A multicenter, retrospective archive study of radiological and clinical features of ALK-positive non-small cell lung cancer patients and crizotinib efficacy.

To evaluate radiological and clinical features in metastatic anaplastic lymphoma kinase+ non-small cell lung cancer patients and crizotinib efficacy in different lines. This national, non-interventional, multicenter, retrospective archive screening study evaluated demographic, clinical, and radiological imaging features, and treatment approaches in patients treated between 2013-2017. Totally 367 patients (54.8% males, median age at diagnosis 54 years) were included. Of them, 45.4% were smokers, and 8.7% had a family history of lung cancer. On radiological findings, 55.9% of the tumors were located peripherally, 7.7% of the patients had cavitary lesions, and 42.9% presented with pleural effusion. Pleural effusion was higher in nonsmokers than in smokers (37.3% vs. 25.3%, P = .018). About 47.4% of cases developed distant metastases during treatment, most frequently to the brain (26.2%). Chemotherapy was the first line treatment in 55.0%. Objective response rate was 61.9% (complete response: 7.6%; partial response: 54.2%). The highest complete and partial response rates were observed in patients who received crizotinib as the 2nd line treatment. The median progression-free survival was 14 months (standard error: 1.4, 95% confidence interval: 11.2-16.8 months). Crizotinib treatment lines yielded similar progression-free survival (P = .078). The most frequent treatment-related adverse event was fatigue (14.7%). Adrenal gland metastasis was significantly higher in males and smokers, and pleural involvement and effusion were significantly higher in nonsmokers-a novel finding that has not been reported previously. The radiological and histological characteristics were consistent with the literature data, but several differences in clinical characteristics might be related to population characteristics.

A Hypofractionated Radiotherapy Schedule with a Simultaneous Integrated Boost for Breast Cancer: Outcomes including Late Toxicity and Health Quality.

Introduction: This study aimed to evaluate the long-term adverse effects on the physical appearance and overall well-being of breast cancer patients who receive hypofractionated radiotherapy as whole breast and simultaneous integrated boost (SIB) treatment, utilizing intensive modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), or a hybrid therapy approach. Material/Methods: This investigation involved administering hypofractionated SIB-VMAT therapy to individuals diagnosed with early-stage breast cancer. Treatment was carried out over a three-week period in which a total dose of 48.06 Gy was given to the entire breast and 54 Gy was given to the tumor bed. Data on skin toxicity and cosmetic outcomes were analyzed both during the acute phase and during the three-month and five-year follow-up periods after treatment. Results: A total of 125 patients treated between December 2014 and December 2016 were included in the study. The data of these patients with at least 5 years of follow-up were analyzed. Conclusions: Considering these long-term results, hypofractionated SIB-VMAT can be considered a viable treatment choice, even for patients with unfavorable conditions.

Prognostic and Predictive Role of Angiogenic Markers in Non- Small Cell Lung Cancer

Objective: Despite the existence of detailed consensus guidelines, challenges remain regarding the role angiogenetic factors on non-small cell lung cancer (NSCLC). This study was conducted to determine the role of the vascular endothelial growth factor (VEGF), interleukin-8 (IL-8) and angiopoietin2 (Ang2) in patients with NSCLC. Methods: This study included 64 consecutive patients with non-small cell lung cancer, who admitted to clinic. Pre-treatment serum VEGF, IL-8 and Ang2 levels were evaluated. Patients were treated according to internationally accepted guidelines. Results: VEGF and IL-8 serum levels of patients with both squamous cell carcinoma and adenocarcinoma were significantly higher than controls (p<0.05). In addition, IL-8 levels were lower among treatment-responders than non-responders (p:0.031). Impact of elevated or decreased levels of VEGF, Ang2 and IL-8 on survival was evaluated, accepting median level as reference. There was no correlation between the serum levels of VEGF, Ang2, IL-8 and survival. Conclusion: We found that the levels of angiogenic markers were significantly different between non-small cell lung cancer patients and controls. These markers could elicit more information related to stage and prognosis.

