Geoff Delaney

The Role of Radiotherapy in Cancer Treatment Estimating Optimal Utilization from a Review of Evidence-Based Clinical Guidelines

Radiotherapy utilization rates for cancer vary widely internationally. It has previously been suggested that approximately 50% of all cancer patients should receive radiation. However, this estimate was not evidence-based. The aim of this study was to estimate the ideal proportion of new cases of cancer that should receive radiotherapy at least once during the course of their illness based on the best available evidence. An optimal radiotherapy utilization tree was constructed for each cancer based upon indications for radiotherapy taken from evidence-based treatment guidelines. The proportion of patients with clinical attributes that indicated a possible benefit from radiotherapy was obtained by adding epidemiologic data to the radiotherapy utilization tree. The optimal proportion of patients with cancer that should receive radiotherapy was then calculated using TreeAge (TreeAge Software, Williamstown, MA) software. Sensitivity analyses using univariate analysis and Monte Carlo simulations were performed. The proportion of patients with cancer in whom external beam radiotherapy is indicated according to the best available evidence was calculated to be 52%. Monte Carlo analysis indicated that the 95% confidence limits were from 51.7% to 53.1%. The tightness of the confidence interval suggests that the overall estimate is robust. Comparison with actual radiotherapy utilization data suggests a shortfall in actual radiotherapy delivery. This methodology allows comparison of optimal rates with actual rates to identify areas where improvements in the evidence-based use of radiotherapy can be made. It provides valuable data for radiotherapy service planning. Actual rates need to be addressed to ensure better radiotherapy utilization. Cancer 2005.

Prediction of Local Recurrence, Distant Metastases, and Death After Breast-Conserving Therapy in Early-Stage Invasive Breast Cancer Using a Five-Biomarker Panel

PURPOSE To determine the clinical utility of intrinsic molecular phenotype after breast-conserving therapy (BCT) with lumpectomy and whole-breast irradiation with or without a cavity boost. PATIENTS AND METHODS Four hundred ninety-eight patients with invasive breast cancer were enrolled into a randomized trial of BCT with or without a tumor bed radiation boost. Tumors were classified by intrinsic molecular phenotype as luminal A or B, HER-2, basal-like, or unclassified using a five-biomarker panel: estrogen receptor, progesterone receptor, HER-2, CK5/6, and epidermal growth factor receptor. Kaplan-Meier and Cox proportional hazards methodology were used to ascertain relationships to ipsilateral breast tumor recurrence (IBTR), locoregional recurrence (LRR), distant disease-free survival (DDFS), and death from breast cancer. RESULTS Median follow-up was 84 months. Three hundred ninety-four patients were classified as luminal A, 23 were luminal B, 52 were basal, 13 were HER-2, and 16 were unclassified. There were 24 IBTR (4.8%), 35 LRR (7%), 47 distant metastases (9.4%), and 37 breast cancer deaths (7.4%). The overall 5-year disease-free rates for the whole cohort were: IBTR 97.4%, LRR 95.6%, DDFS 92.9%, and breast cancer-specific death 96.3%. A significant difference was observed for survival between subtypes for LRR (P = .012), DDFS (P = .0035), and breast cancer-specific death (P = .0482), but not for IBTR (P = .346). CONCLUSION The 5-year and 10-year survival rates varied according to molecular subtype. Although this approach provides additional information to predict time to IBTR, LRR, DDFS, and death from breast cancer, its predictive power is less than that of traditional pathologic indices. This information may be useful in discussing outcomes and planning management with patients after BCT.

