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BACKGROUND: There is limited data on the role of art therapy used in cancer patients. We wanted to test the effect of painting art therapy provided by a dedicated professional painting artist on quality of life and anxiety and depression levels in patients having chemotherapy. METHODS: Cancer patients having chemotherapy in the day unit of a medical oncology department of a university hospital were offered to take part in a painting art therapy program (PATP). This program consisted of a professional painting artist facilitating and helping patients to perform painting during their chemotherapy sessions while they were in the day unit, as well as supplying them painting material for home practice. The changes in quality of life domains of EORTC-QLQ-C30 questionnaire and in Hospital Anxiety and Depression Scores (HADS) were assessed before and after the PATP. These results were contrasted with a reference group of cancer patients on chemotherapy but not taking part in the PATP. In order to adjust for multiple comparisons of quality of life parameters between patient groups, we utilized the Bonferroni correction. RESULTS: A total of 48 patients, of which 26 patients did and 22 did not have prior exposure to PATP, were enrolled in the PATP. A control group of 24 patients who did not have any PATP activity during the study period also took part in the study. With PATP, there was significant improvement in global quality of life (F=7.87, P=0.001), and depression scores (F=7.80, P=0.001). CONCLUSIONS: To our knowledge, this is the largest comparative PATP experience in cancer patients on chemotherapy and show that PATP is feasible in the clinics. Our results confirm that art therapy in the form of painting improves quality of life and depression in cancer patients having chemotherapy. This effect was more pronounced in patients without any previous experience of PATP.

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CONTEXT: Introduction of trastuzumab, a recombinant monoclonal antibody against the extracellular domain of HER-2, is a cornerstone in the treatment of HER-2+ breast carcinoma. However, many cancers that have an initial response to trastuzumab will progress some time later. After progression on trastuzumab-based first-line treatment, there are several options. Although TDM-1 (Trastuzumab emtansine) has prolonged progression-free survival (PFS) and overall survival in patients previously treated with trastuzumab and taxane, it is still not available in Turkey. Patients may be switched to lapatinib (an oral tyrosine kinase inhibitor targeting both HER-1 and HER-2), or they may re-challenge with trastuzumab. There is no clear definition of the patients who should be switched to lapatinib. AIM: In this study, we investigated the factors predicting the efficacy of lapatinib. SUBJECTS AND METHODS: Totally, 94 patients treated with lapatinib for metastatic breast carcinoma was included in our study. Retrospective data including pathology, treatments and treatment results, metastatic sites, and laboratory tests were collected. RESULTS: Progression-free survival was 9.1 months. Histologic subtypes other than invasive ductal carcinoma and liver metastasis were inversely related with PFS. Overall survival was 22.1 months, and patients with histologic subtypes other than invasive ductal carcinoma and who progress with brain metastasis had a worse prognosis. CONCLUSION: Clinicians should give attention to histologic subtype and metastatic sites when choosing patients for lapatinib treatment.

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OBJECTIVE: We present our data comparing retrospectively the efficacy of abiraterone and cabazitaxel in patients who progress after docetaxel treatment. PATIENTS AND METHODS: The study included 56 patients diagnosed with hormone-refractory metastatic prostate cancer who were previously treated with abiraterone therapy at four oncology centers in Turkey. RESULTS: With abiraterone, the patients had a median progression-free survival (PFS) of 5.9 months (95% confidence interval (CI) for hazard ratio (HR) (4.4-7.4)) and an overall survival of 13.4 months (95% CI for HR (5.5-21.3)). When we compared the disease-free survival (DFS) of reference patients treated with cabazitaxel as a second-line treatment with those receiving second-line abiraterone therapy, there was no significant difference. (PFS = 5.9 months with cabazitaxel vs. 6.7 months with abiraterone, P = 0.213). CONCLUSION: This study has shown that in our experience abiraterone acetate is an effective agent in metastatic castration-resistant prostate cancer (mCRPC) regardless of the line of treatment.

