Efficacy of ipilimumab 3 mg/kg following progression on low-dose ipilimumab in metastatic melanoma.

BACKGROUND: Differing doses of ipilimumab (IPI) are used in combination with an anti-PD1 antibody in advanced melanoma. There is no data on the outcomes of patients who progress following low-dose IPI (< 3 mg/kg) and are subsequently treated with IPI 3 mg/kg (IPI3). We conducted a multicentre retrospective survey to assess the efficacy of this strategy. METHODS: Patients with resected stage III, unresectable stage III or IV melanoma who received low dose IPI (< 3 mg/kg) with an anti-PD1 antibody with recurrence (neo/adjuvant) or progressive disease (metastatic), who then received IPI3± anti-PD1 antibody were eligible. Best investigator-determined Response Evaluation Criteria in Solid Tumours response, progression-free survival (PFS) and overall survival (OS) were analysed. RESULTS: Total 36 patients received low-dose IPI with an anti-PD1 antibody, 18 (50%) in the neo/adjuvant and 18 (50%) in the metastatic setting. Of which, 20 (56%) had primary resistance and 16 (44%) had acquired resistance. All patients received IPI3 for unresectable stage III or IV melanoma; median age 60 (29-78), 18 (50%) M1d disease, 32 (89%) Eastern Cooperative Oncology Group performance status 0-1. Around 35 (97%) received IPI3 with nivolumab and 1 received IPI3 alone. The response rate to IPI3 was 9/36 (25%). In patients with primary resistance, the response rate was 6/20 (30%). After a median follow-up of 22 months (95% CI: 15-27 months), the median PFS and OS were not reached in patients who responded; 1-year PFS and OS were 73% and 100%, respectively. CONCLUSIONS: IPI3 following recurrence/progression on low dose IPI has clinical activity, including in primary resistance. IPI dosing is therefore critical in a subset of patients.

Merkel cell carcinoma in Turkey: A multicentric study.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare but highly aggressive neuroendocrine carcinoma of the skin. In this study, we aimed to evaluate the clinicopathologic characteristics, treatment outcomes, and survival of MCC cases in Turkey. MATERIALS AND METHODS: The patients diagnosed with MCC between 1999 and 2018 at twenty different centers in Turkey were included in the study. Patient and tumor characteristics and adjuvant and metastatis treatment outcomes were analyzed retrospectively. RESULTS: The median age of totally 89 patients was 70 (26-93). The most common primary location was lower limbs (n = 29, 32.5%). Immunohistochemically, CK20 positivity was present in 59 patients (66.3%). Only two patients had secondary malignancy. The majority of the patients (n = 76, 85.4%) were diagnosed at the localized stage. Surgery was performed for all patients in the early stage, and adjuvant radiotherapy or/and chemotherapy was applied to 52.6% (n = 40) of nonmetastatic patients. The median follow-up was 29 months. Recurrence developed in 21 (27.6%) of the 76 patients who presented with local or regional disease. Two-year disease-free survival (DFS) was 68.1% and 5-year DFS was 62.0% for localized stage. The 5-year DFS was similar for patients receiving adjuvant treatment (chemotherapy, radiotherapy, or sequential chemoradiotherapy) and without adjuvant therapy (P > 0.05). Two-year overall survival in patients who presented with localized disease was 71.3% and 18.5% in metastatic patients (P < 0.001). In the metastatic stage, platinum/etoposide combination was the most preferred combination regimen. Median progression-free survival (PFS) in first-line chemotherapy was 7 months (95% confidence interval: 3.5-10.5 months; standart error: 1.78). CONCLUSIONS: Although MCC is rare in Turkey, the incidence is increasing. Gender, CK20 status, tumor size, lymph node involvement, and adjuvant treatment were not associated with recurrence.

Retrospective evaluation of patients diagnosed solid pseudopapillary neoplasms of the pancreas.

