Efficacy of Systemic Treatments in Patients With Metastatic Lung Invasive Mucinous Adenocarcinoma.

BACKGROUND: Invasive mucinous adenocarcinoma (IMA) is a rare histological subtype of lung invasive adenocarcinoma with unique clinical, radiological, histopathological, and genomic characteristics. There have been limited studies on the effectiveness of systemic therapy for lung IMA, with conflicting results reported. METHODS: We retrospectively investigated the medical records of patients diagnosed with lung IMA. Patients who were ≥ 18 years of age and received at least 1 course of treatment for metastatic or locally advanced inoperable disease were included in the study. Archive records of 113 patients diagnosed with IMA were screened for the study. RESULTS: A total of 41 patients with lung IMA were included. The targetable mutation rate was 20.6% (in 6 of 29 patients). Most patients (83.1%) had received platinum-based chemotherapy as a first-line treatment. The objective response rate (ORR) was 25.7%, and median progression-free survival (PFS) and overall survival (OS) were 8.1 months (95% CI, 5.02-11.2) and 17.5 months (95% CI, 11.7-23.3 months), respectively, in the patients who received chemotherapy. The median PFS and ORR were 20.6 (95% CI, 18.9-66.5) and 66.6%, respectively, in epidermal growth factor receptor (EGFR) mutation-positive patients (n = 3) with relevant targeted therapy. Only 1 patient used oxaliplatin and capecitabine combination (XELOX) as chemotherapy in the second-line treatment and achieved a partial response (PR) at 7.2 months. CONCLUSION: Platinum-based chemotherapies moderately enhance IMA patients' survival rates. Anti-EGFR-targeted drugs are seen as potentially effective in patients with EGFR driver mutation positive. Large, prospective studies are needed to confirm our findings.

Emerging targeted therapies and strategies to overcome resistance in biliary tract cancers.

In the last decade, targeted therapies have shown rapid advancement in biliary tract cancer (BTC). Today, many targeted agents are available and under investigation for patients with BTC. More recently, immune checkpoint inhibitors (ICI) such as durvalumab and pembrolizumab in combination with gemcitabine plus cisplatin (gem/cis) have resulted in improved overall survival and progression-free survival in the first-line setting. However, the efficacy benefit of these novel therapeutics is often short-lived, with literature outlining concerns about both primary and secondary resistance to these agents. Investigators also need to consider toxicity profiles that can emerge using this strategy. There have been efforts to reduce evolving resistance through combinatory approaches, both pre-clinically and in early clinical settings. This review summarizes the emerging targeted therapies in BTC, evolving biomarkers of resistance, strategies to overcome them, and an analysis of ongoing clinical trials of patients with advanced BTC.

Breast Cancer Patients with Brain Metastases: A Cross-Sectional Study.

The prognosis of breast cancer patients with brain metastasis is poor. It was aimed to define the clinicopathological features of breast cancer patients with brain metastases and to determine the risk factors and survival outcomes associated with brain metastasis. This is a single-center, retrospective, cross-sectional study. A total number of 127 patients diagnosed with breast cancer and who developed brain metastasis between January 2011 and March 2021 were retrospectively analyzed. The survival and clinicopathological data of these patients according to 4 biological subtypes were evaluated (luminal A, luminal B, HER-2 overexpressing, and triple-negative). The median overall survival for all patients was 45.6 months. The median time from the diagnosis of breast cancer to the occurrence of brain metastasis was 29.7 months, and the median survival time after brain metastasis was 7.2 months. The time from the diagnosis of breast cancer to brain metastasis development was significantly shorter in HER-2 overexpressing and triple-negative subtypes than in luminal A and B subtypes. The median time from breast cancer diagnosis to brain metastasis was 33.5 months in luminal A, 40.6 months in luminal B, 16.8 months in HER-2 overexpressing, and 22.8 months in the triple-negative groups (p=0.003). We found the worst median survival after brain metastasis in the triple-negative group with 3.5 months. Early and close surveillance of high-risk patients may help early diagnosis of brain metastasis and may provide to perform effective treatments leading to longer overall survival times for this patient population.

