Investigation of the risk factors in the development of radionecrosis in patients with brain metastases undergoing stereotactic radiotherapy.

OBJECTIVE: To investigate the incidence, timing, and the factors predictors radionecrosis (RN) development in brain metastases (BMs) undergoing stereotactic radiotherapy (SRT). METHODS: The study evaluated 245 BMs who exclusively received SRT between 2010 and 2020. RN was detected pathologically or radiologically. RESULTS: The median of follow-up was 22.6 months. RN was detected in 18.4% of the metastatic lesions, and 3.3% symptomatic, 15.1% asymptomatic. The median time of RN was 22.8 months (2.5-39.5), and the rates at 6, 12, and 24 months were 16.8%, 41.4%, and 66%, respectively. Univariate analysis revealed that Graded Prognostic Assessment (P = .005), Score Index of Radiosurgery (P = .015), Recursive Partitioning Analysis (P = .011), the presence of primary cancer (P = .004), and localization (P = .048) significantly increased the incidence of RN. No significant relationship between RN and brain-gross tumour volume doses, planning target volume, fractionation, dose (P > .05). Multivariate analysis identified SIR > 6 (OR: 1.30, P = .021), primary of breast tumour (OR: 2.33, P = .031) and supratentorial localization (OR: 3.64, P = .025) as risk factors. CONCLUSIONS: SRT is used effectively in BMs. The incidence of RN following SRT is undeniably frequent. It was observed that the incidence rate increased as the follow-up period increased. We showed that brain-GTV doses are not predictive of RN development, unlike other publications. In study, a high SIR score and supratentorial localization were identified as factors that increased the risk of RN. ADVANCES IN KNOWLEDGE: RN is still a common complication after SRT. Symptomatic RN is a significant cause of morbidity. The causes of RN are still not clearly identified. In many publications, brain dose and volumes have been found to be effective in RN. But, with this study, we found that brain dose volumes and fractionation did not increase the incidence of RN when brain doses were taken into account. The most important factor in the development of RN was found to be related to long survival after SRT.

Predictors of local control after robotic stereotactic radiotherapy for brain metastases: 10-years-experience after Cyberknife installation.

BACKGROUND: To evaluate the factors influencing brain metastases (BM) local control (LC) after stereotactic radiotherapy (SRT). METHODS: Between 2010 and 2020, a cohort of 145 patients (246 BM) treated consecutively with robotic radiosurgery was analysed. RESULTS: Median age was 61 years (range, 29-90 years). Median radiological follow-up of the lesions was 21.7 months (range, 3-115 months). The mean overall survival and LC were 33.0 and 82.7 months, respectively. On univariate analysis, sex, primary cancer site, histological type, use of systemic steroids, maximum diameter, volume, early MRI response, isodose line, number of fractions, BED10 value, and BED10 value proportional to volume and maximum diameter were significant factors for LC. On multivariate analysis, female sex (hazard ratio [HR]: 2.10 P: 0.035), adenocarcinoma histology (HR: 6.54 P: 0.001), no steroid use (HR: 3.60 P: 0.001), maximum diameter (≤1 cm) (HR: 2.64 P: 0.018), complete response of lesion at first follow-up MRI compared to stable or progressive disease (HR: 4.20, P = 0.024; HR: 19.15, P < 0.001), isodose line (≥90%) (HR: 2.00 P: 0.036), and tumour volume (PTV ≤2 cc) (HR: 5.19 P: 0.001) were independent factors improving LC. CONCLUSIONS: SRT is an effective treatment for patients with a limited number of BM with a high LC rate. There are many factors related to the patient, tumour, and radiotherapy plan that have an impact on LC after SRT in brain metastases. These results warrant further investigation in a prospective setting.

Adverse risk factors for salvage radiotherapy outcomes after radical prostatectomy in prostate cancer patients.

