Molecular Subtypes, microRNAs and Immunotherapy Response in Metastatic Colorectal Cancer.

Currently, only a limited set of molecular traits are utilized to direct treatment for metastatic CRC (mCRC). The molecular classification of CRC depicts tumor heterogeneity based on gene expression patterns and aids in comprehending the biological characteristics of tumor formation, growth and prognosis. Additionally, it assists physicians in tailoring the therapeutic approach. Microsatellite instability (MSI-H)/deficient mismatch repair proteins (MMRd) status has become a ubiquitous biomarker in solid tumors, caused by mutations or methylation of genes and, in turn, the accumulation of mutations and antigens that subsequently induce an immune response. Immune checkpoint inhibitors (ICI) have recently received approval for the treatment of mCRC with MSI-H/MMRd status. However, certain individuals experience either initial or acquired resistance. The tumor-programmed cell death ligand 1 (PD-L1) has been linked to the ability of CRC to evade the immune system and promote its growth. Through comprehensive research conducted via the PUBMED database, the objectives of this paper were to review the molecular characteristics linked to tumor response in metastatic CRC in light of improved patients' outcomes following ICI therapies as seen in clinical trials and to identify particular microRNAs that can modulate the expression of specific oncoproteins, such as PD-L1, and disrupt the mechanisms that allow the immune system to be evaded.

Advances in Cancer Therapy from Research to Clinical Practice-Surgical, Molecular or Systemic Management of Cancer.

Cancer represents one of the most important general health problems of our day [...].

Baseline Expression of Exosomal miR-92a-3p and miR-221-3p Could Predict the Response to First-Line Chemotherapy and Survival in Metastatic Colorectal Cancer.

The status of predictive biomarkers in metastatic colorectal cancer is currently underdeveloped. Our study aimed to investigate the predictive value of six circulating exosomal miRNAs derived from plasma (miR-92a-3p, miR-143-3p, miR-146a-5p, miR-221-3p, miR-484, and miR-486-5p) for chemosensitivity, resistance patterns, and survival. Thirty-one metastatic colorectal cancer patients were selected before receiving first-line irinotecan- or oxaliplatin-based chemotherapy. Blood samples were harvested at baseline and 4-6 months after the initiation of chemotherapy. The levels of exosomal expression for each miRNA were analyzed by qPCR. Our results for patients receiving first-line FOLFOX showed significantly higher baseline levels of miR-92a-3p (p = 0.007 **), miR-146a-5p (p = 0.036 *), miR-221-3p (p = 0.047 *), and miR-484 (p = 0.009 **) in non-responders (NR) vs. responders (R). Of these, miR-92a-3p (AUC = 0.735), miR-221-3p (AUC = 0.774), and miR-484 (AUC = 0.725) demonstrated a predictive ability to discriminate responses from non-responses, regardless of the therapy used. Moreover, Cox regression analysis indicated that higher expression levels of miR-92a-3p (p = 0.008 **), miR-143-3p (p = 0.009 **), miR-221-3p (p = 0.016 *), and miR-486-5p (p = 0.019 *) at baseline were associated with worse overall survival, while patients expressing higher baseline miR-92a-3p (p = 0.003 **) and miR-486-5p (p = 0.003 **) had lower rates of progression-free survival. No predictive values for candidate microRNAs were found for the post-chemotherapy period. In line with these findings, we conclude that the increased baseline exosomal expression of miR-92a-3p and miR-221-3p seems to predict a lack of response to chemotherapy and lower OS. However, further prospective studies on more patients are needed before drawing practice-changing conclusions.

Therapeutic Plasma Exchange in Catastrophic Antiphospholipid Syndrome (CAPS): A Rare Case Report and Literature Review.

