Merdan Fayda

Do circulating long non-coding RNAs (lncRNAs) (LincRNA-p21, GAS 5, HOTAIR) predict the treatment response in patients with head and neck cancer treated with chemoradiotherapy?

Long non-coding RNAs (lncRNAs) have been shown to be aberrantly expressed in head and neck cancer (HNC). The aim of the present study was to evaluate plasma levels of three lncRNA molecules (lincRNA-p21, GAS5, and HOTAIR) in the treatment response in HNC patients treated with radical chemoradiotherapy (CRT). Forty-one patients with HNC were enrolled in the study. Most of the patients had nasopharyngeal carcinoma (nu2009=u200927, 65.9xa0%) and locally advanced disease. Blood was drawn at baseline and treatment evaluation 4.5xa0months after therapy. lncRNAs in plasma were measured by semiquantitative PCR. Treatment response was evaluated according to clinical examination, RECIST and PERCIST criteria based on magnetic resonance imaging (MRI), and positron emission tomography with computed tomography (PET/CT) findings. Complete response (CR) rates were 73.2, 36.6, and 50xa0% for clinical investigation, PET/CT-, or MRI-based response evaluation, respectively. Predictive value of lncRNAs was investigated in patients with CR vs. those with partial response (PR)/progressive disease (PD). We found that post-treatment GAS5 levels in patients with PR/PD were significantly higher compared with patients with CR based on clinical investigation (pu2009=u20090.01). Receiver operator characteristic (ROC) analysis showed that at a cutoff value of 0.3 of GAS5, sensitivity and specificity for clinical tumor response were 82 and 77xa0%, respectively. Interestingly, pretreatment GAS5 levels were significantly increased in patients with PR/PD compared to those with CR upon MRI-based response evaluation (pu2009=u20090.042). In contrast to GAS5, pretreatment or post-treatment lincRNA-p21 and HOTAIR levels were not informative for treatment response. Our results suggest that circulating GAS5 could be a biomarker in predicting treatment response in HNC patients.

Colon cancer with isolated metastasis to the kidney at the time of initial diagnosis

Blood-borne metastases to the kidneys from solid tumors have received little attention in the medical literature because they usually occur in a setting of advanced systemic disease, and renal involvement is a elatively minor cause of symptoms. Although the frequency of metastases to the kidney in cancer patients is 7–13% in large autopsy series, incidental discovery of a renal metastasis as the first manifestation of a primary tumor is a very rare event. The most common primary malignancy to involve the kidney is bronchogenic carcinoma, followed by breast and gastrointestinal cancers. In this article, we report a patient with left colon cancer and isolated metastasis to the right kidney at the time of initial diagnosis. Left hemicolectomy and right nephrectomy were performed. Adjuvant systemic chemotherapy consisting of 5-fluorouracil (5-FU) and folinic acid (FA) was given. 5-FU and FA were stopped after four cycles because metastases to the lung and liver occurred about 3 mo after the surgery during adjuvant chemotherapy. Capecitabine was started. The patient died 9 mo after the discovery of the isolated renal metastasis. Nephrectomy is more for diagnostic clarification in the setting of synchronous primary because it has no effect on survival and its effect on quality of life is minimal; as seen in our case, the other organ metastases rapidly occur and the survival is limited. Nephrectomy may also compromise the choice of chemotherapy agents that require renal clearance, thus a careful evaluation of renal functions is necessary if a nephrectomy is performed. In the matter of a decreased renal clearance, the doses of these drugs should be decreased or the choice should be reevaluated.

