A multi-institutional evaluation of carboplatin plus docetaxel regimen in elderly patients with advanced gastric cancer.

PURPOSE: Albeit the majority of gastric cancers occur at advanced age, little is known regarding the optimal systemic treatment of elderly patients with advanced gastric cancer (AGC). METHODS: Patients with AGC who were ≥ 65 years old and were treated with carboplatin (area under the curve/AUC 5,on day 1, every 3 weeks) plus docetaxel (75 mg/m(2), on day 1, every 3 weeks) at 3 institutions were included in this retrospective analysis. The efficacy and the safety data of the regimen were analyzed. RESULTS: A total of 30 patients were enrolled. They received 128 cycles of chemotherapy, with a median of 4 cycles (range 2-8). Complete response (CR) and partial response (PR) were observed in 2 (6.7%) and 10 patients (33.3%), respectively, amounting to an overall objective response rate (ORR) of 40%. Seven patients (23.3%) had disease stabilization (SD), and 11 (36.7%) showed disease progression (PD). The most common grade 3-4 toxicity was neutropenia occurring in 19 patients (63.3%). The mean progression-free survival (PFS) was 6.0 ± 0.5 months (95% CI: 5.0-7.4), and the mean overall survival (OS) 12.0 ± 1.0 months (95% CI: 9.2-12.1). CONCLUSION: Carboplatin plus docetaxel seems to be an active and well-tolerated regimen, representing a valuable alternative to cisplatin- and/or fluoropyrimidine-containing regimens for the treatment of elderly patients with AGC.

Prognostic significance of estrogen receptor, progesterone receptor, HER2/neu, Ki-67, and nm23 expression in patients with invasive breast cancer.

PURPOSE: To determine the prognostic significance of estrogen receptor (ER), progesterone receptor (PR), HER2/neu, Ki-67, and nm23 immunohistochemical expression with respect to progression free survival (PFS) and overall survival (OS) in Turkish patients with invasive breast cancer (IBC). METHODS: Patients with IBC (n = 81; mean age = 51.9 ± 11.1 years) were prospectively enrolled at the Department of Oncology, Uludag University Medical Center, Bursa, Turkey. Immunohistochemistry was performed on formalin- fixed, paraffin-embedded tissue sections. RESULTS: We did not find any significant association between immunohistochemical expression of ER, PR, HER2/ neu, Ki-67, and nm23 and the baseline characteristics of IBC patients. The median patient PFS was 30 months (range 22-45), and the median OS was 32 months (range 23-46). Stratification of the patient population according to nm23 immunohistochemical expression revealed a statistically significant difference in terms of both OS (p < 0.05) and DFS (p < 0.05). Multivariate Cox regression analysis indicated that tumor grade, axillary lymph node status, and nm23 immunohistochemical expression were the 3 main independent prognostic factors for PFS and OS in IBC patients. CONCLUSION: Reduced nm23 immunohistochemical expression is an independent negative prognostic factor for OS and PFS. Patients with negative nm23 expression may require a more intensive follow-up.

Identification of prognostic factors in patients with metastatic gastrointestinal stromal tumors.

PURPOSE: Gastrointestinal stromal tumors (GISTs) have a complex biology which is reflected by a marked clinical heterogeneity. Thus, there has been great interest in identifying prognostic factors influencing tumor recurrence and survival. The aim of this study was to identify potential clinical and immunohistochemical prognostic factors that may affect survival and treatment outcomes in patients with metastatic GISTs. METHODS: Between 2000 and September 2011, a total of 41 patients with metastatic GISTs (29 males and 12 females; mean age: 57.4±11.8 years; range 29-74) were referred to the Department of Oncology, Uludag University Medical School. Survival analysis for a number of potential prognostic factors was made with the main outcome results of progression-free survival (PFS) and overall survival (OS7rpar;. RESULTS: The most common sites of isolated metastases comprised the liver (n=18), followed by lymph nodes (n=5), the omentum (n=1), and the mesothelium (n=1). The remaining patients had metastases at multiple sites. Cox regression analysis identified ileal location as the only significant predictor of poor PFS both after first-line (p=0.023) and second-line therapy (p=0.016). Tumor location in the ileum (p=0.025) and S100 immunoreactivity (p=0.041) were both independent predictors of OS. CONCLUSION: Tumor site and S100 positivity were the main significant independent predictors of clinical outcomes in patients with metastatic GISTs treated by standard of care.

