Background

Invasive cervical cancer is the most common form of gynecological cancer in Kazakhstan, which occupies the 5th position among all neoplasiases and occupies 10th place in mortality in the general population. The national cervical screening program in the Republic of Kazakhstan uses cytology (Pap test) from 2008, and is free of charge for women aged 30 to 60 years of age with an interval of 5 years.

Methods

Incidence data and mortality statistics have been sourced from the cancer registry database. All incidence and mortality rates have been directly age-standardized to the World Standard population. Data on survival have been obtained from specific reports (form № 7, № 35, № 090/Y). Extensive, intensive and standardized indicators, both general and age-specific have been calculated by the standard method of health statistics.

Results

For the period from 2007 till 2016 nearly 15000 women in Kazakhstan have been estimated to be diagnosed with cervical cancer. According to the analysis of incidence rates of cervical cancer is noted the increase in the detection rate of this disease from 2007 to 2016: from 15.3 to 19.1 per 100 000 female population. The analysis of age in incidence rates shows that the risk of the disease appears at a young age and significantly increases to 40-44 years. In the context of the stages of the analysis of cervical cancer is a marked increase of the detection rate of the disease at the first stage for the period from 2007 to 2016. 888 women were diagnosed with cervical cancer in the first stage in 2007 and 1484 women in 2016, which is characterised by a 50% increase in potency. For the period of 10 years from 2007 to 2016 more than 6000 women have died from cervical cancer. According to cancer registry database the five-year relative survival for cervical cancer in 2016 is 53%.

Conclusions

Analysis of cervical cancer incidence in the whole country shows the increase in incidence of this oncopathology among the female population and a consistently high mortality rate. Due to the introduction of the national screening program there is a marked increase in the detection of cervical cancer in the first stage in 2016 in comparision with 2007.

Legal entity responsible for the study

Dilyara Kaidarova

Funding

None

Disclosure

All authors have declared no conflicts of interest.

Background

SIRT1, a class III histone deacetylase has cancer relevance because it regulates lifespan in multiple organisms and down-regulates p53 function through deacetylation. Cancer Stem Cells are a small subset of cells that are responsible for initiation, development, and recurrence of tumors. Therefore, it is important to understand the molecular mechanism of Cancer Stem Cells for translational applications in the treatment of patients with cancer. Role of SIRT1 in enhancing tumorigenesis has been well documented in many cancers. However, its functional role in glioma cancer stem cells is largely unknown.

Methods

In order to comprehend the role of SIRT1 in glioma cancer stem cells, we used EX-527, a nanomolar inhibitor of SIRT1 in three glioma Grade IV cell lines –U87MG, A172 and LN229. This was followed by expression analysis by Q-PCR, Immunofluorescence and Tumor sphere assay in glioma and cancer stem cells of glioma. Cell proliferation was assessed by XTT. Expression of genes in 20 grade IV glioma patient samples was compared to normal brain sample.

Results

U87MG, A172 and LN229 cells cultured in Stem Media exhibited an increase in SIRT1 expression compared to Normal media. XTT assay after EX527 treatment (10nM to 100µM) did not exhibit any change in cell proliferation compared to control cells in all the three glioma cell lines. SIRT1 inhibition exhibited a decreased expression of stemness markers –Sox-2 and Oct-4 and a decreased capacity to form gliomaspheres compared to the Control cells. Finally, we have correlated our in-vitro results with human GBM samples and found that SIRT1 and stemness markers correlated well in native tumor samples.

Conclusions

The results indicate a role of SIRT1 as a pluripotent marker in cancer stem cells of glioma. SIRT1 deacetylates p53 rendering it inactive and thus initaiting a ascade of events with oncogenic potential. Cancer stem cells are the cells responsible for drug resistance and tumor relapse Thus knowing the mechanism of SIRT1 action in cancer stem cells would open doors for more target specific therapy. Our study provides a functional interaction of SIRT1 with the stemness markers in cancer stem cells of glioma and glioma patient samples thus aiming for target specific approaches in glioma.

Legal entity responsible for the study

All India institute of Medical Sciences

Funding

Indian Council of Medical Research

Disclosure

The author has declared no conflicts of interest.

