A-blockers for the management of lower urinary tract symptoms in patients with prostate cancer treated with external beam radiotherapy: a randomized controlled study.

BACKGROUND: This is a prospective study aiming to assess the efficacy of α-blockers in treating radiotherapy-induced symptoms of the lower urinary tract and its possible prophylactic role on acute urinary retention (AUR) in patients undergoing radical external beam radiotherapy (EBRT) for localized prostate cancer (PCa). METHODS: Overall, 108 patients with localized PCa were recruited and randomly assigned in to two groups; 54 patients of Group 1 received tamsulosin 0.4 mg once daily with the initiation of EBRT and for 6 months and 54 patients of Group 2 served as the control group. All patients received radical EBRT and had post-void volume (Vres) assessment. The International Prostate Symptom Score (IPSS) questionnaire and evaluation of episodes of AUR were performed after the end of radiotherapy, at 3 and at 6 months. RESULTS: The incidence of AUR was significantly (p = 0.027) lower in group 1 compared to group 2. No independent predictive factors for AUR were identified in regression analysis. The IPSS changes in univariate and multivariate analysis at 3 months showed significant correlation with α-blockers only, while at 6 months showed significant correlation with Vres assessments (at 3 and 6 months) and with α-blockers. Side effects due to medication were mild and none of the patients discontinued the treatment. CONCLUSIONS: The selective use of α-blocker appears to prevent AUR in EBRT-treated patients. Although the administration of α-blockers might relieve patient-reported symptoms, there are no established independent predictive factors to distinguish patients who may benefit.

A randomized study comparing two hypofractioned 3-D conformal radiotherapy for stage IIIb-IV non small cell lung cancer.

PURPOSE: We compared the safety and efficacy of two hypofractionated irradiation schedules for elderly and low performance status patients with inoperable symptomatic non-small cell lung cancer (NSCLC). METHODS: Patients that entered the study were either unfit or without response concerning chemotherapy. We randomized 14 patients (group A) vs 15 patients (group B) who underwent two different hypofractionated radiotherapy schedules. Group Α patients underwent a scheme of 13x3 Gy, while group B patients received 2x8.5 Gy and one fraction of 6 Gy one week apart. Efficacy was assessed in terms of disease-free survival (DFS), tumor response and overall survival (OS).Toxicity according to RTOG/EORTC criteria and duration of symptoms were also evaluated. RESULTS: Median follow up was 3 years. Median age was 64.5 years (group A) and 73 years (group B). Mean values for symptom palliation were higher for group B vs group A (3.20±1.21 vs 2.21±0.97, p=0.037), respectively. EORTC/RTOG toxicity was significantly higher (p=0.046) for group A (1.57±0.51) vs group B (1.13±0.35). Duration of toxicity was significantly lower in group B compared to group A (p=0.001). Median OS was similar between groups, while DFS was better in group B than group A (p=0.023). CONCLUSIONS: Although safe conclusions are difficult to be ascertained, hypofractionated schedule B might be an alternative scheme in elderly and low performance status patients offering adequate palliation, good tumor control and acceptable toxicity.

Toxicity and efficacy of a hypofractionated (3 weekly fractions of 850c Gy) irradiation schedule for stage IIIb / IV non-small cell lung cancer elderly patients with low performance status and unfit for chemotherapy.