Estimating the demand for radiotherapy from the evidence: A review of changes from 2003 to 2012

BACKGROUND AND PURPOSE In 2003 we estimated that 52.3% of new cases of cancer in Australia had an indication for external beam radiotherapy at least once at some time during the course of their illness. This update reviews the contemporary evidence to define the optimal proportion of new cancers that would benefit from radiotherapy as part of their treatment and estimates the changes to the optimal radiotherapy utilisation rate from 2003 to 2012. MATERIALS AND METHODS National and international guidelines were reviewed for external beam radiotherapy indications in the management of cancers. Epidemiological data on the proportion of new cases of cancer with each indication for radiotherapy were identified. Indications and epidemiological data were merged to develop an optimal radiotherapy utilisation tree. Univariate and Monte Carlo simulations were used in sensitivity analysis. RESULTS The overall optimal radiotherapy utilisation rate (external beam radiotherapy) for all registered cancers in Australia changed from 52.3% in 2003 to 48.3% in 2012. Overall 8.9% of all cancer patients in Australia have at least one indication for concurrent chemo-radiotherapy during the course of their illness. CONCLUSIONS The reduction in the radiotherapy utilisation rate was due to changes in epidemiological data, changes to radiotherapy indications and refinements of the model structure.

Estimation of an optimal radiotherapy utilization rate for melanoma: a review of the evidence.

Radiotherapy utilization rates for breast carcinoma vary widely, both within and between countries. Current estimates of the proportion of patients with carcinoma who optimally should receive radiotherapy are based either on expert opinion or on the measurement of actual utilization rates, and not on the best scientific evidence.

Do variations in hospital mortality patterns after weekend admission reflect reduced quality of care or different patient cohorts? A population-based study

Background Proposed causes for increased mortality following weekend admission (the ‘weekend effect’) include poorer quality of care and sicker patients. The aim of this study was to analyse the 7 days post-admission time patterns of excess mortality following weekend admission to identify whether distinct patterns exist for patients depending upon the relative contribution of poorer quality of care (care effect) or a case selection bias for patients presenting on weekends (patient effect). Methods Emergency department admissions to all 501 hospitals in New South Wales, Australia, between 2000 and 2007 were linked to the Death Registry and analysed. There were a total of 3 381 962 admissions for 539 122 patients and 64 789 deaths at 1 week after admission. We computed excess mortality risk curves for weekend over weekday admissions, adjusting for age, sex, comorbidity (Charlson index) and diagnostic group. Results Weekends accounted for 27% of all admissions (917 257/3 381 962) and 28% of deaths (18 282/64 789). Sixteen of 430 diagnosis groups had a significantly increased risk of death following weekend admission. They accounted for 40% of all deaths, and demonstrated different temporal excess mortality risk patterns: early care effect (cardiac arrest); care effect washout (eg, pulmonary embolism); patient effect (eg, cancer admissions) and mixed (eg, stroke). Conclusions The excess mortality patterns of the weekend effect vary widely for different diagnostic groups. Recognising these different patterns should help identify at-risk diagnoses where quality of care can be improved in order to minimise the excess mortality associated with weekend admission.

Gaps in Optimal Care for Lung Cancer

Purpose: Lung cancer is the leading cause of cancer death in Australia, but little is known about how Australian patients with this disease are managed. Methods: Lung cancer patients diagnosed from November 1, 2001 to December 31, 2002 were identified through the population-based New South Wales Central Cancer Registry. Information was collected on diagnosis, staging, referrals, and treatment. Cross-tabulations and logistic regression examined factors related to not receiving cancer-specific therapy. Results: There were 2931 potentially eligible patients registered by the Central Cancer Registry and completed questionnaires were obtained for 1812 patients (62%); median age 71 years and 66% men. The pathology was non-small cell in 71%, small cell in 15% and not confirmed in 13% of patients. Eleven percent of patients did not see a lung cancer specialist and 33% received no cancer-specific therapy after initial diagnosis. Treatment utilization rates were 17% for surgery, 39% for radiotherapy, and 30% for chemotherapy. Factors significantly associated with having no cancer-specific therapy included female gender, older age, weight loss, poorer performance status, advanced or unknown disease stage, and consultation with a low patient volume lung cancer specialist or a non-lung cancer specialist. The median survival was 172 days and 2-year crude survival was 17%. Conclusions: Treatment patterns were in broad concordance with present national guidelines. Nevertheless, a significant proportion of lung cancer patients did not receive cancer-specific therapy. Treatment decisions should be multidisciplinary and decision-makers should include experienced lung cancer specialists.

