Retrospective evaluation of the contribution of radiotherapy to survival in breast cancer treatment with propensity score based on stage and subgroup.

BACKGROUND: Breast cancer has been a disease in which treatment strategy has changed over time under the influence of different hypotheses and evidence for more than a century. We analyzed the contribution of radiotherapy to disease-free survival and overall survival by classifying according to stage, 1-3 lymph node involvement, and molecular subgroups. METHODS: Following the approval of the Institutional Review Board, records of patients with breast cancer who were admitted to University School of Medicine Departments of Radiation Oncology and Medical Oncology between July 1999 and December 2020 were reviewed. Using data propensity score matching was performed between the groups that did and did not receive radiotherapy using an optimal matching algorithm (optimum, 1:1). Disease-free survival and overall survival after propensity score matching were calculated using the Kaplan-Meier method. Univariate and multivariate Cox regression analysis was used to estimate hazard ratios. RESULTS: In the radiotherapy and non-radiotherapy groups, disease-free survival was 257.42 ± 5.46 (246.72- 268.13), 208,96 ± 8,15 (192,97-224,94) months respectively, (p = < 0.001), overall survival was 272,46 ± 8,68 (255,43-289,49), 219,05 ± 7,32 (204,70-233,41) months respectively (p = .002). We compared the 19 N1 patient groups who received radiotherapy with the 19 patients who did not receive radiotherapy and calculated the disease-free survival times was 202,21 ± 10,50 (181,62-222,79) and 148,82 ± 24,91 (99,99-197,65) months respectively (p = .011) and overall survival times was 200,85 ± 12,79 (175,77-225,92) and 166,90 ± 20,39 (126,93-206,82) months respectively (p = .055). We examined disease-free survival and overall survival times in both groups according to Luminal A, Luminal B, TNBC, and HER2-enriched subgroups. In the Luminal B subgroup, the disease-free survival duration in the groups receiving radiotherapy and not receiving radiotherapy was 264.83 ± 4.95 (255.13-274.54) and 187.09 ± 11.06 (165.41-208.78) months (p < .001), and overall survival times were 252.29 ± 10.54 (231.62-272.97) and 197.74 ± 9.72 (178.69-216.80) months (p = .001) respectively. CONCLUSIONS: Thanks to studies proving that RT increases long-term survival rates in breast cancer as a result of reducing locoregional recurrence and systemic metastasis rates, it has been understood that the spectrum hypothesis is the hypothesis that most accurately describes breast cancer to date. We found that patients with Luminal B invasive breast cancer benefited significantly more from RT compared to other subgroups.

Classifying invasive lobular carcinoma as special type breast cancer may be reducing its treatment success: A comparison of survival among invasive lobular carcinoma, invasive ductal carcinoma, and no-lobular special type breast cancer.

PURPOSE: The literature contains different information about the prognosis of invasive lobular carcinoma of breast cancer (BC). We aimed to address the inconsistency by comparatively examining the clinical features and prognosis of invasive lobular carcinoma patients in our university and to report our experience by dividing our patients into various subgroups. PATIENTS AND METHODS: Records of patients with BC admitted to Trakya University School of Medicine Department of Oncology between July 1999 and December 2021 were reviewed. The patients were divided into three groups (No-Special Type BC, Invasive Lobular Special Type BC, No-Lobular Special Type BC). Patient characteristics, treatment methods and oncological results are presented. Survival curves were generated using the Kaplan-Meier method. Statistical significance of survival among the selected variables was compared by using the log-rank test. RESULTS: The patients in our study consisted of 2142 female and 15 male BC patients. There were 1814 patients with No-Special Type BC, 193 patients with Invasive Lobular Special Type BC, and 150 patients with No-Lobular Special Type BC. The duration of disease-free survival (DFS) was 226.5 months for the No-Special Type BC group, 216.7 months for the No-Lobular Special Type BC group, and 197.2 months for the Invasive Lobular Special Type BC group, whereas the duration of overall survival (OS) was 233.2 months for the No-Special Type BC group, 227.9 for the No-Lobular Special Type BC group, and 209.8 for the Invasive Lobular Special Type BC group. The duration of both DFS and OS was the lowest in the Invasive Lobular Special Type BC group. Multivariate factors that were significant risk factors for OS were Invasive Lobular Special Type BC histopathology (p = .045), T stage, N stage, stage, skin infiltration, positive surgical margins, high histological grade, and mitotic index. Modified radical mastectomy, chemotherapy, radiotherapy and use of tamoxifen and aromatase inhibitors for more than 5 years were significant protective factors for overall survival. CONCLUSION: The histopathological subgroup with the worst prognosis in our study was Invasive Lobular Special Type BC. Duration of DFS and OS were significantly shorter in Invasive Lobular Special Type BC than No-Lobular Special Type BC group. The classification of Invasive Lobular BC under the title of Special Type BC should be reconsidered and a more accurate treatment and follow-up process may be required.