PURPOSE: To evaluate in an observational way the clinical impact of a hypofractionated irradiation schedule in patients with unresectable non-small cell lung cancer (NSCLC). METHODS: Forty elderly patients (24 men/16 women) diagnosed with unresectable stage IIIb/IV NSCLC unfit for chemotherapy, were treated with once-a-week hypofractionation schedule. All patients had a poor performance status. A dose of 255 Gy in 3 weekly fractions was prescribed while a 3D conformal technique (3D-CRT) was used for irradiation. The primary study endpoints were to assess the therapeutic impact of this schedule in terms of relapse free survival (RFS), overall survival (OS) survival and palliation of symptoms. The secondary endpoints were the evaluation of acute toxicity of the lung, esophagus and the skin. The intended followup was 3 years. The median age was 73.5 years (range 71-85). RESULTS: The median RFS was 12 months, while the median OS was 17 months. Symptoms relief was up to 20% for cough, 52.5% for haemoptysis, 40% for thoracic pain and 17.5% for dyspnoea. Acute lung toxicity in terms of radiation pneumonitis was recorded as 6/40 (15%) grade 1, 26/40 (65%) grade 2 and 8/40 (25%) grade 3. Additionally, grade 1 and 2 acute esophageal toxicity was recorded in 10/40 (25%) and 30/40 (75%) patients, respectively. Acute skin toxicity with grade 2 erythema was recorded in only 2/40 (5%) patients while most patients developed grade 1 skin erythema. Grade 3 late lung toxicity was recorded in 10/40 (25%) patients. CONCLUSIONS: This study showed that the proposed scheme has a moderate radiation-induced lung toxicity rate and an acceptable therapeutic ratio. Taking into consideration its cost effectiveness, the proposed hypofractionated scheme is a good alternative to conventional fractionation.

A Retrospective Analysis of Toxicity and Efficacy for 2 Hypofractionated Irradiation Schedules Versus a Conventional One for Post-Mastectomy Adjuvant Radiotherapy in Breast Cancer.

INTRODUCTION: The aim of this analysis was a retrospective evaluation of the efficacy and toxicity of 2 hypofractionated irradiation schedules compared to conventional therapy in post-mastectomy patients. METHODS: 3 irradiation schedules were analyzed: 48.30 Gy in 21 fractions (group A, n = 60), 42.56 Gy in 16 fractions (group B, n = 27) and 50 Gy in 25 fractions (group C, n = 30) of the front chest wall. All groups were also treated with a supraclavicular field, with 39.10 Gy in 17 fractions (group A), 37.24 Gy in 14 fractions (group B) or 45 Gy in 25 fractions (group C). RESULTS: No local recurrences were noted in any group during 36 months of follow-up. Acute skin toxicity presented in all groups, with 58.3%, 70.4% and 60% of grade I; 35%, 25.9% and 40% of grade II; 6.7%, 3.7% and 0% of grade III being seen in groups A, B and C, respectively. Late skin toxicity was noted only as grade I in 16.7%, 25.9% and 26.7% of groups A, B and C, respectively. No significant difference was noted among all groups for either acute or late skin toxicity, or for radio-pneumonitis (chi2 test, p > 0.05). CONCLUSION: All schedules were equally effective with equivalent toxicity. A prospective randomized study is needed to confirm our results.

Splenic irradiation as palliative treatment for symptomatic splenomegaly due to secondary myelofibrosis: a multi-institutional experience.

PURPOSE: To evaluate the impact of splenic irradiation as a palliative treatment for symptomatic splenomegaly due to secondary myelofibrosis. METHODS: Seventeen patients with chronic myelogenous leukemia and 3 with idiopathic polycythaemia presented with splenomegaly, splenic pain and anemia. Due to symptomatic splenomegaly, despite first-line treatment, the patients underwent splenic irradiation. Two patients received two different schedules of external radiotherapy (580 cGy in 5 fractions and 600 cGy in 6 fractions). Eight patients received 980 cGy in 14 fractions. Ten patients received two courses of 360 cGy in 6 fractions, 3 months apart. Median follow-up was 12 months post irradiation. RESULTS: The patients showed excellent response to treatment one month post-radiotherapy, while treatment was well tolerated without severe toxicity. The dimensions of the spleen decreased significantly. Pain-related Visual Analogue Score (VAS) regressed after completion of irradiation. During 12-month follow-up all patients maintained the benefit of radiotherapy. CONCLUSION: This study indicates that splenic irradiation could be a safe and effective palliative treatment for symptomatic splenomegaly due to secondary myelofibrosis.

Adjuvant chemotherapy and acute toxicity in hypofractionated radiotherapy for early breast cancer.

