Comparing the efficacy of regorafenib and 5-fluorouracil-based rechallenge chemotherapy in the third-line treatment of metastatic colorectal cancer.

BACKGROUND: The optimal treatment for metastatic colorectal cancer (mCRC) after the second line is still controversial. Regorafenib has been the standard of care in this setting as it improved overall survival (OS) compared to placebo. In real-world practice chemotherapy rechallenge is also a preferred option even though supporting evidence is not enough. We aim to compare the efficacy of regorafenib and 5-fluorouracil-based (5-FU) rechallenge treatment in the third line setting of mCRC. METHODS: In this retrospective multi-institutional trial, mCRC patients from 21 oncology centers who progressed after 2 lines of chemotherapy were analyzed. Patients who were treated with regorafenib or rechallenge therapy in the third-line setting were eligible. Rechallenge chemotherapy was identified as the re-use of the 5-FU based regimen which was administered in one of the previous treatment lines. OS, disease control rate (DCR), progression free survival (PFS) and toxicity were analyzed. RESULTS: Three hundred ninety-four mCRC patients were included in the study. 128 (32.5%) were in the rechallenge, and 266 (67.5%) were in the regorafenib group. Median PFS was 5.82 months in rechallenge and 4 months in regorafenib arms (hazard ratio:1.45,95% CI, p = 0.167). DCR was higher in the rechallenge group than regorafenib (77% vs 49.5%, respectively, p = < 0.001). Median OS after the third-line treatment was 11.99 (95% CI, 9.49-14.49) and 8.08 months (95% CI, 6.88-9.29) for rechallenge and regorafenib groups, respectively (hazard ratio:1.51, 95% CI, p < 0.001). More adverse effects and discontinuation were seen with regorafenib treatment. CONCLUSION: Our study revealed that higher disease control and OS rates were achieved with rechallenge treatment compared to regorafenib, especially in patients who achieved disease control in one of the first two lines of therapy.

Dealing with the gray zones in the management of gastric cancer: The consensus statement of the Istanbul Group.

The geographical location and differences in tumor biology significantly change the management of gastric cancer. The prevalence of gastric cancer ranks fifth and sixth among men and women, respectively, in Turkey. The international guidelines from the Eastern and Western countries fail to manage a considerable amount of inconclusive issues in the management of gastric cancer. The uncertainties lead to significant heterogeneities in clinical practice, lack of homogeneous data collection, and subsequently, diverse outcomes. The physicians who are professionally involved in the management of gastric cancer at two institutions in Istanbul, Turkey, organized a consensus meeting to address current problems and plan feasible, logical, measurable, and collective solutions in their clinical practice for this challenging disease. The evidence-based data and current guidelines were reviewed. The gray zones in the management of gastric cancer were determined in the first session of this consensus meeting. The second session was constructed to discuss, vote, and ratify the ultimate decisions. The identification of the T stage, the esophagogastric area, imaging algorithm for proper staging and follow-up, timing and patient selection for neoadjuvant treatment, and management of advanced and metastatic disease have been accepted as the major issues in the management of gastric cancer. The recommendations are presented with the percentage of supporting votes in the results section with related data.

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.

Epidemiology of colorectal cancer in Turkey: A cross-sectional disease registry study (A Turkish Oncology Group trial).

BACKGROUND/AIMS: This study aimed to determine the epidemiological characteristics of colorectal cancer in Turkey. MATERIALS AND METHODS: In this multicenter, prospective, and cross-sectional registry study, data for 968 patients with colorectal cancer from 21 centers in 7 geographic regions were analyzed. RESULTS: Diagnosis was colon cancer in 662 (68.4%) and rectum cancer in 306 (31.6%) patients. In total, 60.9% of patients was male; mean age was 58.9±12.6 years. Among patients, 15.0% was drinking alcohol, 17.5% was smoking, 1.5% had familial history of polyposis, 15.0% had diabetes mellitus, 1.0% had inflammatory bowel disease. Fruit and vegetable consumption was low (<3 times/week) in 35.5% and red meat consumption was high (≥3 times/week) in 47.4% of the patients. Median time-to diagnosis was 3.0 months and 4.0 months for patients with colon and rectum cancer, respectively. Mean body mass index was >25 in all group of patients. Distal rectum (61.3%) and sigmoid colon (36.8%) were the most common locations of cancer, for rectum and colon respectively. In total, 85.6% of patients were operated; 25.8% had emergency surgery. Low anterior resection rate was 64.2% in rectum cancer. In majority (89.8%) of the patients with rectum cancer who received preoperative treatment, conventional chemo-radiotherapy regimen was given. pTNM staging at diagnosis showed that stage III and IV patients were in majority (35.9% and 29.7%, respectively). CONCLUSION: Colon cancer is more frequent than rectum cancer in Turkey. Colorectal cancer patients are diagnosed at later stages. Most of the cases were operated. Interregional differences for risk factors are worthwhile for evaluation in future trials.

