Prognostic factors for survival in patients with mucosal and ocular melanoma treated with ipilimumab: Turkish Oncology Group study.

OBJECTIVE: To evaluate prognostic factors associated with the use of ipilimumab in patients with mucosal and uveal melanoma. METHODS: In this multicenter, retrospective study, 31 patients with uveal and mucosal melanoma diagnosed between 2010 and 2017 were enrolled. Patients' characteristics, metastatic disease sites, treatment before ipilimumab therapy, performance status, hemoglobin, lactate dehydrogenase levels, B-RAF and c-kit mutation status, toxicity, and survival data were assessed for patients with mucosal and uveal melanoma. SPSS version 17 was used for statistical analysis. Kaplan-Meier method was used for survival analysis. The log-rank test was used for univariate analyses. The Cox regression analysis was used to test the association between multivariate variables and survival. The p-value of less than 0.05 was considered statistically significant. RESULTS: Twenty patients had uveal and eleven patients had mucosal melanoma. The median overall survival was seven months (95% confidence interval: 1.1-12.7). In univariate analysis, while bone metastasis, anemia, high lactate dehydrogenase level, and more metastatic sites were associated with lower overall survival, better treatment response and administration of ipilimumab in first or second lines were associated with favorable overall survival. In multivariate analysis, only treatment response status and administration of ipilimumab in first or second lines were found to be significant as independent prognostic factors for survival. CONCLUSION: Ipilimumab therapy may be associated with increased survival, but this retrospective small N study makes that hard to definitely conclude.

Prognostic factors for survival in patients with metastatic malign melanoma treated with ipilimumab: Turkish Oncology Group study.

PURPOSE: Studies in the last decade show survival improvement with checkpoint blocker therapy in patients with metastatic malign melanoma. Our purpose was to define the efficacy of ipilimumab according to the patient's baseline characteristics including absolute lymphocytes count. METHODS: We collected the data of 97 patients with advanced malign melanoma treated with ipilimumab (3 mg/kg, q3w) retrospectively. Log-rank test was used to analyze the univariate effects of patient's characteristics (age, gender, metastatic sites, ECOG PS, type of melanoma, lactic dehydrogenase levels, anemia, lymphocytes (L), neutrophils (N), N/L ratio), c-kit and BRAF status. Survival analyses were estimated with Kaplan-Meier method. Cox regression analysis was used to assess the possible factors identified with log-rank test. RESULTS: The median age was 58, and 58% were male and 90% of patients had at least one prior systemic therapy. The median survival was 9.7 months for all patients; and the 12- and 24-month survival rates were 43% and 19%, respectively. Absolute lymphocytes count, lactic dehydrogenase level, bone metastasis, the number of metastatic sites, and RECIST response were significantly related to survival. After Cox regression analysis, RECIST response (complete or partial response), absolute lymphocytes count (more than 1500/mm3) and the number of metastatic sites (less than three sites) remained as significant independent prognostic factors for longer survival. CONCLUSION: Ipilimumab improved survival of patients with metastatic malign melanoma. However, patients with fewer metastatic sites and higher absolute lymphocytes count have a significantly better benefit. To determine if these markers could be used to direct patient therapy, further validation analysis is needed.

Distribution of lymphomas in Turkey: data of 4239 cases from a single institution using the WHO classification

Background/aim: Lymphoma cases diagnosed at one of the largest tertiary reference centers in Turkey were reviewed and findings were compared to those reported from other regions of the world. Materials and methods: Lymphomas diagnosed between 2000 and 2017 in the pathology laboratory of Hacettepe University were identified. A total of 4239 cases were analyzed. The WHO 2008 classification was used. Results: Hodgkin lymphomas accounted for almost 20% of cases. T-cell lymphomas were much more frequent (23% of our non- Hodgkin lymphoma (NHL) cases) in comparison to all other regions of the world. The reason for this difference was the high frequency of mycosis fungoides (MF) cases. We had significantly more cases of high-grade B-cell lymphoma (43.9% of NHLs) and fewer cases of low-grade B-cell lymphoma (33.5% of NHLs) in comparison to the rates of developed regions of the world and the reverse was true when compared to developing parts of the world. Burkitt lymphoma frequency (4% of NHLs) was also higher than in most parts of the world. Conclusion: Our data reveal that the frequency of MF, Burkitt lymphoma, and Hodgkin lymphoma are considerably higher, whereas follicular lymphoma rates are considerably lower than in most other parts of the world.