PURPOSE: To investigate salvage treatment approaches and treatment outcomes in high-risk prostate cancer after radical prostatectomy (RP). METHODS: In this retrospective, multicenter study, 272 patients who underwent salvage radiotherapy (RT) ± androgen deprivation therapy (ADT) for recurrent prostate cancer after RP between 2007 and 2021 were analysed. Univariate analyses of time to biochemical and clinical relapse after salvage therapies were conducted using Kaplan-Meier plots and log-rank tests. Multivariate analyses were performed using a Cox proportional hazards model to determine the risk factors for disease relapse. RESULTS: Median age was 65 (48-82) years. All patients underwent salvage prostate bed RT. Pelvic lymphatic RT was performed in 66 patients (24.3%) and ADT was included in 158 (58.1%) patients. The median PSA value before RT was 0.35 ng/mL. The median follow-up time was 64 (12-180) months. 5-years bRFS, cRFS, and OS were 75.1%, 84.8%, and 94.9% respectively. In multivariate cox regression analysis; seminal vesicle invasion (HR 8.64, 95% CI 3.47-21.48, p < 0.001), pre-RT PSA higher than 0.14 ng/mL (HR 3.79, 95% CI 1.47-9.78, p = 0.006), and ≥ 2 positive pelvic lymph nodes (HR 2.50, 95% CI 1.11-5.62, p = 0.027) were found to be unfavorable prognostic factors for bRFS. CONCLUSION: Salvage RT ± ADT provided 5-years biochemical disease control in 75.1% of patients. Seminal vesicle invasion, ≥ 2 positive pelvic nodes and delayed administration of salvage RT (PSA levels higher than 0.14 ng/mL) were found to be adverse risk factors for relapse. Such factors should be taken into account during the decision process on salvage treatment.

Reparative, Neuroprotective and Anti-neurodegenerative Effects of Granulocyte Colony Stimulating Factor in Radiation-Induced Brain Injury Model.

OBJECTIVE: This animal model aimed to compare the rat group that received brain irradiation and did not receive additional treatment (only saline) and the rat group that underwent brain irradiation and received Granulocyte colony stimulating factor (G-CSF) treatment. In addition, the effects of G-CSF on brain functions were examined by magnetic resonance (MR) imaging and histopathologically. METHODS: This study used 24 female Wistar albino rats. Drug administration (saline or G-CSF) was started at the beginning of the study and continued for 15 days after whole-brain radiotherapy (WBRT). WBRT was given on day 7 of the start of the study. At the end of 15 days, the behavioral tests, including the three-chamber sociability test, open field test, and passive avoidance learning test, were done. After the behavioral test, the animals performed the MR spectroscopy procedure. At the end of the study, cervical dislocation was applied to all animals. RESULTS: G-CSF treatment positively affected the results of the three-chamber sociability test, open-space test and passive avoidance learning test, cornu Ammonis (CA) 1, CA3, and Purkinje neuron counts, and the brain levels of brain-derived neurotrophic factor and postsynaptic density protein-95. However, G-CSF treatment reduced the glial fibrillary acidic protein immunostaining index and brain levels of malondialdehyde, tumor necrosis factor-alpha, nuclear factor kappa-B, and lactate. In addition, on MR spectroscopy, G-CSF had a reversible effect on brain lactate levels. CONCLUSION: In this first designed brain irradiation animal model, which evaluated G-CSF effects, we observed that G-CSF had reparative, neuroprotective and anti-neurodegenerative effects and had increased neurotrophic factor expression, neuronal counts, and morphology changes. In addition, G-CSF had a proven lactate-lowering effect in MR spectroscopy and brain materials.

Escitalopram co-prescription in anastrozole-treated breast cancer patients.

