Beyond traditional therapies: clinical significance of complex molecular profiling in patients with advanced solid tumours-results from a Turkish multi-centre study.

OBJECTIVE: The objective of this multi-centre, real-world study was to examine the potential influence of comprehensive molecular profiling on the development of treatment decisions or adjustments for patients with advanced solid malignancies. We then evaluated the impact of these informed choices on patient treatment outcomes. METHODS: The study encompassed 234 adult patients (mean age: 52.7 ± 14.3 years, 54.7% women) who were diagnosed with solid tumours at 21 different medical centres in Turkey. Remarkably, 67.9% of the patients exhibited metastasis at the time of diagnosis. We utilized an OncoDNA (Gosselies, Belgium) platform (OncoDEEP) integrating next-generation sequencing with additional tests to harvest complex molecular profiling data. The results were analyzed in relation with two specific outcomes: (i) the impact on therapeutic decisions, including formulation or modifications, and (ii) associated treatment response. RESULTS: Out of the 228 patients with final molecular profiling results, 118 (50.4%) had their treatment modified, whilst the remaining 110 (47.0%) did not. The response rates were comparable, with 3.9 versus 3.4% for complete response, 13.6 versus 29.3% for partial response, 66.9 versus 51.7% for progressive disease and 15.5 versus 15.5% for stable disease for treatments informed and not informed by complex molecular profiling, respectively (P = 0.16). CONCLUSION: Our real-world findings highlight the significant impact of complex molecular profiling on the treatment decisions made by oncologists for a substantial portion of patients with advanced solid tumours. Regrettably, no significant advantage was detected in terms of treatment response or disease control rates.

Real-world treatment outcomes from nationwide Onco-colon Turkey registry in RAS wild-type patients treated with biologics second-line mCRC.

BACKGROUNDS AND OBJECTIVES: Colorectal cancer is one of the leading causes of mortality both globally and in our country. In Turkey, we conducted a multicenter investigation into the effectiveness of second-line treatments and real-life data for patients with RAS wild-type metastatic colorectal cancer (NCT04757311). MATERIALS AND METHODS: In this retrospective analysis, records from 28 centers were collected, and histopathological, molecular, and clinical characteristics were documented. Patients were categorized into groups based on their second-line biological treatments: anti-EGFR (Group A and Group B, panitumumab and cetuximab) and anti-VEGF (Group C, bevacizumab and aflibercept). They were then compared within these groups. RESULTS: A total of 588 patients with documented RAS wild-type status were evaluated. The median OS was 15.7, 14.3 and 14.7 months in Group A, Group B and Group C, respectively (p = 0.764). The median PFS of the patients in second-line setting that received panitumumab, cetuximab and bevacizumab/aflibercept were 7.8, 6.6 and 7.4 months, respectively (p = 0.848). CONCLUSION: According to the results of our real-life data study, there is no significant difference in efficiency between the combination of biological agent and chemotherapy used in the second-line treatments.

Impact of adding pertuzumab to trastuzumab plus chemotherapy in neoadjuvant treatment of HER2 positive breast cancer patients: a multicenter real-life HER2PATH study.

AIM: To investigate the pathological complete response (pCR) achieved after neoadjuvant therapy with versus without adding pertuzumab (P) to trastuzumab (H) plus neoadjuvant chemotherapy (NCT) in HER2+ breast cancer (BC) patients in a real-life setting. METHODS: A total of 1528 female HER2+ BC patients who received NCT plus H with or without P were included in this retrospective real-life study. Primary endpoint was pCR rate (ypT0/Tis ypN0). Clinicopathological characteristics, event-free survival (EFS) time, and relapse rates were evaluated with respect to HER2 blockade (NCT-H vs. NCT-HP) and pCR. RESULTS: Overall, 62.2% of patients received NCT-H and 37.8% received NCT-HP. NCT-HP was associated with a significantly higher pCR rate (66.4 vs. 56.8%, p < 0.001) and lower relapse (4.5 vs. 12.2%, p < 0.001) in comparison to NCT-H. Patients with pCR had a significantly lower relapse (5.6 vs. 14.9%, p < 0.001) and longer EFS time (mean(SE) 111.2(1.9) vs. 93.9(2.7) months, p < 0.001) compared to patients with non-pCR. Patients in the NCT-HP group were more likely to receive docetaxel (75.0 vs. 40.6%, p < 0.001), while those with pCR were more likely to receive paclitaxel (50.2 vs. 40.7%, p < 0.001) and NCT-HP (41.5 vs. 32.1%, p < 0.001). Hormone receptor status and breast conservation rates were similar in NCT-HP vs. NCT-H groups and in patients with vs. without pCR. Invasive ductal carcinoma (OR, 2.669, 95% CI 1.596 to 4.464, p < 0.001), lower histological grade of the tumor (OR, 4.052, 95% CI 2.446 to 6.713, p < 0.001 for grade 2 and OR, 3.496, 95% CI 2.020 to 6.053, p < 0.001 for grade 3), lower T stage (OR, 1.959, 95% CI 1.411 to 2.720, p < 0.001) and paclitaxel (vs. docetaxel, OR, 1.571, 95% CI 1.127 to 2.190, p = 0.008) significantly predicted the pCR. CONCLUSIONS: This real-life study indicates that adding P to NCT-H enables higher pCR than NCT-H in HER2+ BC, while pCR was associated with lower relapse and better EFS time.

Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): overall survival and updated results of a randomised, double-blind, phase 3 trial.

BACKGROUND: Ramucirumab-an IgG1 vascular endothelial growth factor receptor 2 antagonist-plus docetaxel was previously reported to improve progression-free survival in platinum-refractory, advanced urothelial carcinoma. Here, we report the secondary endpoint of overall survival results for the RANGE trial. METHODS: We did a randomised, double-blind, phase 3 trial in patients with advanced or metastatic urothelial carcinoma who progressed during or after platinum-based chemotherapy. Patients were enrolled from 124 investigative sites (hospitals, clinics, and academic centres) in 23 countries. Previous treatment with one immune checkpoint inhibitor was permitted. Patients were randomly assigned (1:1) using an interactive web response system to receive intravenous ramucirumab 10 mg/kg or placebo 10 mg/kg volume equivalent followed by intravenous docetaxel 75 mg/m2 (60 mg/m2 in Korea, Taiwan, and Japan) on day 1 of a 21-day cycle. Treatment continued until disease progression, unacceptable toxicity, or other discontinuation criteria were met. Randomisation was stratified by geographical region, Eastern Cooperative Oncology Group performance status at baseline, and visceral metastasis. Progression-free survival (the primary endpoint) and overall survival (a key secondary endpoint) were assessed in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT02426125; patient enrolment is complete and the last patient on treatment is being followed up for safety issues. FINDINGS: Between July 20, 2015, and April 4, 2017, 530 patients were randomly allocated to ramucirumab plus docetaxel (n=263) or placebo plus docetaxel (n=267) and comprised the intention-to-treat population. At database lock (March 21, 2018) for the final overall survival analysis, median follow-up was 7·4 months (IQR 3·5-13·9). In our sensitivity analysis of investigator-assessed progression-free survival at the overall survival database lock, median progression-free survival remained significantly improved with ramucirumab compared with placebo (4·1 months [95% CI 3·3-4·8] vs 2·8 months [2·6-2·9]; HR 0·696 [95% CI 0·573-0·845]; p=0·0002). Median overall survival was 9·4 months (95% CI 7·9-11·4) in the ramucirumab group versus 7·9 months (7·0-9·3) in the placebo group (stratified HR 0·887 [95% CI 0·724-1·086]; p=0·25). Grade 3 or worse treatment-related treatment-emergent adverse events in 5% or more of patients and with an incidence more than 2% higher with ramucirumab than with placebo were febrile neutropenia (24 [9%] of 258 patients in the ramucirumab group vs 16 [6%] of 265 patients in the placebo group) and neutropenia (17 [7%] of 258 vs six [2%] of 265). Serious adverse events were similar between groups (112 [43%] of 258 patients in the ramucirumab group vs 107 [40%] of 265 patients in the placebo group). Adverse events related to study treatment and leading to death occurred in eight (3%) patients in the ramucirumab group versus five (2%) patients in the placebo group. INTERPRETATION: Additional follow-up supports that ramucirumab plus docetaxel significantly improves progression-free survival, without a significant improvement in overall survival, for patients with platinum-refractory advanced urothelial carcinoma. Clinically meaningful benefit might be restricted in an unselected population. FUNDING: Eli Lilly and Company.

Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): a randomised, double-blind, phase 3 trial.