Intraoperative ultrasound reduces the need for re-excision in breast-conserving surgery

BackgroundThe purpose of this study was to evaluate ultrasound-guided surgery for palpable breast cancer by comparing the standard palpation-guided surgery in terms of the extent of healthy breast tissue resection, the percentage of tumor-free margins, and cosmetic outcomes.MethodsThis was a prospective, observational cohort study conducted from January 2009 to July 2011. Breast cancer patients, diagnosed via biopsy, were operated in guidance with either ultrasound or palpation. Patient demographics, tumor features, intraoperative findings, pathologic and cosmetic results, intraoperative-measured ultrasound margins, and pathology margins were compared.ResultsUltrasound (US)-guided lumpectomy was performed on 84 women and palpation-guided lumpectomy on 80 women. Patient demographics and tumor characteristics showed no differences. The rate of re-excision was 17xa0% for the palpation-guided surgery group, and 6xa0% for the US-guided group (pu2009=u20090.03). There was good correlation between the closest margins recorded by US and pathology margins (ru2009=u20090.76, pu2009=u20090.01). Volume of resection was significantly larger in the palpation-guided group despite the similar size of tumors (pu2009=u20090.048). Cosmetic outcome of surgery was equivalent between groups.ConclusionsIntraoperative ultrasound guidance for excision of palpable breast cancers is feasible and gives results in terms of pathologic margins that are comparable with those achieved by standard palpation-guided excisions.

Metaplastic Breast Carcinoma Versus Triple-Negative Breast Cancer: Survival and Response to Treatment.

AbstractMetaplastic breast carcinoma (MBC) differs from classic invasive ductal carcinomas regarding incidence, pathogenesis, and prognosis. The purpose of this study was to compare patients with MBC with clinicopathologic and treatment-matched patients with triple-negative breast carcinoma (TNBC) in terms of response to treatment, progression, and survival.Fifty-four patients with MBC and 51 with TNBC, who were treated at Istanbul University, Institute of Oncology, between 1993 and 2014, were included in the study. After correctly matching the patients with 1 of the 2 groups, they were compared to determine differences in response to treatment, disease progression, clinical course, and survival.At a median follow-up of 28 months, 18 patients (17.1%) died and 27 (25.5%) had disease progression. Metaplastic histology was significantly correlated with worse 3-year progression-free survival (PFS) (51u200a±u200a9% vs. 82u200a±u200a6%, Pu200a=u200a0.013) and overall survival (OS) (68u200a±u200a8% vs. 94u200a±u200a4%, Pu200a=u200a0.009) compared with TNBC histology. Patients who received taxane-based chemotherapy (CT) regimens or adjuvant radiotherapy had significantly better PFS (Pu200a=u200a0.002 and Pu200a<u200a0.001) and OS (Pu200a<u200a0.001 and Pu200a<u200a0.001) compared with others. In the multivariate analysis, MBC (hazard ratio [HR]: 0.09, Pu200a<u200a0.001), presence of neoadjuvant chemotherapy (NACT) (HR: 12.8, Pu200a=u200a0.05), and metastasis development at any time during the clinical course (HR: 38.7, Pu200a<u200a0.001) were significant factors that decreased PFS, whereas metastasis development was the only independent prognostic factor of OS (HR: 23.8, Pu200a=u200a0.009).MBC is significantly correlated with worse PFS and OS compared with TNBC. Patients with MBC are resistant to conventional CT agents, and more efficient treatment regimens are required.

The diagnostic, predictive, and prognostic role of serum epithelial cell adhesion molecule (EpCAM) and vascular cell adhesion molecule-1 (VCAM-1) levels in breast cancer

