Efficacy and toxicity of primary re-irradiation for malignant spinal cord compression based on radiobiological modelling: a phase II clinical trial.

BACKGROUND: The efficacy and safety of primary re-irradiation for MSCC are not known. Our aim was to establish the efficacy and safety of biologically effective dose-based re-irradiation. METHODS: Patients presenting with MSCC at a previously irradiated spine segment, and not proceeding with surgical decompression, were eligible. A 3 Gray per fraction experimental schedule (minimum 18 Gy/6 fractions, maximum 30 Gy/10 fractions) was used, delivering a maximum cumulative spinal dose of 100 Gy2 if the interval since the last radiotherapy was within 6 months, or 130 Gy2 if longer. The primary outcome was a change in mobility from week 1 to week 5 post-treatment, as assessed by the Tomita score. The RTOG SOMA score was used to screen for spinal toxicity, and an MRI performed to assess for radiation-induced myelopathy (RIM). RESULTS: Twenty-two patients were enroled, of whom eleven were evaluable for the primary outcome. Nine of eleven (81.8%) had stable or improved Tomita scores at 5 weeks. One of eight (12.5%) evaluable for late toxicity developed RIM. CONCLUSIONS: Re-irradiation is an efficacious treatment for MSCC. There is a risk of RIM with a cumulative dose of 120 Gy2. CLINICAL TRIAL REGISTRATION: Cancer Trials Ireland (ICORG 07-11); NCT00974168.

Prospective randomised phase II trial evaluating adjuvant pelvic radiotherapy using either IMRT or 3-Dimensional planning for endometrial cancer.

OBJECTIVE: To compare the incidence of grade ≥2 gastrointestinal (GI) or genitourinary (GU) toxicity for patients undergoing 3DRT versus IMRT in the postoperative setting for endometrial cancer. METHODS: Eligible patients were post-operatively randomly assigned to one of two parallel groups in a 1:1 ratio, to have their RT delivered using either a 3DRT technique or using IMRT. The prescription dose was 45 Gy in 25 fractions over 5 weeks followed by vaginal vault brachytherapy. Toxicity was graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 3.0. Fisher's exact tests were used to test for associations between toxicity and arm. Differences in dosimetric parameters for patients with or without toxicity were tested using Mann-Whitney U-tests. RESULTS: 84 patients with a median age of 62 were evaluable for primary outcome. The median follow-up was 52 months. 14 (35%) participants from the 3DRT arm and 15 (34%) from the IMRT arm experienced acute grade ≥2 GI toxicity with older patients having a statistically higher risk of grade ≥2 acute GI toxicity. 20 (50%) participants from the 3DRT arm and 25 (57%) from the IMRT arm experienced acute grade ≥2 GI or GU toxicity (p = .662). 12 (30%) patients from the 3DRT arm and 17 (39%) from the IMRT arm experienced acute grade ≥2 GU toxicity (p = .493). CONCLUSION: Although IMRT can reduce dose to normal tissue, in this study no benefit in acute GI or GU toxicity outcome was seen.

Prostate radiotherapy and the risk of secondary rectal cancer-a meta-analysis.

PURPOSE: Radiotherapy is being used increasingly in the treatment of prostate cancer. However, ionising radiation may confer a small risk of a radiation-induced secondary malignancy. We aim to assess the risk of rectal cancer following pelvic radiotherapy for prostate cancer. METHODS: A search was conducted of the PubMed/MEDLINE, EMBASE and Web of Science databases identifying studies reporting on the risk of rectal cancer following prostatic radiotherapy. Studies must have included an appropriate control group of non-irradiated prostate cancer patients. A meta-analysis was performed to assess the risk of prostatic radiotherapy on subsequent rectal cancer diagnosis. RESULTS: In total, 4757 articles were screened with eight studies meeting the predetermined criteria. A total of 796,386 patients were included in this meta-analysis which showed an increased odds ratio (OR) for subsequent rectal cancer in prostate cancer patients treated with radiotherapy compared to those treated by non-radiotherapy means (OR 1.45, 1.07-1.97, p = 0.02). CONCLUSION: These findings confirm that prostate radiotherapy significantly increases the risk of subsequent rectal cancer. This risk has implications for treatment selection, surveillance and patient counselling. However, it is crucial that this information is presented in a rational and comprehensible manner that does not disproportionately frighten or deter patients from what might be their most suitable treatment modality.

