Hypofractionated radiotherapy for non-metastatic bone and soft tissue sarcomas.

PURPOSE: To evaluate the efficacy and toxicity of hypofractionated radiotherapy in non-metastatic soft tissue and bone sarcomas. PATIENTS AND METHODS: Thirty patients underwent hypofractionated radiotherapy between 2007 and 2015. Overall, 17 patients underwent primary hypofractionated radiotherapy, nine underwent hypofractionated radiotherapy for reirradiation, and four received a boost dose via hypofractionated radiotherapy after external beam radiotherapy. Most common disease sites were head and neck and retroperitoneum. Hypofractionated radiotherapy was administered with a definitive, adjuvant, or neoadjuvant intent. RESULTS: Median age was 37 years (range: 11-82 years). Median hypofractionated radiotherapy dose was 35Gy (range: 20-50Gy) in three to five fractions. Median follow-up was 21 months (range: 1-108 months). One- and 2-year overall survival rate was 75% and 52%, respectively. One- and 2-year local recurrence-free survival rate was 59% and 48%, with local recurrence rates of 16% and 33% in 1 and 2 years, respectively. Univariate analysis revealed tumour size (P=0.04), hypofractionated radiotherapy intent (P=0.016) and reirradiation (P=0.001) as prognostic factors for local recurrence-free survival. Severe late toxicity was observed in one patient as grade 3 trismus. CONCLUSION: Hypofractionated radiotherapy as the primary treatment or for reirradiation has been shown to be safe in the treatment of bone and soft tissue sarcomas. It can provide relatively good local control and survival rates.

Evaluation of sex hormones and sperm parameters in male epileptic patients.

OBJECTIVES: The aim of this study was to investigate the effect of carbamazepine (CBZ) and sodium valproate (VPA) monotherapy on sexual functions, sex hormones, and semen analysis and quality in male patients with epilepsy. METHODS: A total of 59 male patients with epilepsy, of which 30 were on VPA monotherapy and 29 were on CBZ monotherapy, were included in the study between January 2015 and March 2016. A control group was established with 30 healthy males. Luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL), free testosterone (fT), estradiol (E2), sex hormone-binding globulin (SHBG) levels and bioactive testosterone (BAT)/bioactive estradiol (BAE), and BAT/LH ratio were studied in groups. All groups received semen analysis and International Index of Erectile Function Scale (IIEF-5) test for erectile dysfunction. RESULTS: E2 and DHEAS levels were higher in VPA and CBZ groups compared to control group (P < .001, P = .014). The decrease in fT levels in the VPA group was statistically significant (P = .038). No significant difference was detected in levels of SHBG, LH, and FSH (P > .05). BAT/BAE ratios were low both in VPA and CBZ groups (P < .001; P < .001), while BAT/LH ratios were low only in CBZ group (P = .033). In semen analysis, semen volume and number of normal sperms were found to be significantly lower in patients receiving antiepileptic drugs compared to control group (P < .05). There were no differences between the groups in rates of abnormal sperm morphology. IIEF-5 scores were found to be significantly lower in VPA and CBZ groups (P < .001). CONCLUSION: VPA or CBZ therapy may lead to dysregulation of sex hormones, sexual dysfunction, and alterations in semen analysis in male patients with epilepsy. This must be considered for the selection of antiepileptic drugs in young male patients.

Robotic Stereotactic Body Radiation Therapy in Patients With Recurrent or Metastatic Abdominopelvic Tumors: A Single Institute Experience.

