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.

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 (n = 27, 65.9 %) and locally advanced disease. Blood was drawn at baseline and treatment evaluation 4.5 months 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 50 % 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 (p = 0.01). 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 77 %, respectively. Interestingly, pretreatment GAS5 levels were significantly increased in patients with PR/PD compared to those with CR upon MRI-based response evaluation (p = 0.042). 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.

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

BACKGROUND: The 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. METHODS: This 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. RESULTS: Ultrasound (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 17 % for the palpation-guided surgery group, and 6 % for the US-guided group (p = 0.03). There was good correlation between the closest margins recorded by US and pathology margins (r = 0.76, p = 0.01). Volume of resection was significantly larger in the palpation-guided group despite the similar size of tumors (p = 0.048). Cosmetic outcome of surgery was equivalent between groups. CONCLUSIONS: Intraoperative 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.

Clinical utility of a 1.5 T magnetic resonance imaging-guided linear accelerator during conventionally fractionated and hypofractionated prostate cancer radiotherapy.

Purpose: To report our initial experience with 1.5 T magnetic resonance imaging (MRI) linear accelerator (LINAC) in prostate cancer radiotherapy in terms of its use in a radiation oncology clinic. Methods: The medical records of 14 prostate cancer patients treated with MRI-guided radiotherapy were retrospectively evaluated. The fraction time, adapt-to-position (ATP):adapt-to-shape (ATS) usage rate, machine-associated treatment interruption rate, median gamma pass rate, the percentage of planning target volume receiving at least 95% of the prescription dose coverage value of each ATS fraction, the effect of the learning curve on the fraction time and radiation-related acute gastrointestinal and genitourinary toxicities were evaluated. Results: Fourteen patients have completed their treatment receiving a total of 375 fractions. Six patients (42%) were treated with the moderately hypofractionated regimen, five patients (36%) with conventionally fractionated, and three patients (22%) with the ultra-hypofractionated radiotherapy regimens. The ATP : ATS usage ratio was 3:372. The median fraction time was 46 min (range, 24-81 min). For the 3%/3 mm criterion, median gamma pass rate was 99.4% (range, 94.6-100%). Machine-related treatment interruptions were observed in 11 (2.9%) of 375 fractions, but this interruption rate decreased from 4.1% to 0.8%, after an upgrade. Three patients (22%) had gastrointestinal and five patients (36%) had genitourinary toxicity. No ≥grade 3 toxicity was observed. Conclusion: 1.5 T MRI-LINAC device could be used as a conventional LINAC device, when the conditions of the radiotherapy center are appropriate. MRI-guided prostate radiotherapy is safe and feasible, and high-quality studies with a larger number of patients and long-term results are needed to better evaluate this new technology.

Computed Tomography-Guided Optimization of Needle Insertion for Combined Intracavitary/Interstitial Brachytherapy With Utrecht Applicator in Locally Advanced Cervical Cancer.

PURPOSE: There are no international guidelines for optimal needle insertion during interstitial intracavitary brachytherapy (IS-ICBT) for cervical cancer. We aimed to investigate the clinical feasibility and added value of computed tomography (CT) guidance to optimize needle insertion in IS-ICBT using the Utrecht applicator and to evaluate needle shifts. METHODS AND MATERIALS: We enrolled 24 patients who were treated with interstitial-brachytherapy. Two CT scans each were performed for every patient: (1) after applicator insertion without needles (CTpreneedle) and (2) after needle insertion (CTpostneedle). In addition to magnetic resonance imaging after external-beam radiation therapy, CTpreneedle was used to determine optimal needle locations and insertion lengths based on applicator and organs at risk positioning on the day of treatment; CTpostneedle was used for IS-ICBT planning. The needle-channel axis was used as a reference to determine needle-shift evolution. RESULTS: A total of 266 interstitial needles were inserted in 76 of 93 BT fractions with high intra- and interpatient variations in the number of inserted needles. Based on CTpreneedle findings, needle insertion was avoided in 9, 4, 2, and 2 patients at the first, second, third, and fourth fractions, respectively. The unloaded needle frequency was 4%. Average needle contribution to total dwell time was 37.2% ± 19.2%. Shifting was observed in 68% of the needles (mean shift 2.0 ± 2.3 mm), mostly in the posterior direction, and in needles with a larger insertion length. Needle reinsertion was not needed in any patient. No complication due to needle insertion was observed, except for minor vaginal bleeding in 1 patient after needle removal. CONCLUSIONS: The adaptive CT-guided IS-ICBT application was feasible and resulted in fewer unloaded needle insertions or complications and more efficient use with higher needle contribution to the treatment. Needle shift was frequent but did not require needle reinsertion with the proposed method.