Self-reported and objective taste and smell evaluation in treatment-naive solid tumour patients.

BACKGROUND: Taste and smell abnormalities (TSA) commonly occur in cancer and are associated with anorexia, early satiety, malnutrition, weight loss and reduced quality of life. A recent study found a high TSA prevalence in newly diagnosed cancer patients before treatment. This suggests that TSA may originate from the tumour itself. No previous study has examined TSA, both subjectively and objectively, in newly diagnosed, treatment-naïve cancer patients. This study aimed to address this gap. METHODS: This prospective observational study recruited consecutive, newly diagnosed, treatment-naïve patients with solid tumours at Radiation Oncology Out-patients. Self-reported taste and smell changes since becoming ill were evaluated using modified Taste and Smell Survey, and objective taste and smell tests were conducted using 'Sniffin' Sticks Olfactory Test® and Burghart Taste Strips®. Nutritional status was assessed with abridged Patient-Generated Subjective Global Assessment. RESULTS: Thirty completed the study. Seventy-four per cent had at least one TSA. Taste changes and/or abnormalities were more prevalent than smell, and subjective taste changes more common than objective abnormalities. Although less common, smell abnormalities impacted quality of life more. TSA characteristics were heterogeneous. Forty-seven per cent were at malnutrition risk. No association was found between TSA and nutritional status. CONCLUSIONS: Over two thirds had at least one TSA and almost half were at malnutrition risk. Self-reported TSA included changes in taste and smell perception, and most commonly persistent bad taste. This study demonstrated the complexity of TSA assessment and the prevalence, severity and impact of these and related symptoms in treatment-naïve cancer patients.

PORTEC-4a: international randomized trial of molecular profile-based adjuvant treatment for women with high-intermediate risk endometrial cancer.

BACKGROUND: Vaginal brachytherapy is currently recommended as adjuvant treatment in patients with high-intermediate risk endometrial cancer to maximize local control and has only mild side effects and no or limited impact on quality of life. However, there is still considerable overtreatment and also some undertreatment, which may be reduced by tailoring adjuvant treatment to the patients' risk of recurrence based on molecular tumor characteristics. PRIMARY OBJECTIVES: To compare the rates of vaginal recurrence in women with high-intermediate risk endometrial cancer, treated after surgery with molecular-integrated risk profile-based recommendations for either observation, vaginal brachytherapy or external pelvic beam radiotherapy or with standard adjuvant vaginal brachytherapy STUDY HYPOTHESIS: Adjuvant treatment based on a molecular-integrated risk profile provides similar local control and recurrence-free survival as current standard adjuvant brachytherapy in patients with high-intermediate risk endometrial cancer, while sparing many patients the morbidity of adjuvant treatment and reducing healthcare costs. TRIAL DESIGN: A multicenter, international phase III randomized trial (2:1) of molecular-integrated risk profile-based adjuvant treatment (experimental arm) or adjuvant vaginal brachytherapy (standard arm). MAJOR INCLUSION/EXCLUSION CRITERIA: Women aged 18 years and over with a histological diagnosis of high-intermediate risk endometrioid endometrial cancer after total abdominal or laparoscopic hysterectomy and bilateral salpingo-oophorectomy. High-intermediate risk factors are defined as: (i) International Federation of Gynecology and Obstetrics stage IA (with invasion) and grade 3; (ii) stage IB grade 1 or 2 with age ≥60 and/or lymph-vascular space invasion; (iii) stage IB, grade 3 without lymph-vascular space invasion; or (iv) stage II (microscopic and grade 1). ENDPOINTS: The primary endpoint is vaginal recurrence. Secondary endpoints are recurrence-free and overall survival; pelvic and distant recurrence; 5-year vaginal control (including treatment for relapse); adverse events and patient-reported symptoms and quality of life; and endometrial cancer-related healthcare costs. SAMPLE SIZE: 500 eligible and evaluable patients. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Estimated date for completing accrual will be late 2021. Estimated date for presentation of (first) results is expected in 2023. TRIAL REGISTRATION: The trial is registered at clinicaltrials.gov (NCT03469674) and ISRCTN (11659025).