AIM: To evaluate the effect of chemotherapy to the acute toxicity of a hypofractionated radiotherapy (HFRT) schedule for breast cancer. METHODS: We retrospectively analyzed 116 breast cancer patients with T1, 2N0Mx. The patients received 3-D conformal radiotherapy with a total physical dose of 50.54 Gy or 53.2 Gy in 19 or 20 fractions according to stage, over 23-24 d. The last three to four fractions were delivered as a sequential tumor boost. All patients were monitored for acute skin toxicity according to the European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group criteria. The maximum monitored value was taken as the final grading score. Multivariate analysis was performed for the contribution of age, chemotherapy and 19 vs 20 fractions to the radiation acute skin toxicity. RESULTS: The acute radiation induced skin toxicity was as following: grade I 27.6%, grade II 7.8% and grade III 2.6%. No significant correlation was noted between toxicity grading and chemotherapy (P = 0.154, χ(2) test). The mean values of acute toxicity score in terms of chemotherapy or not, were 0.64 and 0.46 respectively (P = 0.109, Mann Whitney test). No significant correlation was also noted between acute skin toxicity and radiotherapy fractions (P = 0.47, χ(2) test). According to univariate analysis, only chemotherapy contributed significantly to the development of acute skin toxicity but with a critical value of P = 0.05. However, in multivariate analysis, chemotherapy lost its statistical significance. None of the patients during the 2-years of follow-up presented any locoregional relapse. CONCLUSION: There is no clear evidence that chemotherapy has an impact to acute skin toxicity after an HFRT schedule. A randomized trial is needed for definite conclusions.

Carotid sinus malfunction presenting with presyncopal episodes during radiation therapy for head and neck cancer.

We report the case of a 67-year-old Caucasian man with unexplained presyncopal episodes during radiation therapy for oropharyngeal cancer.

A new hypofractionated schedule of weekly irradiation for basal cell carcinoma of the head and neck skin area in elderly patients.

The effectiveness of radiotherapy in patients with basal cell carcinoma (BCC) has been already reported in the literature. However, there is little information about the irradiation of BCC in elderly patients, especially due to the low conformity of them to daily irradiation. Thirty-eight retrospectively selected elderly patients (78 years as median age) diagnosed with skin BCC of the head and neck area were treated with five weekly fractions of 600 cGy by three-dimensional conformal radiotherapy (3DCRT) as an adjuvant treatment. The primary endpoint was the relapse free survival. Acute toxicity, as secondary endpoint, was assessed according to EORTC/RTOG criteria. Among our patients, there were only three local recurrences at 15, 32 and 38 months post-3DCRT. There was no severe toxicity, while only 10 out of 38 patients presented grade II/III skin toxicity. Our proposed irradiation schedule seems effective in terms of local control and acute toxicity and could be an alternative scheme for elderly patients unfit for daily irradiation.

Evaluation of acute/late toxicity and local recurrence in T1-T2 glottic carcinoma treated with accelerated hypofractionated 3D-conformal external beam radiotherapy (3D-CRT).

BACKGROUND: The aim of the study was to evaluate the efficacy, as well as the acute and late toxicity of an accelerated hypofractionated 3DCRT schedule as radical treatment in patients with organ confined glottic cancer cT1-2N0. PATIENTS AND METHODS: Between June of 2004 and September 2010, 47 retrospectively selected patients (29 males, 18 females) diagnosed with organ confined T1 or T2 glottic cancer, were treated with external 3DCRT in an accelerated hypofractionation schedule. The median age was 70 years. A dose of 64.4 Gy in 28 daily fractions was prescribed. The primary study endpoints were to assess the acute and late effects of radiation toxicity, according to the EORTC/ RTOG scale, as well as the therapeutic impact of this schedule in terms of local recurrence. RESULTS: The median follow up was 36 months. At the end of radiotherapy, grade I, II and III acute toxicity was observed in 34, 9 and4 patients, respectively. Late grade I and II toxicity was observed in 25 and in 8 patients respectively. Only two local recurrences were observed, 15 and 24 months post 3DCRT respectively. CONCLUSIONS: Our radiotherapy schedule achieves a high locoregional control rate with the advantage of voice preservation. The proposed hypofractionated schedule can be recommended as a standard radiotherapy treatment, since these results are comparable with those of conventional fractionation schedules.

