Treatment outcomes of prostate cancer patients with Gleason score 8-10 treated with definitive radiotherapy : TROD 09-001 multi-institutional study.

PURPOSE: To validate the clinical outcomes and prognostic factors in prostate cancer (PCa) patients with Gleason score (GS) 8-10 disease treated with external beam radiotherapy (EBRT) + androgen deprivation therapy (ADT) in the modern era. METHODS: Institutional databases of biopsy proven 641 patients with GS 8-10 PCa treated between 2000 and 2015 were collected from 11 institutions. In this multi-institutional Turkish Radiation Oncology Group study, a standard database sheet was sent to each institution for patient enrollment. The inclusion criteria were, T1-T3N0M0 disease according to AJCC (American Joint Committee on Cancer) 2010 Staging System, no prior diagnosis of malignancy, at least 70 Gy total irradiation dose to prostate ± seminal vesicles delivered with either three-dimensional conformal RT or intensity-modulated RT and patients receiving ADT. RESULTS: The median follow-up time was 5.9 years (range 0.4-18.2 years); 5­year overall survival (OS), biochemical relapse-free survival (BRFS) and distant metastases-free survival (DMFS) rates were 88%, 78%, and 79%, respectively. Higher RT doses (≥78 Gy) and longer ADT duration (≥2 years) were significant predictors for improved DMFS, whereas advanced stage was a negative prognosticator for DMFS in patients with GS 9-10. CONCLUSIONS: Our results validated the fact that oncologic outcomes after radical EBRT significantly differ in men with GS 8 versus those with GS 9-10 prostate cancer. We found that EBRT dose was important predictive factor regardless of ADT period. Patients receiving 'non-optimal treatment' (RT doses <78 Gy and ADT period <2 years) had the worst treatment outcomes.

Lymphopaenia and accidental splenic doses: Do they have any prognostic value for locally advanced gastric cancer patients treated with radiochemotherapy?

AIM OF THE STUDY: To determine the effect of chemoradiotherapy (CRT)-induced lymphopaenia, and irradiated splenic volume and splenic doses on oncological outcomes in patients with locally advanced gastric cancer (LAGC). MATERIAL AND METHODS: A consecutive cohort of 52 patients with LAGC treated between 2005 and December 2016 was included. The absolute neutrophil, lymphocyte, and platelet counts were recorded prior to any treatment (baseline), just after the completion of CRT, and 2 -6 weeks after the completion of CRT (control evaluation). RESULTS: The median follow-up time was 30 months (range, 8 -130). The incidence of severe lymphopaenia was only 1% at control evaluation, but it was 93% after CRT (p< 0.001). Both in univariate and multivariate analyses, stage 3 disease (p< 0.001 and p = 0.041, respectively) and metastatic to dissected lymph node (MDLN) ratio > 20% (p< 0.001 and p = 0.032) had a negative effect on OS. Mean splenic dose ≥ 35 Gy was a significant poor prognostic factor for OS and recurrence-free survival (RFS) (p = 0.042 and p = 0.50, respectively). Maximum splenic dose ≥ 58 Gy effected OS unfavourably (p = 0.050). Volumetric modulated arc therapy (VMAT), intravenous CT, and age ≥ 65 years were significant predictors for subsequent severe lymphopaenia. CONCLUSIONS: Severe lymphopaenia could not be accepted as a predictive or prognostic factor for LAGC. Mean and maximum splenic doses should be kept on mind while evaluating the treatment dose-volume histograms (DVHs). Patient age, IV usage of concomitant CT agent, and RT technique can influence the ALC. Disease-related factors such as stage and MDLN ratio were the most important factors.

Chemotherapeutic resistance in anaplastic astrocytoma cell lines treated with a temozolomide-lomeguatrib combination.