Background

The role of adjuvant therapy has not been clearly defined in certain subgroups of salivary gland tumors. Elective LN irradiation has been the subject of debate. Our study analysed various prognostic factors and the role of adjuvant radiotherapy (adj RT) in salivary gland tumors on local control and median survival.

Methods

We analysed the data of 84 patients of malignant salivary gland tumors from 2010 to 2015 who underwent primary surgery at out institute with median follow up of 32 months range (3-84 months) using inclusion and exclusion criteria. None of the patients received adjuvant/concurrent chemotherapy in our study. The role of various factors like type of surgery (conservative/radical), grade of tumor, histology, PNI, margin+, LVSI+, adjuvant RT, Elective LN irradiation, LN dissection and size of primary tumor on two year local recurrence rate was evaluated as primary end point. Median survival was our secondary endpoint. Local reactions were evaluated using RTOG criteria. Stastical analysis was done using SPSS version 22.0

Results

Table: 346P

Patients and tumor characteristics

2 yr local control (LC) in patients who received adj RT is 88.5% and it is 37.5% who didn't receive adj RT which is statistically significant (p < 0.001) [odds ratio 10.6, 95% CI, 2.81-40.3]. High grade, LVSI+, PNI+, margin+, tumor size >4 cm and LN + have shown a trend to decrease LC rate but are not statistically significant. Interestingly, patients with LN dissection have trend towards decreased LC rate, probably due to more conservative/less aggressive LN dissection in patients who are clinically LN+. Patients with elective LN irradiation(ELNI) have a better 2 yr LC rate in high grade and large tumors than low grade and small tumors (70% vs 41%, p=.04, 64% vs 30%, p = 0.03 respectively). Adj RT doses of more than 60 Gy does not seem to improve LC in adjuvant setting and statistically not significant. The expected median survival with adj RT is 47 months vs 40 months for surgery alone(p = 0.14). Grade II reactions are 79% and 84% for xerostomia and dermatitis respectively, Grade III reactions are only 3% for radiotherapy group. There was one treatment related death in surgery alone group.

Conclusions

Adjuvant RT improves local control with trend towards improvement in survival. Elective LN irradiation in high grade and large tumors is beneficial. Radiation doses above 60 Gy doesnot seem to increase therapeutic ratio in adjuvant setting for R0 resection. Large prospective studies are needed for further evidence

Legal entity responsible for the study

MNJ Institute of Oncology, Hyderabad, India

Funding

None

Disclosure

All authors have declared no conflicts of interest.

Background

In clinical practice, we usually evaluate the efficacy of chemotherapy for metastatic colorectal cancer (mCRC) according to the RECIST criteria and determine an appropriate treatment plan. In the case of progressive disease (PD), we change the components of the treatment. However, PD as defined by the RECIST criteria, includes some types of progression and the impact of the type of progression on survival is unclear. The aim of this study was to assess the impact of the type of progression on survival in patients with mCRC.

Methods

Among the patients who received doublet chemotherapy for mCRC as a first-line treatment between 2008 and 2016, 82 patients who stopped the chemotherapy due to PD were enrolled in this study. We classified the types of progression, according to the definitions of RECIST, as follows: growth of measurable target lesion(s); the presence of new lesions; and unequivocal progression of non-target disease. We then evaluated the association between the type of progression and survival after the failure of the first-line chemotherapy.

Results

Fifty percent of patients only experienced target lesion growth, 45.1% of the patients had new lesions, and 7.3% of the patients had non-target PD. The overall survival rate in the new lesion/non-target PD group was significantly worse than that in the patients who only experienced target lesion growth (p = 0.0186).

Conclusions

Patients who stopped chemotherapy due to new lesions or non-target PD had worse overall survival rates than those who stopped the chemotherapy after only experiencing target lesion growth. The type of progression may be useful information for selecting the appropriate treatment after the failure of first-line chemotherapy.

Legal entity responsible for the study

Osaka City Uniersity Graduate School of Medicine

Funding

None

Disclosure

All authors have declared no conflicts of interest.