Chemotherapy plus radiotherapy vs. radiotherapy alone in high-risk endometrioid endometrial carcinoma.

OBJECTIVE: Adding chemotherapy to radiotherapy in patients with high-risk endometrioid endometrial cancer (EEC) remains controversial, particularly in stages I-II. We aimed to investigate the effect of treatment modalities on survival in high-risk EEC patients. PATIENTS AND METHODS: Patients with high-risk EEC were evaluated retrospectively between 2010 and 2019. Patients who did not receive adjuvant treatment were excluded. We included seventy patients and formed two groups: patients who received radiotherapy (RT) alone and those who received chemotherapy and radiotherapy (CT and RT). RESULTS: The median follow-up time was 60.3 months (8.0-143.5). 38.5% of the patients had relapsed. Recurrence-free survival (RFS) rates were 97. 1%, 68.3% , and 60.8% at 12-, 36-, and 60-month, respectively. Overall survival rates were 97.1%, 80.6%, and 72.6% at 12-, 36-, and 60-month, respectively. Hematological adverse events and neuropathy were more common in the CT and RT group than in the RT group. Multivariate Cox regression analysis for RFS revealed that the FIGO stage and treatment modalities were statistically independent factors (p=0.031 and p=0.040, respectively). Stage stratified log-rank test revealed that adding chemotherapy improved RFS in patients with stage III (p=0.020) but not in stage I-II disease (p=0.725). The number of chemotherapy cycles administered (≤4 vs. >4) did not affect survival in all patients and stage III disease (p=0.497, and p=0.436, respectively). CONCLUSIONS: Adding chemotherapy to radiotherapy may be considered in high-risk stage III EEC. Further studies are needed to determine the optimal duration of chemotherapy.

Expression of cyclooxygenase-2 in ovarian serous carcinoma: correlation with angiogenesis, nm23 expression and survival.

OBJECTIVE: To evaluate the expression of cyclooxygenase (COX)-2 in ovarian serous carcinomas (OSC) and its correlation with microvessel density (MVD), nm23 expression, clinicopathologic prognostic factors and survival. METHODS: Specimens from 44 patients with OSC were evaluated by immunohistochemistry for COX-2 and nm23 expression. Tumor MVD was assessed with CD34 immunostaining. The survival data of the patients were found from data files. RESULTS: 40 specimens (90.1%) showed positive COX-2 staining. Patients with high COX-2-expressed tumors had shorter overall survival, but it was not statistically significant. No correlation was found between COX-2 expression and clinicopathologic variables. There was no significant correlation between COX-2 and nm23 expression or MVD. CONCLUSIONS: COX-2 is frequently expressed in OSC. Although we could not confirm the prognostic significance of Cox-2 expression in the present cohort of OSC patients, the p value for overall survival was just slightly greater than alpha, and this result can be referred as almost significant. We considered that the limited number of cases in our study might affect the statistical analysis of our results. Further studies involving a larger number of patients are needed to clarify the prognostic significance of COX-2 expression in ovarian carcinomas.

Capecitabine-induced cardiotoxicity mimicking myocardial infarction.

Capecitabine, a fluoropyrimidine derivative, is an orally administered drug that delivers 5-fluorouracil (5-FU) selectively to the tumour. The drug has demonstrated activity in metastatic colorectal cancer. We describe a male patient receiving capecitabine therapy with typical chest pain and electrocardiographic changes consistent with STsegment elevation myocardial infarction. Capecitabine-induced cardiotoxicity may develop in patients who have had a previous episode of 5-FU-induced cardiotoxicity. Capecitabine-induced cardiotoxicity is a rare condition that may lead to diagnostic and therapeutic dilemmas. (Neth Heart J 2009;17:277-80.).

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.

The predicted probability of having positive non-sentinel lymph nodes in patients who received neoadjuvant chemotherapy for large operable breast cancer.

The accuracy of the nomogram in women with positive sentinel nodes following neoadjuvant chemotherapy (NCT) is unknown. The aim of this study was to evaluate the accuracy of the nomogram in patients receiving NCT. Between December 1999 and December 2005, we identified 233 patients who had a positive sentinel lymph node biopsy (SLNB) and complete axillary lymph node dissection at Magee-Womens Hospital of University of Pittsburgh Medical Center. Thirty-two patients (14%) had presented with clinically N0 breast cancer (BC) for which NCT was administered. The computerised BC nomogram was used to calculate the probability of non-sentinel node metastases utilising tumour size before NCT and after NCT for the same patient. The discrimination of the nomogram was assessed by calculating the area under (AUC) the receiver operating characteristic curve (ROC). The median patient age was 51.5 (range: 39-66) years in the NCT group of patients. Twelve patients (37%) had positive axillary non-sentinel lymph nodes (NSLNs). The nomogram was first validated in our institution for 201 patients without NCT and the predicted accuracy of the nomogram by the AUC was 0.73. The area under the ROC was identical regardless of whether pre- or posttreatment tumour size was used to determine predicted probability of NSLN metastases (0.66). The predictive accuracy of the nomogram was found to have less power for patients receiving NCT (0.66) than the non-NCT group of patients.

