The effect of anaemia on normal tissue toxicity and survival outcomes in prostate cancer treated with radical radiotherapy and neo-adjuvant androgen deprivation.

OBJECTIVE: It has been established that survival and toxicity outcomes in some cancer types could be influenced by haemoglobin (Hb) levels. This study aims to determine if pre-treatment Hb is associated with late toxicity or survival outcomes in prostate cancer. METHODS: Data from one Phase III randomised controlled trial and one single arm translational trial were analysed. Patients had localized prostate cancer and received ≥70 Gy radiotherapy and neo-adjuvant androgen deprivation between 1997 and 2013. RESULTS: 302 males were included. Median follow-up was 6.8 years for toxicity and 10.3 years for survival outcomes. Patients with Hb below the reference range were more likely to experience Grade 2-3 late gastrointestinal toxicity than patients with Hb within the range (p = 0.050). Neither late genitourinary toxicity, erectile function toxicity, prostate-specific antigen relapse free survival nor overall survival of patients were statistically significantly different between groups. CONCLUSION: Anaemia in prostate cancer is found in the minority of patients and is usually mild. Prostate cancer patients undergoing radiotherapy with low Hb were more likely to experience Grade 2-3 late gastrointestinal toxicity. ADVANCES IN KNOWLEDGE: This study is one of the first in the published literature to investigate the role of Hb in prostate cancer toxicity and survival. We have found an association between Hb below the reference range and late GI toxicity. Consideration should be given to further investigating patients with iron deficiency anaemia to guide management options and outrule underlying GI pathology before proceeding with radiotherapy treatment.

Modifiable risk factors for acute skin toxicity in adjuvant breast radiotherapy: Dosimetric analysis and review of the literature.

Acute skin toxicity in adjuvant breast radiation can be reduced with modern radiotherapy (RT) techniques. However, having reviewed the literature, we found no dosimetric constraint for acute skin toxicity that would be applicable to modern RT planning. This study aimed to identify dosimetric factors that are associated with higher rates of acute skin toxicity. A retrospective review was carried out including women who received adjuvant forward-planned intensity-modulated radiotherapy (IMRT) after breast-conserving surgery. Acute skin toxicity grade was prospectively recorded. A total of 131 patients were analyzed. On multivariate analysis, the V105% > 30 cc (p = 0.013) and the use of conventional fractionation (CF) (p = 0.001) were statistically significant for acute skin toxicity. On literature review, current quantitative dosimetric parameters that have shown statistical significance include a V107% > 3 cc in hypofractionation (HF), V107% > 9 cc in CF, treated volume 110% > 5.13%, and V107% > 28.6%. There is little evidence on the predictive value of clinically applicable dosimetric factors in acute skin toxicity. Given the recent improvements in RT planning, we would consider a V107% or a V110% too high a dosimetric value to be useful for the majority of patients. We have shown that a V105% of greater than 30 cc is significantly associated with acute skin toxicity, controlling for other variables. We suggest that this is currently the most useful modifiable parameter available to reduce skin toxicity and is applicable to modern RT planning. We also suggest that consideration be given to hypofractionated schedules to further reduce acute skin toxicity.

Laparoscopic and hand-assisted laparoscopic donor nephrectomy: A systematic review and meta-analysis.

OBJECTIVE: To compare the perioperative outcomes of hand-assisted laparoscopic donor nephrectomy (HALDN) and pure LDN, as HALDN and LDN are the two most widely used techniques of DN to treat end-stage renal disease. METHODS: In this systematic review and meta-analysis, we performed a literature search of PubMed, Embase, Web of Science, and Cochrane from 01/01/1995 to 31/12/2014. The primary outcome was conversion to an open procedure. Secondary outcomes were warm ischaemia time (WIT), operation time (OT), estimated blood loss (EBL), complications, and length of stay (LOS). Data analysed were presented as odds ratios (ORs) or weighted mean differences (WMDs) with 95% confidence intervals (CIs), I2, and P values. Subgroup analysis was performed. RESULTS: There were 24 studies included in the meta-analysis; three randomised controlled trials (RCTs), one randomised pilot study, two prospective, and 18 retrospective cohort studies. There were no differences in conversion to an open procedure between the two techniques for both RCTs (OR 0.42, 95% CI 0.06, 2.90; I2 = 0%, P < 0.001) and cohort studies (OR 1.06, 95% CI 0.63, 1.78; I2 = 0%, P = 0.84). WIT was shorter for the HALDN (-41.79 s, 95% CI -71.85, -11.74; I2 = 96%, P = 0.006), as was the OT (-26.32 min, 95% CI -40.67, -11.97; I2 = 95%, P < 0.001). There was no statistically significant difference in EBL, complications or LOS. CONCLUSION: There is little statistical evidence to recommend one technique. HALDN is associated with a shorter WIT and OT. LDN has equal safety to HALDN. Further studies are required.

An atlas to aid delineation of para-aortic lymph node region in cervical cancer: Design and validation of contouring guidelines.