The role of surgery and radiotherapy in treatment of soft tissue sarcomas of the head and neck region: review of 30 cases.

BACKGROUND: Thirty adult patients with head and neck soft tissue sarcoma (HNSTS) treated between 1987 and 2000 were retrospectively analysed. PATIENTS AND METHODS: The most frequent histopathological subtypes were chondrosarcomas (27%) and malignant fibrous histiocytoma (20%). The surgical resection was performed in 25 of the 30 patients (83%). Twenty-three patients in the surgical resection arm received postoperative radiotherapy. RESULTS: Five-year local control rates for patients with negative surgical margins (n=9), microscopically positive disease (n=10), gross residual disease (n=6) and inoperable cases (n=5) were 64, 70, 20 and 0%, respectively. However, there was no significant difference in local control between patients with negative or microscopically positive disease who received postoperative radiotherapy (71 vs. 70%). The patients who received doses>or=60 Gy had significantly higher local control rates than the ones who received doses lower than 60 Gy (p=0.048). The local control rates were lower in patients with grade 2-3 tumours when compared with grade 1 tumours (44 vs. 83%). The median overall survival of whole group was 31 months. Median survivals of patients receiving both surgery and radiotherapy with negative and microscopically positive margins were significantly better than patients who were not treated with surgery (34.8 and 36 vs. 13.3 months). CONCLUSION: Our results confirm that the optimal treatment of HNSTSs is complete surgical excision, and that postoperative adjuvant radiotherapy clearly improves local control.

The efficiency of single agent docetaxel in patients with platinum-refractory non-small cell lung carcinoma.

BACKGROUND: To evaluate the efficiency of docetaxel as second line chemotherapy in patients with platinum-refractory non-small cell lung carcinoma (NSCLC). PATIENTS AND METHODS: Fifty-two patients with locally advanced or metastatic NSCLC who had platinum-refractory disease (progressed through or within 3 months of completion of first line therapy) and an Eastern Cooperative Oncology Group performance (ECOG) status 0-2 were treated with second-line chemotherapy consisting of single agent docetaxel (100 mg/m(2), intravenously, on day 1 of a 21-day cycle). The median number of treatment cycles was 4 (2-6). Disease-free (DFS) and overall survival (OS), response rates and toxicity were evaluated. RESULTS: The median progression-free survival of patients was 3 months (95% CI: 0.01-5.99) and overall survival was 7.2 months (95% CI: 2.2-9.5). One-year overall survival rate was 29%. Disease control (complete response, partial response, or stable disease) was achieved in 25 patients (48%) and overall response rate was 13% (7 patients). There were no complete responses. Seventeen patients (33%) had stable disease and twenty-seven patients (52%) had progressive disease. Age, gender, stage at diagnosis (IIIB vs. IV), performance status at initiation of second-line therapy (0-1 vs. 2) histopathological type (epidermoid vs. others), grade, LDH, albumin, weight loss were evaluated as prognostic factors; however, none of these had a significant affect on survivals. The protocol was well tolerated and there were no toxic deaths. Grade III-IV anemia was present in 8 patients (15%) and thrombopenia in 12 (23%) patients. The most frequent grade 3-4 toxicities were leucopenia (52%) and neutropenia (48%). Febril neutropenia occurred in 14 patients (26%). No patients experienced grade III-IV mucositis and diarrhea. Totally, the need of a dose reduction was about 25% and treatment delay (4-9 days) occurred in 5 patients (10%) and 7 patients (13%), respectively, because of toxicity. CONCLUSIONS: Second-line chemotherapy with single-agent docetaxel offers a small but significant survival advantage with acceptable toxicity for patients with advanced NSCLC who have platinum-refractory disease.