BACKGROUND: Few treatments with a distinct mechanism of action are available for patients with platinum-refractory advanced or metastatic urothelial carcinoma. We assessed the efficacy and safety of treatment with docetaxel plus either ramucirumab-a human IgG1 VEGFR-2 antagonist-or placebo in this patient population. METHODS: We did a randomised, double-blind, phase 3 trial in patients with advanced or metastatic urothelial carcinoma who progressed during or after platinum-based chemotherapy. Patients were enrolled from 124 sites in 23 countries. Previous treatment with one immune-checkpoint inhibitor was permitted. Patients were randomised (1:1) using an interactive web response system to receive intravenous docetaxel 75 mg/m2 plus either intravenous ramucirumab 10 mg/kg or matching placebo on day 1 of repeating 21-day cycles, until disease progression or other discontinuation criteria were met. The primary endpoint was investigator-assessed progression-free survival, analysed by intention-to-treat in the first 437 randomised patients. This study is registered with ClinicalTrials.gov, number NCT02426125. FINDINGS: Between July, 2015, and April, 2017, 530 patients were randomly allocated either ramucirumab plus docetaxel (n=263) or placebo plus docetaxel (n=267). Progression-free survival was prolonged significantly in patients allocated ramucirumab plus docetaxel versus placebo plus docetaxel (median 4·07 months [95% CI 2·96-4·47] vs 2·76 months [2·60-2·96]; hazard ratio [HR] 0·757, 95% CI 0·607-0·943; p=0·0118). A blinded independent central analysis was consistent with these results. An objective response was achieved by 53 (24·5%, 95% CI 18·8-30·3) of 216 patients allocated ramucirumab and 31 (14·0%, 9·4-18·6) of 221 assigned placebo. The most frequently reported treatment-emergent adverse events, regardless of causality, in either treatment group (any grade) were fatigue, alopecia, diarrhoea, decreased appetite, and nausea. These events occurred predominantly at grade 1-2 severity. The frequency of grade 3 or worse adverse events was similar for patients allocated ramucirumab and placebo (156 [60%] of 258 vs 163 [62%] of 265 had an adverse event), with no unexpected toxic effects. 63 (24%) of 258 patients allocated ramucirumab and 54 (20%) of 265 assigned placebo had a serious adverse event that was judged by the investigator to be related to treatment. 38 (15%) of 258 patients allocated ramucirumab and 43 (16%) of 265 assigned placebo died on treatment or within 30 days of discontinuation, of which eight (3%) and five (2%) deaths were deemed related to treatment by the investigator. Sepsis was the most common adverse event leading to death on treatment (four [2%] vs none [0%]). One fatal event of neutropenic sepsis was reported in a patient allocated ramucirumab. INTERPRETATION: To the best of our knowledge, ramucirumab plus docetaxel is the first regimen in a phase 3 study to show superior progression-free survival over chemotherapy in patients with platinum-refractory advanced urothelial carcinoma. These data validate inhibition of VEGFR-2 signalling as a potential new therapeutic treatment option for patients with urothelial carcinoma. FUNDING: Eli Lilly and Company.

Treatment preferences in stage IA and IB testicular seminoma: multicenter study of Anatolian Society of Medical Oncology.

BACKGROUND: Approximately 75 % of patients with testicular seminoma present with stage I disease, and the probability of long-term survival approaches 100 %. However, the standard adjuvant treatment for stage I seminoma patients remains controversial, and there is no uniform consensus in the literature. The present study was performed to evaluate treatment preference and outcomes for men with stage I testicular seminoma. MATERIALS AND METHODS: From 1997 to 2013, 282 patients with histologically confirmed stage IA and IB testicular seminoma who underwent orchiectomy were included. The outcomes of three management options and survivals were retrospectively analyzed. The prognostic significance of risk factors for relapse on survival was evaluated by univariate and multivariate analysis; in addition, the factors predicting relapse were also evaluated by logistic regression analysis. RESULTS: Of the 282 patients with stage I seminoma, 130 (46.1) received adjuvant radiotherapy (RT), 80 (28.4 %) were treated with adjuvant carboplatin, while the remaining 72 patients (25.5 %) underwent surveillance. At the time of analysis, the median follow-up period of 38.5 months; relapses were observed in 16 patients (22.3 %) on surveillance, in one patient (1.2 %) treated with adjuvant carboplatin and in ten patients (%7.7) who received adjuvant RT. The 5-year disease-free survival (DFS) rate for patients who underwent surveillance was worse than those of patients treated with adjuvant carboplatin and RT (64.2 vs. 97.7 vs. 91.9 %, respectively; p < 0.001). However, the 5-year overall survival (OS) rate for patients on surveillance was similar compared with the adjuvant treatment groups (100 vs. 92.3 vs. 97.4 %, respectively; p = 0.44). Univariate analysis showed that only the treatment approach (surveillance vs. adjuvant carboplatin vs. adjuvant RT) for DFS (p < 0.001), invasion of the rete testis (p = 0.041) and the presence of relapse (p < 0.001) for OS were important prognostic indicators. Multivariate analysis indicated that the treatment strategy for DFS (p < 0.001, HR 0.34) was an independent prognostic factor. Furthermore, a logistic regression analysis showed that adjuvant treatment was found to be an independent factor for predicting relapse (p = 0.004, odds ratio: 0.39). CONCLUSIONS: Our results indicate that adjuvant treatment with carboplatin or RT is associated with improved DFS compared with surveillance for men with stage I testicular seminoma after orchiectomy. Moreover, the treatment strategy is an important prognostic indicator for DFS and a predictive factor for relapse. Although adjuvant treatment, especially carboplatin, seems to be a suitable treatment for patients with risk factors for relapse, surveillance is still feasible and the preferred management option after radical orchiectomy in men with stage I seminoma. More reliable predictive factors are needed to make treatment decisions.