BACKGROUND/AIM: Catastrophic antiphospholipid syndrome (CAPS) may be the first manifestation ("de novo") of antiphospholipid syndrome (APS) or a complication in the clinical course of patients known to have this syndrome. Approximately 40% of patients had an associated autoimmune disease, mainly, systemic lupus erythematosus (SLE). The trigger can be one of the following: infections, surgical interventions, neoplasms, pregnancy, discontinuation of anticoagulant treatment, and others. CAPS is a medical emergency in which early identification and prompt initiation of aggressive therapy is extremely important. According to the Guidelines for the use of Therapeutic Apheresis in Clinical Practice developed by the American Society for Apheresis (ASFA), last updated in April 2023, in CAPS, the indication for therapeutic plasma exchange (TPE) is category I, grade 2C. CASE REPORT: We present a case of probable CAPS secondary to systemic lupus erythematosus (SLE) in an elderly patient in whom clinical and biological improvement was achieved through a multidisciplinary approach and prompt initiation of TPE. Because TPE is considered first-line therapy in CAPS, we initiated the procedure as soon as the attending rheumatologist raised this suspicion. Four plasmapheresis sessions were performed in the Intensive Care Unit. We used TPE by membrane filtration. Following the therapeutic intervention with TPE, corticotherapy (Solumedrol in puls-therapy), cyclophosphamide and anticoagulant treatment, the evolution was favourable, with clinical and biological improvement. CONCLUSION: The prompt initiation of TPE, because of the suspicion of CAPS, increases the chances of a favourable evolution.

A Systematic Review Investigating the Difference between 1 Cycle versus 2 Cycles of Adjuvant Chemotherapy in Stage I Testicular Germ Cell Cancers.

Standard care for stage I testicular germ cell cancers (seminomatous-STC or non-seminomatous-NSTC) is orchiectomy followed by active surveillance, 1 or 2 cycles of adjuvant chemotherapy, surgery or radiotherapy. The decision on the adjuvant therapeutic approach is guided by the associated risk factors of the patient and the potential related toxicity of the treatment. Currently, there is no consensus regarding the optimal number of adjuvant chemotherapy cycles. Although in terms of overall survival, there is no proven inconsistency regarding the number of cycles of adjuvant chemotherapy, and the rate of relapse may vary.

Ovarian Cancer-Insights into Platinum Resistance and Overcoming It.

Ovarian cancer is the most lethal gynecologic malignancy. Platinum-based chemotherapy is the backbone of treatment for ovarian cancer, and although the majority of patients initially have a platinum-sensitive disease, through multiple recurrences, they will acquire resistance. Platinum-resistant recurrent ovarian cancer has a poor prognosis and few treatment options with limited efficacy. Resistance to platinum compounds is a complex process involving multiple mechanisms pertaining not only to the tumoral cell but also to the tumoral microenvironment. In this review, we discuss the molecular mechanism involved in ovarian cancer cells' resistance to platinum-based chemotherapy, focusing on the alteration of drug influx and efflux pathways, DNA repair, the dysregulation of epigenetic modulation, and the involvement of the tumoral microenvironment in the acquisition of the platinum-resistant phenotype. Furthermore, we review promising alternative treatment approaches that may improve these patients' poor prognosis, discussing current strategies, novel combinations, and therapeutic agents.

Absolute and Functional Iron Deficiency in Colon Cancer: A Cohort Study.

Background and Objectives: Iron is an essential micronutrient for many biological functions and has been found to be intimately linked to cancer biology. Although the effects of increased dietary iron consumption in the development of CRC have been previously investigated in several cohort studies, the available evidence on the involvement of iron deficiency in this process is relatively scarce. Previously published papers did not analyze specific outcomes, such as the presence of biologically aggressive histopathological characteristics, that are associated with the subtypes of iron deficiency. The purpose of this study was to investigate the connection between the development of colorectal cancer and the presence of functional iron deficiency (FID), which is defined as insufficient biological availability of iron in the presence of adequate storage reserves, or absolute iron deficiency (AID), which is defined as severely depleted iron storage levels. Materials and Methods: Our paper represents a single center registry-based cohort study. Iron levels were routinely evaluated upon diagnosis of CRC and the collected data were coupled with patient- and tumor-specific data (2018-2022). Spearman's correlation coefficient and the chi-squared test were used to analyze the association. Results: Out of 129 patients, 75 (58.13%) were anemic. AID was identified in 26.35% of cases and FID was encountered in 51.16% of cases. A statistically significant association between FID and lymphatic invasion was encountered. An analysis of the correlation demonstrated a significant association between anemia and right-sided tumor location. Conclusions: Functional iron deficiency seems to be independently associated with lymphatic invasion. Although a statistically significant correlation with the T or N stage was not demonstrated, the analysis suggested a potential positive relationship between the presence of FID and more aggressive tumor characteristics.

Biventricular cardiac metastasis from vulvar squamous cell carcinoma.

