Treatment outcomes and prognostic factors in patients with driver mutant non-small cell lung cancer and de novo brain metastases.

Central nervous system (CNS) metastases can be seen at a rate of 30% in advanced stages for patients with non-small cell lung cancer (NSCLC). Growing evidence indicates the predictive roles of driver gene mutations in the development of brain metastases (BM) in recent years, meaning that oncogene-driven NSCLC have a high incidence of BM at diagnosis. Today, 3rd generation targeted drugs with high intracranial efficacy, which can cross the blood-brain barrier, have made a positive contribution to survival for these patients with an increased propensity to BM. It is important to update the clinical and pathological factors reflected in the survival with real-life data. A multi-center, retrospective database of 306 patients diagnosed with driver mutant NSCLC and initially presented with BM between between November 2008 and September 2022 were analyzed. The median progression-free survival (mPFS) was 12.25 months (95% CI, 10-14.5). While 254 of the patients received tyrosine kinase inhibitor (TKI), 51 patients received chemotherapy as first line treatment. The median intracranial PFS (iPFS) was 18.5 months (95% CI, 14.8-22.2). The median overall survival (OS) was 29 months (95% CI, 25.2-33.0). It was found that having 3 or less BM and absence of extracranial metastases were significantly associated with better mOS and iPFS. The relationship between the size of BM and survival was found to be non-significant. Among patients with advanced NSCLC with de novo BM carrying a driver mutation, long-term progression-free and overall survival can be achieved with the advent of targeted agents with high CNS efficacy with more conservative and localized radiotherapy modalities.

Retrospective comparison of efficacy and safety of CAPOX and FOLFOX regimens as adjuvant treatment in patients with stage III colon cancer.

OBJECTIVE: This study aimed to evaluate the efficacy and safety profile of capecitabine and oxaliplatin (CAPOX) and 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) regimens as adjuvant treatment in patients with stage III colon cancer. METHODS: A total of 243 patients who received CAPOX and FOLFOX chemotherapy between 2014 and 2018 for stage III colon cancer in two centers were retrospectively studied. Among the patients, 106 (43.6%) and 137 (56.4%) were treated using CAPOX and FOLFOX regimens, respectively. Efficacy, treatment-related side effects, and overall survival rates with these two regimens were compared. RESULTS: The rate of disease progression was significantly higher in the presence of moderately/poorly differentiated histology, and KRAS and NRAS mutations. An increased number of metastatic lymph nodes and prolonged time from surgery to chemotherapy significantly increased disease progression. Patients who received CAPOX were significantly older than those who received FOLFOX. Disease progression, metastasis, and mortality rates were significantly higher in the FOLFOX arm than in the CAPOX arm. There was no significant difference in the overall survival rate between the two regimens. CONCLUSION: The CAPOX regimen is preferred in older patients. Disease progression, metastasis, and mortality rates are higher with FOLFOX than with CAPOX.

Primary mesenchymal tumors of the colon: a report of three cases.

Primary mesenchymal tumors of the colon are extremely rare tumors among soft tissue sarcomas. These tumors are more aggressive and have poorer prognosis than adenocarcinoma of the colon. Here, we presented 3 cases of primary mesenchymal tumors of the colon. Their histopathological diagnoses are leiomyosarcoma, pleomorphic liposarcoma, and desmoplastic small round cell tumor, respectively. The rarity of primary mesenchymal tumors of the colon makes it difficult to approach the treatment and predict the prognosis of these rare tumors.

Collagen membrane wrapping around methotrexate-containing calcium-phosphate cement reduces the side effects on soft tissue healing.

OBJECTIVES: This study aims to evaluate whether the collagen membrane (membrane) wrapping around the methotrexate (MTX)-containing calcium-phosphate cement (CPC) reduces the side effects on soft tissue healing. MATERIAL AND METHODS: In 36 rats, femoral bone defects were created and treated in six groups which were CPC only, CPC and membrane wrapping around, CPC containing 2% MTX, CPC containing 2% MTX and membrane wrapping around, CPC containing 5% MTX, CPC containing 5% MTX and membrane wrapping around. RESULTS: Histological examinations revealed a statistically significantly improved healing in the connective tissue samples of the CPC containing 5% MTX group wrapped around by membrane compared to those without membrane (p=0.04). However, this was not seen in other groups. CONCLUSION: Membrane wrapping around the CPC containing MTX reduces the side effect of MTX on cellular proliferation at its highest concentration, particularly. Membrane wrapping may allow administration of higher doses of an anti-neoplastic drug which can be more effective.