Comparison of Gemcitabine monotherapy with Gemcitabine and Cisplatin combination in metastatic pancreatic cancer: a retrospective analysis.

PURPOSE: Gemcitabine is among the standard first-line agents for the treatment of metastatic pancreatic cancer. However, as the median survival with gemcitabine monotherapy is 6 months, different combinations are being studied for better, prolonged survival. In this multicenter study, we aimed to compare the results of gemcitabine monotherapy with those of gemcitabine and cisplatin combination therapy as first-line treatments for metastatic pancreatic cancer. METHODS: Data of 664 patients diagnosed with metastatic pancreatic cancer between January 2007 and December 2016 from seven oncology centers in Turkey were retrospectively evaluated, and 319 patients with gemcitabine alone (n=138) or gemcitabine and cisplatin combination (n=181) as first-line treatment were included. RESULTS: The median patient age was 62 years (range 42-79), being 60 years (42-75) in the gemcitabine/cisplatin arm and 67 years (52-79) in gemcitabine alone arm. no complete response was observed in either arm, whereas partial response rates were 30.1% in gemcitabine/cisplatin arm and 15.3% in gemcitabine alone arm (p=0.001). median overall survival was 8 months (95% CI:7.7-10.2) and was significantly longer in the gemcitabine/cisplatin arm than in the gemcitabine alone arm (10 vs. 6 months, p=0.004). CONCLUSION: The cemcitabine and cisplatin combination therapy as first-line treatment of metastatic pancreatic cancer yields significantly prolonged survival over gemcitabine monotherapy. In patients with favorable performance conditions, the combination therapy should be preferred.

Attitudes of cancer patients after diagnosis: How cancer affects social life? A Turkish Oncology Group study.

PURPOSE: Each year, 12.7 million people learn that they have cancer and 8.2 million people die of cancer worldwide. Cancer is a major public health issue which causes fundamental changes in the lives of patients and their families. The purpose of this study was to evaluate the lives of patients after diagnosis and determine the changes in their lifestyles. METHODS: Between September 2013 to December 2013, a questionnaire consisting of 22 questions was administered during a face to face interview to patients at 13 different Oncology Units in Turkey. Each patient was queried during the administration of his/her chemotherapy. Eight of the questions featured independent choices, and 14 had dependent (multiple) choices. RESULTS: A total of 1300 patients were included in the study. Of patients 9.5% were 71 years of age and older which was the oldest age group. The mean patient age was 54.6±13.8 years. Of the whole group of patients 58.5% were female and 41.5% male. After diagnosis, 64% of the patients reported that they were complying with guidelines for a healthy lifestyle and 80% said that they were eating healthier food. At the time they filled in the questionnaire, more than half of the patients (57.3%) felt optimistic about their disease. CONCLUSIONS: Diagnosis of cancer may change the patients' dietary and reading habits, social relationships, activities and more importantly, their point of life view.

Influence of antimuscarinic therapy on cognitive functions and quality of life in geriatric patients treated for overactive bladder.