What do radiation therapists know about health literacy and the strategies to improve it for patients? A qualitative study.

PURPOSE: Low health literacy leads to poor knowledge and understanding of health information, delayed diagnosis, lower use of preventative medicines/health services, increased likelihood of hospitalisation, and increased patient anxiety. Effective communication facilitates patient understanding and helps patients to manage the adverse side-effects associated with treatment. It is not yet known whether radiation therapists in Ireland tailor their communication to match a patient's health literacy level. The purpose of this research was to investigate radiation therapists' knowledge and awareness of health literacy and perceptions of their role in supporting patients with low health literacy. METHODS: Semi-structured interviews were conducted with sixteen radiation therapists working in four radiotherapy departments in Ireland. Data were analysed using the framework approach. RESULTS: Through discussions with participants, it was apparent that radiation therapists had limited knowledge of the concept of health literacy. Common themes arose from the interviews with four key themes identified: 1. Strategies used to identify patients' health literacy 2. Perceived effect of low health literacy 3. Obstacles faced when addressing low health literacy 4. Recommendations to support lower health literacy groups CONCLUSION: Currently, radiation therapists show some knowledge and awareness of health literacy, but an increased awareness of the prevalence of low health literacy and a structured approach to supporting patients would allow radiation therapists to more effectively communicate with patients, thus improving their treatment experience and reducing the risk of adverse outcomes.

Primary appendicular soft-tissue sarcoma resection: What tumour parameters affect wound closure planning?

Wound closure after wide, local excision of an appendicular soft-tissue sarcoma (STS) can be challenging. This study evaluates the value of magnetic resonance imaging (MRI)-based tumour parameters in planning wound closure. A total of 71 patients with a primary limb-based STS, excluding vascular or osseous involvement, excluding the shoulder or hand and hip or foot were included. Axial MRI images were used to measure the circumferences and cross-sectional areas of the limb, bone, and tumour. The tumour diameter, length, and depth at the level of maximal tumour dimension were measured to identify the tumour's relative contribution to the planning of optimal wound closure management through primary closure (PC) or reconstructive surgery (RS). Eighteen patients required planned wound RS. Wound complications occurred in 14% overall. Tumours, which were closed by PC, were of significantly greater depth, shorter radial diameter, and shorter tumour circumference relative to those closed by RS. On multivariate analysis, tumour depth was the greatest contributory factor in predicting type of wound closure. A quantitative analysis of MRI-based tumour parameters demonstrates tumour depth as the most predictive factor in planning for the type of wound closure and may prove beneficial in providing greater insight into planned wound management of sarcoma resection.

Radiomics; Contemporary Applications in the Management of Anal Cancer; A Systematic Review.

INTRODUCTION: The management of anal cancer relies on clinical and histopathological features for treatment decisions. In recent years, the field of radiomics, which involves the extraction and analysis of quantitative imaging features, has shown promise in improving management of pelvic cancers. The aim of this study was to evaluate the current application of radiomics in the management of anal cancer. METHODS: A systematic search was conducted in Medline, EMBASE, and Web of Science databases. Inclusion criteria encompassed randomized and non-randomized trials investigating the use of radiomics to predict post-operative recurrence in anal cancer. Study quality was assessed using the QUADAS-2 and Radiomics Quality Score tools. RESULTS: The systematic review identified a total of nine studies, with 589 patients examined. There were three main outcomes assessed in included studies: recurrence (6 studies), progression-free survival (2 studies), and prediction of human papillomavirus (HPV) status (1 study). Radiomics-based risk stratification models were found to provide valuable insights into treatment response and patient outcomes, with all developed signatures demonstrating at least modest accuracy (range: .68-1.0) in predicting their primary outcome. CONCLUSION: Radiomics has emerged as a promising tool in the management of anal cancer. It offers the potential for improved risk stratification, treatment planning, and response assessment, thereby guiding personalized therapeutic approaches.

