Prospective Phase II trial of radiation therapy in localised non-gastric marginal zone lymphoma with prospective evaluation of autoimmunity and Helicobacter pylori status: TROG 05.02/ALLG NHL15.

BACKGROUND: This Phase 2 multicentre trial in localised non-gastric marginal zone lymphoma (MZL) evaluated the effectiveness and safety of radiotherapy and documented markers of autoimmunity and Helicobacter pylori infection. PATIENTS AND METHODS: Eligible patients had Stages I and II or paired-organ, non-gastric MZL. Bone marrow evaluation, autoantibody panel, and H. pylori evaluation were mandatory. Involved-field or involved-site radiotherapy was delivered to 24-30.6 Gy. Detected H. pylori infections underwent eradication. RESULTS: Between 2006 and 2014, six centres enrolled 70 patients, and 68 commenced treatment. The median age was 59 (range: 23-84) years, and 31 (46%) were male. Overall, 55 patients had Stage I disease, nine patients had Stage II disease, and four patients had paired organ-confined disease. Involved extranodal sites with three or more cases were orbital (n = 18), conjunctiva (n = 13), lacrimal (n = 8), skin (n = 8), salivary (n = 7), and muscle (n = 4). Eight patients had primary nodal MZL. At the median follow-up of 5 years (range 0.7-9.4), progression-free survival and overall survival were 79% and 95%, respectively. One lymphoma-related death and two in-field failures (after 25 and 30 Gy, respectively) occurred. Distant relapse sites were skin (n = 2), lymph nodes (n = 2), duodenum, stomach, muscle, and conjunctiva (1 each). No paired-organ MZL relapsed. Apart from cataracts (n = 18), only three treatment-related late grade ≥3 adverse events occurred. Autoantibodies or autoimmune events were detected in 26 of 68 patients (38%). H. pylori infection was detected in 15 of 63 patients (24%) tested. Neither autoimmunity nor H. pylori was detected in 27 of 68 patients (40%). CONCLUSIONS: Radiotherapy was a potentially curative treatment with low toxicity in localised non-gastric MZL. Autoimmunity, H. pylori infection or both were detected in 60% of patients.

A prospective, multi-centre trial of multi-parametric MRI as a biomarker in anal carcinoma.

BACKGROUND AND PURPOSE: To investigate the role of multi-parametric magnetic resonance imaging (MP-MRI) as a biomarker for squamous cell carcinoma of the anal canal (SCCAC). MATERIALS AND METHODS: From January 2013 to January 2017, 25 patients with non-metastatic SCCAC were enrolled in a multi-centre prospective clinical trial, of whom 20 completed protocol treatment. MP-MRIs, incorporating diffusion weighted magnetic resonance imaging (DW-MRI) and dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) sequences, were performed before (baseline), during the second and fourth weeks of chemo-radiotherapy (CRT), and 8 weeks following treatment completion. Histogram analysis of multi-parametric maps generated maximum, mean, median, minimum, skewness, kurtosis, and standard deviation metrics. Exact logistic regression and ROC AUC analyses were performed for each metric at every timepoint. An elastic net LASSO logistic regression was also performed using all measures at each timepoint. RESULTS: With a median follow up of 17.1 months, 3/20 patients had a local recurrence, and 5/20 had any recurrence. Several apparent diffusion coefficient (ADC) metrics extracted from DW-MRIs correlated with local recurrence and demonstrated excellent discrimination: baseline skewness (p = 0.04, ROC AUC 0.90) and standard deviation (SD) (p = 0.02, ROC AUC 0.90), week 2 skewness (p = 0.02, ROC AUC 0.91) and SD (p = 0.01, ROC AUC 0.94), week 4 kurtosis (p = 0.01, AUC 0.92) and SD (p = 0.01, ROC AUC 0.96). Changes in minimum ADC between baseline and week 2 (p = 0.02, ROC AUC 0.94) and baseline and week 4 (p = 0.02, ROC AUC 0.94) were prognostic for local recurrence. For prediction of any recurrence, ADC minimum (p = 0.02, ROC AUC 0.87) and SD (p = 0.01, ROC AUC 0.85) at baseline, and ADC maximum (p = 0.03, ROC AUC 0.77) and SD (p = 0.02, ROC AUC 0.81) at week 4 were significant. On LASSO logistic regression, ADC minimum and SD at baseline were retained for any recurrence. The only significant finding for DCE-MRI was a correlation of k-trans min at the second follow-up with local recurrence (p = 0.05, AUC 0.84). CONCLUSION: Several ADC parameters at various time points correlate with recurrence suggesting DW-MRI is a potential biomarker for SCCAC.