Comparison of uroprotective efficacy of mesna and amifostine in Cyclophosphamide- induced hemorrhagic cystitis in rats.

BACKGROUND: Hemorrhagic cystitis (HC) is a dose limiting side effect of cyclophosphamide (CYP). AIM: In this study, we aimed to investigate the role of amifostine in the protection of CYP-induced HC and compare its efficacy with mesna. SETTING AND DESIGN: This animal study was conducted in the Experimental Animals Breeding and Research Center of the Medical Faculty of Uludag University. MATERIALS AND METHODS: Male Wistar rats (150-200 g; 10 rats per group) were randomly assigned to four groups. Group I (control group) received no drugs, group II received CYP (200 mg/kg, i.p.) alone, group III received amifostine (200 mg/kg, i.p.) and CYP, and group IV received CYP and mesna (40 mg/kg, i.p.) immediately and 4 and 8 h after administration of CYP. Bladders of animals were assessed macroscopically and histologically 24 h later. Gross assessment for presence of edema and hemorrhage and histological evaluation of damage to the bladder were scored according to Gray's criteria. STATISTICAL ANALYSIS USED: For macroscopic and microscopic data, we used statistical evaluation by Kruskal-Wallis nonparametric analysis of variance followed by the Mann-Whitney U-test. RESULTS: All the animals in group II had evidence of HC. Significant histological damage and macroscopic changes were present in this group compared to control group (P<0.001). The median scores for bladder damage in group III and IV were significantly lower compared to group II (P<0.001). When the median scores for bladder damage of group I, III, and IV were compared, there was no significant difference among these groups. CONCLUSION: This study demonstrated the efficacy of amifostine in prevention of cyclophosphamide-induced hemorrhagic cystitis.

Comparison of the serum erythropoietin levels in chemotherapy-naive and cisplatin-treated cancer patients.

There are conflicting data about the effects of cisplatin on erythropoietin (EPO) response to anemia. Aim of our study was to investigate whether endogenous EPO response to anemia in cisplatin treated patients was insufficient in comparison to the anemic chemotherapy-naive cancer patients and non cancer patients with iron deficiency anemia. Patients who had hemoglobin (Hb) levels of less than 110 g/l were included in the study. Fifteen chemotherapy- naive cancer patients were enrolled in Group A. Group B consisted of 15 patients who had been treated with three cycles of cisplatin chemotherapy and then became anemic and in Group C were included 15 patients who had iron deficiency anemia, without any malignancy. The mean Hb values were not different between all groups (102.8+/-39.8 g/l, 103.1+/-2.5 g/l and 99.3+/-3.6 g/l in Group A, Group B and Group C, respectively). However, EPO levels were found to be significantly lower in Group A and Group B than Group C (29.63+/-9.09 mU/ml, 20.87+/-2.43 mU/ml and 85.38+/-25.72 mU/ml, respectively; p=0.017 Group A vs. Group C, p=0.005 Group B vs. Group C). No significant difference was found between Group A and B (p=0.917). Opposite the iron deficiency anemia, cancer anemia is associated with an inadequate EPO response to anemia and administration of cisplatin does not lead to it further deterioration.

Malignant peritoneal mesothelioma following asbestos exposure.

Clinical, epidemiological, and pathological studies have demonstrated that asbestosis plays a major role in the etiology of mesothelioma. The direct exposure of workers in industrialized countries to asbestos fibers and nonoccupational household contact elevate the risk of malignant mesothelioma. An increased risk has been found in certain geographic areas of Turkey due to the presence of asbestos deposits and the use of the material known as "white soil" as an insulation. We present a malignant mesothelioma case from rural eastern Turkey with a history of asbestos exposure from using "white soil". We review the epidemiological aspects of asbestos as they relate to mesothelioma.

Helicobacter pylori and intestinal metaplasia.