BACKGROUND: The aim of this study was to evaluate the efficacy and toxicity of robotic CyberKnife (Accuray Incorporated, Sunnyvale, California)-based stereotactic body radiation therapy (SBRT) in patients with recurrent or metastatic abdominopelvic tumors. METHODS AND MATERIALS: A total of 69 patients treated between May 2008 and January 2011 were evaluated retrospectively. Indication for SBRT was persistent disease in 3 (4%) patients, local recurrence in 29 (42%) patients, regional recurrence in 13 (19%) patients, and oligometastatic disease in 24 (35%) patients. Forty-two (61%) patients were previously irradiated to the same region and 27 (39%) patients were treated for the first time. The median age was 59 years (range, 24-86 years). There were 31 (45%) male and 38 (55%) female patients. The median total dose was 30 Gy (range, 15-60 Gy) delivered with a median 3 fractions (range, 2-5 fractions). The tumor response to treatment was assessed by computed tomography, magnetic resonance imaging, or positron emission tomography. RESULTS: At the 12-month (range, 2-44 months) median follow-up, local control was 65% and median overall survival (OS) was 20 months. A larger gross tumor volume (≥ 67 cm(3)) was significantly correlated with worse 1-year OS (81% vs 48%, P = .03). The patients with local recurrence occurring <11 months had a significantly shorter 1-year local control rate than patients with ≥ 11 months (31% vs 91%, P < .001). Grade 3-4 acute and late toxicities were seen in 7% and 15% of patients, respectively. The patients with previous radiotherapy history had significantly higher rate of acute toxicity (19% vs 0%, P = .019). Late toxicity was significantly higher in pelvic tumors than in abdominal tumors (3% vs 28%, P = .004). CONCLUSION: The SBRT seems to be feasible and resulted in good treatment outcomes in patients with recurrent or metastatic abdominopelvic tumors.

C-reactive protein levels in girls with lower urinary tract symptoms.

INTRODUCTION: Daytime lower urinary tract (LUT) conditions are identified as daytime incontinence problems for children in whom any cause of neuropathy and uropathy has been excluded. C-reactive protein (CRP) is a common marker of acute or chronic inflammation and infection. Increased CRP levels have been detected in the studies conducted on adults diagnosed with overactive bladders and interstitial cystitis. OBJECTIVE: This study aimed to investigate the role of serum CRP levels in girls suffering from daytime LUT conditions. STUDY DESIGN: Out of the 752 patients who presented to the outpatient clinics with lower urinary tract symptoms, 709 were excluded due to: being boys, having previous urinary tract surgery, an active urinary tract infection, a neurological anomaly, a urinary system anomaly, having rheumatic disease, any chronic disease, any febrile infection over the past week, a history of constipation, and enuresis nocturna. Forty-three girls with LUT conditions and aged 8-10 years were included in the study as the patient group. Forty girls who attended the urology outpatient clinic without LUT conditions, or active urinary tract infections and any chronic disease requiring follow-up constituted the control group. Under the control of the parents, all subjects were asked to fill out 3-day voiding diaries. The voiding diaries identified frequency, urgency, urgency urinary incontinence, and functional bladder capacity data. All subjects also completed a dysfunctional voiding scoring system (DVSS). The serum CRP levels of all subjects were measured. RESULTS: There was a significant difference in serum CRP levels and DVSS between the patient group and the control group (P = 0.001, P = 0.001). The mean serum CRP levels showed a significant increase when frequency and urgency scores were ≥8, the urge incontinence score was ≥2 and the DVS score DVSS was ≥14 in the voiding diaries of the patient group (Table). DISCUSSION: Lower urinary tract dysfunction is defined as a condition involving abnormalities of filling and/or emptying of the bladder. This frequently encountered problem constitutes >40% of all pediatric urology outpatient visits. The relationship between LUT conditions and serum CRP in both genders has been detected. However, it is believed that to our knowledge, this is the first study looking at the relationship between daytime LUTS and increased CRP levels in children. The most important limitations of the study were: having a small number of patients, and the sample consisting of only one gender and a specific age group. CONCLUSION: The serum CRP levels were significantly higher in the girls with daytime LUT conditions than in the control group. Also, the CRP levels significantly increased as DVSS, frequency, urgency, and urge incontinence scores increased.

Fractionated stereotactic radiosurgery treatment results for skull base chordomas.

