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Background: The Oncotype Dx recurrence score (ODx-RS) guides the adjuvant chemotherapy decision-making process for patients with early-stage hormone receptor-positive, HER-2 receptor-negative breast cancer. This study aimed to evaluate survival and its correlation with ODx-RS in pT1-2, N0-N1mic patients treated with adjuvant therapy based on tumor board decisions., Patients and Methods: Estrogen-positive HER-2 negative early-stage breast cancer patients (pT1-2 N0, N1mic) with known ODx-RS, operated on between 2010 and 2014, were included in this study. The primary aim was to evaluate 5-year disease-free survival (DFS) rates according to ODX-RS., Results: A total of 203 eligible patients were included in the study, with a median age of 48 (range 26-75) and median follow-up of 84 (range 23-138) months. ROC curve analysis for all patients revealed a recurrence cut-off age of 45 years, prompting evaluation by grouping patients as ≤45 years vs. >45 years. No significant difference in five-year DFS rates was observed between the endocrine-only (ET) and chemo-endocrine (CE) groups. However, among the ET group, DFS was higher in patients over 45 years compared to those aged ≤45 years. When stratifying by ODx-RS as 0-17 and ≥18, DFS was significantly higher in the former group within the ET group. However, such differences were not seen in the CE group. In the ET group, an ODx-RS ≥18 and menopausal status were identified as independent factors affecting survival, with only an ODx-RS ≥18 impacting DFS in patients aged ≤45 years. The ROC curve analysis for this subgroup found the ODx-RS cut-off to be 18., Conclusion: This first multicenter Oncotype Dx survival analysis in Turkey demonstrates the importance of Oncotype Dx recurrence score and age in determining treatment strategies for early-stage breast cancer patients. As a different aproach to the literature, our findings suggest that the addition of chemotherapy to endocrine therapy in young patients (≤45 years) with Oncotype Dx recurrence scores of ≥18 improves DFS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ünal, Özmen, Ordu, Pilanci, İlgün, Gökmen, Almuradova, Özdoğan, Güler, Uras, Kara, Demircan, Işık, Alço, Saip, Aydın, Duymaz, Çelebi, Yararbaş, Soybir and Ozmen.)

Objectives: To compare the survival of first- and second-generation tyrosine kinase inhibitors (TKIs) in patients with rare EGFR exon 18 and exon 20 mutation-positive non-small cell lung cancer (NSCLC)., Materials and Methods: We retrospectively evaluated survival characteristics of 125 patients with EGFR exon 18 and exon 20 mutated NSCLC who received erlotinib or afatinib as first line treatment between 2012 and 2021 from 34 oncology centres. Since exon 20 insertion is associated with TKI resistance, these 18 patients were excluded from the study., Results: EGFR exon 18 mutations were seen in 60%, exon 20 mutations in 16%, and complex mutations in 24% of the patients with NSCLC who were evaluated for the study. There were 75 patients in erlotinib treated arm and 50 patients in afatinib arm. Patients treated with erlotinib had progression-free survival time (PFS) of 8.0 months and PFS was 7.0 months in the afatinib arm (p = 0.869), while overall survival time (OS) was 20.0 vs 24.8 months, respectively (p = 0.190). PFS of exon 18 mutated arm was 7.0 months, exon 20 mutated arm was 4.3 months, and complex mutation positive group was 17.3 months, and this was statistically significant (p = 0.036). The longest OS was 32.5 months, seen in the complex mutations group, which was not statistically different than exon 18 and in exon 20 mutated groups (21.0 and 21.2 months, respectively) (p = 0.323)., Conclusion: In this patient group, especially patients with complex mutations are as sensitive to EGFR TKI treatment similar to classical mutations, and in patients with rare exon 18 and exon 20 EGFR mutation both first- and second-generation EGFR-TKIs should be considered, especially as first- and second-line options., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The benefit of breast magnetic resonance imaging (MRI) in breast-conserving surgery (BCS) is unclear. Our study compared breast cancer patients with and without preoperative breast MRI and their long-term oncologic outcomes are reported. A total of 1378 BCS cases with early breast cancer between 1996 and 2017 were reviewed. Patients with carcinoma in situ or neoadjuvant treatment or having breast MRI after tumor excision were excluded. Of 1378 patients, 270 (19.5%) had preoperative MRI. There were no significant differences regarding T and N stage and molecular subtypes between the groups. Surgical margins were significantly wider in the breast MRI group. Five-year overall survival (OS) was 96.9% in the MRI group and 94.3% in the control group, and this difference was not significant (p=0.11). Five-year local-regional recurrence-free survival (LRFS) was not significantly different either (98.8% and 96.5%, respectively, p=0.41). When analyses were repeated only for patients with hormone receptor-negative or triple-negative breast cancer, there was still no significant difference in OS, LRFS, or disease-free survival. In conclusion, MRI does not seem necessary in all patients undergoing BCS. New prospective randomized controlled trials are needed to determine appropriate use of preoperative MRI and its effects on oncologic outcomes in early breast cancer patients.