Assessment and predictors of fatigue in men with prostate cancer receiving radiotherapy and androgen deprivation therapy.

INTRODUCTION: Fatigue is a commonly reported symptom in men receiving radiation therapy and androgen deprivation therapy (ADT) for prostate cancer. Despite this, the complex mechanisms remain unclear. This study aims to investigate factors which correlate with development of fatigue. METHODS: Twenty-seven men with high-risk prostate cancer undergoing radiation therapy and 18 months of ADT were assessed for fatigue, haemoglobin (Hb), testosterone, magnetic resonance imaging (MRI) fat fraction (FF) and apparent diffusion coefficient (ADC), at baseline and at intervals after radiotherapy. Changes from baseline were analysed using paired t-tests. Linear time trends were assessed using linear mixed effect models. RESULTS: Overall, mean fatigue score increased from baseline to the 18-month time interval (difference 4.5, P = 0.0114). The mean value for Hb significantly decreased (P < 0.001) from baseline to 18 months. The mean value for testosterone significantly decreased (P < 0.001) from baseline to 12 months, and remained low. Mean for MRI FF showed a significant increase (P < 0.001) from baseline to 6 months. MRI ADC showed a non-significant decrease from baseline to 6 months (P = 0.4416). CONCLUSION: Radiotherapy and ADT resulted in a significant increase in fatigue scores. Statistically significant changes were noted in Hb, testosterone and MRI FF and ADC, however, none were shown to have a strong association with worsening fatigue. Further investigation in a larger cohort is required to assess the interaction between fatigue and possible biological factors.

FDG-PET parameters predict for recurrence in anal cancer - results from a prospective, multicentre clinical trial.

BACKGROUND: To investigate the prognostic significance of positron emission tomography (PET) parameters from F-18 fluorodeoxyglucose (FDG) PET scans performed pre- and post- chemo-radiotherapy (CRT) for squamous cell carcinoma of the anal canal (AC). METHODS: From January 2013 to January 2017, 19 patients with non-metastatic AC enrolled on a prospective trial underwent FDG-PET/CT imaging before and 12 weeks following CRT. A computer-generated volume of interest (VOI) was snapped around the primary tumour using six different standard uptake value (SUV) thresholds and the following parameters were extracted: SUV max, mean, median, standard deviation and peak as well as metabolic tumour volume (MTV) and total lesion glycolysis. Exact logistic regression and ROC AUC analyses were performed for each metric at each timepoint. RESULTS: With a median follow up of 15.8 months, 3/19 patients had a local recurrence and 5/19 had any recurrence. On post-CRT PET, the median SUV within a VOI bounded by an SUV of 3 correlated with local recurrence (p < 0.01) and demonstrated excellent discrimination (ROC AUC 1.00, perfect separation was achieved at a median SUV of 3.38). The mean SUV at this threshold did not quite reach significance for prediction of local recurrence (p = 0.06) but demonstrated excellent discrimination (ROC AUC 0.91). The MTV bounded by a threshold of 41% SUVmax on the pre-CRT PET predicted for any recurrence (p = 0.03) and showed excellent discrimination (ROC AUC 0.89). CONCLUSIONS: FDG-PET parameters are predictive of recurrence in AC. FDG-PET may represent a valuable tool for prognostication and response assessment in AC. TRIAL REGISTRATION: ANZCTR, ACTRN12614001219673 . Registered 19 November 2014 - Retrospectively registered.

Outcomes and relapse patterns following chemotherapy in advanced Hodgkin lymphoma in the positron emission tomography era.

BACKGROUND: This study evaluated relapse patterns and survival in advanced Hodgkin lymphoma (HL) patients treated with doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) with positron emission tomography (PET) used for staging and response assessment. PATIENTS AND METHODS: Patients aged 18 years or above with newly diagnosed histologically proven Stage III or IV HL treated with ABVD at Calvary Mater Newcastle from January 2005 to December 2012 were included in this study. All patients underwent pre-chemotherapy staging with 18F-fluorodeoxyglucose PET or PET/computed tomography and post-chemotherapy PET or PET/computed tomography for the assessment of response. RESULTS: Forty-three patients were included in the study. The 5-year disease-free survival, progression-free survival and overall survival were 88%, 74% and 86%, respectively. PET complete response was seen in 35 patients (81%), and the 5-year overall survival for this group was 94%. Relapse following a PET complete response was low (three patients) and occurred predominantly at the initial sites of disease. Four of five patients with bulky disease received consolidative radiotherapy and no in-field relapses were observed. CONCLUSION: Advanced stage HL with a PET complete response following ABVD is associated with an excellent prognosis.