Cutaneous melanoma in Turkey: analysis of 1157 patients in the Melanoma Turkish Study.

PURPOSE: To develop a large Turkish National Melanoma registry in order to define demographic and clinicopathologic characteristics of patients with melanoma. METHODS: The data was collected from 1635 patients with melanoma through a web-based registry system in 22 centers. Herein we present the results of 1157 patients with cutaneous melanoma. RESULTS: The patient median age was 56.4 years and 646 (55.8%) were males. The commonest subtype was superficial spreading type (357, 30.9%). The commonest primary site was the lower extremities (N=353, 30.5%). The most common Breslow thickness was 1-2 mm (361 patients, 43.5%). Only 104 (12.5%) patients had a thickness <1mm. Among 694 patients with available data, 136 (19.6%) presented with stage 4 disease while the most frequent stage was stage 3, encountered in 393 (56.6% patients). CONCLUSION: Our melanoma registry is the largest in our country providing a snapshot view of cutaneous melanoma and its care. Our patients presented with more advanced stages and they had worse prognosis compared to SEER database.

Outcome of 561 non-metastatic triple negative breast cancer patients: multi-center experience from Turkey.

PURPOSE: Triple-negative breast cancers account for 15% of breast carcinomas and, when present as early-stage disease, they are associated with higher rates of recurrence and early distant metastasis risk when compared to hormone receptor positive and human epidermal growth factor receptor (HER-2) positive breast cancers. In this study we aimed to explore the basic clinicopathological characteristics, prognostic factors and recurrence patterns of non-metastatic triple negative breast cancer patients. METHODS: In this study 561 non-metastatic triple-negative breast cancer female patients admitted to 8 different cancer centers in Turkey between 2000 and 2010 were retrospectively evaluated through their medical records, to identify the basic clinico-pathological characteristics, prognostic factors and recurrence patterns. RESULTS: The ratio of triple-negative breast cancer was 12%. The median age of patients was 48 years, of whom 311 (55.4%) were premenopausal. The majority had early-stage breast cancer at the time of diagnosis (16.8% stage I, 48.1% stage II, 35.1 % stage III) and the most commonly identified variant was invasive ductal carcinoma (84.1%). Grade II and III tumors were 27.1 and 48.5%, respectively. Adjuvant chemotherapy was administered to 90.5% of women and adjuvant radiotherapy to 41.2%. Median patient follow up was 28 months (range 3-290). During the follow up period 134 (23.8%) patients developed metastatic disease. In most of these cases, metastatic sites were bone, soft tissue, and lung. Factors affecting disease free survival (DFS) and overall survival (OS) were age (both p<0.001), lymph node involvement (both p<0.001), lymphovascular invasion (LVI) (p<0.001 and p=0.004, respectively), tumor stage (both p<0.001), adjuvant administration of anthracycline-based chemotherapy (both <0.001) and type of surgery (not significant for DFS but p=0.05 for OS). Three-year DFS and OS were 72.0 and 93.0%, respectively. CONCLUSION: Age, lymph node involvement, LVI, stage, and adjuvant chemotherapy were determined as prognostic factors for DFS and OS. The most common recurrence sites were bone, soft tissue and the lung. Further prospective randomised trials are needed to confirm the prognostic and predictive factors identified in this study.

