Radiotherapy for benign diseases in Turkey: a patterns of care survey of the Turkish Society for Radiation Oncology (TROD 05-002).

PURPOSE: We aimed to investigate the patterns of radiotherapy (RT) care in cases of benign diseases in Turkey. METHODS: A questionnaire survey was sent to all radiation oncology (RO) departments in Turkey. The number of patients treated for benign disease between 2015 and 2020 was requested. A list of benign conditions was given, and information on the number of patients per disease, single and total doses prescribed, weekly fractions, radiation type, energy, and device was requested. RESULTS: Of the 138 RO departments, 29 (21%) responded. The data received concerned 15 (52%) university, 10 (34%) public, and four (14%) private hospitals. A total of 130,846 patients were treated with RT in these departments. Of these patients, 6346 (4.85%) were treated for benign conditions. The most common benign diseases treated with RT were meningioma (35%), plantar fasciitis (19%), schwannoma (16%), arteriovenous malformation (11%), and pituitary adenoma (7%). Most centers performed RT for paraganglioma, heterotopic ossification, vertebral hemangioma, and Graves' ophthalmopathy, but none treated arthrosis. Wide variations were observed across the departments. Radiosurgery for intracranial pathologies was performed intensively in four centers. By contrast, RT for plantar fasciitis was predominantly treated in five centers, one of which had more than 1000 patients. CONCLUSION: The ratio of patients who underwent RT for benign diseases in Turkey among all patients who underwent RT was 4.85%. The common pattern of RT in 72% of patients was radiosurgery for intracranial benign diseases, followed by low-dose RT for plantar fasciitis in 19%.

Survival and Prognostic Factors in Re-irradiation for Recurrent/Progressive Malignant Gliomas: Turkish Society of Radiation Oncology Neuro-Oncology Group, TROD 007-006 Study.

AIM: To evaluate survival and prognostic factors associated with survival among patients who underwent reirradiation for recurrent/ progressive primary brain tumors. MATERIAL AND METHODS: A multicenter, retrospective study (7 centers, N=236) was conducted by the Neuro-oncology Group of the Turkish Radiation Oncology Association. RESULTS: Median overall survival (OS) was 11 months and 1- and 2-year survival rates were 48% and 22%, respectively. Survival was negatively correlated with cumulative biologically effective dose (BED10) (r=-0.158, p=0.016) and cumulative equivalent dose in 2-Gy fractions (EQD2) (r=-0.158, p=0.016). In univariate analysis, survival was associated with performance status (p < 0.001), histopathology at diagnosis and recurrence (p < 0.001), radiotherapy (RT) method used for recurrence (p=0.025), tumor volume at recurrence (p=0.014), cumulative EQD2 ( < 110 vs. ≥110 Gy, p=0.038), and cumulative BED10 ( < 130 vs. ≥130 Gy, p=0.022). In multivariate analysis, tumor volume at recurrence (HR=1.68, 95% CI=1.06-2.64, p=0.025), Karnofsky Performance Status score (HR=5.7, 95% CI=3.26-9.98, p < 0.001), and histopathology at recurrence (glioblastoma vs. high-grade glioma: HR=0.48, 95% CI=0.26-0.88, p=0.019; glioblastoma vs. low-grade glial tumor: HR=0.16, 95% CI=0.08-0.34, p < 0.001) were found to be independent prognostic factors. Radionecrosis was detected in 25% (n=58) of the patients. Re-resection was associated with a higher rate of radionecrosis (37.7% vs. 18%, p=0.002). CONCLUSION: The prognostic factors most strongly associated with survival in glioma patients undergoing reirradiation were Karnofsky Performance Status score below 70, glioblastoma histopathology, and tumor volume greater than 4.5 cm3. In addition, survival time was negatively correlated with cumulative EQD2 and BED10. The rate of radionecrosis was higher in patients who underwent re-resection compared those who did not.

The effect of P53 expression and smoking/alcohol in P16(+) and P16(-) oropharyngeal carcinoma and risk classification: the Turkish Society of Radiation Oncology Head & Neck Study Group 01-002.