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PURPOSE: There is clinical need to predict risk of febrile neutropenia before a specific cycle of chemotherapy in cancer patients. METHODS: Data on 3882 chemotherapy cycles in 1089 consecutive patients with lung, breast, and colon cancer from four teaching hospitals were used to construct a predictive model for febrile neutropenia. A final nomogram derived from the multivariate predictive model was prospectively confirmed in a second cohort of 960 consecutive cases and 1444 cycles. RESULTS: The following factors were used to construct the nomogram: previous history of febrile neutropenia, pre-cycle lymphocyte count, type of cancer, cycle of current chemotherapy, and patient age. The predictive model had a concordance index of 0.95 (95 % confidence interval (CI) = 0.91-0.99) in the derivation cohort and 0.85 (95 % CI = 0.80-0.91) in the external validation cohort. A threshold of 15 % for the risk of febrile neutropenia in the derivation cohort was associated with a sensitivity of 0.76 and specificity of 0.98. These figures were 1.00 and 0.49 in the validation cohort if a risk threshold of 50 % was chosen. CONCLUSIONS: This nomogram is helpful in the prediction of febrile neutropenia after chemotherapy in patients with lung, breast, and colon cancer. Usage of this nomogram may help decrease the morbidity and mortality associated with febrile neutropenia and deserves further validation.

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PURPOSE: A number of studies have been carried out, showing that the risk for breast carcinoma is decreased in those using non-steroidal anti-inflammatory drugs (NSAIDs). Increased cyclooxygenase-2 (COX-2) level is considered as a factor indicating poor prognosis and responsible for angiogenesis, increased cellular proliferation, apoptotic defect and aromatase enzyme induction. For this reason the level of COX-2 might have a prognostic and predictive value in breast cancer as well. This question has become the basis of the present study. METHODS: Eighty-eight female patients with early stage breast cancer being under adjuvant anthracycline based chemotherapy were prospectively recruited. The patient age, body weight, menopausal status, tumor size and grade as well as axillary lymph node involvement were recorded. Routine pathological examination was performed, and COX-2, CerbB2 (HER2), estrogen (ER) and progesterone receptors (PR) levels in breast cancer tissue were determined immunohistochemically. RESULTS: Multivariate analysis confirmed the independent predictive value of both menopausal status and ER expression for overall survival (OS) (p=0.009, HR=1.92, and p=0.014, HR=0.20, respectively). A negative correlation was observed between COX-2 levels and the levels of ER and PR (p=0.006, R= -0.303, and p=0.004, R=-0.312, respectively) whereas no significant correlation was observed concerning CerbB2. No statistically significant correlation was determined between COX-2 levels and the disease-free (DFS) and OS rates. CONCLUSION: Further studies investigating the role of COX- 2 levels in breast cancer progression are needed.

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OBJECTIVES: We aimed to analyze the predictors of outcome in metastatic germ cell cancer (MGCC) patients treated with High-dose Chemotherapy (HDC) and stem cell rescue. BACKGROUND: Various prognostic factors have been suggested in the treatment of metastatic germ cell cancer. However, there is no comprehensive evaluation of independent prognostic factors for the efficacy of HDC in published patient cohorts. METHODS: Thirty-two published patient cohorts with MGCC (encompassing 2176 patients; 510 patients treated upfront and 1666 at relapse) were identified from PUBMED and Cochrane Registry of Clinical Trials. Weighted Regression Analyses of these trials were conducted to define prognosticators. RESULTS: Independent correlates of overall survival (OAS) when all trials were considered were line of chemotherapy index, an indicator of line of HDC utilization (1st line: 71% vs 2nd or higher line: 40%, p < 0.001), and number of HDC cycles administered (1 cycle: 43%, 1 to 2 cycles: 43%, 2 or more cycles: 64%, p = 0.021). In cohorts having HDC for relapsed disease, lower line of chemotherapy index again (p = 0.004), and higher median age (p = 0.023) were independently associated with better OAS. In trials utilizing upfront HDC, higher number of chemotherapeutics in the HDC regimen was marginally linked with improved OAS (p = 0.047). CONCLUSION: The efficacy of various forms of HDC in MGCC patients with diverse prognostic factors may vary both as an initial or salvage therapy. Clinicians need to be aware of these factors for optimal patient selection for HDC in MGCC (Tab. 3, Fig. 2, Ref. 54).