OBJECTIVES: Incidences of overactive bladder (OAB) and cognitive dysfunction increase with aging. Treatment of OAB with antimuscarinic agents may result in cognitive decline, especially in patients with Alzheimer's disease (AD). The aim of this study is to evaluate the effect of antimuscarinic treatment on cognitive functions, depression, and quality of life (QOL) of patients with OAB. METHODS: This non-interventional prospective observational study was conducted in a geriatric medicine outpatient clinic. Overall, 168 OAB patients were enrolled. Patients were followed up in five groups: oxybutynin, darifenacin, tolterodine, trospium, and control groups. Follow-up visits were done at second, third, and sixth months. Comprehensive geriatric assessment, cognitive and mood assessment, QOL scales (IIQ-7, UDI-6) were performed. RESULTS: Mean age of the patients was 73.5 ± 6.1. Of the 168 patients, 92.3% were female, 83.3% benefited from the treatment, and 37.1% discontinued the medication. Discontinuation rate and frequency of side effects were more frequent in the oxybutynin group. Mini Mental State Examination scores did not decline after treatment, even in AD patients. Geriatric Depression Scale scores, Activities of Daily Living scores, and QOL scores significantly improved after treatment. CONCLUSION: Antimuscarinic agents are effective in OAB treatment. They have a positive impact on daily life activities, depression, and QOL indices. Furthermore, they do not have a negative effect on cognitive function in older adults with or without AD.

Uncommon variants detected via hereditary cancer panel and suggestions for genetic counseling.

OBJECTIVE: Hereditary cancer syndromes constitute 5-10% of all cancers. The development of next-generation sequencing technologies has made it possible to examine many hereditary cancer syndrome-causing genes in a single panel. This study's goal was to describe the prevalence and the variant spectrum using NGS in individuals who were thought to have a hereditary predisposition for cancer. MATERIAL AND METHOD: Analysis was performed for 1254 who were thought to have a familial predisposition for cancer. We excluded 46 patients who were carrying BRCA1/2 variants in this study, for focusing on the rare gene mutations. Sequencing was performed using the Sophia Hereditary Cancer Solution v1.1 Panel and the Qiagen Large Hereditary Cancer Panel. The Illumina MiSeq system was used for the sequencing procedure. The software used for the data analyses was Sophia DDM and QIAGEN Clinical Insight (QCITM) Analyze. The resulting genomic changes were classified according to the current guidelines of ACMG/AMP. RESULTS: Pathogenic/likely pathogenic variants were detected in 172 (13.7%) of 1254 patients. After excluding the 46 BRCA1/2-positive patients, among the remaining 126 patients; there were 60 (4.8%) breast cancer, 33 (2.6%) colorectal cancer, 9 (0.7%) ovarian cancer, 5 (0.4%) endometrium cancer, 5 (0.4%) stomach cancer, 3 (0.2%) prostate cancer patients. The most altered genes were MUTYH in 27 (2.1%) patients, MMR genes (MLH1, MSH6, MSH, MSH2, PMS2 and EPCAM) in 26 (2%) patients, and ATM in 25 (2%) patients. We also examined the genotype-phenotype correlation in rare variants. Additionally, we identified 11 novel variations. CONCLUSION: This study provided significant information regarding rare variants observed in the Turkish population because it was carried out with a large patient group. Personalized treatment options and genetic counseling for the patients are therefore made facilitated.

Effectiveness of bendamustine in relapsed or refractory lymphoma cases: a Turkish Oncology Group study.

INTRODUCTION: We aimed to investigate the efficacy and side effects of bendamustine in relapsed/refractory lymphoma patients in Turkey. MATERIAL AND METHODS: In this retrospective study, we included relapsed/refractory Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) patients who underwent multiple lines of chemotherapy. The primary endpoint was to determine the objective response and toxicity. RESULTS: Ninety-nine patients with a median age of 59.8 years were included in the study. Eighty-one patients had NHL (follicular lymphoma: 10, diffuse large B-cell lymphoma: 27, mantle-cell lymphoma: 18, marginal zone lymphoma: 9, small lymphocytic lymphoma/chronic lymphocytic leukemia: 17) and 18 patients had HL. The patients had previously received a median of three lines of chemotherapy (range: 2-8) except autologous stem cell transplantation (ASCT); 19 patients (HL: 11, NHL: 8) had undergone ASCT. The objective response rate (ORR) was 74.3%, the complete response rate was 57% (= 53), and the partial response rate was 16.6% ( = 19). The overall survival (OS) rate at 1 year was 74.6%. The progression-free survival (PFS) rate at 1 year was 62.5%. The most common side effects were lymphopenia, anemia and neutropenia. Side effects which were observed as grade 3 and higher levels were lymphopenia (14.1%), neutropenia (10.1%) and fatigue (7.1%). CONCLUSIONS: Objective response rate of bendamustine was found to be 74.3% in relapsed/refractory HL and NHL patients. It appears to be an effective option as a salvage treatment for patients who have previously received multiple lines of therapy.

