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.

Prevalence of traumatic dental injuries and associated factors among 8 to 12-years-old schoolchildren in Diyarbakir, Turkey.

BACKGROUND AND OBJECTIVES: This study aimed to assess the prevalence of traumatic injuries of the permanent incisors in public primary schoolchildren from 8 to 12 years old in South-Eastern Anatolia, Turkey. Additionally, the relationship between traumatic dental injuries, parents' education level, family income, size of incisal overjet and the presence of anterior open bite were examined. MATERIALS AND METHODS: Data were collected through oral examinations and structured interviews, and included socio-economic indicators. A total of 2907 children of both genders (1498 boys, 1409 girls) were included in the study. The response rate was 97%. RESULTS: The prevalence of dental injuries was 4.6% (n = 135). The highest frequency of trauma in permanent teeth was observed at the age of 12 (8%). Boys experienced more dental injuries than girls, 5.9% and 3.3% (p = 0.001), respectively. The most commonly reported cause of injuries to the permanent incisors was falls (71.8%), followed by collision with objects or people (17.8%). Maxillary central incisors were the most affected by dental injuries (154, 84.6%). The most common crown fracture was in enamel only (67.58%) followed by crown fracture of enamel and dentin (22.52%). CONCLUSION: Socio-economic indicators and parents' level of education were not statistically significantly associated with the occurrence of traumatic dental injuries. Factors associated with increased risk of dental injuries in permanent teeth were age, gender, having an incisal overjet greater than 5mm and anterior open bite.

Phase II study of lapatinib in combination with vinorelbine in patients with HER2 positive recurrent or metastatic breast cancer: a multicentric Turkish Oncology Group (TOG) trial.

BACKGROUND: The aim of this explorative phase II study was to evaluate the activity and safety of lapatinib in combination with intravenous vinorelbine in women with HER2 positive metastatic or recurrent breast cancer. METHODS: Twenty-nine patients were enrolled. The primary objectives were response and clinical benefit (CB) rates, secondary objectives were toxicity, response duration and progression free survival. Patients received 1250 mg oral lapatinib continuously once daily and intravenous vinorelbine 20-25 mg/m(2) on days 1 and 8, every 3 weeks. RESULTS: Although 25 patients were evaluable for response, according to intend to treat analysis of 28 patients; 14% had confirmed partial response (PR) and 36% had stable disease more than 24 weeks with a CB rate of 50%. Sixty four percent of the patients suffered from grade 3-4 hematologic and 18% from grade 3 extra-hematologic toxicities. CONCLUSION: The results of this trial provide evidence to further investigate the potential of this combination for patients unsuitable for trastuzumab or who become refractory to trastuzumab.

Efficacy, safety and prognostic features of resected colon carcinoma treated in "real world" practice: a retrospective cohort-study.

PURPOSE: Treatment outcomes and prognostic features of a specific cancer generally come from prospective randomized studies. It seems reasonable to ask the question whether the results of prospective randomized studies entirely reflect the results of the population treated in "real world" practice. Therefore we performed a retrospective cohort analysis in order to find out the efficacy of adjuvant chemotherapy as well as the prognostic factors of our patient population treated in daily practice, and compared these findings with those defined in the prospective studies. METHODS: Data of patients with high risk stage II and all stage III colon cancers treated with adjuvant chemotherapy were retrospectively analyzed. RESULTS: A total of 190 patients were retrospectively analyzed. The rates of T2, T3, and T4 tumors were 4.2, 77.9, and 17.9%, respectively. Over 35% of the patients had stage II disease. Of the 5- fluorouracil (5-FU)-based chemotherapy group (n=141), 15% had a dose reduction because of toxicity and 73% were given the total planned dose and cycles, whereas these rates were 18.5 and 66% for oxaliplatin+5-FU treated group, respectively (p=0.66 and 0.44, respectively). The 3-year disease-free survival (DFS) and 5-year cancer-specific overall survival (OS) for all patients were 69.4 and 73%, respectively. In multivariate analysis, cancer-specific OS showed significant correlation with T stage (p=0.015) and with perineural invasion (p=0.024). Also patients ≥ 65 years old had significantly lower OS (p= 0.003) CONCLUSION: This study is the fi rst to report the efficacy of adjuvant treatment in a curatively resected Turkish colon carcinoma population treated in "real world" practice. Our study showed that the treatment results and the prognostic parameters of Turkish colon carcinoma patients treated in "real world" practice are not different from those of selected patients treated in randomized prospective studies.

