 mg/m2) dose escalation up to 350 mg/m2, in the case of good treatment tolerance. OS was estimated using the Kaplan-Meier method. A multivariate Cox regression analysis was used to examine the association between clinical and laboratory parameters and survival. RESULTS: A total of 48 patients were identified. Median OS was 6.2 months [95% confidence interval (CI): 3.9-7.6]. In multivariate analysis, age < 65 years, baseline total lymphocyte count (TLC) < 1500/µl and presence of peritoneal metastases were associated with shorter OS. Most adverse events were grade 1-2 and included: anemia (52.3%), leukocytopenia (40.9%), neutropenia (59.1%), nausea (25.0%), vomiting (31.8%), diarrhea (31.8%), anorexia (29.5%) and fatigue (43.2%). Febrile neutropenia occurred in three patients (6.8%). Nine patients (20.5%) experienced a toxicity grade 3-4 of any kind. CONCLUSIONS: This retrospective analysis confirms clinical effectiveness and manageable toxicity of second-line irinotecan in an unselected cohort of advanced GEA patients. Age < 65 years, baseline TLC < 1500/µl and presence of peritoneal metastases were independent prognostic factors associated with shorter OS.

Evaluation of health-related quality of life and its main influencing factors in a Polish population of patients with bone metastases.

PURPOSE: Regardless of cancer type, the skeleton is one of the most common sites for cancer spread. Health-related Quality of Life (HRQoL) can be considered a primary endpoint in clinical trials concerning cancer patients with palliative disease. The proper measurement of this endpoint requires valid and reliable instruments. The aim of this study was to evaluate HRQoL and its main influencing factors using validated EORTC tools - the QLQ-C30 and the QLQ-BM22 in Polish population of patients with skeletal metastases. METHODS: Patients with bone metastases and histologically confirmed malignancy were qualified for the study. They filled out a personal questionnaire, the Polish version of the EORTC QLQ-C30 and its supplementary module QLQ-BM22. The influence of numerous socio-clinical factors such as age, gender, working status, level of education, performance status, primary location, and previous treatment received was assessed. RESULTS: One hundred and ten patients (65 women) were enrolled into this study (mean age ±SD; 57.8±13.8). The most significant HRQoL issues were fatigue (59.29/100); pain (56.97/100) and insomnia (56.36/100). Men coped worse with pain (p=0.013), fatigue (p=0.050), nausea and vomiting (p=0.024) and financial difficulties (p=0.016) than women. CONCLUSIONS: The main factors influencing HRQoL in Polish patients with bone metastases are fatigue, pain and insomnia, and as such should be a primary focus of patient-centered care in this group.

Acupuncture: could it become everyday practice in oncology?

Acupuncture is a complementary and alternative medical treatment (CAM) which is increasingly used in the care of cancer patients. Traditionally derived from Chinese medicine, nowadays it is becoming a part of evidence-based oncology. The use of acupuncture in these patients has been recommended by the American Cancer Society (ACS) for the treatment of side effects associated with conventional cancer therapy and cancer-related ailments. A growing body of evidence supports the use of acupuncture in the treatment of cancer-induced pain and chemotherapy-related nausea and vomiting. Also other indications, such as xerostomia, fatigue, hot flashes, anxiety and peripheral neuropathy, are being constantly evaluated. This article summarizes the most important discoveries related to the possible usefulness of this method in contemporary oncology. Emphasis is placed on the results of randomized controlled trials with an adequate level of evidence. However, explanation of the mechanisms responsible for these effects requires confirmation in further studies with an adequate level of evidence. In future, acupuncture may become an interesting and valuable addition to conventional medicine.

Comparison of efficacy and safety of first-line palliative chemotherapy with EOX and mDCF regimens in patients with locally advanced inoperable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma: a randomized phase 3 trial.

The aim of the study was to compare efficacy and safety of first-line palliative chemotherapy with (EOX) epirubicin/oxaliplatin/capecitabine and (mDCF) docetaxel/cisplatin/5FU/leucovorin regimens for untreated advanced HER2-negative gastric or gastroesophageal junction adenocarcinoma. Fifty-six patients were randomly assigned to mDCF (docetaxel 40 mg/m(2) day 1, leucovorin 400 mg/m(2) day 1, 5FU 400 mg/m(2) bolus day 1, 5FU 1000 mg/m(2)/d days 1 and 2, cisplatin 40 mg/m(2) day 3) or EOX (epirubicin 50 mg/m(2) day 1, oxaliplatin 130 mg/m(2) day 1, capecitabine 1250 mg/m(2)/d days 1-21). The primary endpoint was overall survival. The median overall survival was 9.5 months with EOX and 11.9 months with mDCF (p = 0.135), while median progression-free survival was 6.4 and 6.8 months, respectively (p = 0.440). Two-year survival rate was 22.2 % with mDCF compared to 5.2 % with EOX. Patients in the EOX arm had more frequent reductions in chemotherapy doses (34.5 vs. 3.7 %; p = 0.010) and delays in subsequent chemotherapy cycles (82.8 vs. 63.0 %; p = 0.171). There was no statistically significant difference in the rates of grade 3-4 adverse events (EOX 79.3 vs. mDCF 61.5 %; p = 0.234). As compared with the mDCF, the EOX regimen was associated with more frequent nausea (34.5 vs. 15.4 %), thromboembolic events (13.8 vs. 7.7 %), abdominal pain (13.8 vs. 7.7 %) and grades 3-4 neutropenia (72.4 vs. 50.0 %), but lower incidences of anemia (44.8 vs. 61.5 %), mucositis (6.9 vs. 15.4 %) and peripheral neuropathy (6.9 vs. 15.4 %). In conclusion, the mDCF regimen was associated with a statistically nonsignificant 2.4-month longer median overall survival without an increase in toxicity. This trial is registered at ClinicalTrials.gov, number NCT02445209.

Assessment of frequency and severity of hypomagnesemia in patients with metastatic colorectal cancer treated with cetuximab, with a review of the literature.

Currently, there are a few systemic treatment options for patients with metastatic colorectal cancer (mCRC). Targeted therapy used in this setting includes the use of monoclonal antibodies, such as cetuximab or panitumumab, directed against epidermal growth factor receptor. The aim of the present study was to estimate the frequency and severity of hypomagnesemia among patients with mCRC treated with cetuximab. The data from the Department of Clinical Oncology, University Hospital of Krakow (Krakow, Poland), concerning 52 patients treated between 2009 and 2013 were collected. Of these, 27 patients fulfilled the inclusion criteria to enter this retrospective study. The National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 were used to grade the level of hypomagnesemia. In total, 29.6% of all patients experienced hypomagnesemia during treatment, and the majority of cases were grade 1 (22.2%). There was no statistically significant correlation between magnesium (Mg) level and patient age, duration of treatment, localization of primary tumor or metastases, and the number of metastases. However, there was an upward trend in a logistic regression model showing that the risk of developing hypomagnesemia increases with age. Hypomagnesemia is a frequent problem among mCRC patients receiving cetuximab. It is essential to introduce guidelines regarding the monitoring of the Mg level and its supplementation in this group of patients.