The purpose of this study was to determine the clinical significance of vascular cell adhesion molecule-1 (VCAM-1) and epithelial cell adhesion molecule (EpCAM) in breast cancer (BC) patients. Ninety-six BC patients and 30 age- and sex-matched healthy controls were enrolled into this study. Pretreatment serum markers were determined by the solid-phase sandwich (enzyme-linked immunosorbent assay (ELISA)). The median age at diagnosis was 48xa0years (range 29–80xa0years). Majority of the patients (71xa0%) had luminal subtype, and 38.5xa0% had metastatic disease. Twenty-nine (30xa0%) patients showed tumor progression, and 20 (21xa0%) patients died during follow-up. Median progression-free survival (PFS) and overall survival (OS) were 8.6u2009±u20091.7 and 35.5u2009±u20091.5xa0months, respectively. The baseline serum EpCAM levels of the patients were significantly higher than those of the controls (pu2009<u20090.001). There was no significant difference in the serum levels of VCAM-1 between the patients and controls (pu2009=u20090.47). No significant correlation was detected between the levels of the serum markers and other clinical parameters (pu2009>u20090.05). Patients with HER-2-positive and triple-negative tumors had significantly poorer PFS (pu2009=u20090.04 and pu2009=u20090.001, respectively), while metastatic disease and chemotherapy unresponsiveness had significantly adverse effect on OS analysis (pu2009<u20090.001 and pu2009<u20090.001, respectively). Neither serum VCAM-1 levels nor serum EpCAM levels were identified to have a prognostic role on either PFS or OS (VCAM-1 pu2009=u20090.76 and pu2009=u20090.32; EpCAM pu2009=u20090.16 and pu2009=u20090.69, respectively). Even though any predictive or prognostic role could not be determined for both markers, serum levels of EpCAM were found to have diagnostic value in BC patients.

GAS5 oligonucleotides as therapeutic agents in breast cancer

Although relatively less is known about the long non-coding RNA (lncRNA) than the essential protein coding genes, several of them have organismal functions such as lethal knockouts, apoptosis etc. (1,2). Growth arrest specific genes 5 (GAS5) has proven to be pro-apoptotic in breast cancer (BC) cell lines (3). In their paper entitled “ The hormone response element mimic sequence of GAS5 lncRNA is sufficient to induce apoptosis in breast cancer cells ” published in March issue of Oncotarget by Pickard and Williams (4) report that an oligonucleotide representing the hormone response element mimic (HREM) sequence within GAS5 alone is able to promote the apoptosis of BC cells similar to full-length GAS5.

Axillary versus sentinel-lymph-node dissection for micrometastatic breast cancer

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Loss of ARID1A expression is associated with poor prognosis in invasive micropapillary carcinomas of the breast: A clinicopathologic and immunohistochemical study with long-term survival analysis

Invasive micropapillary carcinoma (IMPC) of the breast is a highly aggressive and a rare subtype of breast cancer. In this study, we aimed to investigate differences between pure and mixed IMPCs of the breast in terms of clinicopathologic features, and also to analyze the significance of expressions of ARID1A and bcl‐2 regarding prognosis. Sixty‐nine of IMPCs consisting of 21 pure and 48 mixed type diagnosed at Pathology Department of Istanbul Medical Faculty between 2000 and 2011, who had complete follow‐up data, were collected to analyze ARID1A and bcl‐2 expressions immunohistochemically with prognosis. The median follow‐up period was 94 months. No significant difference was found between pure and mixed type IMPC, as well as in luminal subgroups in terms of prognostic and clinicopatologic features. ARID1A and human epidermal growth factor receptor‐2 (Her‐2) status were found to be independent prognostic factors of both overall survival (OS) (HR=6.1, 95% CI 1.4‐26.6, P=.02; HR=15.9, 95% CI 3.5‐71.5, P<.0001, respectively) and disease free survival (DFS) (HR=4, 95% CI 1.1‐14.9, P=.04; HR=7.2, 95% CI 2‐25.4, P=.002, respectively) in multivariate analysis using Cox regression. The loss of ARID1A expression was significantly related with 10 year‐OS (P=.001) and 10 year‐DFS (P=.05). Statistically significant effect of ARID1A expression was also stated on DFS and OS in Luminal B group (P=.05 and P=.001 respectively). Pure and mixed type IMPCs are similar in terms of clinicopathologic and prognostic features. The loss of ARID1A expression and Her‐2 positivity have significant adverse effect clinical outcomes of IMPC patients.