OBJECTIVE: The purpose of the study was to evaluate the impact of escitalopram co-prescription on plasma anastrozole levels in post-menopausal breast cancer patients. METHODS: A total of 24 post-menopausal operated breast cancer patients co-prescribed with escitalopram and anastrozole were included. Blood samples were collected, before and 1-month after the onset of escitalopram to analyze plasma anastrozole and estradiol levels. RESULTS: No significant difference was noted in basal plasma anastrozole levels with respect to age, body mass index (BMI), tumor stage, previous antineoplastic treatments, concomitant medications, and serum estradiol levels. Overall, 17 patients completed the 1-month escitalopram treatment, while 7 patients discontinued escitalopram within the 1st week of the treatment. Basal anastrozole levels of 24 patients were 26.1±2.4 ng/mL. Among 17 patients who continued 1-month escitalopram treatment was associated with significant increase in plasma anastrozole levels (24.5±2.3 ng/mL to 32.2±3.2 ng/mL, p<0.05). Notably, 1-month escitalopram use was associated with significant increase in plasma anastrozole levels only in the subgroup of obese (BMI >29 kg/m2) patients (23.1±2.8 to 35.9±4.7 ng/mL, p<0.01), while no such interaction was noted among non-obese patients. The estradiol levels of the patients were below ≤10 pg/mL in 75% of patients and no change occurred after escitalopram administration. CONCLUSION: Escitalopram co-prescription resulted in significant increase in plasma anastrozole levels without affecting the serum estradiol levels. Our findings emphasize the need for close monitoring in case of concomitant use of anastrozole and escitalopram, especially in obese patients and the potential role of therapeutic drug monitoring.

Push-out bond strength of fiber posts to irradiated and non-irradiated intraradicular dentin.

OBJECTIVES: The aim of this study is to evaluate the influence of ionizing radiotherapy on the resin-dentin interface in endodontically treated teeth restored with fiber posts using a dual-cure resin cement performed with the etch-and-rinse (ER) and self-etch (SE) approaches in terms of push-out bond strength (MPa), and to analyze the post/cement/dentin interface using scanning electron microscopy (SEM). MATERIALS AND METHODS: Seventy-six single-rooted human teeth were used and randomly assigned into two main groups (n = 38): one non-irradiated group (NoRad) and one group subjected to a cumulative radiation dose of 60 Gy (Rad). All root canals were instrumented and were further subdivided into two subgroups (n = 19) following the adhesive approach: ER (RadER; NoRadER) and SE (RadSE; NoRadSE) used for fiber post luting with the universal adhesive and dual cure resin cement. Each root was sectioned perpendicularly to its long axis and sections from the middle third of the roots were chosen for SEM analysis and push-out bond strength test. Two-way ANOVA with post hoc Tukey tests and a dummy variable linear regression analysis were used for data analysis. RESULTS: Regardless of the adhesive approach, push-out bond strength in irradiated teeth resulted in significantly lower values than non-irradiated teeth (p = 0.0001). There were no significant differences between the ER and SE approaches in non-irradiated teeth (p = 0.955), whereas the ER approach showed significantly higher bond strengths than the SE approach in irradiated teeth (p = 0.0001). CONCLUSIONS: Ionizing radiotherapy resulted in dentin structure disruption and negatively affected the push-out bond strength of fiber posts to intraradicular dentin. The reduction in bond strength was also more significant with the SE approach than with the ER approach. CLINICAL RELEVANCE: The alterations resulting from root dentin irradiation seem to influence adhesive systems bond strength to dentin, as these changes contribute to lower push-out bond strength in irradiated groups before fiber post luting. Thus, clinicians should prepare patients with a reasonable restorative treatment plan prior to radiotherapy and simultaneously initiate a preventive program during radiotherapy.

Is fractionated robotic stereotactic body radiosurgery optional salvage treatment for the re-irradiation of locally recurrent nasopharyngeal carcinoma?

Purpose: Recurrent nasopharyngeal carcinoma (NPC) after previous radiation therapy is a significant problem. This study was to determine the potential benefits from re-irradiation by fractionated stereotactic body radiotherapy (FSRT) on survival benefits and effects of severe late toxicities. Materials and Methods: Between 2009 and 2018, treatment outcomes were evaluated retrospectively in 26 patients with locally recurrent NPC treated using FSRT with CyberKnife. Five patients who had metastatic disease and one who had second recurrence were excluded from the study, and the remaining 20 patients were analyzed. The median age was 52 years (range, 28-80 years); re-treatment T stage was as follows: 6 (30%) - T2, 5 (25%) - T3, and 9 (45%) - T4. The median time from initial RT to recurrence was 22 months (range, 8-159 months). The median re-irradiation FSRT dose was 30 Gy in 5 fractions. Results: The median follow-up was 44 months; the overall survival (OS), local failure-free survival, and disease progression-free survival rates at 3 years were 89%, 73%, and 53%, respectively. All patients were evaluated for response after treatment: 9 (45%) had complete, 3 (15%) had partial, and 6 (30%) had no response. Univariate analysis demonstrated that higher cumulative total radiotherapy dose, gross tumor volume, and recurrent time interval were prognostic factors for local failure-free survival. The recurrent time interval was also an independent factor for progression-free survival and OS. The incidence of temporal lobe necrosis and trismus was 10% and 20%, respectively. One patient had Grade 5 toxicity to treatment-related bleeding. Conclusion: Tumor dose coverage is important for treating recurrent NPC, and treatment-related mortality was vascular in nature. FSRT is a promising treatment modality for recurrent NPC.