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PURPOSE: Induction chemotherapy before radiotherapy, although inferior to concomitant chemoradiotherapy, is still used in clinical practice, and improves survival compared to radiotherapy alone in unresectable non-small cell lung cancer (NSCLC). In this setting, we assessed the predictors of benefit from neoadjuvant chemotherapy before radiotherapy. METHODS: Searches were made for randomized clinical trials (RCTs) that compared neoadjuvant chemotherapy with no treatment, administered before definitive radiotherapy. Relative risk (RR) was employed to define the risk of death at 2 and 3 years. Additionally, meta-regression analysis was conducted to explain heterogeneity. RESULTS: Thirteen RCTs to date, encompassing 2776 patients, were identified. In this updated meta-analysis, neoadjuvant chemotherapy significantly reduced the risk of death, both at 2 and 3 years (RR = 0.91 and 0.94, respectively, both p < 0.001). Additionally, time to radiotherapy was inversely associated with the benefit from neoadjuvant chemotherapy at 2 (t = 2.20, p = 0.050) and 3 years (t = 1.84, p = 0.093). CONCLUSION: This meta-analysis confirms the importance of neoadjuvant chemotherapy before radiotherapy and highlights the importance of shorter time to radiotherapy to maximize NSCLC patients' survival.

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We tested whether zoledronic acid, a biphosphonate with proposed apoptotic activity, augmented the cytotoxicity of cisplatin and/or gemcitabine in A549 lung cancer cell line. This cell line was subjected to different concentrations of the above chemotherapeutic agents and zoledronic acid. Cytotoxicity was assessed by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrasodium bromide) assay. Particularly, zoledronic acid in 100 micromolar (microM) concentration augmented the cytotoxicity by cisplatin 1microg/ml from 25% to 70% (Z=3.22, P=0.0072). A significant portion of cells underwent apoptosis with or without zoledronic acid, but more so with the combination treatment as assessed by an Annexin V-FITC apoptosis detection kit. However, 100microM zoledronic acid showed 50% cytotoxicity on its own, but failed to improve cytotoxicity by Gemcitabine. Thus, we show for the first time in a lung cancer cell line that zoledronic acid bears cytotoxic potential on its own and in conjunction with cisplatin. The clinical potential of this finding should be further studied.

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BACKGROUND: Expressions of various biomarkers in non-small cell lung cancer (NSCLC) have been linked with the prognosis and involvement of mediastinal lymph nodes. METHODS: In this study, we utilized recursive partitioning analysis (RPA) by using P53, c-erb-B2, and P-glycoprotein (PGP) expressions evaluated by immunohistochemistry to estimate retrospectively the likelihood of the occult N2 mediastinal lymph node involvement in patients with operable NSCLC. RESULTS: In univariate tests, immunohistochemical staining of the primary tumor for these 3 markers in 61 patients undergoing surgery revealed no direct relationship with the N2 involvement. However, RPA demonstrated in patients aged <75 and with >/=4 mediastinal lymph nodes removed that, high PGP expression frequency (>/=20%) predicted an increased likelihood of the N2 involvement (46.7%, R(2) = 0.25). Univariate nominal logistic regression analysis revealed that RPA group affiliation, and the number of mediastinal lymph nodes resected (logarithmic transformation) were associated with the metastasis to N2 lymph nodes (chi(2) = 17.59, p = 0.0005, and chi(2) = 2.40, p = 0.0654, respectively). Multivariate analysis confirmed that only RPA group affiliation predicted the N2 involvement (chi(2) = 14.63, p = 0.0022). CONCLUSION: This study shows for the first time that PGP expression of the primary tumor may help to predict the occult N2 mediastinal lymph node involvement in NSCLC. Thus, further research is required to understand whether PGP expression may aid in the decision process for preoperative mediastinoscopy.