Pathologic and clinical characteristics of elderly patients with breast cancer: a retrospective analysis of a multicenter study (Anatolian Society of Medical Oncology).

There is very little information about breast cancer characteristics, treatment choices, and survival among elderly patients. The purpose of this multicenter retrospective study was to examine the clinical, pathologic, and biologic characteristics of 620 breast cancer patients age 70 years or older. Between June 1991 and May 2012, 620 patients with breast cancer, recruited from 16 institutions, were enrolled in the retrospective study. Patients had smaller tumors at diagnosis; only 15% of patients had tumors larger than 5 cm. The number of patients who had no axillary lymph node involvement was 203 (32.7%). Ninety-three patients (15.0%) had metastatic disease at diagnosis. Patients were characterized by a higher fraction of pure lobular carcinomas (75.3%). The tumors of the elderly patients were also more frequently estrogen receptor (ER) positive (75.2%) and progesterone receptor (PR) positive (67.3%). The local and systemic therapies for breast cancer differed according to age. An association between age and overall survival has not been demonstrated in elderly patients with breast cancer. In conclusion, the biologic behavior of older patients with breast cancer differs from younger patients, and older patients receive different treatments.

Is lymph node ratio prognostic factor for survival in elderly patients with node positive breast cancer? The Anatolian Society of Medical Oncology.

UNLABELLED: Several studies have now demonstrated that the lymph node ratio (LNR), as a superior indicator of axillary tumor burden to the number of excised nodes. While, about the prognostic value of LNR on the the survival of elderly patients is limited. The aim of this retrospective multicenter study is to evaluate the prognostic value of lymph node ratio in elderly patients with node positive breast cancer. METHODS: Onehundredeightyfour patient with operable breast cancer, recruited from 17 institutions, were enrolled into the retrospectively study. Eleven potential prognostic variables were chosen for analysis in this study. Univariate and multivariate analyses were conducted to identify prognostic factors associated with survival. RESULT: Among the eleven variables of univariate analysis, four variables were identified to have prognostic significance for Overall survival (OS): pathologic tumor size (T), No. of positive nodes (N), LNR and estrogen receptor-positive (ER). Among the eleven variables of univariate analysis, two variables were identified to have prognostic significance for Disease-free survival (DFS): N and LNR. Multivariate analysis by Cox proportional hazard model showed that T, LNR and ER were considered independent prognostic factors for OS. Furthermore, LNR was considered independent prognostic factors for DFS. CONCLUSION: In conclusion, the LNR was associated with the prognostic importance for DFS and OS in elderly patients who were administered adjuvant treatments.

Clinicopathological features in bilateral breast cancer.

INTRODUCTION AND PURPOSE: The frequency of bilateral breast cancer is 1.4-11.0% among all breast cancers. It can present as synchronous (SC) or metachronous (MC). Data regarding clinical course of bilateral breast cancer are scarce. In this study, we therefore evaluated demographic, pathological and clinical characteristics, treatments and responses in bilateral breast cancer cases; making distinctions between metachronous-synchronous and comparing with historic one-sided data for the same parameters. MATERIALS AND METHODS: One hundred fifty bilateral breast cancer cases from ten different centers between 2000 and 2011 were retrospectively scanned. Age of the cases, family history, menopausal status, pathological features, pathological stages, neoadjuvant, surgery, adjuvant and palliative chemotherapy/radiotherapy were examined in the context of the first and second occurrence and discussed with reference to the literature. RESULTS: Metachronous and synchronous groups showed similar age, menopausal status, tumor type, HER2/neu expression; the family history tumor grade, tumor stage, ER-negativity rate, local and distant metastases rates, surgery, adjuvant chemotherapy application rates were identified as significantly different. Palliative chemotherapy response rate was greater in the metachronous group but median PFS rates did not differ between the groups. CONCLUSION: Although bilateral breast cancer is not frequent, MC breast cancer is different from SC breast cancer by having more advanced grade, stage, less ER expression, more frequent rates of local relapse and distant metastasis and better response to chemotherapy in case of relapse/metastasis.