Evaluation of toxic effects of chemotherapy in lung malignancies on cerebral white matter using diffusion tensor imaging.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a leading cause of morbidity and mortality. Carboplatin and cisplatin based regimens are used in the treatment of NSCLC. The aim of the study was to find out whether there is a difference in white matter (WM) changes between two platinum-based chemotherapy agents using diffusion tensor imaging (DTI). PATIENTS AND METHODS: 25 patients who received chemotherapy for NSCLC and 27 age-matched healthy controls were enrolled in the study. Fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity (MD) and radial diffusivity (RD) values of the study population were measured from 11 regions of interest in pre-chemotherapy and post-chemotherapy MRI data. RESULTS: Cisplatin group showed a significant decrease in the FA of the inferior longitudinal fasciculus (P = 0.028). Carboplatin group showed a significant FA decrease and RD increase in the forceps minor (P = 0.022 and P = 0.011, respectively), and a significant reduction in AD and increase in MD in frontal white matter (WM) (P = 0.008 and P = 0.029, respectively). In comparison of post chemotherapy DTI values of the two groups, carboplatin group showed lower FA, and higher MD and RD values than cisplatin group in parieto-occipital WM (P = 0.034, P = 0.034, P = 0.029, respectively). CONCLUSIONS: The findings of the study suggest that subtle effects of chemotherapy detectable with DTI may emerge after the treatment. In addition, carboplatin regimen may have more impact on WM than cisplatin regimen.

Deficient Mismatch Repair and Lymphocytic Response to Tumor as Prognostic Markers in Stage II Colon Cancer Patients.

OBJECTIVE: To investigate the relationship between colon cancer (CC) subtypes defined by the status of tumor-infiltrating lymphocytes (TIL) and mismatch repair (MMR) combination with clinicopathological features and survival. STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: Department of Medical Oncology, Haydarpasa Numune Research and Training Hospital, Istanbul, Turkey, from July 2010 to March 2020. METHODOLOGY: Eighty-three patients with operated stage II colon cancer were included in the study. Pathology, surgery and oncological treatment and follow-up information were obtained from patient files; and statistical analyses were performed on overall survival (OS). Tumor-infiltrating lymphocytes and mismatch repair status was determined with the help of immunohistochemistry. RESULTS: TIL-high and deficient MMR (dMMR) status were detected in 26 patients (31.3%) and 21 patients (25.3%), respectively. Tumors were divided into four subgroups according to TIL and MMR status. TIL-high/dMMR tumors had the most favourable prognosis, while TIL-low/proficient MMR tumors exhibited poor OS. CONCLUSION: The combination of TIL and MMR could enable us to differentiate patients' survival outcomes in more details. Therefore, considering that the TIL and MMR status, evaluated by IHC, may be a cost-effective and effective option for risk classification in patients with stage II colon cancer. Key Word: Lymphocytic response, Mismatch repair, Prognosis, Tumor-infiltrating lymphocytes, Stage II cancer, Colon cancer.

Platelet to lymphocyte ratio is associated with tumor localization and outcomes in metastatic colorectal cancer.

ABSTRACT: The aim of this study was to investigate the predictive and prognostic value of PLR, and the relationship between PLR and tumor localization.A total of 229 patients with de-novo metastatic CRC were retrospectively analyzed. The cutoff value for PLR was defined by the receiver operating characteristic (ROC) curve analysis and threshold value of 196.5 as best cut-off value was found.The higher rate of BRAF mutation was significantly detected for patients with PLRhigh (> 196.5) compared to those with PLRlow (≤196.5) (P = .001). PLR was significantly higher in tumors located on the right colon (P = .012). PLR, tumor localization, the presence of surgery for primary tumor, the presence of curative surgery, the presence of metastasectomy for progression-free survival (PFS) and PLR, gender, BRAF mutation, tumor localization, the presence of surgery for primary tumor, the presence of metastasectomy for overall survival (OS) were found to be prognostic factors by univariate analysis. Multivariate analysis showed that PLR, the presence of curative surgery and the presence of metastasectomy for both PFS and OS were found to be independent prognostic factors. Moreover, a logistic regression analysis indicated that PLR and tumor localization were found to be an independent factors for predicting response to systemic treatment (P < .001 and P = .023 respectively).Our results showed that pretreatment PLR was readily feasible and simple biomarker predicting response to treatment and survival, in addition it was significantly associated with tumor localization.