OBJECTIVE: The aim of this study is to categorize the risk groups of patients with oropharyngeal carcinoma (OPC) according to p16 and p53 status, smoking/alcohol consumption history, and other prognostic factors. STUDY DESIGN: The immunostaining of p16 and p53 of 290 patients was retrospectively evaluated. The history of smoking/alcohol consumption of each patient was noted. p16 and p53 staining patterns were reviewed. The results were compared with demographic findings and prognostic factors. Risk groups have been classified for the p16 status of patients. RESULTS: The median follow-up was 47 months (range 6-240). Five-year disease-free survival (DFS) rates for patients with p16 (+) and (-) were 76% and 36%, and overall survival rates were 83% vs 40%, respectively (HR = 0.34 [0.21-0.57], P < .0001), HR = 0.22 [0.12-0.40] P < .0001, respectively). p16(-), p53(+), heavy smoking/alcohol consumption, performance status; advanced T and N stages in patients with p16(-), and continuing smoking/alcohol consumption after treatment were found to be unfavorable risk factors. Five-year overall survival rates were 95%, 78%, and 36% for low, intermediate, and high-risk groups, respectively. CONCLUSIONS: The results of our study have shown that p16 negativity in patients with oropharyngeal cancer was found to be an important prognostic factor, especially for those with lower p53 expression and not smoking/consuming alcohol.

Multi-institutional analysis of cervical esophageal carcinoma patients treated with definitive chemoradiotherapy: TROD 01-005 study.

The aim of this study was to examine the prognostic factors and treatment outcomes of cervical esophageal carcinoma (CEC) patients who underwent definitive chemoradiotherapy (CRT). The clinical data of 175 biopsy-confirmed CEC patients treated with definitive CRT between April 2005 and September 2021 were retrospectively analyzed. The prognostic factors predicting overall survival (OS), progression-free survival (PFS), and local recurrence-free survival (LRFS) were assessed in uni- and multivariable analyses. The median age of the entire cohort was 56 years (range: 26-87 years). All patients received definitive radiotherapy with a median total dose of 60 Gy, and 52% of the patients received cisplatin-based concurrent chemotherapy. The 2-year OS, PFS, and LRFS rates were 58.8%, 46.9%, and 52.4%, respectively, with a median follow-up duration of 41.6 months. Patients' performance status, clinical nodal stage, tumor size, and treatment response were significant prognostic factors for OS, PFS, and LRFS in univariate analysis. Non-complete treatment response was an independent predictor for poor OS (HR = 4.41, 95% CI, 2.78-7.00, p < 0.001) and PFS (HR = 4.28, 95% CI, 2.79-6.58, p < 0.001), whereas poor performance score was a predictor for worse LRFS (HR = 1.83, 95% CI, 1.12-2.98, p = 0.02) in multivariable analysis. Fifty-two patients (29.7%) experienced grade II or higher toxicity. In this multicenter study, we demonstrated that definitive CRT is a safe and effective treatment for patients with CEC. Higher radiation doses were found to have no effect on treatment outcomes, but a better response to treatment and a better patient performance status did.

A multicenter retrospective analysis of patients with nasopharyngeal carcinoma treated in IMRT era from a nonendemic population: Turkish Society for Radiation Oncology Head and Neck Cancer Group Study (TROD 01-001).

BACKGROUND: We aimed to evaluate patients with nasopharyngeal carcinoma (NPC) in a nonendemic population. METHODS: In a national, retrospective, multicenteric study, 563 patients treated with intensity modulated radiotherapy at 22 centers between 2015 and 2020 were analyzed. RESULTS: Median age was 48 (9-83), age distribution was bimodal, 74.1% were male, and 78.7% were stage III-IVA. Keratinizing and undifferentiated carcinoma rates were 3.9% and 81.2%. Patients were treated with concomitant chemoradiotherapy (48.9%), or radiotherapy combined with induction chemotherapy (25%) or adjuvant chemotherapy (19.5%). After 34 (6-78) months follow-up, 8.2% locoregional and 8% distant relapse were observed. Three-year overall survival was 89.5% and was lower in patients with age ≥50, male sex, keratinizing histology, T4, N3 and advanced stage (III-IVA). CONCLUSIONS: Patients with NPC in Turkey have mixed clinical features of both east and west. Survival outcomes are comparable to other reported series; however, the rate of distant metastases seems to be lower.

Outcomes of carotid sparing intensity-modulated radiotherapy for early stage glottic cancer in 201 patients: Multicenter study of Turkish Radiation Oncology Society/TROD-01-007.

