Implementation of TG-218 for patient-specific quality assurance tolerance and action limits determination: Gamma passing rate evaluation using 3DVH software.

PURPOSE: To determine the tolerance limit (TL) and action limit (AL) of gamma passing rates (%GP) for volumetric-modulated arc therapy (VMAT) patient-specific quality assurance (PSQA) according to the American Association of Physicists in Medicine (AAPM) Task Group (TG)-218 recommendations, and to comparatively evaluate the clinical relevance of 2D %GP and 3D %GP. METHODS: PSQA was performed for 100 head and neck (H&N) and 73 prostate cancer VMAT treatment plans. Measurements were acquired using a cylindrical water equivalent phantom, hollow in the center, allowing measurements with homogeneous or heterogeneous inserts. The LINAC-delivered dose distributions were compared to those calculated from the treatment planning system through the gamma index. TL and AL were determined through the computation of two-dimensional (2D) %GP using the recommended acceptance criteria. Dose-volume histograms were reconstructed from the measurements using a commercially available software to detect the dosimetric errors (%DE) between the compared dose distributions. Utilizing the estimated dose on the patient anatomy, structure-specific %GP (3D %GP) were calculated. The 3D %GP were compared to the 2D %GP ones based on their correlation with the %DE. Each metric's sensitivity was determined through receiver operator characteristic analysis. RESULTS: TL and AL were in concordance with the universal ones, regarding the prostate cancer cases, but were lower for the H&N cases. Evaluation of %DE did not deem the plans unacceptable. The 2D %GP and the 3D %GP did not differ significantly regarding their correlation with %DE. For prostate plans, %GP sensitivity was higher than for H&N cases. CONCLUSIONS: Determination of institutional-specific TL and AL allows the monitoring of the PSQA procedure, yet for plans close to the limits, clinically relevant metrics should be used before they are deemed unacceptable for the process to be of higher sensitivity and efficiency.

Referral for "Neoadjuvant Chemotherapy" for Muscle-Invasive Bladder Cancer to a Multidisciplinary Board: Patterns, Management and Outcomes.

BACKGROUND: Utilization of neoadjuvant chemotherapy for the treatment of muscle invasive bladder cancer in everyday practice differs from that of clinical trials. We describe the patterns of referral for "neoadjuvant chemotherapy", treatment and outcomes in a multidisciplinary tumor board. METHODS: This was an observational study. Patients referred for neoadjuvant chemotherapy received 4 cycles of dose-dense gemcitabine/cisplatin and were then assessed for definitive local therapy. Patients had a minimum follow-up of 2 years. Primary objective was a 3-year disease-free survival rate. RESULTS: Forty-six patients (clinical stages II: 28, IIIA: 9, IIIB: 4, IVA: 3, missing: 2) were included. Following chemotherapy, 30 underwent radical cystectomy, 8 radiotherapy and 8 no further therapy. Pathological downstaging was observed in 14 (46.6%) of the 30 patients who underwent radical cystectomy; clinical TNM staging was correlated with disease-free survival in the whole population, while clinical and pathological stages, as well as pathological downstaging, were correlated with disease-free survival in patients undergoing radical cystectomy. Three-year disease-free survival rates for the whole cohort and for patients undergoing radical cystectomy were 67.3% (95% confidence interval [CI]: 51-79.2) and 65.2 (95% CI: 44.9-79.6), respectively. CONCLUSION: Real-world muscle invasive bladder cancer patients who receive neoadjuvant chemotherapy are characterized by more advanced diseases and less frequent radical surgery than those included in clinical trials. Nevertheless, outcomes were comparable and, therefore, offering patients with stage II-IVA muscle invasive bladder cancer neoadjuvant chemotherapy after assessment by multidisciplinary tumor boards should be strongly encouraged.

Host cystathionine-γ lyase derived hydrogen sulfide protects against Pseudomonas aeruginosa sepsis.