Gastric carcinoma of the intestinal type is assumed to develop from precancerous gastric lesions. It is now widely accepted that Helicobacter pylori (HP) infection causes chronic gastritis and, after a period of time, intestinal metaplasia (IM). It was suggested that these gastric lesions may evolve into gastric carcinoma after a lengthy latency period. HP seropositivity is high in Turkey at early ages. This may explain the high incidence of gastric carcinoma in this geographic region. In this study, we examine the relationship between HP and IM in endoscopic gastric biopsy specimens. We examined 840 biopsies taken from 210 patients. HP positivity and the presence of IM were examined in these specimens by histopathologic methods. HP positivity was also determined by CLO testing. HP was positive in 156 of the 210 patients examined (74.3%). The distribution of HP seropositivity did not differ between age groups (p > 0.05). IM was present in 101 patients in the entire study group (48%). Among the 156 HP-positive patients, the rate of IM was 44.8% (n = 70). The rate of IM among the 54 HP-negative patients was 57.4% (n = 31), which was not statistically significant (p > 0.05). IM positivity has been shown to increase in older age, which was statistically significant (p < 0.001). We were not able to show a relationship between HP seropositivity and IM. Increased HP seropositivity at an early age is a common risk factor in our population. We must consider other factors that may contribute to the increased rate of IM in older age groups.

Subtypes of intestinal metaplasia and their relationship to Helicobacter pylori.

The presence of incomplete colonic type of intestinal metaplasia (IM) is regarded as a risk factor for gastric carcinoma. In this study, we attempted to classify the subtypes of IM in our patients and examine their relationship to Helicobacter pylori (HP). Gastric biopsies were obtained from 210 patients. The HP positivity and the presence and type of IM were determined by histopathologic methods. HP positivity was also tested by the CLO test. The subtypes of IM were classified according to Ming's classification. IM was present in 101 of 210 patients (48%). Complete type intestinal metaplasia was present in 72 of 101 patients (71.3%), incomplete type IM was seen in 29 of 101 patients (28.7%), and incomplete colonic type (Type IIc) was found in 7 of 101 patients (6.9%). No significant relationship was found between subtypes of IM and HP positivity (p > 0.05). Although our patient group is small, our findings suggest that the carcinogenity of HP is mostly related to its own mutagenic activity as well as the mutagenic activity of the inflammatory cells present in response to HP rather than to its supposed effect on precancerous gastric lesions.

Second primary cancer due to radiotherapy and chemotherapy.

Cancer patients are treated successfully with chemotherapy, radiotherapy, or a combination of both. However, many agents used in cancer chemotherapy as well as ionizing radiation are known carcinogens. The long survival of cancer patients treated successfully for their primary cancer made possible the observations of late effects of radiotherapy and chemotherapy and, in particular, the occurrence of second primary cancers. In this report we review the cases of five patients with second primary malignancies and wish to emphasize the importance of a thorough follow-up of patients treated successfully for and possibly cured of a primary cancer.

Successful treatment of cranial metastases of extrapulmonary small cell carcinoma with chemotherapy alone.

Extrapulmonary small cell carcinoma (EPSCC) is a distinct clinical and pathological entity other than small cell carcinoma of the lung. We present a case with EPSCC, with neurologic impairment due to brain metastases at initial diagnosis, which showed a complete response to combination chemotherapy. A 55-year-old male patient was first admitted with a mass of 6 x 6 cm in diameter in the right cervical region. The diagnosis of small cell carcinoma was entertained with immunohistopathologic and light microscopic findings. During the period of investigation the tumor showed rapid progression and the patient had neurologic dysfunction with right hemiparesia, and papilla oedema in fundoscopy. Cranial CT showed supratentorial multiple cranial metastases and peritumoral oedema. Since the patient refused radiotherapy, combination chemotherapy was started (Etoposide 100 mg/sq m i.v., days 1,3,5 and cisplatin 80 mg/sq m i.v., day 1). A fast response to the chemotherapy was observed with rapid disappearance of the cervical mass. Following six cycles of the chemotherapy the patient recovered fully and all the lesions disappeared with CT.

Primary neuroendocrine small cell carcinoma of the breast.