Spinal multiparametric MRI and DEXA changes over time in men with prostate cancer treated with androgen deprivation therapy: a potential imaging biomarker of treatment toxicity.

OBJECTIVES: To explore changes in bone mineral density (BMD) measured by DEXA and MRS fat fraction (FF), Dixon FF, and ADC in lower spinal vertebral bodies in men with prostate cancer treated with androgen deprivation therapy (ADT). METHODS: Twenty-eight men were enrolled onto a clinical trial. All received ADT. DEXA imaging was performed at baseline and 12 months. L-spine MRI was done at baseline and 6 months. RESULTS: The number of patients who underwent DEXA, Dixon, ADC, and MRS at baseline/follow-up were 28/27, 28/26, 28/26, and 22/20. An increase in FF was observed from T11 to S2 (average 1 %/vertebra). There was a positive correlation between baseline MRS FF and Dixon FF (r = 0.85, p < 0.0001) and a negative correlation between MRS FF and ADC (r = -0.56, p = 0.036). Over 6 months, MRS FF increased by a median of 25 % in relative values (p = 0.0003), Dixon FF increased (p < 0.0001) and ADC values decreased (p = 0.0014). Men with >5 % BMD loss after 1 year had triple the percentage increase in MRS FF at 6 months (61.1 % vs. 20.9 %, p = 0.19). CONCLUSIONS: Changes are observed on L-spine MRI after 6 months of ADT. Further investigation is warranted of MRS change as a potential predictive biomarker for later BMD loss. KEY POINTS: • Spinal marrow fat fraction increases after 6 months of androgen deprivation therapy. • More inferior vertebral bodies tend to have higher fat fractions. • MRS fat fraction changes were associated with later changes in DEXA BMD.

Patients' and clinicians' preferences for adjuvant chemotherapy in endometrial cancer: an ANZGOG substudy of the PORTEC-3 intergroup randomised trial.

BACKGROUND: To determine the minimum survival benefits that patients, and their clinicians, judged sufficient to make adjuvant chemotherapy (ACT) worthwhile, in addition to pelvic radiotherapy, for women with high risk and advanced stage endometrial cancer. METHODS: Eighty-three participants in the PORTEC-3 trial completed a time trade-off questionnaire before and after adjuvant therapy; 44 of their clinicians completed it once only. The questionnaire used four hypothetical scenarios including baseline survival times without ACT of 5 and 8 years, and baseline survival rates at 5 years without ACT of 50 and 65%. RESULTS: Over 50% of patients judged an extra 1 year of survival time or an extra 5% in survival rate sufficient to make ACT worthwhile. Over 50% of clinicians judged an extra 1 year of survival time, or an extra 10% in survival rate, sufficient to make ACT worthwhile. Compared with patients, clinicians required similar survival time benefits (medians both 1 year, P=0.4), but larger survival rate benefits (medians 8.5% vs 5%, P=0.03), and clinicians' preferences varied less (IQR 0.5-1.5 years vs 0.4-2 years, P=0.0007; 5-10% vs 1-13%, P=0.004). Patients' preferences changed over time for the survival rate scenarios depending on whether they had ACT or not (change in median benefit - 3 months vs 2.5 months respectively, P=0.028). There were no strong predictors of patients' or clinicians' preferences. CONCLUSIONS: Patients and clinicians judged moderate survival benefits sufficient to make ACT worthwhile after pelvic radiotherapy for endometrial cancer. These benefits are larger than those judged sufficient by patients with breast or colon cancers, but similar to those judged sufficient by patients with lung or ovarian cancers.

A prospective study of nomogram-based adaptation of prostate radiotherapy target volumes.