The treatment of anaplastic astrocytoma (AA) is controversial. New chemotherapeutic approaches are needed for AA treatment. Temozolomide (TMZ) is one of the chemotherapeutic drugs for the treatment of AA. The cytotoxic effects of TMZ can be removed by the MGMT (O(6)-methylguanine-DNA methyltransferase) enzyme. Then, chemotherapeutic resistance to TMZ occurs. MGMT inhibition by MGMT inactivators (such as lomeguatrib) is an important anticancer therapeutic approach to circumvent TMZ resistance. We aim to investigate the effect of TMZ-lomeguatrib combination on MGMT expression and TMZ sensitivity of SW1783 and GOS-3 AA cell lines. The sensitivity of SW1783 and GOS-3 cell lines to TMZ and to the combination of TMZ and lomeguatrib was determined by a cytotoxicity assay. MGMT methylation was detected by MS-PCR. MGMT and p53 expression were investigated by real-time PCR after drug treatment, and the proportion of apoptotic cells was analyzed by flow cytometry. When the combination of TMZ-lomeguatrib (50 µM) was used in AA cell lines, IC50 values were reduced compared to only using TMZ. MGMT expression was decreased, p53 expression was increased, and the proportion of apoptotic cells was induced in both cell lines. The lomeguatrib-TMZ combination did not have any effect on the cell cycle and caused apoptosis by increasing p53 expression and decreasing MGMT expression. Our study is a pilot study investigating a new therapeutic approach for AA treatment, but further research is needed.

Adverse effects of endocrine therapy in breast cancer: single institute experience.

AIM OF THE STUDY: The main purpose of this study is to assess the known adverse effects of adjuvant endocrine therapy for non-metastatic breast cancer patients and to present our single center experience with light of literature. MATERIAL AND METHODS: The breast cancer patients treated with adjuvant radiotherapy in Medical School of Ege University between January 2007 and December 2009 were evaluated for this trial after obtaining their acceptance. Vital findings, bone mineral densitometry, endometrium thickness measured with trans-vaginal ultrasonography, biochemical results including liver function tests and blood lipid profile (total cholesterol, HDL, LDL, VLDL, triglyceride) were recorded for each controls. Socio-demographic data, financial statuses, medical history, co-morbid diseases were obtained from first controls. Patients were followed without any local recurrence and distant metastases until June 2011. RESULTS: Endometrium thickness was not seen in AI using patients. As compared with tamoxifen group, lack of thickness in AI group was statistically significant (p = 0.000). When compared the values before AI, the number of patients who had osteoporosis was gradually increasing. The decrease was seen in the number of patients with osteopenia. The number of patients with normal lipid profile was gradually increasing up to the second evaluation for tamoxifen group (p = 0.000). On the other hand, the number of patients with hyperlipidemia was increasing for AIs group in follow-up period statistically (p = 0.006). CONCLUSIONS: With the aid of careful patient follow and effective disease management strategies, the negative effect over the QoL can be minimized and also the greatest benefit from endocrine therapy can be obtained.

HPV status and immunohistochemical analysis of p16, p53 and PD­L1 expression as prognostic biomarkers in patients with squamous cell anal cancer receiving definitive radiotherapy/chemoradiotherapy.

Anal squamous cell carcinoma (SCC) treated with definitive radiotherapy (RT)/chemoradiotherapy (CRT) has shown high success rates, yet challenges such as treatment resistance and recurrence persist. The present study aimed to investigate the associations between immunohistochemical (IHC) evaluation, treatment response and prognosis in anal SCC. A retrospective cohort analysis included 42 patients with anal SCC treated at a single institution between 2006 and 2022. Human papillomavirus (HPV) status was determined, and the IHC analysis of p16, p53 and PD-L1 expression was conducted using formalin-fixed, paraffin-embedded biopsies. A complete response to RT/CRT was observed in 71.4% of patients. Recurrence occurred in 38.1% of cases, of which 7.1% had local-regional recurrence (LRR), 14.3% had distant recurrence (DR), and 16.7% had both LRR and DR. HPV positivity (71.4%) was significantly associated with p16 positivity. Lack of complete response was associated with HPV-negative status, p16-negative status, increased recurrence and DR. In addition, recurrence was significantly associated with p53-positive status, and p53 positivity was significantly associated with increased LRR. PD-L1 positivity, defined as a combined positive score (CPS) ≥1% was found in 73.8% of the patients, and exhibited significant associations with HPV positivity and p16 positivity. PD-L1 CPS ≥ 1% was also associated with an increased LRR. Univariate analysis revealed that age <65 years, a complete response and HPV positivity were associated with increased 5-year overall survival (OS), while a complete response, HPV positivity and p53-negative status were associated with increased 5-year disease-free survival (DFS). Multivariate analysis identified that age <65 years and HPV positivity are independent prognostic factors for 5-year OS, and a complete response and p53-negative status are independent prognostic factors for 5-year DFS. In conclusion, these findings suggust that the identification of HPV status and poor prognostic biomarkers at diagnosis may be used to guide personalized treatment strategies, with the combination of immunotherapy with standard CRT potentially providing improved outcomes.