Prognostic value of increased HER2 expression in cancers of pancreas and biliary tree.

Increased HER2 expression has a prognostic, and predictive value in many solid cancer types, predominantly in breast cancer. However the effects of HER2 on survival from cancers of pancreas, gall bladder, cholangiocellular, and ampullary region are not known. In this study, the effects of increased HER2 expression on these types of cancer have been analyzed. Immunohistochemical HER2 staining was performed in 31 (44.9 %) female, and 38 (55.1 %) male patients with a mean age of 65 ± 10 years, and various parameters, mostly survival rates of patients with pancreas (n = 30; 43.5 %), gall bladder (n = 17; 24.6 %), cholangiocellular (n = 12; 17.4 %), and ampullary region (n = 10; 14.5 %) carcinomas were evaluated. Strong (3 +) membranous staining for HER2 was observed in 2 patients with gall bladder cancers (11.76 % of all gall bladder cancers). In 2.90 % of all cases strong membranous staining (2+ or 3+) was observed. Weak (1+) membranous staining was noted in one (3.33 %) pancreatic, and one cholangiocellular (8.33 %) cancer patient, and in none of the ampullary region patient membranous staining for HER2 was observed. Since only scarce number of patients demonstrated membranous staining for HER2, survival analysis was not performed on these patients. Based on cytoplasmic HER2 staining scores, the patients were divided into weakly (0-3 pts; n = 17 patients; 24.66 %), moderate (4-5 pts; n = 22; 31.88 %), and strongly (6-7 pts; n = 30; 43.46 %) stained groups. Patients whose specimens demonstrated borderline statistical significant (p = 0.052) low staining for HER2 had higher survival rates when compared with other cases. Increased HER2 expression has no prognostic, and predictive value in cancers of pancreas, biliary tract, and ampulla vateri. If HER2 will be evaluated in these types of cancer, membranous, as well as cytoplasmic staining properties should be taken into account.

Do medical oncologists and cancer patients care about treatment costs of systemic anticancer therapy?

PURPOSE: The incidence, and thus the economic burden of cancer are increasing rapidly with prolongation of lifespan thanks to newly-developed anticancer drugs. Globally the number of newly diagnosed cases is expected to rise to 21.4 million by the year 2030. In this survey, our purpose was to investigate the level of awareness of oncologists and cancer patients concerning the treatment costs of systemic anticancer therapy. METHODS: To this end questionnaire forms were sent via e-mails to 123 medical oncologists which were responded by 119 (96.7%) of them. RESULTS: The responders (21%) stated that they had been attentive about the treatment costs or informed (9.5%) their patients about treatment costs. Half of the informed patients were desperately surprised when they heard the treatment costs. Half of the physicians thought that informing the patients had positive effects on patients compliance to the treatment. Most (83.5%) of the physicians prescribed drugs not paid back by reimbursement, and 79.3% of them indicated that overall survival was more important in the selection of expensive drugs. Still 30.2% of them indicated that they hadn't known to perform cost-effectiveness analyses. CONCLUSION: Creating awareness about costs of different anticancer treatment modalities in the minds of oncologists and their patients will be beneficial regarding rational use of such treatment modalities. Countries with rapidly growing health expenditures, like ours, should possess and implement country-specific criteria of cost-effectiveness in daily practice which hopefull will lead to more proper use of our medical recources.

Nine weeks versus 1 year adjuvant trastuzumab in patients with early breast cancer: an observational study by the Turkish Oncology Group (TOG).