Results of adjuvant FOLFOX regimens in stage III colorectal cancer patients: retrospective analysis of 667 patients.

OBJECTIVE: The aim of this study was to assess the use of 5-fluorouracil (5-FU), leucovorin and oxaliplatin (FOLFOX) regimens in clinical practice according to their efficacy and toxicity. METHODS: Patients who received oxaliplatin-containing regimens after curative resection for colorectal carcinoma from 10 different oncology centers between May 2004 and December 2009 were included in the study. All patients were treated with FOLFOX regimens. Patients with rectal carcinoma were also treated with chemoradiotherapy with 5-FU after 2 cycles of a FOLFOX regimen. RESULTS: The median age of the patients was 56 years (range 17-78). Of the total 667 patients, 326 were given FOLFOX-4, 232 were given modified FOLFOX-4 and 109 were given FOLFOX-6. The distribution according to disease stage was 33 patients with stage IIIA colorectal cancer, 382 patients with stage IIIB and 252 patients with stage IIIC. The most common adverse events were neutropenia (54%), nausea (36.9%), neuropathy (38.2%) and anemia (33.1%) for all grades. The median follow-up time was 23 months (range 1-79). Three-year disease-free survival and overall survival were 65 and 85.7%, respectively. CONCLUSION: The different oxaliplatin-containing 5-FU-based adjuvant chemotherapy regimens in patients with stage III colorectal cancer seemed to be at least equal in terms of efficacy regardless of the method of 5-FU administration or oxaliplatin dose.

Advanced Hepatocellular Cancer Treated with Sorafenib and Novel Inflammatory Markers.

OBJECTIVE: Hepatocellular cancer (HCC) is an aggressive tumor with an increasing incidence in recent years. Life expectancy is limited, especially due to limited effective treatments and tumor biology. In this study, we aimed to examine the effect of neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), prognostic nutritional index (PNI) parameters of treatment efficacy of patients using sorafenib in primary systemic therapy, progression-free survival (PFS), and overall survival (OS). MATERIALS AND METHODS: In this study, we retrospectively analyzed 78 patients who used sorafenib as a first-line systemic treatment. NLR, PLR, and PNI values were calculated with the existing formulas. Cut-off values for these markers were determined by performing ROC curve analysis. These values were determined respectively as 2.88, 111.05, and 38.25. Patients were divided into two groups according to this threshold value. OS and PFS values were calculated using a Cox proportional risk model. The effects of markers on OS and PFS were examined based on the cut-off value. RESULTS: The mean PFS was 7.1 (range 1-46) months, and the mean OS was 14.1 (range 1.5-94) months. The pre-treatment decreased NLR (< 2.88) value was prognostic for higher PFS and OS rates. These values were determined respectively as 9.23 ± 1.79 and 3.45 ± 0.32 months for PFS and 21.17 ± 4.53 and 5.32 ± 0.53 months for OS. Pre-treatment decreased PLR (< 111.05) was found to be a positively significant prognostic value for both survival. These values were determined respectively as 7.37 ± 1.43 months and 3.16 ± 0.47 months for PFS and 21.12 ± 5.52 months and 6.16 ± 0.87 months for OS. And also, low PNI (< 38.25) value was prognostic for lower PFS and rates. These values were determined respectively as 7.47 ± 0.59 months and 3.25 ± 0.21 months for PFS and 16.36 ± 4.37 months and 5.15 ± 0.42 for OS. All three parameters were found to be statistically significant (p < 0.05) for both OS and PFS as independent prognostic markers. CONCLUSION: Today, as the standard first-line treatment of HCC has shifted to combinations with immunotherapy (IO), IO transportation is not possible in most countries of the world. However, there are also patients who achieve great survival with only sorafenib. The important point is to identify the biomarkers that predict which patient will benefit better from which treatment. With the markers in our study and a scoring system that can be obtained with these markers, it can be evaluated which patient will be given IO combination and which patient will be given only TKI treatment. We think that such a scoring system can be used to identify suitable patients, especially in countries where, for financial reasons, not every patient can access Immunotherapy. The advantage of these tests is that they are inexpensive, easily calculable and standardized. TRIAL REGISTRATION: Number and date of registration: 2021/2088, 01-06-2021, retrospectively registered.

Clinical Characteristics and Outcomes of Cancer Cases Among Syrian Refugees From Southern Turkey.