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We aimed to form a risk prediction model to assess the probability of intrahospital death in cancer patients at the time of hospitalisation. The medical records and the relevant clinical parameters of cancer patients who died in or who were discharged from a teaching hospital between 1997 and 2000 (n = 334) were reviewed to explore the determinants of intrahospital death, which later were verified prospectively (n = 131). Eastern Cooperative Oncology Group (ECOG) performance status of four, short duration of disease (on a logarithmic scale), emergency admission, low haemoglobin (Hb) value (on a linear scale) and lactate dehydrogenase (LDH) value greater than 378 micro/ml were significantly and independently associated with the risk of intrahospital death. This model had a receiver operating characteristic area of 0.88 in the derivation cohort and 0.82 in the validation cohort. Using readily available clinical parameters, it is possible to devise an accurate and applicable risk prediction model for the hospitalised cancer patients.

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The aim of this study was to evaluate the clinical value of CEA and CA 19-9 in a potential high-risk population of subjects with gastrointestinal complaints. The basic question was whether the determination of these markers, in addition to some other clinical features in this high risk population, could be helpful in diagnosing intraabdominal cancer. Two hundred and two patients with gastrointestinal complaints underwent standard diagnostic procedures and were followed for at least one year. For every patient, CEA and CA 19-9 levels were obtained at the first examination; the evaluating physician was blinded to the marker levels. The determinants of the likelihood of cancer were evaluated by multivariate analysis. Seventeen patients were diagnosed as having intraabdominal cancers. With the presence of melena (RR = 101.63, p = 0.007), nonspecific gastrointestinal symptoms (RR = 12.54, p = 0.026), increasing age (RR = 1.09, p = 0.028) and abnormal CEA (RR = 240.79, p = 0.000), the risk of having cancer increased significantly and independently. The presence of a primary gastric complaint was associated with a lower risk of cancer in this cohort (RR = 0.01, p = 0.04). Markers were not used in the diagnostic workup. In conclusion, in patients presenting with gastrointestinal complaints, the finding of elevated CEA levels may help in the diagnosis of cancer by prompting a more extensive search for intraabdominal cancer.

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The object of this study was to investigate how the information status with regard to diagnosis, in addition to social and clinical factors, influenced emotional functioning and quality of life in a group of cancer patients in Turkey. A consecutive sample of 100 cancer patients being treated for different diagnoses in a tertiary care centre were prospectively evaluated. Data on patient disease and social characteristics, clinical factors, and scores on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) were analysed by logistic regression models. A significant proportion (44%) of the patients did not know of their diagnosis of cancer. The scores on functional and symptom scales and global health status/quality of life according to QLQ-C30 did not differ according to the information given or not given on diagnosis. However, the independently significant determinants of good emotional functioning were male gender (P=0.002), low serum alanine transferase levels (P=0.025), good social functioning (P=0.002), and the absence of constipation (P=0.005). In Turkey, it is still common for cancer patients not to be informed of their diagnosis, and there is a great need to improve this situation. Honest disclosure of the truth does not worsen any dimension of quality of life in general or emotional functioning in particular. On the contrary, those with hepatic dysfunction, female gender, poor social functioning and constipation are the ones at increased risk of poor emotional functioning, and these patients may benefit from psychological screening.

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PURPOSE: This phase 1/2 study was designed to test toxicity and effectiveness of combination chemotherapy and concurrent radiotherapy in the treatment of invasive bladder cancer. METHODS AND MATERIALS: 17 patients with localised muscle-invasive bladder cancer, clinical stages T2-3 N0, M0, were treated with a radiotherapy schedule of 55 Gy in 20 fractions over 4 weeks restricted to the bladder and 3 cycles of concurrent dose-intensive combination chemotherapy consisting of cisplatin 60 mg/m(2), vincristine 2 mg and methotrexate 60 mg/m(2) at 10-day intervals (MOPq10). RESULTS: The complete remission rate following MOPq10 chemotherapy and radiotherapy was 88% as assessed at first cystoscopy with 82% remaining disease-free at 1 year. Risk factor analysis shows those older than 63 years (median) and those with creatinine clearance equal or less than the mean did worse. Actuarial disease-free survival at 2 years was 68% and of the patients treated 4/17 experienced acute G3/4 toxicity. CONCLUSION: This combination regimen was feasible. Its high initial response rate justifies further exploration in a randomised phase 2/3 trial setting with bladder volume and quality of life assessment.