The access rate to diagnosis and treatment modalities in breast cancer patients in Turkey; multicenter observational study.

PURPOSE: To determine the time elapsed between the first notification of the disease and the access to the diagnosis and treatment modalities and the associated factors in female patients with breast cancer in Turkey. METHODS: Data was acquired from a questionnaire involving 535 patients who applied to 14 various oncology clinics in Turkey between 1st and 28th of February 2010. Analyses were performed by the participating clinics and were divided into 3 groups: centers located in metropolitan areas formed group 1 (n=161), those located in Marmara and central Anatolia region formed group 2 (n=189), and centers located in Karadeniz and East-Southeast Anatolia region formed group 3 (n=185). The groups of these centers were formed according to the socioeconomic development of the provinces. RESULTS: The median patient age was 48 years, 56.1% of patients were less than 50 years of age. Eighty-five percent of the patients detected a mass in their breast by self examination and 27% of the patients older than 50 years never had breast imaging until the definite diagnosis was established. The median time elapsed between disease noticed by the patient and application to a health care center was 10 days, between application and biopsy 19 days, between biopsy and surgery 10 days, and between surgery and systemic therapy 31 days. The median time elapsed between patients applying for surgery in groups 1 and 2 centers was 11 and 21 days, respectively (p=0.01). The median time elapsed between biopsy and surgery in groups 1,2 and 3 centers was 14,1.5, and 12 days, respectively (p<0.05). CONCLUSION: A high level of awareness regarding breast cancer in our country is related with the time that is defined as 10 days between disease recognition and medical application. The time elapsed between the application and biopsy, surgery and systemic therapy was longer compared with the corresponding figures in developed countries.

A case of Kikuchi-Fujimoto disease misdiagnosed as Hodgkin's lymphoma: the importance of second opinion.

Kikuchi-Fujimoto disease (KFD), a rare clinicopathological entity, is a benign and self-limiting disease. It was first described in 1972 by Kikuchi and Fujimoto in Japan independently. KFD is prevalent in Asia, although it may be seen in wide geographical areas, including Turkey. It mainly affects young women. Cervical lymphadenopathy is the most prominent sign and should be differentiated from lymphoproliferative, autoimmune, and infectious diseases. We report on a 30-year-old female patient who was referred to our medical oncology unit for chemotherapy and/or radiotherapy with diagnosis of Hodgkin's lymphoma. Ultimately her diagnosis was corrected as KFD after second opinion of the pathology specimens. We herein provide a brief review about KFD and the importance of second opinion of the pathology specimens.

Prolonged interval in prophylactic heparin flushing for maintenance of subcutaneous implanted port care in patients with cancer.

The long-term use of subcutaneous implanted ports for chemotherapy in cancer patients has been associated with the occurrence of thrombosis and infection. In this study, we compared the safety and efficacy of administration of 1000 U of heparin flushes in prolonged interval (every 6 weeks) with standard dose and schedule (500 U every 4 weeks) for port-related infections and thrombosis during periods of non-use. Data were collected retrospectively from patients treated for various cancer types (matched as 2:1 for age, gender, stage of the disease). Patients who had diseases that could cause thrombosis or bleeding in their past medical history, or were taking oral anticoagulants, or had contraindications for heparin usage were excluded. After completing their chemotherapy, 59 patients received prolonged interval, while 30 patients received standard schedule. All patients were followed for at least 1 year. No clinically documented port-related infection or thrombosis has been found in both groups. Also, none of the devices was removed during this time. Prophylactic flushing of central venous ports with 1000 U of heparin in every 6 weeks might be a safe, easy, cheaper, comfortable and effective alternative to standard dose and schedule for preventing thrombosis and infections.

Impact of body mass index on cancer development.

