Cisplatin plus paclitaxel and bevacizumab versus carboplatin plus paclitaxel and bevacizumab for the first-line treatment of metastatic or recurrent cervical cancer.

OBJECTIVE: Cisplatin-paclitaxel and bevacizumab is a frequently used treatment regimen for metastatic or recurrent cervical cancer, and carboplatin-paclitaxel and bevacizumab are also among the recommended regimens. In this study we aimed to evaluate the efficacy of these two regimens for the treatment of metastatic or recurrent cervical cancer. METHODS: Patients with metastatic or recurrent cervical cancer treated with cisplatin-paclitaxel and bevacizumab or carboplatin-paclitaxel and bevacizumab were retrospectively evaluated in this study. The clinical and demographic characteristics of patients in each group were evaluated. Median overall survival, progression-free survival, and response rates between the two groups were compared. RESULTS: A total of 250 patients were included. Overall, the numbers of patients with recurrent disease and metastatic disease were 159 and 91, respectively. The most common histologic subtype was squamous cell carcinoma (83.2%). The median duration of follow-up was 13.6 (range 0.5-86) months. The median progression-free survival was 10.5 (95% CI 9.0 to 11.8) months in the cisplatin-paclitaxel and bevacizumab group (group 1), and 10.8 (95% CI 8.6 to 13.0) months in the carboplatin-paclitaxel and bevacizumab group (group 2) (HR 1.20; 95% CI 0.88 to 1.63; p=0.25). The median overall survival was 19.1 (95% CI 13.0 to 25.1) months in group 1 and 18.3 (95% CI 15.3 to 21.3) months in group 2 (HR 1.28; 95% CI 0.91 to 1.80; p=0.15). CONCLUSIONS: There is no survival difference between cisplatin or carboplatin combined with paclitaxel and bevacizumab in metastatic or recurrent cervical cancer.

Ginseng and cancer.

Derived from the Greek word Panacea that means 'cure for all', Ginseng (Panax) has had an important place in Chinese Medicine for many of years. As the name suggests, it is believed to be a miraculous plant effective in the treatment of many health problems. It is claimed to have many effects such as sedative, hypnotic, aphrodisiac, antidepressant, diuretic, and stimulating effects, and to be effective in the treatment of certain health problems such as diabetes, Alzheimer's disease, erectile dysfunction and infections. In addition, its effects on the prevention and treatment of cancer as well as on the reduction of cancer-related symptoms have been prioritized in recent years. However, the studies that have been done so far do not confirm these effects. Although certain favorable results have been obtained in some studies intended for investigating its effects on acute nasopharyngitis, diabetes, Alzheimer's disease, and erectile dysfunction, it is early to say anything conclusive. And in cancer patients, it has been shown to be effective in reducing weakness due to cancer and its treatment. On the other hand, ginseng may cause important drug interactions, although it is described as a relatively safe product. For now, it seems to be reasonable to use ginseng only for cancer-related weakness in cancer patients at this point. But this should definitely be done within the knowledge and under the control of oncologists.

Ganoderma Lucidum (Reishi Mushroom) and cancer.

Having a long historical past in traditional Chinese medicine, Ganoderma Lucidum (G. Lucidum) is a type of mushroom believed to extend life and promote health. Due to the increasing consumption pattern, it has been cultivated and marketed intensively since the 1970s. It is claimed to be effective in the prevention and treatment of many diseases, and in addition, it exerts anticancer properties. Almost all the data on the benefits of G. Lucidum are based on laboratory and preclinical studies. The few clinical studies conducted are questionable. Nevertheless, when the findings obtained from laboratory studies are considered, it turns that G. Lucidum is likely to have some benefits for cancer patients. What is important at this point is to determine the components that will provide these benefits, and use them in drug development, after testing their reliability. In conclusion, it would be the right approach to abstain from using and incentivizing this product, until its benefits and harms are set out clearly, by considering its potential side effects.

Curcumin (Turmeric) and cancer.