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BACKGROUND: To investigate the correlation among some of the commonly used clinical, pathological factors and newer biological indicators, and to identify the independent predictors of distant metastasis at presentation in patients with breast cancer. METHODS: The pathological specimens from 73 patients with breast cancer were retrospectively evaluated by immunohistochemistry. Data on 13 biological indicators; ER, PR, P53, c-erbB-2, PCNA, CEA, Ki-67, Vimentin, Ulex, Nm23, Cathepsin D, Factor VIII, PS2 together with clinical and pathological factors were collected. RESULTS: A number of highly significant correlations were found among the biological indicators studied. By logistic regression analysis, the predictors of distant metastasis at presentation in univariate tests were tumor diameter, number of lymph nodes involved, P53, c-erbB-2 and grade. In multivariate analysis, tumor diameter (P = 0.042, HR: 1.88(1.02-3.44)), c-erbB-2 expression (P=0.035, HR: 18.20 (1.23-268.66)) and grade (P=0.010, HR: 8.05(1.66-39.00)) retained their significance. CONCLUSION: Our findings show that inactivation of suppressor genes, expression of oncogenes, loss of differentiation, augmentation of proliferative activity, metastatic potential, angiogenesis and hormone receptor status are all interrelated facets of breast cancer pathogenesis. Patients with tumors overexpressing c-erbB-2 or with bigger or higher-grade tumors probably need to be more carefully evaluated for the presence of distant metastasis, thus be better staged, at presentation. This may be a new reason to test c-erbB-2 routinely in all patients with breast cancer in addition to its well-known prognostic and predictive uses.

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In their search for a cure, a significant number of cancer patients use nonproven treatment (NPT) methods. However, little is known about patient and disease characteristics associated with the use of these methods. In this trial, we evaluated the prevalence of and the factors associated with the usage of nonproven cancer remedies in a teaching hospital in Turkey. A self-administered questionnaire was given to 135 cancer patients attending the outpatient clinics of a medical oncology department. Patients' demographic data, their usage of nonproven methods, and possible contributing factors were explored. Our cohort mainly comprised poor patients with only primary school education. Overall, 50% of our patients had used or were using NPT methods. Medicinal herbs (mainly stinging nettle) were the most frequently used remedy. In contrast, such "complementary therapies" as exercise, relaxation, and meditation were not employed. In multivariate analysis, only duration of disease was found to be significantly associated with NPT utilization [P=0.05, relative risk (RR)=1.94]. In addition, patient education level was marginally significant (P=0.07, RR=0.36). Apart from long duration of disease and being better educated, no other clinical, social, economic and cultural factors evaluated were associated with the use of NPT in our group of Turkish patients. Since these treatments are sometimes costly and have questionable efficacy and toxicity, proper scientific trials are needed to clarify whether such methods have a real role in cancer management.

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We analysed survival in relation both to time to treatment and other clinical parameters in the care pathway of non-small cell lung cancer (NSCLC) patients. Medical notes of 189 patients diagnosed with NSCLC presenting in 1998 were reviewed. Median time to treatment in all patients was 48 days. In multivariate analysis, time to treatment did not affect survival in patients with any stage of disease. Referral from general practitioner to chest department (P=0.032, HR=0.08), and absence of use of surgery (P=0.006, HR=30.30) were independently significant predictors of survival in stages 1 and 2 subgroup. In stage 3 patients, absence of laboratory abnormality (P=0.002, HR=0.39), and use of combined treatment (P=0.015, HR=0.17) were independent prognosticators. Lastly, in patients with stage 4 disease, presence of bone and/or liver metastasis (P=0.005, HR=2.65), and absence of use of chemotherapy (P<0.001, HR=6.25) were significantly associated with shorter survival. As survival is dependent on classical prognosticators, but not on time from referral to treatment (hospital delay), expanding resources in oncology (equipment, drugs and personnel), and, perhaps, reducing patient delay, rather than reducing hospital delay alone, could be better strategies to improve NSCLC survival.