INTRODUCTION: Previous studies have investigated the anatomical distribution of para-aortic lymph nodes (PAN) in patients with cervical cancer. However, an atlas for accurate clinical target volume (CTV) delineation has yet to be defined. The purpose of this study was to design and verify a computerized tomography (CT) atlas to provide guidance for contouring the PAN CTV in patients with cervical cancer. MATERIALS AND METHODS: This prospective study included 21 cervical cancer patients (design cohort) with 39 pathological PAN identified on (18)F-FDG PET-CT. PAN [left lateral para-aortic (LLPA), aorto-caval (AC), right para-caval (RPC) nodes] were delineated on CT simulation scans. Measurements were taken from the volumetric centre of the nodes to the edge of aorta and inferior vena-cava (IVC). Initially the aorta and IVC were expanded by the mean distance to the lymph node centre to create a CTV. Expansion margins were then increased asymmetrically until the CTV resulted in a clinically acceptable number of PAN included. The CTV was validated on a further 10 patients (validation cohort) with 29 PAN. A detailed contouring guide and accompanying visual atlas for elective PAN CTV delineation was created based on the validated margins. RESULTS: For the design cohort (n = 21 patients, 39 PAN), the mean distance from the centre of the node to the aorta was 8 mm (range 4-17) for both LLPA (range 4-17) and AC (range 4-15) regions. Mean distance from the IVC to the centre of the nodes was 5 mm (range 4-6) in the RPC region and 6 mm (range 3-15) in the AC region. No PAN was superior to the T12-L1 interspace or the left renal vein or inferior to the L5-S1 interspace. For validation cohort (n = 10 patients, 29 PAN), mean distance from centre of the node to the aorta was 9 mm (range 5-15) in the LLPA region, 7 mm (range 6.5-14) in the AC region. Mean distance from the ICV to the centre of the nodes was 3 mm (range 2.5-4) in the RPC region and 5 mm (range 3-10) in the AC region. A CTV expansion from the aorta of 10 mm circumferentially and 15 mm laterally, and from the IVC of 8 mm anteromedially and 6 mm posterolaterally resulted in coverage of 97% (38/39) of PAN in the design cohort. On prospective validation, the described CTV included 97% (28/29) of PAN in the validation cohort. CONCLUSION: We propose the following PAN CTV; expansion from aorta of 10 mm circumferentially except 15 mm laterally, expansion from the IVC of 8 mm anteromedial and 6 mm posterolaterally. The suggested CTV includes 97% (28/29) PAN in a validated patient cohort. A detailed guide and accompanying visual atlas is provided to aid delineation of the PAN CTV in patients with cervical cancer.

Assessment of older patients with cancer: Edmonton Frail Scale (EFS) as a predictor of adverse outcomes in older patients undergoing radiotherapy.

OBJECTIVE: In this study we evaluate the usefulness of the Edmonton Frail Scale (EFS) in predicting which older patients are at risk of developing serious toxicities during radiotherapy. MATERIALS AND METHODS: This prospective study was carried out over an 18month period. Our primary aim was to examine the Edmonton Frail Scale (EFS) as a predictor of toxicity in patients over 70years undergoing radical radiotherapy for any malignant diagnosis. RESULTS: 63 patients were recruited: 29% experienced grade 3 or greater toxicities, with very few having multiple grade 3 or greater toxicities. The majority of patients experienced multiple grade 1 or 2 toxicities. Patients were often admitted: either electively due to geographical reasons, or due to toxicities. All patients completed their courses of radiotherapy. All grade 3 or 4 toxicities occurred within five radiotherapy sites; upper GI, gynaecological, lung, prostate and head & neck. There was no statistical correlation between EFS score and the presence of grade 3 or 4 toxicities. CONCLUSION: This study showed that neither EFS score, age nor ECOG performance status were predictive of radiotherapy toxicity, breaks in treatment or hospital admissions. Patients with oesophageal cancer, gynaecological cancers and lung cancer had a high rate of toxicity and hospital admission, which may highlight the need for additional patient support in these groups. Whilst comprehensive geriatric assessment is recommended, further research is needed to conclude if the frail elderly patient is at greater risk of toxicities from radiotherapy, and which geriatric assessment tool may be the most helpful.

Clinical review of treatment outcomes and patterns of failure with adjuvant radiotherapy in node-positive malignant melanoma.

INTRODUCTION: Adjuvant radiotherapy is proven to prevent lymph node field relapse after therapeutic lymphadenectomy for melanoma, but does not improve overall survival based on current data. There remains a high rate of distant relapse. This study reports patterns of failure in patients treated with adjuvant radiotherapy, looking at factors associated with distant metastasis and comparing this to recent literature. METHODS: This retrospective study included patients treated with adjuvant nodal irradiation after lymphadenectomy between June 2012 and March 2015. RESULTS: Twenty-one patients were treated during this period. Median follow-up was 13.5 months. There were no lymph node field recurrences. Distant metastasis (DM) rate was 48%. DM rate was significantly higher (P = 0.027) in patients with extracapsular extension (ECE) (71%) than those without ECE (0%). DM rate was higher in those with a maximum tumour size of >3 cm (71%) than those with tumour size <3 cm (30%) (P = 0.160). Number of nodes, BRAF status or nodal site did not correlate with rate of DM. The median time to DM was 16 weeks after completion of radiotherapy. CONCLUSION: Radiotherapy is well tolerated and effective in regional control. However, patients are at risk of early distant relapse, particularly those with ECE or large tumour size. There are currently no useful prognostic markers to differentiate the risk of regional versus distant recurrence, and the optimal treatment paradigm remains undefined. Research on adjuvant systemic therapies and abscopal effects of radiotherapy have shown improved management of distant metastasis; creating an even greater need for effective regional control strategies.