Who would be the winner? A prognostic nomogram for predicting the benefit of postoperative radiotherapy ± chemotherapy in patients with locally advanced gastric cancer: TROD-02-01 study.

OBJECTIVES: We aimed to develop a basic, easily applicable nomogram to improve the survival prediction of the patients with stage II/III gastric cancer (GC) and to select the best candidate for postoperative radiotherapy (RT). METHODS: In this multicentric trial, we retrospectively evaluated the data of 1597 patients with stage II/III GC after curative gastrectomy followed by postoperative RT ± chemotherapy (CT). Patients were divided into a training set (n = 1307) and an external validation set (n = 290). Nomograms were created based on independent predictors identified by Cox regression analysis in the training set. The consistency index (C-index) and the calibration curve were used to evaluate the discriminative ability and accuracy of the nomogram. A nomogram was created based on the predictive model and the identified prognostic factors to predict 5-year cancer-specific survival (CSS) and progression-free survival (PFS). RESULTS: The multivariate Cox model recognized lymph node (LN) involvement status, lymphatic dissection (LD) width, and metastatic LN ratio as covariates associated with CSS. Depth of invasion, LN involvement status, LD width, metastatic LN ratio, and lymphovascular invasion were the factors associated with PFS. Calibration of the nomogram predicted both CSS and PFS corresponding closely with the actual results. In our validation set, discrimination was good (C-index, 0.76), and the predicted survival was within a 10% margin of ideal nomogram. CONCLUSIONS: In our relatively large cohort, we created and validated both CSS and PFS nomograms that could be useful for underdeveloped or developing countries rather than Korea and Japan, where the D2 gastrectomy is routinely performed. This could serve as a true map for oncologists who must make decisions without an experienced surgeon and a multidisciplinary tumor board.

Evaluation of treatment outcomes and tolerability in older patients with rectal cancer treated with radiotherapy accompanied by the G-8 geriatric score: TROD13-003 multicenter study.

INTRODUCTION: The choice of treatment for rectal cancer often differs in older and younger patients, with the rate of radiotherapy use lower among older adults. In our daily practice, when evaluating a frail older patient with rectal cancer, we usually choose to give less treatment. This may be due to concern that the patient will not be able to tolerate radiotherapy. The Geriatric 8 score (G8GS) is a guide to evaluating treatment tolerability as it relates to frailty in older adults with cancer. The aim of this study was to evaluate treatment outcomes and tolerability in older patients with rectal cancer treated with radiotherapy (RT) accompanied by G8GS. MATERIALS AND METHODS: Patients aged 65 and older with stage I-III rectal adenocarcinoma who were treated with RT and had a G8 evaluation were included in this multicenter retrospective study. Prognostic factors related to G8GS were calculated using Chi-square and logistic regression tests and survival rates were calculated by the Kaplan-Meier test using the SPSS v24.0 software. All p-values ≤0.05 were considered statistically significant. RESULTS: A total of 699 patients from 16 national institutions were evaluated. The median age was 72 years (range 65-96), and the median follow-up was 43 (range 1-190) months. Four hundred and fifty patients (64%) were categorized as frail with G8GS ≤14 points. Frail patients had higher ages (p = 0.001) and more comorbidities (p = 0.001). Ability to receive concomitant and/or adjuvant chemotherapy rates were significantly higher in fit patients (p = 0.002 and p = 0.001, respectively). No significant difference was observed in terms of grade 3-4 early and late toxicity for both groups. Cancer-related death was higher (p = 0.003), and 5- and 8-year survival rates were significantly lower (p = 0.001), in the frail group. Age and being frail were significantly associated with survival. DISCUSSION: Radiotherapy is a tolerable and effective treatment option for older adults with rectal cancer even with low G8GS. Being in the frail group according to G8GS and having multiple comorbidities was negatively associated with survival. Addressing the medical needs of frail patients through a comprehensive geriatric assessment prior to radiotherapy may improve G8GS, allowing for standard treatment and increased survival rates.

