PURPOSE:Metastatic colorectal cancer (mCRC) is a lethal disease and fluorouracil-leucovorin-irinotecan (FOLFIRI) plus bevacizumab (bev) is a standard approach. Hence, there is a strong need for identifying new prognostic factors to show the efficacy of FOLFIRI-bev. METHODS:This is a retrospective study including patients (n = 90) with mCRC from two centers in Turkey. Neutrophil/lymphocyte (N/L) ratio, platelet count, albumin, and C-reactive protein (CRP) were recorded before FOLFIRI-bev therapy. The efficacy of these factors on progression-free survival (PFS) was analyzed with Kaplan Meier and Cox regression analysis. And the cutoff value of N/L ratio was analyzed with ROC analysis. RESULTS:The median age was 56 years (range 21-80). Forty-seven percent of patients with N/L ratio >2.5 showed progressive disease versus 43 % in patients with N/L ratio <2.5 (p = 0.025). The median PFS was 8.1 months for the patients with N/L ratio >2.5 versus 13.5 months for the patients with N/L ratio <2.5 (p = 0.025). At univariate Cox regression analysis, high baseline neutrophil count, LDH, N/L ratio, and CRP were all significantly associated with poor prognosis. At multivariate Cox regression analysis, CRP was confirmed to be a better independent prognostic factor. CRP variable was divided into above the upper limit of normal (ULN) and normal value. The median PFSs of the patients with normal and above ULN were 11.3 versus 5.8 months, respectively (p = 0.022). CONCLUSIONS:CRP and N/L ratio are potential predictors for advanced mCRC treated with FOLFIRI-bev.
The molecular subtypes of male breast cancer are not well-known, but luminal A is generally regarded as the predominant subtype. We present the clinical and histopathological features in a man with triple-negative breast carcinoma.
BACKGROUND For HER2 positive metastatic breast cancer (MBC), continuing anti-HER2 therapy beyond progression is associated with improved outcome. However retreatment with trastuzumab after lapatinib progression is controversial. We retrospectively analyzed the efficacy of trastuzumab-based chemotherapy in HER2+ metastatic breast cancer patients whose disease progressed after lapatinib. MATERIALS AND METHODS Between October 2010 and May 2013, 54 patients whose disease progressed after lapatinib were retreated with trastuzumab-based chemotherapy. Efficacy and toxicity results were evaluated retrospectively. RESULTS The median age of patients was 46 (range 27-67). Fourteen patients (26%) had metastases at the time of diagnosis. All of the patients had received trastuzumab in an adjuvant or metastatic setting, while 16 (30%) had received two lines of trastuzumab. All patients had received lapatinib plus capecitabine. The median chemotherapy line for the metastatic setting was 2 (range 1-7). Cranial metastases were identified in 27 (50%) patients. 53 patients received trastuzumab-based chemotherapy following lapatinib progression while one patient received trastuzumab monotherapy. Combination chemotherapy consisted of navelbin (n=33), taxane (n=10), gemcitabine (n=2), platinum (n=2) and platinum with taxane (n=6). The median treatment cycle was 5 (range 1-44). Among 49 patients assessed for response 2 (4%) showed CR, 12 (25%) PR, 11 (22%) SD and 24 (49%) disease progression. Asymptomatic cardiotoxicity was reported in 2 (4%) of the patients. At a median follow-up of 9 months (1-39), median progression-free survival was 5 months (95% CI 4.1-5.9) and median overall survival was 10 months (95% CI 6.9-13.0). PFS and OS were not affected by the absence/presence of cranial metastases. CONCLUSIONS Retreatment with trastuzumab-based therapy after lapatinib progression showed efficacy in heavily treated MBC patients.
