Intracellular ascorbate is a safe-guard and/or reservoir for plasma vitamin C in prostate cancer patients undergoing radiotherapy.

Prostate cancer (PC) represents one of the most common cancer types worldwide and many patients suffering from this kind of cancer are treated with radiotherapy (RTH). Ionizing irradiation is closely associated with reactive oxygen species (ROS) production and oxidative stress. Over the years the role of vitamin C (VC) in cancer prevention has been highlighted as it may be mediated by its ability to neutralize pro-carcinogenic ROS. However, the debate concerning the presence of VC in blood and its beneficial effect on the survival of cancer patients is inconsistent and controversial. To our best knowledge until recently there have been no studies concerning such a role of intracellular VC (iVC). In the present study, blood and intracellular concentrations of vitamin C were analyzed along with the level of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), as an established marker of the stress condition, in leukocytes of PC patients during the course of radiotherapy. The level of intracellular vitamin C significantly decreased in PC patients in comparison with the healthy group, while there were no differences in blood VC. It was observed that a sub-group of the PC patients reacted to RTH decreasing VC in leukocytes (group A), while the other sub-group acted the other way round, significantly increasing its level (group B). Under stressful conditions (RTH) leukocytes react in two different ways. Both ways are in good agreement with two well recognized functions, proposed for iVC; it may serve as a save factor, to protect the cellular DNA, increasing its concentration inside the cell (group B), and as a reservoir decreasing the VC level inside leukocytes and releasing VC into the plasma to rescue its physiological level (group A). It was also demonstrated that there was a relationship between the level of 8-oxodG in leukocytes' DNA and the markers of RTH toxicity.

Religion and Spirituality in Oncology: An Exploratory Study of the Communication Experiences of Clinicians in Poland.

Communication with patients regarding oncology-related aspects is a challenging experience and requires a high level of skill from the interlocutors. The aim of this study was to verify the influence of religion/spirituality in oncological settings from the health professionals' perspectives in Poland. It assessed the role of religion/spirituality in patient-clinician communication, death or stress self-management, empathy, and breaking bad news skills. Data collection was carried out through a standardized self-administered questionnaire with varying scales. The study cohort consisted of 60 medical practitioners specializing in oncological radiotherapy treatments. It was observed that strategies used for coping with patients' death, stress reduction, empathy, communication with patients and/or their relatives, or breaking bad news skills, may be gender-specific or may depend on the length of time employed, as well as experience in a cancer-related work environment. This study shows that spirituality and religiousness can support clinicians in managing challenging or negative emotions related to their work in cancer settings. Religiousness and spirituality can also serve as a potential therapeutic strategies for those exposed to patient suffering and death.

Acute Lymphoblastic Leukemia in Children: Better Transplant Outcomes After Total Body Irradiation-based Conditioning.

BACKGROUND/AIM: Comparison of transplant outcomes in long-term follow-up of children after total body irradiation (TBI)- or chemotherapy-based conditioning allogeneic hematopoietic cell transplantation (allo-HCT). PATIENTS AND METHODS: Patients undergoing allo-HCT for Acute lymphoblastic leukemia (ALL) conditioned either with TBI (n=55) or chemotherapy (n=84) were compared. The following transplant outcomes were analyzed: overall survival (OS), event-free survival (EFS), relapse incidence (RI), and graft-versus-host-disease (GVHD)-free-relapse-free survival (GRFS). RESULTS: All analyzed long-term transplant outcomes were significantly better for patients conditioned with TBI at 2 years after transplant. OS at 2 years was 84% after TBI and 60.5% after chemotherapy-conditioning (p=0.005). Risk factor analysis showed that two factors, TBI-based conditioning and transplant in first remission of ALL, significantly improved OS, EFS, GRFS, and decreased RI. CONCLUSION: TBI-based conditioning before allogeneic HCT in children with acute lymphoblastic leukemia provides significantly better transplant outcomes, when compared to chemotherapy-based conditioning.

Achievement in active agent structures as a power tools in tumor angiogenesis imaging.

According to World Health Organization (WHO) cancer is the second most important cause of death globally. Because angiogenesis is considered as an essential process of growth, proliferation and tumor progression, within this review we decided to shade light on recent development of chemical compounds which play a significant role in its imaging and monitoring. Indeed, the review gives insight about the current achievements of active agents structures involved in imaging techniques such as: positron emission computed tomography (PET), magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT), as well as combination PET/MRI and PET/CT. The review aims to provide the journal audience with a comprehensive and in-deep understanding of chemistry policy in tumor angiogenesis imaging.