Does neoadjuvant rectal score predict treatment outcomes better than the all grading systems used in neoadjuvantly treated rectal cancer?

BACKGROUND: /Objective: To compare the prognostic value of the yield pathologic (yp) stage, used 4 tumor regression grading (TRG) systems, and neoadjuvant rectal score(NARS) in patients with locally advanced rectal cancer (LARC) who received long-term neoadjuvant chemoradiotherapy (nCRT). METHODS: Between 2005 and 2017, we included 302 patients with LARC who treated with nCRT. Postoperative pathological responses were graded by using Dworak, American Joint Committee on Cancer, Mandart, Memorial Sloan Kettering Cancer Center, grading systems and NARS([5ypN-3(kT-pT)+12]2/9,61) calculations. Their results were compared in terms of treatment outcomes. RESULTS: The median follow-up time was 51 months (range 5-136). There was a significant relation between cT stage and the response in used grading systems(p < 0,001). Median overall(OS), local recurrence free(LRFS), and distant metastasis free(MFS) survival rates were 50, 48, and 45 months, respectively. 5-year OS, LRFS, and MFS rates were 71%, 92%, and 72%, respectively. According to the NARS and treatment response grating systems, a significant difference was found between the low risk and high risk groups in terms of OS, LRFS, and MFS rates. While it was not seen any difference in terms of OS and MFS, NARS was found to predict LRFS better than other grading systems. In multivariate analysis, high NARS was found to be correlated with worse OS and worse MFS. On the other hand, pCR was the another important factor affecting treatment outcomes. CONCLUSIONS: While used systems except NARS group patients according to ypT status in surgical tissue, NARS add the value of ypN status in addition to ypT status. It could be suggested to use NARS to predict LRFS.

Can carotid-sparing radiotherapy approaches replace with conventional techniques for the patients with T1 glottic larynx cancer?

OBJECTIVES: This study aims to compare the carotid artery doses applied with various radiotherapy techniques for the treatment of T1N0 glottic larynx cancer. PATIENTS AND METHODS: Five patients were simulated with using computed tomography (CT). Clinical (CTV) and planning target volumes (PTV) were created for T1N0 glottic larynx cancer. Planning risk volumes (PRV) were constructed for carotid arteries and spinal cord. Three irradiation planning, opposed lateral box field (OLBF), three dimension conformal radiation therapy (3DCRT), intensity modulated radiation therapy (IMRT) were done for each patient. Over 95% of planned target volumes were loaded with predetermined dose (a total of 62.25 Gy of 2.25 Gy daily dose). RESULTS: The comparison of the treatment planning of five T1 glottic larynx cancer, three involving the right vocal cord and two involving the left vocal cord, the technique of IMRT planning was provided the best carotid-sparing doses. Mean carotid V35, V50, and V63 values including OLBF, 3DCRT, and IMRT were 70%, 47%, 35%; 55%, 15%, 5% and 28%, 6%, 0%, respectively. The statistical comparison of V35, V50 and V63 revealed significant values for OLBF and IMRT. Dose of spinal cord did not exceed 45 Gy for any of radiation treatment planning. Between the three techniques, there was no significant difference in terms of conformity index and dose distribution was homogenous with all techniques. CONCLUSION: It is obvious that IMRT planning technique can decrease the carotid artery radiation doses in early stage glottic larynx cancer.