Prognostic factors in medically inoperable early stage lung cancer patients treated with stereotactic ablative radiation therapy (SABR): Turkish Radiation Oncology Society Multicentric Study.

OBJECTIVE: We identified factors influencing outcomes in patients with medically inoperable early stage lung cancer (MIESLC) treated with stereotactic ablative radiation therapy (SABR) at 14 centers in Turkey. MATERIALS AND METHODS: We retrospectively analyzed 431 patients with stage I-II MIESLC treated with SABR from 2009 through 2017. Age; sex; performance score; imaging technique; tumor histology and size; disease stage radiation dose, fraction and biologically effective dose with an α/ß ratio of 10 (BED10 ); tumor location and treatment center were evaluated for associations with overall survival (OS), local control (LC) and toxicity. RESULTS: Median follow-up time was 27 months (range 1-115); median SABR dose was 54 Gy (range 30-70) given in a median three fractions (range 1-10); median BED10 was 151 Gy (range 48-180). Tumors were peripheral in 285 patients (66.1%), central in 69 (16%) and <1 cm from mediastinal structures in 77 (17.9%). Response was evaluated with PET/CT in most cases at a median 3 months after SABR. Response rates were: 48% complete, 36.7% partial, 7.9% stable and 7.4% progression. LC rates were 97.1% at 1 year, 92.6% at 2 years and 91.2% at 3 years; corresponding OS rates were 92.6%, 80.6% and 72.7%. On multivariate analysis, BED10 > 100 Gy (P = .011), adenocarcinoma (P = .025) and complete response on first evaluation (P = .007) predicted favorable LC. BED10 > 120 Gy (hazard ratio [HR] 1.9, 95% confidence interval [CI] 1.1-3.2, P = .019) and tumor size (<2 cm HR 1.9, 95% CI 1.3-3, P = .003) predicted favorable OS. No grade 4-5 acute side effects were observed; late effects were grade ≤3 pneumonitis (18 [4.2%]), chest wall pain (11 [2.5%]) and rib fracture (1 [0.2%]). CONCLUSION: SABR produced encouraging results, with satisfactory LC and OS and minimal toxicity. BED10 > 120 Gy was needed for better LC and OS for large, non-adenocarcinoma tumors.

CT Derived Hounsfield Unit: An Easy Way to Determine Osteoporosis and Radiation Related Fracture Risk in Irradiated Patients.

Background: We aimed to evaluate osteoporosis, bone mineral density, and fracture risk in irradiated patients by computerized tomography derived Hounsfield Units (HUs) calculated from radiation treatment planning system. Methods: Fifty-seven patients operated for gastric adenocarcinoma who received adjuvant abdominal radiotherapy were included in the study group. Thirty-four patients who were not irradiated after surgery comprised the control group. HUs of T12, L1, L2 vertebral bodies were measured from the computerized tomographies imported to the treatment planning system for all the patients. While the measurements were obtained just after surgery and 1 year later after surgery in the control group, the same measurements were obtained just before irradiation and 1 year after radiotherapy in the study group. Percent change in HU values (Δ%HU) was determined for each group. Vertebral compression fractures, which are the consequence of radiation induced osteoporosis and bone toxicity were assessed during follow-up. Results: There was no statistical significant difference in HU values measured for all the vertebrae between the study and the control group at the onset of the study. While HU values decreased significantly in the study group, there was no significant reduction in HU values in the control group after 1 year. significant correlation was found between Δ%HU and the radiation dose received by each vertebra. Insufficiency fractures (IFs) were observed only in the irradiated patients (4 out of 57 patients) with the cumulative incidence of 7%. Conclusions: HU values are very valuable in determining bone mineral density and fracture risk. Radiation treatment planning system can be utilized to determine HU values. IFs are common after abdominal radiotherapy in patients with low vertebral HU values detected during radiation treatment planning. Radiation dose to the vertebral bones with low HU values should be limited below 20 Gy to prevent late radiation related bone toxicity.

