Comparison of Doses to Parotid, Temporomandibular Joint, and Pharyngeal Constrictor Muscles Using Different Techniques in Radiotherapy for Oropharyngeal Cancer.

OBJECTIVE: The purpose of this research was to compare two treatment techniques for oropharyngeal cancers: conventional linac-based static intensity-modulated radiotherapy (sIMRT) and helical tomotherapy (HT). The study examined several parameters, including target coverage, organs at risk, integral dose, and beam on time. Additionally, the study evaluated the doses to the parotid, temporomandibular joint, and pharyngeal constrictor muscles, which are important for swallowing. METHOD: The present study retrospectively analyzed the data of 13 patients with oropharyngeal cancer who underwent radiotherapy between 2019 and 2021. The treatment plans for each patient were regenerated using both sIMRT and HT treatment planning systems with the sequential boost method. The techniques were evaluated and compared based on dose-volume histogram, homogeneity index, and conformity index parameters. The target coverage and organs at risk were statistically compared for two techniques. Additionally, the doses received by the healthy tissue volume were obtained for integral dose evaluation. The beam on time for each technique was assessed. RESULTS: When considering planning target volume evaluation, there was no difference in Dmeans between the two techniques and sIMRT demonstrated higher D2% values compared to the HT. The HT technique had better results for all organs at risk, such as the parotid, temporomandibular joint, and pharyngeal constrictor muscle. As for integral dose, it has been shown that the sIMRT technique provides better protection compared to HT. In addition, the beam on time was also longer with the HT technique. CONCLUSION: Both techniques may provide optimal target coverage for patients with oropharyngeal cancer. HT conferred notable advantages, especially with regard to critical structures implicated in swallowing, such as the parotid, temporomandibular joint, and pharyngeal constrictor muscle, in comparison to sIMRT.

Radiotherapy for vertebral hemangioma: the single-center experience of 80 patients.

PURPOSE: This study aimed to evaluate the therapeutic effect of radiotherapy and to determine possible prognostic factors in patients with painful vertebral hemangioma. METHODS: In the last two decades, 80 patients with vertebral hemangioma who received radiotherapy in our institute were evaluated in terms of pain response, treatment-related side effects, and prognostic factors. All patients were questioned 3 months after radiotherapy for the evaluation of pain response and were divided into three groups (complete response, partial response, and no change). Moreover, the visual analog scale (VAS) was used for pain response assessment in 46 patients. Pain status was assessed to detect recurrence at each clinical examination during the follow-up period. Possible prognostic factors such as gender, size of the hemangioma, location, multilevel involvement and additional musculoskeletal disease on pain response were analyzed. RESULTS: In this study, 45 individuals had lesions in the lumbar spine, 28 in the thoracic, and 7 in the cervical region. Furthermore, 51 patients had additional musculoskeletal conditions such as disc herniation, degenerative diseases, spondylolisthesis, and compression fracture. Radiotherapy was performed with a median daily dose of 2 Gy and a median total dose of 40 Gy. Complete pain response occurred in 58.8% of patients, 26.2% of patients had partial pain response, and 15% of patients had no pain response. The overall response rate was 85%, and 7 patients showed recurrent pain symptoms in the overall response group at routine follow-up. Additional musculoskeletal disorders were found to be the only prognostic factor associated with pain response. The median follow-up time was 60 months. Secondary malignancy was not found in any of the patients in this short follow-up time. No acute or late radiation-associated side effects greater than grade II were observed. CONCLUSION: To our best knowledge, this study is one of the largest single-institution radiotherapy series on vertebral hemangiomas reported to date. The obtained data support the efficacy and safety of radiotherapy in the treatment of painful vertebral hemangioma. Our study showed that additional musculoskeletal disease plays an important role in pain response. Other prognostic factors and treatment of vertebral hemangioma with stereotactic radiosurgery should be investigated in future studies.

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.

Endostatin and irradiation modifies the activity of ADAM10 and neprilysin in breast cancer cells.