Prognostic significance of primary tumor localization in patients with metastatic colorectal cancer: Is it beneficial to select targeted treatment? Real-life experience from Turkey.

PURPOSE: The purpose of this study was to investigate the prognostic value,and the effect of primary tumor location on targeted therapy selection in patients with metastatic colorectal cancer (mCRC). METHODS: A total of 201 patients with de novo mCRC who received first line treatment were retrospectively analyzed. Clinicopathological features, treatment outcomes, the primary tumor surgery, metastasectomies/local therapies and survivals were evaluated in terms of both RAS mutation status and primary tumor sidedness. RESULTS: Tumor localization showed 140 (69.7%) patients with left-sided and 61 (30.3%) with right-sided tumors. Median progression-free survival (PFS) and overall survival (OS) were significantly shorter in patients with right-sided tumor than those with left-sided tumors (10.1 vs 12.9 months, p=0.005; 25 vs 44.4 months, p=0.008, respectively). In addition,the median OS interval of patients receiving anti-VEGF containing regimen was better than those treated with anti-EGFR containing regimen (50.7 vs. 26.9 months, p=0.001). Multivariate analysis indicated that age (HR:0.41,p=0.045), primary tumor resection (HR:0.41,p=0.037) and primary tumor localization (HR:0.38,p=0.021) for PFS and age (HR:0.39, p=0.09), the presence of BRAF mutation (HR:0.59,p=0.019) and the type of targeted therapy (HR:3.16,p=0.025) for OS were independent prognostic factors. CONCLUSIONS: Our results showed that primary tumor location is a prognostic factor in mCRC patients regardless of RAS status. Primary tumor location before treatment decision may be a simple indicator predicting survival and in choosing targeted agent.

Primitive Neuroectodermal Tumor of the Testis.

A 21-year male presenting with left testicular mass and retroperitoneal lymphadenopathy underwent radical orchiectomy; and his pathological examination showed a mixed germ cell tumor composed of primitive neuroectodermal tumor mixed with mature teratoma. Six cycles of IE (ifosfamide, etoposide) and VAC (vincristine, doxorubicin, cyclophosphamide) chemotherapy were given after sperm preservation. He then underwent retroperitoneal lymph node dissection (RPLND). No tumor was detected in the removed lymph nodes, and all lymph nodes were reported as showing reactive changes. Key Words: Chemotherapy, Primitive neuroectodermal tumor, Surgery, Teratom, Testis.

Is the Duration of Temozolomide Predictive for Sequential Bevacizumab Treatment Responses in the Glioblastoma Multiforme Cancer Setting?

OBJECTIVE: To evaluate the predictive significance of the duration of temozolomide (TMZ) in patients with glioblastoma multiforme (GBM) who were treated with bevacizumab (Beva) as second-line setting. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Bezmialem Vakif University School of Medicine Hospital, Istanbul, Turkey, from January 2014 to September 2020. METHODOLOGY: A total of 109 patients, 47 (43.1%) females and 62 (56.9%) males, were retrospectively included in the study. All patients received TMZ as first-line and Beva as second-line treatment. Kaplan-Meier method and Cox regression model were performed for survival and univariate/multivariate analyses, respectively. RESULTS: Patients treated with first-line TMZ were divided into two groups according to the PFS. Group 1 is <9 months and group 2 is ≥9 months. Overall survival (OS) of group 1 and group 2 patients was evaluated  after the initiation of second-line bevacizumab treatment. The OS in group 1 was 7.8 months (6.9-8.6, 95% CI), and group 2 was eight months (6.4-9.5, 95% CI), but it was statistically non-significant (p = 0.837). CONCLUSION: Duration of first-line TMZ treatment was not a predictor for OS of the GBM patients, who were treated with Beva as second-line setting. Key Words: Bevacizumab, Duration of treatment, Glioblastoma multiforme, Predictive score, Temozolomide.