MDR1 single nucleotide polymorphism C3435T in Turkish patients with non-small-cell lung cancer.

We assessed whether single nucleotide polymorphisms (SNPs) in MDR1 gene C3435T predicted the outcome of platinum-based chemotherapies and survival in our non small cell lung cancer (NSCLC) patients. A total of 79 non-small cell lung cancer patients were enrolled to study. We determined the MDR1 C3435T single nucleotide gene polymorphisms. Median age was 60years: 91.7% male, 8.9% female. We found that CC, CT, TT genotype and T, C allele frequencies in lung cancer patients as 24.1%, 62%, 13.9% and 44.3%, 55.7%, respectively. Patients with CT genotype had a higher response rate (11.4%) than the other genotypes. However, this difference is not statistically significant (p=0.743). Cox regression analysis for overall survival showed that ECOG PS status 0 (HR PS 1 vs. 0, 5.68 p=0.002; HR of PS 2 vs. 0 is 21.579, p=0.001; HR of PS 3 vs. 0 is 35.35, p=0.001), stage ≤II (HR of stage III vs. I+II is 17.77; p=0.016, HR of stage IV vs. I+II is 26.97, p=0.006), and albumin level ≥3g/dl (HR of albumin <3g/dl vs. ≥3g/dl is 2.46, p=0.044) were the most important prognostic factors (also, time to progression was related to these factors). There was no significant association between the genotypes and clinicopathologic parameters; however, good performance status, early stage and ≥3g/dl albumin level were found to be the most important prognostic factors for overall survival and progression-free survival.

Bevacizumab every 4 weeks is as effective as every 2 weeks in combination with biweekly FOLFIRI in metastatic colorectal cancer.

PURPOSE: The efficacy and tolerability of bevacizumab every 2 or 4 weeks using the same dosage in combination with biweekly FOLFIRI were retrospectively evaluated in metastatic colorectal cancer (mCRC) patients in the first-line and second-line therapy. PATIENTS AND METHODS: A total of 332 patients from six centers were evaluated. The patients had received biweekly FOLFIRI in combination with bevacizumab 5 mg/kg every 2 weeks or every 4 weeks schedule for various reasons in individual patients. RESULTS: Approximately 70 % of all patients had 2-week treatment schedule. In the first-line therapy (n = 240), the overall response rate (ORR) was 34.1 % in 2-week and 36.3 % in 4-week groups. Median progression-free survival (PFS) was 8 months (95 %CI, 6.8-9.2) and 9 months (95 %CI, 6.6-11.4) (p = 0.074), and median overall survival (OS) was 22 months (95 %CI, 15.8-28.2) and 20 months (95 %CI, 8.1-31.9) (p = 0.612) in 2- and 4-week groups, respectively. One-year survival rate was 76.2 % for 2-week group and 73.2 % for 4-week group. In the second-line therapy (n = 92), the ORR was similar between the groups (24.5 vs 25.9 % in 2- and 4-week groups, respectively). Median PFS was 6 months (95 %CI, 4.7-7.3) and 11 months (95 %CI, 6.3-15.7) (p = 0.074), and median OS was 15 months (95 %CI, 9.6-20.4) and 17 months (95 %CI, 13.7-20.3) (p = 0.456) for 2-week and for 4-week groups, respectively. One-year survival rate was 61.3 % for 2-week and 71.3 % for 4-week groups. Toxicity profile was similar in 2- and 4-week groups and included neutropenia, febrile neutropenia, nausea and vomiting, diarrhea, mucositis, bleeding, hypertension, thromboembolism and fistulization. CONCLUSION: Bevacizumab 5 mg/kg every 2 weeks or every 4 weeks in combination with biweekly FOLFIRI had similar efficacy and tolerability in mCRC. Because of the retrospective nature of our study, the data should be examined cautiously. However, our study clearly points out the need for determination of optimum biological dosing interval of bevacizumab in well-designed, prospective, randomized trials.

Multicentric study on malignant pleural mesothelioma in Turkey: clinicopathologic and survival characteristics of 282 patients.