Identification of biomarkers used for the prognostic evaluation of non-small cell lung cancer (NSCLC) patients is important. The aim of this study was to evaluate the potential prognostic value of XRCC1, ERCC1, ERCC2, and TP53 single nucleotide polymorphisms (SNPs) in completely resected NSCLC patients. In total, 130 patients, surgically treated for NSCLC between 2000 and 2012, were included. An analysis of SNPs from peripheral blood cells was performed by polymerase chain reaction. XRCC1 Arg399Gln, ERCC1 Asn118Asn, ERCC2 Lys751Gln, and TP53 Arg72Pro polymorphisms were evaluated in conjunction with clinical and pathological parameters and survival. Kaplan–Meier method and Cox regression analysis were used. Median age rate was 59.3, ranging between 36 and 78 years. Median relapse-free survival duration (RFS) was found as 46.2 months. In those with ERCC2 CC allele, median RFS was detected as 28.3 months (95 % confidence interval (CI), 20.8−35.8), 46.9 months in those with CT heterozygous (95 % CI, 18.6−75.2), and 80.1 months for those with TT mutant allel (95 % CI, 33.0−127.2). Median RFS was seen to be longer in mutant group and also statistically significant (P = 0.018). Additionally, upon evaluating CC normal group with CT + TT alleles including mutant alleles, median RFS was found as 56.5 months (95 % CI, 24.6−88.4) in CT + TT group, and this was statistically significant (P = 0.005) Also, median RFS was 15.1 months in those including ERCC2 CC allele and 56.5 months in CT + TT allele in the group with no adjuvant treatment (P = 0.001). In conclusion, our study showed that ERCC2/XPD polymorphism is an independent prognostic factor in operated NSCLC patients, and these findings should be supported with prospective studies.
e19109 Background: DNA repair pathway genes are associated with lung cancer development. The aim of this study was to evaluate the association of XRCC1, ERCC1, ERCC2 and, TP53 SNPs with the stage at the diagnosis in NSCLC patients. Methods: In total 275 patients, who had been treated for NSCLC between 2000 and 2012, were included in this study. Analysis of SNPs from peripheral blood cells was performed by polymerase chain reaction. XRCC1 Arg399Gln, ERCC1 Asn118Asn, ERCC2 Lys751Gln and, TP53 Arg72Pro polymorphisms were evaluated in conjunction with clinical and pathological parameters. Logistic regression analysis were used. Results: In the univariate analysis for the metastatic stage at the diagnosis of patients XRCC1 genotype (Wald = 34.37; P<0.001), ERCC2 genotype (Wald = 5.15; P=0.07), TP53 genotype (Wald=10.06; P=0.007) and non-squamous histology (Wald=10.28; P=0.001) were significant parameters. ERCC1 genotype, age and smoking amount were not significant. In the multivariate analysis XRCC1 genotype (Wald = 39.27; P<0.001), TP53 genotype (Wald = 13.59; P=0.001), and non-squamous histology (Wald=15.03; P<0.001) were the independent risk factors associated with the metastatic stage at the diagnosis of patients. The risk of metastatic stage at the diagnosis for the XRCC1 normal (AA) versus mutant (GG) genotypes (Exp(B)=24.29; P<0.001) and heterozygote (AG) versus mutant (GG) genotypes (Exp(B)= 5.39; P=0.001) were significantly increased. The risk of metastatic stage at the diagnosis for the TP53 normal (CC) versus mutant (GG) genotypes (Exp(B) = 5.02;P=0.002) were significantly increased. Conclusions: XRCC1 and TP53 genotypes are independently associated with metastatic stage at the diagnosis of NSCLC patients. Future prospective studies are needed for the further evaluation of the relationship between DNA repair system SNPs and the stage at the diagnosis in NSCLC.
INTRODUCTION Breast cancer in young women is a relatively rare disease; however it tends to be more aggressive and is the leading cause of cancer death in this population. The aim of this study is to investigate the clinical and biological features of breast cancer arising in young Turkish breast cancer patients. MATERIALS AND METHODS Patients with breast cancer aged 35 or less (≤35 years) were selected for the study. In total 211 cases were included. Pathologic features; histologic subtypes, grade, lymphovascular invasion, axillary involvement, and stage were recorded for each. RESULTS The most common subtype was luminal B (36.5%), followed by luminal A (30.8%), triple negative (23.2%) and HER2+(9.5%) subtypes. Twelve percent of the patients had stage 4, 32.7% had stage 3, 46.4% had stage 2, and 6.2% had stage 1 disease at the time of diagnosis. Mean tumour diameter was 3.87 cm (range 0.3-13 cm). The axillary lymph nodes were positive in 74.4% of the patients, while lympho-vascular invasion was seen in 56.4%. Some 9.5% of patients had grade 1, 51.2% had grade 2, and 31.8% had grade 3 tumors. CONCLUSIONS Young women with breast cancer in Turkey are more likely to present with luminal B subtype. Tumors in young women are more likely to present with advanced disease, to be high grade and and to have more lymphovascular invasion. Further research should focus on whether we need new treatment strategies for young patients with breast carcinoma.