The correlation between fear of falling and upper extremity muscle strength.

OBJECTIVES: To determine the relationship between fear of falling (FOF) and upper extremity muscle strength. METHODS: This cross-sectional study included 112 hospitalized, mobile patients. Forty-seven (42%) were males and 65 (58%) were females, and the mean age was 72.3. The study was carried out between September 2018 and September 2019 at Balikli Rum Hospital Nursing Homes, Istanbul, Turkey. Patients were tested using geriatric tools (such as Mini-Mental State Examination) and physical tests such as handgrip, key pinch and 6-meter up and go tests. RESULTS: The average annual falling number of elderly people with FOF was statistically significantly higher than that in those without FOF (p=0.001). Right handgrip, left handgrip, right key pinch, and left key-pinch mean values in elderly individuals with FOF were statistically significantly lower than those without FOF (p< 0.001, p< 0.001, p< 0.001, p< 0.001, respectively). CONCLUSION: The measurement of upper extremity strength could be a predicting parameter of FOF.

Systemic Inflammatory Markers for Prediction of Bevacizumab Benefit in Glioblastoma Multiforme.

OBJECTIVE:  To evaluate the predictive significance of systemic inflammation markers (SIMs) in patients with glioblastoma multiforme (GBM), who were treated with bevacizumab (Beva). STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: The study was conducted at the Bezmialem Vakif University School of Medicine Hospital, Istanbul, Turkey, from January 2014 to September 2019. METHODOLOGY: A total of 107 patients, 49 (45.8%) female and 58 (54.2%) male, were retrospectively included in the study. The cut-off values for the SIMs-C-reactive protein to albumin ratio (CAR), neutrophil to lymphocyte (NLR) platelet to lymphocyte ratio (PLR), and systemic immune-inflammatory index (SIII))-were defined by receiver operating characteristic (ROC) analysis. Overall survival (OS) was plotted using the Kaplan-Meier method and compared using the log-rank test. Cox regression analysis was performed for univariate and multivariate analyses. RESULTS: ROC analysis was performed to determine the optimal prognostic value of each parameter. CAR: 1.32, NLR: 2.9, PLR: 159, and SIII: 785 were determined as cut-off values for predicting OS based on the areas under the curve (AUC) in the ROC analysis. CAR at 0.626, had sensitivity of 67%, and specificity of 71% (p=0.129); NLR at 0.725 had sensitivity of 67%, and specificity of 79% (p=0.007); PLR at 0.675 had sensitivity of 67%, and specificity of 64% (p=0.036); and SIII at 0.685, had sensitivity of 56%, and specificity of 71% (p=0.026). A multivariate analysis demonstrated that CAR (p=0.006) and PLR (p=0.024) were independent prognostic factors for OS in patients with GBM, treated by Beva. CONCLUSION:  The present study's findings suggest that pretreatment CAR and PLR might be an independent predictive marker for patients with GBM, who are treated by Beva. Key Words: C-reactive protein-to-albumin ratio (AR), Glioblastoma multiforme, Neutrophil-to-lymphocyteratio (NLR), Platelet-to-lymphocyte ratio (PLR), Predictive score.

Systemic therapy of liver cancer.

