Dose Volume and Liver Function Test Relationship following Radiotheraphy for Right Breast Cancer: A Multicenter Study.

OBJECTIVE: The liver is a critical organ at risk during right breast radiotherapy (RT). Liver function tests (LFTs) such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) serve as biochemical markers for hepatobiliary damage. In this multicenter cross-sectional study, the effects of liver dose-volume on changes in LFTs pre- and post-RT in patients treated for right breast cancer were evaluated. MATERIALS AND METHODS: Between January 2019 and November 2022, data from 100 patients who underwent adjuvant right breast RT across three centers were retrospectively assessed. Target volumes and normal structures were contoured per the RTOG atlas. Patients were treated with a total dose of 50 Gy in 25 fractions to the CTV, followed by a boost to the tumor bed where indicated. The percentage change in LFT values in the first two weeks post-RT was calculated. Statistics were analyzed with SPSS version 22 software, with significance set at p < 0.05. Statistical correlation between liver doses (in cGy) and the volume receiving specific doses (Vx in cc) on the change in LFTs were analyzed using Kolmogorov-Smirnov, Mann-Whitney U test. RESULTS: The median age among the 100 patients was 56 (range: 29-79). Breast-conserving surgery was performed on 75% of the patients. The most common T and N stages were T1 (53%) and N0 (53%), respectively. None of the patients had distant metastasis or simultaneous systemic treatment with RT. A total of 67% of the treatments utilized the IMRT technique and 33% VMAT. The median CTV volume was 802 cc (range: 214-2724 cc). A median boost dose of 10 Gy (range: 10-16 Gy) was applied to 28% of the patients with electrons and 51% with IMRT/VMAT. The median liver volume was 1423 cc (range: 825-2312 cc). Statistical analyses were conducted on a subset of 57 patients for whom all three LFT values were available both pre- and post-RT. In this group, the median values for AST, ALT, and GGT increased up to 15% post-RT compared to pre-RT, and a median liver Dmean below 208 cGy was found significant. While many factors can influence LFT values, during RT planning, attention to liver doses and subsequent regular LFT checks are crucial. CONCLUSION: Due to factors such as anatomical positioning, planning technique, and breast posture, the liver can receive varying doses during right breast irradiation. Protecting patients from liver toxicity secondary to RT is valuable, especially in breast cancer patients with a long-life expectancy. Our study found that, even in the absence of any systemic treatment or risk factors, there was an average increase of nearly 15% in enzymes, indicating acute liver damage post-RT compared with pre-RT. Attention to liver doses during RT planning and regular follow-up with LFTs is essential.

Revisiting the Radical Radiotherapy-Radiochemotherapy Results in Anal Canal Cancers: (TROD Gastrointestinal Group Study 02-005).

BACKGROUND AND AIM: This study aimed to determine treatment outcomes and factors affecting prognosis in patients diagnosed with anal canal cancer who received radical radiotherapy (RT) or radiotherapy combined with chemotherapy (CT-RT) in radiation oncology centers in Turkey and compare the results with literature. MATERIAL AND METHOD: The study included 193 patients with anal canal cancer reported between 1995 and 2019, of which 162 had complete data. The study was conducted in 11 radiation oncology centers, and a joint database was shared among them. Patients received radiotherapy doses of 45 Gy to 60 Gy. Data analysis was done using SPSS for Windows version 20. RESULTS: Median follow-up was 48.51 months (2-214). All patients received radiotherapy, and 140 (86.4%) received concurrent chemotherapy. Radiotherapy doses of 50.4 Gy to 60 Gy were administered to 74 patients (45.7%) using 2-dimensional-3-dimensional (2D-3D) conformal therapy and 70 patients (43.2%) using intensity modulated radiotherapy technique (IMRT). Acute phase hematologic toxicity was observed in 62 patients (38.3%), and nonhematologic toxicity in 123 patients (75.9%). The 5-year overall survival (OS) rate was 75.1% and disease-specific survival (DSS) rate was 76.4%. OS without colostomy was achieved in 79,8 % at 5 years, and complete response in 112 patients (69.1%). OS rate was significantly higher in 142 patients with positive response (P < .000) and 112 with complete response (P < .000). Anemia (P < .002), local progression, and systemic progression (P < .000) resulted in lower OS (P < .002). In univariate analysis, factors affecting OS rate were: gender, age, stage, lymph node status, T stage, RT treatment duration, and treatment planning with PET fusion, which were found to be statistically significant. Completing radiotherapy in less than 45 days, concurrent chemotherapy, and continued administration of mitomycin and 5 FU as chemotherapy had a significant positive effect on overall survival. OS rate was higher in patients receiving RT dose of 58 Gy or less and undergoing IMRT planning in radiotherapy. IMRT was associated with lower acute and late side effects. CONCLUSION: Radiochemotherapy is the primary treatment for anal canal cancer and advanced radiotherapy techniques may increase survival by reducing side effects and improving treatment continuation. Higher treatment doses require further investigation. The efficacy of treatment can be improved by including patients treated with modern radiotherapy techniques in multicenter prospective studies using new and more effective chemotherapy and immunotherapy agents.

