Medical students' perception of e-learning approach (MeSPeLA) - a mixed method research.

There is a discrepancy between the research exploring e-learning at medical universities in Central/Eastern and Western European countries. The aim of the MeSPeLA study was to explore the understanding, experience and expectations of Polish medical students in terms of e-learning. Questionnaire containing open-ended and closed questions supplemented by focus group discussion was validated and performed among 204 medical students in Poland before COVID-19 pandemia. Several domains: understanding of e-learning definitions; students' experience, preferences, expectations and perceptions of e-learning usefulness, advantages and disadvantages were addressed. The qualitative data were analyzed using an inductive approach. 46.0% of students chose a communication-oriented definition as the most appropriate. 7.4% claimed not to have any experience with e-learning. 76.8% of respondents indicated they had contact with e-learning. The main reported e-learning advantages were time saving and easier time management. The most common drawback was limited social interactions. The acceptance of the usage of e-learning was high. Medical undergraduates in Poland regardless of the year of studies, gender or choice of future specialization showed positive attitudes towards e-learning. Students with advanced IT skills showed a better understanding of the e-learning definition and perceived e-learning to be a more useful approach. The expectations and perceptions about e-learning in Polish medical schools seems similar to some extent to that in Western European and the United States so we can be more confident about applying some lessons from these research to Poland or other post-communist countries. Such application has been accelerated due to COVID-19 pandemia.

A Risk-Adapted Approach to Patients with Stage I Seminoma according to the Status of Rete Testis: The Fourth Spanish Germ Cell Cancer Group Study.

OBJECTIVE: The aim of this study was to assess a risk-adapted strategy for stage I seminoma guided by the presence of rete testis invasion. METHODS: Between January 2013 and December 2015, a total of 135 consecutive patients with stage I seminoma from 18 Spanish tertiary hospitals were included in a prospective multicenter study. Median patient age was 38 years (range 22-60). Preoperative beta-human chorionic gonadotropin was elevated in 9.6% of patients. Rete testis invasion was present in 47.4% of patients. After orchiectomy, subjects with rete testis invasion were treated with 2 courses of adjuvant carboplatin (area under the curve of 7, with 21-day interval). Those without this risk factor were managed by surveillance. Disease-free survival (DFS) and overall survival (OS) were estimated with the Kaplan-Meier method. RESULTS: After a median follow-up time of 33 months, only 6 relapses were recorded (5 on surveillance, 1 after carboplatin). These cases were rescued with BEP or EP chemotherapy, and all 135 patients are currently disease free without sequelae. Three-year DFS was 92.0 and 98.2% for patients on surveillance and after carboplatin, respectively. Three-year OS was 100%. CONCLUSION: A risk-adapted approach based on rete testis invasion as a single risk factor is feasible and yielded an excellent outcome with a 3-year DFS of 94.9%.

Adjuvant anti-PD1 immunotherapy of resected skin melanoma: an example of non-personalized medicine with no overall survival benefit.

Randomized clinical trials demonstrated a recurrence-free survival benefit with adjuvant anti-programmed death-1 (anti-PD1) inhibitors of resected stage IIB-IV melanoma. However, no improvement in overall survival has been observed thus far. Furthermore, there are no predictive markers for immunotherapy response in melanoma, therefore adjuvant treatment is offered to all comers based exclusively on the pathological and clinical stages. Additionally, one year of treatment duration and the risk of chronic immune-related adverse effects may negatively impact patients´ quality of life. In this review, we will try to answer whether the currently available data on adjuvant anti-PD1 therapy of stage IIB-IV resected melanoma is sufficient to make this strategy available to all patients. We will also discuss the economic impact of this therapy on healthcare system budgets. Recent studies suggest that the high cost of cancer drugs may affect access to these agents globally by raising questions of sustainability for patients and society.

Rationale for the Initiation, Outcomes, and Characteristics of Chemotherapy Following CDK4/6 Inhibitors in Breast Cancer: A Real-World Cohort Study.