Survival Impact of Optimal Surgical Cytoreduction in Recurrent Epithelial Ovarian Cancer with Brain Metastasis.

AIM: The aim of this study was to determine the clinicopathological characteristics, treatment details and outcome of patients with brain metastasis from epithelial ovarian carcinoma (EOC). METHODS: This study included 21 patients diagnosed with brain metastasis from EOC between 1999 and 2009. RESULTS: Median age was 61 years (range 38-77). The median time elapsed from EOC diagnosis to brain metastasis detection was 32 months. Single brain metastases were found in 10 (48%) cases, and there was extra-cranial disease in 11 (52%) cases. During the mean 86 months of follow-up, 18 of the patients (86%) died of the disease and 3 (14%) were alive with disease. The median survival time after the initial diagnosis of brain metastasis was 9 months. The median overall survival (OS) from initial diagnosis of EOC was 50 months. In univariate analysis, prolonged time from initial diagnosis to central nervous system metastasis (more than 32 months) (p = 0.001), treatment with radiotherapy (p < 0.001), optimal cytoreductive operation (p = 0.02) were all positively correlated with OS. CONCLUSION: The prognosis of patients with brain metastasis from EOC is still poor. The significant predictors of survival in our series were whole brain radiotherapy, prolonged elapsed time from initial diagnosis to brain metastasis and optimal cytoreductive surgery.

Current adjuvant treatment modalities for gastric cancer: From history to the future.

The discrepancy between the surgical technique and the type of adjuvant chemotherapy used in clinical trials and patient outcomes in terms of overall survival rates has led to the generation of different adjuvant treatment protocols in distinct parts of the world. The adjuvant treatment recommendation is generally chemoradiotherapy in the United States, perioperative chemotherapy in the United Kingdom and parts of Europe, and chemotherapy in Asia. These options mainly rely on the United States Intergroup-0116, United Kingdom British Medical Research Council Adjuvant Gastric Infusional Chemotherapy, and the Asian Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer and Capecitabine and Oxaliplatin Adjuvant Study in Stomach Cancer trials. However, the benefits were evident for only certain patients, which were not very homogeneous regarding the type of surgery, chemotherapy regimens, and stage of disease. Whether the dissimilarities in survival are attributable to surgical technique or intrinsic biological differences is a subject of debate. Regardless of the extent of surgery, multimodal therapy may offer modest survival advantage at least for diseases with lymph node involvement. Moreover, in the era of individualized treatment for most of the other cancer types, identification of special subgroups comprising those who will derive more or no benefit from adjuvant therapy merits further investigation. The aim of this review is to reveal the historical evolution and future reflections of adjuvant treatment modalities for resected gastric cancer patients.

Same Chemotherapy Regimen Leads to Different Myelotoxicity in Different Malignancies: A Comparison of Chemotherapy-Associated Myelotoxicity in Patients With Advanced Ovarian and Non-Small-Cell Lung Cancer.

Carboplatin-paclitaxel chemotherapy combination is the standard first-line treatment of advanced ovarian cancer and is the most commonly used treatment combination shown to be effective in advanced non-small-cell lung cancer (NSCLC). The most important dose-limiting side effect is hematologic toxicity. In this study, the severity of treatment-related myelotoxicity is compared in patients with advanced ovarian and lung cancers who received same schedule of carboplatin-paclitaxel. The study was prospectively performed from February 2009 to July 2011 and involved 103 patients with stages Ic-IV ovarian (n = 51) and advanced NSCLC (n = 52) who were administered a maximum of 6 cycles of carboplatin-paclitaxel as a first-line treatment. Full blood counts were measured before treatment, before each chemotherapy cycle during therapy, and at the first and sixth month after therapy. The median ages were 59 years (range, 35-77 years) for patients with NSCLC and 56 years (range, 38-75 years) for patients with ovarian cancer. The frequencies of anemia were 17% and 28.6% before the initiation of chemotherapy, 39.2% and 68.0% at the third cycle of treatment, and 44.2% and 45.2% at the sixth cycle of treatment in patients with NSCLC and ovarian cancer, respectively. Initial leukopenia rates were 3.4% and 0%; at the third cycle 46.0% and 41.2%; and at the sixth cycle 41.9% and 48.8% in patients with NSCLC and ovarian cancer, respectively. At the third cycle, 2.5% of the patients with NSCLC and 10.4% of the patients with ovarian cancer had thrombocytopenia, and at the sixth cycle, 23.3% of the patients with NSCLC and 25% of the patients with ovarian cancer had thrombocytopenia. Hemoglobin, leukocyte, and platelet values at the third cycle were significantly lower than those at admission in both cancer groups. Declines in hemoglobin levels in patients with NSCLC and in platelets in patients with ovarian cancer at the sixth cycle were statistically significant compared with the third cycle. In conclusion, the same schedule of chemotherapy may lead to different myelotoxicities in different types of cancer. These results should be taken into consideration in terms of supportive care and management of toxicity.