Hepatocellular carcinoma (HCC) is a lethal malignancy with poor prognosis. More than 80% of patients are diagnosed at an advanced stage, and most patients with HCC also have liver cirrhosis that complicates cancer management. No targeted treatment options currently exist outside genomics-based clinical trials. Multiple tyrosine kinase inhibitors (mTKIs) such as sorafenib, lenvatinib, cabozantinib, and regorafenib have been used to treat advanced hepatocellular carcinoma (aHCC). Immune checkpoint inhibitors including nivolumab and pembrolizumab have shown survival benefit. More recently, atezolizumab in combination with bevacizumab resulted in improved overall survival and progression-free survival, compared with sorafenib in patients with aHCC in the first-line setting. The combination of nivolumab with ipilimumab as an alternative in the treatment of patients treated with sorafenib has inspired various combination studies of immune checkpoint inhibitors. Currently, ongoing studies of systemic therapy consist of various immune-based combination therapies. Finally, there is no established adjuvant and neoadjuvant therapy although a few early phase studies show promising results. In this chapter, we summarize current approaches of systemic treatment in patients with liver cancer.

Is lymph node dissection necessary for staging while undergoing nephrectomy in patients with renal cell carcinoma?

OBJECTIVE: The essential treatment for patients with renal cell carcinoma is nephrectomy. As no lymph node dissection (LND) could be performed in the majority of these patients, healthy staging could not be carried out. In this study, we investigated the impact of LND during nephrectomy on patient survival. METHODS: A total of 181 patients-58 (32%) were female and 123 (68%) were male-were included in the study. Median follow-up period was 48 months. The patients were separated into 4 groups according to their stage during diagnosis; group 1 (T1-3N0M0), group 2 (T1-3NXM0), group 3 (T1-3N1M0), and group 4 (T1-4N0/XM1). The disease-free survival of nonmetastatic patients and the overall survival of all groups were calculated. RESULTS: Mean age was 58.4 ± 12.0 years. Median survival for Group 1 could not be reached. Median survival was 89 months in Group 2, 50 months in Group 3, and 39 months in Group 4 (P <0.001). There was no statistically significant difference between the N1 and M1 groups (P = 0.297). For the NX patient group without LND, median survival was 89 months, which is worse than the N0 group and better than the N1 group (P = 0.002). CONCLUSIONS: Our study presumes that the patients without LND are not staged sufficiently, NX patients have worse survival rates when compared with N0 patients, node-positive patients have poor survival rates as do the metastatic patients, and it should be defined as TNM stage4.

Which is the worse prognostic factor in patients with stage III colorectal cancer: tumor 4 or node 2?

PURPOSE: In the tumor (T), node (N), metastasis (M) American Joint Committee on Cancer (AJCC), and Union for International Cancer Control (UICC) (8th edition) staging system, N stage is more prominent than T stage. Our study aimed to compare the lymph node status of T4 tumors in stage III colorectal cancer (CRC). METHODS: A total of 475 patients (209; 44% female and 266; 56% male) were included in the study. The median follow-up period was 49 (4-176) months. The patients were separated into four groups according to their stage during diagnosis: group 1 (T4N2), group 2 (T4N1), group 3 (T1-3N2), and group 4 (T1-3N1). The disease-free survival (DFS) and overall survival (OS) of all the groups were calculated. RESULTS: The median OS was 40.5 months in group 1, 67 months in group 2, 87 months in group 3, and 138.5 months in group 4 (p<0.001). The N2 patients were separated into two groups according to their T stage: group 1 and group 3. Group 1 patients were associated with a worse OS than group 3 patients (p=0.017). The T4 patients were separated into two groups according to their N stage: group 1 and group 2. There was no statistically significant difference between group 1 and group 2 (p=0.243). CONCLUSIONS: Our study showed that patients with T4 stage have worse survival rates when compared with N2 patients in stage III CRC. These results support the TNM staging system to be T-dominant rather than N-dominant.

Clinicopathological Features of Gastroenteropancreatic Neuroendocrine Neoplasms.