Evaluation of the relationship between the eighth edition of TNM staging, the mMasoaka, and World Health Organization histopathological classification for thymoma.

Aim of Study: The aim of this study was to describe the correlation between the eighth tumor, node, and metastasis (TNM), mMasaoka staging, and the World Health Organization (WHO) histopathologic classification and to identify prognostic values in predicting survival and recurrence of thymoma. Materials and Methods: Medical files of 90 patients with thymoma diagnosed between 1992 and 2018 were evaluated for this trial. Results: The distributions of patients were similar between mMasaoka and eighth TNM staging according to early (I, II) and advanced stages (IIIA, IIIB, IV). Interestingly, 55 of 63 stage I patients with TNM staging showed difference as 31 of them up-staged to stage IIA and 24 of them up-staged to stage IIB in mMasoaka staging. Both staging systems closely correlated with WHO classification (p < 0.001); stages I and II were associated with low-risk groups (type A, AB, B1), and stages III and IV were associated with high-risk groups (type B2, B3). WHO classification was not a prognostic factor for overall survival (OS) (P = 0.13) and progression-free survival (PFS) (p = 0.08), but it was a prognostic factor for 10-year cancer-specific survival (CSS) (p = 0.04). Myasthenia gravis was associated to early stages (stage I, II) (p = 0.007) and related with better prognosis. Conclusions: Our study showed a correlation between both staging system and WHO classification. A certain difference was found between eighth TNM staging and the mMasoaka staging in terms of stage I disease. Both staging systems effectively prognosticated OS, CSS, and PFS. To clarify the prognostic relevance and clinical usefulness of the WHO classification may be beneficial in clinical practice for the treatment decision.

Fractionated charge variants of biosimilars: A review of separation methods, structural and functional analysis.

The similarity between originator and biosimilar monoclonal antibody candidates are rigorously assessed based on primary, secondary, tertiary, quaternary structures, and biological functions. Minor differences in such parameters may alter target-binding, potency, efficacy, or half-life of the molecule. The charge heterogeneity analysis is a prerequisite for all biotherapeutics. Monoclonal antibodies are prone to enzymatic or non-enzymatic structural modifications during or after the production processes, leading to the formation of fragments or aggregates, various glycoforms, oxidized, deamidated, and other degraded residues, reduced Fab region binding activity or altered FcR binding activity. Therefore, the charge variant profiles of the monoclonal antibodies must be regularly and thoroughly evaluated. Comparative structural and functional analysis of physically separated or fractioned charged variants of monoclonal antibodies has gained significant attention in the last few years. The fraction-based charge variant analysis has proved very useful for the biosimilar candidates comprising of unexpected charge isoforms. In this report, the key methods for the physical separation of monoclonal antibody charge variants, structural and functional analyses by liquid chromatography-mass spectrometry, and surface plasmon resonance techniques were reviewed.

Trends in the incidence and overall survival of multiple primary cancers in Turkey.

PURPOSE: Multiple primary malignant tumors (MPCs) are defined as at least two histologically distinct malignancies in one individual. We aimed to present the risk of developing multiple primary cancers and to give information about the periods and prediction data regarding survival outcome for MPCs. METHODS: All patients with MPCs between 1992-2017 were included in this study. Patients were compared in terms of the primary cancer number, age at diagnosis of first primary cancer, gender, time interval after first cancer detected, cancer types seen mostly together, and the rate of MPCs during the years. RESULTS: The total number of included patients was 117,139. The proportion of patients with MPCs during the follow-up period was 4.95% (n=5,796). Eighteen percent of the cases were synchronous and 82% metachronous. MPCs were most commonly detected in the gastrointestinal tract and were detected more commonly in men than in women (p<0.001). Patients receiving radiotherapy (RT) (p<0.001) and chemotherapy (CT) (p <0.001) had more MPCs than those who never received RT or CT. Survival in MPCs was worse than in single primary cancers. The 5- and 10-year survival rates were 28.1%, and 12.4%, respectively. CONCLUSION: We identified approximately 5% MPCs among 117,139 patients in our database. MPCs are more common at 60-69 years in males and at 50-59 years in females. In terms of the risk of MPCs, we should be aware of the cancers that have risk factors, habits, and genetic features commonly affecting primary cancers.