A 60-year-old Turkish woman presented with a left breast mass, which was considered for neoadjuvant chemotherapy. By the end of the treatment cycles, the tumor had decreased in size, and the patient underwent modified radical mastectomy with axillary lymph node dissection. Pathologic examination of the tumor revealed a small cell carcinoma with neuroendocrine features confirmed by immunohistochemical stains. Multiple axillary lymph nodes were involved by metastatic small cell carcinoma carrying the same morphologic characteristics noted in the primary breast tumor. We hereby present this case as a primary neuroendocrine small cell carcinoma of the breast. This entity occurs very rarely in the breast, and fewer than a dozen cases have been reported in the literature. Extrapulmonary small cell carcinoma of the breast is reportedly a very aggressive tumor for which no consensus for treatment has yet been drawn.

99mTc-MIBI scintigraphy in untreated stage III multiple myeloma: comparison with X-ray skeletal survey and bone scintigraphy.

Technetium-99m 2-methoxyisobutylisonitrile (99mTc-MIBI) is a lipophilic agent that has been proposed as a useful tracer for the detection of disease sites in patients with multiple myeloma (MM). We performed a prospective study to determine the potential of 99mTc-MIBI imaging for the evaluation of the extent of primary disease in patients with advanced stage MM, compared with skeletal survey and bone scintigraphy. Twenty patients with advanced stage MM at initial diagnosis underwent whole-body 99mTc-MIBI imaging, together with contemporaneous skeletal survey and bone scintigraphy. The findings of 99mTc-MIBI imaging were correlated with the results of skeletal survey and bone scan. All 99mTc-MIBI scans were positive for the presence of active MM, whereas skeletal surveys were positive in 18 patients (90%) with osteolytic lesions. Bone scintigraphy demonstrated MM in only 15 patients (75%). In two patients with no detectable lesions on skeletal survey, 99mTc-MIBI imaging revealed uptake in the spine, corresponding to the abnormalities seen on magnetic resonance imaging (MRI). With respect to the localization of bone lesions, 99mTc-MIBI imaging was superior to bone scintigraphy in 15 patients (75%) and had concordant results with bone scintigraphy in four (20%). 99mTc-MIBI imaging is a very sensitive imaging modality for the identification of the extent of disease in patients with advanced MM. It is clearly superior to bone scintigraphy and complements the results of skeletal survey by finding additional disease sites. Hence, in active MM patients, 99mTc-MIBI imaging has the potential to detect bone marrow disease that cannot be detected by skeletal survey and bone scintigraphy.

A case of primary spinal intramedullary lymphoma.

A 41-year-old male presented to our clinic with a 1-month history of left hemiparesis. He had marked left arm weakness. The diagnostic work-up revealed an intramedullary mass at spinal level C2-4. Laminectomies were performed at C2-3-4 and the tumor was subtotally resected. Histological examination identified the mass as a non-Hodgkin's diffuse B-cell lymphoma. The patient was treated with corticosteroids, chemotherapy, and adjuvant radiotherapy. The residual tumor tissue had completely disappeared by 6 months of follow-up; however, the patient presented with intraventricular metastasis at 11 months postsurgery.

The immunohistochemical expression of c-Met is an independent predictor of survival in patients with glioblastoma multiforme.

BACKGROUND AND AIMS: Because the outcome of glioblastoma multiforme (GBM) remains dismal, there is an urgent need for a better molecular characterization of this malignancy. The aim of this prospective study was to investigate the prognostic impact of the expression of c-mesenchymal-epithelial transition (c-Met) a receptor tyrosine kinase implicated in expression growth, survival, motility/migration, and invasion in GMB patients managed according to the established diagnostic and therapeutic protocols. METHODS: Between May 2003 and March 2011, a total of 69 patients (33 males and 36 females; mean age: 52.2 ± 12.9 years, age range: 23-81 years) referred to our Department for the surgical removal of GBM were evaluated immunohistochemically for c-Met expression. Progression-free survival (PFS) and overall survival (OS) served as the main outcome measures. RESULTS: Compared with c-Met- subjects (n = 38), c-Met+ subjects (n = 31) had both a significantly lower OS (15.3 ± 2.3 vs. 22.6 ± 2.5 months, respectively, p < 0.01) and PFS (12.3 ± 2.1 vs. 19.1 ± 2.6 months, respectively, p < 0.05). After allowance for potential confounders, multivariate Cox regression analysis identified c-Met+ as an independent predictor of both OS (hazard ratio = 1.7; 95 % confidence interval = 1.2-1.9, p < 0.01) and PFS (hazard ratio = 1.6; 95 % confidence interval = 1.1-2.3, p < 0.05). CONCLUSIONS: Our findings suggest that c-Met immunohistochemical expression is an independent predictor of outcomes in patients with GBM treated by standard of care.