Curcumin is a substance obtained from the root of the turmeric plant, which has the feature of being a yellow or orange pigment. It is also the main component of curry powder commonly used in Asian cuisine. Curcumin, a substance that has had an important place in traditional Indian and Chinese medicines for thousands of years, has been the center of interest for scientific studies especially in the field of cancer treatment for several years. Laboratory studies have presented some favorable results in terms of curcumin's antioxidant, antiinflammatory and anticancer properties in particular. However, since such findings have yet to be confirmed in clinical studies, its effect on humans is not clearly known. Therefore, when its advantages in terms of toxicity, cost and availability as well as the favorable results achieved in laboratory studies are considered, it would not be wrong to say that curcumin is a substance worth being studied. However, for now the most correct approach is to abstain from its use for medical purposes due to lack of adequate reliable evidence obtained from clinical studies, and because of its potential to interfere with other drugs.

Prognostic factors in clinical stage T4N2 locally advanced non-small cell lung cancer.

PURPOSE: Relatively few studies have focused on T4N2 (stage IIIB) locally advanced non-small cell lung cancer (NSCLC). In this study, we tried to identify prognostic factors for patients with clinical stage T4N2 NSCLC. METHODS: We retrospectively identified 223 patients, of which 168 met the inclusion criteria. Patients treated with curative intent using concurrent chemoradiotherapy (CRT) with or without adjuvant chemotherapy, or concurrent CRT after induction chemotherapy, were included in this study. Relevant patient, treatment, and disease factors were evaluated for their prognostic significance in both univariate and multivariate analyses using the Cox proportional hazards model. RESULTS: The median progression-free survival (PFS) was 13 months (95% confidence interval [CI], 10.6-15.4). The median overall survival (OS) was 20 months (95% CI, 16.8-23.1), and 71, 40.3 and 28.2% of the patients survived for 1, 2 and 3 years after diagnosis, respectively. Multivariate analysis showed Eastern Cooperative Oncology Group (ECOG) performance status (PS) was independent predictor of PFS (hazard ratio [HR], 0.24; 95% CI, 0.13-0.43; p=0.001), and OS [HR, 0.48; 95% CI, 0.26-0.87; p=0.015). Absence of multifocal T4 tumors was also associated with a significantly longer OS (HR, 046; 95% CI, 0.31-0.7; p=0.001). There was no statistically significant difference in OS and PFS between treatment modalities. CONCLUSION: PFS and OS were significantly shorter in patients with poor ECOG PS. OS was also significantly shorter in patients with multifocal T4 tumors. There were no differences between the two therapeutic approaches with respect to outcome.

Use of chemotherapy at the end of life in Turkey.

BACKGROUND: An increasing number of patients receive palliative chemotherapy near the end of life. The aim of this study is to evaluate the aggressiveness of chemotherapy in Turkish individuals near the end of life. METHODS: Patients diagnosed with solid tumors and died from 2010 to 2011 in the medical oncology department of Akdeniz University were included in the study. Data about the diagnosis, treatment details and imaging procedures were collected. RESULTS: Three hundred and seventy-three people with stage IV solid tumors died from 2010 to 2011 in our clinic. Eighty-nine patients (23.9%) patients underwent chemotherapy in the last month of life while 39 patients (10.5%) received chemotherapy in the last 14 days. The probability of undergoing chemotherapy in the last month of life was influenced by: age, 'newly diagnosed' patients, and performance status. There was no significant association of chemotherapy in the last month of life with gender and tumor type. Having a PET-CT scan did not alter the chemotherapy decision. CONCLUSION: In conclusion, chemotherapy used in the last month of life in a tertiary care center of Turkey is high. Increasing quality of life should be a priority near the end of life and physicians should consider ceasing chemotherapy and direct the patient to early palliative care.

Yttrium-90 radioembolization in patients with unresectable liver metastases: determining the factors that lead to treatment efficacy.