Chordomas are uncommon neoplasms and there is still controversy regarding establishment of diagnosis and management. The aim of this study was to evaluate efficacy and toxicity of fractionated stereotactic radiosurgery (FSRS) in skull base chordomas. There were 4 female (36%) and 7 male (64%) patients. FSRS was delivered with CyberKnife (Accuray Inc., Sunnyvale, CA). The median tumor volume was 14.7 cc (range, 3.9-40.5 cc). The median marginal tumor dose was 30 Gy (range, 20-36 Gy) in a median 5 fractions (range, 3-5 fractions). The median follow-up time was 42 months (range, 17-63 months). At the time of analysis, 10 (91%) patients were alive and 1 (9%) had died due to tumor progression. Of 10 patients, 8 (73%) had stable disease and the remaining 2 (18%) had progressive disease. The actuarial overall survival (OS) after FSRS was 91% at two-years. Two patients developed radiation-induced brain necrosis as a complication in the 8th and 28th months of follow-up, respectively. Our results with robotic FSRS in skull base chordomas are promising for selected patients. However, due to the slow growth pattern of skull base chordomas, a longer follow-up is required to determine exact treatment results and late morbidity.

Robotic stereotactic radiosurgery in patients with unresectable glomus jugulare tumors.

We evaluated the treatment results of robotic stereotactic radiosurgery (SRS) in our patients with unresectable glomus jugulare tumors (GJTs). The medical charts of fourteen patients with GJT, who were treated with robotic SRS, were retrospectively evaluated. The gross tumor volume was described as the clinical target volume. The median dose to the tumor was 25 Gy in median 5 fractions. The dose was normalized to 80% isodose line. All patients were evaluated for tumor growth and clinical outcome every 6 months in the first 2 years and then annually. Median follow-up was 39 months (range, 7-60 months). Lesions were stable in 8 patients, and tumor regression was observed in 6 patients. We did not observe any treatment related toxicity in our patients. In conclusion, according to our early experience, robotic SRS seems to be successful treatment option in the management of unresectable GJTs.

Premature ejaculation in patients with ankylosing spondylitis.

We aimed to evaluate the premature ejaculation (PE) among ankylosing spondylitis (AS) patients. Fifty male patients with AS who were diagnosed according to the modified New York criteria and fifty normal healthy controls (NHC) were included in this study. The details of patient age, disease duration, morning stiffness, laboratory activity, disease severity and medication use were obtained by reviewing the medical record. The Bath AS Functional Index (BASFI) was used to measure the functional status of the patients with AS. By taking a careful medical and sexual history, patients were classified as lifelong, natural variable, acquired PE or premature ejaculatory dysfunction. In addition to medical and sexual history, self-estimated intravaginal ejaculatory latency times (IELT) of patients were used in the classification of patients. To our knowledge, this is the first study of frequency of PE in men with AS. The prevalence rates of PE in patient and healthy controls were 32 and 30%, respectively (p = 0.331). The prevalence of PE was not significantly different between AS patients and NHC groups as regards the four PE syndromes. Average estimated IELT was 10,009 ± 51.9 sec in the PE group and 145.26 ± 43.01 sec in the non-PE group (p = 0.000). Patients with lifelong PE had a significantly lower mean estimated IELT than the other group (p = 0.000). Patients with premature-like ejaculatory dysfunction had the highest estimated IELT (p = 0.000). There was a significant association between self-estimated IELT and distribution of the patients according to the four PE syndromes (p = 0.01). Both AS patients and NHC groups have the same results. The present study demonstrates that PE in men with AS is as prevalent as it is in the general population. Although this study is restricted in terms of the number of patients, it is the first study ever conducted. For more meaningful results, multi centred studies with more patients are required.

Pineal region tumors in children: a single center experience.