BACKGROUND: Optimal duration of adjuvant trastuzumab in early breast cancer is an unresolved issue. In this observational study, we compared the outcome of 9 weeks and 1 year adjuvant trastuzumab in early breast cancer patients in Turkey. METHODS: Records of 680 patients with HER2-positive early breast cancer who received adjuvant trastuzumab plus chemotherapy were obtained and patients were followed up to compare the disease-free survival (DFS) outcome of 9 weeks versus 1 year trastuzumab. RESULTS: Nine weeks and 1 year trastuzumab was given to 202 (29.7 %) and 478 (70.3 %) patients, respectively. There was a significantly lower rate of patients with negative lymph nodes in the 9-week trastuzumab group. At median 3 years of follow-up from the date of starting trastuzumab, the DFS rates were 88.6 and 85.6 %, respectively (p = 0.670). When adjusted for all the prognostic factors that were significant on univariate analysis, again there was no significant difference in DFS between the groups (HR 0.675; 95 % CI 0.370-1.231; p = 0.200). Cardiac toxicity defined as a ≥15 % decrease in LVEF was significantly higher in the 1-year trastuzumab group (1.88 % versus none for 1-year and 9-week trastuzumab groups, respectively; p = 0.050). CONCLUSION: The results of this observational study suggest that DFS outcome of 9 weeks of adjuvant trastuzumab may be comparable to 1 year adjuvant trastuzumab: this needs confirmation by randomized trials.

Investigational tests and treatments performed in terminal stage cancer patients in two weeks before death: Turkish oncology group (TOG) study.

Although more palliative care is necessary for terminally ill cancer patients, excess investigational tests, invasive procedures, and treatments are given instead. Between November 2009 and December 2013, six hundred and twenty-four patients with end-stage cancer who were died at inpatient setting evaluated retrospectively. Patients' characteristics, sites of tumor and metastasis, tests and invasive procedures, treatments performed in the last 2 weeks before death were collected from the hospital files and analyzed. Median age of 624 patients was 58 (range 16-96) years. More than half of the patients (370, 59.3%) were men. The most frequent cancer sites were gastrointestinal (GI) system (32.2%), lung (24.0%), and breast (11.1%). Frequent metastatic sites were liver (34.8%), bone (31.5%), lung (23.3%), and/or brain (16.9%). Causes of death were respiratory failure, infections, and/or liver failure in 49.9, 23.9, and 19.4% of patients, respectively. Radiological tests performed in the last 2 weeks before death were ultrasonography, computed tomography, magnetic resonance imaging, bone scan in 25.6, 16.3, 11.4, and 3.8% of patients, respectively. Treatments received were intravenous (i.v) serum infusion, blood transfusion, total parenteral nutrition (TPN), human albumin infusion in 55.9, 44.1, 34.9, and 9.5% of patients, respectively. Invasive procedures such as invasive pain relief, terminal sedation, and chemotherapy performed in 12.6, 4.4, and 10.0% of patients, respectively. Central venous catheter application, paracentesis, thoracentesis, and GI endoscopy were applied in 41.7, 9.8, 5.6, and 3.4% of the patients, respectively. Radiological tests, invasive procedures, TPN, and human albumin transfusion were used excessively in terminal stage cancer patients in our medical oncology inpatient clinics. Invasive pain relief and terminal sedation were still underused in our cancer clinics. There is an urgent need in developing national palliative care program to improve the understanding of end-of-life care in our medical oncology clinics.

Primary extranodal non-Hodgkin's lymphoma: clinicopathological features, survival and treatment outcome in two cancer centers of southern Turkey.

BACKGROUND: The aim of this study was to assess the epidemiological and clinicopathological characteristics of primary extranodal non-Hodgkin's lymphoma (pENL) patients, focusing on treatment and survival outcome. MATERIALS AND METHODS: Between October 2003 and March 2012, 802 patients with non-Hodgkin's lymphoma (NHL) were diagnosed and treated in two different cancer centers of Southern Turkey. RESULTS: pENL, constituted 12.4% (100/802) of all NHL studied during this period. Median age of the patients was 56 years (range 17-87 years) and the male: female distribution was 3:2. Eighty-five of 100 patients (85%) were in stage I/II, 9/100 (9%) in stage III, whereas 6/100 (6%) were in stage IV. Head and neck constituted the most common site (51/100, 51%), followed by gastrointestinal tract (GIL) (37/100, 37%), and cerebrum (CL) (5/100, 5%). Diffuse large B cell lymphoma (DLBCL) was the most common histological type, observed in 53% of patients, followed by marginal zone extranodal lymphoma (13%). Most of patients (76%) received a CHOP containing regimen. Complete remission (CR) were achieved in 71% of patients. The median follow-up duration of all patients was reported as 37.6 months (range, 0.8-165 months). This period was reported as 137.5 months (range, 117.5- 1578.6 months) in gastrointestinal lymphoma (GIL) patients, 119.0 months (range, 91.8-146.1 months) in head and neck lymphoma (HNL) patients, and 18.4 months (range, 12.6-24.1 months) in cerebral lymphoma (CL) patients. CONCLUSIONS: Head and neck, and the gastrointestinal tract were the two most common extranodal sites observed. Histologically DLBC accounted for the majority of cases. Most patients were on earlier stages, had low-low intermediate IPI scores and had a favorable prognosis.