Importance: Cancer was a common noncommunicable disease in Syria before the present conflict and is now a major disease burden among 3.6 million Syrian refugees in Turkey. Data to inform health care practice are needed. Objective: To explore sociodemographic characteristics, clinical characteristics, and treatment outcomes of Syrian patients with cancer residing in the southern border provinces of Turkey hosting more than 50% of refugees. Design, Setting, and Participants: This was a retrospective hospital-based cross-sectional study. The study sample consisted of all adult and children Syrian refugees diagnosed and/or treated for cancer between January 1, 2011, and December 31, 2020, in hematology-oncology departments of 8 university hospitals in the Southern province of Turkey. Data were analyzed from May 1, 2022, to September 30, 2022. Main Outcomes and Measures: Demographic characteristics (date of birth, sex, and residence), date of first cancer-related symptom, date and place of diagnosis, disease status at first presentation, treatment modalities, date and status at last hospital visit, and date of death. The International Statistical Classification of Diseases and Related Health Problems, Tenth Revision and International Classification of Childhood Cancers, Third Edition, were used for the classification of cancer. The Surveillance, Epidemiology, and End Results system was applied for staging. The diagnostic interval was defined as the number of days from first symptoms until the diagnosis. Treatment abandonment was documented if the patient did not attend the clinic within 4 weeks of a prescribed appointment throughout the treatment. Results: A total of 1114 Syrian adult and 421 Syrian children with cancer were included. The median age at diagnosis was 48.2 (IQR, 34.2-59.4) years for adults and 5.7 (IQR, 3.1-10.7) years for children. The median diagnostic interval was 66 (IQR, 26.5-114.3) days for adults and 28 (IQR, 14.0-69.0) days for children. Breast cancer (154 [13.8%]), leukemia and multiple myeloma (147 [13.2%]), and lymphoma (141 [12.7%]) were common among adults, and leukemias (180 [42.8%]), lymphomas (66 [15.7%]), and central nervous system neoplasms (40 [9.5%]) were common among children. The median follow-up time was 37.5 (IQR, 32.6-42.3) months for adults and 25.4 (IQR, 20.9-29.9) months for children. The 5-year survival rate was 17.5% in adults and 29.7% in children. Conclusions and Relevance: Despite universal health coverage and investment in the health care system, low survival rates were reported in this study for both adults and children with cancer. These findings suggest that cancer care in refugees requires novel planning within national cancer control programs with global cooperation.

Major and minor salivary gland cancers: A multicenter retrospective study.

BACKGROUND: Most of the studies on salivary gland cancers are limited for various reasons such as being single-center, small number of patients, including only major or minor SGCs, or only including epidemiological data. METHODS: A total of 37 medical oncology clinics from different regions of Turkey participated in this retrospective-multicenter study. The analyzed data included clinical and demographical features, primary treatment, metastasis localizations, and treatments and includes certain pathologic features. RESULTS: The study included data from a total of 443 SGCs. 56.7% was in major salivary glands and 43.3% was in minor salivary glands. Distant metastasis in the major SGCs was statistically significantly more common than in the minor SGCs, locoregional recurrence was statistically significantly more common in the minor SGCs than in the major SGCs (p = 0.003). CONCLUSIONS: Epidemiological information, metastasis and recurrence patterns, treatment modalities, and survival analysis of the patients over 20 years of follow-up are presented.

Lapatinib plus capecitabine for brain metastases in patients with human epidermal growth factor receptor 2-positive advanced breast cancer: a review of the Anatolian Society of Medical Oncology (ASMO) experience.

BACKGROUND: We investigated the clinical outcome of patients with brain metastases (BMs) from human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) treated with lapatinib and capecitabine (LC). PATIENTS AND METHODS: A total of 203 patients with HER2+ MBC, who had progressed after trastuzumab-containing chemotherapy, were retrospectively evaluated in 11 centers between September 2009 and May 2011. 85 patients who had developed BMs before the initiation of treatment with LC were included. All patients had received prior cranial radiotherapy. All patients were treated with the combination of lapatinib (1,250 mg/day continuously) and capecitabine (2,000 mg/m(2) on days 1-14 of a 21-day cycle). RESULTS: The median follow-up was 10.5 months (range 1-38 months). An overall response rate of 27.1% was achieved, including complete response in 2 (2.4%) and partial response in 21 (24.7%) patients. Median progression-free survival was 7 months (95% confidence interval (CI) 5-9), with a median overall survival of 13 months (95% Cl 9-17). The most common side effects were hand-foot syndrome (58.8%), nausea (55.3%), fatigue (48.9%), anorexia (45.9%), rash (36.5%), and diarrhea (35.4%). Grade 3-4 toxicities were hand-foot syndrome (9.4%), diarrhea (8.3%), fatigue (5.9%), and rash (4.7%). There were no symptomatic cardiac events. CONCLUSION: LC combination therapy was effective and well-tolerated in patients with HER2+ MBC with BMs, who had progressive disease after trastuzumab-containing therapy.

