Background: Hodgkin's lymphoma (HL) survivors who undergo radiotherapy experience increased risks of second cancers (SC) and cardiac sequelae. To reduce such risks, extended-field radiotherapy (RT) for HL has largely been replaced by involved field radiotherapy (IFRT). While it has generally been assumed that IFRT will reduce SC risks, there are few data that quantify the reduction in dose to normal tissues associated with modern RT practice for patients with mediastinal HL, and no estimates of the expected reduction in SC risk.

BACKGROUND.Estimates of radiation‐related second cancer risk among Hodgkin lymphoma survivors are largely based on radiation therapy (RT) fields and doses no longer in use, and these estimates do not account for differences in normal tissue dose among individual patients. This study gives individualized estimates for the risks of lung and female breast cancer expected with contemporary involved‐field RT and low‐dose (20 Gy) RT for mediastinal Hodgkin lymphoma.METHODS.Three RT plans were constructed for 37 consecutive patients with mediastinal Hodgkin lymphoma: 35 Gy mantle RT, 35 Gy involved‐field RT (IFRT), and 20 Gy IFRT. For each of the 111 RT plans, individual‐level dosimetry data were incorporated into a cell initiation/inactivation/proliferation model to estimate the excess relative risk (ERR) and cumulative incidence of radiation‐induced second cancer.RESULTS.ERR estimates were compatible with results of epidemiological studies. Compared with 35 Gy mantle radiation therapy, 35 Gy IFRT was predicted to reduce the 20‐year ERRs of breast and lung cancer by 63% and 21%, respectively, primarily because of lower normal tissue doses with the omission of axillary RT. Low‐dose (20 Gy) IFRT was associated with a 77% and 57% decrease in these ERRs. Patient‐specific differences in normal tissue dose with IFRT led to 11‐fold and 3.6‐fold variations among individual's estimates of breast and lung cancer ERR, respectively.CONCLUSIONS.Contemporary IFRT is predicted to substantially reduce risk of secondary breast and lung cancer compared with mantle RT, with considerable variation in risk among individuals. Individualized prospective risk estimates could facilitate patient‐specific counseling and the development of more effective RT techniques. Cancer 2007. © 2007 American Cancer Society.

Background Despite the acceptability and efficacy of e–patient-reported outcome (ePRO) systems, implementation in routine clinical care remains challenging. Objective This pragmatic trial implemented the PROMPT-Care (Patient Reported Outcome Measures for Personalized Treatment and Care) web-based system into existing clinical workflows and evaluated its effectiveness among a diverse population of patients with cancer. Methods Adult patients with solid tumors receiving active treatment or follow-up care in four cancer centers were enrolled. The PROMPT-Care intervention supported patient management through (1) monthly off-site electronic PRO physical symptom and psychosocial well-being assessments, (2) automated electronic clinical alerts notifying the care team of unresolved clinical issues following two consecutive assessments, and (3) tailored online patient self-management resources. Propensity score matching was used to match controls with intervention patients in a 4:1 ratio for patient age, sex, and treatment status. The primary outcome was a reduction in emergency department presentations. Secondary outcomes were time spent on chemotherapy and the number of allied health service referrals. Results From April 2016 to October 2018, 328 patients from four public hospitals received the intervention. Matched controls (n=1312) comprised the general population of patients with cancer, seen at the participating hospitals during the study period. Emergency department visits were significantly reduced by 33% (P=.02) among patients receiving the intervention compared with patients in the matched controls. No significant associations were found in allied health referrals or time to end of chemotherapy. At baseline, the most common patient reported outcomes (above-threshold) were fatigue (39%), tiredness (38.4%), worry (32.9%), general wellbeing (32.9%), and sleep (24.1%), aligning with the most frequently accessed self-management domain pages of physical well-being (36%) and emotional well-being (23%). The majority of clinical feedback reports were reviewed by nursing staff (729/893, 82%), largely in response to the automated clinical alerts (n=877). Conclusions Algorithm-supported web-based systems utilizing patient reported outcomes in clinical practice reduced emergency department presentations among a diverse population of patients with cancer. This study also highlighted the importance of (1) automated triggers for reviewing above-threshold results in patient reports, rather than passive manual review of patient records; (2) the instrumental role nurses play in managing alerts; and (3) providing patients with resources to support guided self-management, where appropriate. Together, these factors will inform the integration of web-based PRO systems into future models of routine cancer care. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12616000615482; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370633 International Registered Report Identifier (IRRID) RR2-10.1186/s12885-018-4729-3

Toxicity to cardiac and coronary structures is an important late morbidity for patients undergoing left-sided breast radiotherapy. Many current studies have relied on estimates of cardiac doses assuming standardised anatomy, with a calculated increase in relative risk of 7.4% per Gy (mean heart dose). To provide individualised estimates for dose, delineation of various cardiac structures on patient images is required. Automatic multi-atlas based segmentation can provide a consistent, robust solution, however there are challenges to this method. We are aiming to develop and validate a cardiac atlas and segmentation framework, with a focus on the limitations and uncertainties in the process. We present a probabilistic approach to segmentation, which provides a simple method to incorporate inter-observer variation, as well as a useful tool for evaluating the accuracy and sources of error in segmentation. A dataset consisting of 20 planning computed tomography (CT) images of Australian breast cancer patients with delineations of 17 structures (including whole heart, four chambers, coronary arteries and valves) was manually contoured by three independent observers, following a protocol based on a published reference atlas, with verification by a cardiologist. To develop and validate the segmentation framework a leave-one-out cross-validation strategy was implemented. Performance of the automatic segmentations was evaluated relative to inter-observer variability in manually-derived contours; measures of volume and surface accuracy (Dice similarity coefficient (DSC) and mean absolute surface distance (MASD), respectively) were used to compare automatic segmentation to the consensus segmentation from manual contours. For the whole heart, the resulting segmentation achieved a DSC of , with a MASD of mm. Quantitative results, together with the analysis of probabilistic labelling, indicate the feasibility of accurate and consistent segmentation of larger structures, whereas this is not the case for many smaller structures, where a major limitation in segmentation accuracy is the inter-observer variability in manual contouring.