Predicted cardiac and second cancer risks for patients undergoing VMAT for mediastinal Hodgkin lymphoma.

BACKGROUND AND PURPOSE: To predict treatment-related cardiovascular disease (CVD) and second cancer 30-year absolute mortality risks (AMR30) for patients with mediastinal Hodgkin lymphoma in a large multicentre radiation oncology network in Ireland. MATERIAL AND METHODS: This study includes consecutive patients treated for mediastinal lymphoma using chemotherapy and involved site radiotherapy (RT) 2016-2019. Radiation doses to heart, left ventricle, cardiac valves, lungs, oesophagus, carotid arteries and female breasts were calculated. Individual CVD and second cancer AMR30 were predicted using Irish background population rates and dose-response relationships. RESULTS: Forty-four patients with Hodgkin lymphoma were identified, 23 females, median age 28 years. Ninety-eight percent received anthracycline, 80% received 4-6 cycles ABVD. Volumetric modulated arc therapy (VMAT) ± deep inspiration breath hold (DIBH) was delivered, median total prescribed dose 30 Gy. Average mean heart dose 9.8 Gy (range 0.2-23.8 Gy). Excess treatment-related mean AMR30 from CVD was 2.18% (0.79, 0.90, 0.01, 0.13 and 0.35% for coronary disease, heart failure, valvular disease, stroke and other cardiac diseases), 1.07% due to chemotherapy and a further 1.11% from RT. Excess mean AMR30 for second cancers following RT were: lung cancer 2.20%, breast cancer in females 0.34%, and oesophageal cancer 0.28%. CONCLUSION: For patients with mediastinal lymphoma excess mortality risks from CVD and second cancers remain clinically significant despite contemporary chemotherapy and photon-RT. Efforts to reduce the toxicity of combined modality treatment, for example, using DIBH, reduced margins and advanced RT, e.g. proton beam therapy, should be continued to further reduce potentially fatal treatment effects.

External validation of a radiomic signature to predict p16 (HPV) status from standard CT images of anal cancer patients.

The paper deals with the evaluation of the performance of an existing and previously validated CT based radiomic signature, developed in oropharyngeal cancer to predict human papillomavirus (HPV) status, in the context of anal cancer. For the validation in anal cancer, a dataset of 59 patients coming from two different centers was collected. The primary endpoint was HPV status according to p16 immunohistochemistry. Predefined statistical tests were performed to evaluate the performance of the model. The AUC obtained here in anal cancer is 0.68 [95% CI (0.32-1.00)] with F1 score of 0.78. This signature is TRIPOD level 4 (57%) with an RQS of 61%. This study provides proof of concept that this radiomic signature has the potential to identify a clinically relevant molecular phenotype (i.e., the HPV-ness) across multiple cancers and demonstrates potential for this radiomic signature as a CT imaging biomarker of p16 status.

Prognostic value of pre-operative mean corpuscular volume (MCV) in colorectal cancer.

BACKGROUND: Mean corpuscular volume (MCV) has been shown to have some correlation to oncological outcomes in oesophageal cancer, with high pre-operative MCV associated with disease recurrence. A similar association has previously been reported in colorectal cancer. AIMS: This study is aimed at investigating whether high MCV bears similar relation to post-operative outcome and disease recurrence in colorectal cancer (CRC). METHODS: Patients undergoing elective CRC resection with curative intent between January 2008 and December 2019 were identified from our prospective database. Review of patient demographic details, American Society of Anaesthesiologists (ASA) grade, smoking and alcohol intake were performed. In addition, tumour location and staging, operation performed, pre-operative laboratory data and oncological management of each patient were noted. Post-operative morbidity (Clavien-Dindo (CD) score > 2), 30-day mortality, in-hospital mortality and cancer recurrence were examined and multivariable regression analysis was performed to predict these outcomes. RESULTS: A total of 1,293 CRCs were resected, with 1,159 patients (89.7%) experiencing a hospital course without major morbidity (CD < 3). 30-day mortality rate was less than 1% (12/1293). There were 176 patients (13.6%) with recurrence at follow-up. When multivariable regression analysis was performed, high pre-operative MCV did not predict negative post-operative or oncological outcomes. CONCLUSION: MCV does not appear to be an independent prognostic factor for outcomes following elective CRC resection.