Angiogenesis, the formation of new blood vessels, is regarded as a key cancer cell property. Endostatin (ES) is a potential antiangiogenic agent and it may be useful when implemented in combination with other cancer therapeutic strategies. The present study investigated the in vitro effects of ES, radiotherapy (RT) or combination therapy (ES + RT) on two important proteases, a disintegrin and metalloproteinase domain­containing protein 10 (ADAM10) and neprilysin (NEP) in 4T1 mouse breast cancer cells and the more metastatic phenotype of 4THMpc breast cancer cells. 4T1 and 4THMpc cells were treated with recombinant murine ES (4 µg/ml) alone, RT (45 Gy) alone or with ES + RT. ADAM10 enzyme activity was determined using a tumor necrosis factor­α converting enzyme (α­secretase) activity assay kit, and NEP enzyme activity was measured with a fluorometric assay based on the generation of free dansyl­D­Ala­Gly from N-dansyl-Ala-Gly-D-nitro-Phe-Gly, the substrate of NEP. Western blotting analysis was performed to determine whether the altered enzyme activity levels of the two cell lines occurred due to changes in expression level. These data indicate that ES independently potentiates the activity of ADAM10 and NEP enzymes in 4T1 and 4THMpc breast cancer cells.

Thalidomide combined with irradiation alters the activity of two proteases.

The aim of the present study was to investigate the effects of thalidomide, a drug known for its anti­angiogenic and antitumor properties, at its cytotoxic dose previously determined as 40 µg/ml (according to four cytotoxic test results). The effect of the drug alone and in combination with radiotherapy using Cobalt 60 (60Co) at 45 Gy on the enzymatic activity of substance­P degrading A disintegrin and metalloproteinase (ADAM)10 and neprilysin (NEP) was investigated in the mouse breast cancer cell lines 4T1 and 4T1 heart metastases post­capsaicin (4THMpc). Thalidomide (40 µg/ml) exerted differing effects on the activities of ADAM10 and NEP enzymes. In 4T1 cells, 40 µg/ml thalidomide alone did not alter ADAM10 enzyme activity. 60Co irradiation at 45 Gy alone caused a 42% inhibition in ADAM10 activity, however, the inhibition increased to 89% when combined therapy was used. By contrast, in the 4THMpc cell line, 40 µg/ml thalidomide alone induced a 66.6% increase in ADAM10 enzyme activity. Radiotherapy alone and thalidomide with 60Co combined therapy caused a 33.3 and 40% inhibition of ADAM10 activity, respectively. In 4T1 cells, thalidomide alone caused a 40.9% increase in NEP activity. Radiation therapy alone or in combination with the drug caused a 40.7% increase in NEP activity. In more aggressive 4THMpc cells, thalidomide alone caused a 26.6% increase in NEP activity. Radiotherapy alone and combined therapy caused a 33.3 and 37% increase in enzyme activity, respectively. To the best of our knowledge, the present study is the first to demonstrate that thalidomide alone or in combination with radiotherapy exhibits significant cytotoxic effects on 4T1 and 4THMpc mouse breast cancer cell lines indicating that this drug affects the enzymatic activity of ADAM10 and NEP in vitro.

Clinical prognostic factors of adjuvant radiation therapy for low-grade gliomas: results of 10 years survival.

OBJECTIVE: Low-grade gliomas compose 5-20% of all glial tumors. The prognosis of the disease can be anticipated by specific clinical factors determined during diagnosis. For this purpose, our study investigated the clinical prognostic factors for low-grade gliomas. METHODS: Patients diagnosed with histopathologically confirmed low-grade glioma, followed by Akdeniz University and Süleyman Demirel University School of Medicine, Department of Radiation Oncology between 1999 and 2013 were included in the study. The examination of survival by single variable analyses were performed by log rank test. For the multivariate analysis, independent factors for the prediction of survival by using possible factors determined by previous analyses were examined by using Cox regression analysis. RESULTS: Fifty-five patients were included in the study. The mean follow-up period was determined as 60 ± 57 (4.5-168.1) months. Five-year overall survival was determined as 69% and 10-year overall survival was determined as 40%. When the potential prognostic factors were studied in Cox regression model, pre-radiotherapy age below 40 and gross-total excision were determined as good prognostic factors. CONCLUSION: We demonstrated that the aggressive surgical resection provided a better survival advantage both in single variable analyses and multivariate analyses. Consequently, although the low number of patients was the most important limitation in our study, we consider that patient age and extent of resection are the most important clinical prognostic factors in low-grade gliomas.