BACKGROUND: A prospective clinical trial was conducted to evaluate the feasibility of a novel approach to the treatment of patients with high risk prostate cancer (HRPC) through the use of a nomogram to tailor radiotherapy target volumes. METHODS: Twenty seven subjects with HRPC were treated with a mildly hypofractionated radiotherapy regimen using image-guided IMRT technique between Jun/2013-Jan/2015. A set of validated prognostic factors were inputted into the Memorial-Sloan-Kettering Cancer Center (MSKCC) prostate cancer nomogram to estimate risk of loco-regional spread (LRS). The nomogram risk estimates for extra-capsular extension (ECE), seminal vesicles involvement (SVI), and pelvic lymph nodes involvement (LNI) were used to adapt radiotherapy treatment volumes based on a risk threshold of ≥15 % in all cases. A planning guide was used to delineate target volumes and organs at risk (OAR). Up to three dose levels were administered over 28 fractions; 70Gy for gross disease in the prostate +/- seminal vesicles (2.5Gy/fraction), 61.6Gy for subclinical peri-prostatic disease (2.2Gy/fraction) and 50.4Gy to pelvic nodes (1.8Gy/fraction). Data regarding protocol adherence, nomogram use, radiotherapy dose distribution, and acute toxicity were collected. RESULTS: Nomogram use 100 % of patients were treated for ECE, 88.9 % for SVI, and 70.4 % for LNI. The three areas at risk of LRS were appropriately treated according to the study protocol in 98.8 % cases. The MSKCC nomogram estimates for LRS differed significantly between the time of recruitment and analysis. Contouring protocol compliance Compliance with the trial contouring protocol for up to seven target volumes was 93.0 % (159/171). Compliance with protocol for small bowel contouring was poor (59.3 %). Dose constraints compliance Compliance with dose constraints for target volumes was 97.4 % (191/196). Compliance with dose constraints for OAR was 88.2 % (285/323). Acute toxicity There were no grade 3 acute toxicities observed. 20/27 (74.1 %) and 6/27 (22.2 %) patients experienced a grade 2 genitourinary and gastrointestinal toxicity respectively. CONCLUSIONS: We have demonstrated the feasibility of this novel risk-adapted radiation treatment protocol for HRPC. This study has identified key learning points regarding this approach, including the importance of standardization and updating of risk quantification tools, and the utility of an observer to verify their correct use. TRIAL REGISTRATION: ClincialTrials.gov identifier NCT01418040 . Hunter New England Human Research Ethics Committee (HNEHREC) reference number 12/08/15/4.02.

Involved-field radiotherapy for patients with mantle cell lymphoma.

INTRODUCTION: Retrospective analysis was performed at a single institution to assess the responsiveness of mantle cell lymphoma (MCL) to involved-field radiotherapy (IFRT). METHODS: All patients treated with IFRT to at least one site of MCL between 1998 and 2012 were included. There were 25 patients who received radiotherapy to 60 disease sites. Primary endpoint was overall response rate (ORR) infield for the first site of MCL treated per patient. Predictors of ORR were analysed for the primary endpoint. Time to local progression (TLP) infield and progression-free survival were calculated from the start of the first treatment course. Analysis of all sites collectively was also undertaken. Survival analysis was conducted by the Kaplan-Meier method. RESULTS: ORR rate was 84% for the first site treated per patient. Complete response and partial response rates were 68% and 16% respectively. Median TLP following radiotherapy to the first site was not reached. Infield control rate was 91% at 12 months (95% confidence interval 69-97%). When analysis was performed on all 60 sites, ORR was 85%. Symptomatic improvement occurred after IFRT to 93% of all sites. Systemic progression outside the radiotherapy field was the predominant form of failure following IFRT. CONCLUSION: Radiotherapy generally induced a clinical response at all levels of dose administered, ranging from 3 to 36 Gy. However, increased durability of local control was suggested with higher doses. Radiotherapy is an effective treatment for palliation of MCL with objective and symptomatic responses seen over a range of radiotherapy doses.

Infections after fiducial marker implantation for prostate radiotherapy: are we underestimating the risks?

BACKGROUND: The use of gold fiducial markers (FM) for prostate image-guided radiotherapy (IGRT) is standard practice. Published literature suggests low rates of serious infection following this procedure of 0-1.3%, but this may be an underestimate. We aim to report on the infection incidence and severity associated with the use of transrectally implanted intraprostatic gold FM. METHODS: Three hundred and fifty-nine patients who underwent transrectal FM insertion between January 2012 and December 2013 were assessed retrospectively via a self-reported questionnaire. All had standard oral fluoroquinolone antibiotic prophylaxis. The patients were asked about infective symptoms and the treatment received including antibiotics and/or related hospital admissions. Potential infective events were confirmed through medical records. RESULTS: 285 patients (79.4%) completed the questionnaire. 77 (27.0%) patients experienced increased urinary frequency and dysuria, and 33 patients (11.6%) reported episodes of chills and fevers after the procedure. 22 patients (7.7%) reported receiving antibiotics for urinary infection and eight patients (2.8%) reported hospital admission for urosepsis related to the procedure. CONCLUSION: The overall rate of symptomatic infection with FM implantation in this study is 7.7%, with one third requiring hospital admission. This exceeds the reported rates in other FM implantation series, but is in keeping with the larger prostate biopsy literature. Given the higher than expected complication rate, a risk-adaptive approach may be helpful. Where higher accuracy is important such as stereotactic prostate radiotherapy, the benefits of FM may still outweigh the risks. For others, a non-invasive approach for prostate IGRT such as cone-beam CT could be considered.