Epidermal growth factor receptor in CRC patients in the era of the RAS.

The aim of this study was to investigate EGFR expression patterns and the effect of EGFR expression on stage, prognosis and response to conventional chemotherapy agents other than monoclonal antibodies in CRC patients. This study included 59 metastatic CRC patients. The expression of EGFR was quantified by immunochemistry in biopsy specimens that were obtained before treatment was initiated. The cases were considered to be positive for EGFR if >1% of the tumor cells had complete circumferential membranous staining. The median age of the patients was 54.6 years, and 59% of the patients were male. Twenty-six patients presented with stage IV disease, and the remaining patients developed distant metastasis during follow-up. Fifty-one patients were treated with regimens containing irinotecan. The numbers of patients with EGFR expression in the primary tumors, the metastatic lymph nodes and the normal colonic tissue were 34 (65.4%), 10 (76.9%) and 34 (65.4%) respectively. The initial disease stage and lymph node stage were correlated with EGFR expression (p<0.05). Additionally, EGFR positivity was correlated with a statistically significant reduction in the response rate to chemotherapy, the overall survival (21 vs. 28 months) and the progression-free survival (15 vs. 22 months) in metastatic patiens treated with chemotherapy other than targeted therapies. In conclusion, EGFR expression in correlated with stage in all CRC patients and response to chemotherapy and survival in metastatic CRC patients.

Favorable survival time provided with radioembolization in hepatocellular carcinoma patients with and without portal vein thrombosis.

PURPOSE: Although some algorithms are defined for the treatment of advanced hepatocellular carcinoma (HCC), the expected survival cannot be prolonged as it is intended. Treatment options for this group of patients are limited. Radioembolization with yttrium-90 (Y-90) microspheres is a new treatment modality, which has also been used in advanced HCC patients. In this study, the authors aimed to assess the efficiency of radioembolization with Y-90 microspheres and evaluate prognostic factors that influence the survival in HCC patients. PATIENTS AND METHODS: The authors retrospectively evaluated data of 29 HCC patients who had radioembolization with Y-90 resin or glass microspheres between May 2009 and January 2014. Patient survival was evaluated by using the Kaplan-Meier method. Subgroup comparisons in terms of age, sex, prior treatment status before radioembolization, tumor burden, time between HCC diagnosis and radioembolization, alpha fetoprotein (AFP) level before radioembolization, presence of portal vein thrombosis (PVT), hepatopulmonary shunt ratio, extrahepatic disease burden, multifocality, bilaterality, Eastern Cooperative Oncology Group (ECOG), Child-Pugh, and Barcelona Clinic Liver Cancer (BCLC) status were performed to evaluate prognostic factors that affected survival. RESULTS: There were 29 HCC patients (mean age: 59.9±12 years) in the patient group. Grade ≤1 and 2 ECOG performance status was present in 19 and 10 patients, respectively. Twenty-six patients were classified as Child A and 3 patients as Child B. According to the BCLC staging system, 18 patients were in stage B and 11 patients were in stage C. PVT was diagnosed in 12 patients. The median follow-up was 15 months. The median overall survival was 17±2.5 months. BCLC disease stage was a significant prognostic variable associated with survival, but other parameters, even the presence of PVT, were found to be not significantly affecting survival. CONCLUSION: Radioembolization provides favorable survival time in advanced HCC patients. Even patients who are not eligible for transarterial chemoembolization due to PVT can have radioembolization without a decrease in the median survival time.