Prognostic significance of early complete response in patients with locally advanced rectal cancer undergoing preoperative chemoradiotherapy: Multicentric study of Turkish Society for Radiation Oncology Group (TROD).

BACKGROUND/AIMS: To assess the effect of various parameters on the oncologic outcomes, including the time interval between therapy and surgery (S) in locally advanced rectal cancer (LARC) patients receiving preoperative chemoradiotherapy (CRT). MATERIALS AND METHODS: The data of 914 LARC patients who received preoperative CRT between 1994 and 2015 were collected retrospectively. Patients received 45-50.4 Gy RT with 5FU based chemotherapy (CT). They all underwent radical resection followed by maintenance CT. Clinical and pathologic variables were compared between the pCR and no-pCR groups. Survival was estimated by the Kaplan-Meier method and Cox proportional hazard model was used in multivariate analysis. RESULTS: After median follow-up of 60.5 (range=12-297.6) months, median overall survival (OS) was 58.75 months and disease-free survival (DFS) 53.32 months. pCR was observed in 18.9% of all cases. pCR, lymphovascular invasion and metastatic lymph node ratio (mLNR) were significantly associated with OS and DFS on multivariate analysis. The 5-year OS and DFS rates were better in pCR group (95.3% vs 80.7% for OS, p<0.0001 and 87.4% vs 71% for DFS, p<0.0001). pCR patients with 4-8 weeks interval had lower rates of distant metastasis (9% vs 20%, p=0.01) and any recurrences (13.6% vs 29.6%, p=0.001) than the remaining. Both OS and DFS were better in favor of pCR achieved at 4-8 week interval time (p<0.0001 for each). CONCLUSION: pCR after preoperative CRT in LARC correlated with better oncologic outcome. The best OS and DFS durations were achieved in patients who experienced pCR after 4-8-weeks interval before surgery.

Patterns of failure for early-stage glottic carcinoma: 10 years' experience in conformal radiotherapy era.

PURPOSE: Larynx cancer is the most common head-and-neck cancer in Turkey. Vocal cords are involved nearly 70%-80% of laryngeal carcinomas. We aim to present our 10 years' experience and failure patterns of the patients with T1 and T2 glottic laryngeal carcinoma by same manner, technique, doses, and physician in conformal radiotherapy (RT) era. METHODS: Between January 2005 and December 2015, a total of 143 patients treated with definitive RT for early-stage glottis laryngeal cancer were selected. The total dose was 65.25 Gy in 29 fractions. RESULTS: The median follow-up time was 64 (range: 12-150) months. All of the patients had a complete clinical response to the treatment. A 5-year local control (LC) rates were 84.5%, 91.8%, 74%, and 56% for overall, T1a, T1b, and T2, respectively. Ultimate LC rates (after salvage treatment) for 5 years were 90%, 95%, 92%, and 75% for overall, T1a, T1b, and T2, respectively. Regional neck control for the whole group was 92% for 5 years. After the initial RT, a total of 22 (15.4%) patients had disease recurrence at any site of the neck or larynx. Median time to disease recurrence was 59.5 months (range: 5-150). CONCLUSION: This study represents a large and long-term analysis of early-stage glottic carcinoma treated by same manner, technique, doses, and physician in conformal RT era. Definitive RT provides a high LC rate, tolerable toxicity, and favorable voice quality. Extension beyond the vocal cords and T2 stage are the most important unfavorable prognostic factors regarding LC.

Role of consolidative radiation therapy for patients with mediastinal diffuse large B-cell lymphoma in the rituximab era.