Purpose: To compare the efficacy and adverse effect profiles of the first-line treatment of patients with KRAS wild type metastatic colorectal cancer (CRC) in Turkey who were treated based on regimens including bevacizumab, cetuximab and panitumumab., Methods: This retrospective multicenter observational study involved a total of 238 patients who received chemotherapy in combination with either bevacizumab or cetuximab or panitumumab as first-line therapy for KRAS wild-type metastatic colorectal cancer. Patients with full medical records having pathological diagnosis of CRC adenocarcinoma were included in the study. The demographic, laboratory, histopathological and clinical characteristics of the patients were determined, and three groups were compared based on the study variables., Results: The mean age of the entire sample (n=238) was 58±11 years, 64% of which were male. The most frequent tumor localization was the rectum (37%) and G2 was the most common tumor grade (59.7%). About 63% of the patients had metastatic disease at diagnosis, with the most common site of metastasis being lung (14.7%) and liver (52.5%). Overall survival (OS) was 63.9%, while 1-, 3- and 5-year survival rates were 91.7, 56.6 and 36.9%, respectively. The expected mean survival was 49.1 months (95% CI, 42.9-55.3). The 1-, 3- and 5-year progression-free survival (PFS) rates following first-line treatment were 65.3, 26.1 and 5.6%, respectively, while disease free survival (DFS) in patients without metastasis at diagnosis was 68.5%. An analysis carried out disregarding which treatment the patients received (FOLFOX or FOLFIRI) revealed that a panitumumab-containing combination resulted in poorer prognosis compared to bevacizumab or cetuximab-containing combination (p<0.001). With regard to the adverse effect profile, the most common adverse effects were neuropathy and neutropenia in patients receiving FOLFOX-bevacizumab; neutropenia and perforation in patients receiving FOLFIRI-bevacizumab; rash and pustular infection in patients receiving FOLFIRI-cetuximab; and diarrhea in patients who received FOLFIRI-panitumumab combination., Conclusion: This is the first multicenter study performed in Turkey evaluating the response to treatment and adverse effects in patients with KRAS wild-type metastatic colorectal cancer.

Objectives: To analyze the relationship between clinical features, hormonal receptor status, and survival in patients who were diagnosed with medullary breast cancer (MBC). Methods: Demographic characteristics, histopathological features, and survival statuses of 201 patients diagnosed with MBC between 1995 and 2015 were retrospectively recorded. Survival analyses were conducted with uni- and multivariate cox regression analysis., Results: Median follow-up time was 54 (4-272) months. Median patient age at the time of diagnosis was 47 years old (26-90). Of the patients, 91.5% were triple negative. Five-year recurrence free survival time (RFS) rate was 87.4% and overalll survival (OS) rate 95.7%. For RFS, progesterone receptor (PR) negativity, atypical histopathological evaluation, absence of lymphovascular invasion, smaller tumor, lower nodal involvement were found to be favourable prognostic factors by univariate analysis (p less than 0.05). The PR negativity and smaller tumor were found to be favourable factors by univariate analysis (p less than 0.05). However, none of these factors were determined as significant independent prognostic factors for OS (p greater than 0.05).  Conclusion: Turkish MBC patients exhibited good prognosis, which was comparable with survival outcomes achieved in the literature. The PR negativity was related to a better RFS and OS rates.

The discrepancy between the surgical technique and the type of adjuvant chemotherapy used in clinical trials and patient outcomes in terms of overall survival rates has led to the generation of different adjuvant treatment protocols in distinct parts of the world. The adjuvant treatment recommendation is generally chemoradiotherapy in the United States, perioperative chemotherapy in the United Kingdom and parts of Europe, and chemotherapy in Asia. These options mainly rely on the United States Intergroup-0116, United Kingdom British Medical Research Council Adjuvant Gastric Infusional Chemotherapy, and the Asian Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer and Capecitabine and Oxaliplatin Adjuvant Study in Stomach Cancer trials. However, the benefits were evident for only certain patients, which were not very homogeneous regarding the type of surgery, chemotherapy regimens, and stage of disease. Whether the dissimilarities in survival are attributable to surgical technique or intrinsic biological differences is a subject of debate. Regardless of the extent of surgery, multimodal therapy may offer modest survival advantage at least for diseases with lymph node involvement. Moreover, in the era of individualized treatment for most of the other cancer types, identification of special subgroups comprising those who will derive more or no benefit from adjuvant therapy merits further investigation. The aim of this review is to reveal the historical evolution and future reflections of adjuvant treatment modalities for resected gastric cancer patients.