Hydrogen sulfide (H2S) has recently been recognized as a novel gaseous transmitter with several anti-inflammatory properties. The role of host- derived H2S in infections by Pseudomonas aeruginosa was investigated in clinical and mouse models. H2S concentrations and survival was assessed in septic patients with lung infection. Animal experiments using a model of severe systemic multidrug-resistant P. aeruginosa infection were performed using mice with a constitutive knock-out of cystathionine-γ lyase (Cse) gene (Cse-/-) and wild-type mice with a physiological expression (Cse+/+). Experiments were repeated in mice after a) treatment with cyclophosphamide; b) bone marrow transplantation (BMT) from a Cse+/+ donor; c) treatment with H2S synthesis inhibitor aminooxyacetic acid (ΑΟΑΑ) or propargylglycine (PAG) and d) H2S donor sodium thiosulfate (STS) or GYY3147. Bacterial loads and myeloperoxidase activity were measured in tissue samples. The expression of quorum sensing genes (QS) was determined in vivo and in vitro. Cytokine concentration was measured in serum and incubated splenocytes. Patients survivors at day 28 had significantly higher serum H2S compared to non-survivors. A cut- off point of 5.3 µΜ discriminated survivors with sensitivity 92.3%. Mortality after 28 days was 30.9% and 93.7% in patients with H2S higher and less than 5.3 µΜ (p = 7 x 10-6). In mice expression of Cse and application of STS afforded protection against infection with multidrug-resistant P. aeruginosa. Cyclophosphamide pretreatment eliminated the survival benefit of Cse+/+ mice, whereas BMT increased the survival of Cse-/- mice. Cse-/- mice had increased pathogen loads compared to Cse+/+ mice. Phagocytic activity of leukocytes from Cse-/- mice was reduced but was restored after H2S supplementation. An H2S dependent down- regulation of quorum sensing genes of P.aeruginosa could be demonstrated in vivo and in vitro. Endogenous H2S is a potential independent parameter correlating with the outcome of P. aeruginosa. H2S provides resistance to infection by MDR bacterial pathogens.

Radiation therapy for the prevention of heterotopic ossification: Efficacy and toxicity of single fraction radiotherapy.

Numerous nonmalignant diseases can be treated with radiation therapy (RT). Among them, Heterotopic Ossification (HO) is a benign condition resulting from several causes that can be successfully managed with ionizing radiation. More often seen in the hip area after major surgical procedures, HO is of major concern as it can lead to functional disorders, pain and even to joint ankylosis. We retrospectively analyzed the outcome of therapeutic irradiation for the prevention of HO in 14 patients treated in our hospital between 2005 and 2011. All patients were irradiated with a dose ranging from 7 to10 Gy in a single fraction for prevention of HO after surgery. After a median follow up of 126 months (range 96 - 156 months) none of our patients developed HO. Impaired wound healing or other post surgery complications like trochanteric nonunion were not observed. A single fraction of RT seems to be a sufficient, cost effective and safe treatment regimen. In our study we report excellent results as none of our patients developed HO.

Low dose total skin electron beam therapy for the management of T cell cutaneous lymphomas.

Mycosis fungoides (MF) represent the most common type of primary cutaneous lymphomas. Total skin electron beam (TSEB) therapy to a total skin administered dose of 36 Gy represents a very effective treatment regimen and its role in the management of MF is well established. Unfortunately, the issue in MF is that despite the proved effectiveness of radiation therapy, disease regress, and the main goal of TSEB treatment seems to be the prolongation of the overall response duration time. Taking into consideration the high radio-sensitivity of the disease, lower radiation doses have been tested with acceptable and comparable results. We prospectively analyzed low dose TSEB in 14 patients treated at ATTIKON University Hospital from 2011 to 2017. After a median duration of follow up time of 39 months we found that low dose TSEB is an effective treatment option, since therapeutic results are more than acceptable, with minimal toxicity. The fact that it can be repeated safely in the natural course of a "regressive" disease makes it more attractive than the standard full dose scheme of 36 Gy.

Clinical application of Total Skin Electron Beam (TSEB) therapy for the management of T cell cutaneous lymphomas. The evolving role of low dose (12 Gy) treatment schedule.

BACKGROUND & PURPOSE: Although rare, cutaneous lymphomas represent a separate entity in hematologic oncology. T cell origin lymphomas are most common, with Mycosis Fungoides (MF) accounting for about 50-70% of cases. Sezary Syndrome (SS), which represents the leukemic varian of MF, accounts for 3% of Cutaneous T Cell Lymphomas (CTCL). Total Skin Electron Beam Therapy (TSEB) is included at the mainstream of treatment choices for CTCL. The scope of this study is to evaluate the effectiveness and toxicity of two treatment schedules of TSEB. METHODS AND MATERIALS: We report our experience with TSEB in the management of MF and SS, as of 14 patients treated in our institution from 2011 to 2015. 8 patients received the 12 Gy (low dose) scheme while 6 patients were managed with 36 Gy (standard or full dose scheme) according to six dual field Stanford technique. The endpoints were overall response rate, duration of response and toxicity of treatment. RESULTS: After a median follow up of 2.5 years we noted excellent treatment outcome, with both schemes being well tolerated and resulting in comparable response rates. The overall response rate for both treatment regimens was over 87.5%. Treatment was well tolerated with mild toxicity. CONCLUSION: The role of TSEB in the management of MF and SS is well established. The low dose TSEB schedule of 12 Gy is an effective treatment option, since therapeutic results are more than acceptable, compliance is excellent and toxicity is minimal. Moreover, the evidence that it can be repeated safely makes it more attractive than the standard 36 Gy scheme, when a patient is referred to radiation treatment according to treatment guidelines.