Background: Several clinical studies have shown the effect of mefformine on survival in pancreatic cancer. We aimed to evaluate whether the use of mefformin in diabetic pancreatic cancer patients provides a survival advantage or not. Methods: The data of 467 pancreatic adenocarcinoma patients diagnosed between 2003 and 2012 from five centers were analyzed, retrospectively. The groups were pancreatic cancer patients with diabetes who use metfonnin, who don't use metfornzin and non-diabetics. Results: Median overall survival was 8 months for the whole cohort, and 8 months for the group of non-diabetic patients. Overall survival was 8 months for the diabetic patients who use metfonnin whereas 10 months for the patients who do not use metformin. There was no statistically significant survival difference between the groups (p:0,76). Conclusion: Our study did not support clinical benefit of metformin in diabetic pancreatic cancer patients.
Presentation with bone marrow metastasis at diagnosis is a rare event in breast carcinoma. Here, we report a rare presentation of metastatic breast cancer patient with bone marrow metastases, who was successfully treated with trastuzumab combined chemotherapy. The regimens initially applied for bone marrow metastasis were docetaxel/adriamycin, gemcitabine/vinorelbine, epirubicin/cyclophosphamide, capecitabine, docetaxel, gemcitabine, and paclitaxel. But, the best response to these regimens was not satisfactory. Our patient was completely treated with etoposide-cisplatin and trastuzumab combination. She is still on remission after five years of metastatic breast cancer diagnosis using letrozole and trastuzumab without complication. Physicians should be careful in treating bone marrow metastases in breast cancer, since patients can show improved marrow function after chemotherapy and long-lasting survival is possible.
OBJECTIVESThis study was performed to evaluate the sociodemographic characteristics, smoking status and the frequency of the cancer types attributable to cigarette smoking in the cancer patients treating at Medical Oncology Department.METHODSThis descriptive and cross-sectional study was performed among 459 cancer inpatients treating at Medical Oncology Department. Data were obtained via a questionnaire form revealed socio-demographic characteristics, smoking-related attitude and behaviors.RESULTSOf the participants, the mean age was 57.42 +/- 13.29 (range: 1891), 52.9% were male. The prevalence of current smokers was 9.6%, former smokers 48.1%, never-smokers 42.3%. respectively. While respiratory tract cancers (32.1%), GIS (24.3%) and colorectal cancers (18.9%) were seen frequently in the male gender, breast cancer (46.8%) GIS cancers (15.3%) and colorectal cancers (12.5%) were seen frequently in the female. While the frequency of the respiratory tract cancers was 30.6% in the smoker cancer patients, this rate was 4.6% in never smokers. The frequency of the respiratory tract cancers was higher in the smoker cancer patients than never smoker cancer patients (RR=6.65). Of the respiratory tract cancers, 26.0% was attributed to cigarette smoking.CONCLUSIONParticularly, smoking plays an important role in the development of lung cancer. Common cancers shows differences according to gender and age. So, the socio-demographic characteristics should be considered while the cancer screening programs are developing.