Breast Cancer Subtypes and Prognosis: Answers to Subgroup Classification Questions, Identifying the Worst Subgroup in Our Single-Center Series.

Purpose: Many studies report the triple negative breast cancer (TNBC) as the worst subgroup, as such patients do not benefit from anti-hormonal therapy and human epidermal growth factor receptor 2 (HER2) antagonists. While HER2 overexpression was a poor prognostic factor in breast cancer before trastuzumab (Herceptin) was available, TNBC is often reported as the worst BC subgroup since targeted therapy is currently not possible. Since the patience-specific experiences and the current literature did not always align, we aimed to determine the BC subgroup with the shortest survival in our center. Methods: The records of patients with BC who were admitted to Trakya University Faculty of Medicine Department of Medical and Radiation Oncology between July 1999 and December 2019 were reviewed. Patients were divided into four main groups (Luminal A, Luminal B, TNBC, and HER2-enriched) according to the St Gallen International Consensus Panel and four subgroups in accordance with estrogen receptor, progestin receptor and HER2 positivity. Patient characteristics, treatment characteristics and clinical outcomes of the four main subgroups were evaluated. Survival curves were generated using the Kaplan-Meier method, and the significance of survival differences among the selected variables was compared by using the Log rank test. Factors affecting disease-free survival (DFS) and overall survival (OS) were analyzed by Cox regression analysis. Results: Statistical analysis was performed on 2017 patients, after excluding patients with phyllodes tumor, carcinoma-in-situ and missing information from a total of 2474 patients with BC. There were 952 (47.1%) patients in the Luminal A group, 236 (34.1%) in the Luminal B group, 236 (11.7%) in the TNBC group and 142 (7.1%) patients in the HER2 enriched group. HER2-enriched patients had the shortest survival (p < 0.001), with 113.70 ± 7.17 months of DFS and 125.45 ± 3.03 months of OS. For patients who received Herceptin, DFS was 101.50 ± 6.4 months and OS was 118.14 ± 6.16. Patients who did not receive Herceptin had 92.79 ± 18 months of DFS and 94.44 ± 15.23 months of OS. Conclusion: The HER2-enriched subgroup had the worst prognosis despite receiving targeted therapy. While the duration of DFS and OS had no significant difference between TNBC and Luminal A-B subgroups, HER2 enriched subgroup had significantly shorter survival when compared to any other subgroup. HER2-enriched subgroup had a 10-fold greater risk of death compared to the Luminal A subgroup.

Does Gender Difference Effect Radiation-Induced Lung Toxicity? An Experimental Study by Genetic and Histopathological Predictors.