Evaluation of hereditary/familial breast cancer patients with multigene targeted next generation sequencing panel and MLPA analysis in Turkey.

Breast cancer, a worldwide leading cause of cancer in women, may occur in familial cases. Germline mutations in BRCA1/2 genes are responsible for 15% of the familial cases. With the power of next generation sequencing (NGS) analysis, it is possible to analyze genes related to hereditary susceptibility to breast cancer and investigate the genetic etiology more thoroughly. In this study, we investigated 30 genes identified frequent pathogenic alleles in Turkish population. The study includes 495 unrelated individuals diagnosed with breast cancer who are selected for genetic testing according to NCCN criteria for hereditary breast cancer. All patients were analyzed by NGS for BRCA1/2 genes. Deletion/duplication investigation by Multiplex ligation-dependent probe amplification (MLPA) and massive sequencing of 30 breast cancer-related genes (Oncorisk Gene Panel) were performed in a stepwise manner. BRCA1/2 variants are the most frequent pathogenic variants which are found in 45 of 495 (9.1%) patients. Four previously unreported, novel, pathogenic variants of BRCA2 gene are identified. In four cases, exonic deletions of BRCA1/2 genes are determined and there is no duplication of these genes. NGS panel investigation involving other moderate-high risk genes contributed genetic diagnosis in an extra 39 out of 419 (9.3%) cases. Our study presents the cost effectiveness of the gene panel approach. We suggest that gene panels should be the first-tier genetic testing for hereditary breast cancer and MLPA analysis of BRCA1/2 genes should be investigated as a complementary method of NGS analysis.

Cross-sectional areas of rectus abdominis and psoas muscles reduces following surgery in rectal cancer patients.

PURPOSE: To evaluate the trophic changes in rectus abdominis and psoas muscles in patients who underwent open or laparoscopic rectum resection for rectal cancer. METHODS: We retrospectively analyzed preoperative staging computerized tomographies (CT) and postoperative first oncological follow-up CTs of the patients who underwent low anterior resection (LAR) for rectal cancer from 2010 through 2015. We measured cross-sectional area of left and right rectus abdominis muscles from two levels (above and below umbilicus) where they are widest and psoas muscle at mid-level of the fourth lumbar vertebral body in axial CT images and compared preoperative and postoperative measurements. We investigated the effects of age, sex, administration of preoperative chemoradiotherapy (CRT), type of surgery (open or laparoscopic), or construction of a diverting ileostomy on cross-sectional muscle area changes. RESULTS: After applying inclusion and exclusion criteria 60 patients found to be eligible for the study. Muscle areas of all measurement sites were reduced postoperatively compared to paired preoperative values. There was no significant effect of age, sex, administration of preoperative CRT, type of surgery (open or laparoscopic), or construction of a diverting ileostomy to muscle cross-sectional area reductions. CONCLUSION: Cross-sectional areas of the rectus abdominis and the psoas muscles of rectal cancer patients reduces following rectum resection which indicates atrophy of these muscles. Clinicians should be aware of this problem and focus on prevention of muscle atrophy during the treatment of rectal cancer patients.

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.

Prognostic Importance of Tumor Deposits in the Ipsilateral Axillary Region of Breast Cancer Patients.

Tumor deposits (TD) are irregular discrete tumor masses in adipose tissue, discontinuous from the primary tumor, that are described in various cancers. The incidence and/or prognostic value of TD in breast carcinomas have not been studied so far. We reevaluated 145 breast cancer patients, diagnosed and treated between 2001 and 2006 at our institution for the presence and incidence of TD. Histologic type, grade, size of the primary tumor, estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2 status of the tumor, and presence of peritumoral lymphovascular invasion were included in the data. TD were detected in 42 cases (29.0%). The mean age of the patients was 52.2 years (27-82). Most patients (79.3%) had either invasive carcinoma of no special type (NST) or invasive lobular carcinoma, and most tumors (86.9%) were either grade 2 or 3. After excluding TD from the number of metastatic lymph nodes, the pN status of 9 patients changed. Univariate analysis of 110 patients with follow-up information revealed that the new pN status (p = 0.036), presence of local recurrence (p = 0.016) and TD (p = 0.003) were significantly correlated with distant metastases. The median follow-up of the patients was 84 months (5-161), 10-year disease-free survival and overall survival were 67.2% and 73.7%, respectively. In multivariate analysis, presence of TD remained independently associated with distant metastasis (p = 0.002). The probability of distant metastasis was 3.3 times higher in patients with TD. These results emphasize that TD are present in breast cancer patients, and that their presence should warn the clinician in terms of possible distant metastasis. Therefore, presence of TD, the evaluation of which is neither time consuming nor require sophisticated methods, should be included in pathology reports.