An Exploratory Study of Radiation Dermatitis in Breast Cancer Patients.

BACKGROUND/AIM: Radiation dermatitis is observed in 95% of breast cancer patients receiving radiotherapy. The aim of this study was to explore the correlation between protein expression in tumor cells and the risk of developing radiation dermatitis. PATIENTS AND METHODS: Breast cancer patients receiving postoperative radiotherapy were included in this study. Tumor specimens from 122 patients were examined by immunohistochemistry for the expression of Ki67, ataxia telangiectasia mutated (ATM) kinase, hypoxia-inducible factor-1-alpha (HIF-1a), inducible nitric oxide synthase (iNOS), and a-glucosidase (aGluc). The findings were correlated with the occurrence and severity of radiation dermatitis (Radiation therapy oncology group-RTOG grading scale), taking into consideration body weight and skin type (Fitzpatrick system). Data were explored further via pathway and network analyses. RESULTS: Correlation of radiation dermatitis (RTOG scale) with the observed increased expression of Ki67, ATM, iNOS, HIF-1a and aGluc, failed to reach statistical significance when skin type and/or body weight were considered. Network interactions of proteins involved in tumor growth (Ki67, ATM) and/or affect the oxidation state of the cell (HIF-1a, iNOS, aGluc) were revealed, that may contribute to the risk of developing acute radiation dermatitis. CONCLUSION: Correlation of the increased expression of the studied proteins and the occurrence and severity of radiation dermatitis in women undergoing postoperative radiotherapy, failed to reach statistical significance. Pathway and network analyses predicted that vasodilation and angiogenesis may contribute to radiation-induced dermatitis via mechanisms that need to be further explored. Our strategy serves as a paradigm for coupling histopathological data to molecular findings and network analyses for risk assessment in the clinic.

A novel Hemi-Body Irradiation technique using electron beams (HBIe-).

PURPOSE: Certain radiation responsive skin diseases may develop symptoms on the upper or the lower half of the body. The concept of a novel Hemi-Body Electron Irradiation (HBIe-) technique, described in this work, provides a low cost, LINAC based, intermediate treatment option in between extremely localized and Total Skin irradiation techniques. MATERIALS AND METHODS: The HBIe- technique, developed in our department, incorporates a custom crafted treatment chamber equipped with adjustable Pb shielding and a single electron beam in extended Source-Skin Distance (SSD) setup. The patient is positioned in 'Stanford' technique positions. The geometrical setup provides both optimal dose homogeneity and dose deposition up to a depth of 2 cm. To confirm this, the following characteristics were measured and evaluated: a) percentage depth dose (PDD) on the treatment plane produced by a single electron beam at perpendicular incidence for six fields at 'Stanford' angles, b) 2D profile of the entrance dose on the treatment plane produced by a single field and c) the total surface dose on an anthropomorphic phantom delivered by all 6 fields. RESULTS: The resulting homogeneity of the surface dose in the treatment plane for an average patient was 5-6%, while surface dose homogeneity on the anthropomorphic phantom was 7% for both the upper and the lower HBIe- variants. The total PDD exhibits an almost linear decrease to a practical range of 2 g/cm2. CONCLUSION: In conclusion, HBIe- was proven effective in delivering the prescribed dose to the target area, while protecting the healthy skin.

Samarium-153Sm-EDTMP as an equivalent variant to pharmaceutical analgesic treatment.

PURPOSE: Cancer pain is the most serious symptom for patients, especially during their terminal phase, when palliative medicine is needed. Our study tried to verify the usefulness of single-shot intravenous administration of Samarium (Sm)-153EDTMP in patients with bone metastases (group-A, N=53, males=25, females=28, age range: 30-69 years), as well as to compare a series of variables, using as a control group (group-B, N=37, males=17, females=20, age range: 30-69 years) with patients who were under drug treatment given from a physician specialized in palliative medicine. METHODS: Both groups answered the following questionnaires: Greek Brief Pain Inventory (GBPI), Brief Multidimensional Life Satisfaction Scale (BMLSS), Hospital Anxiety Depression Scale (HADS) and ECOG performance status. RESULTS: Pain severity and pain interference improvement p=0.0005 for both groups. HADS-anxiety: Samarium group, p= 0.397, drugs group p= 0.031. HADS-depression improvement for both groups p=0.031 and p=0.003, respectively. BMLSS improvement p=0.029 and p=0.265, while EGOG PS improvement was p=0.005 and p=0.014, respectively (numeric values). CONCLUSION: Intravenous administration of Sm-153EDTMP was equivalent to drug treatment against cancer pain for patients with multiple bone metastasis, an option for those patients who are intolerant or resistant to drug treatment. Samarium-treated patients needed less or not at all pain killers, having a better cost-effective result.