Several studies have reported differences in radiation toxicity between the sexes, but these differences have not been tested with respect to histopathology and genes. This animal study aimed to show an association between histopathological findings of radiation-induced lung toxicity and the genes ATM, SOD2, TGF-ß1, XRCC1, XRCC3 and HHR2. In all, 120 animals were randomly divided into 2 control groups (male and female) and experimental groups comprising fifteen rats stratified by sex, radiotherapy (0 Gy vs. 10 Gy), and time to sacrifice (6, 12, and 24 weeks postirradiation). Histopathological evaluations for lung injury, namely, intra-alveolar edema, alveolar neutrophils, intra-alveolar erythrocytes, activated macrophages, intra-alveolar fibrosis, hyaline arteriosclerosis, and collapse were performed under a light microscope using a grid system; the evaluations were semi quantitatively scored. Then, the alveolar wall thickness was measured. Real-time quantitative reverse transcription PCR (RT-qPCR) was used to determine gene expression differences in ATM, TGF-ß1, XRCC1, XRCC3, SOD2 and HHR2L among the groups. Histopathological data showed that radiation-induced acute, subacute, and chronic lung toxicity were worse in male rats. The expression levels of the evaluated genes were significantly higher in females than males in the control group, but this difference was lost over time after radiotherapy. Less toxicity in females may be attributable to the fact that the expression of the evaluated genes was higher in normal lung tissue in females than in males and the changes in gene expression patterns in the postradiotherapy period played a protective role in females. Additional data related to pulmonary function, lung weights, imaging, or outcomes are needed to support this data that is based on histopathology alone.

Angiosarcoma of common iliac vein.

Angiosarcoma is a rare malignant tumour of endothelial cells. Primary angiosarcoma of venous origin is extremely rare, and has a very poor prognosis. A 63-year-old woman with retroperitoneal mass underwent en bloc resection on a part of iliac vein followed by adjuvant radiotherapy. No recurrence was detected during 3 years of follow-up.

Carnitine or dimethyl sulfoxide, or both, for the treatment of anthracycline extravasation in rats.

This study aimed to compare the efficacy of topical dimethyl sulfoxide (DMSO), intralesional and systemic carnitine as monotherapy and in combination against ulceration in rats induced by intradermal doxorubicin extravasation. Sixty-nine 3-month-old male Wistar albino rats, weighing between 200-225 g, were used in this study. Rats were applied monotherapy or a combination of topical DMSO, intraperitoneal or intralesional carnitine. Control groups received saline or no drug. The necrotic area was measured and extravasated neutrophil leukocytes were counted in healthy tissue adjacent to necrotic areas. Monotherapy with topical and systemic carnitine did not significantly reduce the size of necrotic areas. However, topical DMSO had reduced necrotic areas and inflammatory cells significantly and the addition of systemic carnitine to topical DMSO had increased the efficacy. DMSO is an effective, safe, and easy-to-apply treatment for doxorubicin-induced extravasation. Further clinical studies are needed to evaluate the use of carnitine in combination with DMSO.

Radiation-induced chronic oxidative renal damage can be reduced by amifostine.

In the current study, amifostine is evaluated for its radioprotective role in serum and kidney tissue by oxidative (malondialdehyde-MDA, advanced oxidation protein product-AOPP) and antioxidative markers (catalase, glutathione-GSH, free-thiols-F-SH). Thirty Wistar albino 3-4 months old, female rats, were randomly divided into Group I (n = 10): Control, Group II (n = 10): Irradiation-alone, Group III (n = 10): Amifostine before irradiation. In Group II and III, right kidneys of the rats were irradiated with a single dose of 6 Gy using a 60Co treatment unit. Rats in Group III received 200 mg/kg amifostine intraperitoneally, 30 min prior to irradiation. Following sacrification at 24th week, blood and kidney tissue samples were collected. Statistical analysis was done by One-way ANOVA, Post hoc Bonferroni, Dunnett T3, and Mann-Whitney U tests. Administration of amifostine significantly decreased the serum AOPP and MDA levels when compared to the irradiation-only group (P = 0.004, P = 0.006; respectively). Also amifostine significantly increased serum catalase activities and GSH levels, when given 30 min prior to irradiation (P = 00.02, P = 0.000; respectively). In the kidney tissue, administration of amifostine significantly decreased AOPP and MDA levels (P = 0.002, P = 0.016; respectively). Tissue GSH activity was increased following amifostine administration (P = 0.001). There was no statistically significant result on histopathological evaluation. Amifostine may reduce radiation-induced nephropathy by inhibiting chronic oxidative stress. Biomarkers of oxidative stress in serum and kidney tissue may be used for evaluation of the radiation-induced nephropathy.

Postmastectomy irradiation in breast in breast cancer patients with T1-2 and 1-3 positive axillary lymph nodes: is there a role for radiation therapy?