Malignant pleural mesothelioma (MPM) is a relatively rare, but aggressive tumor that causes high mortality. The major risk factor involved in the etiology is environmental and occupational exposure to asbestos. The optimal modality of therapy is controversial. The present study retrospectively evaluated the data pertinent to 282 patients who were examined and treated in 11 different medical oncology centers in Turkey. There were 161 males (57.1 %) and 121 females (42.9 %), with a mean age of 56.38 ± 12.07 years. Surgery was used in 74 patients, 21 patients (28.4 %) received only chemotherapy and 28 patients (37.8 %) received chemoradiotherapy after surgery. The median survival in patients who were administered adjuvant therapy after surgery was 24 months, while the median survival in patients who had only surgery was 6 months (p = 0.029). 106 patients were administered pemetrexed-platinum combination and 35 patients were administered gemcitabine-platinum combination as front-line chemotherapy. Median survival, 1- and 2-year survival rates in patients who received platinum analogues and pemetrexed or gemcitabine combinations were found statistically similar (p = 0.15). The median survival for all patients with MPM in our study was 18 months. The main factors influencing the overall survival were stage of the disease (p = 0.020), performance status (p < 0.001), asbestos exposure (p = 0.030) and mesothelioma histological subtypes (p < 0.001). Results of our study suggest that multi-modality treatment regimens consisting of surgery, radiotherapy and chemotherapy prolong overall survival. Survival rates in patients who received combining platinum analogues with pemetrexed or gemcitabine as front-line chemotherapy were found similar.

Primary malignant melanoma of the penis: a case report.

We present the case of a patient with malignant melanoma of the glans penis and urethral meatus, which was found in a 60-year-old man with non-healing ulcerative penile lesion and bilateral clinically palpable inguinal lymphadenopathies at diagnosis. A diagnostic biopsy showed the characteristics of a malignant melanoma. Incisional biopsies from the cutaneous lesions on his glans penis and urethra were performed. Histopathological examination of both specimens showed generally ulceronecrotic surface and numerous atypical melanocytic cells. The diagnosis of giant cell melanoma was made. Two months later, bilateral inguinal lymph nodes dissection was performed. Histopathological examination of both specimens demonstrated malignant melanoma metastasis. Three months after the diagnosis, the patient underwent partial penectomy. High-dose interferon-alpha-2b treatment was started. Early diagnosis is of paramount importance, as the prognosis becomes very poor with an advanced tumor stage.

Risk factors of nasopharyngeal carcinoma in Turkey-an epidemiological survey of the Anatolian Society of Medical Oncology.

BACKGROUND: Nasopharyngeal carcinoma is a rare disease in most parts of the world with a multifactorial etiology involving an interaction of genetic, viral, environmental and dietary risk factors. This is the first epidemiologic study aimed to evaluate the risk factors of nasopharyngeal carcinoma in the Turkish population. METHODS: We conducted a multicentric, retrospective, case-control study using a standardized questionnaire which captured age, sex, occupation, household type, blood group, dietary habits, smoking, alcohol consumption and oral hygiene. The study included 183 cases and 183 healthy controls matched by sex and age. Multiple logistic regression and univariate analysis were employed. RESULTS: The peak age incidence was 40-50 years and the male to female ratio was 2:1. We observed significant associations between elevated nasopharyngeal carcinoma risk and low socioeconomic status, rural household type (OR:3.95, p<0.001), farming (OR:4.24, p<0.001) and smoking (OR:3.15, p<0.001). Consumption of french fries (OR:1.44, p=0.024), fried meat (OR:1.05, p=0.023) and tea (OR:5.55, p<0.001) were associated with elevated risk, while fresh fruit consumption was associated with reduced risk (OR:0.59, p=0.011). An irregular meal pattern was also a risk factor (OR:1.75, p=0.012). There were no significant associations between consumption of grain, diary products, alcohol and nasopharyngeal carcinoma risk (p>0.05); furthermore salty foods had a borderline p value (OR:2.14, p=0.053). Blood type A increased the risk (OR:2.03, p=0.002) while blood type 0 was a protective factor (OR:0.53, p=0.009). Rare habit of teeth brushing (OR:6.17, p<0.001) and ≥ 10 decayed teeth before diagnosis (OR:2.17, p<0.001) increased the risk. CONCLUSIONS: The nasopharyngeal carcinoma risk factors described in the literature are also applicable for the Turkish population. People with type A blood are at risk in Turkey. Salted foods have also a border risk out of the endemic regions. This is the only study showing that poor oral hygiene is a serious risk factor for nasopharyngeal carcinoma.

Cisplatin plus docetaxel combination in the first-line treatment of metastatic non-small cell lung cancer.