The standard therapy for hormone-receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer includes the use of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) with endocrine therapy. The optimal post-CDK4/6i treatment sequence is unclear. This cohort study evaluated the initiation, characteristics, and outcomes of chemotherapy following CDK4/6i-based treatment. Among the 227 patients who began CDK4/6i therapy, 114 completed it. Seventy-nine female patients received further treatment, including 55 receiving chemotherapy. The average age was 60.1 years. Post-CDK4/6i chemotherapy was typically (69.1%) first-line due to an impending visceral crisis. The median progression-free survival (mPFS) was 3.0 months (range 0.5-18.9), and the median overall survival (mOS) was 8.3 months (0.5-26.1). The median OS from the end of CDK4/6i treatment was 12.4 months (1.5-26.8). In univariate analysis, neither mPFS nor mOS was associated with age, tumor grade, receptor status, Ki67 status, time from diagnosis to CDK4/6i cessation, therapy line, or CDK4/6i type. Dose reduction occurred in 12 patients (21.8%), and chemotherapy was ceased due to adverse events in 8 patients (14.6%). Chemotherapy showed limited benefit regardless of the regimen. The role of chemotherapy may evolve with broader CDK4/6i use in adjuvant treatment.

Cytokine release syndrome and immune effector cell­associated neurotoxicity syndrome in a melanoma patient treated with adjuvant pembrolizumab.

The emergence of immune checkpoint inhibitors (ICIs) has significantly improved the prognosis of patients with solid tumors. However, along with their efficacy, new toxicities related to immune system activation have surfaced, some of which pose life-threatening risks. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are among the serious, albeit rare, immune-related adverse effects (irAEs) observed. Although commonly associated with hematologic malignancies and chimeric antigen receptor T cell therapies, CRS has been reported in patients treated with ICIs, with ICANS being a less documented complication. The present study presents a case report of a 76-year-old patient with resected melanoma who developed clinical symptoms of CRS and ICANS following adjuvant pembrolizumab therapy. The patient presented with neurological symptoms of weakness and encephalopathy with confusion, bradypsychia, dysarthria, tremors and visual hallucinations. Laboratory tests revealed elevated serum levels of tumor necrosis factor-alpha and interleukin-6 along with inflammatory markers, hepatic and renal dysfunction, as well as rapidly progressive normochromic-normocytic anemia. Treatment with corticosteroids led to rapid symptom resolution, albeit with subsequent symptom recurrence after tapering its dose. This case underscores the importance of recognizing and managing irAEs associated with ICIs and highlights the need for vigilant monitoring and individualized therapeutic approaches.

Main influencing factors and health-related quality of life issues in patients with oesophago-gastric cancer - as measured by EORTC tools.

AIM OF THE STUDY: To assess influencing factors and main health-related quality of life (HRQoL) issues in patients with cancers of the oesophago-gastric region using the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire Core 30 (QLQ-C30) and its oesophago-gastric module (QLQ-OG25). MATERIAL AND METHODS: Patients were qualified for this study based on the histological confirmation of oesophageal, oesophago-gastric or gastric cancers. Each patient filled out the Polish version of the EORTC QLQ-C30, the QLQ-OG25 module and a personal questionnaire. Patients were divided into groups based on gender, age, treatment intention, tumour localization, working status and level of education. RESULTS: Our study included 112 patients - 39 women (35%) and 73 men (mean age ± SD; 60.2 ±10.9). Thirty-five patients (31.3%) completed the questionnaires twice. Eighty-four (75%) patients had gastric cancer (GC), twenty-six (23.2%) oesophageal cancer (OC) and two (1.8%) cancer of the oesophago-gastric junction (OGJC). Eighty (71.4%) patients underwent surgical treatment prior to either chemo-, radio- or chemoradiotherapy. The Global Health Status scale of the QLQ-C30 inversely correlated with all the other QLQ-C30 and QLQ-OG25 symptom scales (r = -0.26 to -0.61; p < 0.05). CONCLUSIONS: The main HRQoL problems of Polish OC, OGJC and GC patients are fatigue, insomnia, anxiety, and appetite and weight loss. Older age, receiving palliative treatment, having gastric cancer, being on retirement and having lower education are factors associated with higher symptom scores (worse symptoms) and thus poorer HRQoL.

Characteristics and outcomes of advanced melanoma patients with complete response and elective discontinuation of first-line anti-programmed death-1 monotherapy: A real-world multicentre observational cohort study.

Anti-programmed death-1 (anti-PD1) treatment has significantly improved outcomes of advanced melanoma with a considerable percentage of patients achieving complete response (CR). This real-world study analyzed the feasibility of elective anti-PD1 discontinuation in advanced melanoma patients with CR and evaluated factors related to sustained response. Thirty-five patients with advanced cutaneous or primary unknown melanoma with CR to nivolumab or pembrolizumab from 11 centers were included. Mean age was 66.5 years, and 97.1% had ECOG PS 0-1. 28.6% had ≥3 metastatic sites with 58.8% having M1a-M1b disease; 8.6% had liver and 5.7% had brain metastases. At baseline, 80% had normal LDH, and 85.7% had a neutrophil-to-lymphocyte ratio ≤3. 74.3% of patients had CR confirmed in PET-CT. Median duration of anti-PD1 was 23.4 months (range 1.3-50.5). 24 months after therapy discontinuation, 91.9% of patients were progression-free. Estimated PFS and OS at 36, 48, and 60 months from the start of anti-PD1 were 94.2%, 89.9%, 84.3%, and 97.1%, 93.3%, 93.3%, respectively. Antibiotics use after anti-PD1 discontinuation increased the odds of progression (OR 16.53 [95% CI 1.7, 226.03]). The study confirms the feasibility of elective anti-PD1 discontinuation in advanced melanoma patients with CR and favorable prognostic factors at baseline.