Clinicopathologic Features of Gastroenteropancreatic Neuroendocrine Tumors: A Single-center Experience

Background: Gastroenteropancreatic neuroendocrine tumors, a heterogeneous group of neoplasms, originates from the neuroendocrine system of the gastrointestinal tract and pancreas. There are limited number of studies investigating neuroendocrine tumors in Turkey. Aims: To define the clinicopathologic, demographic, and survival features of patients with gastroenteropancreatic neuroendocrine tumors. Study Design: A retrospective observational cohort study. Methods: We reviewed hospital records of patients and data was analyzed retrospectively. We investigated the clinical, pathological, survival features, and prognosis of patients with gastroenteropancreatic neuroendocrine tumors (n=128) admitted to the medical oncology department between year 2003 and 2014. Survival estimation was performed by the Kaplan-Meier method. Univariate and multivariate Cox regression models were utilized to investigate the prognostic factors for survival. Results: Of 128 patients with gastroenteropancreatic neuroendocrine tumors, 61 (47.7%) were female and 67 (52.3%) were male. The most common site of the tumor was stomach (36.7%), while the most common stage of tumor at diagnosis was stage 4 (40.9%). The median follow-up period was 37 months, while the 3- and 5-year overall survival rates were 78% and 69%, respectively. The factors significantly affecting overall survival rate were clinical stage, grade, presence of metastasis at diagnosis, and Ki-67 proliferation index. These factors were associated with the 3- and 5-year overall survival rate. Moreover, grade (hazard ratio: 8.34, 95% confidence interval: 2.16-32.22, p=0.01) and presence of metastasis at diagnosis (hazard ratio: 3.18, 95% confidence interval: 1.30-7.77, p=0.01) independently predicted overall survival in multivariate model following adjustment for age and gender. Conclusion: Higher-grade and presence of metastasis at diagnosis are negative independent prognostic indicators of survival in patients with gastroenteropancreatic neuroendocrine tumors.

Enzalutamide Treatment in Metastatic Castration-resistant Prostate Cancer: Before and after Docetaxel.

ABSTRACT  Objective: To evaluate the efficacy and safety of enzalutamide in metastatic castration-resistant prostate cancer (mCRPC) in docetaxel-naive and docetaxel-pretreated patients. STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: HSU Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital, Department of Medical Oncology, Ankara, Turkey, from March 2017 to July 2019. METHODOLOGY: A total of 67 patients with mCRPC were retrospectively evaluated. Castration-naive patients and non-metastatic patients were excluded from the study. Comorbid diseases, ECOG performance status, PSA response, and the radiological response of the patients were recorded. Kaplan-Meier method was used for survival analysis, and a Cox regression model was formed. RESULTS: The overall survival (OS) was significantly longer in patients with eastern cooperative oncology group performance status (ECOG PS) 0 (26.0 vs. 14.0 months, p=0.031), PSA response (26.0 vs. 7.0 months, p=0.002), radiological response (26.0 vs. 10.0 months, p=0.006) and duration of enzalutamide ≥9 months (26.0 vs. 7.0 months, p<0.001) compared to ECOG PS 1. According to Cox regression analysis, patients with PSA response had 0.35 fold (CI.95% 0.13-0.94) reduced the risk of death and 0.36-fold (CI.95%0.16-0.85) reduced the risk of progression compared to those without PSA response. Moreover, longer enzalutamide treatment (≥9 months) was noted to decrease the risk of death. CONCLUSION: PSA response, radiological response and duration of enzalutamide treatment may predict the improvement of survival in patients with mCRPC treated with enzalutamide.   Key Words: Enzalutamide, Docetaxel, Castration-resistant prostate cancer, Overall survival, Progression-free survival.