PURPOSE: Solid pseudopapillary neoplasm (SPN) is a rare, low-grade neoplasm with excellent prognosis. In this study, we evaluated clinicopathological characteristics of patients diagnosed with SPN retrospectively. METHODS: This is a retrospective study intended to characterize patients with the diagnosis of SPN between 2005 and 2015. Clinicopathological features, recurrence rate, and overall survival of 28 patients were recorded. Malignant SPN criteria were defined as the presence of distant metastasis (developed at diagnosis or during follow up) or lymph node involvement. RESULTS: The mean age at diagnosis was 42 (range: 17-41). Among patients, 82% (n = 23) were female and 17.9% (n = 5) were male. The mean size of tumor was 5.81 cm (range: 2-15). The mean follow up period was 55.6 months, 1-year survival was 96.5% and 5-year survival rate was 88%. A total of 25 patients were alive at the end of follow-up period and 3 of the patients became exitus due to disease. Two patients had a metastatic presentation in livers at the diagnosis and metastasis developed in 3 patients during follow-up (liver of 1 patient, peritoneum in 1 patient and liver and peritoneum in 1 patient). The reason of admission was headache in 68% patients. The type of operation was frequently subtotal pancreatectomy (n = 11, 39.3%) and distal pancreatectomy (n = 10, 35.7%). Tumors were located frequently in body and tail regions (n = 18, 64.3%) and the number of patients with malignant criteria was 6 (21.4%). Although the mean age of malignant patients was significantly higher than benign patients (P = 0.046), there was no significant difference between 2 groups in terms of gender, tumor size, capsule invasion, perineural invasion, vascular invasion, and margin status. CONCLUSION: SPN is a rarely seen tumor with low malignity potential. Surgical resection provides long-term survival rate even in local invasion or metastasis conditions.

The clinical importance of serum galectin-3 levels in breast cancer patients with and without metastasis.

OBJECTIVE: Studies have investigated expression status of galectin-3 (Gal-3), but very little is known about the importance of circulating Gal-3 in patients with breast cancer (BC). The purpose of the study was to investigate the clinical significance and potential diagnostic value of plasma Gal-3 levels in patients with BC. MATERIALS AND METHODS: Fifty-two patients with BC and 35 age-matched healthy controls were enrolled. Levels of Gal-3 were investigated in BC patients and healthy controls. Gal-3 levels were determined using ELISA method. RESULTS: Serum Gal-3 levels were significantly higher in BC patients than in controls (P = 0.002). Gal-3 levels did not significantly differ according to patients' statuses of lymph node involvement, hormone receptor, lymphovascular invasion, e-cadherin, menopausal, stage, serum hemostatic markers (prothrombin time, partial thromboplastin time, and international normalized ratio), platelet counts, mean platelet volume, lactate dehydrogenase, carcinoembryonic antigen, and carbohydrate antigen 15-3 values (P > 0.05 for all). A cut-off value of Gal-3 to predict BC was determined at ≥3.17 ng/ml with a sensitivity of 75.0%, a specificity of 65.71%, a positive and negative predictive values of 76.5 and 63.9%, respectively (area under the curve: 0.705 [95% confidence interval, 0.598-0.798], P = 0.0002). CONCLUSION: Serum Gal-3 levels were significantly higher in BC patients and did not significantly differ according to clinical and tumoral characteristics of patients. Furthermore, there was no difference in Gal-3 levels between BC patients with and without metastatic disease. Serum Gal-3 levels can be used as an adjunct to other diagnostic or screening tests for BC regardless of clinical and tumoral characteristics of patients.

The value of serum survivin level in early diagnosis of cancer.

OBJECTIVE: Survivin is one of the apoptosis inhibitor proteins, and it plays a key role in tumor angiogenesis and cancer progression. This study was conducted to investigate the serum level of survivin to determine its diagnostic value in cancer patients. MATERIALS AND METHODS: Blood samples were taken from cancer patients (n = 67) prior to surgery or chemo/radiotherapy and age-matched healthy volunteers (n = 23). The serum levels of survivin were analyzed by enzyme-linked immunosorbent assays. The difference in serum levels between patients and control was evaluated by using statistical methods. Correlation between the serum levels of survivin and clinicopathological features of cancer patients were also evaluated. RESULTS: The diagnoses of patients were breast cancer (49.3%), colon cancer (25.4%), ovarian cancer (14.9%), and other cancers (10.4%). Serum survivin levels were significantly higher in cancer patients than healthy subjects (196.23 pg/ml vs. 117.73 pg/ml, respectively, P = 0.019). No significant relations were found between serum survivin level and demographic characteristics of cancer. The optimal cut-off value of serum survivin was determined at >120.8 pg/ml, and its serum levels above this cut-off value were associated with 4.198 times increased risk of cancer. CONCLUSION: Our study results may suggest that high serum survivin levels can show 4 times increased risk of cancer in a subject with a high suspicion of cancer. Furthermore, survivin level was not influenced with demographic characteristics of breast, gastric, colorectal, prostate, ovarian cancer, and glioblastome multiforme.