BACKGROUND: The most common subtype of aggressive non-Hodgkin Lymphomas is diffuse large B-cell lymphoma (DLBCL). Mediastinal DLBCL is a distinct entity with unique clinical, pathologic, and genetic features and accepted as a subtype of DLBCL. The aim of this study is to evaluate the patients treated with consolidative radiotherapy (RT) after rituximab-containing chemotherapy for mediastinal DLBCL regarding treatment outcomes and relapse patterns. MATERIAL AND METHODS: Forty-two patients with the diagnosis of mediastinal DLBCL who were treated at the Ege University Hospital between January 2008 and December 2014 were evaluated. All patients received 2-10 cycles of rituximab-containing chemotherapy schedule (mostly CHOP). RT was delivered to a total dose of 30.6-45 Gy with 1.8 Gy daily fractions in 4-5 weeks. The irradiation fields were designed by using involved lymphatic site technique. RESULTS: The median age at diagnosis was 53 years (range, 18-85 years). Ann Arbor clinical stage at diagnosis was as follows: 8 patients (19%) at Stage I, 20 patients (47.6%) at Stage II, 7 patients (16.7%) at Stage III, and 7 patients (16.7%) at Stage IV. The median follow-up period was 47 months (range, 7-96 months). Complete response was obtained in 27 patients (64.3%), partial response was obtained in 14 patients (33.3%) across all stages. Estimated 5-year overall survival (OS) and progression-free survival (PFS) rates were, respectively, 84% and 77% for all patients, 100% and 92% for the patients without residual disease after chemotherapy. CONCLUSION: The response to chemotherapy is the most important factor affecting both OS and PFS. The role of consolidative RT is not clear in the rituximab era due to the lack of phase III trial. However, available literature shows that consolidative RT may still have a role in mediastinal DBLCLs.

Evaluation of unusual and highly aggressive variant of endometrium cancer: nonendometrioid endometrium carcinoma of the uterus.

AIMS: To evaluate the survival and treatment outcomes of patients with nonendometrioid endometrium carcinoma after postoperative radiotherapy. METHODS: The records of 94 patients treated with postoperative radiotherapy (RT) between January 2005 and December 2011 were retrospectively reviewed. Postoperative RT was delivered with a dose of 45-50.4 Gy with 1.8 Gy daily fractions and brachytherapy was added to external RT for 62 patients with a dose of 3 × 6 Gy. Median follow-up time was 35 months (range 6-95 months). RESULTS: Median age was 63 years (range 43-83 years) and lymph node metastasis (LNM) was positive in 15 (16.0%) patients. The stage distribution of the patients was as follows: stage I, 58 (61.7%); stage II, 16 (17.0%); stage III, 18 (19.1%); stage IV, 2 (2.2%). Five-year locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) rates were 92.3%, 68.2%, and 78.6%, respectively. In univariable analysis, it was determined that the factors affecting OS rates were stage (p = 0.003), presence of LNM (p = 0.003), and presence of lymphovascular space invasion (LVSI) (p = 0.007); factors affecting DFS rates were stage (p = 0.019), presence of LVSI (p = 0.002), and having LNM (p = 0.049); and the factor affecting LRC rates was tumor size (>5 cm) (p = 0.011). In subgroup analyses, among all stage I patients, the DFS rates were lower for those with histologic grade 3 tumors and more than ½ myometrial invasion. CONCLUSIONS: Due to its rarity, the prognostic factors and outcomes of nonendometioid endometrium carcinoma are not fully understood. In our analysis, stage, LNM, and presence of LVSI were found to be the most important prognostic factors. In order to tailor the optimal treatment strategy, prospective studies are needed.

Oncoplastic reduction mammoplasty for breast cancer in women with macromastia: Oncological long-term outcomes.

OBJECTIVE: To evaluate the long-term results of tumorectomy and concomitant bilateral oncoplastic reduction mammoplasty (ORM) for early stage breast cancer patients with macromastia in terms of local disease control and long-term oncological results. PATIENTS AND METHOD: Data of 82 patients with macromastia undergoing ORM for breast cancer between 1996 and 2011 were retrospectively examined and evaluated with regard to oncological results. RESULTS: The median age was 50 years. The median follow-up was 121 months (range 28-212 months). The median breast volume was 1402 cm3 and the median weight of excised breast material was 679 g. The median surgical margin was 16 mm. Ten-year local recurrence rate was 8.7%. The 10-year overall survival rate was 82.2% and the disease-free survival rate was 73.2%. Early and late complication rates were 12.2% and 14.6%, respectively. CONCLUSIONS: From the standpoint of local disease control and long-term observation, ORM can be considered a very safe and acceptable treatment for early stage breast cancer in women with macromastia.