Stereotactic Radiotherapy in Recurrent Glioblastoma: A Valid Salvage Treatment Option.

BACKGROUND: Glioblastoma (GBM) is a dismal disease. Recurrence is inevitable despite initial surgery and postoperative temozolomide (TMZ) and radiotherapy. Salvage surgery is the standard treatment in selected patients. Chemotherapy, biological agents, and re-irradiation are other treatment approaches available. Stereotactic radiotherapy (SRT) is nowadays a common treatment as a salvage treatment option. MATERIALS AND METHODS: We reviewed the files of 132 GBM cases treated between 2010 and 2018. All patients received TMZ and radiotherapy after surgery or biopsy. Among the patients who had recurrence, we identified 42 cases treated with salvage SRT. The CyberKnife robotic system was used to administer SRT. RESULTS: While the median follow-up time for all patients was 16 months (range 1-123), the median follow-up time for patients treated with SRT after initial diagnosis was 26.5 months (range 9-123). The median follow-up time after SRT was 10 months (range 2-107). SRT was performed in a median of 3 fractions (range 2-5). The median prescription dose was 20 Gy (range 18-30). While the median actuarial survival after initial diagnosis for patients treated with salvage SRT was 30 months (range 9-123), it was only 14 months (range 1-111) for patients who could not be treated with salvage SRT (p = 0.001). The median survival time after SRT was 12 months, and 1- and 2-year survival rates were 48 and 9%, respectively. The time to progression after SRT was 5 months (range 1-62), and 6-month and 1-year progression-free survival rates were 50 and 22%, respectively. Patients with longer time to recurrence >12 months had longer overall survival with respect to the ones having recurrence <12 months (p < 0.001). Salvage surgery had been performed in 7 out of 42 patients before SRT. These reoperated patients had significantly worse survival after SRT when compared to the patients who underwent SRT alone (p = 0.02). SRT was well tolerated and there was no grade III/IV toxicity. CONCLUSIONS: SRT is a viable salvage treatment option for recurrent GBM. SRT provides acceptable local control and survival benefit for recurrent GBM cases. SRT can be considered especially in patients with long time to recurrence.

Prognostic factors for survival in patients with gastric cancer: Single-centre experience.

OBJECTIVE: We aimed to investigate survival outcomes and survival-related prognostic factors in gastric cancer patients who were followed-up or received adjuvant therapy in our center. METHODS: Patients with gastric cancer treated between 2005 and 2016 were evaluated retrospectively. We included 345 non-metastatic (stage I-III) gastric cancer patients in the study. The clinical, demographic, histologic data of the patients and treatment characteristics were obtained from the patient's files. RESULTS: While 50 patients were stage I, 94 patients were stage II, 201 patients were stage III. While 221 patients (64%) presenting with serosal or adjacent visceral organ invasion or with involved lymph nodes were treated with adjuvant chemoradiotherapy, 124 patients presenting with early-stage disease were followed after surgery. Median follow up time was 34 months (4-156 months). While the median overall survival (OS) was 51 months, median disease-free survival (DFS) was 35 months. Overall survival and disease-free survival rates for 1st, 3rd and 5th years were 85%, 55%, 45% and 72%, 49%, 38%, respectively. According to univariate analysis, tumor size, T stage (p<0.001), N stage (p<0.001), TNM stage (p<0.001), grade (p<0.001) and presence of lymphovascular invasion (p=0.005) were determined as prognostic factors that affect overall survival significantly. According to the multivariate analysis, only T and N stage (p<0.001) were determined as independent prognostic factors for overall survival. CONCLUSION: Many different prognostic factors have been defined for gastric cancer. In concordance with the literature, we found T and N stages as prognostic factors in univariate and multivariate analysis.