Zoledronic acid and atrial fibrillation in cancer patients.

BACKGROUND AND PURPOSE: Treatment with a bisphosphonate was found to be associated with a significantly increased risk for atrial fibrillation (AF) in a few studies. A recent study showed that once-yearly infusions of intravenous zoledronic acid (ZA) significantly increased the risk of serious AF in postmenopausal women with osteoporosis. This study was conducted to determine the frequency of atrial fibrillation among cancer patients receiving the standard treatment of ZA. METHODS: Patients with bone metastases who presented to our outpatient clinic for any reason (routine control, chemotherapy, or ZA administration) were included in the study. All patients had been receiving 4 mg ZA at 4-week intervals, with each dose administered over 15 min. A short survey was completed and standard 12-lead ECG recordings were obtained. RESULTS: One hundred and twenty-four cancer patients with documented bone metastases were evaluated. Mean age of the patients was 55 ± 13.0 years, 60% of the patients were female. Forty-one percent of the patients had breast cancer, 18% had non-small cell lung cancer, and the remainder had other solid tumors. Mean duration of ZA administration was 13.4 ± 15.0 months. Mean total cumulative dose was 54 ± 15.0 mg per patient. Sixty patients (48%) had previously been treated with anthracycline-containing regimens, and 37 (30%) had received chest radiotherapy that might affect the heart. Twenty-three percent of the patients had hypertension, 10% had diabetes mellitus, 3.7% had myocardial infarction history, 1.9% had congestive heart failure, and 1% had valvular disease; 10.5% were current smokers and 32% ex-smokers. On ECG evaluation, we observed normal sinus rhythm in 58%, sinus tachycardia in 15%, sinus bradicardia in 3.2%, and ventricular extrasystole in 5.7% of the patients. There was no AF in any of the cases. CONCLUSIONS: There was no increase in the risk of AF frequency in cancer patients who were treated with intravenous ZA, although most of the patients had additional risk factors including previous treatment with cardiotoxic agents or with chest radiotherapy. We believe that the risk of AF is negligible in this patient population and does not affect treatment decisions.

Acute sunitinib neurotoxicity.

Sunitinib malate is a multitargeted oral tyrosine kinase inhibitor (TKI) which is used in treatment of metastatic renal cell carcinoma with side effects such as diarrhea, mucositis, asthenia and myelosuppression. Serious toxicity associated with sunitinib is a rare situation. However; there are few cases reported in the literature. As a result of the inhibition that is caused by sunitinib malate agent at the receptor level, vascular endothelial growth factor (VEGF) level increases. These increased VEGF levels are considered to having a positive contribution on neurological side effects. Neurotoxicity that is related with the usage of sunitinib malate for two weeks will be presented in this case report.

Is excision repair cross-complementation Group1 expression a biological marker in nasopharynx carcinoma?

OBJECTIVE: To determine the prognostic value of excision repairs cross-complementation group1 (ERCC1) gene in cases with nasopharyngeal carcinoma (NPC) treated with platinum-containing chemotherapy (PCT). SUBJECTS AND METHODS: The present study was included 33 cases in local advanced stage with NPC. ERCC1 expression was evaluated by using immunohistochemical staining in biopsy specimens. We evaluated the relationship between the degree of ERCC1 expression and clinicopathological features, response to therapy, survival rates in cases with NPC, retrospectively. RESULTS: ERCC1 expression was not observed in 5 (15.15%) of all cases. Thirteen (39.9%) cases weakly positive (+1, +2) and 15 (45.5%) cases of all them were rather strongly positive (+3). There was no statistically significant difference between the degree of ERCC1 expression and clinicopathological features, response to treatment, survival rates (P > 0.05) in cases with NPC. CONCLUSIONS: ERCC1 expression has no predictive value for survival in cases locally advanced stage with NPC. Evaluation of ERCC1 expression is not appropriate with a biomarker to detect cases who can benefit from PCT in NPC.

Lower bone mineral density in geriatric patients with monoclonal gammopathy of undetermined significance.