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OBJECTIVE: To assess whether the response visible on computed tomography (CT) 21 days after the first course of chemotherapy in patients with nonseminomatous germ cell tumour predicts the need for surgery and whether three-dimensional (3D) reconstruction adds to the diagnostic accuracy. PATIENTS AND METHODS: CT scans from 52 patients treated with cisplatin-based chemotherapy were assessed for tumour shrinkage by measuring the changes of a one-dimensional (1D) measurement of the maximum transverse diameter, and comparing CT scans before, 21 days after the first course and at the end of chemotherapy (1D method). In a subset of patients, using a special formula, the 1D-derived 2D and 3D shrinkage (2Dder and 3Dder) were compared with four other computed or calculated methods (1D, 2D, 3Dcalc, 3Dcomp). RESULTS: At day 21, in 32 of 52 patients (62%) there was < 50% tumour shrinkage using the 1D assessment; 21 of them (66%) needed surgery, compared with none of the 20 patients with > 50% tumour shrinkage by day 21 (chi2 = 22.83, P < 0.001). The 1D method showed significantly less shrinkage than all the other methods but when this was used to derive a 3D shrinkage, assuming the mass to be spherical (3Dder), it was not statistically different from that of 3Dcomp. CONCLUSIONS: The assessment of the response from 1D CT scan estimates 21 days after initiating chemotherapy identifies a subgroup of patients who have a high probability of needing surgery. Although expected to be more accurate, the 3Dcomp estimate of tumour shrinkage was no better than the 3Dder estimate.

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Secondary infections related to neutropenia and functional defects of phagocytes are common consequences in patients treated for cancer. The hematopoietic colony-stimulating factors (CSF) have been introduced into clinical practice as additional supportive measures that can reduce the incidence of infectious complications in patients with cancer and neutropenia. The aim of this study was to determine the role of granuolcyte/macrophage(GM)-CSF and granulocyte(G)-CSF in enhancing in vivo human neutrophil function. A luminol-dependent chemiluminescence assay was developed to evaluate whether the repair in neutropenia accompanies the ability of neutrophils to function. A dose of 5 microg G-CSF kg(-1) day(-1) [recombinant human (rHu) G-CSF; filgrastim] or 250 microg GM-CSF m(-2) day(-1) (rHu GM-CSF; molgramostim) was administered subcutaneously once daily to 12 metastatic cancer patients being treated with different cytotoxic regimens. All injections of CSF were given after the initiation of neutropenia and continued until the occurrence of an absolute neutrophil recovery. rHu GM-CSF and rHu G-CSF, administered once daily at the 250 microg m(-2) day(-1) and 5 microg kg(-1) day(-1) level, were effective in increasing the absolute neutrophil count and neutrophil function, as measured by an automated chemiluminescence system.

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In this study, a third-generation cephalosporin with proposed immunomodulatory properties, cefodizime, was investigated to see if it has any effect on the chemotactic activity of human peritoneal monocyte and polymorphonuclear cell populations ex vivo. Ten continuous ambulatory peritoneal dialysis patients with peritonitis were entered in the study. Monocytes and polymorphonuclear cells were isolated from the patients' peritoneal effluent prior to initiation of any antibiotic therapy. Chemotaxis was measured by the Boyden chamber method before and after 2-hour incubation with cefodizime (200 mg/2L). Following 2-hour incubation with 200 mg/2L cefodizime, monocyte chemotaxis was increased from 36.8 +/- 5.6 microns to 50.2 +/- 6.6 microns (P = 0.0005). A similar increase was observed in polymorphonuclear cells from 42.0 +/- 8.8 microns to 48.7 +/- 10.3 microns (P = 0.02). We conclude that cefodizime acts as a priming agent on peritoneal polymorphonuclear cells, particularly on monocytes, and increases their chemotactic movements.

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