PURPOSE: To determine the impact of body mass index (BMI) on cancer in a hospital-based Turkish population. PATIENTS AND METHODS: The study group consisted of 2015 (1172 females: 423 pre- and 749 postmenopausal; and 843 males) patients with histologically proven cancer who applied to Marmara University Medical School, Medical Oncology Clinic. The control group included 305 healthy caregivers (192 females: 110 pre- and 82 postmenopausal; and 113 males). RESULTS: Mean BMI of the patients with breast, ovarian and cervical carcinoma was significantly higher than that of the healthy female controls (p<0.001, 0.003, <0.001, respectively). Postmenopausal breast cancer patients had significantly higher BMI than postmenopausal female controls (odds ratio [OR] 1.3; 95% confidence interval [CI], 1.06-1.6; p=0.012), while this was not seen in premenopausal patients. When compared with controls obese postmenopausal female patients had 3.26-fold (95% CI 1.54-6.90) increased risk for breast cancer (p=0.002). Mean BMI of lung, stomach, esophagus, pancreas and head and neck carcinoma patients was significantly lower than that of the healthy controls. Female patients with lung and colorectal carcinoma had higher BMI than female controls. CONCLUSION: Elevated BMI might be a risk factor for breast cancer in postmenopausal women. Case-control studies may not show the actual association between BMI and cancers that present with pre-diagnosis weight loss and advanced stage.

Concomitant administration of uracil-tegafur and leucovorin during adjuvant radiotherapy for locally advanced rectal cancer.

PURPOSE: We report the feasibility and toxicity profile, and the impact on local control, disease-free survival and overall survival rates of our study which consisted of postoperative concurrent chemoradiotherapy, followed by adjuvant chemotherapy using uracil-tegafur (UFT)/leukovorin (LV) in locally advanced rectal cancer patients. PATIENTS AND METHODS: Thirty-one patients operated for rectal adenocarcinoma (pT3/4 or N+) were enrolled onto the study. Twenty-three patients were males and 8 females with median age 62 years (range 21-85). Radiotherapy (RT) to the pelvis with conformal technique and individual blocks was delivered within 8 weeks following surgery. Total RT dose was 50.4 Gy and was given in a conventional single fraction of 1.8 Gy per day. Chemotherapy was administered concomitantly and consisted of UFT (300 mg/m(2)/day) and LV (30 mg/day) during RT-days. Following chemoradiotherapy, chemotherapy alone was administered for 4 cycles in the same dose for 28 days every 35 days. RESULTS: No lethal toxicity occurred. All patients completed the scheduled RT. Concurrent chemotherapy continued in 22 (70.9%) patients until the end of RT. Seventeen (54.8%) patients completed the whole concurrent chemoradiotherapy and adjuvant chemotherapy as planned. No grade 3-4 stomatitis/mucositis or haematological toxicities were observed during the whole treatment period. During concomitant therapy grade 1-2 toxicities were: nausea/vomiting 60%, dyspepsia/gastric pain 39%, diarrhea 39% and dysuria 10%, whereas grade 3 nausea and diarrhea occurred in 6% and 19%, respectively. Median follow-up was 22 months. Two-year local control, disease-free survival and overall survival rates were 96.3%, 72.3% and 83.2%, respectively. CONCLUSION: The acute toxicity profile of UFT/LV, local control, disease-free survival and overall survival in the concurrent chemoradiotherapy setting for operated, locally advanced rectal cancer seem comparable with the standard 5-fluorouracil (5-FU)-based therapies.

HPV DNA frequency and subset analysis in human breast cancer patients' normal and tumoral tissue samples.

Viruses are known to be associated with human malignancies, e.g., Epstein-Barr virus, human papillomavirus (HPV) and human T-cell leukemia virus type I. We conducted a prospective study to define the role of HPV in breast cancer. The malignant and normal breast tissue samples of 50 consecutive breast cancer patients were obtained postoperatively. DNA extracted from all tissues was amplified with the polymerase chain reaction using HPV primers. HPV 11, 16, 18, 33 subtypes were searched in HPV-DNA positive samples. Thirty-seven samples (74%) of tumoral breast tissue expressed HPV-DNA, 16 normal breast tissue samples (32%) were positive as well. There was a significant difference in HPV-DNA positivity between normal and tumoral breast tissue samples. HPV 18 was detected in 20 of the HPV-DNA positive tumoral tissue (54.4%) and in 9 of the HPV-DNA positive normal tissue (56.3%). HPV-33 also was detected in 35 (94.6 %) of the HPV-DNA positive tumoral tissue and in 14 (87.5 %) of the HPV-DNA positive normal tissue samples. HPV DNA was significantly associated with breast tumor tissue compared to normal breast tissue. Additional studies looking at HPV and HPV subtypes are needed to clarify the etiological role of the HPV in breast cancer.