Extramural venous invasion (EMVI) in colorectal cancer is associated with increased cancer recurrence and cancer-related death.

INTRODUCTION: Colorectal cancer (CRC) outcomes vary depending on tumour biology, with several features used to predict disease behaviour. Extramural venous invasion (EMVI) is associated with negative outcomes and its presence has been established as an indicator of more aggressive disease in CRC. METHODS: A prospectively maintained database was examined for patients undergoing curative resection for non-metastatic CRC between 2012 and 2018 in a tertiary institution. Clinicopathological factors were compared to assess their impact on recurrence, all-cause mortality and cancer-related death. Kaplan Meier analysis of the association between EMVI and these endpoints was performed, and univariable and multivariable analysis was carried out to establish the relationship of predictive factors in oncological outcomes. RESULTS: Eighty-eight (13.5%) of 654 patients developed recurrence. The mean time to recurrence was 19.8 ± 13.5 months. There were 36 (5.5%) cancer-related deaths at a mean duration of follow-up of 46.3 ± 21.6 months. Two hundred and sixty-six patients had extramural venous invasion (40.7%). EMVI was significantly associated with reduced overall recurrence-free survival, systemic recurrence-free survival, and increased cancer-related death on univariate analysis (p < 0.001 for all, Fig. 1), and multivariable analysis (OR 1.8 and 2.1 respectively, p < 0.05 for both). CONCLUSION: EMVI is associated with a poor prognosis, independent of stage, nodal status and other histopathological features. The presence of EMVI should be strongly considered as an indication for adjuvant therapy.

Anal squamous cell carcinoma: a retrospective case series.

BACKGROUND: Anal cancer is a relatively rare cancer with 660 cases diagnosed in 2000-2015 in Ireland (1). The current standard treatment is radical chemoradiotherapy (CRT). The aim of our study was to review the treatment and outcomes of patients with localised anal squamous cell carcinoma (SCC), who received radical treatment in our radiation oncology network between 2008 and 2014 inclusive. METHODS: Data were collected retrospectively from ARIA® oncology information system and patient charts. Statistical analyses were performed using IBM® SPSS® statistical software version 25.0. RESULTS: Seventy-nine cases of anal SCC were identified. Mean age of patients at commencement of radiotherapy (RT) was 60.2 years (standard deviation: 13.1 years). The most common total RT dose was 50.4 Gy in 28 fractions (N = 58; 73.4%). Median follow-up was 5.6 years. Two (2.6%) patients had persistent disease, seventeen (21.8%) patients developed loco-regional recurrence and nine (11.5%) patients developed solid organ metastases, four of whom had complete treatment response at the primary site. Eight patients underwent salvage anal surgery following completion of RT. Median overall survival was 10.5 years (95% confidence interval (CI) 5.1-15.8 years), median loco-regional relapse-free survival was 10.4 years (95% CI 4.4-16.3 years) and median disease-free survival was 9.3 years (95% CI 6.3-12.2 years). CONCLUSION: Our study demonstrates that treatment for anal SCC and outcomes following definitive CRT in Ireland during the study period were comparable to international standards.

Deep inspiration breath hold versus free breathing technique in mediastinal radiotherapy for lymphoma.