Psychosexual and body image aspects of quality of life in Turkish breast cancer patients: a comparison of breast conserving treatment and mastectomy.

AIMS AND BACKGROUND: Assessing psychosexual and body image aspects of quality of life in Turkish breast cancer patients treated by either mastectomy or breast conserving treatment (BCT). METHODS: The study group consisted of 112 patients who had undergone all treatment at a single institution under the care of a multidisciplinary breast team. Following surgery, all patients underwent adjuvant radiotherapy with or without chemotherapy and hormone therapy. At the time of this study all patients were disease free with at least 2 years' follow-up. Twenty percent of the patients were premenopausal and 80% postmenopausal. The patients completed a questionnaire consisting of 42 questions related to their sexual relations and body image. RESULTS: Forty-one percent of sexually active patients had experienced a deterioration of sexual functioning after treatment. This was mainly due to loss of libido (80%), loss of interest in partner (54%), and sexual dissatisfaction (59%). Problems tended to develop early in the course of treatment. Decreased sexual desire was significantly more frequent in patients undergoing mastectomy versus BCT (80% vs 61%; P = 0.043) and in premenopausal versus postmenopausal patients (P = 0.024). Although 80% of patients were satisfied with their appearance as a whole, only 54% liked their naked bodies. There was no significant difference in body image scores between patients undergoing mastectomy or BCT apart from a general feeling of physical unattractiveness in mastectomy patients (3.4 vs 2.8; P = 0.03). CONCLUSIONS: Significant, similar psychosexual and body image problems occur in patients treated for breast cancer with either mastectomy or BCT. Problems arise early in the course of the disease and therefore detection and treatment of these problems should be addressed during the patients' initial assessment and at the start of treatment. These findings are similar to those reported on similar groups of treated women in American and European populations.

Importance of patient, tumour and treatment related factors on quality of life in head and neck cancer patients after definitive treatment.

The purpose of this study is to assess patient, tumour and treatment related factors on quality of life (QoL) outcomes of patients who received definitive or postoperative radiotherapy +/- chemotherapy for head and neck (H&N) cancer. In this cross-sectional study, 110 H&N cancer patients were evaluated in follow-up visit and were asked to fill out the European Organisation for Research and Treatment of Cancer QoL Core Questionnaire (QLQ-C-30) and H&N Module (QLQ-H&N35). Patients were also graded for their late side effects using EORTC/RTOG scoring system. The QLQ C-30 and QLQ-H&N35 mean scores were compared using ANOVA analysis for these variables: age, gender, occupation, educational status, social security status, place of residence, tumour localization, clinical stage, comorbidity, Karnofsky performance score, treatment modality and side effects. Median follow-up was 29 (4-155) months. Tumour localization was significant factor affecting physical (P = 0.03), social (P = 0.01), cognitive (P = 0.002) functioning. Treatment modality had significant impact on the physical (P = 0.02) and cognitive scores (P = 0.008). Global QoL was affected significantly by disease stage (P = 0.01) and occupation (P = 0.01). The QLQ-H&N35 scores were found significantly higher in patients with moderate/severe late morbidity. Tumour localization and the treatment modality are the most important factors affecting the QoL of H&N cancer patients treated definitively.

Patterns of care for lung cancer in radiation oncology departments of Turkey.

PURPOSE: To determine the patterns of care for lung cancer in Turkish radiation oncology centers. METHODS AND MATERIALS: Questionnaire forms from 21 of 24 (87.5%) centers that responded were evaluated. RESULTS: The most frequent histology was non-small cell lung cancer (NSCLC) (81%). The most common postoperative radiotherapy (RT) indications were close/(+) surgical margins (95%) and presence of pN2 disease (91%). The most common indications for postoperative chemotherapy (CHT) were ">/= IB" disease (19%) and the presence of pN2 disease (19%). In Stage IIIA potentially resectable NSCLC, the most frequent treatment approach was neoadjuvant concomitant chemoradiotherapy (CHRT) (57%). In Stage IIIA unresectable and Stage IIIB disease, the most frequent approach was definitive concomitant CHRT (91%). In limited SCLC, the most common treatment approach was concomitant CHRT with cisplatin+etoposide for cycles 1-3, completion of CHT to cycles 4-6, and finally prophylactic cranial irradiation in patients with complete response (71%). Six cycles of cisplatin + etoposide CHT and palliative thoracic RT, when required, was the most commonly used treatment (81%) in extensive SCLC. Sixty-two percent of centers did not have endobronchial brachytherapy (EBB) facilities. CONCLUSION: There is great variation in diagnostic testing, treatment strategies, indications for postoperative RT and CHT, RT features, and EBB availability for LC cases. To establish standards, national guidelines should be prepared using a multidisciplinary approach.