Prognostic value of the 2017 World Health Organization Classification System for gastric neuroendocrine tumors: A single-center experience.

BACKGROUND/AIMS: Gastric neuroendocrine tumors (G-NETs) are rare tumors, but their incidence is gradually increasing. Despite the existence of many classification systems, determining prognosis and planning treatment in patients with G-NETs remains a clinical challenge. In this study, the prognostic value of the World Health Organization (WHO) 2017 grading system and the effect of surgery on survival in low grade neuroendocrine tumors were investigated. MATERIALS AND METHODS: G-NETs who were diagnosed between January 2000 and May 2017 were included in the study. Patients' demographic characteristics, treatment details, and survival data were obtained from medical charts. Pathological samples were re-classified according to the WHO 2017 grading system. RESULTS: Of the total 94 evaluated patients, 50 (53.2%) were classified with G1 NETs, 37(39.4%) with G2 NETs, 4(4.2%) with well-differentiated G3 NETs, and the remaining 3 patients with poorly differentiated G3 neuroendocrine carcinoma (NEC). The median follow-up time was 83.2 months. There was a statistically significant difference in 5-year progression free survival (PFS) between G1 tumors (100%) and G2 tumors (76%) (p<0.001). However, there was no statistically significant deference in 5-year overall survival rate (OS) for G1 (97%) and G2 (82%) tumors (p=0.141). When G2 and G1 NETs were compared according to their surgical approach, radical surgery was more frequently performed in patients with G2 tumors (p<0.001). However, radical surgery did not improve PFS in G1 and G2 NETs. CONCLUSION: The WHO 2017 NET classification system may have low prognostic value for determining the prognosis of patients with G1 and G2 tumors. Radical surgery for G1 and G2 NETs did not improve PFS in our study.

What is the optimal high-dose treatment following autologous stem cell transplantation in relapsed or refractory germ cell cancer: a retrospective comparison of high-dose ICE and high-dose CE.

PURPOSE: Testicular cancer is the most commonly diagnosed solid organ malignancy in 15 to 35 year-old men with 1% incidence among all malignancies. Sixty percent of patients with mild and poor-risk factors need additional treatments. Starting in 1980s, high dose chemotherapy regimens (HDCT) that were not applicable before due to hematological toxicity have been brought into use, and survival and cure possibility have increased. To date, no randomized trial has been conducted to demonstrate superiority of high-dose chemotherapy protocols used for autologous stem cell transplantation (ASCT). Our study aims to compare two commonly used HDCT regimens for a long period, with real-life data. METHODS: Approval for thiss retrospective study was obtained from the ethics committee of Gülhane Training and Research Hospital. Fifty refractory testicular cancer patients above 18 years were treated with HDCT and ASCT at Gülhane Training and Research Hospital (January 2011-July 2018). RESULTS: Fifty metastatic, refractory testicular carcinoma patients with a median age of 34 were included in the study. Ninety per cent of the cases had stage III disease at diagnosis. Except for 8 patients (16%) at mild risk group, all the other patients were at high risk. CE was used as salvage treatment for half of the patients and ICE was used for the other half. Four patients responded completely and 30 responded partially to ASCT. Post transplantation median progression-free survival (PFS) was 22 months. Median overall survival (OS) in the general population was 223.4 months (76.1-370.7). Although there was a difference in OS between chemotherapy groups, the difference was not statistically significant. The mean duration of engraftment in patients treated with CE was 11.2 ± 2.3 days, while in patients receiving ICE it was 15.5 ± 2.1 days. This difference between chemotherapy groups was statistically significant (p<0.001).