Implications for dosimetric changes when introducing MR-guided brachytherapy for small volume cervix cancer: a comparison of CT and MR-based treatments in a single centre.

To evaluate cervix brachytherapy dosimetry with the introduction of magnetic resonance (MR) based treatment planning and volumetric prescriptions and propose a method for plan evaluation in the transition period. The treatment records of 69 patients were reviewed retrospectively. Forty one patients were treated using computed tomography (CT)-based, Point A-based prescriptions and 28 patients were treated using magnetic resonance (MR)-based, volumetric prescriptions. Plans were assessed for dose to Point A and organs at risk (OAR) with additional high-risk clinical target volume (HR-CTV) dose assessment for MR-based brachytherapy plans. ICRU-38 point doses and GEC-ESTRO recommended volumetric doses (D2cc for OAR and D100, D98 and D90 for HR-CTV) were also considered. For patients with small HR-CTV sizes, introduction of MR-based volumetric brachytherapy produced a change in dose delivered to Point A and OAR. Point A doses fell by 4.8 Gy (p = 0.0002) and ICRU and D2cc doses for OAR also reduced (p < 0.01). Mean Point A doses for MR-based brachytherapy treatment plans were closer to those of HR-CTV D100 for volumes less than 20 cm(3) and HR-CTV D98 for volumes between 20 and 35 cm(3), with a significant difference (p < 0.0001) between Point A and HR-CTV D90 doses in these ranges. In order to maintain brachytherapy dose consistency across varying HR-CTV sizes there must be a relationship between the volume of the HR-CTV and the prescription dose. Rather than adopting a 'one size fits all' approach during the transition to volume-based prescriptions, this audit has shown that separating prescription volumes into HR-CTV size categories of less than 20 cm(3), between 20 and 35 cm(3), and more than 35 cm(3) the HR-CTV can provide dose uniformity across all volumes and can be directly linked to traditional Point A prescriptions.

Circulating tumor cell detection in high-risk non-metastatic prostate cancer.

PURPOSE: The detection of circulating tumor cells (CTCs) provides important prognostic information in men with metastatic prostate cancer. We aim to determine the rate of detection of CTCs in patients with high-risk non-metastatic prostate cancer using the CellSearch® method. METHOD: Samples of peripheral blood (7.5 mL) were drawn from 36 men with newly diagnosed high-risk non-metastatic prostate cancer, prior to any initiation of therapy and analyzed for CTCs using the CellSearch® method. RESULTS: The median age was 70 years, median PSA was 14.1, and the median Gleason score was 9. The median 5-year risk of progression of disease using a validated nomogram was 39 %. Five out of 36 patients (14 %, 95 % CI 5-30 %) had CTCs detected in their circulation. Four patients had only 1 CTC per 7.5 mL of blood detected. One patient had 3 CTCs per 7.5 mL of blood detected, which included a circulating tumor microemboli. Both on univariate analysis and multivariate analysis, there were no correlations found between CTC positivity and the classic prognostic factors including PSA, Gleason score, T-stage and age. CONCLUSION: This study demonstrates that patients with high-risk, non-metastatic prostate cancer present infrequently with small number of CTCs in peripheral blood. This finding is consistent with the limited literature available in this setting. Other CTC isolation and detection technologies with improved sensitivity and specificity may enable detection of CTCs with mesenchymal phenotypes, although none as yet have been validated for clinical use. Newer assays are emerging for detection of new putative biomarkers for prostate cancer. Correlation of disease control outcomes with CTC detection will be important.

Optimal single 3T MR imaging sequence for HDR brachytherapy of cervical cancer.