BACKGROUND: We aimed to evaluate retrospectively the correlation of loco-regional relapse (LRR) rate, distant metastasis (DM) rate, disease free survival (DFS) and overall survival (OS) in a group of breast cancer (BC) patients who are at intermediate risk for LRR (T1-2 tumor and 1-3 positive axillary nodes) treated with or without postmastectomy radiotherapy (PMRT) following modified radical mastectomy (MRM). METHODS: Ninety patients, with T1-T2 tumor, and 1-3 positive nodes who had undergone MRM received adjuvant systemic therapy with (n = 66) or without (n = 24) PMRT. Patient-related characteristics (age, menopausal status, pathological stage/tumor size, tumor location, histology, estrogen/progesterone receptor status, histological grade, nuclear grade, extracapsular extension, lymphatic, vascular and perineural invasion and ratio of involved nodes/dissected nodes) and treatment-related factors (PMRT, chemotherapy and hormonal therapy) were evaluated in terms of LRR and DM rate. The 5-year Kaplan-Meier DFS and OS rates were analysed. RESULTS: Differences between RT and no-RT groups were statistically significant for all comparisons in favor of RT group except OS: LRR rate (3% vs 17%, p = 0.038), DM rate (12% vs 42%, p = 0.004), 5 year DFS (82.4% vs 52.4%, p = 0.034), 5 year OS (90.2% vs 61.9%, p = 0.087). In multivariate analysis DM and lymphatic invasion were independent poor prognostic factors for OS. CONCLUSION: PMRT for T1-2, N1-3 positive BC patients has to be reconsidered according to the prognostic factors and the decision has to be made individually with the consideration of long-term morbidity and with the patient approval.

Protective effect of L-carnitine versus amifostine against cisplatin-induced nephrotoxicity in rats.

We aimed to compare the protective effect of L-carnitine (CAR) and amifostine (AMF) against cisplatin (CDDP)-induced nephrotoxicity through biochemical markers and histopathological evaluation. Fifty-seven Wistar albino male rats were randomly classified into six groups, which were AMF+CDDP (n = 11; 200 mg/kg AMF 30 min prior to 7 mg/kg CDDP), CAR+CDDP (n = 11; 300 mg/kg CAR 30 min prior to 7 mg/kg CDDP), CDDP (n = 11; 1 mL/kg isotonic saline 30 min prior to 7 mg/kg CDDP), AMF (n = 8; 200 mg/kg AMF alone), CAR (n = 8; 300 mg/kg CAR alone), and control (n = 8; 1 mL/kg isotonic saline alone). All drugs were given intraperitoneally. Five days after medication, animals were killed, and samples of blood and kidney tissues were collected for biochemical and histopathological evaluation. The serum urea level was highest in AMF+CDDP group among CDDP-applied groups without statistical significance (median, range: 88, 56-21 mg/dL; P > 0.05). There was no statistical significance among CDDP-applied groups in terms of creatinine level (P > 0.05). In the AMF+CDDP group, the median glomerular, tubular, and tubulointerstitial inflammatory damage scores were significantly higher than the other CDDP-applied groups (P < 0.001). The difference between CAR+CDDP and CDDP groups was not statistically significant in terms of renal damage scores. AMF+CDDP group had significantly higher median total nephrotoxicity score than all the other groups (P < 0.001). To conclude, AMF or CAR has no protective effect on CDDP-induced nephrotoxicity. Furthermore, our findings suggest that application of AMF before CDDP may enhance CDDP-induced nephrotoxicity histopathologically.

Triple negative breast cancer compared to hormone receptor negative/HER2 positive breast cancer.