Prognostic factors of patients who received chemotherapy after cranial irradiation for non-small cell lung cancer with brain metastases: A retrospective analysis of multicenter study (Anatolian Society of Medical Oncology).

PURPOSE: Almost half of all patients diagnosed with non-small cell lung cancer (NSCLC) have distant metastases at presentation. One-third of patients with NSCLC will have brain metastases. Without effective treatment, the median survival is only 1 month. However, it is difficult to treat brain metastases with systemic chemotherapy since the agents have difficulty crossing the blood-brain barrier. Therefore, it is important to estimate the patient's survival prognosis. The aim of this study was to analyze prognostic factors for survival in Turkish patients who received chemotherapy after cranial irradiation for NSCLC with brain metastases. METHODS: We retrospectively reviewed 698 patients with brain metastases resulting from NSCLC. Ten potential prognostic variables were chosen for analysis. Univariate and multivariate analyses were conducted to identify prognostic factors associated with overall survival (OS). RESULTS: Among the 10 variables for univariate analysis, six were identified to have prognostic significance; these included sex, smoking history, histology, number of brain metastases, extracranial metastases, and neurosurgical resection. Multivariate analysis by the Cox proportional hazard model showed that a smoking history, extracranial metastases, and neurosurgical resection were independent negative prognostic factors for OS. CONCLUSION: Smoking history, extracranial metastases, and neurosurgical resection were considered independent negative prognostic factors for OS. These findings may facilitate pretreatment prediction of survival and can be used for selecting patients for more appropriate treatment options.

The clinical importance of serum urokinase plasminogen activator receptor and carbonic anhydrase IX levels and the effect of anthracycline-based adjuvant chemotherapy on these biomarkers in breast cancer.

INTRODUCTION: Breast cancer mortality rates after metastasis is high. Urokinase plasminogen activator receptor (uPAR) and carbonic anhydrase IX (CAIX) play very important roles during tumor cell invasion and metastasis. The purpose of this study was to evaluate plasma levels of uPAR and CAIX and the effect of anthracycline-based chemotherapy on these biomarkers in patients with operable breast cancer. MATERIALS AND METHODS: Sixty-five patients and 25 age-matched healthy controls were enrolled. Levels of uPAR and CAIX were investigated before and after adjuvant chemotherapy. Basal (prechemotherapy) uPAR and CAIX levels in patients were compared with those in healthy controls and in patients after 3 cycles of chemotherapy. Levels of uPAR and CAIX were determined using the ELISA method. RESULTS: uPAR and CAIX levels were significantly higher in patients (P: 0.02 and P: 0.03, respectively). Postchemotherapy uPAR and CAIX levels were higher than basal levels (P: 0.645 and P < 0.001, respectively). A cut-off value of 27.99 pg/mL for uPAR was associated with 45.31% sensitivity and 84.62% specificity, and with a positive predictive value (PPV) of 87.9% and a negative predictive value (NPV) of 38.6%. A cut-off value of 777.84 pg/mL for CAIX was associated with 90.62% sensitivity and 30.77% specificity, and with a PPV of 76.3% and an NPV of 57.1%. CONCLUSION: We determined that uPAR and CAIX levels were higher in the fluorouracil, epirubicin, and cyclophosphamide (FEC) chemotherapy group than in the control group, but there was no difference between the FEC and epirubicin/adriamycin chemotherapy groups in terms of basal and postchemotherapy uPAR, CAIX levels. Furthermore, uPAR is more specific, and CAIX is more sensitive in the diagnosis of breast cancer.