e11586 Background: We retrospectively analyzed efficacy of trastuzumab-based chemotherapy in patients whose disease progressed after lapatinib. Methods: Between October 2010 and May 2013, 54 patients whose disease progressed after lapatinib received trastuzumab-based treatment. Survival and toxicity results were evaluated retrospectively. Results: Median age of patients were 46 (27-67), 53 were female and 1 was male. 24 patients (44,4%) were ER-positive and 20 (37%) were PR-positive. 14 patients (25,9%) had metastasis at the time diagnosis. 36 of the patients (66,6%) had received adjuvant/neoadjuvant anthracycline and taxane therapy, while 24 (44,4%) had received adjuvant/neoadjuvant anthracycline and 14 (25,9%) adjuvant trastuzumab therapy. 47 patients had received trastuzumab in metastatic setting and all patients received lapatinib plus capecitabine. Median chemotherapy line for metastatic setting was 2 (1-7), 26 patients (48%) had received at least 3 lines of treatments. 39 patients (72,2%) had at least 2 organ metastasis and 27 (50%) had cranial metastasis. 53 patients recevied trastuzumab+chemotherapy following lapatinib while one patient received trastuzumab monotherapy. Combination chemotherapy consisted of navelbin (n=33), taxane (n=16) and gemcitabine or carboplatin (n=4). 6 patients received platinum as triple combination therapy. Median treatment cycle was 5 (1-44). Among 49 patients assessed for response 2 showed CR, 12 PR, 11 SD and 24 disease progression. No unexpected toxicity was observed. At a median follow-up of 9 months (1-39), 45 patients had disease progression, 34 patients died and 4 patients were still on treatment. Median progression-free survival was 5 months (%95 CI 4,1-5,9) and median overall survival was 10 months (%95 CI 6,9-13,0). PFS and OS were not effected by absence/presence of cranial metastasis. Conclusions: Retreatment with trastuzumab-based therapy after lapatinib showed efficacy in patients heavily treated with trastuzumab. Continuing HER2 blockade provides clinical benefit for patients who have received several anti-HER2 treatments.
Erlotinib is a potent inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, with single-agent antitumor activity which improves symptom control and quality of life compared with placebo in non-small-cell-lung cancer (NSCLC) patients.We aimed to determine the efficacy and safety of the second, third or fourth-line erlotinib in advanced NSCLC patients in Turkish population.Eighty patients (33 males and 47 females) were retrospectively evaluated.All patients had received a platinum-based regimen as the first-line metastatic therapy.Most of the patients (62.5%) had received erlotinib as the second-line treatment.None of the patients had EGFR mutation studied.One patient achieved a complete response, 10 patients partial response and 21 stable diseases.The overall response rate was 14% and disease control rate was 40%.The median progression-free survival (PFS) and overall survival (OS) were 12 months and 18 months, respectively.Although, there was no survival difference between male and female patients, the median PFS of females was significantly better than male patients (p=0.03).There was no significant difference in disease control rate in terms of age, smoking status, erlotinib line, performance status (PS), stage and skin rash.The most common adverse events were skin rash (56%), diarrhea (9%) and anorexia (8%).Sixteen patients (20%) developed grade 3 toxicities.Grade 4 toxicity or treatment related interstitial lung disease were not observed.Erlotinib showed an acceptable response rate, survival time and toxicity after disease progression with chemotherapy.It's an alternative therapy as a second or third-line therapy in patients with NSCLC.Prospective studies are needed to evaluate the efficiency of the treatment in Turkish population.
Purpose: To evaluate the clinicopathologic characteristics and treatment outcomes of young patients with colorectal cancer (CRC).Methods: Between May 2003 and June 2010, 76 patients were found eligible for this retrospective study. Age, sex, presenting symptoms, patients with acute presentation, family history, presence of polyps, histologic features, localization and stage of the tumor, treatment outcomes, time and site of recurrence, sites of metastasis, and survival outcomes were recorded from the patient files.Results: Seventy-six patients (55.3% male) with a median age of 23 years were evaluated. Patients were evaluated in 2 groups as follows: child-adolescent (0 to 19 y, n=20) and young adult (20 to 25 y, n=56). Sex and symptoms (abdominal pain and rectal bleeding) were significantly differed between the groups and acute presentation was close to statistical significance. Overall survival significantly increased in patients undergoing curative surgery (P<0.001). Other parameters affecting the survival was stage of disease (P=0.004). Response to palliative chemotherapy in metastatic patients (P=0.042) and postoperative adjuvant chemotherapy had a statistically significant survival advantage (P=0.028).Conclusions: Diagnosis of CRC should not be excluded solely on the basis of age. CRC features in young-adult patients are more similar to adults compared with that of child-adolescent patients according to the symptoms and presentation. In patients with CRC in this age group, curative surgery, adjuvant chemotherapy, and palliative chemotherapy provide survival advantage.