Amantadine monotherapy of chronic hepatitis C patients infected with genotype lb.

We aimed to test the efficacy of amantadine in chronic hepatitis C (CHC) patients infected with genotype b. Twenty patients completed treatment with amantadine HCl, 100 mg b.i.d., for 6 months. Non-sustained biochemical improvement was observed without loss of HCV-RNA. We conclude that amantadine monotherapy is not effective in CHC.

Prognostic significance of deletion and over-expression of the p53 gene in epithelial ovarian cancer.

PURPOSE OF INVESTIGATION: To define the deletion or over-expression of p53 genes and their prognostic significance in epithelial ovarian cancers. METHODS: A total of 26 patients with epithelial ovarian cancer, who had undergone second-look laparotomy after primary surgery and six courses of platinum-based chemotherapy were included in the study. Paraffin-embedded archival tissue samples of all cases were examined for deletion and over-expression of p53 gene by FISH and immunohistochemical methods, respectively. The relation between these findings and clinico-pathological prognosticators or survival of the patients were analyzed by the Fisher Exact chi2 test, Cox regression model and life table analysis. RESULTS: p53 gene deletion, related to single or double allele, was determined in all cases with a range of 6% to 75% of the cancer cells. When 40% was accepted as the cut-off ratio for the deletion rate, seven (26.9%) of the cases were observed to have p53 deletion. Although p53 over-expression was defined in 12 (46.1%) patients, four of whom were also accompanied by p53 deletion, there was no relation between the p53 deletion and over-expression (p>0.05). p53 deletion was also not related to any prognostic factors or survival of the patients (p>0.05). However, cases with p53 over-expression had significantly more advanced stage and higher-grade tumors, and shorter median survival (p>0.05-0.01). CONCLUSION: p53 gene mutation determined by over-expression of p53 protein has been suggested as an important prognostic factor for epithelial ovarian cancer, however, it has not always been accompanied by p53 deletion.

Rectodynamic and radiological assessment in modified mainz pouch II cases.

OBJECTIVE: To evaluate the radiologic findings and to measure the pressure changes in a modified sigmoidorectal pouch (Mainz pouch II procedure). METHODS: A total of 26 patients who had a radical cystectomy because of muscle-invasive bladder tumor underwent a Mainz pouch II procedure between 1993 and 1998. The differences from the original definition was a reverse ureteral anastomosis and a detubularized segment at least 30 cm in length. In all cases, sigmoidoscopy was done and sigmoidal pressure and capacity were measured preoperatively and at the 3rd and 6th months postoperatively besides the colon X-rays. The 24-hour pouch pressure changes called 'natural pouch pressure' was measured using a handmade system with a central venous pressure (CVP) manometer at the 3rd month postoperatively. RESULTS: Preoperative colon X-rays showed a passage of opaque substance through the descending colon at an average volume of 150 ml (average sigma capacity), whereas postoperative anteroposterior and oblique pouch X-rays showed no passage up to an average volume of 520 ml (270-650) though the descending colon. The sigmoidal colon pressure that was on average 20 cm H(2)O at the preoperative evaluation was measured as 6 cm H(2)O at the 3rd month and 6.5 cm H(2)O at the 6th months during the postoperative period. 24 hour natural pouch pressure was found to be 8.7 cm H(2)O on average while the pressure was found to be 13.8 cm H(2)O on average when the patient felt abdominal discomfort, in other words the desire to defecat (miction). CONCLUSIONS: A modified sigmoidorectal pouch procedure not only provides a reservoir with a higher capacity and lower pressure without a reflux to the upper urinary tract and descending colon with lower metabolic acidosis problem, but it is also a good alternative diversion procedure that whould be preferable especially in Muslim countries as it does not cause any difficulties in terms of Islamic worship.

The ten-year mortality in Behçet's syndrome.

We surveyed the 10-yr mortality among 152 Behçet's syndrome (BS) patients who had registered at a BS out-patient clinic and compared it to the expected mortality in the general population. Information on mortality was available in 79% of the study group, among whom six patients (all males) had died. The observed mortality of two patients in the 15-24 yr age bracket was significantly above that expected in the general population. BS is a cause of increased mortality in the young male patients