Clinical reasoning: a 51-year-old man with cervical pain and progressively deteriorating gait.

A 51-year-old Caucasian man presented with cervical pain, right hand weakness, and progressively deteriorating gait. Onset of symptoms occurred 1 month before admission with cervical pain that worsened during neck flexion. A few days later he noticed reduced dexterity and numbness of his right hand. During the following 3 weeks, his gait became increasingly unstable. Additionally, he reported erectile dysfunction and urinary hesitancy. No previous trauma was recalled. His medical and family history was unremarkable except for hypertension that was treated with angiotensin-converting enzyme inhibitors.

Granulosa cell tumor of the ovary: tumor review.

Granulosa cell tumors of the ovary are rare neoplasms that originate from sex-cord stromal cells. The long natural history of granulosa cell tumors and their tendency to recur years after the initial diagnosis are the most prominent of their characteristics. The secretion of estradiol is the reason for signs at presentation such as vaginal bleeding and precocious puberty. Abdominal pain and hemoperitoneum, which occasionally can occur, are attributable to tumor rupture. The most common finding in pelvic examination is a tumor mass, which is subsequently confirmed with imaging techniques. Surgery is the mainstay of initial management for histological diagnosis, appropriate staging, and debulking. A more conservative unilateral salpingo-oophorectomy is indicated in patients with stage I disease and patients of reproductive age. Total abdominal hysterectomy with bilateral salpingo-oophorectomy is the appropriate surgical treatment for postmenopausal women and those with more advanced disease. The stage of disease is the most important prognostic factor associated with the risk of relapse. There are no clear conclusions regarding the role of postoperative chemotherapy or radiotherapy in stage I disease and in those with completely resected tumor. The use of adjuvant chemotherapy or radiotherapy has sometimes been associated with prolonged disease-free survival and possibly overall survival. Chemotherapy is the treatment of choice for patients with advanced, recurrent, or metastatic disease, and BEP (bleomycin, etoposide, and cisplatin) is the preferred regimen. Although the overall rate of response to treatment is high, the impact of treatment on disease-free or overall survival is unknown. Prolonged surveillance is mandatory because tumors tend to recur years after the initial diagnosis.

The efficacy of caelyx and hyperthermia for anticancer treatment.

The efficacy of hyperthermia and caelyx as single modalities of therapy in progressed and refractory cancer of different primary sites is well known. Nevertheless, it remains question mark whether they can work together to that direction. We have recently published a paper which demonstrates some excellent results in treatment of recurrent breast cancer with hyperthermia in conjunction with caelyx and radiotherapy. The mechanism of action of those different therapeutic options and a review in literature are presented in this paper. Despite the limited number of studies, they all show that the combined treatment is effective and well tolerated. It would be interesting to mention another treatment patent of cancer which can be done by a combination of non-ionizing radiation and androgen deprivation. Also, combined therapy for tumors and tumor metastases comprised administration of integrin ligands and co-therapeutic agents have synergistic efficacy in isolated organ perfusion. Finally, the treatment of solid tumors can be done by glycolytic inhibitors.

The effect of contrast media on the synovial membrane.

OBJECTIVE: To examine the effect of intra-articular injection of contrast media, sorbitol and normal saline on the synovial membrane. MATERIALS AND METHODS: Sixty three rabbits (126 knees) were used in this study. We injected the knees with amidotrizoate, ioxaglate, iopamidol, iotrol and diluted gadolinium-DTPA (2 mmol/l). Normal saline and sorbitol 27.25% were used for comparison. A histological and histochemical examination of the knees was carried out 1, 2, 10, 20, 30, 40 and 60 days after the injection. RESULTS: On histological examination, the knees injected with normal saline, ioxaglate and gadolinium-DTPA had a normal appearance. Intra-articular injection of amidotrizoate, iopamidol, iotrol and sorbitol caused early, mild and transient histological changes of the synovium (synovial hyperplasia, infiltration by leucocytes). Furthermore, the knees injected with amidotrizoate presented with late, extensive histological changes (severe synovial hyperplasia, moderate vascular dilatation, severe infiltration by leukocytes). CONCLUSION: The results suggest that the chemical structure and not the osmolality of the contrast media is the main cause for the histological changes of the synovium.