Background

BCR/ABL fusion gene usually occurs as a result of Philadelphia (Ph) translocation between chromosomes 9 and 22 in Chronic Myeloid leukemia (CML) as well as in Acute Lymphoblastic Leukemia (ALL). This rearrangement results in the formation a chimeric BCR/ABL fusion gene on the derivative chromosome 22. Fluorescence in-situ hybridization (FISH) analysis using dual color BCR/ABL translocation probes allows the visualization of BCR/ABL rearrangements in both interphase and metaphase cell, and the presence of the BCR/ABL fusion gene on chromosomes 22 has been reported in substantial subset of these patients. The pattern of rearrangement may be classical, variable or mixed. Only classical pattern has been reported to have good prognosis with lesser disease progression and good response to tyrosine kinase inhibitors.

Methods

The incidence of both classical and variable BCR/ABL gene rearrangement was determined in all the patients suspected of CML and ALL using dual fusion fluorescence in situ hybridization (D-FISH) probes. A minimum of 200 nuclei scored where possible.

Results

This study investigated 860 patients of CML and ALL between January 2016 and September 2016 at the Aga Khan University Hospital. Out of 860 patients 775(90%) were diagnosed as CML and 85 cases (10%) were diagnosed as ALL. About 659 cases (76%) of both CML and ALL patients displayed the classical DF-FISH signal pattern and 201(24%) of CML and ALL showed variable DF-FISH signal pattern. In variable DF-FISH signal, various different patterns were analyzed: 1F1G1R is 31%, 1F2G1R is 27%, 1F2G2R is 26% and 1F1G2R is 14% were observed in both CML (22%) and ALL (2%). The rare combination of classical and variable was observed in around 2% cases with CML.Table: 319O

Conclusions

The classical pattern was the commonest pattern identified in both CML and ALL, predicting a good prognosis. Variable patterns were identified in equal proportion except for 1F1G2R which was the least common.

Legal entity responsible for the study

Aga Khan Hospital

Funding

None

Disclosure

All authors have declared no conflicts of interest.

Background

Despite effective local tumor control with radioactive plaque brachytherapy, endoresection, or enucleation, many UM (uveal melanoma) patients ultimately developed fatal metastases. This study aims to evaluate the adjuvant treatment of UM patients after surgery.

Methods

Between March 2008 and Jan 2016, consecutively admitted uveal melanoma patients to Renal & melanoma department at the Beijing Cancer Hospital, were included in this cohort study. Choice of adjuvant therapy, recurrence-free survival and first metastatic sites, were analysed retrospectively.

Results

In total, 97 uveal melanoma patients were investigated retrospectively. From this 97 pts, 57 were male, 47 pts had primary lesions in their left eyes, median age 46 year-old (20-72yrs). Most pts had UM arising from the choroid (97%). Seven pts were stage IV when first diagnosed. The rest 90 pts receive enucleation (61/90), endoresection (8/90), bradytherapy (21/90) respectively after initial uveal melanoma detection. Sixty-nine pts who received radical surgery of UM were divided in to observation group (n = 39), interferon group (n = 15), chemo group (n = 13), dendritic cell vaccination group (n = 2) with respect of post-surgery treatment. Of 69 pts, 57 had developed metastasis. Median replase-free survival was 2.6 years in observation group and 4.6 years in the chemo group (P < 0.05). Median replase-free survival (3.5+years) was not reached in the interferon group partly because 60% of them were admitted in recent 3 years. Liver is the most common first metastatic sites were (n = 38), the others included bone (n = 7), lung (n = 5), subcutaneous mets (n = 5). 29 pts had elevated LDH when developed distant metastasis, 9 of them were Grade 3(>5×ULN).

Conclusions

Adjuvant chemotherapy or interferon might be reasonable options for patients with UM melanoma after surgery. We need more potent adjuvant therapy for this long term dormant but fatal disease.

Legal entity responsible for the study

Beijing Cancer Hospital

Funding

(Supported by the National Natural Science Foundation of China (81301984), Beijing Nova Program (XX2013027) and Program for New Century Excellent Talents in University (NCET-13-0007).

Disclosure

All authors have declared no conflicts of interest.

