To report interim cosmetic and toxicity results of a multicenter randomized trial comparing accelerated partial-breast irradiation (APBI) using three-dimensional conformal external beam radiation ...therapy (3D-CRT) with whole-breast irradiation (WBI).
Women age > 40 years with invasive or in situ breast cancer ≤ 3 cm were randomly assigned after breast-conserving surgery to 3D-CRT APBI (38.5 Gy in 10 fractions twice daily) or WBI (42.5 Gy in 16 or 50 Gy in 25 daily fractions ± boost irradiation). The primary outcome was ipsilateral breast tumor recurrence (IBTR). Secondary outcomes were cosmesis and toxicity. Adverse cosmesis was defined as a fair or poor global cosmetic score. After a planned interim cosmetic analysis, the data, safety, and monitoring committee recommended release of results. There have been too few IBTR events to trigger an efficacy analysis.
Between 2006 and 2011, 2,135 women were randomly assigned to 3D-CRT APBI or WBI. Median follow-up was 36 months. Adverse cosmesis at 3 years was increased among those treated with APBI compared with WBI as assessed by trained nurses (29% v 17%; P < .001), by patients (26% v 18%; P = .0022), and by physicians reviewing digital photographs (35% v 17%; P < .001). Grade 3 toxicities were rare in both treatment arms (1.4% v 0%), but grade 1 and 2 toxicities were increased among those who received APBI compared with WBI (P < .001).
3D-CRT APBI increased rates of adverse cosmesis and late radiation toxicity compared with standard WBI. Clinicians and patients are cautioned against the use of 3D-CRT APBI outside the context of a controlled trial.
To evaluate factors associated with adverse cosmesis outcome in breast cancer patients randomized to accelerated partial breast irradiation (APBI) using 3-dimensional conformal radiation therapy or ...whole-breast irradiation in the RAPID (Randomized Trial of Accelerated Partial Breast Irradiation) trial.
Subjects were trial participants with nurse-assessed global cosmetic scores at baseline and at 3 years. Adverse cosmesis was defined as a score of fair or poor. Cosmetic deterioration was defined as any adverse change in score from baseline to 3 years. The analysis is based on data from the previously reported interim analysis. Logistic regression models were used to assess the association of risk factors for these outcomes among all patients and those treated with APBI only.
Clinicopathologic characteristics were similar between subjects randomized to APBI (n=569) or whole-breast irradiation (n=539). For all subjects, factors associated with adverse cosmesis at 3 years were older age, central/inner tumor location, breast infection, smoking, seroma volume, breast volume, and use of APBI; factors associated with cosmetic deterioration were smoking, seroma volume, and use of APBI (P<.05). For APBI subjects, tumor location, smoking, age, and seroma volume were associated with adverse cosmesis (P<.05), and smoking was associated with cosmetic deterioration (P=.02). An independent association between the V95/whole-breast volume ratio and adverse cosmesis (P=.28) or cosmetic deterioration (P=.07) was not detected. On further exploration a V95/whole-breast volume ratio <0.15 was associated with a lower risk of cosmetic deterioration (p=.04), but this accounted for only 11% of patients.
In the RAPID trial, a number of patient tumor and treatment-related factors, including the use of APBI, were associated with adverse cosmesis and cosmetic deterioration. For patients treated with APBI alone, the high-dose treatment volume was not independently associated with an adverse cosmetic outcome, and a useful clinical threshold could not be identified.
Whole breast irradiation (WBI) after conservative surgery for ductal carcinoma in situ (DCIS) reduces local recurrence. We investigated whether a tumour bed boost after WBI improved outcomes, and ...examined radiation dose fractionation sensitivity for non-low-risk DCIS.