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.

Durable Response to Vemurafenib and Cobimetinib for the Treatment of BRAF-Mutated Metastatic Melanoma in Routine Clinical Practice.

BACKGROUND: The combination of BRAF and MEK inhibitors delays the onset of resistance and provides more sustained and dramatic responses in comparison with a BRAF inhibitor in monotherapy. The objective of the study was to evaluate the effectiveness of the combination therapy with vemurafenib/cobimetinib in terms of durability, and to describe differential characteristics in patients associated to durable responses in real-world settings. PATIENTS AND METHODS: Retrospective, observational, cross-sectional, multicenter study involving 41 patients with advanced melanoma harboring a BRAF V600 mutation who initiated a combination therapy with vemurafenib/cobimetinib between May 2018 and March 2019. Participants were differentiated regarding the durability of the response: durable (complete response, CR, or a partial response, PR, for at least 12 months) and non-durable (stable disease, SD, progressive disease, PD, or CR/PR <12 months). Secondary endpoints included treatment adherence, labor productivity, anxiety/depression, and safety profile. RESULTS: During the combination therapy, 12 patients (29.3%) had a CR, 19 a PR (46.3%), 5 showed SD (12.2%), and 5 had PD. A total of 12 patients (29.3%) were considered as achieving a durable response and 29 (70.7%) as a non-durable one. Practically all sociodemographic and clinical characteristics were similar between patients. Body mass index was the only differential factor (with higher body mass index achieving a non-durable response). The treatment adherence was 100% in patients with durable response and 66.7% in those with non-durable. CONCLUSION: The combination treatment with vemurafenib/cobimetinib results in an important impact on long-term survival, leading to a steady CR in one-third of the patients.

Intermittent BRAF inhibition in advanced BRAF mutated melanoma results of a phase II randomized trial.

Combination treatment with BRAF (BRAFi) plus MEK inhibitors (MEKi) has demonstrated survival benefit in patients with advanced melanoma harboring activating BRAF mutations. Previous preclinical studies suggested that an intermittent dosing of these drugs could delay the emergence of resistance. Contrary to expectations, the first published phase 2 randomized study comparing continuous versus intermittent schedule of dabrafenib (BRAFi) plus trametinib (MEKi) demonstrated a detrimental effect of the "on-off" schedule. Here we report confirmatory data from the Phase II randomized open-label clinical trial comparing the antitumoral activity of the standard schedule versus an intermittent combination of vemurafenib (BRAFi) plus cobimetinib (MEKi) in advanced BRAF mutant melanoma patients (NCT02583516). The trial did not meet its primary endpoint of progression free survival (PFS) improvement. Our results show that the antitumor activity of the experimental intermittent schedule of vemurafenib plus cobimetinib is not superior to the standard continuous schedule. Detection of BRAF mutation in cell free tumor DNA has prognostic value for survival and its dynamics has an excellent correlation with clinical response, but not with progression. NGS analysis demonstrated de novo mutations in resistant cases.

Targeted therapy in advanced colorectal cancer: more data, more questions.

Colorectal cancer (CRC) remains the third most common malignancy and the third leading cause of cancer death worldwide. The introduction of new chemotherapeutics and monoclonal antibodies into the treatment protocols for advanced CRC has significantly improved the outcomes. Nowadays, oncologists have a wide range of agents to choose for the treatment of advanced CRC; however, their optimal administration remains unclear. This article presents recently published data from the trials evaluating the use of monoclonal antibodies in advanced CRC with a particular emphasis on the predictive and prognostic factors of response to targeted therapy. The results from the CRYSTAL and OPUS studies indicate that the benefit from the addition of cetuximab to first-line chemotherapy is restricted to patients with the wild-type KRAS gene, with the best outcomes observed among those with unmutated forms of both the KRAS and BRAF genes. However, that has not been confirmed in the preliminary data from the COIN trial. Panitumumab has been shown to improve the outcomes when combined with first-line and second-line chemotherapy, but again mostly in patients with wild-type KRAS. The article also describes the detrimental effect of combined anti-vascular endothelial growth factor and anti-epidermal growth factor blockade in the first-line setting observed in the PACCE and the CAIRO-2 trials. Finally, results from the BRiTE registry indicating benefit from continuation of bevacizumab after progression on the first-line regimen are discussed in the context of maintenance therapy. Modern treatment for advanced CRC is based not only on clinical and anatomo-pathological but also molecular tumour characteristics. Our knowledge of the optimal administration of monoclonal antibodies in advanced CRC has extended significantly over the last few years; however, there are still many questions that have to be answered in future trials.