Thalidomide and irradiation combination therapy increases substance P levels in vitro.

Thalidomide is an anti-angiogenic agent that is used in the treatment of cancer. However, in many cases, particularly in patients with breast cancer, thalidomide treatment alone is insufficient and must be combined with other drugs or therapies. In the clinical setting, thalidomide is most commonly used in combination with radiation therapy. However, the exact mechanisms of its effect are unkown. Radiotherapy alters the expression of substance P, which is considered a crucial pro-angiogenic peptide. To determine whether thalidomide and radiotherapy in combination overcome the limitations of each as monotherapy, we examined the effects of the combination on the growth of breast cancer cells as well as on the expression of substance P in vitro. Mouse breast cancer cells (4T1) and cells produced from metastatic lesions (4THMpc) were treated with radiotherapy (RT) (45 Gy) alone, thalidomide (Thal) (40 µg/ml) alone or combination therapy (40 µg/ml Thal + 45 Gy RT), and compared with control cells. MTS, Live/Dead and trypan blue exclusion assays were used to evaluate the cytotoxic effects of the treatments. The levels of substance P in the conditioned media and in the cell lysates were determined by a substance P ELISA kit, and changes in the protein content were analyzed by Western blotting. Thalidomide alone resulted in a significant inhibition in the growth of the 4T1 (34.1%) and 4THMpc (52.6%) cell lines. RT alone inhibited the growth of the 4T1 (19.2%) and 4THMpc (23.31%) cell lines. The combination therapy enhanced the growth inhibition noted in the 4T1 (47.9%) and 4THMpc (62.03%) cell lines. The expression of substance P in the conditioned media and in the cell lysates increased within 72 h of RT. This increase was significantly enhanced with the combination therapy. These data indicate that thalidomide inhibits breast cancer cell growth and potentiates the anti-tumor effects of radiation at appropriate doses.

The results of adjuvant radiotherapy in endometrial carcinoma.

AIM: To examine the clinical characteristics and treatment outcomes in patients with endometrial cancer receiving adjuvant radiotherapy. METHODS: A total of 157 patients who received postoperative radiotherapy (RT) between 1999 and 2008 were evaluated, retrospectively. The mean age was 59 years (34-82). All patients received RT following surgery. Stage distribution was as follows: 92 patients (59%) stage I, 21 patients (13%) stage II, and 44 patients (28%) stage III. RESULTS: Overall survival rate was 95% at 2 years and 84% at 5 years. By the end of follow up, 135 patients (86%) were disease-free, and 4 (2%) were alive with disease. Univariate and multivariate analyses identified stage, grade, and serosal involvement as significant predictors for overall survival. CONCLUSION: The results of our study suggests that early stage, low-grade endometrial cancer with no serosal involvement is associated with a better survival and adjuvant radiotherapy is a well tolerated and effective therapeutic option.

High TRAIL death receptor 4 and decoy receptor 2 expression correlates with significant cell death in pancreatic ductal adenocarcinoma patients.