Vulvar cancers make up just 3% to 5% of all gynecological cancers, and they are most typically found in postmenopausal women. Vulvar cancer distant metastases are uncommon and usually arise late. Only six cases of vulvar cancer metastasizing to the heart have been reported in the literature, and none of them included both the left and right ventricles. We describe the case of a 68-year-old patient diagnosed with vulvar cancer arising from lichen sclerosus, initially localized, treated with chemotherapy, surgery, and radiation therapy. Less than two months after the end of the treatment sequence, the patient returned to our clinic with bone pain. Imaging investigations have shown multiple disseminated metastases, but not in the heart at that moment. Chemotherapy was initiated, and after two cycles, the patient developed an arrhythmia (atrial fibrillation with rapid ventricular rate), which was later determined to be caused by cardiac metastases discovered by echocardiography and computed tomography. Vulvar cancer metastatic to the heart represents a rare clinical condition, requiring multidisciplinary care. The case's uniqueness is the biventricular metastasis, which resulted in STEMI despite angiographically normal epicardial coronary arteries.

Signet ring cell gastric carcinoma with breast and leptomeningeal metastases: a case report.

Gastric cancer is the 5th most common malignancy worldwide. Signet ring cell histology represents an aggressive subtype of gastric cancer, presenting at a younger age. Both breast and leptomeningeal metastases are rare locations of tumor dissemination, requiring correct and immediate diagnosis and treatment. We present a case of a 45-year old female with signet ring cell gastric carcinoma who developed both left breast and leptomeningeal metastases, requiring multiple chemotherapy lines. As far as we know, this is the first published case in literature following multiple lines of treatment for both breast and leptomeningeal metastases from signet ring cell gastric carcinoma.

The comparative effects of Resveratrol and Curcumin in combination with photodynamic therapy.

Background and aim: Photodynamic therapy, PDT, is a promising option among the local treatments with oncolytic potential. Although the basic principle is simple, its intricate mechanisms allow for a broad range of optimization methods. The purpose of this study was to assess the effects of Resveratrol and Curcumin as adjuvants of PDT on experimental tumors. Methods: Sixty-six Wistar male rats were divided into 11 groups: control, Curcumin (CUR), Resveratrol (RES) alone or followed by irradiation (IR) (CUR+IR and RES+IR, respectively), 5,10,15,20-tetra-sulphonato-phenyl-porphyrin (TSPP), TSPP+IR (PDT), and CUR or RES administered prior to or after PDT (CUR+TSPP+IR, RES+TSPP+IR, TSPP+IR+CUR, TSPP+IR+RES). Results: Both CUR and RES significantly decreased lipid peroxidation, while RES also showed an increase in glutathione (GSH) levels, especially when it was administered before PDT (p<0.01). Both antioxidants decreased cyclooxygenase (COX)2 expression, to a minimum when they administered prior to PDT (p<0.001 and p<0.01) while nitric oxide synthase (NOS)2 expression diminished in the combined regimen, particularly in RES associated with PDT. CUR and RES induced similar changes in terms of cell death, but CUR seemed to be more efficient on tumor necrosis and showed a higher apoptotic index when was administered after PDT (p<0.001). Conclusion: Both RES and CUR in association with PDT decreased oxidative stress, diminished the COX2 and NOS2 expressions and increased cell death by positively influencing the necrotic rate and apoptotic index, particularly when CUR was administered after PDT. The results show that CUR is a promising class to study in PDT optimization and further invites to exploit its promises.

Radiopharmaceuticals for PET and SPECT Imaging: A Literature Review over the Last Decade.

Positron emission tomography (PET) uses radioactive tracers and enables the functional imaging of several metabolic processes, blood flow measurements, regional chemical composition, and/or chemical absorption. Depending on the targeted processes within the living organism, different tracers are used for various medical conditions, such as cancer, particular brain pathologies, cardiac events, and bone lesions, where the most commonly used tracers are radiolabeled with 18F (e.g., [18F]-FDG and NA [18F]). Oxygen-15 isotope is mostly involved in blood flow measurements, whereas a wide array of 11C-based compounds have also been developed for neuronal disorders according to the affected neuroreceptors, prostate cancer, and lung carcinomas. In contrast, the single-photon emission computed tomography (SPECT) technique uses gamma-emitting radioisotopes and can be used to diagnose strokes, seizures, bone illnesses, and infections by gauging the blood flow and radio distribution within tissues and organs. The radioisotopes typically used in SPECT imaging are iodine-123, technetium-99m, xenon-133, thallium-201, and indium-111. This systematic review article aims to clarify and disseminate the available scientific literature focused on PET/SPECT radiotracers and to provide an overview of the conducted research within the past decade, with an additional focus on the novel radiopharmaceuticals developed for medical imaging.