PURPOSE: The superior image quality of 3 tesla (3T) magnetic resonance (MR) imaging in cervical cancer offers the potential to use a single image set for brachytherapy. This study aimed to determine a suitable single sequence for contouring tumour and organs at risk, applicator reconstruction, and treatment planning. MATERIAL AND METHODS: A 3T (Skyra, Siemens Healthcare AG, Germany) MR imaging system with an 18 channel body matrix coil generated HDR cervical cancer brachytherapy planning images on 20 cases using plastic-based treatment applicators. Seven different T2-weighted Turbo Spin Echo (TSE) sequences including both 3D and contiguous 2D scans based on sagittal, axial (transverse), and oblique planes were analysed. Each image set was assessed for total scanning time and usefulness in tumour localization via inter- and intra-observer analysis of high-risk clinical target volume (HR CTV) contouring. Applicator reconstruction in the treatment planning system was also considered. RESULTS: The intra-observer difference in HR CTV volumes between 2D and 3D axial-based image sets was low with an average difference of 3.1% for each observer. 2D and 3D sagittal image sets had the highest intra- and inter observer differences (over 15%). A 2D axial 'double oblique' sequence was found to produce the best intra- (average difference of 0.6%) and inter-observer (mean SD of 9.2%) consistency and greatest conformity (average 0.80). CONCLUSIONS: There was little difference between 2D and 3D-based scanning sequences; however the increased scanning time of 3D sequences have potential to introduce greater patient motion artifacts. A contiguous 2D sequence based on an axial T2-weighted turbo-spin-echo (TSE) sequence orientated in all planes of the treatment applicator provided consistent tumour delineation whilst allowing applicator reconstruction and treatment planning.

Dosimetric comparison of optimization methods for multichannel intracavitary brachytherapy for superficial vaginal tumors.

PURPOSE: Multichannel vaginal applicators allow treatment of a more conformal volume compared with a single, central vaginal channel. There are several optimization methods available for use with multichannel applicators, but no previous comparison of these has been performed in the treatment of superficial vaginal tumors. Accordingly, a feasibility study was completed to compare inverse planning by simulated annealing (IPSA), dose point optimization (DPO), and graphical optimization for high-dose-rate brachytherapy using a multichannel, intracavitary vaginal cylinder. METHODS AND MATERIALS: This comparative study used CT data sets from five patients with superficial vaginal recurrences of endometrial cancer treated with multichannel intracavitary high-dose-rate brachytherapy. Treatment plans were generated using DPO, graphical optimization, surface optimization with IPSA (surf IPSA), and two plans using volume optimization with IPSA. The plans were evaluated for target coverage, conformal index, dose homogeneity index, and dose to organs at risk. RESULTS: Best target coverage was achieved by volume optimization with IPSA 2 and surf IPSA with mean V100 values of 93.89% and 91.87%, respectively. Doses for the most exposed 2-cm(3) of the bladder (bladder D2cc) was within tolerance for all optimization methods. Rectal D2cc was above tolerance for one DPO plan. All volume optimization with IPSA plans resulted in higher vaginal mucosa doses for all patients. Greatest homogeneity within the target volume was seen with surf IPSA and DPO. Highest conformal indices were seen with surf IPSA and graphical optimization. CONCLUSIONS: Optimization with surf IPSA was user friendly for the generation of treatment plans and achieved good target coverage, conformity, and homogeneity with acceptable doses to organs at risk.

The impact of breast cosmetic and functional outcomes on quality of life: long-term results from the St. George and Wollongong randomized breast boost trial.

The aims of this study were to evaluate the impact of cosmetic and functional outcomes after breast-conserving surgery (BCS) and radiation on quality of life (QOL). In this exploratory analysis; baseline, 5 and 10 years data of patient's assessment of breast cosmesis, arm swelling/pain, limitation of movement, loss of feeling in fingers and breast sensitivity/tenderness were dichotomized and their impact on QOL (QLQ-C30) were assessed. Multivariable modelling was also performed to assess associations with QOL. The St. George and Wollongong randomized trial randomized 688 patients into the boost and no boost arms. 609, 580, and 428 patients had baseline, 5 and 10 years cosmetic data available, respectively. Similar numbers had the various functional assessments in the corresponding period. By univariate analysis, cosmesis and a number of functional outcomes were highly associated with QOL. Adjusted multivariate modelling showed that cosmesis remained associated with QOL at 5 and 10 years. Breast sensitivity, arm pain, breast separation, age and any distant cancer event were also associated with QOL on multivariate modelling at 10 years. This study highlights the importance of maintaining favorable cosmetic and functional outcomes following BCS. In addition, the clinically and statistically significant relationship between functional outcomes and QOL shows the importance for clinicians and allied health professionals in identifying, discussing, managing, and limiting these effects in women with breast cancer in order to maintain QOL.