Quality of life assessment in women with breast cancer: a prospective study including hormonal therapy.

PURPOSE: Evaluating the effect of hormonal treatment on quality of life (QoL) in breast cancer patients by using the Functional Assessment of Cancer Treatment (FACT) questionnaire is the main purpose of this trial. METHODS: Breast cancer patients treated with adjuvant between January 2007 and December 2009 were evaluated. The first survey was done after patients completed their whole adjuvant treatment except for the hormonal therapy and this was as 'basal assessment.' The second survey was done 6 to 12 months after the basal surveys during their routine policlinic controls. The last survey was done within the last 18 to 24 months of the follow-up period. RESULTS: The effect of marital status, number of pregnancies, residence in the village or city, hemoglobin levels, chemotherapy and hormonal therapy for any other reason except for breast cancer on the QoL could not be seen. Endocrine subscale scores were detected to be higher in patients aged >60 years than in younger ones. The other dimension scores were low in the elderly patient group. There was a statistically significant relationship between being >30 years old and improvement in the social well-being score (p=0.028). The functional well-being scores were found to be significantly higher in the patient group that had no comorbid disease (p=0.018). Endocrine subscale scores were statistically worse in patients who had psychiatric disease (p=0.057) but the general QoL data were similar with others. It was shown that all QoL scores for all dimensions had statistically significant changes (p<0.001) in terms of hormonal regimes. CONCLUSION: The diagnosis of breast cancer was found to be an independent factor that affects social well-being and social life in a negative way. We must give attention to complaints including complaints about sexual life and hormonal status in order to ensure compliance of patients with the required hormonal regimens. By the help of future research, we can improve the prognosis of this disease through increased treatment adherence and belief of patients.

MicroRNA changes in advanced radiotherapy techniques and its effect to secondary cancers.

MicroRNAs (miRNAs) are a kind of RNA, produced copies of endogenous hairpin-shaped, are 21-25 nucleotide length, small, and single chain. Recent studies have revealed that hundreds of miRNAs are found in the human genome and are responsible for diverse cellular processes including the control of developmental timing, cell proliferation, apoptosis and tumorigenesis. miRNAs can activate the initiation of apoptosis, cessation of the cell cycle and aging in case of DNA damage by stimulating the tumor suppressor target gene p53 directly and indirectly. DNA damage is composed by multiple stress factors including ionizing radiation, reactive oxygen species, UV exposure and drugs like doxorubicin and camptothecin. Radiation is used widely in health, academic area, and industry for producing electricity. As a result of using radiation widely in different fields, environmental radiation exposure is increasing as well. Whereas high dose radiation exposure causes DNA damage and gives rise to ionization to molecules of living cells by accelerating malignant tumor formation. Fields receiving high dose radiation are evaluated in terms of adverse effects, therapeutic efficacy and secondary malignancies in radiotherapy applications. Dose distributions are re-created when it is required. On the other hand, fields received low dose and the doses that the patient is exposure in simulation and/or portal imaging are often overlooked. The changes in miRNA levels arising in low dose radiation field and its effect to neoplastic process in cell will be pathfinder in terms of secondary cancers or second primary cancers. It is shown that there are differences between the level changes of miRNA in low dose fields which are overlooked in daily practical applications because of not resulting with acute or chronic side effect and the level changes of miRNA in high dose fields. With the help of verifying so-called differences in low dose fields which are seen in advanced radiation techniques, radiation oncologists must be careful when using these techniques in childhood cancers and the patient group which have long overall survival period. Additionally, demonstrating the pathway which is influenced by miRNA changes can provide us the opportunity to focus on the exact cancer type which has to be followed. So that we can detect the secondary cancers earlier and can treat them with long expected survival period.