INTRODUCTION: Locoregional treatments, such as radioembolization, can be used to treat patients with unresectable liver metastases. We aimed to determine the progression-free survival and factors that predict survival of patients with liver metastases whose response to selective internal radiation therapy (SIRT) with Y-90 was assessed by positron emission tomography-computed tomography (PET-CT). PATIENTS: Our study included 78 liver cancer patients who were treated with Y-90 radioembolization. RESULTS: The post-treatment response rates were as follows: 7 patients (9%) had stable disease (SD), 26 patients (33.3%) had a partial response (PR), 4 patients (5.1%) had a complete response (CR). The median hepatic progression-free survival (HPFS) was 4.4 months while median overall survival was 10.1 months. Univariate analysis revealed that HPFS is significantly affected by international normalized ratio (INR) levels and age (Hazard Ratio(HR)=0.54 (95%CI:0.30-096), P=0.034, HR=1.03(95%CI:1.00-1.05), P=0.051). However, only INR levels retained significance with multivariate analysis (HR=0.53 (95%CI:0.30-0.93), P=0.028), while age had limited significance (HR =1.02 (95% CI:1.00-1.05), P=0.051). CONCLUSIONS: We determined that Y-90 radioembolization is effective as a salvage therapy in patients with predominant liver metastases. For the first time, we showed that age and INR values reflecting the functional hepatic reserve can be used as positive predictive factors for HPFS.

Prolonged progression-free survival with maintenance metronomic oral cyclophosphamide and etoposide treatment in macroscopic residual disease or recurrent/advanced stage ovarian cancer.

PURPOSE: In ovarian cancer permanent remission may be provided with optimal cytoreductive surgery and adjuvant chemotherapy. However survival is short in patients with residual macroscopic disease after surgery or recurrent ovarian cancer. Applicable maintenance therapies with low toxicity are required to prolong progression-free survival (PFS) for patients with no curative treatment options. In this study, we investigated the effect of maintenance metronomic oral cyclophosphamide and etoposide (CE) in ovarian cancer patients with post operative residual or recurrent disease. METHODS: Forty five patients that received metronomic oral CE (cyclophosphamide 50 mg/daily and etoposide 50 mg for 1-5 days, every 21 days) as maintenance therapy for residual disease due to incomplete surgical resection or recurrent advanced-stage ovarian cancer were evaluated. The time between the beginning of oral CE and disease progression was also evaluated. RESULTS: The mean patient age was 58 years, the vast majority had serous adenocarcinoma (78%) and received a mean of 2 (range 1-4) lines of various intravenous regimens for postoperative residual or recurrent disease. Mean duration of oral CE was 11.3 months (range 2.9-29). Median PFS was 10.3 months (range 7.9-12.8). Only 5 patients discontinued treatment due to intolerance and grade 3-4 toxicity was recorded in 3 patients (7%). CONCLUSION: Maintenance metronomic oral CE treatment was found effective, minimally toxic and sustainable in patients with macroscopic residual or recurrent advanced-stage ovarian cancer. However, randomized and placebo-controlled well designed studies are required.

Evaluation of the efficacy and safety of nivolumab in the second- or later-line treatment of patients with locally advanced/metastatic non-small cell lung cancer in Türkiye: a retrospective multicenter non-interventional registry study.