Acoustic diagnosis of elastic properties of human tooth by 320 MHz scanning acoustic microscopy after radiotherapy treatment for head and neck cancer.

BACKGROUND: On the elastic profiles of human teeth after radiotherapy for head and neck cancers, generation of dental complications, which may bring several side effects preventing the quality of life, has not well clarified. Thus, we aimed to show the applicability of using 320 MHz Scanning Acoustic Microscopy (SAM) in the evaluation of the tooth damage acoustically at the micrometer level following radiation therapy, and also in the determination of the safe dose limits to impede severe dental damage. METHODS: This prospective study was performed by SAM employed at 320 MHz by an azimuthal resolution of 4.7 µm resolving enamel and dentin. A total of 45 sound human third molar teeth collected between September 2018 and May 2019 were used for the acoustic impedance measurements pre- and post irradiation. Nine samples for each group (control, 2 Gy, 8 Gy, 20 Gy, 30 Gy and 60 Gy) were evaluated to acquire the acoustic images and perform a qualitative analysis. Scanning Electron Microscopy (SEM) images were obtained to establish a relationship between micromechanical and morphological characteristics of the teeth. Statistical analysis was conducted using the Student t-test succeded by Mann-Whitney U investigation (p < .05), while SEM images were assessed qualitatively. RESULTS: The analysis included 45 sound teeth collected from men and women 18 to 50 years old. Post irradiation micromechanical variations of human teeth were significant only in the radiation groups of 30 Gy and 60 Gy compared to pre-irradiation group for enamel (7.24 ± 0.18 MRayl and 6.49 ± 028 MRayl; p < 0.05, respectively). Besides, the teeth subjected to radiation doses of 20, 30 and 60 Gy represented significantly lower acoustic impedance values relative to non-irradiated group for dentin (6.52 ± 0.43 MRayl, 5.71 ± 0.66 MRayl and 4.82 ± 0.53 MRayl p < 0.05), respectively. CONCLUSIONS: These results are evidence for a safe acoustic examination device which may be a useful tool to visualize and follow the safe dose limits to impede severe dental damage through the radiation therapy treatment for head and neck cancers.

Is stereotactic body radiotherapy an alternative to surgery in early stage non small cell lung cancer?

PURPOSE: To determine local control and overall survival of patients with medically inoperable early-stage non-small cell lung cancer (NSCLC) treated with stereotactic ablative radiotherapy. METHODS: Included were a total of 52 patients (7;13% females and 45;87% males) with medically inoperable early-stage NSCLC and who were treated with stereotactic ablative body radiotherapy (SBRT) by a CyberKnife robotic radiotherapy machine between 2009 and 2017. Depending on tumor size and location, median 45 Gy (30-60) were delivered in median 3 fractions (3-5) to Planning Target Volume. As regards the tumor-tracking system; X-Sight lung tracking system was used in 43 (83%) patients, gold fiducials in 4 (8%) patients, and X-Sight spine tracking system in 5 (9%) patients. RESULTS: The median age of patients was 67 years (54-86). Tumor was staged as cT1 in 38 (73%) patients and cT2 in 14 (27%) patients. Median follow up was found to be 23 months (10-84 months). Median survival time was 38 months and, 1-3-5 year survival rates were respectively 94%-53%-33.6%. Locoregional recurrence occurred in 8 (15%) patients and recurrence was local only in 4 (8%) patients, while it was regional only in 3 (6%) and distant only in 12 (23%) patients. During follow up, local, regional and distant recurrence was detected in 27 (52%) cases and median progression free survival was found to be 25 months. 1-3-5 year progression free survival was 71.2%-39%-26%, respectively. Grade 3 toxicity was observed in only one patient; no grade 4-5 toxicity was observed. CONCLUSION: A high local control rate with no major toxicity was obtained by SBRT in the patients with medically inoperable early-stage NSCLC. In the near future, SBRT may be an alternative that has growing evidence to support comparable outcomes in selected stage I patients.

Pretreatment SUVmax value to predict outcome in patients with stage III NSCLC receiving concurrent chemoradiotherapy.