A cross-sectional survey of the diagnosis and management of bone metastasis in breast cancer patients in Turkey.

PURPOSE: This study aimed to report the practice of managing breast cancer with bone metastasis in Turkey and to determine the adherence to the British Association of Surgical Oncology (BASO) guidelines. METHODS: This multicenter, cross-sectional epidemiological survey was conducted in 38 centers across Turkey. Data from 1,026 breast cancer patients with bone metastases (mean age 54.0 ± 11.9 years) were analyzed. RESULTS: Over 30 % of patients had a diagnosis of metastatic breast cancer (stage IV) at the time of primary diagnosis. The imaging modalities used for diagnosing bone metastases were bone scintigraphy (57.8 %), radiography (22.8 %), and bone survey (4.4 %). Tumor markers were detected in 94.9 %, and markers of bone metabolism were measured in 90.4 % of patients. A total of 3.5 % of patients underwent surgery for bone metastasis, 26.4 % underwent palliative chemotherapy (most commonly docetaxel + capecitabine), and 56.5 % endured radiotherapy. Most patients (96 %) also received bisphosphonate. Radiography, bone scintigraphy, and CT were the main imaging tools used for postoperative follow-up of bone metastasis. Our results were >95 % in line with the BASO guidelines for the management of bone metastasis, except that interventional procedures, such as biopsy, were applied less frequently in our survey. CONCLUSIONS: The diagnosis and management practices of breast cancer with bone metastasis in Turkey were generally compatible with international guidelines. However, the awareness and knowledge of physicians on the current guidelines should be increased, and equipment for the appropriate interventional procedures should be provided in every clinic to obtain optimal and standard management of bone metastases.

Lack of prognostic significance of C-erbB-2 expression in low- and high- grade astrocytomas.

BACKGROUND: Astrocytic tumors, the most common primary glial tumors of the central nervous system, are classified from low to high grade according to the degree of anaplasia and presence of necrosis. Despite advances in therapeutic management of high grade astrocytic tumors, prognosis remains poor. In the present study, the frequency and prognostic significance of c-erb-B2 in astrocytic tumors was investigated. MATERIALS AND METHODS: Records of 72 patients with low- and high-grade astrocytic tumors were evaluated. The expression of C-erbB-2 was determined immunohistochemically and intensity was recorded as 0 to 3+. Tumors with weak staining (1+) or no staining (0) were considered Her-2 negative, while tumors with moderate (2+) and strong (3+) staining were considered Her-2 positive. RESULTS: Of the 72 patients, 41 (56.9%) had glioblastoma (GBM), 10 (13.9%) had diffuse astrocytoma, 15 (20.8%) had anaplastic astrocytoma, 6 (8.3%) had pilocytic astrocytoma. C-erbB-2 overexpression was detected in the tumor specimens of 17 patients (23.6%). Six (8.3%) tumors, all GBMs, exhibited strong staining, 2 (2.7%) specimens, both GBMs, exhibited moderate staining, and 9 specimens, 5 of them GBMs (12.5%), exhibited weak staining. No staining was observed in diffuse astrocytoma and pilocytic astrocytoma specimens. Median overall survival of patients with C-erbB-2 negative and C-erbB-2 positive tumors were 30 months (95%CI: 22.5-37.4 months) and 16.9 months (95%CI: 4.3-29.5 months), respectively (p=0.244). CONCLUSIONS: Although there was no difference in survival, C-erbB-2 overexpression was observed only in the GBM subtype.

Impact of Surgery Type on Quality of Life in Breast Cancer Patients.

