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Assessment of neurocognitive function (NCF) is important in brain tumor clinical trials, however there are varying methodologies available. We used the Cogstate computerized NCF testing battery and the mini-mental state examination (MMSE) to prospectively assess cognition in adult patients with recurrent glioblastoma (GBM) enrolled in the CABARET randomized phase II clinical trial of bevacizumab versus bevacizumab plus carboplatin chemotherapy. We determined completion rates; compared NCF results between trial arms; and assessed baseline NCF as a predictor of survival outcome. 93 of 103 eligible patients completed baseline Cogstate NCF testing. Completion rates were between 60 and 100% across each timepoint, and 38% at disease progression. There was no evidence of difference between arms in time to deterioration in NCF using either test. Prior to disease progression, deterioration on the Cogstate tests was substantially more common (90%) than deterioration on the MMSE (37%), and decline in the Cogstate composite score within the first 8 weeks was associated with shorter overall survival. This testing methodology may be useful when determining net clinical benefit for therapies in patients with recurrent GBM.

BACKGROUND: Multiple meta-analyses have demonstrated that routine surveillance following colorectal cancer surgery improves survival outcomes. There is limited data on how recurrence patterns and post-recurrence outcomes vary by individual tumor stage. METHODS: Using a multi-site community cohort study, we examined the potential impact of primary tumor stage on the sites of recurrence, management of recurrent disease with curative intent, and post-resection survival. We also explored changes over time. RESULTS: Of 4257 new colon cancers diagnosed 2001 through 2016, 789 (21.1%) had stage I, 1584 (42.4%) had stage II, and 1360 (36.4%) had stage III colon cancer. For consecutive 5-year periods (2001-2005, 2006-2010, 2011-2016), recurrence rates have declined (23.4 vs. 17.1 vs. 13.6%, p

BACKGROUND: Metastatic colorectal cancer (mCRC) patients with a right-sided primary (RC) have an inferior survival to mCRC arising from a left-sided primary (LC). Previous analyses have suggested multiple factors contribute. METHODS: The Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) Registry prospectively captured data on consecutive mCRC patients. RC were defined as tumors proximal to the splenic flexure; LC were those at and distal to the splenic flexure and included rectal cancers. Patient, tumor, treatment, and survival data were analyzed stratified by side. RESULTS: Of 2306 patients enrolled from July 2009-March 2018, 747 (32%) had an RC. Patients with RC were older, more likely to be female and have a Charlson score ≥3. RC were more frequently BRAF mutated, deficient in mismatch repair, associated with peritoneal metastases, and less likely to receive chemotherapy. Progression-free survival on first-line systemic therapy was inferior for RC patients (8.1 vs. 10.8 months, hazard ratio [HR] for progression in RC 1.38, P