OBJECTIVE: Stage III disease accounts for approximately one-fourth of all non-metastatic non-small cell lung cancer (NSCLC). The patients who are not candidates for curative resection are offered concomitant chemoradiotherapy. In this subgroup, which is difficult to manage, studies that address the role of PET-CT to predict outcome measures specifically for stage III NSCLC receiving concurrent chemoradiotherapy may help better risk stratification. This study aimed to assess whether baseline PET maximum standardized uptake value (SUVmax) value in stage III NSCLC treated with concurrent chemoradiotherapy would independently identify patients with high risk of progression and death. METHODS: The study population consisted of patients aged 18 years or more with unresectable stage III histologically or cytologically proven NSCLC who received concurrent chemoradiotherapy. From 2007 to 2014, medical records of patients admitted to our institution were retrospectively analyzed. Pretreatment PET-CT SUVmax values were recorded for each patient. These values were categorized as low or high according to the median SUVmax measure of the study population. RESULTS: A total of 175 patients were analyzed. The median follow-up time was 23 months (range 6-109). The PET-CT SUVmax values ranged from 3.5 to 46 with a median value of 14. The median overall survival was 25 months in SUVmax <14 and 18 months in SUVmax ≥14 group (p=0.023). The median progression-free survival was 16 months in SUVmax <14 and 11 months in SUVmax ≥14 group (p=0.033). Multivariate analysis revealed that both PET-CT SUVmax value (p<0.001) and age (p=0.016) were independent significant predictors for overall survival (OS). CONCLUSION: The results of this study involving patients with stage III NSCLC receiving concurrent chemoradiotherapy provide evidence that suggests that high values of pretreatment SUVmax, an indicator of metabolic tumor burden, predicted a higher risk of disease progression and death.

Anal canal squamous cell cancer: surgical therapy, when?

Aim To describe a therapeutic approach, indications for abdominoperineal resection (APR), survival and oncological results for patients who received treatment in our surgical clinic for anal canal squamous cell cancer (SCC). Methods Patients were randomized into two groups according to the treatment method: Group 1- Chemoradiotherapy (CRT) without surgery, Group 2- CRT + APR. Results Eighteen patients with anal canal SCC were included in the study; 11 (61.1%) patients were in Group 1 and 7 (38.8%) in Group 2. Reasons for APR was as follows: three patients had insufficient CRT, two had recurrence after CRT, one had complete faecal incontinence and one patient had rectovaginal fistula. Overall five year survival (OS) and disease free survival (DFS) was 77.7% and 72.7%, respectively. Comparing two groups five year OS was 90.9% and 57.1%, whereas DFS was 81.8%, 57.1%, respectively (p=0.389 and 0.324, respectively). Conclusion Gold standard therapy for anal canal SCC is CRT. However, APR should be applied as an escape treatment for patients suffering from tumour progression, insufficient CRT and recurrence (30%).

Volumetric decrease of pancreas after abdominal irradiation, it is time to consider pancreas as an organ at risk for radiotherapy planning.

BACKGROUND: Volumetric shrinkage of normal tissues such as salivary glands, kidneys, hippocampus are observed after radiotherapy. We aimed to assess the alterations in pancreatic volume of patients who received abdominal radiotherapy and define pancreas as an organ at risk for radiation treatment planning. MATERIAL-METHODS: Forty-nine patients operated for gastric adenocarcinoma who received adjuvant abdominal radiotherapy were in the study group, 27 patients with early stage disease who did not need adjuvant treatment after surgery comprised the control group. An experienced radiologist contoured the pancreas of all the patients from computed tomographies imported to the planning system obtained either for radiation planning purpose or for follow-up after surgery. The same procedure was repeated one year later for both groups. Measured volume of the pancreas was expressed in cm3. RESULTS: Mean pancreatic volumes were similar in both groups at the onset of the study, 51,34 ± 20,33 cm3, and 50,12 ± 23,75 cm3 in the irradiated and the control groups respectively (p = 0,63). One year later, mean pancreatic volumes were significantly decreased in each group; 22,48 ± 10,53 cm3, 44,18 ± 23,08 cm3 respectively, p < 0,001. However, the decrease in pancreatic volume was significantly more pronounced in the irradiated group in comparison to the control group, p < 0,001. CONCLUSION: Volumetric decrease in normal tissues after radiotherapy is responsible for loss of organ function and radiation related late side effects. Although pancreas is a radiation sensitive organ losing its volume and function after radiation exposure, it is not yet considered as an organ at risk for radiation treatment planning. Pancreas should be contoured as an organ at risk, dose-volume histogram for the organ should be created, and safe organ doses should be determined. This is the first study declaring pancreas as an organ at risk for radiation toxicity and the necessity of defining dose constraints for the organ.