Posttraumatic stress disorder and risk factors in parents of children with a cancer diagnosis.

The purpose of this study was to determine the prevalence of posttraumatic stress disorder (PTSD) in parents of children with cancer. Five questionnaires were administered to 104 parents, including a sociodemographic questionnaire, a traumatic events check list, the Structured Clinical Interview for DSM-IV PTSD and Major Depressive Disorder modules, and the self-rating instrument General Health Questionnaire-12. The prevalence of PTSD was 34.6%. The statistically significant tendency to develop PTSD were found in the female gender, better educational status, death of a loved one, previous history of psychiatric disorder, having a child with poorer prognosis, and the presence of radiotherapy in child's treatment. The vulnerable parents must receive psychosocial support.

Spinal cord compression due to vertebral hemangioma.

This article presents a case of multiple vertebral hemangiomas in a 58-year-old man with pain in the dorsal region and bilateral progressive foot numbness. Magnetic resonance imaging revealed multiple vertebral hemangiomas. One hemangioma at the T7 level demonstrated epidural extension, causing spinal cord compression. After treatment with radiotherapy, the patient's symptoms improved significantly.

Neoadjuvant volumetric modulated arc therapy in rectal cancer and the correlation of pathological response with diffusion-weighted MRI and apoptotic markers.

PURPOSE: In this prospective observational study, we aimed to report the applicability and tolerability of neoadjuvant volumetric modulated arc therapy with simultaneous integrated boost (SIB-VMAT) and concurrent chemotherapy in patients with locally advanced rectal cancer (LARC), and to evaluate the correlation of pathological response with apparent diffusion coefficient (ADC) measurements on diffusion-weighted magnetic resonance imaging (DW-MRI) and apoptotic markers. METHODS: The study enrolled 30 patients with T3 to T4 and/or N+ rectal cancer who preoperatively received SIB-VMAT and concurrent chemotherapy. Before and after the neoadjuvant treatment, apoptotic markers including the nucleosomes and cell-free DNA fragments in the serum samples were examined; DNA integrity was assessed by amplifying the ACTB gene; and the ADC measurements on the DW-MRI were analyzed. RESULTS: No patients had acute or chronic grade III-IV toxicity. Pathologic complete response (pCR) was achieved in 8 patients (27%), while in 10 patients (33%) near-complete pathological response was obtained. Posttreatment ADC was significantly higher in patients with pCR compared with the others (1.28 vs. 1.10, p = 0.017). ROC curve analysis showed that posttreatment ADC values had a sensitivity of 75% and a specificity of 77.3% for distinguishing the patients with pCR from other responders. On the other hand, posttreatment DNA integrity values were revealed lower than the pretreatment values (p = 0.36). Also, the results revealed an insignificant increase in the posttreatment serum level of nucleosomes (p = 0.72). CONCLUSIONS: Neoadjuvant SIB-VMAT with concurrent chemotherapy was proved to be a feasible treatment regimen in LARC with tolerable side effects, and improved local control rate and pCR rate.

Malignant peripheral primitive neuroectodermal (pPNET) of tongue.

Primitive neuroectodermal tumors (PNETs) are relatively rare tumors. Tumors that once would have been diagnosed as Ewing's sarcoma are now often designated as peripheral neuroepithelioma or synonymously PNET. This paper reports a case of PNET located orally on the tongue, which is, to our knowledge, the first case reported in medical literature. The patient was treated with postoperative radiotherapy and chemotherapy. Multiple liver metastases occurred 5 months after the initial diagnosis and following extensive chemotherapy the patient was only able to survive for a further 10 months.

[The results of combined treatment (surgery and postoperative radiotherapy) for tongue cancer and prognostic factors]. / Dil kanserinde kombine tedavi (cerrahi ve radyoterapi) sonuçlari ve prognostik faktörler.