e15110 Background: Risk factors for the pancreatic cancer are cigarette smoking, obesity, family history, chronic pancreatitis and type 2 diabetes mellitus. Diabetes mellitus is associated with 2-3 fold increase in the risk of pancreas cancer development. Down-regulation of mTOR pathway which begins with the insulin signaling is the possible protective effect of metformin in the oncogenesis of pancreatic cancer. In this study, we aimed to evaluate whether the use of metformin in diabetic pancreas cancer patients has an advantage or not. Methods: The data of 467 patients with the diagnosis of pancreas cancer in from 2003 to 2012 were analyzed, retrospectively. Results: Four hundred and sixty seven patients with the median age of 62 (20-85) were reviewed Median tumour size was 42 mm (14-145 mm). According to 2010 TNM staging, 23 patients had stage 1 (4.9%), 97 patients stage 2 (20.8%), 70 patients stage 3 (15%) and 277 patients had stage 4 disease (59.3%). Diabetes mellitus was detected in 173 (37%) patients. In this group 23 patients had stage 1 (4.9%), 97 patients stage 2 (20.8%), 70 patients stage 3 (15%) and 98 patients had stage 4 disease (56.6%). Thirty seven percent (64 patients) of the patients with diabetes were using metformin. Median time for metformin usage was 14±2,3 months. Median follow-up time was 7 months (1-88 months). Median overall survival (OS) of all pancreas cancer patients was 8 months. Surprisingly, median OS of diabetic pancreas cancer patients and non-diabetics was 9 and 8 months, respectively (statistically not significant). Median OS of diabetic patient subgroup who use metformin or not was 7 versus 10 months, respectively (statistically not significant). In the subgroup of stage 3 pancreatic cancer patients with diabetes mellitus, the median OS were 16 months and 10 months according to metformin usage or not, respectively (p=02). Conclusions: In this study, the median OS of diabetic pancreas cancer patients was superior from the non-diabetics. Multi-center prospective trials including large number of patients are needed to understand well enough the benefit of metformin in diabetic pancreas carcinoma patients.
CNS metastases usually appears late in the progression of metastatic breast cancer. Classical approach is evaluating and treating them when symptoms become evident. We evaluated the survival and described clinicopathologic characteristics of patients in whom the brain metastases after adjuvant treatment or at initial diagnosis are the first and the only side. Authors retrospectively evaluated about 3600 patients with breast cancer treated in two university hospitals. In those 31 patients with first and only metastases to brain and no other metastases were evaluated. ER, PR, cerbB2 status T, N stage, grade, adjuvant taxane, trastuzumab, hormonal treatment, trastuzumab and platine use after brain metastases didn't effect the survival. Surgery and WBRT may be more effective in cerbB2 negative patients, WBRT in cerbB2 positive ones. (p=0.06). The survival outcome may be better in pre and perimenouposal women. The mOS of pre and perimenopausal, postmenopausal women were 17.7 months and 10.3 months respectively (p=0.06) and lapatinib may affect the mOS of patients with isolated brain metastases. Some prognostic factor may help us to foresee which group may benefit more from which treatment modality. The need for studies with larger groups of patients is obvious.
Patients with advanced gastric carcinoma have still had bad prognosis despite advances in the modern treatment era. Docetaxel, cisplatin, 5-fluorouracil (DCF) is effective, but highly toxic regimen for advanced cases. In this study, we modified the standard doses of DCF (mDCF) to evaluate the effectiveness and side effects. From July 2005 to July 2008, 37 advanced gastric cancer patients treated with at least one course of mDCF protocol as first-line treatment were included. The mDCF protocol included 60 mg/m(2) docetaxel and cisplatin for 1 day and 600 mg/m(2)/day, 5-flourouracil infusion for 5 days, repeated every 3 weeks. No patients used prophylactic granulocte -colony stimulating factor. Of the patients, 28 were male and nine were female; the median age was 53 (23-65) years. Of them, 83.8% received at least four courses of chemotherapy and 64.9% completed the preplanned six courses of treatment. Eleven (29.7%) of those patients who received mDCF in the first-line treatment used the FOLFIRI (5-FU, folinic acit, irinotekan) regimen for the second-line treatment. Response rates were evaluated according to RECIST criteria in 30 out of 37 patients. The median follow-up time was 7.1 months. The longest follow-up time was 19.9 months. Two patients (5.4%) had complete response, nine (21.6%) had partial response, and 14 (37.9%) had stabilized disease; overall, the disease was controlled in 25 patients (64.9%) whereas five patients (13.5%) had progression. Median time to progression was 6.7 months and overall survival was 10 months. The assessment of patients for grade 3-4 toxicity revealed that while 5.4% had anemia and 8.1% had neutropenia, 5.4% nausea and 5.4% diarrhea. Neutropenic fever developed in two patients, requiring hospitalization. G-CSF was used in three patients. Two patients with neutropenic fever and two with severe anemia (total number 4; 10.8%) received delayed chemotherapy. Dose reduction was required in four patients (10.8%), one due to neutropenia, one due to nephrotoxicity, and two due to nausea. No patient died due to chemotherapy toxicity. This retrospective study suggested that mDCF might have comparable efficacy with classical DFC, with better toxicity profile. However, its small size and retrospective nature should be considered when interpreting the results.