OBJECTIVE: Radiotherapy plays an important role in the management of lymphoma and many patients with lymphoma are cured with treatment. Risk of secondary malignancy and long-term cardiac and pulmonary toxicity from mediastinal radiotherapy exists. Delivery of radiotherapy using a deep inspiration breath-hold (DIBH) technique increases lung volume and has the potential to reduce dose to heart and lungs. We undertook a prospective study to assess the dosimetric differences in DIBH and free breathing (FB) plans in patients requiring mediastinal radiotherapy in clinical practice. METHODS: We performed both FB and DIBH planning scans on 35 consecutive patients with mediastinal lymphoma needing radiotherapy. Contours and plans were generated for both data sets and dosimetric data were compared. All patients were planned using volumetric modulated arc therapy (VMAT). Data were compared for FB and DIBH plans with each patient acting as their own control using the related-samples Wilcoxon signed rank test. RESULTS: DIBH significantly reduced lung doses (mean 10.6 vs 11.4Gy, p < 0.0005; V20 16.8 vs 18.3%, p = 0.001) and spinal cord maximum dose (20.6 vs 22.8Gy, p = 0.001). DIBH increased breast V4 (38.5% vs 31.8%, p = 0.006) and mean right breast dose (4.2 vs 3.6Gy, p = 0.010). There was no significant difference in heart doses when the entire study cohort was considered, however, mean heart dose tended to be lower with DIBH for upper mediastinal (UM) tumours (4.3 vs 4.9Gy, p = 0.05). CONCLUSION: Our study describes the potential benefit of DIBH in a population reflective of clinical practice. DIBH can decrease radiation dose to lungs, heart and spinal cord, however, may increase dose to breasts. DIBH is not always superior to FB, and the clinical significance of differences in dose to organs at risk in addition to the time required to treat patients with DIBH must be considered when deciding the most appropriate radiotherapy technique for each patient. ADVANCES IN KNOWLEDGE: To our knowledge, this is the largest study comparing DIBH and FB planning for patients with lymphoma receiving mediastinal radiotherapy in clinical practice. It demonstrates the impact of an increasingly common radiotherapy technique on dose to organs at risk and the subsequent potential for long-term radiotherapy side-effects.

Results of image guided brachytherapy for stage IB cervical cancer in the RetroEMBRACE study.

OBJECTIVE: Multiple treatment options are used in early local-stage cervical cancer, including combinations of surgery with neoadjuvant/adjuvant radiotherapy and chemotherapy. Our aim was to determine the outcome for definitive chemoradiation with image guided brachytherapy (IGBT). METHODS: FIGO1994 staging system was used in our study. We included 123 patients with stage IB cervical cancer, treated at 12 centers with external beam radiotherapy (EBRT) ± Chemotherapy and IGBT. Three- and 5-year actuarial local control (LC), pelvic control (PC), overall survival (OS), cancer-specific survival (CSS) and late morbidity (CTCAE v 3.0) were computed. RESULTS: Median age was 48 (23-82) years. FIGO1994 stage distribution was: IB1 68% and IB2 32%; 41% of the entire cohort had nodal metastases and 73% squamous-cell carcinoma. MRI-based tumor size was >40 mm in 63%. Median EBRT dose was 45 (40-50) Gy; 84% received chemotherapy. At IGBT, mean CTV-HR D90 was 93 ± 17 Gy (EQD210). D2cc for bladder was 76 ± 14 Gy, rectum 66 ± 11 Gy, sigmoid 66 ± 10 Gy, bowel 67 ± 7 Gy (EQD23). At 43-months median follow-up, 9% of patients had systemic, 6% paraaortic, 3% pelvic-nodal and 2% local failure. Five-year LC was 98%, PC 96%, CSS 90%, OS 83%. Intestinal G3--4 morbidity was 8%, urinary 7% and vaginal 0%. CONCLUSIONS: Chemoradiation with IGBT for FIGO1994 stage IB cervical cancer leads to excellent loco-regional control with limited morbidity. In IB node-negative disease, it can be regarded equivalent to surgery in terms of oncologic outcome. In tumors with unfavorable pre-treatment characteristics, chemoradiation is the first choice to avoid combining surgery with adjuvant therapy.

Fibromatosis of the breast: a 10-year multi-institutional experience and review of the literature.