Religion and Faith Perception in a Pandemic of COVID-19.

The COVID-19 pandemic has impacted religion and faith in different ways. Numerous restrictions have been implemented worldwide. Believers are in conflict with authorities' warnings that gatherings must be limited to combat the spread of the virus. Religion has always played a role of the balm for the soul, and the regular religious participation is associated with better emotional health outcomes. In our study, we examined whether the exposure to COVID-19 enhances the faith. The instrument used was a survey verifying the power of spirituality in the face of the coronavirus pandemic.

Ciprofloxacin and Graphene Oxide Combination-New Face of a Known Drug.

Drug modification with nanomaterials is a new trend in pharmaceutical studies and shows promising results, especially considering carbon-based solutions. Graphene and its derivatives have attracted much research interest for their potential applications in biomedical areas as drug modifiers. The following work is a comprehensive study regarding the toxicity of ciprofloxacin (CIP) modified by graphene oxide (GO). The influence on the morphology, viability, cell death pathway and proliferation of T24 and 786-0 cells was studied. The results show that ciprofloxacin modified with graphene oxide (CGO) shows the highest increase in cytotoxic potential, especially in the case of T24 cells. We discovered a clear connection between CIP modification with GO and the increase in its apoptotic potential. Our results show that drug modification with carbon-based nanomaterials might be a promising strategy to improve the qualities of existing drugs. Nevertheless, it is important to remember that cytotoxicity effects are highly dependent on dose and nanomaterial size. It is necessary to conduct further research to determine the optimal dose of GO for drug modification.

Current Perspectives of the Applications of Polyphenols and Flavonoids in Cancer Therapy.

The development of anticancer therapies that involve natural drugs has undergone exponential growth in recent years. Among the natural compounds that produce beneficial effects on human health, polyphenols have shown potential therapeutic applications in cancer due to their protective functions in plants, their use as food additives, and their excellent antioxidant properties. The possibility of combining conventional drugs-which are usually more aggressive than natural compounds-with polyphenols offers very valuable advantages such as the building of more efficient anticancer therapies with less side effects on human health. This review shows a wide range of trials in which polyphenolic compounds play a crucial role as anticancer medicines alone or in combination with other drugs at different stages of cancer: cancer initiation, promotion, and growth or progression. Moreover, the future directions in applications of various polyphenols in cancer therapy are emphasized.

Encapsulation for Cancer Therapy.

The current rapid advancement of numerous nanotechnology tools is being employed in treatment of many terminal diseases such as cancer. Nanocapsules (NCs) containing an anti-cancer drug offer a very promising alternative to conventional treatments, mostly due to their targeted delivery and precise action, and thereby they can be used in distinct applications: as biosensors or in medical imaging, allowing for cancer detection as well as agents/carriers in targeted drug delivery. The possibility of using different systems-inorganic nanoparticles, dendrimers, proteins, polymeric micelles, liposomes, carbon nanotubes (CNTs), quantum dots (QDs), biopolymeric nanoparticles and their combinations-offers multiple benefits to early cancer detection as well as controlled drug delivery to specific locations. This review focused on the key and recent progress in the encapsulation of anticancer drugs that include methods of preparation, drug loading and drug release mechanism on the presented nanosystems. Furthermore, the future directions in applications of various nanoparticles are highlighted.

Detection of somatic mutations in ctDNA derived from adenocarcinoma patients - EGFR tyrosine kinase inhibitor monitoring preliminary study.