Adjuvant Radiation Therapy After Preoperative Chemotherapy

The decision to treat patients with radiotherapy after preoperative chemotherapy is still largely based on the initial clinical staging of the patients. The use of three-field radiotherapy (RT) including the chest wall/breast and regional lymphatics after surgery in locally advanced, node-positive patients receiving neoadjuvant systemic chemotherapy is well established. Patients with clinically staged T3–T4 tumors, pathological non-complete responders in the axilla, and younger patients ( 40 years old) with pathological complete response (pCR) (ypT0, ypTis, ypN0) and non-triple-negative histology after neoadjuvant chemotherapy could possibly be followed without postmastectomy radiotherapy (PMRT) and without regional irradiation in a breast-conserving setting. Well-designed randomized, controlled studies are urgently needed in this controversial area.

Is sentinel lymph node biopsy enough for axillary macrometastasis

includes patients with both micro and macrometastasis in sentinel lymph node(s). Early stage breast cancer patients with clinical N0 disease and one or two positive sentinel lymph node(s) are randomized to axillary lymph node dissection (ALND) vs. sentinel lymph node dissection (SLND) alone. At a median follow-up of 6.3 years, both 5-year overall survival (91.8% vs. 92.5%; ALND vs. SLND) and 5-year diseasefree survival (82.2% vs. 83.9%; ALND vs. SLND) are not significantly different between the arms (1, 2). Arguably, Z0011 study is one of the most important practice changing or at least practice questioning randomized study in recent years. The second trial is the International Breast Cancer Study Group (IBCSG) 23-01 study, which has the same patient population of Z0011 but with only one or 2 sentinel micrometastatic lymph node(s) and also the same randomization. In IBCSG 23-01 trial, the 5-year disease-free survival is also not significantly different between the groups (84.4% vs. 87.8%; ALND vs. SLND) (3). IBCSG 23-01 trial not only further strengthens the results of the Z0011 for the omittance of axillary dissection in patients with sentinel micrometastatic lymph node breast cancer but also shows that the quality of life (QOL) of patients could be improved with sentinel biopsy alone in terms of sensory motor neuropathy and lymphedema (3, 4). In the consensus report of Saint Gallen 2013, the policy of avoiding full axillary clearance after one or two positive sentinel nodes is endorsed in situations of conservative surgery and radiotherapy (73%, YES; 21%, NO), including several opinions that the inclusion criteria of the available trial results should be considered (5). Although the Z0011 trial provokes us to omit axillary dissection in patients with cT1-2cN0 disease finally staged at pT1-2pN1(sn), it creates more problems than it solves in terms of radiotherapy fields (1). The radiotherapy directed to axillary basins (i.e., third field nodal radiotherapy) is not allowed in the protocol of the Z0011 trial. However, the details of radiotherapy fields could not be clearly understood from the original report (1). Many radiation oncologists try to irradiate at least some part of the axillary level 1-2 (i.e., high-tangential fields) and even think of using third field (i.e., supraclavicular level 3), particularly for patients with no reasonable systemic treatment option (i.e., triple negative case). Recently, the detail of radiotherapy fields at least for some part of the patients in the Z0011 trial is presented at the San Antonio Breast Cancer Symposium 2013 (6). Detailed radiotherapy records were received for 228 patients only: 104/389 (26.7%) ALND vs. 124/404 (30.7%) SLND. Sixty-one of 104 (59%) patients in ALND arm also received some form of lymphatic radiotherapy [supraclavicular, n=22 (21%), posterior axillary boost n=6 (6%), and high tangents n=33 (32%)]. In the SLND arm, some form of lymphatic radiotherapy was also used for 73 of 124 (59%) patients [supraclavicular n=21 (17%), posterior axillary boost n=12 (10%), and high tangents n=40 (32%)] (6). Although the data of the central radiotherapy review of the entire Z0011 population could not be available currently, approximately 60% of the patients have received some form of lymphatic radiotherapy and 18.9% of them have major protocol violation (i.e., third field nodal radiotherapy is not allowed in the protocol). Thus, regional radiotherapy may contribute to the results that have been obtained from both arms of the Z0011 trial.