Retrospective multicenter evaluation of patients diagnosed with mucosal melanoma: a study of Anatolian Society of Medical Oncology.

Mucosal melanoma (MM) is a rare type of cancer that differs significantly from cutaneous melanoma. In this study, we aimed to evaluate clinical and demographical characteristics, prognoses and factors influencing survival, treatment alternatives, and features of different subtypes of the patients. The patients were followed up with and treated in different centers due to their diagnoses of MM. We retrospectively analyzed data of 107 patients who were diagnosed with MM in 14 different institutions in Turkey. The mean age of the patients was 64.5 years. Of the patients, 47 % were female and 53 % were male. The median overall survival (OS) was 17 months, and the mean follow-up duration was 27 months. The 2-year survival rate was 42 %, and the 5-year survival rate was 23 %. The best survival rate appeared in those patients with MM in the head-neck region (median survival rate was 27 months, P = 0.034). The most common anatomical site was the head-neck region. In a univariate analysis, variables including age ≥65 years, the anatomical site of the primary lesion other than head and neck region, the metastatic stage of the disease, high levels of lactate dehydrogenase (LDH), and an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of ≥1 were found to be associated with poor survival (P < 0.05). However, in a multivariate analysis, only advanced stage disease (HR = 2.70; 95 % CI, 1.64-4.45; P = 0.000) and high LDH levels (HR = 2.31; 95 % CI, 1.40-3.80; P = 0.001) were determined to be adverse prognostic variables. Primary MM presents a more aggressive behavior and offers a poorer prognosis compared to cutaneous melanoma. Because the disease is rarely seen, is heterogeneous, and lacks randomized studies, issues concerning optimal treatment approaches and management and clinical characteristics of the disease have not been clarified yet.

Elevated Serum Levels of SCUBE1, a Marker for Coagulation, in Patients with Breast Cancer.

Breast cancer (BC) is the most common cancer among women and a major cause of death. Signal Peptide-Cub-Epidermal growth factor domain-containing protein-1 (SCUBE1) is secreted under hypoxia and inflammatory conditions from platelet alpha granules. Its biological function is uncertain, although it may be a procoagulant substance in cancer patients. SCUBE1 is useful for identifying thrombotic diseases, including cancers and acute coronary syndromes. D-dimer reflects the relationship between coagulation activation and fibrinolysis; namely, thrombosis and D-dimer levels are closely linked. This is the first investigation of the potential diagnostic and prognostic value of SCUBE1 levels in patients with BC. Fifty patients and 33 age-matched and body mass index-matched healthy controls were enrolled. Blood samples were collected before chemotherapy regimens commenced. Serum SCUBE1 and D-dimer levels were measured before adjuvant chemotherapy and were compared to the healthy controls. SCUBE1 levels were determined using an enzyme-linked immunosorbent assay (ELISA) method. SCUBE1 and D-dimer levels were significantly higher in patients than in the controls (p = 0.03 and p < 0.001, respectively). A cut-off value of 1.55 ng/mL for SCUBE1 was associated with 62% sensitivity and 72.7% specificity and with positive predictive value of 77.5% and negative predictive value of 55.8%. Two patients with high SCUBE1 and D-dimer levels also developed pulmonary embolism. SCUBE1 may indicate hypercoagulability in patients with BC and thus help identify patients at greater risk of thrombosis and requiring anti-thrombosis treatment. SCUBE1 may also be used as an assistant test for identifying patients at risk of BC.

Impact of adjuvant treatment modalities on survival outcomes in curatively resected pancreatic and periampullary adenocarcinoma.

BACKGROUND: We examined the impact of adjuvant modalities on resected pancreatic and periampullary adenocarcinoma (PAC). METHODS: A total of 563 patients who were curatively resected for PAC were retrospectively analyzed between 2003 and 2013. RESULTS: Of 563 patients, 472 received adjuvant chemotherapy (CT) alone, chemoradiotherapy (CRT) alone, and chemoradiotherapy plus chemotherapy (CRT-CT) were analyzed. Of the 472 patients, 231 were given CRT-CT, 26 were given CRT, and 215 were given CT. The median recurrence-free survival (RFS) and overall survival (OS) were 12 and 19 months, respectively. When CT and CRT-CT groups were compared, there was no significant difference with respect to both RFS and OS, and also there was no difference in RFS and OS among CRT-CT, CT and CRT groups. To further investigate the impact of radiation on subgroups, patients were stratified according to lymph node status and resection margins. In node-positive patients, both RFS and OS were significantly longer in CRT-CT than CT. In contrast, there was no significant difference between groups when patients with node-negative disease or patients with or without positive surgical margins were considered. CONCLUSIONS: Addition of radiation to CT has a survival benefit in patients with node-positive disease following pancreatic resection.