MRI Evaluation of Complete and Near-Complete Response after Neoadjuvant Therapy in Patients with Locally Advanced Rectal Cancer.

Purpose To evaluate MRI performance in restaging locally advanced rectal cancers (LARC) after neoadjuvant chemoradiotherapy (nCRT) and interobserver agreement in identifying complete response (CR) and near-complete response (nCR). Methods 40 patients with CR and nCR on restaging MRI, surgery and/or endoscopy were enrolled. Two radiologists independently scored the restaging MRI and reported the presence of split scar sign (SSS) and MRI tumor regression grade (mrTRG). Diagnostic accuracy and ROC curves were calculated for single and combined sequences, with inter-reader agreement. Results Diagnostic performance was good for detecting CR and weaker for nCR. T2WI had the highest AUCs among individual sequences. There was a significant positive correlation between SSS and CR, with high Sp (89.5%/73.7%) and PPV (90%/79.2%) for both Readers. Similar accuracy rates were observed for the combination of sequences, with AUCs of 0.828-0.847 for CR and 0.690-0.762 for nCR. Interobserver agreement was strong for SSS, moderate for T2WI, weak for the combination of sequences. Conclusions Restaging MRI had good diagnostic performance in identifying CR and nCR. SSS had high Sp and PPV in diagnosing CR, with a strong level of interobserver agreement. T2WI with DWI was the optimal combination of sequences for selecting good responders.

Current and New Challenges in the Management of Pancreatic Neuroendocrine Tumors: The Role of miRNA-Based Approaches as New Reliable Biomarkers.

Pancreatic neuroendocrine tumors (PanNETs) are rare tumors; however, their incidence greatly increases with age, and they occur more frequently among the elderly. They represent 5% of all pancreatic tumors, and despite the fact that low-grade tumors often have an indolent evolution, they portend a poor prognosis in an advanced stages and undifferentiated tumors. Additionally, functional pancreatic neuroendocrine tumors greatly impact quality of life due to the various clinical syndromes that result from abnormal hormonal secretion. With limited therapeutic and diagnostic options, patient stratification and selection of optimal therapeutic strategies should be the main focus. Modest improvements in the management of pancreatic neuroendocrine tumors have been achieved in the last years. Therefore, it is imperative to find new biomarkers and therapeutic strategies to improve patient survival and quality of life, limiting the disease burden. MicroRNAs (miRNAs) are small endogenous molecules that modulate the expression of thousands of genes and control numerous critical processes involved in tumor development and progression. New data also suggest the implication of miRNAs in treatment resistance and their potential as prognostic or diagnostic biomarkers and therapeutic targets. In this review, we discusses the current and new challenges in the management of PanNETs, including genetic and epigenetic approaches. Furthermore, we summarize the available data on miRNAs as potential prognostic, predictive, or diagnostic biomarkers and discuss their function as future therapeutic targets.

T4 retroperitoneal liposarcoma. Challenges of big size sarcomas surgical treatment.

Our article presents some of the challenges of the surgical treatment of T4 (>15 cm) retroperitoneal liposarcomas (up to 65∕56∕30 cm, 25.5 kg) series of cases treated by the Department of Surgical Oncology, Prof. Dr. Ion Chiricuta Oncology Institute, Cluj-Napoca (IOCN), Romania, with illustrations, insisting on important blood vessels and nerves dissection and preservation and discussions of strategies with references to important articles from the last 10 years specialty literature. Challenges do not come only from intraoperative difficulties but also from establishing the right attitude from the extent of resection and oncological safety point of view, the role of the pathologist being very important because histological subtype and completeness of the resections are the most important prognostic factors for such tumors. Despite all today available aids in decision making, like nomograms or high-resolution imagery, sometimes this decision is to be taken intraoperative based on surgeon's expertise and skills. That is why is strongly advised that such cases to be treated in high-volume specialized tertiary centers of surgical oncology.

Next Generation Sequencing Technology in Lung Cancer Diagnosis.