The aim of this study is to reveal likely demographic, clinical, and pathological differences among hormone receptor negative breast cancer patients according to their HER-2 status. The medical records of hormone receptor negative breast cancer patients with known HER-2 status between January 1999 and December 2006 were reviewed, retrospectively. A total of 91 cases were included in the study (68 HER-2 negative cases and 23 HER-2 positive cases). The results obtained showed that median age, menarche age, childbearing age, number of children, menopause age, and body-mass indexes were similar in both groups. The HER-2 negative patients had more family history of breast cancer than HER-2 positive patients (13.2% and 0%, respectively, P = 0.091). Eighty-three patients received neoadjuvant/adjuvant chemotherapy. Recurrence occurred in 41 (46.6%) patients. Neither recurrence nor disease-free survival of those patients was associated with HER-2 status. Tumor size (P = 0.042) and number of involved lymph nodes (P = 0.001) were found to be independent prognostic factors for disease-free survival. A tendency for more frequent cerebral metastasis was found in HER-2 positive advanced stage patients (P = 0.052). HER-2 positive patients were less responsive to taxanes (P = 0.071). The number of involved lymph nodes (P = 0.004) and HER-2 status (P = 0.043) were found to be prognostic factors for overall survival. HER-2 positive and negative patients should be followed and treated with different strategies. HER-2 positive patients are at least as resistant to systemic therapies as the HER-2 negative patients. Genetic counseling should be routinely provided to triple negative patients and their families. HER-2 positive patients may be candidates for prophylactic treatment strategies concerning cerebral metastasis.

Prognostic significance of hemoglobin concentration in nasopharyngeal carcinoma: does treatment-induced anemia have negative effect?

PURPOSE: To assess the value of hemoglobin concentration (HC) in predicting treatment outcomes in nasopharyngeal carcinoma (NPC) patients treated with chemotherapy (CT) and radiotherapy (RT). PATIENTS AND METHODS: Ninety-eight NPC patients treated with three courses of platinum-based neoadjuvant CT (NCT) and conventional RT were grouped as having normal HC (> or = 12.0 g/dl in females and > or = 13 g/dl in males), having mild anemia (MA) (13.0 g/dl > Hb > or = 11 g/dl in males, 12.0 g/dl > Hb > or = 11 g/dl in females) and having severe anemia (SA) (Hb < 11 g/dl). Massive decrease in HC (MDHC) was defined as > or = 1.5 g/dl decline with NCT. Along with other known risk factors (sex, age, histopathology, T stage, N stage, bilateral neck involvement, cranial nerve involvement and total RT time), the prognostic value of SA and MDHC were evaluated by Cox-regression. RESULTS: SA increased from 7 to 33% with NCT (p < 0.0001). Patients with SA had lower 5-year locoregional control (LRC) (49 vs. 73%, p = 0.03), disease-free survival (DFS) (42 vs. 68%, p = 0.01) and overall survival (OS) (43 vs. 69%, p = 0.01) rates than patients with normal HC or MA. The presence of MDHC worsened 5-year LRC (p = 0.002), DFS (p = 0.001) and OS (p = 0.02) rates. In multivariate analyses, MDHC and SA had pronounced effect on LRC and survival, respectively. CONCLUSION: MDHC and SA adversely affect treatment outcome in NPC patients treated with CT and RT. This may favour concomitant scheduling of RT and CT over neoadjuvant setting. Correction of HC before RT can improve the efficacy of RT and should be further evaluated.

Prognostic factors in localized soft-tissue sarcomas.

The prognostic factors associated with local failure and overall survival and the effect of radiotherapy were determined in 77 patients with localized (extremity and nonextremity) operable soft-tissue sarcoma. There were 52 male and 25 female patients; median age was 50 years (range: 15-83). Histologic grade of the tumors was as follows: low-intermediate grade in 32 cases and high grade in 29 cases. The primary tumors were treated by marginal resection (20 patients), wide resection (52 patients), and radical resection (5 patients). Adjuvant radiotherapy was applied to 50 (65%) patients. The 5-year local recurrence-free survival rate was 70.6%. Treatment with adjuvant radiotherapy and development of metastases were the significant prognostic factors associated with local recurrence. Radiotherapy was more effective in patients with tumors 10 cm or larger, marginally resected, extremity located, and high grades. The overall survival rate was 64.4% at 5 years. Significant adverse prognostic factors were high grade tumors, presence of local recurrence, and development of metastases in univariate analyses. Development of metastases and old age were the only adverse prognostic factors by multivariate analysis. The best 5-year survival rate was obtained in female patients younger than 50 years (90%). The present study demonstrated the importance of adjuvant radiotherapy and development of metastases as prognostic factors for local control. Again, development of metastases and age were the most important prognostic factors in operable soft-tissue sarcomas.