Background

Antiangiogenesis therapy plays an important role in cancer treatment.Apatinib showed good safety, tolerance and treatment efficacy in Phase I/II studies. In a Phase III study, apatinib prolonged the median overall survival of patients with chemotherapy-refractory metastatic gastric cancer by 55 days and the median progression-free survival by 25 days compared with placebo.This trial investigated the safety and efficacy of apatinib combined with docetaxel compared with docetaxel in second-line treatment of advanced gastric cancer.

Background

Antiangiogenesis therapy plays an important role in cancer treatment. Apatinib showed good safety and efficacy as third-line therapy for advanced gastric cancer. We conducted this trial to investigate the safety and efficacy of apatinib combined with docetaxel compared with docetaxel in second-line treatment of advanced gastric cancer.

Background

Antiangiogenesis therapy plays an important role in cancer treatment.Apatinib showed good safety, tolerance and treatment efficacy in Phase I/II studies.This trial investigated the safety and efficacy of apatinib combined with docetaxel compared with docetaxel in second-line treatment of advanced gastric cancer.

Methods

Patients with advanced or metastatic gastric cancer after failure of first-line chemotherapy were randomized to receive docetaxel (60mg/m², i.v. gtt, d1, q21d) with or without apatinib (500mg, po, qd). Study treatment was continued as a 21-day cycle until progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS). The secondary endpoints were disease-free control rate (DCR), overall survival (OS) and objective response rate (ORR). All adverse events were reported using CTCAE v4.0. Tumor assessment were performed every 2 cycle. Kaplan-Meier survival analysis was used.

Methods

From July 2014 to June 2017,We enrolled 59 patients into this study who were chemotherapy failure,disease progression or refractory and metastasis,the pathologic diagnosis of gastric cancer. he patients were randomly divided into experiment group and control group,the experiment group received apatinib combined with docetaxel,the control group received docetaxel,the efficiency and safety were evaluated after 2 cycles,the clinical efficiency and safety were assessed respectively,collecting their baseline demographic and clinical characteristics,past treatment,and apatinib initial dose and dose adjustment,analyzing apatinib treatment efficiency and safety,and graphing K-M curve for PFS,OS.

Results

59 patients were enrolled. Mean age was 55.4±11.48 years in the experiment group (n = 30), and 58.76±12.62 years in control group (n = 29). The average progression-free survival (PFS) was 3.22±3.65 months in the combined group vs 2.52±2.98 months in the docetaxel group (P > 0.05), which showed no significant differences. Partial response rate (PR), stable disease rate (SD), and progression disease rate (PD) were 43.33% (n = 13), 16.67% (n = 5), 40% (n = 12) in the combined group, and 13.79% (n = 4), 17.24% (n = 5), 68.97% (n = 20) in the docetaxel group, respectively. Disease control rate in combined group was significantly higher (P < 0.05). Patients in the combined group suffered higher hypertension and proteinuria, but Myelo-suppression was similar in the two groups.

Results

Fifty-nine patients were enrolled in this trial.The experiment group enrolled 30 patients, mean age was 55.4±11.48 years.The control group enrolled 29 patients,the mean age was 58.76±12.62 years.In experiment group,the average progression-free survival (PFS) was 3.22±3.65 months.In control group,the average PFS was 2.52±2.98 months,there were no statistically significant differences (P>0.05).In experiment group,13 patients achieved partial response(PR)(43.33%),5 patients achieved stable disease(SD)(16.67%), 12 patients achieved progression disease(PD)(40%).In control group,4 patients achieved PR (13.79%),5 patients achieved SD (17.24%),20 patients achieved PD (68.97%),there were statistically significant differences(P<0.05).About the adverse events (AEs) of the two groups,it mainly were hypertension and proteinuria in experiment group,which were super than that of in control group.About myelo-suppression,there was no significant difference between two groups(P>0.05).

Conclusions

Combination therapy with apatinib and docetaxel as a second-line treatment exhibits superior activity and manageable toxicity for patients with advanced gastric cancer.

Conclusions

Apatinib combined with docetaxel had certain therapeutic effect in second-line treatment of advanced gastric cancer.Apatinib combined with docetaxel can also prolonged the PFS,and the toxicities of the two groups were tolerable or could be clinically managed.

Clinical trial identification

AHEAD-301.

Legal entity responsible for the study

Chinese PLA General Hospital

Funding

None

Disclosure

All authors have declared no conflicts of interest.