The aim of this study was to describe the clinicopathological characteristics and prognostic factors of carcinoma of ampulla Vateri. The medical records of 32 patients (24 men, 8 women) were evaluated. Median age was 59 years (range, 36-80 years). The performance status at the time of admission of (European Cooperative Oncology Group) 18 patients (56.3%) were ECOG-1; 8 patients (25.0%) were ECOG-2. Fifteen patients had early stage, 15 patients had locally advanced stage. Twenty-eight of 32 patients underwent curative surgery. Eleven, nine, and four patients had high-, moderate-, and low-grade histology, respectively. Fourteen patients received adjuvant treatment. Ten out of 14 patients were treated with chemotherapy. ECOG performance status (P = 0.06), stage (P = 0.05), perineural invasion (P = 0.01), tumor grade (P = 0.01), and treatment with chemotherapy, chemoradiotherapy, or only radiotherapy (P = 0.001) had a statistically significant impact on overall survival, whereas only tumor histopathology (P < 0.001) was shown to have a statistically significant effect on disease-free survival. Carcinoma of ampulla Vateri is a rare gastrointestinal tumor. Prospective trials with larger number of patients are needed to determine the prognostic factors to help select patients for adjuvant treatment.
Methotrexate, a folate antimetabolite, is a widely-used anti-cancer agent against various cancers including osteosarcoma, non-Hodgkin’s lymphoma, leukemias and breast cancer. Aside from cytosine arabinoside, it is one of the few agents which can be used intrathecally to treat, or for prophylaxis against malignant meningeal involvement. Although neurotoxicity is a well-known side effect of intrathecal methotrexate, owing to systemic release, it may cause myelosuppression, which is usually overlooked [1-4]. However, severe myelosuppression is unusual without concomittant systemic chemotherapy. Here, we share our experience a patient who suffered from severe myelosuppression secondary to intrathecal chemotherapy and who subsequently tolerated well a high dose of methotrexate and cytosine arabinoside. A 37-year-old man was admitted to our institution because of non-Hodgkin’s lymphoma with central nervous system (CNS) relapse. Two years earlier, he had been diagnosed elsewhere as having “lymphoblastic lymphoma,” staged as IIA. After he had responded completely to the salvage chemotherapy for his 2nd relapse, he had been referred to our institution for high-dose chemotherapy with hematopoietic stem cell support. Radiological imaging, peripheral smear, bone marrow aspiration and biopsy did not reveal any sign of relapse. Soon after his admission, he had complaints of diplopia and headache. Cranial magnetic resonance imaging was normal. A diagnostic lumbar puncture was performed and methotrexate 15 mg, cytarabine 40 mg and dexamethasone 4 mg were given intrathecally for probable meningeal involvement. As cytological examination revealed atypical lymphocytes proving CNS involvement, it was decided to continue intrathecal chemotherapy. Seven days after the 2nd dose, his neutrophil and thrombocyte counts unexpectedly dropped to 20/mL and 9000/mL, and he developed febrile neutropenia and imipenem and amikacin were started. However, he was febrile despite the antibiotic therapy for three days and flucaonazole and acyclovir were instituted for oral Good tolerance of high dose cytosine arabinoside and methotrexate after severe myelosuppression secondary to intrathecal administration of the same agents