BACKGROUND: Breast fibromatosis is a rare clinical entity, but poses significant diagnostic and therapeutic challenges. In light of recent changes in management practices, the aim was to review our institutional experience of breast fibromatosis and provide a review of current available literature on such management. METHODS: A search of pathological databases within two tertiary institutions for all patients diagnosed with fibromatosis of the breast over a 10-year period (2007-2016) was performed. Clinicopathological characteristics and modes of treatment were recorded for each patient. Concurrently a comprehensive literature search was performed and studies relating to breast fibromatosis and its management were identified and reviewed. RESULTS: Sixteen patients were identified. Median age at diagnosis was 42 (range 21-70) and all patients were diagnosed with core biopsy. The most useful imaging modality in diagnosis was ultrasonography and magnetic resonance imaging. 13/16 were treated surgically whilst 3/16 were treated using a watch-and-wait approach. 6/13 (46%) required re-excision of margins and 2/13 (15%) had recurrence after surgery. On review of the literature, there is no dedicated guideline in place for the management of breast fibromatosis. Currently a 'watch and wait' approach is favoured over surgical intervention due to high levels of recurrence and associated surgical morbidity. All cases should be discussed at a sarcoma multidisciplinary team meeting and tyrosine kinase inhibitors should be considered in advanced cases. CONCLUSIONS: Breast fibromatosis is rare but affects young patients. Active surveillance is now favoured over surgical resection due to high recurrence rates and extensive morbidity. Dedicated guidelines are required to ensure best outcomes.

Nomogram Predicting Overall Survival in Patients With Locally Advanced Cervical Cancer Treated With Radiochemotherapy Including Image-Guided Brachytherapy: A Retro-EMBRACE Study.

PURPOSE: To present a nomogram for prediction of overall survival (OS) in patients with locally advanced cervical cancer (LACC) undergoing definitive radiochemotherapy including image-guided adaptive brachytherapy (IGABT). METHODS AND MATERIALS: Seven hundred twenty patients with LACC treated with radiochemotherapy including IGABT in 12 institutions (median follow-up 56 months) were analyzed; 248 deaths occurred. Thirteen candidate predictors for OS were a priori chosen on the basis of the literature and expert knowledge. Missing data (7.2%) were imputed using multiple imputation and predictive mean matching. Univariate analysis with a multivariable Cox regression model for OS stratified by center was performed. Stepwise selection of predictive factors with the Akaike Information Criterion was used to obtain a predictive model and construct a nomogram for OS predictions 60 months from diagnosis; this was internally validated by concordance probability as a measure of discrimination and a calibration plot. RESULTS: Thirteen potential predictive factors were evaluated; 10 factors reached statistical significance in univariate analysis (age, Hemoglobin, FIGO Stage2009, tumor width, corpus involvement, lymph node involvement, concurrent chemotherapy, dose to 90% of the high-risk clinical target volume, volume of CTV at the first brachytherapy [CTVHRVolumeBT], overall treatment time [OTT]). Four factors were confirmed significant within the multivariable Cox regression model (FIGO Stage2009, lymph node involvement, concurrent chemotherapy, CTVHRVolumeBT). The predictive model and corresponding nomogram were based on 7 Akaike Information Criterion-selected factors (age, corpus involvement, FIGO Stage2009, lymph node involvement, concurrent chemotherapy, CTVHRVolumeBT, OTT) and showed promising calibration and discrimination (cross-validated concordance probability c = 0.73). CONCLUSIONS: This is the first nomogram to predict OS in patients with LACC treated with IGABT. In addition to previously reported factors (age, FIGO2009 stage, corpus involvement, chemotherapy delivery, OTT, lymph node involvement), status of primary tumor at the time of brachytherapy seems to be an essential outcome predictor. These results can facilitate individualized tailoring of treatment and patient counseling during the treatment.

Gene expression analysis of diagnostic biopsies predicts pathological response to neoadjuvant chemoradiotherapy of esophageal cancer.