ABSTRACT  Objective: To describe the clinical, pathological and survival characteristics of Turkish patients with gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Bezmialem Vakif University School of Medicine Hospital from April 2012 to September 2018. METHODOLOGY: Sixty-one patients with GEP-NENs were analysed in retrospect for the clinical, pathological and survival characteristics. The Kaplan-Meier method was used for survival analysis and the Log-rank test was performed to analyse the comparisons between the groups. RESULTS:  Forty-five of the 61 GEP-NENs patients (73.8%) were neuroendocrine tumor (NET) and 26.2% of patients were neuroendocrine carcinoma (NEC). The mean age of patients was 55.5 ± 11.3 years. The most frequent localisation of tumors was stomach (34.4%), and the most common symptom was abdominal pain (27.9%). The rate of distant metastases was 31.1% at diagnosis and 63.9% of the patients were operated. The median follow-up period was 27 months. The rate of three-years overall survival (OS) was 88.5% and the five-years OS rate was 86.9%. The variables that can significantly influence the OS rate were high grade (grade 3; p= 0.005), Ki-67 proliferation index (Ki-67 >20%; p= 0.002) and distant metastases (p= 0.018). CONCLUSION: GEP-NENs may develop anywhere in the digestive tract. Approximately one-third of the patients may be metastatic due to delay in diagnosis. Key Words: Gastroenteropancreatic neuroendocrine tumor, Neuroendocrine cancers, Neuroendocrine neoplasms.

Usefulness of serum M30 and M65 levels to predict response to neoadjuvant chemotherapy in patients with breast cancer.

OBJECTIVE: M30 and M65 levels reflect tumor cell activity in patients with epithelial cancer. Cytokeratin 18 is one of the cell skeletal elements. M30 is a apoptotic marker of cytokeratin 18. M65 levels are both an apoptosis and a necrosis marker. The aim of our study was to determine the predictive value of M30 and M65 levels in neoadjuvant treatment of breast cancer. MATERIALS AND METHODS: In this prospective study, 41 patients with breast cancer who underwent neoadjuvant chemotherapy were included. Following 4 cycles of chemotherapy with anthracycline containing regimen, patients received paclitaxel treatment for 12 weeks. Blood was collected from the patients before chemotherapy and on day 21, after the 2nd, 4th, and 8th cycles. M30 and M65 levels were measured with the ELISA method. RESULTS: While there was an increase in M30 and M65 levels at the 4th cycle (P < 0.05), levels were decreased after the 8th cycle. In addition, there was no significant relationship among M30, M65 levels, and prognostic factors such as ER, PR, c-Erb-2, Ki-67, pathologic-T, pathologic-N, and chemotherapy responses. CONCLUSION: M30 and M65 levels are not of predictive values of response to breast cancer patients receiving neoadjuvant chemotherapy. Nevertheless, M30 and M65 levels increased when patients kept receiving anthracycline containing chemotherapy.

Prognostic Factors for Operated Gallbladder Cancer.

PURPOSE: The prognosis of gallbladder cancer is poor. Lymph node metastasis and the stage are known to be the strongest prognostic factors for survival. The aim of this study was to determine the importance of complementary surgery and other prognostic factors for survival of operated gallbladder cancer. MATERIAL AND METHOD: We retrospectively analyzed 62 localized gallbladder cancers. The prognostic factors for survival were evaluated by univariate and multivariate analysis. RESULTS: The 3-year overall survival (OS) and disease-free survival (DFS) rates were 52.8 and 43.5%, respectively. Totally, 37 patients (59.6%) were diagnosed incidentally during simple cholecystectomy which was performed for benign causes but only 56.4% of them underwent complementary surgery. 51.6% of the recurrence was detected during 18.4 months of follow-up time. R0 resection, T stage, and pathological stage were found to be related with both OS and DFS by univariate analysis. Grade, lymph node metastasis, and adjuvant chemotherapy were also related with DFS. Presence of recurrence, recurrence side, performance score (PS), and perineural invasion (PNI) were related with OS. Peritoneal metastasis, advanced stage disease, and lymph node metastasis were more common among patients who did not undergo complementary surgery. Adjuvant chemotherapy was given more frequently to patients who undergone complementary surgery group. The multivariate analysis indicated that grade, lymph node metastasis, stage, recurrence site, PS, and adjuvant chemotherapy stage were independent prognostic factors for DFS on the other and only stage was a prognostic factor for OS. CONCLUSION: Our results showed that incidental diagnosis or complementary surgery was not related with DFS or OS but stage was only an independent prognostic factor for both OS and DFS in resected gallbladder cancer.