Does primary tumor localization has prognostic importance in seminoma patients?: Turkish Oncology Group Study.

PURPOSE: The purpose of this study was to determine whether primary tumor localization may be a risk factor for relapse and survival in seminomatous germ cell tumors (GCT) patients. METHODS: In our study, 612 seminomatous GCT patients diagnosed in 22 centers between 01.01.1989 and 03.02.2019 were retrospectively evaluated. Patient interview information, patient files and electronic system data were used for the study. RESULTS: The primary tumor was localized in the right testis in 305 (49.9%) patients and in 307 (50.1%) in the left testis. Mean age of the patients was 36 years (range 16-85±10.4). The median follow-up period was 47 months (1-298). Recurrence was observed in 78 (12.7%) patients and 29 (4.7%) died during the follow-up period. Four-year overall survival (OS) was 95.4% and 4-year progression-free survival (PFS) was 84.5%. The relationship between localization and relapse was significant in 197 patients with stage 2 and stage 3 (p=0.003). In this patient group, 41 (20.8%) relapses were observed. Thirty (73.2%) of the relapses were in the right testis and 11 (26.8%) in the left testis. Four-year OS was 92.1% in patients with right tumor; and 98.7% in patients with left tumor (p=0.007). When 612 patients were evaluated with a mean follow-up of 4 years, there was a 6.6% survival advantage in patients with left testicular tumor and this difference was significant (p=0.007). CONCLUSION: Survival rates of patients with primary right testicular localization were worse compared with left testicular localization, and relapse rates were higher in stage 2 and 3 patients with right testicular localization.

Metronomic Chemotherapy: A Systematic Review of the Literature and Clinical Experience.

Metronomic chemotherapy, continuous and dose-dense administration of chemotherapeutic drugs with lowered doses, is being evaluated for substituting, augmenting, or appending conventional maximum tolerated dose regimens, with preclinical and clinical studies for the past few decades. To date, the principle mechanisms of its action include impeding tumoral angiogenesis and modulation of hosts' immune system, affecting directly tumor cells, their progenitors, and neighboring stromal cells. Its better toxicity profile, lower cost, and easier use are main advantages over conventional therapies. The evidence of metronomic chemotherapy for personalized medicine is growing, starting with unfit elderly patients and also for palliative treatment. The literature reviewed in this article mainly demonstrates that metronomic chemotherapy is advantageous for selected patients and for certain types of malignancies, which make it a promising therapeutic approach for filling in the gaps. More clinical studies are needed to establish a solidified role for metronomic chemotherapy with other treatment models in modern cancer management.

Pertuzumab, trastuzumab and taxane-based treatment for visceral organ metastatic, trastuzumab-naïve breast cancer: real-life practice outcomes.

PURPOSE: In this study, we aimed to describe the real-life practice outcomes of pertuzumab-trastuzumab-taxane (PTT) combination in visceral organ metastatic, trastuzumab-naive breast cancer (BC) patients. METHODS: This study was conducted by Turkish Oncology Group and included 317 patients' data from 36 centers. RESULTS: Median age was 51 (22-82). Median PFS was 28.5 months, while median OS was 40.3 months. Patients with brain metastases (n: 13, 4.1%) had worse PFS (16.8 m vs. 28.5 m; p = 0.002) and OS (26.7 m vs. 40.3 m; p = 0.009). Patients older than 65 years of age (n: 42, 13.2%) had significantly lower OS results (19.8 m vs. 40.3 m; p = 0.01). Two hundred sixty-eight patients (86.7%) received docetaxel while 37 patients (11.7%) received paclitaxel. PFS and OS were similar between taxane groups. In eight patients (2.5%), 5-40% ejection fraction decrement from baseline was detected without any clinical sign of heart failure. CONCLUSIONS: Our RLP trial included only visceral metastatic, trastuzumab-naïve BC patients including cases with brain involvement who received PTT combination in the first-line treatment. Regardless of negative prognostic characteristics, our results are in parallel with pivotal trial. Further strategies for brain metastasis should be developed to improve outcomes despite encouraging results with PTT treatment. Taxane selection can be personalized and endocrine maintenance may further improve outcomes after taxanes were discontinued. To our knowledge, this is the largest scale real-life clinical practice study of pertuzumab-trastuzumab-taxane therapy to date.