Aim of the Study: Sunitinib-related side effects may develop as a result of the pharmacokinetic pathway affects the of the drug., Material and Methods: Data on mRCC patients were obtained from the hospital archives. Outcomes of patients were evaluated in terms of related prognostic factors, sunitinib adverse events during the treatment, and two different sunitinib dosing schedules., Results: Seventy patients diagnosed with mRCC and treated with sunitinib were analyzed for prognostic factors and survival rates. During the mean follow-up of 33.5 months, 38 (54%) patients were alive and 32 (46%) patients died. The median time of overall survival (OS) and progression-free survival (PFS) was 27 months (12-61) and 19 months (5-45), respectively. In univariate analysis, good prognostic risk group according to the Memorial Sloan-Kettering Cancer Center (MSKCC), hypothyroidism as sunitinib toxicity and patients on sunitinib treatment more than 1 year were favorable prognostic factors for OS. Leukopenia and fatigue as sunitinib toxicity were poor prognostic factors for OS. PFS and OS of the patients were not significantly different when we compared intermittent (4/2) vs. continuous treatment dosing schedules., Conclusions: As a result of this trial, having hypothyroidism as an adverse effect of sunitinib was a favorable prognostic factor for OS and PFS in mRCC patients. It was also found that 4/2 and continuous dosing schedules of sunitinib did not give rise to different outcomes in mRCC patients.

One of the most important adverse effects of zoledronic acid (ZA) is osteonecrosis of the jaw (ONJ). In previous literature, several risk factors have been identified in the development of ONJ. In this study, we aimed to determine the role of trastuzumab, an antiangiogenic agent, as an independent risk factor for the development of this serious side effect.Our study included 97 patients (mean age: 54 ± 10 years) with breast cancer, recorded in the archives of the Istanbul Florence Nightingale Breast Study Group, who received ZA therapy due to bone metastases between March 2006 and December 2013. We recorded the patients' ages, weights, duration of treatment with ZA, number of ZA infusions, dental procedures, anticancer treatments (chemotherapy, aromatase inhibitor, trastuzumab), the presence of diabetes mellitus or renal dysfunction, and smoking habits.Thirteen patients (13.40%) had developed ONJ. Among the patients with ONJ, the mean time of exposure to ZA was 41 months (range: 13-82) and the mean number of ZA infusions was 38 (range: 15-56). The duration of treatment with ZA and the use of trastuzumab were observed to be 2 factors that influenced the development of ONJ (P = 0.049 and P = 0.028, respectively).The development of ONJ under ZA treatment may be associated solely with the duration of ZA treatment and the concurrent administration of trastuzumab. These findings show that patients who are administered trastuzumab for metastatic breast cancer while undergoing ZA treatment are prone to developing ONJ. Therefore, we recommend intense clinical observation to avoid this particular condition in patients receiving ZA and trastuzumab.

Angiosarcoma is an extremely rare, high-grade malignancy, which accounts for <2% of all soft-tissue sarcomas. Cases of primary renal angiosarcoma represent 1% of these. Angiosarcomas involving the kidney usually originate from metastatic skin lesions or primary visceral lesions and most often occur in the sixth and seventh decades of life. The present study describes a case of primary renal angiosarcoma that presented as a large right-sided renal mass with symptoms of flank pain. Despite surgical removal of the tumor, recurrent disease with associated lung metastases was identified at the surgical site following adjuvant chemotherapy. The patient succumbed to the disease 13 months after the diagnosis.