The Potential for an Enhanced Role for MRI in Radiation-Therapy Treatment Planning

The exquisite soft-tissue contrast of magnetic resonance imaging (MRI) has meant that the technique is having an increasing role in contouring the gross tumor volume (GTV) and organs at risk (OAR) in radiation therapy treatment planning systems (TPS). MRI-planning scans from diagnostic MRI scanners are currently incorporated into the planning process by being registered to CT data. The soft-tissue data from the MRI provides target outline guidance and the CT provides a solid geometric and electron density map for accurate dose calculation on the TPS computer. There is increasing interest in MRI machine placement in radiotherapy clinics as an adjunct to CT simulators. Most vendors now offer 70 cm bores with flat couch inserts and specialised RF coil designs. We would refer to these devices as MR-simulators. There is also research into the future application of MR-simulators independent of CT and as in-room image-guidance devices. It is within the background of this increased interest in the utility of MRI in radiotherapy treatment planning that this paper is couched. The paper outlines publications that deal with standard MRI sequences used in current clinical practice. It then discusses the potential for using processed functional diffusion maps (fDM) derived from diffusion weighted image sequences in tracking tumor activity and tumor recurrence. Next, this paper reviews publications that describe the use of MRI in patient-management applications that may, in turn, be relevant to radiotherapy treatment planning. The review briefly discusses the concepts behind functional techniques such as dynamic contrast enhanced (DCE), diffusion-weighted (DW) MRI sequences and magnetic resonance spectroscopic imaging (MRSI). Significant applications of MR are discussed in terms of the following treatment sites: brain, head and neck, breast, lung, prostate and cervix. While not yet routine, the use of apparent diffusion coefficient (ADC) map analysis indicates an exciting future application for functional MRI. Although DW-MRI has not yet been routinely used in boost adaptive techniques, it is being assessed in cohort studies for sub-volume boosting in prostate tumors.

The effect of oral sucralfate on the acute proctitis associated with prostate radiotherapy: a double-blind, randomized trial.

PURPOSE Acute rectal complications occur in the majority of patients receiving external-beam radiotherapy for carcinoma of the prostate. Sucralfate has been proposed to reduce radiation-induced mucosal injury by forming a protective barrier on ulcer bases, binding local growth factors, and stimulating angiogenesis. However, there is conflicting clinical evidence as to whether sucralfate, taken prophylactically during radiotherapy, can ameliorate the symptoms of acute radiation proctitis. METHODS AND MATERIALS A double-blind randomized trial was conducted at four Radiation Oncology Departments in Sydney, Australia, between February 1995 and June 1997. A total of 338 patients with clinically localized prostate cancer receiving small volume radiotherapy, of whom 335 were evaluable, were randomized to receive either 3 g of oral sucralfate suspension or placebo twice a day during radiotherapy. Patients kept a daily record of their bowel symptoms and were graded according to the RTOG/EORTC acute toxicity criteria. RESULTS One hundred sixty-four patients received sucralfate and 171 received placebo. Both groups were well balanced with regard to patient, tumor, treatment factors, and baseline symptoms, except that the placebo group had a significantly more liquid baseline stool consistency score (p = 0.004). Patients kept a daily diary of symptoms during radiotherapy. After adjusting for baseline values, there was no significant difference between the two groups with regard to stool frequency (p = 0.41), consistency (p = 0.20), flatus (p = 0.25), mucus (p = 0.54), and pain (p = 0.73). However, there was more bleeding in the sucralfate group, with 64% of patients noticing rectal bleeding, compared with 47% in the placebo group (p = 0.001). There was no significant difference between the two groups with respect to RTOG/EORTC acute toxicity (p = 0.88; sucralfate 13%, 44%, 43% and placebo 15%, 44%, 40% for grade 0, 1, and 2, respectively). CONCLUSION This study suggests that oral sucralfate taken prophylactically during radiotherapy does not ameliorate the symptoms of acute radiation proctitis and may increase acute bleeding. The cause of the increased bleeding in the sucralfate group is unclear. As the pathogenesis of acute and late reactions are different, late follow-up, which includes sigmoidoscopic evaluation, is currently being performed on this cohort of patients.