Background In patients with resectable colorectal liver metastases (CRLM), the role of pre- and postoperative systemic therapy continues to be debated. Previous studies have shown that circulating tumor DNA (ctDNA) analysis, as a marker of minimal residual disease, is a powerful prognostic factor in patients with nonmetastatic colorectal cancer (CRC). Serial analysis of ctDNA in patients with resectable CRLM could inform the optimal use of perioperative chemotherapy. Here, we performed a validation study to confirm the prognostic impact of postoperative ctDNA in resectable CRLM observed in a previous discovery study. Methods and findings We prospectively collected plasma samples from patients with resectable CRLM, including presurgical and postsurgical samples, serial samples during any pre- or postoperative chemotherapy, and serial samples in follow-up. Via targeted sequencing of 15 genes commonly mutated in CRC, we identified at least 1 somatic mutation in each patient’s tumor. We then designed a personalized assay to assess 1 mutation in plasma samples using the Safe-SeqS assay. A total of 380 plasma samples from 54 patients recruited from July 2011 to Dec 2014 were included in our analysis. Twenty-three (43%) patients received neoadjuvant chemotherapy, and 42 patients (78%) received adjuvant chemotherapy after surgery. Median follow-up was 51 months (interquartile range, 31 to 60 months). At least 1 somatic mutation was identified in all patients’ tumor tissue. ctDNA was detectable in 46/54 (85%) patients prior to any treatment and 12/49 (24%) patients after surgery. There was a median 40.93-fold (19.10 to 87.73, P < 0.001) decrease in ctDNA mutant allele fraction with neoadjuvant chemotherapy, but ctDNA clearance during neoadjuvant chemotherapy was not associated with a better recurrence-free survival (RFS). Patients with detectable postoperative ctDNA experienced a significantly lower RFS (HR 6.3; 95% CI 2.58 to 15.2; P < 0.001) and overall survival (HR 4.2; 95% CI 1.5 to 11.8; P < 0.001) compared to patients with undetectable ctDNA. For the 11 patients with detectable postoperative ctDNA who had serial ctDNA sampling during adjuvant chemotherapy, ctDNA clearance was observed in 3 patients, 2 of whom remained disease-free. All 8 patients with persistently detectable ctDNA after adjuvant chemotherapy have recurred. End-of-treatment (surgery +/− adjuvant chemotherapy) ctDNA detection was associated with a 5-year RFS of 0% compared to 75.6% for patients with an undetectable end-of-treatment ctDNA (HR 14.9; 95% CI 4.94 to 44.7; P < 0.001). Key limitations of the study include the small sample size and the potential for false-positive findings with multiple hypothesis testing. Conclusions We confirmed the prognostic impact of postsurgery and posttreatment ctDNA in patients with resected CRLM. The potential utility of serial ctDNA analysis during adjuvant chemotherapy as an early marker of treatment efficacy was also demonstrated. Further studies are required to define how to optimally integrate ctDNA analyses into decision-making regarding the use and timing of adjuvant therapy for resectable CRLM. Trial registration ACTRN12612000345886., Author summary Why was this study done? Recurrence risk remains high in patients who underwent curative-intent surgical resection of colorectal cancer liver metastases (CRLM), with limited additional benefit from pre- or postoperative chemotherapy. There is currently no validated biomarker of recurrence for resected CRLM that could help guide the use of chemotherapy for the individual patient. Circulating tumor DNA (ctDNA), representing DNA shed from tumor cells into the circulation, is a versatile blood-based biomarker that can provide real-time assessment of cancer burden. It has been shown in a previous small study of 18 patients that ctDNA detection after surgery for CRLM is highly predictive of eventual cancer relapse. What did the researchers do and find? We performed a larger study involving 54 patients with resectable CRLM to confirm the ability of postoperative ctDNA to detect microscopic residual disease and predict relapse. We also analysed serial ctDNA during and after chemotherapy. ctDNA was detected in 24% of patients immediately after surgery, and these patients had a very high recurrence risk of 83% compared to only 31% in those with undetectable ctDNA after surgery. All patients with detectable postoperative ctDNA who failed to clear their ctDNA following adjuvant chemotherapy experienced recurrence, while 67% of patients whose ctDNA became undetectable after chemotherapy remained disease-free. What do these findings mean? ctDNA detection after surgery or after completion of adjuvant chemotherapy is associated with a very high risk of recurrence and death in patients with resectable CRLM; ctDNA dynamics before and after adjuvant chemotherapy reflected adjuvant treatment efficacy. Future studies should aim to assess how best to incorporate ctDNA testing into clinical practice to guide adjuvant treatment decision.

Multiple studies have defined the prognostic and potential predictive significance of the primary tumor side in metastatic colorectal cancer (CRC). However, the currently available data for early-stage disease are limited and inconsistent.We explored the clinicopathologic, treatment, and outcome data from a multisite Australian CRC registry from 2003 to 2016. Tumors at and distal to the splenic flexure were considered a left primary (LP).For the 6547 patients identified, the median age at diagnosis was 69 years, 55% were men, and most (63%) had a LP. Comparing the outcomes for right primary (RP) versus LP, time-to-recurrence was similar for stage I and III disease, but longer for those with a stage II RP (hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.52-0.90; P .01). Adjuvant chemotherapy provided a consistent benefit in stage III disease, regardless of the tumor side. Overall survival (OS) was similar for those with stage I and II disease between LP and RP patients; however, those with stage III RP disease had poorer OS (HR, 1.30; 95% CI, 1.04-1.62; P .05) and cancer-specific survival (HR, 1.55; 95% CI, 1.19-2.03; P .01). Patients with stage IV RP, whether de novo metastatic (HR, 1.15; 95% CI, 0.95-1.39) or relapsed post-early-stage disease (HR, 1.35; 95% CI, 1.11-1.65; P .01), had poorer OS.In early-stage CRC, the association of tumor side and effect on the time-to-recurrence and OS varies by stage. In stage III patients with an RP, poorer OS and cancer-specific survival outcomes are, in part, driven by inferior survival after recurrence, and tumor side did not influence adjuvant chemotherapy benefit.