Feasibility and radiation induced toxicity regarding the first application of transperineal implementation of biocompatible balloon for high dose radiotherapy in patients with prostate carcinoma.

OBJECTIVE: To evaluate the feasibility of the transperineal implementation of biocompatible balloon (Prospace) and the acute toxicity of high dose 3DCRT in patients with localized low risk prostate cancer. MATERIALS AND METHODS: Between December 2011 and April 2012, fifteen patients were treated with external 3DCRT consisted of 76-78 Gy in 38-39 daily fractions (2.0 Gy/ fraction). Before 3DCRT, we placed the Prospace though the perineum by a minimally invasive procedure in the intermediate space between the rectum and the prostate. The primary study endpoint was the evaluation of acute toxicity according to the EORTC/RTOG radiation toxicity scale. Erectile function was evaluated with the IIEF-5 questionnaire. Rectosigmoidoscopy was performed at baseline, at the end of 3DCRT and 3 months thereafter in order to assess also the rectal toxicity according to Subjective-RectoSigmoid (S-RS) scale. The evaluation of pain related to Prospace implementation was done with the visual analogue score (VAS). RESULTS: The acute toxicities were as follows: grade I GI toxicity in two patients and for GU toxicity, three patients with grade I of nocturia, four patients with grade I of frequency, two patients with grade I and two patients with grade II of dysouria. The mean score of rectal toxicity according to S-RS score was 1.8(±0.6). The mean VAS score related to Prospace was 1.4(±0.5). Erectile function was unchanged. The Prospace device was found stable in sequential CTs during irradiation. CONCLUSIONS: The implementation of PROSPACE was feasible, while the acute radiation toxicity was low and comparable with IMRT techniques.

Three-dimensional conformal radiotherapy for hepatocellular carcinoma in patients unfit for resection, ablation, or chemotherapy: a retrospective study.

PURPOSE: The purpose is to evaluate the feasibility, efficacy, and the toxicity of three-dimensional conformal radiotherapy (3DCRT) in patients with advanced hepatocelluar carcinoma (HCC) and inferior vena cava tumor thrombosis (IVCTT). METHODS: Between 2007 and 2012, in a retrospective way, 9 patients (median age 69 years) with advanced HCC and IVCTT unfit for surgery, radiofrequency ablation, embolization, or chemotherapy were treated with three-dimensional conformal radiotherapy (3DCRT). The radiotherapy volume included both primary tumor and IVTT. The radiotherapy schedule was 50-52 Gy in 2 Gy fractions. Overall survival (OS), response to radiotherapy, visual analogue scale (VAS), and toxicity were assessed. RESULTS: All patients demonstrated a response rate up to 60%. During radiotherapy, 3 patients experienced grade 1 nausea/vomit toxicity. All patients demonstrated an elevation of the liver enzymes (3 patients with grade 1 and 6 patients with grade 2). The mean VAS-score was decreased from 6.11 to 3.11, while the median overall survival was 24 months. CONCLUSION: 3DCRT achieves a very high local control rate and is suitable for patients with HCC and IVTT, while the documented radiation induced toxicity is moderate. It can be recommended for palliation in patients unable to undergo curative therapies.

Photoacclimation in spathiphyllum.