OBJECTIVE: To evaluate the efficacy and safety of nivolumab in the second-line (2L) or later-line (LL) treatment of patients with locally advanced/metastatic non-small cell lung cancer (NSCLC) in real-life setting in Türkiye. METHODS: This study was designed as a national, multi-center, retrospective study. The study population was evaluated in two groups for the line of nivolumab therapy: those receiving nivolumab in the 2L (Group 2L) and third-line (3L) or LL (Group 3L/LL). Efficacy was evaluated based on one-year overall survival (OS) and progression-free survival (PFS). Safety was evaluated based on treatment-related adverse events (AEs) and nivolumab discontinuation rate. RESULTS: Of 244 patients, 52.9% were in Group 2L and 47.1% were in Group 3L/LL. Demographic and clinical characteristics did not differ between the groups. In Group 2L and Group 3L/LL, one-year OS and PFS rates were 60.8% and 61.4% (p = 0.592) and 31.2% and 21.3% (p = 0.078), respectively. The objective response rate (ORR) was 34.7% in Group 2L and 27.3% in Group 3L/LL (p = 0.262). The percentage of patients reporting at least one AE in Groups 2L and 3L/LL was 34.9% and 43.5%, respectively (p = 0.169). Fatigue was the most common (16.4%) treatment-related AE in each group. The groups were comparable regarding the AE frequency. Nivolumab was discontinued in 61 patients in Group 2L and 53 patients in Group 3L/LL, with the most common reason being disease progression (57.4% and 66.0%, respectively). CONCLUSION: Nivolumab is safe and effective in the 2L or 3L/LL treatment of locally advanced/metastatic NSCLC and associated with acceptable AEs in real-life setting.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer (around 85% of all lung cancers). Patients with NSCLC are usually diagnosed at advanced or metastatic stages. When cancer cells spread to other areas from where they first formed, it is called metastatic cancer. Surgery may not be a treatment option for such patients. Currently, immunotherapeutic agents are used in the treatment of NSCLC. Nivolumab is one of the approved immunotherapeutic agents in the treatment of patients with metastatic NSCLC, who have failed after receiving chemotherapy. Our study explored the efficacy and safety of nivolumab in real-life setting in Türkiye. Nivolumab effectiveness was evaluated by overall survival (OS) and progression-free survival (PFS) rates. OS indicates the proportion of patients who are still alive at a given time after diagnosis or treatment initiation. PFS refers to "the length of time during and after cancer treatment that a person lives with the disease but does not get worse." In the present study, one-year OS for 244 patients who received nivolumab was 61.1% and one-year PFS was 26.4%. Nivolumab safety was evaluated based on the frequency of adverse events observed during nivolumab therapy. Of the patients 38.9% had at least one side effect, with fatigue being the most common (16.4%). Our results support the earlier studies and showed that nivolumab was a safe and effective agent and is associated with acceptable side effects.

Assessment High-Risk Breast Cancer in Older Patients: A Comparative Analysis of PREDICT Scores and TAILORx Risk Categorization.

Objective: This study aimed to evaluate the relationship between PREDICT tool overall survival (OS) scores and high-risk patients according to TAILORx risk categorization in elderly hormone reseptor (HR) positive human epidermal growth factor negative early breast-cancer patients. Materials and Methods: We conducted a retrospective study, extracting data from medical records of 64 patients diagnosed with breast cancer. A retrospective analysis was performed on all patients who had Oncotype Dx Recurrence Scores across five medical centers between 2017 and 2022. PREDICT scores were defined as calculated 10-year OS rates via PREDICT tool. Results: The median age of the patients was 67, with a range between 65-75 years. Low-risk patients had a slightly higher two PREDICT scores compared to high-risk patients (78% vs. 73%), (81% vs. 77%), which were statistically significant. The progesterone receptor (PR) level was significantly lower in the high-risk group (3.5% vs. 80%). A unit decrease in the PREDICT scores was associated with a 11% increase in the odds of being in the high-risk group. However, these effects weren't statistically significant in the multivariate analysis. A unit decrease in the PR level was significantly associated with increased odds (by 5% in the multivariate analysis) of being in the high-risk group. Conclusion: Our study underscores the importance of using a combination of tools, including the PREDICT tool, PR levels, and TAILORx risk categorization, for a comprehensive risk assessment in these patients, especially in the older population. Accurate risk assessment is crucial for tailoring the treatment and optimizing outcomes in this vulnerable population. Future studies are warranted to further validate these findings in larger cohorts and to explore additional biomarkers and genomic signatures that may aid in the risk assessment and management of breast cancer in older patients.