Anthracycline-induced cardiotoxicity prevention with angiotensin-converting enzyme inhibitor ramipril in women with low-risk breast cancer: results of a prospective randomized study.

BACKGROUND: Anthracycline­induced cardiotoxicity (AIC) remains the main long­term irreversible side effect in malignancy survivors. Cardiotoxicity prevention is one of the most reasonable approaches. AIMS: In this prospective randomized open­label study, we aimed to verify whether ramipril protects from early­onset AIC in women with breast cancer (BC). METHODS: We analyzed data from 96 women (median age, 47 years) with BC after breast surgery, without significant cardiovascular diseases, who were eligible for adjuvant anthracyclines. They were randomized to a ramipril or control arm. Cardiotoxicity was estimated with repeat echocardiography and themeasurement of troponin I and N­terminal fragment of the prohormone brain natriuretic peptide (NT­proBNP) levels over 1­year follow­up. Anthracycline­induced cardiotoxicity was defined as a decrease in left ventricular ejection fraction (LVEF), elevated biomarker levels, and/or occurrence of heart failure (HF) or cardiac death. RESULTS: A decrease in LVEF above 10­percent points occurred in 6.3% of ramipril patients and 18.5% ofcontrols (P = 0.15). No cases of HF, cardiac death, or LVEF decline below 50% were reported. The percentage of patients with elevated NT­proBNP levels increased with time in controls (P = 0.003) and remained unchanged in the ramipril arm. At the end of follow­up, an increase in NT­proBNP levels was more common and decline was less common in the control than ramipril arm (P = 0.01). No significant differences in troponin levels were found between the study arms. Ramipril was well tolerated in normotensive women. CONCLUSIONS: In relatively young women with BC without serious comorbidities, who received anthracyclines, 1­year treatment with ramipril exerts potentially protective effects on cardiotoxicity assessed with NT­proBNP levels.

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.

Paraneoplastic limbic encephalitis in a patient with extensive disease small-cell lung cancer.

Paraneoplastic limbic encephalitis (PLE) is a rare disorder infrequently accompanying malignancy, coexisting in ~50% of the cases with small-cell lung cancer (SCLC). The pathomechanism of PLE is considered to be immune-mediated, with production of specific anti-Hu antibodies and activation of T-cells directed against onconeural antigens present on both tumor cells and neurons. We herein report the case of a 50-year-old male patient who, prior to being diagnosed with SCLC, presented with typical symptoms of PLE (seizures, subacute cognitive dysfunction with severe memory impairment, anxiety and hallucinations). The initial brain magnetic resonance imaging examination revealed mild enlargement and hyperintensity of the hippocampal gyri bilaterally, with narrowed temporal horns of the lateral ventricles; the findings of the cerebrospinal fluid examination were compatible with the diagnosis of lymphocytic meningitis. Due to the suspected infectious origin of the disease, treatment with acyclovir and antibiotics was initially applied. However, following subsequent diagnosis of the underlying SCLC and the presence of antineuronal anti-Hu antibodies in the patient's serum, the diagnosis of PLE accompanying extensive-disease (ED) SCLC was confirmed. In addition to the standard cytotoxic therapy, throughout the course of his disease the patient also continued treatment with valproic acid (VPA) as prophylaxis for the initial seizures. VPA is known to be a potent histone deacetylase inhibitor that may reverse epigenetic changes in tumor cells and potentially improve the outcome of cancer patients. The patient succumbed to the disease 25 months after the diagnosis of malignancy; such a long course is observed in only ~5% of patients with ED SCLC. Therefore, it was hypothesized that the accompanying paraneoplasia and treatment with VPA may have improved the outcome in this patient.

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.

Do we really need the full compliance with ERAS protocol in laparoscopic colorectal surgery? A prospective cohort study.