The study was an international, randomised, unmasked, phase 3 trial involving 136 participating centres of six clinical trials organisations in 11 countries (Australia, New Zealand, Singapore, Canada, the Netherlands, Belgium, France, Switzerland, Italy, Ireland, and the UK). Eligible patients were women aged 18 years or older with unilateral, histologically proven, non-low-risk DCIS treated by breast-conserving surgery with at least 1 mm of clear radial resection margins. They were assigned to one of four groups (1:1:1:1) of no tumour bed boost versus boost after conventional versus hypofractionated WBI, or randomly assigned to one of two groups (1:1) of no boost versus boost after each centre prespecified conventional or hypofractionated WBI. The conventional WBI used was 50 Gy in 25 fractions, and hypofractionated WBI was 42·5 Gy in 16 fractions. A boost dose of 16 Gy in eight fractions, if allocated, was delivered after WBI. Patients and clinicians were not masked to treatment allocation. The primary endpoint was time to local recurrence. This trial is registered with ClinicalTrials.gov (NCT00470236).
Between June 25, 2007, and June 30, 2014, 1608 patients were randomly assigned to have no boost (805 patients) or boost (803 patients). Conventional WBI was given to 831 patients, and hypofractionated WBI was given to 777 patients. Median follow-up was 6·6 years. The 5-year free-from-local-recurrence rates were 92·7% (95% CI 90·6–94·4%) in the no-boost group and 97·1% (95·6–98·1%) in the boost group (hazard ratio 0·47; 0·31–0·72; p<0·001). The boost group had higher rates of grade 2 or higher breast pain (10% 8–12% vs 14% 12–17%, p=0·003) and induration (6% 5–8% vs 14% 11–16%, p<0·001).
In patients with resected non-low-risk DCIS, a tumour bed boost after WBI reduced local recurrence with an increase in grade 2 or greater toxicity. The results provide the first randomised trial data to support the use of boost radiation after postoperative WBI in these patients to improve local control. The international scale of the study supports the generalisability of the results.
National Health and Medical Research Council of Australia, Susan G Komen for the Cure, Breast Cancer Now, OncoSuisse, Dutch Cancer Society, Canadian Cancer Trials Group.
BIG 3-07/TROG 07.01 is an international, multicentre, randomised, controlled, phase 3 trial evaluating tumour bed boost and hypofractionation in patients with non-low-risk ductal carcinoma in situ ...following breast-conserving surgery and whole breast radiotherapy. Here, we report the effects of diagnosis and treatment on health-related quality of life (HRQOL) at 2 years.
The BIG 3-07/TROG 07.01 trial is ongoing at 118 hospitals in 11 countries. Women aged 18 years or older with completely excised non-low-risk ductal carcinoma in situ were randomly assigned, by use of a minimisation algorithm, to tumour bed boost or no tumour bed boost, following conventional whole breast radiotherapy or hypofractionated whole breast radiotherapy using one of three randomisation categories. Category A was a 4-arm randomisation of tumour bed boost versus no boost following conventional whole breast radiotherapy (50 Gy in 25 fractions over 5 weeks) versus hypofractionated whole breast radiotherapy (42·5 Gy in 16 fractions over 3·5 weeks). Category B was a 2-arm randomisation between tumour bed boost versus no boost following conventional whole breast radiotherapy, and category C was a 2-arm randomisation between tumour bed boost versus no boost following hypofractionated whole breast radiotherapy. Stratification factors were age at diagnosis, planned endocrine therapy, and treating centre. The primary endpoint, time to local recurrence, will be reported when participants have completed 5 years of follow-up. The HRQOL statistical analysis plan prespecified eight aspects of HRQOL, assessed by four questionnaires at baseline, end of treatment, and at 6, 12, and 24 months after radiotherapy: fatigue and physical functioning (EORTC QLQ-C30); cosmetic status, breast-specific symptoms, arm and shoulder functional status (Breast Cancer Treatment Outcome Scale); body image and sexuality (Body Image Scale); and perceived risk of invasive breast cancer (Cancer Worry Scale and a study-specific question). For each of these measures, tumour bed boost was compared with no boost, and conventional whole breast radiotherapy compared with hypofractionated whole breast radiotherapy, by use of generalised estimating equation models. Analyses were by intention to treat, with Hochberg adjustment for multiple testing. This trial is registered with ClinicalTrials.gov, NCT00470236.