AIM OF THE STUDY: The main purpose of this study was to assess detection of mutations in the epidermal growth factor receptor (EGFR) gene in circulating tumor DNA (ctDNA) as a tool for EGFR tyrosine kinase inhibitor (TKI) monitoring therapy. MATERIAL AND METHODS: The study was conducted using 20 samples from 7 adenocarcinoma patients treated with TKIs. Blood samples for ctDNA analysis were collected in 2015-2016. ctDNA was isolated using the QIAamp Circulating Nucleic Acid Kit (Qiagen) and analyzed using the ctEGFR Mutation Detection Kit (EntroGen). RESULTS: The most common exon 19 deletion and p.Leu858Arg mutation in exon 21 of the EGFR gene were detected. We observed a correlation between stabilization of patient condition and the lack of p.Thr790Met mutation detection in ctEGFR during TKI treatment (2 out of 7 patients). We also observed a correlation between progression of the disease and p.Thr790Met mutation detection in ctEGFR (3 out of 7 cases). We did not detect ctDNA p.Thr790Metp in two patients in whom progression occurred shortly thereafter. Last but not least, we noticed that good organization during plasma collection and transportation (average time of 6 minutes and 30 seconds) allows to use K2EDTA tubes. CONCLUSIONS: When tissue is limited or insufficient, analysis of the ctEGFR mutational status can be considered as an alternative tool for qualifying patients with non-small cell lung cancer (NSCLC) for TKI therapy, also as a potential monitoring tool. The plasma p.Thr790Met-negative result needs to be verified for the presence of p.Thr790Met-positive tumor tissue.

Prognostic value of subventricular zone involvement in relation to tumor volumes defined by fused MRI and O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET imaging in glioblastoma multiforme.

BACKGROUND: Subventricular zone (SVZ) involvement is associated with a dismal prognosis in patients with glioblastoma multiforme (GBM). Dual-time point (dtp) O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET/CT (PET) may be a time- and cost-effective alternative to dynamic FET PET, but its prognostic value, particularly with respect to SVZ involvement, is unknown. METHODS: Thirty-five patients had two scans 5-15 and 50-60 min after i.v. FET injection to define tumor volumes and SVZ involvement before starting radiotherapy. Associations between clinical progression markers, MRI- and dtp FET PET-based tumor volumes, or SVZ involvement and progression-free (PFS) and overall survival (OS) were assessed in univariable and multivariable analyses. RESULTS: The extent of resection was not related to outcomes. Albeit non-significant, dtp FET PET detected more SVZ infiltration than MRI (60% vs. 51%, p = 0.25) and was significantly associated with poor survival (p < 0.03), but PET-T1-Gad volumes were larger in this group (p < 0.002). Survival was shorter in patients with larger MRI tumor volumes, larger PET tumor volumes, and worse Karnofsky performance status (KPS), with fused PET-T1-Gad and KPS significant in multivariable analysis (p < 0.03). Uptake kinetics was not associated with treatment outcomes. CONCLUSIONS: FET PET-based tumor volumes may be useful for predicting worse prognosis glioblastoma. Although the presence of SVZ infiltration is linked to higher PET/MRI-based tumor volumes, the independent value of dtp FET PET parameters and SVZ infiltration as prognostic markers pre-irradiation has not been confirmed.

FDG PET/CT as a survival prognostic factor in patients with advanced renal cell carcinoma.

Accurate prediction of the outcome of molecular target-based treatment in advanced renal cell carcinoma (RCC) is an important clinical problem. Positron emission tomography/computed tomography using [18F]-2-fluoro-2-deoxyglucose (FDG PET/CT) is a noninvasive tool for the assessment of glucose accumulation which can be a marker of the biological characteristics of the tumor. In this paper, we assess FDG PET/CT as a survival prognostic marker in patients with advanced RCC. The study included 121 patients treated in the years 2011-2016 with a diagnosis of advanced renal cell carcinoma (stage IV, multifocal metastases in all patients). Assessment using FDG PET/CT was conducted by measuring the maximum standard uptake value (SUVmax) for the marker used (the highest SUV measurement result for each patient in a single examination). SUVmax measurements were compared with various clinical risk factors used as prognostic markers. The median follow-up period was 19 months (ranging from 3 to 61 months). SUVmax measurements in all patients ranged from 1.3 to 30.0 (median 6.9). Higher SUVmax was correlated with poorer prognosis. Multi-way analysis with standard risk factors revealed that SUVmax was an independent factor for overall survival (OS; p < 0.003, hazard ratio 1.312, 95% CI 1.147-1.346). For SUVmax < 7.0, median OS was 32 months. For 7.0 ≤ SUVmax < 12.0, median OS was 12.5 months. For SUVmax ≥ 12.0, median OS was 10 months. The differences were statistically significant. A preliminary SUVmax assessment conducted using FDG PET/CT can provide information useful in the prediction of survival of patients with advanced RCC.