OBJECTIVES: We evaluated the results of surgical treatment and postoperative radiotherapy and prognostic factors in patients with primary tongue carcinoma. PATIENTS AND METHODS: The study included 60 patients (31 males, 29 females; median age 54 years; range 22 to 82 years) who underwent surgery and postoperative radiotherapy for oral tongue cancer. Tumor staging based on the AJCC-1997 criteria was as follows: stage I (n=1), stage II (n=21), stage III (n=12), and stage IVA (n=26). Surgery included hemiglossectomy (n=46, 76%), partial (n=13, 22%) and total (n=1, 2%) glossectomy. Neck dissection was performed in 47 patients (78%). Radiotherapy dose was generally 6000 cGy/30 fr. The median follow-up was 51 months (range 5 to 180 months). RESULTS: The five-year overall and relapse-free survival rates were 50% and 47%, respectively. Survival at five years was 70% for stage I-III, and 20% for stage IVA. Most of the relapses occurred in the first two years after treatment. Recurrences were encountered in 31 patients (52%). The median survival after recurrence was eight months (range 1 to 53 months). In multivariate analyses, significant prognostic factors for overall survival and locoregional control were tumor size, stage, N stage, extracapsular lymph node spread, and total duration of radiotherapy. Complications were within acceptable limits. CONCLUSION: Postoperative radiotherapy should be standard for patients with stage III and IVA tongue cancer.

The value of postoperative radiotherapy in renal cell carcinoma: a single-institution experience.

AIM: To evaluate the efficacy of postoperative irradiation in renal cell carcinoma. PATIENTS AND METHODS: Forty patients with localized renal cell carcinoma admitted to our hospital between 1986 and 1999 were evaluated. All patients were initially treated with radical nephrectomy. Postoperative radiotherapy was given to 26 of 40 patients (65%). Fourteen patients (35%) received no adjuvant therapy. Median age was 55 years (range, 20-70 years). Twenty-four patients (60%) were men and 16 patients (40%) were women. Histopathological diagnosis was renal cell carcinoma in all of the patients. N+ disease was present in 3 patients (7%). Stage I and II disease was present in 25 patients (63%) and stage III and IV disease in 15 patients (37%). Two patients (5%) had T1a disease, 11 patients (27%) had T1b, 15 patients (38%) had T2, 11 patients (27%) had T3a and 1 (3%) patient had T3b. In the radiotherapy group, renal bed and regional lymphatic fields were irradiated with daily fractions of 180-200 cGy/fraction to a total dose of 46-50 Gy, using parallel opposing fields. RESULTS: The 5-year overall survival rates were 70% in the postoperative radiotherapy group and 20% in the no adjuvant treatment group, showing no significant difference (P = 0.1). The 5-year disease-free survival rates were 66% in the radiotherapy group and 16% in the no treatment group, with a significant difference in both univariate and multivariate analyses (P = 0.045 and P = 0.0007, respectively). Stage III and IV disease, tumor size 27 cm, presence of distant metastasis and lactate dehydrogenase level > 450 U/L were found to be adverse prognostic factors for overall survival in both univariate and multivariate analyses. Analyzing the factors affecting disease-free survival, absence of postoperative radiotherapy and tumor size > or = 7 cm were found to be adverse prognostic factors in univariate and multivariate analyses. CONCLUSION: Multi-institutional prospective randomized trials using modern radiotherapy techniques such as conformal radiotherapy and intensity-modulated radiotherapy are necessary to evaluate the real role of radiotherapy and its effect on survival in renal cell carcinoma, especially in selected patients with a high risk of local or regional failure.

Primary glioblastoma multiforme in younger patients: a single-institution experience.