AIMS: To evaluate activity and toxicity of cisplatin plus docetaxel combination in the first-line treatment of chemotherapy-naive patients with metastatic non-small cell lung cancer. PATIENTS AND METHODS: Between October 2004 and July 2008, 186 patients with metastatic non-small cell lung cancer treated with first-line cisplatin plus docetaxel were retrospectively evaluated in 7 centers. The chemotherapy schedule consisted of cisplatin, 75 mg/m(2) iv infusion, and docetaxel, 75 mg/m(2) iv infusion on day 1, every 3 weeks. RESULTS: Median age was 56 years (range, 28-75). Eighteen patients (9.7%) were females and 168 (90.3%) were males, with a median ECOG performance status of 1 (range, 0-2). A total of 833 cycles of chemotherapy was administered (median, 4 cycles; range, 1-6). Two patients (1.1%) achieved clinical complete response, 77 patients (41.4%) partial response, and 66 patients (35.5%) stable disease. Median time to disease progression was 6 months (95% CI, 5.54-6.46). Median overall survival was 14.6 months (95% CI, 11.47-17.73). One- and 2-year overall survival was 55.2% and 19.7%, respectively. The most common grade 3-4 hematological toxicities were neutropenia (n = 32, 17.2%) and anemia (n = 4, 2.2%). CONCLUSIONS: The cisplatin plus docetaxel combination was effective and safe in the first-line treatment of patients with metastatic non-small cell lung cancer.

Prognostic value of excision repair cross-complementing gene 1 expression for cisplatin-based chemotherapy in advanced gastric cancer.

BACKGROUND: Association of excision repair cross-complementing gene 1 (ERCC1) expression and treatment response and survival was evaluated in advanced stages of gastric cancer patients who were given different platinum-based chemotherapy. PATIENTS AND METHODS: Forty-one patients with advanced gastric cancer were enrolled into the study from January 2000 to December 2009. ERCC1 expression was evaluated by immunohistochemistry (IHC). RESULTS: Thirteen of the 41 patients (31%) were shown to have ERCC1 positive lesions. Although the clinical benefit from platin based chemotherapy was the same for ERCC1 positive and negative patients, survival times were statistically significantly better in ERCC1 negative gastric cancer patients. CONCLUSION: We suggest that IHC studies for ERCC1 may be useful in prediction of the clinical outcome of advanced gastric cancer patients treated with platin-based chemotherapy.

Triple-negative breast cancer: immunohistochemical correlation with basaloid markers and prognostic value of survivin.

OBJECTIVE: Among the subgroups of breast cancer, basaloid type has the shortest disease-free survival. Survivin is an apoptosis inhibitor and its prognostic and predictive value in breast cancer is under investigation. In this study, we examined the basaloid markers CK5/6, CK14, CK17, and EGFR in triplet-negative patients and evaluated the impact of survivin on survival. MATERIALS AND METHODS: Thirty patients with breast cancer in triplet-negative form admitted to Erciyes University Medical Oncology Department between 2001 and 2005 were included in the study. Median follow up and age were 45 months (range 5-76 months) and 47 years (range 23-76), respectively. Eighteen patients (60%) were premenopausal and 12 (40%) were postmenopausal. In total, 2, 12, and 14 patients had stage I, II, and III disease, respectively. When cytokeratines and survivin were analyzed independently, association between CK5/6 positivity and lymph node involvement was statistically significant (P = 0.014). In 70% of patients, CK5/6 or EGFR was found positive, and positive results were only had statistically significant correlation with age and menopausal status (P = 0.049 and 0.049, respectively). Ten patients (33.3%) totally and nine patients (42.8%) in the basaloid subgroup had positive staining for survivin. Survivin was not correlated with any of the clinical or histopathological features. While correlation between the number of involved lymph nodes, lymphovascular invasion, histopathological grade, and disease-free survival was statistically significant (P = 0.036, 0.002, and 0.035, respectively), this is not valid for CK5/6, EGFR, and survivin. CONCLUSION: CK5/6 or EGFR was accepted as determinants of basaloid breast cancer. The correlation between basaloid form and other histopathological markers did not reveal any significant difference with respect to prognostic and clinical parameters. We were unable to demonstrate the prognostic impact of survivin in patients with basaloid form or triplet-negative breast cancer.