Survival results according to Oncotype Dx recurrence score in patients with hormone receptor positive HER-2 negative early-stage breast cancer: first multicenter Oncotype Dx recurrence score survival data of Turkey.

Background: The Oncotype Dx recurrence score (ODx-RS) guides the adjuvant chemotherapy decision-making process for patients with early-stage hormone receptor-positive, HER-2 receptor-negative breast cancer. This study aimed to evaluate survival and its correlation with ODx-RS in pT1-2, N0-N1mic patients treated with adjuvant therapy based on tumor board decisions. Patients and methods: Estrogen-positive HER-2 negative early-stage breast cancer patients (pT1-2 N0, N1mic) with known ODx-RS, operated on between 2010 and 2014, were included in this study. The primary aim was to evaluate 5-year disease-free survival (DFS) rates according to ODX-RS. Results: A total of 203 eligible patients were included in the study, with a median age of 48 (range 26-75) and median follow-up of 84 (range 23-138) months. ROC curve analysis for all patients revealed a recurrence cut-off age of 45 years, prompting evaluation by grouping patients as ≤45 years vs. >45 years. No significant difference in five-year DFS rates was observed between the endocrine-only (ET) and chemo-endocrine (CE) groups. However, among the ET group, DFS was higher in patients over 45 years compared to those aged ≤45 years. When stratifying by ODx-RS as 0-17 and ≥18, DFS was significantly higher in the former group within the ET group. However, such differences were not seen in the CE group. In the ET group, an ODx-RS ≥18 and menopausal status were identified as independent factors affecting survival, with only an ODx-RS ≥18 impacting DFS in patients aged ≤45 years. The ROC curve analysis for this subgroup found the ODx-RS cut-off to be 18. Conclusion: This first multicenter Oncotype Dx survival analysis in Turkey demonstrates the importance of Oncotype Dx recurrence score and age in determining treatment strategies for early-stage breast cancer patients. As a different aproach to the literature, our findings suggest that the addition of chemotherapy to endocrine therapy in young patients (≤45 years) with Oncotype Dx recurrence scores of ≥18 improves DFS.

The Utility of NGS Analysis in Homologous Recombination Deficiency Tracking.

Several tumor types have been efficiently treated with PARP inhibitors (PARPis), which are now approved for the treatment of ovarian, breast, prostate, and pancreatic cancers. The BRCA1/2 genes and mutations in many additional genes involved in the HR pathway may be responsible for the HRD phenomenon. The aim of the present study was to investigate the association between genomic loss of heterozygosity (gLOH) and alterations in 513 genes with targeted and immuno-oncology therapies in 406 samples using an NGS assay. In addition, the %gLOHs of 24 samples were calculated using the Affymetrix technology in order to compare the results obtained via the two methodologies. HR variations occurred in 20.93% of the malignancies, while BRCA1/2 gene alterations occurred in 5.17% of the malignancies. The %LOH was highly correlated with alterations in the BRCA1/2 genes, since 76.19% (16/21) of the BRCA1/2 positive tumors had a high %LOH value (p = 0.007). Moreover, the LOH status was highly correlated with the TP53 and KRAS statuses, but there was no association with the TMB value. Lin's concordance correlation coefficient for the 24 samples simultaneously examined via both assays was 0.87, indicating a nearly perfect agreement. In conclusion, the addition of gLOH analysis could assist in the detection of additional patients eligible for treatment with PARPis.

Only 32.3% of Breast Cancer Families with Pathogenic Variants in Cancer Genes Utilized Cascade Genetic Testing.