A correlation study of fluorouracil pharmacodynamics with clinical efficacy and toxicity.

PURPOSE: Plasma 5-fluorouracil (5-FU) concentrations vary greatly between individuals who have received standard dosage. Pharmacokinetic adjusted doses have been hypothesized to overcome the possibility of potential toxicity and ineffectiveness related to inappropriate plasma levels of 5-FU. In this study, we prospectively investigated the clinical benefit and toxicity of 5-FU in relation to its pharmacokinetic properties. METHODS: Pharmacokinetics, effectiveness, and toxicity of 5-FU were investigated in 101 patients. The 5-FU pharmacokinetics were measured on day 2 of chemotherapy infusions. Clinicodemographic characteristics are outlined. RESULTS: All 101 patients who received adjuvant chemotherapy were alive at the end of a median 45 months of the follow-up period. At least one grade 1 adverse event (AE) was observed in 69.3% of the patients and grade two AEs were observed in 10.1% of the patients. The 5-FU levels ranged between 103 and 4311 µg/L and area under the curve (AUC) measurements ranged between 4.5 and 189.7 mg min/L. Pharmacokinetic measurements were not significantly correlated with clinical efficacy (log-rank p = 0.21). However, higher AUC levels were positively correlated with toxicity (p = 0.02) and with the severity of adverse events. The risks of mucositis (odds ratio [OR] 1.45; p = 0.042) and neurotoxicity (OR 2.01; p = 0.009) were significantly increased in a logistic regression model. CONCLUSIONS: There is no clear evidence that increased plasma levels or pharmacokinetic adjusted doses of 5-FU were related to better efficacy. However, toxicity might be closely associated with increased plasma levels of 5-FU. Toxicities can be deferred via dose adjustments without any expense in efficacy.

Real world survival data of a rare malignancy: Anal cancer results in HIV negative patients from Turkey.

BACKGROUND/AIMS: An organ preservation approach using chemoradiotherapy has been established for anal cancer. This retrospective cohort study aimed to define the clinico-demographic characteristics and outcomes of cases of human immunodeficiency virus (HIV)-negative anal carcinoma during a period of 20 years in a single comprehensive cancer institute. MATERIALS AND METHODS: This was a single-center retrospective cohort study of patients who were treated between January 1995 and January 2015. The primary outcome measures that were investigated included overall survival (OS), progression-free survival (PFS), colostomy rates, and colostomy-free survival (CFS). RESULTS: A total of 28 patients who were principally treated with standard 5-fluorouracil + mitomycin combination chemoradiotherapy were eligible for analysis. The 3- and 5-year PFS rates were 92.4% and 63%, respectively. The lower T stage was found to be associated with a prolonged PFS (p=0.001). The 3- and 5-year CFS rates were 84.3% and 74.9%, respectively. A longer CFS was observed with lower T stages (p=0.05). At the last follow-up, 75% of the patients with anal cancer were alive, and 71.4% of the patients were disease free. The median OS was not reached with a median follow-up of 54 months (range, 6-115 months). The 3- and 5-year OS rates were 82% and 71.1%, respectively. No late toxicity was observed during the follow-up period. DISCUSSION: The short- and long-term prognoses of HIV-negative patients with anal squamous cell carcinoma were good, and low-grade toxicity was rare, thereby demonstrating that these patients can be successfully treated in a real-life setting with favorable outcomes.