AIMS AND BACKGROUND: To report our experience of patients with primary glioblastoma multiforme of young age by evaluating the characteristics, prognostic factors, and treatment outcomes. PATIENTS AND METHODS: Seventy patients with primary glioblastoma multiforme (GBM) treated at our department between 1996 and 2004 were studied. The male-female ratio was 2.6:1. The median age was 53 (16-74). Sixty-eight patients (97%) were operated on before radiotherapy and 2 patients (3%) underwent only stereotactic biopsy. All patients received radiotherapy. Postoperative chemotherapy as an adjuvant to radiotherapy was given to 9 patients (12%). The patients were divided into 2 groups according to their age (group A < or = 35 years, n = 21 vs group B > 35 years, n = 49). Survival was determined with the Kaplan-Meier method and differences were compared using the log-rank test. Cox regression analysis was performed to identify the independent prognostic factors. Karnofsky performance status (> or = 70 vs < 70), age (< or = 35 vs > 35 years), gender, tumor size (< or = 4 vs > 4 cm), number of involved brain lobes (1 vs more than 1), type of surgery (total vs subtotal), preoperative seizure history (present vs absent), radiotherapy field (total cranium vs partial), total radiotherapy dose (60 vs 66 Gy), and adjuvant chemotherapy (present vs absent) were evaluated in univariate analysis. RESULTS: The median survival was 10.3 months in the whole group, 19.5 months in the younger age group and 5.7 months in the older age group. During follow-up re-craniotomy was performed in 2 patients (3%), and 1 patient (1%) developed spinal seeding metastases and was given spinal radiotherapy. In univariate analysis younger age vs older age: median 19.5 months vs 5.27 months (P = 0.0012); Karnofsky performance status > or = 70 vs < 70: median 15.3 months vs 2.67 months (P < 0.0001), and external radiotherapy dose 60 Gy vs 66 Gy: median 11.6 months vs 3 months (P = 0.02) were found as significant prognostic factors for survival. In regression analysis a worse performance status (KPS <70) was found to be the only independent factor for survival (P = 0.014, 95% CI HR = 0.0043 [0.0001-0.15]). CONCLUSIONS: Younger patients with primary glioblastoma multiforme had a relatively long survival (median, 19.5 months, with a 2-year survival rate of 30%) compared to older patients. This was due particularly to their better performance status.

Comparison of three dimensional conformal radiation therapy, intensity modulated radiation therapy and volumetric modulated arc therapy for low radiation exposure of normal tissue in patients with prostate cancer.

Radiotherapy has an important role in the treatment of prostate cancer. Three-dimensional conformal radiation therapy (3D-CRT), intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) techniques are all applied for this purpose. However, the risk of secondary radiation-induced bladder cancer is significantly elevated in irradiated patients compared surgery-only or watchful waiting groups. There are also reports of risk of secondary cancer with low doses to normal tissues. This study was designed to compare received volumes of low doses among 3D-CRT, IMRT and VMAT techniques for prostate patients. Ten prostate cancer patients were selected retrospectively for this planning study. Treatment plans were generated using 3D-CRT, IMRT and VMAT techniques. Conformity index (CI), homogenity index (HI), receiving 5 Gy of the volume (V5%), receiving 2 Gy of the volume (V2%), receiving 1 Gy of the volume (V1%) and monitor units (MUs) were compared. This study confirms that VMAT has slightly better CI while thev olume of low doses was higher. VMAT had lower MUs than IMRT. 3D-CRT had the lowest MU, CI and HI. If target coverage and normal tissue sparing are comparable between different treatment techniques, the risk of second malignancy should be a important factor in the selection of treatment.

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

Metaplastic 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) (51 ±â€Š9% vs. 82 ±â€Š6%, P = 0.013) and overall survival (OS) (68 ±â€Š8% vs. 94 ±â€Š4%, P = 0.009) compared with TNBC histology. Patients who received taxane-based chemotherapy (CT) regimens or adjuvant radiotherapy had significantly better PFS (P = 0.002 and P < 0.001) and OS (P < 0.001 and P < 0.001) compared with others. In the multivariate analysis, MBC (hazard ratio [HR]: 0.09, P < 0.001), presence of neoadjuvant chemotherapy (NACT) (HR: 12.8, P = 0.05), and metastasis development at any time during the clinical course (HR: 38.7, P < 0.001) were significant factors that decreased PFS, whereas metastasis development was the only independent prognostic factor of OS (HR: 23.8, P = 0.009).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.