A paired, double-blind, randomized comparison of a moisturizing durable barrier cream to 10% glycerine cream in the prophylactic management of postmastectomy irradiation skin care: trans Tasman Radiation Oncology Group (TROG) 04.01.

PURPOSE: A previous, unblinded study demonstrated that an alcohol-free barrier film containing an acrylate terpolymer (ATP) was effective in reducing skin reactions compared with a 10% glycerine cream (sorbolene). The different appearances of these products precluded a blinded comparison. To test the acrylate terpolymer principle in a double-blinded manner required the use of an alternative cream formulation, a moisturizing durable barrier cream (MDBC); the study was conducted by the Trans Tasman Radiation Oncology Group (TROG) as protocol 04.01. METHODS AND MATERIALS: A total of 333 patients were randomized; 1 patient was ineligible and 14 patients withdrew or had less than 7 weeks' observations, leaving 318 for analysis. The chest wall was divided into medial and lateral compartments, and patients were randomized to have MDBC applied daily to the medial or lateral compartment and sorbolene to the other compartment. Weekly observations, photographs, and symptom scores (pain and pruritus) were collected to week 12 or resolution of skin reactions if earlier. Skin dose was confirmed by centrally calibrated thermoluminescent dosimeters. RESULTS: Rates of medial and lateral compartment Common Toxicity Criteria (CTC), version 3, greater than or equal to grade 3 skin reactions were 23% and 41%, but rates by skin care product were identical at 32%. There was no significant difference between MDBC and sorbolene in the primary endpoint of peak skin reactions or secondary endpoints of area-under-the-curve skin reaction scores. CONCLUSIONS: The MDBC did not reduce the peak skin reaction compared to sorbolene. It is possible that this is related to the difference in the formulation of the cream compared with the film formulation. Skin dosimetry verification and double blinding are essential for radiation skin care comparative studies.

Treatment-related morbidity in prostate cancer: a comparison of 3-dimensional conformal radiation therapy with and without image guidance using implanted fiducial markers.

PURPOSE: To estimate the prevalence of rectal and urinary dysfunctional symptoms using image guided radiation therapy (IGRT) with fiducials and magnetic resonance planning for prostate cancer. METHODS AND MATERIALS: During the implementation stages of IGRT between September 2008 and March 2010, 367 consecutive patients were treated with prostatic irradiation using 3-dimensional conformal radiation therapy with and without IGRT (non-IGRT). In November 2010, these men were asked to report their bowel and bladder symptoms using a postal questionnaire. The proportions of patients with moderate to severe symptoms in these groups were compared using logistic regression models adjusted for tumor and treatment characteristic variables. RESULTS: Of the 282 respondents, the 154 selected for IGRT had higher stage tumors, received higher prescribed doses, and had larger volumes of rectum receiving high dosage than did the 128 selected for non-IGRT. The follow-up duration was 8 to 26 months. Compared with the non-IGRT group, improvement was noted in all dysfunctional rectal symptoms using IGRT. In multivariable analyses, IGRT improved rectal pain (odds ratio [OR] 0.07 [0.009-0.7], P=.02), urgency (OR 0.27 [0.11-0.63], P=<.01), diarrhea (OR 0.009 [0.02-0.35], P<.01), and change in bowel habits (OR 0.18 [0.06-0.52], P<.010). No correlation was observed between rectal symptom levels and dose-volume histogram data. Urinary dysfunctional symptoms were similar in both treatment groups. CONCLUSIONS: In comparison with men selected for non-IGRT, a significant reduction of bowel dysfunctional symptoms was confirmed in men selected for IGRT, even though they had larger volumes of rectum treated to higher doses.

Digital photography as source documentation of skin toxicity: an analysis from the Trans Tasman Radiation Oncology Group (TROG) 04.01 post-mastectomy radiation skin care trial.