OBJECTIVE: This study explored gene expression differences in predicting response to chemoradiotherapy in esophageal cancer. PURPOSE: A major pathological response to neoadjuvant chemoradiation is observed in about 40% of esophageal cancer patients and is associated with favorable outcomes. However, patients with tumors of similar histology, differentiation, and stage can have vastly different responses to the same neoadjuvant therapy. This dichotomy may be due to differences in the molecular genetic environment of the tumor cells. BACKGROUND DATA: Diagnostic biopsies were obtained from a training cohort of esophageal cancer patients (13), and extracted RNA was hybridized to genome expression microarrays. The resulting gene expression data was verified by qRT-PCR. In a larger, independent validation cohort (27), we examined differential gene expression by qRT-PCR. The ability of differentially-regulated genes to predict response to therapy was assessed in a multivariate leave-one-out cross-validation model. RESULTS: Although 411 genes were differentially expressed between normal and tumor tissue, only 103 genes were altered between responder and non-responder tumor; and 67 genes differentially expressed >2-fold. These included genes previously reported in esophageal cancer and a number of novel genes. In the validation cohort, 8 of 12 selected genes were significantly different between the response groups. In the predictive model, 5 of 8 genes could predict response to therapy with 95% accuracy in a subset (74%) of patients. CONCLUSIONS: This study has identified a gene microarray pattern and a set of genes associated with response to neoadjuvant chemoradiation in esophageal cancer. The potential of these genes as biomarkers of response to treatment warrants further investigation.

Intravenous contrast media in radiation therapy planning computed tomography scans - Current practice in Ireland.

INTRODUCTION: While Computerised Tomography (CT) remains the gold standard in radiation therapy (RT) planning, inferior soft tissue definition remains a challenge. Intravenous contrast (IVC) use during CT planning can enhance soft tissue contrast optimising Target Volume (TV) and Organ at Risk visualisation and delineation. Despite this known benefit, there are no guidelines for when and how to use IVC in RT planning scans in Ireland. AIM: The study aims to examine the patterns of practice in relation to the use of IVC in RT planning scans in Ireland and to determine the level of compliance with international guidelines. Radiation Therapists (RTT) IVC training will also be investigated. MATERIALS AND METHODS: An anonymised online survey was designed based on previously-reported literature. This was distributed to all RT departments in Ireland. The survey contained open, closed and Likert scale questions that investigated IVC practices in each department. RESULTS: 75% (n = 9/12) of Irish departments responded. All responding departments reported using IVC. RTTs cannulated patients in 67% (n = 6/9) of the departments and administration contrast in all departments. Variations from recommended guidelines were found in disease sites where IVC was routinely used and in the assessment of renal functioning prior to contrast administration. IVC training varied in duration and number of supervised procedures required to fulfill competencies. CONCLUSION: IVC is used extensively in Irish RT departments. There are variations in IVC practice between departments and with international recommended guidelines.

Change in Patterns of Failure After Image-Guided Brachytherapy for Cervical Cancer: Analysis From the RetroEMBRACE Study.

PURPOSE: Image guided adaptive brachytherapy (IGABT) for cervical cancer improves pelvic control and survival across all stages. Improvement in pelvic control is larger in advanced stages, but improvement in survival is similar across stages. This paper analyzes the patterns of failure in the RetroEMBRACE cohort to investigate this discrepancy. METHODS AND MATERIALS: 731 patients from 12 institutions treated with chemoradiation therapy and magnetic resonance imaging or computed tomography-based IGABT were evaluated. The pattern of failure at time of first relapse was analyzed. RESULTS: Three hundred twenty-five failures (single and synchronous) occurred in 222 of 731 patients (30%). Among the 325 failures, 9% were local and 6% regional. Pelvic (local or regional) failures made up 13%, paraaortic node (PAN) 9%, systemic 21%, and distant (systemic + PAN) 24%. Of the 222 patients with treatment failure, 21% had pelvic failure alone, 57% had distant failure alone, and 23% had both pelvic and distant failure. Of all failures that occurred, 40% to 50% occurred in the first year, with a further 20% to 30% occurring in the second year. Although local, regional, and PAN failure tended to plateau after year 3, systemic failure continued to occur up to year 10. CONCLUSIONS: Implementation of IGABT has changed the patterns of relapse after chemoradiation therapy for cervical cancer. The predominant failure after IGABT is systemic, whereas the predominant failure with conventional brachytherapy is pelvic. Effective treatments to eradicate micrometastases in PAN and distant organs are needed in addition to IGABT and chemoradiation therapy to maximize local, regional, PAN, and systemic control and improve survival.