D-dimer and international normalized ratio (INR) are correlated with tumor markers and disease stage in colorectal cancer patients.

BACKGROUND: The aim of this study is to evaluate the correlation of coagulation tests with various clinicopathological variables and tumor markers among colorectal cancer (CRC) patients. MATERIALS AND METHODS: Ninety-four CRC patients were included for evaluation of clinicopathological factors, coagulation assays and tumor marker levels. RESULTS: Metastatic disease was related with elevated INR (p= 0.03). Stage III patients had higher D-dimer values compared with stage II patients (p= 0.03). Correlation of tumor markers indicated a tendency towards elevated D-dimer levels for CEA values higher than median (p= 0.01). High CA 19-9 levels were also associated with higher INR (p= 0.007). Elderly age, distant metastasis, high CEA, CA-19-9 and LDH levels were associated with poorer overall-survival. CEA level was the only independent prognostic factor in multivariate analysis. CONCLUSIONS: Coagulation assays can be utilized as predictors of disease extent in CRC. Elevated D-dimer and INR values may indicate higher disease stage. Correlation of D-dimer levels with CEA supports their value for assessing tumor burden.

Abundant circulating microRNAs in breast cancer patients fluctuate considerably during neoadjuvant chemotherapy.

Previous studies have revealed the aberrant expression of a number of microRNAs (miRNA/miRs) in the blood circulation of patients with breast cancer (BC). The aim of the present study was to assess the effect of neoadjuvant chemotherapy on the levels of a panel of BC-associated miRNAs, which are at relatively low (let-7, miR-10b, miR-34, miR-155, miR-200c and miR-205) or abundant (miR-21, miR-195 and miR-221) levels in the circulation. Patients with primary operable or locally advanced BC were enrolled in the study. The plasma levels of the miRNAs at baseline and at the fourth cycle of treatment were compared. Patients with stage II disease exhibited higher basal miRNAs levels than those with higher stages. The difference was most evident for miR-155 and miR-21 (P=0.05). From the initial to the fourth cycle of chemotherapy, the miRNA levels changed substantially. In samples in which the miRNA levels generally declined, a marked decrease (≤15,500-fold) was evident for the abundant miRNAs. Notably, the occurrence of a decrease in miRNA levels was more frequent in patients with smaller tumor sizes (P<0.05 for miR-21 and miR-195). This proof-of-concept study provides evidence that highly expressed miRNAs are affected most frequently by chemotherapy, particularly in patients with early stage tumors. This information may be valuable in assessing the response of the patients to therapy.

The behavior of Turkish cancer patients in fasting during the holy month of Ramadan.

OBJECTIVE: Fasting during the holy month of Ramadan is one of the major obligations for all adult Muslims. We performed a survey of Turkish Muslim cancer patients to examine the extent of their fasting status and to compare various clinical characteristics of fasting and non-fasting cancer patients during the month of Ramadan. METHODS: This study was conducted on 701 adult cancer patients who attended ambulatory patient care units answered the questionnaires. RESULTS: The population comprised 445 women (63.5%), and the median age was 54 years. Before diagnosis of cancer, 93.1% of the patients used fast consists of completely (78.3%) and partial (14.8%). However, 15% of cases were fasting on the day of interview, either partially (7.4%) or completely (7.6%) with equal distributions. Patients who were females, those with good performance status, those without any comorbid disease, who had non-metastatic disease, those with history of surgery, those treated with radiotherapy and those being treated with oral chemotherapeutic agents were more likely to be fasting than others. The fasting ones had more prevalent among patients with lymphoma, urogenital cancer and breast cancer; conversely, the rate of fasting status among patients with lung and gastrointestinal cancer was quite low. Only 20.8% of all patients asked their physician whether it was alright for them to fast and physicians generally had a negative attitude towards fasting (83.2%). CONCLUSIONS: Majority of cancer patients are not fasting during the month of Ramadan, and a small part of patients consult this situation to their physician.