Between June 1, 2007, and Aug 14, 2013, 1208 women were enrolled and randomly assigned to receive no tumour bed boost (n=605) or tumour bed boost (n=603). 396 of 1208 women were assigned to category A: conventional whole breast radiotherapy with tumour bed boost (n=100) or no boost (n=98), or to hypofractionated whole breast radiotherapy with tumour bed boost (n=98) or no boost (n=100). 447 were assigned to category B: conventional whole breast radiotherapy with tumour bed boost (n=223) or no boost (n=224). 365 were assigned to category C: hypofractionated whole breast radiotherapy with tumour bed boost (n=182) or no boost (n=183). All patients were followed up at 2 years for the HRQOL analysis. 1098 (91%) of 1208 patients received their allocated treatment, and most completed their scheduled HRQOL assessments (1147 95% of 1208 at baseline; 988 87% of 1141 at 2 years). Cosmetic status was worse with tumour bed boost than with no boost across all timepoints (difference 0·10 95% CI 0·05–0·15, global p=0·00014, Hochberg-adjusted p=0·0016); at the end of treatment, the estimated difference between tumour bed boost and no boost was 0·13 (95% CI 0·06–0·20; p=0·00021), persisting at 24 months (0·13 0·06–0·20; p=0·00021). Arm and shoulder function was also adversely affected by tumour bed boost across all timepoints (0·08 95% CI 0·03–0·13, global p=0·0033, Hochberg adjusted p=0·045); the difference between tumour bed boost and no boost at the end of treatment was 0·08 (0·01 to 0·15, p=0·021), and did not persist at 24 months (0·04 –0·03 to 0·11, p=0·29). None of the other six prespecified aspects of HRQOL differed significantly after adjustment for multiple testing. Conventional whole breast radiotherapy was associated with worse body image than hypofractionated whole breast radiotherapy at the end of treatment (difference –1·10 95% CI –1·79 to –0·42, p=0·0016). No significant differences were reported in the other PROs between conventional whole breast radiotherapy compared with hypofractionated whole breast radiotherapy.
Tumour bed boost was associated with persistent adverse effects on cosmetic status and arm and shoulder functional status, which might inform shared decision making while local recurrence analysis is pending.
National Health and Medical Research Council, Susan G Komen for the Cure, Breast Cancer Now, OncoSuisse, Dutch Cancer Society.
Purpose:
This work presents an algorithm used to quantify intra-fraction motion for patients treated using deep inspiration breath hold (DIBH). The algorithm quantifies the position of the chest wall ...in breast tangent fields using electronic portal images.
Methods:
The algorithm assumes that image profiles, taken along a direction perpendicular to the medial border of the field, follow a monotonically and smooth decreasing function. This assumption is invalid in the presence of lung and can be used to calculate chest wall position. The algorithm was validated by determining the position of the chest wall for varying field edge positions in portal images of a thoracic phantom. The algorithm was used to quantify intra-fraction motion in cine images for 7 patients treated with DIBH.
Results:
Phantom results show that changes in the distance between chest wall and field edge were accurate within 0.1 mm on average. For a fixed field edge, the algorithm calculates the position of the chest wall with a 0.2 mm standard deviation. Intra-fraction motion for DIBH patients was within 1 mm 91.4% of the time and within 1.5 mm 97.9% of the time. The maximum intra-fraction motion was 3.0 mm.
Conclusions:
A physics based algorithm was developed and can be used to quantify the position of chest wall irradiated in tangent portal images with an accuracy of 0.1 mm and precision of 0.6 mm. Intra-fraction motion for patients treated with DIBH at our clinic is less than 3 mm.
•Cosmetic outcomes of BCS for DCIS were independent of treating centre geography.•Conventional and hypofractionated WBI achieved similar 3-year cosmesis.•Tumour bed boost (16 Gy in 8 fractions) ...doubled the risk of cosmetic deterioration.•The adverse impact of a tumour bed boost was independent of WBI fractionation.