BACKGROUND: Hereditary cancer predisposition syndromes are responsible for approximately 5-10% of all diagnosed cancer cases. In order to identify individuals at risk in a cost-efficient manner, family members of individuals carrying pathogenic alterations are tested only for the specific variant that was identified in their carrier relative. The purpose of this study was to investigate the clinical use and implementation of cascade family testing (CFT) in families of breast cancer patients with pathogenic/likely pathogenic variants (PVs/LPVs) in cancer-related predisposition genes. METHODS: Germline sequencing was carried out with NGS technology using a 52-gene panel, and cascade testing was performed by Sanger sequencing or MLPA. RESULTS: In a cohort of 1785 breast cancer patients (families), 20.3% were found to have PVs/LPVs. Specifically, 52.2%, 25.1%, and 22.7% of patients had positive findings in high-, intermediate-, and low-penetrance breast cancer susceptibility genes, respectively. Although CFT was recommended to all families, only 117 families (32.3%) agreed to proceed with genetic testing. Among the first-degree relatives who underwent CFT, 70.3% were female, and 108 of 121 (89.3%) were cancer free. Additionally, 42.7%, 36.7%, and 20.6% were offspring, siblings, and parents of the subject, respectively. Our data suggest that CFT was mostly undertaken (104/117, 88.8%) in families with positive findings in high-risk genes. CONCLUSIONS: Cascade family testing can be a powerful tool for primary cancer prevention by identifying at-risk family members. It is of utmost importance to implement genetic counseling approaches leading to increased awareness and communication of genetic testing results.

Effects and permanency of the training program "communication with cancer patients" on the opinions of students.

Learning to develop the doctor-patient relationship is very important in the treatment of patients with cancer. We aim to train our students in the early years of study about this subject with a course on the patient-doctor communication, prepared for third year students. One hundred fifty-four third year students participated in our study during the 2006-2007 academic years. The same questionnaire was given to the students in the 2009-2010 academic year; their sixth year of study. The rate of return for the questionnaire is 88.7%. Based on this study, we have the opinion that the training given in the third year is beneficial; however, the efficacy of the training diminishes with the advancing years, and therefore, the length of this training should be increased in the upper classes and additional hours should be added.

Cetuximab-induced rash is associated with overall survival in patients with recurrent/metastatic squamous cell carcinoma of head and neck.

PURPOSE: In this study, we looked for whether treatment-induced rash predicts treatment efficacy in patients with recurrent/metastatic HNSCC treated with Cetuximab and chemotherapy. METHODS: Patients who were treated with platinum-based chemotherapy and cetuximab for the first line treatment of recurrent/metastatic HNSCC were recruited. Presence of rash, hypomagnesemia, hypopotassemia, anemia, neutropenia, thrombocytopenia during treatment and treatment response, date of progression, date of last visit and death were recorded. RESULTS: A total of 138 patients' data were available for analysis. Any grade of rash was detected in 57 (44.5%) of the patients. The incidence of rash was significantly higher in patients with objective response than in patients with disease progression (%56.8 vs %14.3, p < 0.001). Progression free survival was 7.06 months (4.98-9.15) in patients treated with cetuximab and chemotherapy as first line treatment. In the multivariate analysis; rash was significantly correlated with longer PFS (HR 2.136; 95% CI 1.067-4.278; p = 0.032). Progression free survival was 9.65 months in patients who experienced rash, and 6.02 months in patients without rash, (p = 0.019, log-rank test). Overall survival was 11.24 months (9.65-12.82). In multivariate analysis, the survival of patients with rash was significantly longer than patients without rash (HR 1.954; 95% CI 1.162-3.285; p = 0.012). Overall survival was 15.08 months in patients who experienced rash, and 8.61 months in patients without rash (p = 0.05, log-rank test). CONCLUSION: Cetuximab-induced rash is associated with better ORR and longer PFS and OS in patients with recurrent/metastatic HNSCC treated with Cetuximab and platinum-based chemotherapy.

Comprehensive tumor molecular profile analysis in clinical practice.