Osteoporosis development and vertebral fractures after abdominal irradiation in patients with gastric cancer.

BACKGROUND: Decrease in bone mineral density, osteoporosis development, bone toxicity and resulting insufficiency fractures as late effect of radiotherapy are not well known. Osteoporosis development related to radiotherapy has not been investigated properly and insufficiency fractures are rarely reported for vertebral bones. METHODS: Ninety-seven patients with gastric adenocarcinoma were evaluated for adjuvant treatment after surgery. While 73 out of 97 patients treated with adjuvant chemoradiotherapy comprised the study group, 24 out of 97 patients with early stage disease without need of adjuvant treatment comprised the control group. Bone mineral densities (BMD) of lumbar spine and femoral neck were measured by dual energy x-ray absorptiometry after surgery, and one year later in both groups. RESULTS: There was statistically significant decline in BMDs after one year in each group itself, however the decline in BMDs of the patients in the irradiated group was more pronounced when compared with the patients in the control group; p values were 0.02 for the decline in BMDs of lumbar spine, and 0.01 for femoral neck respectively. Insufficiency fractures were observed only in the irradiated patients (7 out of 73 patients) with a cumulative incidence of 9.6%. CONCLUSIONS: Abdominal irradiation as in the adjuvant treatment of gastric cancer results in decrease in BMD and osteoporosis. Insufficiency fracture risk in the radiation exposed vertabral bones is increased. Calcium and vitamin D replacement and other measures for prevention of osteoporosis and insufficiency fractures should be considered after abdominal irradiation.

Radiation field size and dose determine oncologic outcome in esophageal cancer.

BACKGROUND: Locoregional recurrence is a major problem in esophageal cancer patients treated with definitive concomitant chemoradiotherapy. Approximately half of the patients fail locoregionally. We analyzed the impact of enlarged radiation field size and higher radiation dose incorporated to chemoradiotherapy on oncologic outcome. METHODS: Seventy-four consecutive patients with histologically proven nonmetastatic squamous or adenocarcinoma of the esophagus were included in this retrospective analysis. All patients were locally advanced cT3-T4 and/or cN0-1. Treatment consisted of either definitive concomitant chemoradiotherapy (Def-CRT) (n = 49, 66 %) or preoperative concomitant chemoradiotherapy (Pre-CRT) followed by surgical resection (n = 25, 34 %). Patients were treated with longer radiation fields. Clinical target volume (CTV) was obtained by giving 8-10 cm margins to the craniocaudal borders of gross tumor volume (GTV) instead of 4-5 cm globally accepted margins, and some patients in Def-CRT group received radiation doses higher than 50 Gy. RESULTS: Isolated locoregional recurrences were observed in 9 out of 49 patients (18 %) in the Def-CRT group and in 1 out of 25 patients (3.8 %) in the Pre-CRT group (p = 0.15). The 5-year survival rate was 59 % in the Def-CRT group and 50 % in the Pre-CRT group (p = 0.72). Radiation dose was important in the Def-CRT group. Patients treated with >50 Gy (11 out of 49 patients) had better survival with respect to patients treated with 50 Gy (38 out of 49 patients). Five-year survivals were 91 and 50 %, respectively (p = 0.013). CONCLUSIONS: Radiation treatment planning by enlarged radiation fields in esophageal cancer decreases locoregional recurrences considerably with respect to the results reported in the literature by standard radiation fields (18 vs >50 %). Radiation dose is as important as radiation field size; patients in the Def-CRT group treated with ≥50 Gy had better survival in comparison to patients treated with 50 Gy.