BACKGROUND: To assess and report clinical outcomes after carotid sparing intensity-modulated radiotherapy for early stage laryngeal cancer. METHODS: We retrospectively analyzed 201 patients with early stage glottic laryngeal cancer treated with carotid sparing intensity-modulated radiotherapy (IMRT)/volumetric modulated arc therapy (VMAT) techniques in six TROD centers. RESULTS: After a median follow-up of 31 months the actuarial 1- and 3-year local and locoregional control rates were 99.4% and 94.7%, 98.4% and 93%, respectively. T classification, anterior commissure involvement, IMRT technique, and type of fractionation were not found to be prognostic for local control. Overall, eight patients had lost their organ function due to recurrence or toxicity. Grade 3 and 4 acute laryngeal edema was seen in eight (4%) and one (0.5%) of patients, respectively. Grade 3 and 4 late laryngeal edema developed in two (1%) and one patient (0.5%), respectively. CONCLUSION: Oncologic outcomes of patients treated with carotid sparing IMRT were excellent; comparable with historical series, with acceptable side effects. Longer follow-up is needed to estimate long term effect on stroke.

Outcome of Early-Stage Glottic Laryngeal Carcinoma Patients Treated with Radical Radiotherapy Using Different Techniques.

PURPOSE: The aim was to evaluate the treatment outcomes and prognostic characteristics of patients with early-stage glottic laryngeal carcinoma who underwent radical radiotherapy (RT) with different techniques. PATIENTS AND METHODS: Radiotherapy was applied using the 2D conventional technique between 1991 and 2004 (130 patients), 3DCRT until 2014 (125 patients), and by VMAT until January 2017 (44 patients). Clinical T stages were 38 (12.7%) for Tis, 209 (69.9%) for T1, and 52 (17.4%) for T2. Radiotherapy technique and energy, anterior commissure involvement, and stage were analyzed as prognostic factors. RESULTS: The median total dose was 66 (50-70) Gy, and median follow-up time was 72 (3-288) months; 5-year disease-specific survival (DSS) rates were 95.8%, 95.5%, and 88.6%, respectively, in Tis, T1, and T2 stages. In multivariate analyses, anterior commissure involvement was found significant for all survival and local control rates. The patients treated with VMAT technique had better local control and DSS rates. However, these results were not statistically significant. CONCLUSION: In early-stage laryngeal carcinomas, radical RT is a function sparing and effective treatment modality, regardless of treatment techniques.

Assessment of treatment-related thyroid dysfunction in patients with head and neck cancer.

OBJECTIVE: To assess thyroid dysfunction in head and neck cancer patients who have received external beam radiotherapy according to radiotherapy fields and dose, tumor site and other local or systemic treatments retrospectively and prospectively and propose a follow-up schedule. MATERIAL AND METHODS: A total of 378 patients was classified into two groups. Group I (n = 345) consisted of surgically treated 153 laryngeal, 80 nasopharyngeal and 112 oral cavity/oropharyngeal carcinoma patients; these patients were evaluated retrospectively for treatment-related thyroid dysfunction using their data files. Group II included 33 patients with head and neck cancer who were evaluated prospectively. Thyroid function tests were performed at the beginning of the radiotherapy and every three months after the radiotherapy course, and thyroid dysfunction regarding surgery, radiotherapy and chemotherapy was evaluated. RESULTS: In Group I, the median follow-up for 153 operated laryngeal carcinoma patients was 44 months. Four (2.6%) of them were found to have clinically apparent hypothyroidism. After a median follow-up of 36 months, none of the 80 nasopharyngeal carcinoma patients showed signs of hypothyroidism. Clinically apparent hypothyroidism was detected in only 1 (0.8%) of the oral cavity/oropharyngeal carcinoma patients after a median follow-up of 25 months. In Group II, 1 (3%) patient was found to have thyroid dysfunction postoperatively prior to radiotherapy. At the time of analysis, 29 (87.8%) patients were euthyroidic, 2 (6.1%) patients had subclinical and 2 (6.1%) patients had clinical hypothyroidism. All patients with thyroid dysfunction have had combined surgery and radiotherapy, and none of the patients treated with radical radiotherapy has experienced hypothyroidism. CONCLUSIONS: Even after a short follow-up, the incidence of thyroid dysfunction was 12.2% in head and neck cancer patients treated with combined surgery and radiotherapy. We recommend thyroid function tests in these patients prior to and once every 3-6 months after the radiotherapy course.

Malignant peripheral primitive neuroectodermal (pPNET) of tongue.

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

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

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

Anti-inflammatory and Anti-apoptotic Effect of Valproic Acid and Doxycycline Independent from MMP Inhibition in Early Radiation Damage.