We studied photoacclimation in Spathiphyllum grown at an irradiance of 40 or 420 micromol/m2 s (LL or HL, respectively). All parameters studied responded to acclimation. Leaves at LL, in contrast to HL, were thinner and oriented perpendicular to the incident light, had more chlorophyll per g f w, fewer stomata on the upper leaf surface and a reduced layer of mesophyll cells. Their chloroplasts at HL had wider grana with less thylakoids per granum, and better organized photosystems than at LL. PSI and PSII activities per mg chlorophyll ( Vmax ), and PSI and PSII content (total activity per g f w), were lower at LL than at HL and so was the light requirement for saturation of the PSI or PSII partial photoreactions, suggesting that fewer photosystems with larger antenna size prevail at LL, but many more with smaller antenna size at HL. Analysis of chlorophyll distribution among the thylakoid pigment-protein complexes showed less antenna chlorophyll serving PSII (CPa+LHCP1+LHCP3) than that serving PSI (CPIa+CPI+LHCP2) at LL as compared to HL, and thus a lower PSII/PSI ratio at LL, in agreement with the general finding that LL plants, with larger PSII antenna size, have lower PSII/PSI ratio. The increase in PSI antenna size at LL was correlated with the increase in the distribution of chlorophyll in pigment-protein complexes serving PSI, and a very large chlorophyll/protein molar ratio in the isolated CPI complex. On the other hand, the PSII antenna chlorophyll (CPa+LHCP1+LHCP3) on a g f w basis, and the chlorophyll a/b ratio remained more or less constant at LL or HL. This may reflect our finding that Spathiphyllum contains mainly the 27 kDa inner LHCII antenna protein, the size of which remains unaffected by photoacclimation. The increase in the distribution of chlorophyll in pigment-protein complexes serving PSII at HL, therefore, reflects the higher population of PSII at HL. Very high PSI activity was found at HL, which we attribute to the highly organized small in size PSI.

Proteolytic activity against the light-harvesting complex and the D1/D2 core proteins of Photosystem II in close association to the light-harvesting complex II trimer.

Light-harvesting complex II (LHCII) prepared from isolated thylakoids of either broken or intact chloroplasts by three independent methods, exhibits proteolytic activity against LHCII. This activity is readily detectable upon incubation of these preparations at 37 degrees C (without addition of any chemicals or prior pre-treatment), and can be monitored either by the LHCII immunostain reduction on Western blots or by the Coomassie blue stain reduction in substrate-containing "activity gels". Upon SDS-sucrose density gradient ultracentrifugation of SDS-solubilized thylakoids, a method which succeeds in the separation of the pigment-protein complexes in their trimeric and monomeric forms, the protease activity copurifies with the LHCII trimer, its monomer exhibiting no activity. This LHCII trimer, apart from being "self-digested", also degrades the Photosystem II (PSII) core proteins (D1, D2) when added to an isolated PSII core protein preparation containing the D1/D2 heterodimer. Under our experimental conditions, 50% of LHCII or the D1, D2 proteins are degraded by the LHCII-protease complex within 30 min at 37 degrees C and specific degradation products are observed. The protease is light-inducible during chloroplast biogenesis, stable in low concentrations of SDS, activated by Mg(2+), and inhibited by Zn(2+), Cd(2+), EDTA and p-hydroxy-mercury benzoate (pOHMB), suggesting that it may belong to the cysteine family of proteases. Upon electrophoresis of the LHCII trimer on substrate-containing "activity gels" or normal Laemmli gels, the protease is released from the complex and runs in the upper part of the gel, above the LHCII trimer. A polypeptide of 140 kDa that exhibits proteolytic activity against LHCII, D1 and D2 has been identified as the protease. We believe that this membrane-bound protease is closely associated to the LHCII complex in vivo, as an LHCII-protease complex, its function being the regulation of the PSII unit assembly and/or adaptation.

Sex pheromone biosynthesis in the female olive fruit-fly. Double labelling from [18O2]-dioxygen into 1,7-dioxaspiro[5.5]undecane.

The demonstration that both oxygen atoms of 1,7-dioxaspiro[5.5]undecane (1), the sex-pheromone of the female olive fly, originate from dioxygen, strongly implicates monooxygenase mediated processes in assembly of (1), and reveals unexpected complexity in the formation of its nine-carbon precursor.