Pineal region tumors are a relatively uncommon, deep-seated heterogeneous group of mass lesions of the brain. Their management is much more complicated in children with cancer, both in terms of survival and sequelae, due to primary location of the tumor and treatment modality. The goal of this retrospective study was to report the presentation, treatment, and outcome of tumors that arose from this region in 24 children treated at our institution between March 1975 and May 2006. In all, 15 (62.5%) of the 24 children were initially treated with partial or complete resection, adjuvant radiotherapy was given to 18 (75%) patients, and chemotherapy was given to 15 (62.5%) of the patients. Overall survival was 44.5%. Although statistically insignificant, the most favorable outcome were obtained in patients with grossly resected tumors (66%) and in children >10 years of age (80%). Long-term sequelae occurred at a high rate in this study due to the primary location of the tumors and treatment modalities, which warrants further investigation.

Malignant pleural mesothelioma with brain metastasis.

Malignant pleural mesothelioma (MPM) is a rare neoplasm associated with poor prognosis. Local disease progression is the major cause of death rather than distant metastasis. Intracranial metastases are seen very rarely. Herein, we report a case of MPM with brain metastasis treated with cranial irradiation.

Breast cancer with diabetes insipidus.

UNLABELLED: Diabetes insipidus (DI) is a rare clinical condition, which is usually caused by neurohypophyseal or pituitary stalk infiltration in cancer patients. CASE REPORT: we present a 62-year old metastatic breast cancer woman with DI. She admitted to the hospital because of nausea, vomiting, polyuria and polydipsia, while she was on no cytotoxic medication. She had no electrolyte imbalance except mild hypernatremia. The CT scan of the brain yielded a suspicious area in pituitary gland. A pituitary stalk metastasis was found on magnetic resonance imaging (MRI) of pituitary. Water deprivation test was compatible with DI. A clinical response to nasal vasopressin was achieved. CONCLUSIONS: Cancer patients who have symptoms such as nausea, vomiting, polyuria and polydipsia while they are not on chemotherapy should be evaluated for not only metabolic complications like hypercalcemia but also posterior pituitary or stalk metastasis MRI could be the choice of imaging for pituitary metastasis.

Prognostic significance of flow cytometric DNA analysis in patients with malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) due to environmental exposure to asbestos and erionite is a relatively common cancer in Turkey. In this study, we investigated the value of flow cytometric (FCM) DNA analysis and other prognostic factors such as age and etiologic factor in the patients with MPM, treated with surgery+/-combination chemotherapy+/-radiotherapy. A total of 40 patients with a median age of 50 (range 30-68) were included in the study. Twenty-nine patients had asbestos exposure in etiology, while 11 had fibrous zeolite (erionite). Paraffin-embedded tumor specimens were studied by FCM for DNA analysis. Twelve patients (30%) had aneuploid tumors and 28 (70%) had diploid ones. Mean S-phase fraction (SPF; %) was 9.1+/-1.1 and proliferation index (PI, SPF+G2/M phase; %) was 11.3+/-0.9. While the median overall survival (OS) was 10+/-2 months (6-14; 95% CI), 1-year survival rate was 45.2%. Only PI was found to be statistically significant for OS in univariate analysis (P=0.013). PI was also found to be an independent prognostic factor for all patients (P=0.035). Aneuploidy was significantly higher in erionite group compared with asbestos group. Male predominance and poor survival were also prominent in erionite group, though not statistically significant. In conclusion, PI is an independent prognostic factor for patients with MPM and the biologic features of the disease may show differences with respect to different etiologies.

Dermatofibrosarcoma protuberans metastasizing to cavernous sinuses and lungs: a case report.

Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive tumor with a low potential for distant metastases. We report a 22-year-old female patient with a typical cutaneous DFSP who developed five local recurrences followed by left cavernous sinus metastasis at the eighth year and right cavernous sinus and lung metastases at the ninth year. In each local recurrence the tumor showed histological signs of progression as being more cellular, having higher mitotic index and being aggressively invasive through the underlying soft tissues. The histopathological evaluation of the metastatic tumor resected from the left cavernous sinus revealed dedifferentiation from low-grade DFSP to higher grade fibrosarcomatous morphology. Immunohistochemical studies of the primary tumor and also the recurrent and metastatic tumors showed diffuse CD34 positivity in all specimens and p53 positivity was detected in the metastatic tumor resected from left cavernous sinus.

Tamoxifen increases membrane fluidity at high concentrations.

There are contradictory results in the literature relating to the effect of tamoxifen on membrane fluidity. The present work investigates the effect of tamoxifen on membrane dynamics to find out whether the concentration of tamoxifen can be one of the factors in this discrepancy. Turbidity (absorbance at 440 nm) and Fourier transform infrared spectroscopic studies reveal that tamoxifen causes opposite effects on membrane fluidity at low (1 mol.%) and high (30 mol.%) tamoxifen concentrations. Low tamoxifen concentrations increase the absorbance in the gel and liquid crystalline phase, whereas high tamoxifen concentrations decrease the absorbance in gel and liquid crystalline phase, whereas tamoxifen concentrations decrease the absorbance. Observations on both phases show that the bandwidth of the CH2 stretching bands decreases with 1 mol.% tamoxifen and increases with 30 mol.% tamoxifen present, indicating a decrease in membrane fluidity at low tamoxifen concentrations and an increase in fluidity at high tamoxifen concentrations. It is seen that the apparent discrepancy in the literature on the effect of tamoxifen on membrane fluidity mainly arises from the tamoxifen concentration used and the confusion on the concept of lipid fluidity and lipid order.

Prevention of intimal hyperplasia by single-dose pre-insertion external radiation in canine-vein interposition grafts.

OBJECTIVES: to evaluate the efficacy of single-dose pre-insertion gamma radiation of vein grafts in the prevention of intimal hyperplasia. METHODS: femoral artery interposition grafts with internal jugular vein were inserted in 12 mongrel dogs. The animals were randomly divided into two groups. Immediately before graft replacement, jugular veins were treated with a single dose of cobalt-60 radiation at 14 Gy or received no radiation (control group). Six weeks after graft insertion, the vein grafts were pressure-perfusion fixed and harvested for the histomorphometric analysis. Quantitative data on anastomotic stenosis were calculated from Gilman parameters after cross-sectional image analysis. RESULTS: vein grafts treated with radiation demonstrated significantly decreased neointima formation compared with grafts in the control group. The mean Gilman parameter for the control group was 1.09 S.E.M. 0.34 mm and for the radiotherapy group was 0.65 S.E. M. 0.23 mm (p<0.05). All vein grafts in the radiotherapy group had a decreased amount of intimal and cellular infiltration. CONCLUSION: single-dose external pre-insertion gamma radiation of vein grafts reduced the amount of intimal hyperplasia in this animal model.

Conventional external radiotherapy in the management of clivus chordomas with overt residual disease.

Cranial chordomas are uncommon tumors accounting for less than 1% of all intracranial neoplasms. Although they are slowly growing, rarely metastasizing tumors, cranial chordomas are challenging to treat due to their critical location, invasive nature and aggressive recurrence. The aim of this retrospective study was to evaluate the role of conventional irradiation in the treatment of clival chordomas with overt residual disease after incomplete surgery. Between January 1979 and December 1997, 18 patients with histologically confirmed clival chordoma were treated with radiotherapy. Median age at the time of diagnosis was 32 years. The mean duration of the symptoms before diagnosis was 33.9 months. Median tumor diameter at initial presentation was 5 cm (range, 3-7 cm). The type of surgical procedure was subtotal excision in 11 patients and biopsy in 7. Radiation treatment was delivered with megavoltage units, and total doses between 50 Gy and 64 Gy (median, 60 Gy) were administered with conventional daily fractions. One patient received additional 12.50 Gy with linear accelerator-based stereotactic radiosurgery after subtotal excision and external irradiation. The mean follow-up time was 43.2 months. Overall survival at 5 years was 35%. Eleven patients showed progression after radiotherapy. The median time to progression after radiotherapy was 40.8 months (38.4-43.2) with a 5-year progression-free survival of 23%. Five patients (29.4%) showed symptomatic relief after radiotherapy while persistent symptoms were recorded for 6 patients. Incomplete surgery and conventional external radiotherapy with a dose of around 60 Gy seem to be inadequate in the treatment of clival chordomas.