To assess the cosmetic impact of breast conserving surgery (BCS), whole breast irradiation (WBI) fractionation and tumour bed boost (TBB) use in a phase III trial for women with ductal carcinoma in situ (DCIS) of the breast.
Baseline and 3-year cosmesis were assessed using the European Organization for Research and Treatment of Cancer (EORTC) Cosmetic Rating System and digital images in a randomised trial of non-low risk DCIS treated with postoperative WBI +/− TBB. Baseline cosmesis was assessed for four geographic clusters of treating centres. Cosmetic failure was a global score of fair or poor. Cosmetic deterioration was a score change from excellent or good at baseline to fair or poor at three years. Odds ratios for cosmetic deterioration by WBI dose-fractionation and TBB use were calculated for both scoring systems.
1608 women were enrolled from 11 countries between 2007 and 2014. 85–90% had excellent or good baseline cosmesis independent of geography or assessment method. TBB (16 Gy in 8 fractions) was associated with a >2-fold risk of cosmetic deterioration (p < 0.001). Hypofractionated WBI (42.5 Gy in 16 fractions) achieved statistically similar 3-year cosmesis compared to conventional WBI (50 Gy in 25 fractions) (p ≥ 0.18). The adverse impact of a TBB was not significantly associated with WBI fractionation (interaction p ≥ 0.30).
Cosmetic failure from BCS was similar across international jurisdictions. A TBB of 16 Gy increased the rate of cosmetic deterioration. Hypofractionated WBI achieved similar 3-year cosmesis as conventional WBI in women treated with BCS for DCIS.
Emamectin benzoate (EMB) is a biopesticide which used in agriculture as an insecticide. It is easier to reach ecologically and affects human health. This study aims to evaluate the protective effect ...of chitosan and chitosan nanoparticles against EMB-induced hepatotoxicity.
Male mice were distributed into four groups: G1: the negative control, G2: EMB group (5 mg/kg diet), G3: EMB with Chitosan, (600 mg/kg diet), and G4: EMB with Chitosan nanoparticles (600 mg/kg diet). The experiment continues for 8 weeks, and the animals were sacrificed, and their organs were removed and immediately weighed after sacrifice. The liver was quickly removed and processed for histopathological and genetic studies.
Emamectin benzoate (EMB) treatment induced oxidative stress by increased levels of Malondialdehyde (MDA), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) with inhibition of acetylcholinesterase (AChE), Superoxide dismutase (SOD) and Catalase (CAT) levels. EMB produced several histopathological changes in the liver. Relative expressions of studied genes elevated in the liver with increase in DNA damage. Co-treatment with chitosan and chitosan nanoparticles reduced EMB related liver toxicity that belong to biochemical, histopathological, gene expression, and DNA damage by increasing antioxidant capacity.
This study offers insight into the potential for Chitosan and chitosan nanoparticles as a novel natural material against the oxidative stress induced by EMB.
Sequential injection chromatography (SIC) has been recently proposed as an alternative separation technique with potential benefits and some limitations. In the current study, a more pressure ...resistant selection valve (SV) with additional ports was installed in an SIC assembly. The current SV allowed using a buffer in a Mobile phase (MP) without leakage and analyzing ten solutions with a one-shot run. In addition, a new method for sildenafil assay in tablets, bulk, and synthetic pharmaceutical samples was proposed utilizing the newly developed SIC assembly. Response surface approach was adopted to screen the effect of MP composition on t
R
, PH, and B and, accordingly, to optimize the method. Sample volume and flow rate were optimized using the univariate approach. The optimum chromatographic conditions were: C
18
monolithic column (4.6 × 25 mm), an MP composition of 0.3 M ammonium acetate:acetonitrile (50:50, v/v) at pH 6.8, sample volume 40 µL and flow rate 40 µL/s. UV detection at 240 nm was carried out using miniaturized fiber optic spectrometric devices. A comparative study on some analytical features of the SIC method with those of previous HPLC methods was conducted. The SIC method is more rapid and more reagent-saving and thus safer to the environment. The sample frequency was 40 samples/hr. The total volume of consumed reagents and sample was 2.54 mL.
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