BACKGROUND: Tumor molecular profile analysis by Next Generation Sequencing technology is currently widely applied in clinical practice and has enabled the detection of predictive biomarkers of response to targeted treatment. In parallel with targeted therapies, immunotherapies are also evolving, revolutionizing cancer therapy, with Programmed Death-ligand 1 (PD-L1), Microsatellite instability (MSI), and Tumor Mutational Burden (TMB) analysis being the biomarkers employed most commonly. METHODS: In the present study, tumor molecular profile analysis was performed using a 161 gene NGS panel, containing the majority of clinically significant genes for cancer treatment selection. A variety of tumor types have been analyzed, including aggressive and hard to treat cancers such as pancreatic cancer. Besides, the clinical utility of immunotherapy biomarkers (TMB, MSI, PD-L1), was also studied. RESULTS: Molecular profile analysis was conducted in 610 cancer patients, while in 393 of them a at least one biomarker for immunotherapy response was requested. An actionable alteration was detected in 77.87% of the patients. 54.75% of them received information related to on-label or off-label treatment (Tiers 1A.1, 1A.2, 2B, and 2C.1) and 21.31% received a variant that could be used for clinical trial inclusion. The addition to immunotherapy biomarker to targeted biomarkers' analysis in 191 cases increased the number of patients with an on-label treatment recommendation by 22.92%, while an option for on-label or off-label treatment was provided in 71.35% of the cases. CONCLUSIONS: Tumor molecular profile analysis using NGS is a first-tier method for a variety of tumor types and provides important information for decision making in the treatment of cancer patients. Importantly, simultaneous analysis for targeted therapy and immunotherapy biomarkers could lead to better tumor characterization and offer actionable information in the majority of patients. Furthermore, our data suggest that one in two patients may be eligible for on-label ICI treatment based on biomarker analysis. However, appropriate interpretation of results from such analysis is essential for implementation in clinical practice and accurate refinement of treatment strategy.

Purified micronized flavonoid fraction ameliorates the injury of spleen and ileum secondary to hepatic ischemia-reperfusion in rats.

BACKGROUND: Flavonoids have been subjected to considerable investigations due to their antioxidant and anti-inflammatory properties. Yet the effects of flavonoids on the ileum and spleen against hepatic ischemia-reperfusion injury have so far not been addressed. AIMS: We aimed to investigate whether micronized purified flavonoid fraction (MPFF) protects the ileum and spleen against hepatic ischemia-reperfusion injury. METHODS: Rats were subjected to hepatic ischemia by clamping the hilar area of the rats for 60 min, followed by 60 min of reperfusion. Rats in the treatment group were treated with MPFF (80 mg/kg/day) by gavage for 3 days before surgery, 30 min prior to ischemia and just before the reperfusion. After the reperfusion period, all rats were sacrificed. Ileal and splenic tissues were taken for histological evaluation and determination of the total antioxidant capacity (TAC), catalase, total oxidant status (TOS), oxidative stress index (OSI) and myeloperoxidase (MPO) levels. RESULTS: TAC levels in the splenic tissue and intestinal tissue were significantly higher in the treatment group than in the control group (P < 0.01 for both). TOS, OSI, and MPO in splenic tissue (P < 0.01, P < 0.05, and P < 0.05, respectively) and intestinal tissue (P < 0.01, P < 0.01, and P < 0.001, respectively) were significantly lower in the treatment group than in the control group. Histological tissue damage of intestinal tissue was milder in the treatment group than in the control group. CONCLUSION: The results of this study indicated that MPFF pretreatment significantly limited the injury to the small intestine and spleen induced by hepatic ischemia-reperfusion in rats.

Protective effects of resveratrol on small intestines against intestinal ischemia-reperfusion injury in rats.