High serum transforming growth factor beta 1 (TGFB1) level predicts better survival in breast cancer.

The transforming growth factor beta 1 (TGFB1) is a regulatory cytokine with both tumor suppressor and tumor-promoting effects in breast cancer (BC) cell lines and tissue. Data about level of circulating TGFB1 and its prognostic significance in BC patients is conflicting. The objective of this study is to determine the clinical significance of the serum TGFB1 levels in BC patients. We enrolled 96 female patients with histopathologically diagnosed BC who did not receive chemotherapy (CT) or radiotherapy. Serum TGFB1 levels were measured by ELISA method and compared with 30 healthy controls. The mean serum TGFB1 level of BC patients was significantly higher than controls (0.08 vs. 0.04 ng/ml, p < 0.001). There was no significant difference according to known disease-related clinicopathological or laboratory parameters. Serum TGFB1 level had a significant impact on overall survival in both univariate (p = 0.01) and multivariate analysis (p = 0.013). Serum TGFB1 level is elevated in BC patients and has a favorable prognostic value. However, it has no predictive role on CT response.

Biweekly triplet chemotherapy with gemcitabine, cisplatin and vinorelbine for advanced chemotherapy naïve non-small cell lung cancer.

AIMS AND BACKGROUND: To investigate the efficacy and tolerability of biweekly scheduled triplet chemotherapy consisting of gemcitabine, cisplatin and vinorelbine for chemotherapy-naïve advanced non-small cell lung cancer. METHODS AND STUDY DESIGN: Patients with stage IIIB/IV non-small cell lung cancer and performance status of 0-2 were eligible. Patients who had brain metastasis and of an older age were also enrolled in the study. The triplet combination chemotherapy consisted of gemcitabine, cisplatin and vinorelbine at the doses of 1000 mg/m(2), 25 mg/m(2) and 50 mg/m(2), respectively, were administered on day 1 and 14, every 28 days, up to 6 cycles. RESULTS: Thirty patients were enrolled in the study. Median age was 60 years (range, 42-74). Most of the patients (83%) had metastatic disease and 7 patients (23%) had brain metastasis. In assessing 24 patients for response evaluation, none had complete response. Partial responses were achieved in 18 (60%) patients. Four patients (13%) had stable disease and 2 (7%) progressed. Thirteen percent and 20% of the patients developed severe (grade 3-4) neutropenia and anemia, respectively. Febrile neutropenia, severe thrombocytopenia, hepatic and renal toxicity were not seen. Overall and progression-free survival were 8.15 and 7.15 months, respectively. Patients who had no brain metastasis ( P = 0.069), who had more than 3 courses of chemotherapy (P <0.001), and who had chemotherapy applied without dose reduction (P = 0.018) had better survivals. CONCLUSIONS: The biweekly schedule of the triplet chemotherapy combination including gemcitabine, cisplatin and vinorelbine was effective in advanced, mostly metastatic non-small cell lung cancer with acceptable and manageable side effects.

Effect of increased body mass index (BMI) on time to tumour progression (TTP) in unresectable metastatic colorectal cancer (mCRC) patients treated with bevacizumab-based therapy.

High BMI is a well-known risk factor for the development and recurrence of several solid tumours, including CRC. Obesity is associated with increased levels of vascular endothelial growth factor (VEGF). Bevacizumab is the main targeted therapy for inhibiting tumour angiogenesis by blocking the VEGF/VEGF receptor pathway. Elevated VEGF in obese patients might provoke resistance to anti-VEGF therapy. We evaluated the efficacy of bevacizumab on TTP among mCRC patients through stratifying them according to their BMI. Patients with mCRC who had been treated with fluoropyrimidine-based combination chemotherapy with bevacizumab were included in the study. Patients were assigned according to their BMI before initiation of therapy (group A: BMI < 25 kg/m(2), group B: BMI ≥ 25 kg/m(2)). Multivariate analysis was performed to evaluate the risk of tumour progression. Between April 2007 and June 2011, 80 patients were treated with chemotherapy and bevacizumab as first-line therapy (n = 37 for group A, n = 43 for group B). Tumours in 56.3 % of the patients in group A (n = 21) and 76.3 % of the patients in group B (n = 33) progressed during a median 10-months (3-57 months) follow-up. The median TTP was 11.7 months in the group A and 6 months in the group B (p = 0.004). In a multivariate analysis, high BMI (≥25 kg/m(2)) was associated with significantly shorter TTP (p = 0.01; HR: 4.37). High BMI among mCRC patients treated with bevacizumab is associated with shorter TTP. Further study in larger databases is warranted for confirming the negative prognostic effect of obesity during treatment with anti-VEGF agents.