The aim of this study was to investigate the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in a geriatric population in Turkey and compare bone mineral densities and related laboratory parameters of MGUS patients with those who do not have MGUS. Among 1,012 patients enrolled, monoclonal band was detected in serum samples of 22 patients (2.17%), most of which were IgG type. Further tests revealed multiple myeloma and lung carcinoma in two patients. The remaining 20 patients were diagnosed with MGUS (1.97%). The clinical and laboratory parameters of patients with and without MGUS were mostly comparable; however, bone mineral density measurements of patients with MGUS were significantly lower than those without MGUS (p = 0.007). We suggest evaluation of geriatric patients with MGUS for the presence of osteopenia/osteoporosis considering the high frequency observed in this study.

Liver dysfunction after chemotherapy in lymphoma patients infected with hepatitis C.

Reactivation of hepatitis B virus (HBV) infection in asymptomatic hepatitis B surface antigen carriers undergoing chemotherapy or immunosuppressive therapy is a well-documented complication. However, data on the consequence of chemotherapy on the course of hepatitis C virus (HCV) infection in HCV+ patients have been controversial. Here, we review the current knowledge about the complications related to HCV in lymphoma patients receiving chemotherapy/immunosuppressive therapy. Although less frequent than HBV, these complications occur in a subset of patients with mortality rates up to 45%. Therefore, baseline screening for HBV and HCV before initiation of chemotherapy is crucial. High-risk patients having chronic active hepatitis, high baseline HCV viral load, HBV co-infection and receiving cytotoxic drugs, corticosteroids and rituximab (particularly if combined) should be closely monitored for serum transaminase, bilirubin and HCV RNA levels.

Renal safety of zoledronic acid administration beyond 24 months in breast cancer patients with bone metastases.

Zoledronic acid (ZA) delays the onset or reduces the incidence of skeletal complications in breast cancer patients with bone metastases. However, there are few data on the long-term renal safety of ZA. We retrospectively evaluated 43 breast cancer patients with bone metastases who received ZA more than 24 months. The following parameters measured prior to first ZA use and after the last dose of ZA administration were compared: serum creatinine (SCr), blood urea nitrogen (BUN), alkaline phosphatase (ALP), calcium (Ca), and phosphorous (P). Forty-three breast cancer patients with documented bone metastases were evaluated. Median age at the start of treatment was 53 years (range 37-77). Median overall duration of ZA administration was 36 months (25-62). There were no statistically significant differences in the pre- and post-treatment levels of SCr, BUN, Ca and P. However, ALP levels after long-term ZA administration were decreased significantly (P<0.05). More than 24 months of ZA administration did not adversely affect the renal function. ZA can be used safely in breast cancer patients with bone metastases beyond 2 years.

Addition of rituximab to chop does not increase the risk of cardiotoxicity in patients with non-Hodgkin's lymphoma.

BACKGROUND: The addition of rituximab to doxorubicin-containing standard chemotherapy significantly improves response to therapy and reduces the risk of death in B-cell non-Hodgkin's lymphoma (NHL) patients. However, the impact of this approach on doxorubicin-induced cardiotoxicity has not been elucidated. METHODS: Patients who had been planned to receive CHOP or rituximab plus CHOP (R-CHOP) combination chemotherapy with a diagnosis of NHL were included in the study. In all patients, systolic and diastolic parameters were measured by using conventional and pulsed-wave tissue Doppler echocardiography, which is more sensitive than conventional lead-dependent techniques, both before and in the sixth month of therapy. RESULTS: There were 28 (M/F; 14/14) patients on CHOP and 33 (M/F; 16/17) patients on R-CHOP. Median age in CHOP and R-CHOP was 49 and 50 years (P = 0.44), respectively. Cumulative doxorubicin doses were 280 and 286 mg/m(2) on CHOP and R-CHOP (P = 0.65), respectively. None of the patients developed clinically evident congestive heart failure. Parameters of systolic function such as LVEF and FS did not significantly change in any patients. In both arms, tissue Doppler parameters of diastolic function such as lateral E and septal E velocity of mitral annulus decreased significantly after therapy (P < 0.001). However, the decrease in diastolic function was similar in both arms (P > 0.05). Conventional Doppler echocardiography yielded consistent findings. CONCLUSION: Both CHOP and R-CHOP cause diastolic dysfunction in the early period following their administration. The addition of rituximab to CHOP chemotherapy does not significantly increase the risk of doxorubicin-induced cardiotoxicity during this period.