INTRODUCTION: This study evaluated digital photographs as a method of providing auditable source documentation for radiotherapy-induced skin toxicity and the possibility therefore of centralised, blinded scoring for a multicentre randomised controlled trial. METHODS: Digital photograph sets from the first five patients from each of 12 participating centres were audited. Minimum camera specifications and photograph requirements were protocol specified. Three readers rated photographs for four key quality items. They also scored skin reactions according to National Cancer Institute Common Terminology Criteria (CTC) v3.0 acute skin score and also for the presence of any moist desquamation. RESULTS: Five hundred fifty-two images were available. Field of view was scored as inadequate in 1-10%, focus inadequate in 0.4-4%, lighting inadequate in 0.2-3% and dividing line marking inadequate for scoring of skin reactions within sectors in 18-23% of photographs by three readers. Reader pairwise inter-observer agreement was 83-88% for CTC acute skin scores, but the kappa value ranged from 0.58 to 0.73. The percentage of image sectors not scored by readers due to difficulty in assessing was 1-10%. Moist desquamation was scored by clinicians in 8 (medial)-13% (lateral) of patients compared with 3-5% and 5-11% by readers. CONCLUSION: Photo reader inter-observer agreement is only moderate. Photo readers tended to underscore the frequency of moist desquamation, but the trend by sector parallels the clinical scorers. Photographs are useful source documents for auditing and monitoring, but not a replacement for clinical scoring.

An atlas-based electron density mapping method for magnetic resonance imaging (MRI)-alone treatment planning and adaptive MRI-based prostate radiation therapy.

PURPOSE: Prostate radiation therapy dose planning directly on magnetic resonance imaging (MRI) scans would reduce costs and uncertainties due to multimodality image registration. Adaptive planning using a combined MRI-linear accelerator approach will also require dose calculations to be performed using MRI data. The aim of this work was to develop an atlas-based method to map realistic electron densities to MRI scans for dose calculations and digitally reconstructed radiograph (DRR) generation. METHODS AND MATERIALS: Whole-pelvis MRI and CT scan data were collected from 39 prostate patients. Scans from 2 patients showed significantly different anatomy from that of the remaining patient population, and these patients were excluded. A whole-pelvis MRI atlas was generated based on the manually delineated MRI scans. In addition, a conjugate electron-density atlas was generated from the coregistered computed tomography (CT)-MRI scans. Pseudo-CT scans for each patient were automatically generated by global and nonrigid registration of the MRI atlas to the patient MRI scan, followed by application of the same transformations to the electron-density atlas. Comparisons were made between organ segmentations by using the Dice similarity coefficient (DSC) and point dose calculations for 26 patients on planning CT and pseudo-CT scans. RESULTS: The agreement between pseudo-CT and planning CT was quantified by differences in the point dose at isocenter and distance to agreement in corresponding voxels. Dose differences were found to be less than 2%. Chi-squared values indicated that the planning CT and pseudo-CT dose distributions were equivalent. No significant differences (p > 0.9) were found between CT and pseudo-CT Hounsfield units for organs of interest. Mean ± standard deviation DSC scores for the atlas-based segmentation of the pelvic bones were 0.79 ± 0.12, 0.70 ± 0.14 for the prostate, 0.64 ± 0.16 for the bladder, and 0.63 ± 0.16 for the rectum. CONCLUSIONS: The electron-density atlas method provides the ability to automatically define organs and map realistic electron densities to MRI scans for radiotherapy dose planning and DRR generation. This method provides the necessary tools for MRI-alone treatment planning and adaptive MRI-based prostate radiation therapy.

A magnetic resonance imaging-based workflow for planning radiation therapy for prostate cancer.

Dose planning for prostate radiation therapy is performed using computed tomography (CT) scans that provide the electron density information needed for individual patients' radiation dose calculations. For visualising the prostate and determining the target volume for radiation treatment, magnetic resonance imaging (MRI) gives vastly superior soft-tissue contrast. However, currently, MRI scans cannot be used for dose planning, as they do not provide the electron density information. We aimed to develop an alternative and efficient MRI-only image-based workflow, enabling both organ delineation and dose planning to be performed using MRI, with "pseudo-CT scans" generated from MRI scans supplying the information for dose planning. The feasibility of implementing MRI-based prostate radiation therapy planning is being investigated through collaboration between the clinical and medical physics group at the Calvary Mater Newcastle Hospital/University of Newcastle and the biomedical imaging processing group at the CSIRO (Commonwealth Scientific and Industrial Research Organisation) Australian e-Health Research Centre. Results comparing Hounsfield units calculated from CT scans and from MRI-based pseudo-CT scans for 39 patients showed very similar average values for the prostate, bladder, bones and rectum, confirming that pseudo-CT scans can replace CT scans for accurate radiation dose calculations. MRI-based radiotherapy planning can also be used for tumours in other locations, such as head and neck, and breast cancers.