Comparison of two different adjuvant treatment modalities for pN3 gastric cancer patients after D2 lymph node dissection: can we avoid radiotherapy in a subgroup of patients?

Adjuvant chemoradiotherapy (CRT) is the standard of care for gastric cancer patients in the USA. However, in countries where D2 lymph node dissection is performed, the effect of radiotherapy on locoregional recurrence is controversial. The aim of this study is to compare the outcomes in pN3 gastric cancer patients following two adjuvant treatment modalities: chemotherapy (CT) and CRT after D2 lymph node dissection. Between 2005 and 2009, 71 gastric cancer patients who underwent D2 lymph node dissection and had pTanyN3M0 stage (according to AJCC 6th edition) were identified. Fifty-three patients were treated with CT and 18 patients received CRT. CRT consisted of bolus fluorouracil (FU) 425 mg/m(2) and leucovorin 20 mg/m(2) before, after, and during radiotherapy. For the CT arm, treatment protocols consisted of combination therapies involving FU and cisplatin as the backbone. Median overall survival (OS) and disease-free survival (DFS) rates for all patients were 26.3 months (15-37.7 months) and 12.5 months (8-17.1 months). Median OS in CT arm was 26.8 months and it was 34.2 months for CRT arm (p = 0.74). DFS rates did not differ statistically either (p = 0.56, 12.5 and 15.2 months for CT and CRT, respectively). Locoregional recurrence rates were also similar (p = 0.63). Only metastatic/dissected lymph node ratio (≥0.75) was identified as a prognostic factor in both univariate and multivariate analyses for DFS. Comparison of CT versus CRT for N3 stage gastric cancer patients with D2 lymph node dissection did not reveal any statistically significant difference in survival rates and locoregional recurrence.

Mucosal melanoma in the head and neck region: different clinical features and same outcome to cutaneous melanoma.

Mucosal melanoma (MM) in the head and neck (H&N) is relatively rare and behaves in distinct pattern from cutaneous melanoma (CM). We performed this study to define clinical characteristics and outcomes of patients and emphasize MM differences from CM. Forty-one patients with MM located in H&N were assessed. 94 CM patients originated from H&N region were also used for comparison. Patients had oral cavity (51%) and sinonasal location (49%).The median age was 60 years and gender distribution was equal. Thirty-two (78%) patients had localized stage, four (10%) patients had regional lymph node metastasis, and five (12%) patients had distant metastasis. The 1- and 5-year overall survival rates were 81% and 58%, respectively. Outcomes were similar between sinonasal and oral cavity patients (P = 0.67). Advanced disease was the significant prognostic factor for outcome (P = 0.03). MM patients are older (P = 0.008) and more diagnosed as a localized disease patients at presentation than those with CM (P = 0.06). Overall survival rates were identical in patients with MM and CM (P = 0.53). In conclusion, despite different clinical features, outcome was identical in patients with MM and CM located in the H&N region.

Triplet chemotherapy combination with cisplatin, gemcitabine and docetaxel in patients with chemotherapy-naive advanced non-small cell lung cancer.