Human Adipose-Derived and Amniotic Fluid-Derived Stem Cells: A Preliminary In Vitro Study Comparing Myogenic Differentiation Capability.

BACKGROUND Around the world, disabilities due to musculoskeletal disorders have increased and are a major health problem worldwide. In recent years, stem cells have been considered to be powerful tools for musculoskeletal tissue engineering. Human adipose-derived stem cells (hADSCs) and amniotic fluid-derived stem cells (hAFSCs) undergo typical differentiation process into cells of mesodermal origin and can be used to treat muscular system diseases. The aim of the present study was to compare the biological characteristic of stem cells isolated from different human tissues (adipose tissue and amniotic fluid) with respect to myogenic capacity and skeletal and smooth muscle differentiation under the same conditions. MATERIAL AND METHODS hAFSCs and hADSCs were isolated during standard medical procedures and widely characterized by specific markers expression and differentiation potential. Both cell types were induced toward smooth and striated muscles differentiation, which was assessed with the use of molecular techniques. RESULTS For phenotypic characterization, both stem cell types were assessed for the expression of OCT-4, SOX2, CD34, CD44, CD45, and CD90. Muscle-specific markers appeared in both stem cell types, but the proportion of positive cells showed differences depending on the experimental conditions used and the source from which the stem cells were isolated. CONCLUSIONS In this study, we demonstrated that hADSCs and hAFSCs have different capability of differentiation toward both muscle types. However, hADSCs seem to be a better source for myogenic protocols and can promote skeletal and smooth muscle regeneration through either direct muscle differentiation or by paracrine mechanism.

Comprehensive analysis of haemostatic profile depending on clinicopathological determinants in breast cancer patients.

Thrombosis is one of the leading causes of mortality in cancer patients. The aim of the study was to evaluate the concentrations and activities of selected haemostatic parameters in the plasma of patients diagnosed with breast cancer (BrCa) and to make an attempt at finding associations with their levels and selected clinicopathological factors; clinical classification, histological grading, and molecular subtype of BrCa. The study involved 145 Caucasian ethnicity women. Eighty-five women aged 45-66 with primary BrCa without distant metastases (M0). Inclusion criteria were as follows: histopathological examination confirming the diagnosis of primary BrCa, without previous radiotherapy and chemotherapy. The control group consisted of 60, post-menopausal women, aged 45-68. Haemostatic profile expressed by concentrations and activities of tissue factor (TF) and its inhibitor (TFPI) as well as concentrations of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) were measured applying immunoassay techniques. A significantly higher concentration of PAI-1 was noted in patients with BrCa localized in the left breast. We observed significantly lower activity of TFPI and significantly higher concentration of PAI-1 in the group of patients with invasive ductal carcinoma as compared with invasive lobular carcinoma. A significantly higher concentration of t-PA in patients with pT2 BrCa in relation to pT1 cases was noted. Based on comprehensive analysis of haemostatic profile depending on clinicopathological features, we suggest that haemostatic parameters play crucial roles in invasion and metastases of malignant tumours.

Relationship between Glioblastoma Dose Volume Parameters Measured by Dual Time Point Fluoroethylthyrosine-PET and Clinical Outcomes.

Glioblastoma multiforme (GBM) is highly invasive. Despite irradiation with wide margins, GBM usually recurs in-field. Recent in vitro data have suggested that progression might be promoted by sublethal irradiation. Fluoroethylthyrosine-PET (FET-PET) can be used to detect glioblastoma invasion not apparent on MRI. We therefore performed a retrospective analysis of a prospective clinical study to examine whether glioblastoma outcomes depend on dose volume parameters measured by MRI and FET-PET. Twenty-three patients were prospectively recruited to a study examining the role of dual time point FET-PET in the treatment planning of GBM radiotherapy. The dose delivered to the site of recurrence was subdivided into suboptimal-dose (SOD) and high-dose (HD) areas. Types of progression were defined for correlation with dosimetric parameters including V100% of gross tumor volume (GTV)PET, GTVPETMRI, and GTVMRI. The HD area did not cover the entire GTVPETMRI in any case. Recurrences were significantly more frequent in the SubD area (chi-squared test, p = 0.004). There was no relationship between increasing dose volume and progression. The V100% for GTVPET and progression-free survival (PFS) was positively correlated (Spearman's rho 0.417; p = 0.038). Progression is more common in areas with suboptimal dosing. Dose heterogeneity within GTVPET may be responsible for shorter PFS.