OBJECTIVES: The importance of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and TRAIL receptor expression in pancreatic carcinoma development is not known. To reveal the putative connection of TRAIL and TRAIL receptor expression profile to this process, we analyzed and compared the expression profile of TRAIL and its receptors in pancreatic tissues of both noncancer patients and patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: Thirty-one noncancer patients and 34 PDAC patients were included in the study. TRAIL and TRAIL receptor expression profiles were determined by immunohistochemistry. Annexin V binding revealed the apoptotic index in pancreas. Lastly, the tumor grade, tumor stage, tumor diameter, perineural invasion, and number of lymph node metastasis were used for comparison purposes. RESULTS: TRAIL decoy receptor 2 (DcR2) and death receptor 4 expression were up-regulated in PDAC patients compared with noncancer patients, and the ductal cells of PDAC patients displayed significant levels of apoptosis. In addition, acinar cells from PDAC patients had higher DcR2 expression but lower death receptor 4 expression. Increased DcR2 expression was also observed in Langerhans islets of PDAC patients. CONCLUSIONS: Differential alteration of TRAIL and TRAIL receptor expression profiles in PDAC patients suggest that the TRAIL/TRAIL receptor system may play a pivotal role during pancreatic carcinoma development.

Radiotherapy-induced decreases in substance P levels may potentiate melanoma growth.

Substance P, a member of the tachykinin family, is expressed in primary invasive malignant melanomas, metastatic melanomas, melanomas in situ, atypical naevi, and spindle and epithelioid cell naevi. The role of substance P in cancer development and progression is not clear. Radiotherapy, which is used extensively in the treatment of malignancies, alters substance P levels. It is, however, not known whether radiotherapy affects substance P levels in melanomas or in the tumor microenvironment. Given the fact that melanomas express substance P, possible radiation-induced changes in substance P content may underlie their radio-resistance. Hence, the aim of the present study was to determine the effects of radiotherapy on the growth of B16F10 melanomas as well as on the tumor and systemic expression of substance P. In vivo exposure of tumor-bearing C5BL/6 mice to ionizing radiation (45 Gy administered in three fractions) arrested tumor growth for three weeks and induced 3-fold increases in survival, as well as decreasing substance P levels in primary tumors and the surrounding skin. Although radiotherapy was applied locally (1 x 1 cm) at the mid-flank region of the animal, it also induced systemic changes in the levels of substance P. Specifically, radiotherapy decreased substance P levels in skin distant from the radiation field as well as in the lungs and adrenals. In order to understand the significance of this effect, B16F10 cells and cells made from metastatic lesions (B16LNAD cells) were treated with substance P. Substance P inhibited the growth of B16F10 and B16LNAD cells and further potentiated the inhibitory effects of radiotherapy. These findings demonstrate for the first time that substance P inhibits melanoma growth, and that radiotherapy-induced decreases in substance P levels may underlie the radio-resistance of melanomas.

[Treatment modalities of nasopharyngeal angiofibroma]. / Nazofarenks anjiyofibromlarinda tedavi yaklasimlari.

Nasopharyngeal angiofibroma is a rare, benign vascular tumor originating from the sphenopalatine foramen. It primarily affects adolescent males. Due to its propensity to locally destructive growth, the tumor may lead to fatal epistaxis, intracranial extension, and life-threatening complications such as intraoperative hemorrhage. Many treatment modalities have been used for the management of nasopharyngeal angiofibroma, but surgery and external beam radiation therapy have proved to be the only effective treatment modalities with acceptable morbidity. While endoscopic surgery provides successful results for early stage tumors, recent technological advances in radiotherapy offer significant advantages in advanced and recurrent tumors.

High levels of endogenous tumor necrosis factor-related apoptosis-inducing ligand expression correlate with increased cell death in human pancreas.

OBJECTIVES: Type 1 diabetes (T1D) has been characterized by the T cell-mediated destruction of pancreatic beta cells. Although various members of the tumor necrosis factor (TNF) family, such as Fas ligand or TNF, have recently been implicated in the development of T1D, the lack of TNF-related apoptosis-inducing ligand (TRAIL) expression or function facilitates the onset of T1D. Thus, the goal of the present study was to investigate the expression profiles of TRAIL and its receptors in human pancreas. METHODS: Pancreata of 31 patients were analyzed by immunohistochemistry using antibodies developed against TRAIL and its receptors. Apoptosis was confirmed by Annexin V-fluorescein isothiocyanate binding and terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end labeling assays. RESULTS: Acinar cells displayed high levels of TRAIL and death receptor 4, but only low levels of death receptor 5. In contrast, only TRAIL and TRAIL decoy receptors (DcR1, DcR2) were detected in ductal cells. Similarly, Langerhans islets expressed only TRAIL and TRAIL decoy receptor. High levels of TRAIL expression in pancreas correlated with increased number of apoptotic cells. CONCLUSIONS: Although the expression of TRAIL decoy receptors might be necessary for defense from TRAIL-induced apoptosis, high levels of TRAIL may provide protection for Langerhans islets from the immunological attack of cytotoxic T cells.