Radiotherapy in the management of giant pituitary adenomas.

BACKGROUND AND PURPOSE: The description of giant pituitary adenoma is not clear yet. In this study we tried to identify which adenomas can be defined as giant pituitary adenomas when tumor control and progression free survival (PFS) are taken as end points and we also tried to evaluate prognostic factors other than tumor size. MATERIALS AND METHODS: Between January 1981 and December 1997, 74 patients with pituitary macroadenomas more than 2 cm in size were treated. Of these 30 had tumors of more than 4 cm, while 44 patients were with tumors of 2-4 cm. Two patients received primary radiotherapy, while 72 were treated postoperatively. In the postoperative group, 52 patients underwent immediate radiotherapy after surgery and 20 were treated with irradiation after regrowth or progression of the tumor after initial surgery. The mean and median tumor doses were 5518 and 5425 cGy, respectively. RESULTS: Overall primary tumor control rate was 84%. The local control rates among patients with tumors more than 4 cm and among patients with tumors 2-4 cm after radiotherapy were 73 and 91%, respectively. PFS was 65% for patients who had a tumor size of more than 4 cm and 87% for the patients with tumor size of 2-4 cm (P = 0.09). Young age (<20) and tumors of unclassified histology were the bad prognostic factors. Six months after radiotherapy normalisation or improvement in hormonal hypersecretion and visual field and acuity deficits were 82 and 63%, respectively. CONCLUSION: Tumors more than 4 cm in size may be more convenient for the definition of 'giant pituitary adenoma' when tumor control and PFS are taken as the end points.

Reduced incidence of the somnolence syndrome after prophylactic cranial irradiation in children with acute lymphoblastic leukemia.

A prospective double blind randomized trial comparing two different dose schedules of continuous steroid coverage during prophylactic cranial radiotherapy (CRT) in leukemic children was conducted to find out the optimum dose to be prescribed to reduce the incidence of Somnolence Syndrome (SS). Between April 1994 and February 1996, 32 patients with acute lymphoblastic leukemia received CRT of 18 Gy in 10 fractions. Patients were randomized to receive oral dexamethasone of 2 or 4 mg/m2 during radiotherapy. The diagnosis of SS was made clinically based on symptoms of somnolence. All patients were followed for a minimum of 8 months. The overall incidence of SS was 40%. The development of SS was steroid dose dependent. In low dose steroid arm the incidence of SS was 64.3% (9/14), compared to 17.6% (3/17) in high dose arm with statistically significant difference (P = 0.008). The median time to development of SS was 4 weeks. The most common symptom of SS was drowsiness followed by anorexia, headache, nausea, vomiting, decreased activity, irritability, fever and ataxia, respectively. The duration of symptoms ranged from 2 to 14 days. The development of SS was not related to the presence of acute reactions, age at the time of CRT and sex. In all cases the symptoms subsided completely and spontaneously. Our results suggest that steroid coverage at a dose of 4 mg/m2 during CRT reduces the incidence of SS. However, a multicentric prospective randomized trial is needed to determine the role and the optimal dose of steroid.

Basal cell carcinomas developing in a case of medulloblastoma associated with Gorlin's syndrome.

We report a case of a 20-year-old male with Gorlin's syndrome (nevoid basal cell carcinoma syndrome), developing multiple basal cell carcinomas within irradiation fields 10 years after the treatment of medulloblastoma.