Lung cancer is still one of the most commonly diagnosed cancers, and one of the deadliest. The high death rate is mainly due to the late stage of diagnosis and low response rate to therapy. Previous and ongoing research studies have tried to discover new reliable and useful cbiomarkers for the diagnosis and prognosis of lung cancer. Next generation sequencing has become an essential tool in cancer diagnosis, prognosis, and evaluation of the treatment response. This article aims to review the leading research and clinical applications in lung cancer diagnosis using next generation sequencing. In this scope, we identified the most relevant articles that present the successful use of next generation sequencing in identifying biomarkers for early diagnosis correlated to lung cancer diagnosis and treatment. This technique can be used to evaluate a high number of biomarkers in a short period of time and from small biological samples, which makes NGS the preferred technique to develop clinical tests for personalized medicine using liquid biopsy, the new trend in oncology.

A Comparative Study between 18F-FDG PET/CT and Conventional Imaging in the Evaluation of Progressive Disease and Recurrence in Ovarian Carcinoma.

The aim of this study is to compare the efficiency of conventional imaging and 18F-FDG PET-CT in detecting progressive disease and recurrences over a period of one year (2018), in the case of ovarian cancer, and also to assess the importance of 18F-FDG PET/CT in changing the course of the treatment for these patients. This study included 29 patients diagnosed in various stages with ovarian carcinoma, most of them of epithelial origin. All patients were evaluated throughout their treatment using 18F-FDG PET/CT and various conventional techniques (computed tomography (CT), magnetic resonance imaging (MRI), abdominal and intravaginal ultrasound, chest X-ray). PET/CT was more useful and effective in our group of patients in detecting progressive disease compared with conventional imaging (37.93% vs. 17.24%) and also in establishing the recurrences (24.14% vs. 6.90%). Moreover, F18-FDG PET-CT led to a therapeutic change in 55.17% of the patients of our group, compared with only 17.24% after conventional imaging. This underlines the crucial aspect of the metabolic changes of tumors that should be assessed alongside the morphological ones, with PET-CT imaging remaining the only viable tool for achieving that at present. PET/CT with 18F-FDG represents one of the most important imaging techniques used in the diagnosis and management of ovarian carcinoma. Our results seem to fall in line with what other authors reported, indicating that 18F-FDG PET-CT is potentially gaining more ground in the management of ovarian carcinoma, by influencing therapeutic strategies and by being able to detect relapse and progression accurately.

Continuous Intravenous Administration of Granulocyte-Colony-Stimulating Factors-A Breakthrough in the Treatment of Cancer Patients with Febrile Neutropenia.

(1) Background: Febrile neutropenia (FN) remains one of the most challenging problems in medical oncology and is a very severe side effect of chemotherapy. Its late consequences, when it is recurrent or of a severe grade, are dose reduction and therapy delays. Current guidelines allow the administration of granulocyte-colony-stimulating factors (G-CSF) for profound FN (except for the case when a pegylated form of G-CSF is administrated with prophylactic intention) in addition to antibiotics and supportive care. (2) Methods: This is a prospective study that included 96 patients with confirmed malignancy, treated with chemotherapy, who developed FN during their oncological therapy, and were hospitalized. They received standard treatment plus a dose of G-CSF of 16 µg/Kg/day IV continuous infusion. (3) Results: The gender distribution was almost symmetrical: Male patients made up 48.96% and 51.04% were female patients, with no significance on recovery from FN (p = 1.00). The patients who received prophylactic G-CSF made up 20.21%, but this was not a predictive or prognostic factor for the recovery time from aplasia (p = 0.34). The median chemotherapy line where patients with FN were included was two and the number of previous chemotherapy cycles before FN was three. The median serological number of neutrophils (PMN) was 450/mm3 and leucocytes (WBC) 1875/mm3 at the time of FN. Ten patients possess PMN less than 100/mm3. The median time to recovery was 25.5 h for 96 included patients, with one failure in which the patient possessed grade 5 FN. Predictive factors for shorter recovery time were lower levels of C reactive protein (p < 0.001) and procalcitonin (p = 0.002) upon hospital admission and higher WBC (p = 0.006) and PMN (p < 0.001) at the time of the provoking cycle of chemotherapy for FN. The best chance for a shorter duration of FN was a short history of chemotherapy regarding the number of cycles) (p < 0.0001). (4) Conclusions: Continuous IV administration of G-CSF could be an alternative salvage treatment for patients with profound febrile neutropenia, with a very fast recovery time for neutrophiles.

Decrease of oncological patients' hospital visits during Covid-19 pandemic; the experience of a tertiary Romanian centre.