Effect of complementary and alternative medicine during radiotherapy on radiation toxicity.

GOAL OF WORK: To examine the frequency and types of complementary and alternative medicine use in patients undergoing radiotherapy and to analyze the effects these therapies have on the toxicities of radiotherapy. MATERIALS AND METHODS: A total of 210 consecutive cancer patients undergoing radiation therapy were included. After radiation therapy, each patient completed a standard questionnaire, and the association between radiation toxicity and complementary and alternative medicine use was analyzed. MAIN RESULTS: Among the study population, 44.3% of patients reported using at least one form of complementary and alternative medicine during radiotherapy. The most commonly chosen complementary and alternative medicine was stinging nettle. Complementary and alternative medicine use decreased lower gastrointestinal (F = 3.26, P = .009) and genitourinary toxicities (F = 2.38, P = .043), while it increased laryngeal toxicity (F = 2.63, P = .028). A significant correlation between the type of complementary and alternative medicine used and the degree of these toxicities was not demonstrated. CONCLUSIONS: Use of complementary and alternative medicine among cancer patients during radiation therapy may affect the degree of radiation toxicity. Further randomized controlled clinical trials are needed to determine the benefits and risks of complementary and alternative medicine use during radiation therapy.

Stage I small cell carcinoma of the endometrium: survival and management options.

Small cell carcinoma (SCC) of the endometrium is a rare but aggressive disease with early systemic involvement. Patient survival is short. To date, no effective treatment protocol has been established. Surgery, radiotherapy, and chemotherapy have been used either alone or in combination. The case of a patient with stage IB endometrial SCC is presented with an overview based on all reported cases of SCC of the endometrium and its treatment with particular reference to stage I cases.

Small cell carcinoma of the cervix: a case report.

Small cell carcinoma of the uterine cervix accounts for 1-3% of all cervix cancers. It is an aggressive disease with a poor prognosis. To date, no effective treatment protocol has been determined. Surgery, radiotherapy, and chemotherapy have been used either alone or in combination. Recent data suggests that survival in patients with early staged small cell carcinoma of the cervix is better with surgery combined with chemo-radiotherapy. Here, we presented two patients with stage IB1 small cell carcinoma of the uterine cervix. For both patients, definitive surgery was performed with pelvic and para-aortic lymphadenectomy. Subsequently, they were treated with pelvic external radiotherapy and high-dose-rate intracavitary brachytherapy with concurrent cisplatin based chemotherapy. They were alive with no evidence of disease at 91 and 65 months, respectively.

Primary follicular lymphoma of the cervix uteri: a review.

Primary non-Hodgkin's lymphoma of the cervix is a rare disease, of which a subgroup of follicular lymphoma constitutes only 8.5%. There is not an established treatment protocol neither for primary cervical lymphoma nor for its follicular subgroup. We presented a case with Ann Arbor stage IEA (Extra-nodal involvement and absence of weight loss, fever, night sweat) primary follicular lymphoma of the cervix. She was treated with chemotherapy followed by pelvic radiotherapy. Upon relapse with a nodal neck mass, she was treated with rituximab alone. She remained well for 23 months after rituximab. In the 39 months of follow-up, there was no evidence of disease. In the light of our case, we reviewed the reported cases of primary follicular lymphoma of the cervix while discussing their treatment protocols and the cases of primary cervix lymphoma treated with rituximab.