BACKGROUND AND AIM: The aim of this study was to determine whether resveratrol could prevent intestinal tissue injury induced by ischemia-reperfusion (I/R). METHODS: Intestinal I/R was induced in rats' intestines by 60-min occlusion of the superior mesenteric artery, followed by a 60-min reperfusion. Thirty rats were divided into three groups as follows: sham (group 1), control (group 2), and the treatment groups (group 3). The rats in the treatment group received resveratrol both before ischemia and before reperfusion. In all groups, serum aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase levels were determined. Total antioxidant capacity (TAC), catalase, total oxidative status (TOS), oxidative stress index (OSI), and myeloperoxidase (MPO) in the intestinal tissue were measured. Intestinal tissue histopathology was also evaluated by light microscopy. RESULTS: The levels of liver enzymes in group 3 were significantly lower than those in group 2 (P < 0.05). TAC in the intestinal tissue was significantly higher in group 3 than in group 2 (P < 0.05). TOS, OSI, and MPO in the intestinal tissue were significantly lower in group 3 than in group 2 (P < 0.05 for all). Histological tissue damage was milder in the resveratrol treatment group than in the control group. CONCLUSIONS: The results of this study indicated that resveratrol treatment limits the oxidative injury of the small intestine induced by I/R in rats. However, more precise investigations are required to evaluate the antioxidative effect of resveratrol on small intestine tissue damage in clinical and experimental models.

Hyperprogression after immunotherapy: A comprehensive review.

Immune checkpoint inhibitors have revolutionized cancer treatment with patient improved survival, quality of life, and a longer response. However, up to 30% of patients experience paradoxical accelerated tumor progression early after immune-checkpoint blockade therapy. This phenomenon is also known as hyperprogression (HP). Unlike other responses, such as pseudoprogression or natural progression, HP causes worse survival outcomes in patients. Older age, higher metastatic burden, and previous radiation have been independently associated with HP. Even though the exact molecular mechanism underlying HP after immune-checkpoint blockade therapy remains unknown, oncogenic signaling activation including MDM2 amplification or EGFR alterations, the modification of tumor microenvironment by radiotherapy with immune checkpoint inhibitors, and alterations in immune landscape of tumors have been hypothesized as the biological mechanisms behind HP. Patients with HP have been presented with poor prognosis and increased deleterious mutations in cancer genes, along with alterations in the tumor microenvironment. As immune checkpoint inhibitors have been more widely accepted by oncologists, proper assessment of this unique tumor response remains challenging in clinical practice. This work documents the recent findings on epidemiology, biological and clinicopathological factors of HP after immunotherapy.

Cost effectiveness of Gene Expression Profiling in Patients with Early-Stage Breast Cancer in a Middle-Income Country, Turkey: Results of a Prospective Multicenter Study.

OBJECTIVE: Breast cancer is a heterogenous disease, and genetic profiling helps to individualize adjuvant treatment. The Oncotype DX is a validated test to predict benefit of adjuvant systemic treatment. The aims of this study are to determine the costs of chemotherapy in government hospitals in Turkey and evaluate the cost-effectiveness of the Oncotype DX from the national insurance perspective. MATERIALS AND METHODS: A Markov model was developed to make long term projections of distant recurrence, survival, quality adjusted life expectancy, and direct costs for patients with ER+, HER2-, node-negative or up to 3 node-positive early stage breast cancer. Turkish decision impact study patient data were captured for model reference. In that study, ten academic centers across Turkey participated in a prospective trial. Of 165 patients with pT1-3, pN0-N1mic, ER-positive, and HER-2 negative tumors, 57% had low recurrence score (RS), 35% had intermediate RS, and 8% had high RS, respectively. The overall rate of change in chemotherapy treatment decisions following Oncotype DX was 33%. RESULTS: The cost of adjuvant chemotherapy in public hospitals was estimated at $3.649, and Oncotype Dx test was $5.141. Based on the cost-effectiveness analysis, Oncotype DX testing was estimated to improve life expectancy (+0.86 years) and quality-adjusted life expectancy (+0.68 QALYs) versus standard care. The incremental cost-effectiveness ratio (ICERs) of Oncotype DX was estimated to be $7207.9 per QALY gained and $5720.6 per LY gained versus current clinical practice. CONCLUSION: As Oncotype DX was found both cost-effective and life-saving from a national perspective, the test should be introduced to standard care in patients with ER+, HER-2 negative early-stage breast cancer in Turkey.