Potential Role of Methylation Marker in Glioma Supporting Clinical Decisions.

The IDH1/2 gene mutations, ATRX loss/mutation, 1p/19q status, and MGMT promoter methylation are increasingly used as prognostic or predictive biomarkers of gliomas. However, the effect of their combination on radiation therapy outcome is discussable. Previously, we demonstrated that the IDH1 c.G395A; p.R132H mutation was associated with longer survival in grade II astrocytoma and GBM (Glioblastoma). Here we analyzed the MGMT promoter methylation status in patients with a known mutation status in codon 132 of IDH1, followed by clinical and genetic data analysis based on the two statuses. After a subtotal tumor resection, the patients were treated using IMRT (Intensity-Modulated Radiation Therapy) with 6 MeV photons. The total dose was: 54 Gy for astrocytoma II, 60 Gy for astrocytoma III, 60 Gy for glioblastoma, 2 Gy per day, with 24 h intervals, five days per week. The patients with MGMT promoter methylation and IDH1 somatic mutation (OS = 40 months) had a better prognosis than those with MGMT methylation alone (OS = 18 months). In patients with astrocytoma anaplasticum (n = 7) with the IDH1 p.R132H mutation and hypermethylated MGMT, the prognosis was particularly favorable (median OS = 47 months). In patients with astrocytoma II meeting the above criteria, the prognosis was also better than in those not meeting those criteria. The IDH1 mutation appears more relevant for the prognosis than MGMT methylation. The IDH1 p.R132H mutation combined with MGMT hypermethylation seems to be the most advantageous for treatment success. Patients not meeting those criteria may require more aggressive treatments.

Melanin content in melanoma metastases affects the outcome of radiotherapy.

Melanin possess radioprotective and scavenging properties, and its presence can affect the behavior of melanoma cells, its surrounding environment and susceptibility to the therapy, as showed in vitro experiments. To determine whether melanin presence in melanoma affects the efficiency of radiotherapy (RTH) we evaluated the survival time after RTH treatment in metastatic melanoma patients (n = 57). In another cohort of melanoma patients (n = 84), the relationship between melanin level and pT and pN status was determined. A significantly longer survival time was found in patients with amelanotic metastatic melanomas in comparison to the melanotic ones, who were treated with either RTH or chemotherapy (CHTH) and RTH. These differences were more significant in a group of melanoma patients treated only with RTH. A detailed analysis of primary melanomas revealed that melanin levels were significantly higher in melanoma cells invading reticular dermis than the papillary dermis. A significant reduction of melanin pigmentation in pT3 and pT4 melanomas in comparison to pT1 and T2 tumors was observed. However, melanin levels measured in pT3-pT4 melanomas developing metastases (pN1-3, pM1) were higher than in pN0 and pM0 cases. The presence of melanin in metastatic melanoma cells decreases the outcome of radiotherapy, and melanin synthesis is related to higher disease advancement. Based on our previous cell-based and clinical research and present research we also suggest that inhibition of melanogenesis can improve radiotherapy modalities. The mechanism of relationship between melanogenesis and efficacy of RTH requires additional studies, including larger melanoma patients population and orthotopic, imageable mouse models of metastatic melanoma.

High copy number variation of cancer-related microRNA genes and frequent amplification of DICER1 and DROSHA in lung cancer.

A growing body of evidence indicates that miRNAs may be a class of genetic elements that can either drive or suppress oncogenesis. In this study we analyzed the somatic copy number variation of 14 miRNA genes frequently found to be either over- or underexpressed in lung cancer, as well as two miRNA biogenesis genes, DICER1 and DROSHA, in non-small-cell lung cancer (NSCLC). Our analysis showed that most analyzed miRNA genes undergo substantial copy number alteration in lung cancer. The most frequently amplified miRNA genes include the following: miR-30d, miR-21, miR-17 and miR-155. We also showed that both DICER1 and DROSHA are frequently amplified in NSCLC. The copy number variation of DICER1 and DROSHA correlates well with their expression and survival of NSCLC and other cancer patients. The increased expression of DROSHA and DICER1 decreases and increases the survival, respectively. In conclusion, our results show that copy number variation may be an important mechanism of upregulation/downregulation of miRNAs in cancer and suggest an oncogenic role for DROSHA.