Why Do Some Lung Cancer Patients Receive No Anticancer Treatment

Introduction: A significant proportion of lung cancer patients receive no anticancer treatment. This varies from 19% in USA, 33% in Australia, 37% in Scotland, and 50% in Ireland. The aim of this study was to identify the reasons behind this. Methods: The Lung Cancer Multidisciplinary Meeting (MDM) in South-West Sydney prospectively collects data on all patients presented. All new lung cancer patients presented between December 1, 2005, and December 31, 2007, were reviewed. Patients were assigned optimal treatment based on evidence-based guidelines. Those patients in whom guidelines recommended no treatment (GNT) were compared with those whom the MDM recommended no treatment (MNT) and with those who actually received no treatment (ANT). Results: There were 335 patients with a median age of 69 years. A total of 82% had non-small cell lung cancer, 14% had small cell lung cancer, and 4% had no pathologic diagnosis. Eighty-five percent had locally advanced or metastatic disease. GNT was recommended in 4% (n = 13), MNT in 10% (n = 32) but ANT comprised 20% (n = 66). The differences between GNT and MNT were mainly due to patient comorbidities and clinician decision, but the differences between MNT and ANT were due to patient preference and declining performance status. In multivariate analysis, older age, poorer Eastern Cooperative Oncology Group status, non-small cell lung cancer, and non-English language predicted for ANT. Conclusions: The proportion of patients with lung cancer receiving no treatment is greater than that predicted by guidelines or recommended by the MDM but lower than that described in population-based studies suggesting that MDMs can improve treatment utilization in lung cancer.

Do multidisciplinary meetings follow guideline-based care?

PURPOSE Multidisciplinary meetings (MDMs) are increasingly being mandated as essential to oncology practice. However, there is a paucity of data on their effectiveness. The aim of this study was to assess whether MDM recommendations were concordant with guidelines in the treatment of lung cancer. PATIENTS AND METHODS The Lung Cancer Multidisciplinary Meeting in South West Sydney, Australia, prospectively collects data on all patients whose cases have been presented. New patients with lung cancer who presented between December 1, 2005, and December 31, 2007, were reviewed. Patients were assigned to treatment on the basis of evidence-based guidelines according to pathology, stage, and Eastern Cooperative Oncology Group (ECOG) performance status. MDM recommendations were compared with guideline treatment, and reasons for discrepancy were noted. RESULTS There were 335 patients with a median age of 69 years. Of these, 82% had non-small-cell lung cancer (NSCLC), 14% had small-cell lung cancer, and 4% had no pathologic diagnosis. Eighty-four percent had locally advanced or metastatic disease. Concordance of MDM recommendations with guideline treatment existed in 29 (58%) of 50 cases for surgery, 201 (88%) of 228 cases for radiotherapy, and 200 (77%) of 260 cases for chemotherapy. Overall concordance with guideline treatment was 71% (239 of 335 cases). On multivariate analysis, age greater than 70 years, ECOG performance status of 2 or higher, and stage III NSCLC were associated with the MDM not recommending guideline treatment. The primary reasons for this were physician decision (39%), comorbidity (25%), and technical factors (22%). CONCLUSION MDM recommendations were largely concordant with guidelines. Physician discretion in not recommending guideline treatment was most often exercised in older patients and those with borderline performance status. Individual factors that may preclude guideline treatment cannot be accounted for by guidelines.