BACKGROUND: Matrix metalloproteinase (MMP) inhibitors decrease inflammation in normal tissues and suppress cancer progress in normal tissues. Valproic acid (VA) and doxycycline (DX) are MMP inhibitors that have radio-protective effects. Their ability to inhibit MMPs in irradiated tissue is unknown and the role of MMPs in radio-protective effects has not been tested to date. AIMS: The purpose of this study was to examine whether administration of VA and DX to rats before irradiation affects tissue inflammation and apoptosis in the early phase of radiation, and whether the effect of these drugs is mediated by MMP inhibition. STUDY DESIGN: Animal experimentation. METHODS: Twenty-six Wistar rats were randomized into four groups: control (CTRL), radiation (RT), VA plus radiation (VA+RT), and DX plus radiation (DX+RT). Three study groups were exposed to a single dose of abdominal 10 Gy gamma radiation; the CTRL group received no radiation. Single doses of VA 300 mg/kg and DX 100 mg/kg were administered to each rat before radiation and all rats were sacrificed 8 hours after irradiation, at which point small intestine tissue samples were taken for analyses. Levels of inflammatory cytokines (TNF-α, IL-1ß, and IL-6) and matrix metal-loproteinases (MMP-2 and MMP 9) were measured by ELISA, MMP activities were measured by gelatin and casein zymography and apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. RESULTS: VA decreased the levels of TNF-α and IL-1ß proteins insignificantly and decreased apoptosis significantly in the irradiated tissue, but did not inhibit MMPs. In contrast, VA protected the basal MMP activities, which decreased in response to irradiation. No effect of DX was observed on the levels of inflammatory cytokines or activities of MMPs in the early phases of radiation apoptosis. CONCLUSION: Our findings indicated that VA protects against inflammation and apoptosis, and DX exhibits anti-apoptotic effects in early radiation and these effects are independent from MMP inhibition.

Improvement of colonic healing by preoperative oral partially hydrolyzed guar gum (Benefiber) in rats which underwent preoperative radiotherapy.

BACKGROUND: Neoadjuvant radiotherapy in rectal cancer could interfere with anastomotic healing. We investigated the effects of preoperative oral administration of Benefiber on the healing irradiated colonic anastomosis. METHODS: Forty male Wistar rats were divided into four groups. Group I (control group), Group II (Benefiber® pretreatment group), Group III (preoperative radiotherapy group) and Group IV (preoperative radiotherapy and Benefiber® pretreatment group). All animals underwent 1 cm left colon resection and primary anastomosis. On the 3rd and 7th postoperative days, all the rats were anesthetized to assess the anastomotic healing clinically, mechanically, histologically and biochemically. RESULTS: The mean bursting pressure was significantly lower in-group III and significantly higher in-group II on day 7. The histologic parameters of anastomotic healing, such as epithelial regeneration and formation of granulation tissue, were significantly improved by use of preoperative Benefiber® on day 7. The amount of acid-soluble collagen concentrations significantly increased in-group IV compared to group III on day 3. The amount of salt-soluble collagen concentrations significantly increased in group II compared to group III on day 3. CONCLUSIONS: Colonic anastomotic healing can be adversely affected by preoperative radiotherapy, but orogastric feeding with Benefiber may improve the healing process.

Tumor budding as a prognostic marker in laryngeal carcinoma.

Tumor budding is recognized as an adverse prognostic factor for a few carcinoma types. We evaluated the importance of this finding in 64 laryngeal carcinoma patients treated with surgery and radiotheraphy, with a median follow up of 53 (6-181) months. Budding was determined by re-evaluating hematoxylin-eosin (H&E) stained tumor sections, and classified as mild, moderate, and marked. Budding was not identified in 14 (21.88%) cases. Mild, moderate, and marked budding was observed in 21 (32.81%), 15 (23.44%), and 14 (21.88%) cases, respectively. Only when cases with marked budding were compared with the others, statistically significant results were obtained. In patients with and without marked budding, local disease-free survival, metastatic disease-free survival, and overall survival were 71% and 97% (p=0.72), 77% and 93% (p=0.038), and 77% and 75% (p=0.71), respectively. Marked budding was identified as a prognostic factor by univariate analysis for distant metastasis-free survival. Multi-variate analysis, by which well-recognized prognostic histopathologic parameters were evaluated, revealed that only the number of metastatic lymph nodes and budding were significantly associated with distant metastasis (p=0.02 and p=0.044), respectively. These results suggest that budding might be a valuable prognostic factor, particularly for distant metastasis in laryngeal carcinomas.