Potential survival markers in cancer patients undergoing chemotherapy.

Due to the importance of the identification of chemotherapy outcome prognostic factors, we attempted to establish the potential of oxidative stress/DNA damage parameters such as prognostic markers. The aim of the study was to determine whether platinum derivative-based chemotherapy in cancer patients (n = 66) is responsible for systemic oxidatively damaged DNA and whether damage biomarkers, such as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) and the modified base 8-oxo-7,8-dihydroguanine (8-oxo-Gua), in urine and DNA may be used as a prognostic factor for the outcome of chemotherapy. All the aforementioned modifications were analyzed using techniques involving high-performance liquid chromatography/electrochemical detection (HPLC/EC) or HPLC/gas chromatography-mass spectrometry (GC-MS). Among all the analyzed parameters, the significantly decreased levels of 8-oxo-Gua in urine collected from a subgroup of patients 24 h after the first infusion of the drug, as compared with the baseline levels, correlated with a significantly longer overall survival (OS) (60 months after therapy) than in the subgroup without any decrease of this parameter after therapy (median OS = 24 months, p = 0.007). Moreover, a significantly longer OS was also observed in a group with increased urine levels of 8-oxo-dG after chemotherapy (38.6 vs. 20.5 months, p = 0.03). The results of our study suggest that patients with decreased 8-oxo-Gua levels and increased 8-oxo-dG levels in urine 24 h after the first dose should be considered as better responders to the administered chemotherapy, with a lower risk of death. The conclusion may permit the use of these parameters as markers for predicting the clinical outcome of platinum derivative-based chemotherapy.

Cancer treatment in pregnant women.

In general, strategies for the treatment of cancer in pregnancy should not differ significantly from the treatment regimens in non-pregnant women. However, this is difficult due to either the effects of anticancer drugs on the developing foetus or the possibility of long-term complications after the exposure to drugs and radiation. The decision about the introduction and continuation of treatment in the event of pregnancy should be preceded by a detailed analysis of the potential benefits and risks. There are no data to suggest that pregnancy termination alters the biological behaviour of the tumour or patient prognosis in the presence of appropriate antineoplastic therapy. All patients should be given appropriate advice and informed that there are insufficient scientific data to determine any generally accepted consensus. It is very important to always respect the will of the patient, and the moral judgment of the physician should have no impact on the decisions taken by the woman. If the woman decides to undergo active treatment and maintain her pregnancy, it is necessary to carry out consultations with experts in the field appropriate to the type of cancer. This paper presents a basic review of the literature on the targeted therapies currently used in selected cancers diagnosed during pregnancy: breast cancer, cervical cancer, Hodgkin's disease, melanoma, thyroid cancer, ovarian cancer, and colorectal cancer.

Impact of specific KRAS mutation in exon 2 on clinical outcome of chemotherapy- and radiotherapy-treated colorectal adenocarcinoma patients.

BACKGROUND AND OBJECTIVES: Knowledge obtained via high-throughput technologies, used for tumor genome sequencing or identifying gene expression and methylation signatures, is clinically applicable thanks to molecular characterization in the context of tumor development and progression. This study was conducted to assess the impact of specific KRAS mutation in codons 12 and 13 on clinical outcome of chemotherapy and radiotherapy in colorectal cancer patients. METHODS: A total of 239 samples of colorectal adenocarcinoma underwent histological evaluation and DNA isolation. RESULTS AND CONCLUSIONS: Patients with a mutation in KRAS codon 13 experienced worse outcome than those with a mutation in KRAS codon 12. Moreover, the cases of mutations in KRAS codons 12 or 13 were associated with a significantly higher mortality than the cases of wild-type KRAS, and some patients with KRAS mutated in codon 12 had an exceptionally long overall survival. Finally, primary preoperative radiation therapy followed by surgery significantly increased overall survival more efficiently than surgery followed by chemotherapy. This should be investigated in further studies. The fact that all patients treated with radiotherapy + surgery were alive, again focused our attention on the effect of preoperative radiation therapy on the prognosis for colorectal cancer patients. However, the number of patients in this subgroup is too small to allow any specific explanation for this observation. We should, rather, point out a problem for further investigation.