Introduction: Lung cancer is the leading cause of cancer mortality in Western nations, and associated health‐care costs are escalating. The aim of this study was to describe the current pattern of resource use and direct medical costs associated in managing lung cancer in South Western Sydney, Australia. Methods: All new cases of primary lung carcinoma discussed at the Liverpool and Macarthur Cancer Therapy Centre (CTC) Lung Cancer Multidisciplinary Team meeting or seen at CTC between 1 December 2005 and 21 December 2006 were reviewed. Staging investigations, hospitalisation, treatment and follow‐up investigations were documented from first consultation to last follow‐up (31 October 2008 or death). Cost estimates were based on the Australian Medicare Benefits Schedule and reported in Australian dollars. Infrastructure, staff and non‐medical costs were excluded. Results: There were 210 patients, median age 68.2 years (range 39–90) with median follow‐up of 16.6 months. The pathology and stage distribution were: 3.8% limited stage small cell lung cancer (SCLC), 10.0% extensive stage SCLC, 13.4% stage I and II non‐small cell lung cancer (NSCLC), 28.5% stage III NSCLC and 44.3% stage IV NSCLC. The estimated total cost for managing this patient cohort was A$2.91 million. The cost components were: staging investigations (10.1%), treatment 41.2% (2.8% surgery, 15.8% radiotherapy and 22.6% chemotherapy), hospitalisation (43.7%) and follow‐up investigations (5%). The median costs for managing NSCLC and SCLC subgroups were A$10 675 (range A$669–612 789) and A$14 799 (range A$908–31 057), respectively. Conclusion: Hospitalisation and cancer treatment, particularly chemotherapy, accounted for the major components of direct medical costs in the management of lung cancer.

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IntroductionThis study aimed to assess psychological distress (PD) as scored by the Distress Thermometer (DT) in adult primary brain tumor patients and caregivers (CGs) in a clinic setting and ascertain if any high-risk subgroups for PD exist.Material and methodsFrom May 2012 to August 2013, n = 96 patients and n = 32 CG underwent DT screening at diagnosis, and a differing cohort of n = 12 patients and n = 14 CGs at first recurrence. Groups were described by diagnosis (high grade, low grade, and benign) and English versus non English speaking. Those with DT score ≥4 met caseness criteria for referral to psycho-oncology services. One-way ANOVA tests were conducted to test for between-group differences where appropriate.ResultsAt diagnosis and first recurrence, 37.5 and 75.0% (respectively) of patients had DT scores above the cutoff for distress. At diagnosis, 78.1% of CGs met caseness criteria for distress. All CGs at recurrence met distress criterion. Patients with high-grade glioma had significantly higher scores than those with a benign tumor. For patients at diagnosis, non English speaking participants did not report significantly higher DT scores than English speaking participants.DiscussionPsychological distress is particularly elevated in CGs and in patients with high-grade glioma at diagnosis. Effective PD screening, triage, and referral by skilled care coordinators are vital to enable timely needs assessment, psychological support, and effective intervention.

Background Temozolomide offers minimal benefit in patients with glioblastoma with unmethylated O 6-methylguanine-DNA methyltransferase (MGMT) promoter status, hence the need for novel therapies. This study evaluated whether veliparib, a brain-penetrant poly ADP-ribose polymerase (PARP) inhibitor, acts synergistically with radiation and temozolomide. Methods VERTU was a multicenter 2:1 randomized phase II trial in patients with newly diagnosed glioblastoma and MGMT-unmethylated promotor status. The experimental arm consisted of veliparib and radiotherapy, followed by adjuvant veliparib and temozolomide. The standard arm consisted of concurrent temozolomide and radiotherapy, followed by adjuvant temozolomide. The primary objective was to extend the 6-month progression-free survival (PFS-6m) in the experimental arm. Results A total of 125 participants were enrolled, with 84 in the experimental arm and 41 in the standard arm. The median age was 61 years, 70% were male, 59% had Eastern Cooperative Oncology Group (ECOG) performance status of 0, and 87% underwent macroscopic resection. PFS-6m was 46% (95% confidence interval [CI]: 36–57%) in the experimental arm and 31% (95% CI: 18–46%) in the standard arm. Median OS was 12.7 months (95% CI: 11.4–14.5 months) in the experimental arm and 12.8 months (95% CI: 9.5–15.8 months) in the standard arm. The most common grade 3–4 adverse events were thrombocytopenia and neutropenia, with no new safety signals. Conclusion The veliparib-containing regimen was feasible and well tolerated. However, there was insufficient evidence of clinical benefit in this population. Further information from correlative translational work and other trials of PARP inhibitors in glioblastoma are still awaited.