Regorafenib or rechallenge chemotherapy: which is more effective in the third-line treatment of metastatic colorectal cancer?

PURPOSE: To assess the efficacy and safety of regorafenib versus rechallenge chemotherapy in previously treated mCRC patients in third-line setting. MATERIALS AND METHODS: The data of 104 patients diagnosed with mCRC enrolled from 2010 to 2017 in six oncology centers were analyzed. Tumor treatment options were obtained from follow-up and treatment files. Rechallenge chemotherapy was identified as the re-use of the regimen which was previously administered to patients in one of the therapy lines and obtained disease control, these were the patients whose disease did not progress within 3 months. RESULTS: A total of 104 patients had received previously two lines of chemotherapy regimens for mCRC. Of these, 73 patients with mCRC who received regorafenib and 31 those who received rechallenge chemotherapy in third-line therapy were analyzed. Overall survival was better with rechallenge than it was with regorafenib (HR 0.29 95% CI 0.16-0.54, p < 0.001). Median OS was 12.0 months (95% CI 8.1-15.9) in rechallenge versus 6.6 months (95% CI 6.0-7.3) in regorafenib group (p < 0.001). Progression-free survival in the rechallenge group showed a higher median value of 9.16 months (95% CI 7.15-11.18) versus with that recorded in the regorafenib group of 3.41 months (95% CI 3.01-3.82), in favor of rechallenge chemotherapy. The most common adverse events of regorafenib was liver function test abnormality and hand-foot syndrome. Although grade 3 or 4 adverse events were similar, non-hematologic toxicities were more common than those of rechallenge. CONCLUSIONS: Rechallenge is still a valuable option against regorafenib in patients who achieved disease control in one of the first two lines of therapy. Even though mCRC patients treated with regorafenib benefited clinically from this treatment, we revealed that chemotherapy rechallenge compared to regorafenib was more effective in the third-line treatment for mCRC patients.

Role of Urotensin-2 in 5-Fluorouracil-Related Arterial Vasoconstriction in Cancer Patients.

BACKGROUND: The aim of this study was to identify the possible relationship of 5-fluorouracil (5-FU)-related arterial vasoconstriction with urotensin-2 (UT-2), which has a high potential as an endogenic vasoconstrictor. METHODS: We assigned the patients to 1 of 3 groups. Patients in group 1 received a bolus of 5-FU, those in group 2 a continuous infusion (CI) of 5-FU, and those in group 3 no 5-FU, which was also a control group. Pre- and post-treatment UT-2 levels and brachial arterial diameters were measured and recorded in all patients. RESULTS: 132 patients were included in the study. Pre- and post-treatment brachial artery diameters were similar in all groups: in group 1 (3.28 ± 0.52 vs. 3.25 ± 0.44 mm, p = 0.740), in group 2 (3.57 ± 0.47 vs. 3.46 ± 0.45 mm, p = 0.441) and in the control group (3.51 ± 0.52 vs. 3.25 ± 0.44 mm, p = 0.818). Pre- and post-treatment UT-2 levels were significantly different in each group: in group 1 (39.5 ± 30.9 vs. 56.7 ± 27.1 ng/ml, p = 0.0001), in group 2 (37.7 ± 33.7 vs. 62.5 ± 37.7 ng/ml, p = 0.0001) and in the control group (52.9 ± 40.2 vs. 60.8 ± 40.7 ng/ml, p = 0.006). CONCLUSION: Our findings suggest that UT-2 has a high potential as a vasoconstrictor agent in our bodies and its level increases through a bolus or CI 5-FU. Increased UT-2 levels are likely to play a role in 5-FU-related cardiac toxicity pathogenesis.