PURPOSE: The outbreak of COVID-19 pandemic has changed the provision of medical services worldwide. We assessed the impact of the pandemic on the oncological patients' visits to a tertiary cancer centre. METHODS: We analysed registrations from the administrative data system of in- and outpatients in all of the departments of the Cluj-Napoca Oncology Institute, during March-October 2020, and compared to the same 7-month period of the previous year. RESULTS: The decrease during March-October 2020 was 40.2% for new referrals overall (with the most significant drop in April, of 80%), 52.5% for medical oncology inpatients, 39% for paediatric oncology department inpatients, 69% for radiotherapy inpatients, 34.9% for surgical interventions and 31% decrease of issued pathology reports. The decrease was less important for outpatients: only 10% for medical oncology outpatient department, 33% for radiotherapy and 27% for breast cancer unit outpatients. Imaging investigations were only slightly influenced by the pandemic (reduction of 5% for MRI scans, 19% for mammograms,whereas performed CT scans were even more after the outbreak of COVID-19). CONCLUSION: Our results show a decrease in the number of patients during the period after the outbreak of the COVID-19 pandemic, more for inpatients and less significant for outpatient departments, probably because of the internal circuits reorganization but also because of health care measures taken nationally and locally to limit the spread of the pandemic.

Predictive Efficacy of MiR-125b-5p, MiR-17-5p, and MiR-185-5p in Liver Metastasis and Chemotherapy Response Among Advanced Stage Colorectal Cancer Patients.

MicroRNAs (miRNAs), a class of small non-coding RNAs represent potential biomarkers for colorectal cancer (CRC). The study hypothesized that miRNAs associated with liver metastases may also contribute to assessing treatment response when associated to plasma exosomes. In this study, we used two sets of biological samples, a collection of tumor tissues harvested from patients with CRC with and without liver metastases, and a collection of plasma from CRC patients with and without response to FOLFOX4/FOLFIRI regimens. We investigated 10 target miRNAs in the tissue of 28 CRC patients and identified miR-125b-5p, miR-17-5p, and miR-185-5p to be associated with liver metastasis. Further, we investigated the three miRNAs at the exosomal level in a plasma collection to test their association with chemotherapy response. Our data suggest that the elevated plasma levels of miR-17-5p and miR-185-5p could be predictive of treatment response. Overexpression of miR-17-5p and underexpression of miR-125b-5p and miR-185-5p in CRC tissue seem to be associated with metastatic potential. On the other hand, an increased expression of miR-125b-5p in plasma exosomes was potentially correlated with a more aggressive CRC phenotype.

Partnering bevacizumab with irinotecan as first line-therapy of metastatic colorectal cancer improves progression free survival-A retrospective analysis.

Colorectal cancer remains one of the most frequent malignancies (third place at both genders) worldwide in the last decade, owing to significant changes in modern dietary habits. Approximately half of the patients develop metastases during the course of their disease. The available therapeutic armamentarium is constantly evolving, raising questions regarding the best approach for improving survival. Bevacizumab remains one of the most widely used therapies for treating metastatic colorectal cancer and can be used after progression. This study aimed to identify the best chemotherapy partner for bevacizumab after progression. We performed a retrospective analysis of patients with metastatic colorectal cancer who were treated with bevacizumab as first- and second-line chemotherapy. Data were collected for 151 patients, 40 of whom were treated with double-dose bevacizumab after the first progression. The two standard chemotherapy regimens combined with bevacizumab were FOLFIRI/CAPIRI and FOLFOX4/CAPEOX. The initiation of first-line treatment with irinotecan-based chemotherapy improved progression-free survival and time to treatment failure but not overall survival. After the first progression, retreatment with the same regimen as that used in the induction phase was the best approach for improving overall survival (median overall survival: 46.5 vs. 27.0 months for the same vs. switched strategy, respectively). No correlations were observed between the dose intensity of irinotecan, oxaliplatin, 5-fluorouracil, or bevacizumab and the overall survival, progression-free survival in the first-/second-line treatment, and time to treatment failure. Interaction between an irinotecan-based regimen as a second-line treatment and double-dose bevacizumab after progression was associated with an improved overall survival (p = 0.06). Initiating systemic treatment with an irinotecan-based regimen in combination with bevacizumab improved the progression-free survival in the first-line treatment and time to treatment failure. In terms of overall survival, bevacizumab treatment after the first progression is better partnered with the same regimen as that used in the induction phase.