The synergistic effects of new generation chemotherapeutics when combined with cisplatin have encouraged the development of new triplet combination regimens in the treatment of advanced non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the feasibility of triplet chemotherapy using weekly cisplatin-gemcitabine-docetaxel (CGD) for patients with chemotherapy-naive NSCLC. Twenty-seven patients with stage IIIB/IV disease and performance status of 0 to 2 were included in this prospective trial. A combination of gemcitabine 750 mg/m2, cisplatin 25 mg/m2 and docetaxel 25 mg/m2 was administered on days 1, 8 and 15, with cycles repeated every 3 weeks. Leucopenia and/or neutropenia and to a lesser extent thrombocytopenia were the main dose-limiting toxicities. Grade III-IV neutropenia and thrombocytopenia occurred in 26 and 7% of the patients, respectively. Only one patient developed febrile neutropenia. Dose reductions were required in 26% of patients, delays in 44% of patients and early treatment discontinuation in 15% of patients. The overall response rate was 52% and all of them experienced a partial response. The median progression-free (PFS) and overall survival (OS) times were 6 and 13 months, respectively. The one-year survival rate was 46%. In conclusion, weekly administration of CGD is an active first-line therapy with acceptable toxicity in advanced NSCLC patients.

A high serum level of M65 is associated with tumour aggressiveness and an unfavourable prognosis for epithelial ovarian cancer.

PURPOSE: This study was conducted to determine the clinical significance of serum M30 and M65 in epithelial ovarian cancer (EOC). METHODS: A total of 56 patients with EOC and 56 healthy women were included in the study. All of the patients received platinum-based chemotherapy. Pretreatment levels of M30 and M65 were measured using the quantitative ELISA method. RESULTS: The median M30 and M65 serum levels were significantly elevated in the EOC patients compared with the healthy controls (96.7 vs. 69.5, p = 0.028 and 436.4 versus 166.3, p < 0.001, respectively). The cut-off value of 423.4 U/L for M65 determined with ROC analysis, predicted progression with 75.1 % sensitivity and 65.6 % specificity (AUC = 0.708, p = 0.008). Patients with higher M65 levels had shorter progression-free survival (PFS) (p = 0.021). Both M30 and M65 serum levels were significantly higher for serous-type histology (p = 0.001 and p < 0.001, respectively). Increased M65 serum levels were associated with advanced disease (p = 0.005) and higher grade (p = 0.005). Moreover, M65 levels were higher for chemotherapy-resistant patients (p = 0.04). Multivariate analysis revealed that an elevated serum M65 level was the only significant independent prognostic factor (p = 0.039, HR 3.792). CONCLUSIONS: These results indicated that serum M30 and M65 levels were significantly elevated in patients with EOC compared with healthy women. Particularly, high serum M65 levels were associated with poor prognosis and resistance to platinum-based chemotherapy.

Serum M65 as a biomarker for metastatic renal cell carcinoma.

INTRODUCTION/BACKGROUND: Effective cancer biomarkers for early detection, prognosis, or therapy response prediction are urgently need in metastatic RCC. M30 and M65 are released during apoptotic cell death and precisely reflect epithelial tumor cell death. The aim of this study was to determine the prognostic value of plasma M30 and M65 levels in predicting survival rates for patients with metastatic RCC. PATIENTS AND METHODS: Thirty-nine patients with metastatic RCC and 39 healthy control subjects were included in this study. Serum M30 and M65 levels were measured by ELISA. RESULTS: The median ages of the patients and control subjects were 60 and 58 years, respectively. No difference was detected in the median serum M30 level between the patients and control subjects (53.7 vs. 49.1 U/L; P = .31). The median serum M65 level was significantly higher in patients than in control subjects (334.0 vs. 179.1 U/L; P < .001). Receiver operating characteristic analysis revealed that the best cutoff value for serum M65 level for predicting progression-free survival (PFS) was 313.6 U/L. The median PFS of patients whose M65 levels were ≤ 313.6 U/L was better than that of patients whose M65 levels were > 313.6 U/L (P = .03). CONCLUSION: To the best of our knowledge, this is the first study to evaluate serum M30 and M65 levels in patients with RCC. Serum M65 levels were significantly elevated in patients with metastatic RCC compared with healthy individuals. In addition, the serum M65 level could be predictive of PFS in patients with RCC.