Global cancer control: responding to the growing burden, rising costs and inequalities in access.

The cancer burden is rising globally, exerting significant strain on populations and health systems at all income levels. In May 2017, world governments made a commitment to further invest in cancer control as a public health priority, passing the World Health Assembly Resolution 70.12 on cancer prevention and control within an integrated approach. In this manuscript, the 2016 European Society for Medical Oncology Leadership Generation Programme participants propose a strategic framework that is in line with the 2017 WHO Cancer Resolution and consistent with the principle of universal health coverage, which ensures access to optimal cancer care for all people because health is a basic human right. The time for action is now to reduce barriers and provide the highest possible quality cancer care to everyone regardless of circumstance, precondition or geographic location. The national actions and the policy recommendations in this paper set forth the vision of its authors for the future of global cancer control at the national level, where the WHO Cancer Resolution must be implemented if we are to reduce the cancer burden, avoid unnecessary suffering and save as many lives as possible.

Clinical Applications of Immunotherapy Combination Methods and New Opportunities for the Future.

In the last decade, we have gained a deeper understanding of innate immune system. The mechanism of the continuous guarding of progressive mutations happening in a single cell was discovered and the production and the recognition of tumor associated antigens by the T-cells and elimination of numerous tumors by immune-editing were further understood. The new discoveries on immune mechanisms and its relation with carcinogenesis have led to development of a new class of drugs called immunotherapeutics. T lymphocyte-associated antigen 4, programmed cell death protein 1, and programmed cell death protein ligand 1 are the classes drugs based on immunologic manipulation and are collectively known as the "checkpoint inhibitors." Checkpoint inhibitors have shown remarkable antitumor efficacy in a broad spectrum of malignancies; however, the strongest and most durable immune responses do not last long and the more durable responses only occur in a small subset of patients. One of the solutions which have been put forth to overcome these challenges is combination strategies. Among the dual use of methods, a backbone with either PD-1 or PD-L1 antagonist drugs alongside with certain cytotoxic chemotherapies, radiation, targeted drugs, and novel checkpoint stimulators is the most promising approach and will be on stage in forthcoming years.

Maintenance strategy in metastatic colorectal cancer: A systematic review.

PURPOSE: Colorectal cancer is the third most common cancer in men and second in women, estimated to cause 694,000 deaths worldwide in 2012. Although 5-year survival rate of CRC has increased, inoperable metastatic colorectal cancer (mCRC) is almost always fatal. The aim of this systematic review is to outline the maintenance strategies that increase the chance and duration of survival with less toxicity and sustained quality of life. DESIGN: Literature search in PubMed, in American Society of Clinical Oncology (ASCO) Annual Meetings and in ASCO Gastrointestinal Symposia and European Society for Medical Oncology (ESMO) Congresses was performed. Studies conducted in adult patients were written in English language and were published in peer-reviewed journals as phase II or III randomized controlled trials (RCTs) comparing continuous chemotherapy to intermittent chemotherapy, each with or without maintenance therapy was included along with at least one of the outcomes of interest. RESULTS: Twenty randomized controlled trials and systematic reviews were included from Medline search, together with 4 abstracts from ASCO meetings and 2 abstracts from ESMO meetings. CONCLUSION: Existing evidence-based data show that prolonged progression free survival (PFS) can be achieved with less toxic regimens compared to complete drug holidays or continued treatment. However, the impact of maintenance on overall survival is less clear. The specific data for maintenance with biological agents are evolving, while in general fluoropyrimidine based maintenance with bevacizumab is better than Bev alone or observation for PFS. Data regarding Cetuximab maintenance are less pronounced than that of Bev maintenance. Preliminary data show that erlotinib-Bev combination may be of benefit as maintenance. Although maintenance may provide significant clinical benefit in clinical studies, the optimal strategy should still be individualized.