The effect of adjuvant chemotherapy on plasma TAT and F 1+2 levels in patients with breast cancer.

INTRODUCTION: Increased thromboembolic disorders and chemotherapy-induced thromboembolic events are well known phenomena in patients with breast cancer. Antithrombin III (AT III) inactivates thrombin, resulting in increased thrombin-antithrombin (TAT) levels. Activated factor X cleaves prothrombin and thrombin, resulting in increased levels of prothrombin fragment 1+2 (F 1+2). Increased TAT and F 1+2 levels show coagulation activation. The aim of this study was to examine plasma levels of TAT and F 1+2 and the effect of anthracycline-based chemotherapy on plasma TAT and F 1+2 in patients with operable breast cancer. MATERIALS AND METHODS: Seventy patients and 30 age-matched healthy controls were enrolled. Levels of TAT and F 1+2 were investigated before and after adjuvant chemotherapy. Basal levels (pre-chemotherapy) of TAT and F 1+2 in patients were compared with those in healthy controls and patient levels after 3 cycles of chemotherapy. Levels of TAT and F 1+2 were determined using the ELISA method. RESULTS: TAT and d-dimer levels were significantly higher in patients, (P: 0.02 and P<0.001, respectively). Post-chemotherapy F 1+2 levels were higher than basal levels (P: 0.02). F 1+2 levels were higher in patients, although the difference was not statistically significant (P: 0.52). There was no difference between basal and post-chemotherapy TAT levels. DISCUSSION: In conclusion, while higher post-chemotherapy F 1+2 levels suggest that the cumulative effect of chemotherapy increases the risk of thrombosis, TAT and d-dimer levels indicate that the effect of the cancer further increases the risk of thrombosis in patients with operable breast cancer.

Adjuvant radiotherapy in stage 1 seminoma: Evaluation of prognostic factors and results of survival.

PURPOSE: The purpose of this study was to evaluate the prognostic factors affecting overall survival (OS), cause-specific survival (CSS), progression-free survival (PFS), and survival among patients undergoing adjuvant radiotherapy (RT) for stage-1 seminoma. MATERIALS AND METHODS: Between August 1997 and May 2013, 68 patients diagnosed with stage-1 seminoma were retrospectively evaluated. The median age was 39 (24-74) years. All patients received adjuvant RT after inguinal orchiectomy. Fifty-eight (85.3%) patients received paraaortic RT; 10 (14.7%) received dog-leg field RT. The median RT dose was 23.4 (23.4-30.6) Gy. RESULTS: The median follow-up period was 77.5 (6.7-198.5) months. During the follow-up period, two patients developed distant metastasis, and none developed local recurrence. Two patients died from seminoma, and three died for other reasons. The 5, 10, and 15-year OS rates were 94.7%, 89.6%, and 89.6%, respectively. The 5, 10, and 15-year CSS rates were 98.5%, 96%, and 96%, respectively. The 5, 10, and 15-year PFS rate was 96.1%. The univariate analysis showed that only histological subtype was significant for OS. The 10-year survival rate was 100% among patients with seminoma histology, 90.8% among patients with a classic seminoma histology, and 50% among patients with an anaplastic seminoma histology (P < 0.001). A multivariate analysis showed that the anaplastic seminoma was a negative prognostic indicator for OS (P = 0.042). CONCLUSION: Adjuvant RT resulted in excellent long-term survival and local control in patients with stage-1 seminoma after orchiectomy. During a short follow-up, secondary malignancy (SM) and late cardiovascular morbidity were not observed. Despite those results, concern of SM and late cardiovascular morbidity remains.