The aim of the present study was to identify the optimal Ki-67 cut-off value in breast cancer (BC) patients, and investigate the association of Ki-67 expression levels with other prognostic factors. Firstly, a retrospective search was performed to identify patients with stage I-III BC (n=462). A range of Ki-67 index values were then assigned to five groups (<10, 10-14, 15-19, 20-24 and ≥25%). The correlation between the Ki-67 index and other prognostic factors [age, tumor type, histological and nuclear grade, tumor size, multifocality, an in situ component, lymphovascular invasion (LVI), estrogen and progesterone receptor (ER/PR) expression, human epidermal growth factor receptor (HER-2) status, axillary involvement and tumor stage] were investigated in each group. The median Ki-67 value was revealed to be 20% (range, 1-95%). A young age (≤40 years old), tumor type, size and grade, LVI, ER/PR negativity and HER-2 positivity were revealed to be associated with the Ki-67 level. Furthermore, Ki-67 was demonstrated to be negatively correlated with ER/PR expression (P<0.001), but positively correlated with tumor size (P<0.001). The multivariate analysis revealed that a Ki-67 value of ≥15% was associated with the largest number of poor prognostic factors (P=0.036). In addition, a Ki-67 value of ≥15% was identified to be statistically significant in association with certain luminal subtypes. The rate of disease-free survival was higher in patients with luminal A subtype BC (P=0.036). Following the correlation analysis for the Ki-67 index and the other prognostic factors, a Ki-67 value of ≥15% was revealed to be the optimal cut-off level for BC patients.

Background: The phosphatidylinositol 3'-kinase/Akt (PI3K/Akt) pathway is a key regulator for HER2- overexpressing breast cancer, but data about whether activation of PI3K/Akt is associated with poor prognosis and resistance to trastuzumab therapy is controversial. In this study we investigated predictive and prognostic significance of expression of p27, Akt, PTEN and PI3K, which are components of the PI3K/Akt signaling pathway, in HER2-positive metastatic breast cancer (MBC), retrospectively., Materials and Methods: Fifty-four HER2- positive MBC patients who had received first-line trastuzumab-based therapy were recruited for the study group. All of the patient's breast tissue samples were examined for p27 and Akt expression. In addition, twenty-five patients with sufficient amount of tumor tissue were also examined for PTEN and PI3K expression. p27, Akt, PTEN and PI3K were evaluated by immunohistochemistry and their relationship with patient demographic features, tumor characteristics, response to trastuzumab-based treatment and survival outcomes were analyzed., Results: p27, Akt, PTEN and PI3K were positive in 25.9%, 70.4%, 24% and 96% of the cases, respectively. Nomne were significantly associated with response to trastuzumab and time to progression (TTP). A trend toward statistical significance for longer overall survival (OS) was found for PTEN-positive patients (p=0.058); there was no significant relationship between the other immunohistochemical variables and OS. When we analyzed groups regarding co-expression, the PTEN-negative/Akt-negative group had a significantly lower objective response rate (ORR) (20% vs 80%, p=0.023) and the PTEN-negative/p27-negative and PTEN-negative/Akt-negative groups had significantly lower median OS compared to other patients (26.4 months vs 76.1 months, p=0.005 and 25.6 months vs 52.0 months, p=0.007, respectively)., Conclusions: p27, Akt, PTEN and PI3K expression is not statistically significantly associated with ORR, TTP and OS, individually. However, the combined evaluation of p27, Akt and PTEN could be helpful to predict the response to trastuzumab-based therapy and prognosis in HER2-positive MBC.

Background: Several prognostic factors have been studied in NSCLC, although it is unknown which is most useful. In this study, we aimed to investigate whether pre-treatment serum albumin level has prognostic value in patients with Stage IIIB NSCLC., Materials and Methods: This cross-sectional study included a total of 204 patients with Stage IIIB NSCLC who met the inclusion criteria. Pre-treatment serum albumin levels and demographic, clinical, and histological characteristics, as well as laboratory variables were recorded. A cut-off value was defined for serum albumin level and the patients were stratified into four groups on thios basis., Results: The majority of the patients was males and smokers, with a history of weight loss, and squamous histological type of lung cancer. The mean serum albumin level was 3.2±1.7 g/dL (range, 2.11-4.36 g/dL). A cut-off value 3.11 g/dL was set and among the patients with a lower level, 68% had adenocarcinoma and 82% were smokers. The patients with low serum albumin levels had a lower response rate to e first-line chemotherapy with a shorter progression-free survival and overall survival. Multivariate analysis showed that low serum albumin level was an independent poor prognostic factor for NSCLC., Conclusions: This study results suggest that low serum albumin level is an independent poor prognostic factor in patients with Stage IIIB NSCLC, associated with reduction in the response rate to first-line therapy and survival rates.