OBJECTIVE: Breast cancer can lead to alterations in quality of life of the patients. The aim of this study is to evaluate the changes in quality of life of the female patients who had undergone surgical treatment for breast cancer. MATERIALS AND METHODS: A total of 250 female patients (breast-preserving surgery (BPS), n=27, 11%; modified radical mastectomy (MRM), n=194, 77%, and simple mastectomy (SM), n=29; 11%) aged between 28-55 years (47.4±6.4 yrs) were included in the study. Patient information, demographic characteristics, income, and treatment modalities applied were recorded. Validated Turkish versions of EORTC QLQ-C30, and EORTC-BR23 questionnaires were used for all patients. RESULTS: Breast-preserving surgery has a more favorable impact on general well-being, physical role, cognitive, psychological, and social functions, and symptom scale scores. When the identical parameters were taken into consideration, relatively favorable outcomes of BPS on the patients were observed relative to mastectomized patients. Besides, though not statistically significant, BPS has more patient-friendly effects on sexual function and sexual satisfaction in comparison with mastectomy. Patients with advanced stage disease and elder patients had more unfavorable health related quality of life (HRQoL) scores than younger patients, and those in their early stages of breast cancer. CONCLUSION: Quality of life of BPS patients is less adversely affected relative to mastectomized patients. In the decision-making process, quality of life should be taken into consideration.

Contribution of DOG1 expression to the diagnosis of gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract, and the majority contain KIT or PDGFRA-activating mutations. However, up to 10% of GISTs are c-kit-negative. Antibodies with increased sensitivity and specificity for the detection of c-kit-negative GIST cases may be of value, especially because some of these cases may also benefit from tyrosine kinase inhibitor therapy. Hematoxylin and Eosin sections of 33 GISTs were re-examined in order to define histopathological criteria used in risk assessment of these tumors. Immunohistochemistry with a panel of antibodies [c-kit, DOG1 (discovered on GIST 1), CD34, smooth muscle actin (SMA), Desmin, S100 and Ki67] was performed on 5µm-thick paraffin sections of all tumors. Statistical analysis of immunohistochemical studies showed that DOG1 and CD117 were the most sensitive and specific antibodies in the diagnosis of GISTs. Other antibodies were unhelpful in confirming a diagnosis of GIST, but were particularly useful in the differential diagnosis. Reactivity for DOG1 may aid in the diagnosis of GISTs, which fail to express c-kit antigen, and lead to appropriate treatment with imatinib mesylate, an inhibitor of the KIT tyrosine kinase.

Serum levels of cancer biomarkers in diabetic and non-diabetic proteinuric patients: a preliminary study.

BACKGROUND: Cancer biomarkers (CBs) can be used in early detection of several cancers as well as in detection of recurrence and following response to treatment. We aimed to investigate the levels of CBs in proteinuric patients with primary glomerular disease (PGD) and diabetes mellitus, and compare them with healthy controls. METHODS: One hundred and two patients with untreated PGD, 62 proteinuric patients with diabetic nephropathy, and 84 healthy controls were enrolled. Levels of cancer antigen 125 (CA 125), cancer antigen 15-3 (CA 15-3), carcinoembriogenic antigen (CEA), α-fetoprotein (AFP), total prostate specific antigen (TPSA), free prostate specific antigen (FPSA) and carbohydrate antigen 19-9 (CA 19-9) were measured. RESULTS: Compared to healthy controls, levels of CA 125, CA 15-3 and CA 19-9 were higher in patients with PGD and diabetic patients (all p<0.05), while levels of TPSA, FPSA, AFP and CEA were lower (all p<0.05). There was no correlation between levels of cancer biomarkers and serum fibrinogen and serum amyloid A protein levels (all p>0.05). Both urinary protein excretion rate and serum albumin levels were correlated with all CBs (all p<0.05). CONCLUSIONS: CBs levels seem to be changed in different proteinuric patients. This condition should be kept in mind when evaluating CBs levels in proteinuric patients.

Nephrotic syndrome associated with gemcitabine use in a patient with ovarian cancer.

BACKGROUND: Here we present a patient who developed nephrotic syndrome associated with gemcitabine use. CASE REPORT: Gemcitabine therapy was initiated following tumor recurrence in a patient with ovarian cancer, who was previously treated twice with carboplatin and paclitaxel. Radiological findings waned and tumor marker concentrations decreased after gemcitabine treatment. However, edema and ascites development was observed on the fifth treatment cycle. Laboratory results revealed increased blood urea nitrogen and creatinine levels, decreased serum albumin concentrations, and increased 24-hour urinary protein excretion. Renal biopsy findings were compatible with membranous glomerulonephritis. Gemcitabine administration was stopped and the cyclophosphamide and steroid therapy were initiated. The symptoms and findings disappeared after the cessation of gemcitabine and immunosuppressive treatment. CONCLUSIONS: Gemcitabine treatment may be associated with proteinuria to the extent of nephrotic syndrome.