BACKGROUND: Although the relation between adherence to the ERAS protocol and clinical outcomes was extensively studied, there is still ongoing discussion on the need and feasibility of full compliance in laparoscopic colorectal surgery. In this study, we aimed to verify whether a strict adherence to the protocol (>90%) leads to further improvement in clinical outcomes compared to high (70-90%) and low (<70%) compliance groups. MATERIALS AND METHODS: The analysis included consecutive prospectively registered patients operated laparoscopically for colorectal cancer between January 2012 and December 2015. Patients were divided into three groups depending on the compliance with the ERAS protocol: <70% (Group 1), 70-90% (Group 2), >90% (Group 3). The measured outcomes were: complication rate, readmission rate, recovery parameters (tolerance of early oral diet on 1st postoperative day and mobilization of a patient on the day of surgery), length of stay (LOS). RESULTS: Group 1 consisted of 70, Group 2 of 65 and Group 3 of 116 patients. There were no statistical differences between the groups based on demographic parameters, stage of cancer and operative parameters (operative time, blood loss, conversion rate). The overall compliance with the protocol in the study group was 85.6 ± 11.9%. There was a significant decrease in complication rate with increasing compliance (35.7% vs. 36.4% vs. 16.4%, p = 0.0024) and severity of complications according to the Clavien-Dindo classification (p = 0.0198). Moreover, we observed differences in recovery parameters between the groups: tolerance of oral diet on the 1st postoperative day (52.8% vs. 79.5% vs. 87.9%, p < 0.0001), mobilization of a patient on the day of surgery (68.6% vs. 92.3% vs. 99.1%, p < 0.0001), respectively. We also observed that with compliance increase, the median LOS decreased (6 vs. 4 vs. 3 days, p < 0.0001). CONCLUSION: Full implementation of the ERAS protocol significantly improves short term outcomes both in comparison to the high- and low-compliant groups.

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.

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 skin-related toxicity in patients with metastatic colorectal cancer treated with cetuximab.

Monoclonal antibodies (mAbs) blocking the epidermal growth factor receptor (EGFR) pathway, such as cetuximab, have been widely used in recent years for the treatment of metastatic colorectal cancer (mCRC). The purpose of this study was to evaluate the profile of the side effects of cetuximab affecting the skin and its appendages. We gathered the medical records on skin-related toxicity in 46 patients treated with cetuximab for mCRC in the Department of Clinical Oncology, University Hospital in Krakow in 2009-2013. Skin toxicity was classified according to the National Cancer Institute Common Toxicity Criteria for Adverse Events version 4.0. The typical side effects of cetuximab were observed. The most common skin toxicity was an acne-like skin rash (80% of patients) and paronychia (20%). Other side effects were trichomegaly, hypertrichosis, and allergic reactions. In view of high incidence of skin lesions during treatment with cetuximab, it is essential to observe patients carefully and to control the side effects during therapy. Previous experience from clinical trials shows that in some cases proper care and prevention can improve the quality of the patients' lives.

Enhanced recovery (ERAS) protocol in patients undergoing laparoscopic total gastrectomy.

INTRODUCTION: Laparoscopic technique combined with the ERAS (Enhanced Recovery after Surgery) protocol enables a shorter hospital stay and a lower complication rate. Although it has been widely used in many patients undergoing elective abdominal surgery, especially in patients with colorectal cancer, there are only a few papers describing laparoscopic total gastrectomy and the enhanced recovery protocol in patients with gastric cancer. Minimally invasive gastrectomy is still an uncommon procedure, mostly because of its difficulty. AIM: To present the preliminary results of treatment of patients with gastric neoplasms who underwent laparoscopic gastrectomy D2 with perioperative care according to ERAS principles. MATERIAL AND METHODS: Eleven patients (5 male and 6 female, age 52-77 years) underwent laparoscopic D2 gastrectomy with intracorporeal esophagojejunal anastomosis. In all patients the ERAS protocol was implemented. We analyzed operation time, complications and hospital stay. Additionally we focused on operative technique as well as the perioperative care protocol. RESULTS: The mean duration of the procedure was 245 min. There was 1 conversion due to unclear tumor infiltration. Mean hospital stay was 4.6 days. One postoperative complication (central venous catheter sepsis) was reported. Histological analysis confirmed the tentative diagnosis (R0 resection) in 10/11 patients. There were no readmissions. CONCLUSIONS: Laparoscopic gastrectomy is a valuable alternative to the classical approach and combined with the ERAS protocol can result in reduced hospital stay. However, due to the small group of patients it is difficult to adequately assess the incidence of early and late complications of the laparoscopic procedures; therefore further research is needed.