Background: Vitamin D deficiency is a potentially modifiable risk factor that may be targeted for breast cancer (BC) prevention. It may also be related to prognosis after diagnosis and treatment. The aim of our study was to determine the prevalence of vitamin D deficiency as measured by serum 25-hydroxy vitamin D (25-OHD) levels in patients with BC and to evaluate its correlations with life-style and treatments., Materials and Methods: This study included 186 patients with stage 0-III BC treated in our breast center between 2010-2013. The correlation between serum baseline 25-OHD levels and supplement usage, age, menopausal status, diabetes mellitus, usage of bisphosphonates, body-mass index (BMI), season, dressing style, administration of systemic treatments and radiotherapy were investigated. The distribution of serum 25-OHD levels was categorized as deficient (<10ng/ ml), insufficient (10-24 ng/ml), and sufficient (25-80 ng/ml)., Results: The median age of the patients was 51 years (range: 27-79 years) and 70% of them had deficient/insufficient 25-OHD levels. On univariate analysis, vitamin D deficiency/insufficiency was more common in patients with none or low dose vitamin D supplementation at the baseline, high BMI (≥25), no bisphosphonate usage, and a conservative dressing style. On multivariate analysis, none or low dose vitamin D supplementation, and decreased sun-exposure due to a conservative dressing style were found as independent factors increasing risk of vitamin D deficiency/insufficiency 28.7 (p=0.002) and 13.4 (p=0.003) fold, respectively., Conclusions: The prevalence of serum 25-OHD deficiency/insufficiency is high in our BC survivors. Vitamin D status should be routinely evaluated for all women, especially those with a conservative dressing style, as part of regular preventive care, and they should take supplemental vitamin D.

Background: Megestrol acetate (MA) is a steroid origin medicine often used for control of cachexia in oncologic palliative care. Thrombosis is a common problem in oncology patients. One question is whether MA can cause thrombosis. This retrospective, registry-based analysis was therefore conducted to assess thrombotic processes in oncology patients using MA concurrent with chemotherapy., Materials and Methods: Data on oncology patients at the metastatic stage using MA were obtained from the archives of our center. Outcomes of patients were evaluated for thromboembolic events (VTEs) during treatment., Results: Ninety-seven oncology patients with a median age of 62 (33-84) years were included. During the median follow-up of 17 months, 58 (59.8%) died leaving 39 (31.2%) still alive. Median overall survival (OS) was 19 months (6-180). Mean time of MA use was 8.69 months(±3.53), with a median dose of 160mg (range 160-480mg). Eleven VTEs were detected after MA use, 4 of these in pancreatic cancer cases. The patients with thrombosis non-significantly had worse OS, than those without thrombosis (p=0.106)., Conclusions: This trial revealed that the 11.3% of all patients developed thrombosis,who had been treated with MA and chemotherapy concomittantly. There was no statistically significant difference regarding to occurrence of thrombotic process, among the patients receiving different chemotherapy regimens with MA concomittantly. Pancreatic cancer seemed to be related to thrombosis rather than MA use.

Background: The increase in breast cancer awareness and widespread use of mammographic screening has led to an increased detection of (non-palpable) breast cancers that cannot be discovered through physical examination. One of the methods used in the diagnosis of these cancers is vacuum-assisted core biopsy, which prevents a considerable number of patients from undergoing surgical procedures. The aim of this study was to present the results of stereotactic vacuum-assisted core biopsy for suspicious breast lesions., Materials and Methods: Files were retrospectively scanned and data on demographic, radiological and pathological findings were recorded for patients who underwent stereotactic vacuum-assisted core biopsy due to suspicious mammographic findings at the Interventional Radiology Centre of the Florence Nightingale Hospital between January 2010, and April 2013. Statistical analysis was carried out using Pearson's Chi-square, continuity correction, and Fisher's exact tests., Results: The mean age of the patients was 47 years (range: 36-70). Biopsies were performed due to BIRADS 3 lesions in 8 patients, BIRADS 4 lesions in 77 patients, and BIRADS 5 lesions in 3 patients. Mammography elucidated clusters of microcalcifications in 73 patients (83%) and focal lesions (asymmetrical density, distortion) in 15 patients (17%). In terms of complications, 1 patient had a hematoma, and 2 patients had ecchymoses (3/88; 3.3%). The histopathologic results revealed benign lesions in 63 patients (71.6%) and malignant lesions in 25 patients (28.4%). The mean duration of the procedure was 37 minutes (range: 18-55). Although all of the BIRADS 3 lesions were benign, 22 (28.6%) of the BIRADS 4 lesions and all of the BIRADS 5 lesions were malignant. Among the malignant cases, 80% were in situ, and 20% were invasive carcinomas. These patients underwent surgery., Conclusions: In cases where non-palpable breast lesions are considered to be suspicious in mammography scans, the vacuum-assisted core biopsy method provides an accurate histopathologic diagnosis thus preventing a significant number of patients undergoing unnecessary surgical procedures.