The classification of central nervous system tumours has more recently been shaped by a focus on molecular pathology rather than histopathology. We re-classified 82 glial tumours according to the molecular-genetic criteria of the 2016 revision of the World Health Organization (WHO) Classification of Tumours of the Central Nervous System. Initial diagnoses and grading were based on the morphological criteria of the 2007 WHO scheme. Because of the impression of an oligodendroglial component on initial histological assessment, each tumour was tested for co-deletion of chromosomes 1p and 19q and mutations of isocitrate dehydrogenase (IDH-1 and 2) genes. Additionally, expression of proteins encoded by alpha-thalassemia X-linked mental retardation (ATRX) and TP53 genes was assessed by immunohistochemistry. We found that all but two tumours could be assigned to a specific category in the 2016 revision. The most common change in diagnosis was from oligoastrocytoma to specifically astrocytoma or oligodendroglioma. Analysis of progression free survival (PFS) for WHO grade II and III tumours showed that the objective criteria of the 2016 revision separated diffuse gliomas into three distinct molecular categories: chromosome 1p/19q co-deleted/IDH mutant, intact 1p/19q/IDH mutant and IDH wild type. No significant difference in PFS was found when comparing IDH mutant grade II and III tumours suggesting that IDH status is more informative than tumour grade. The segregation into distinct molecular sub-types that is achieved by the 2016 revision provides an objective evidence base for managing patients with grade II and III diffuse gliomas based on prognosis.

BACKGROUND Bevacizumab has been associated with prolonged progression-free survival for patients with recurrent glioblastoma; however, not all derive a benefit. An early indicator of efficacy or futility may allow early discontinuation for nonresponders. This study prospectively assessed the role of early magnetic resonance imaging (eMRI) and its correlation with subsequent routine magnetic resonance imaging (MRI) results and survival. METHODS Patients were part of a randomized phase 2 clinical trial (CABARET) comparing bevacizumab with bevacizumab plus carboplatin for recurrent glioblastoma. eMRI was conducted after 4 weeks in the trial (after 2 treatments with bevacizumab [10 mg/kg every 2 weeks]). The results were compared with the results of the subsequent 8-week MRI standard. RESULTS For 119 of 122 patients, eMRI was available, and 111 had subsequent MRI for comparison. Thirty-six (30%) had an early radiological response, and 17 (14%) had progressive disease. The concordance between eMRI and 8-week MRI was moderate (κ = 0.56), with most providing the same result (n = 79 [71%]). There was strong evidence that progression-free survival and overall survival were predicted by the eMRI response (both P values < .001). The median survival was 8.6 months for an eMRI response, 6.6 months for stable disease, and 3.7 months for progressive disease; the hazard ratio (progressive disease vs stable disease) was 3.4 (95% confidence interval, 1.9-6.0). Landmark analyses showed that eMRI progression was a strong predictor of mortality independent of other potential baseline predictors. CONCLUSIONS In this study, early progression on MRI appears to be a robust marker of a poor prognosis for patients on bevacizumab. Cancer 2017. © 2017 American Cancer Society.

Background Emerging evidence on the optimal use of chemotherapy and biologics in patients with metastatic colorectal cancer should impact management in routine care. Recent studies have demonstrated benefits for initial triplet chemotherapy (5-fluorouracil, oxaliplatin and irinotecan, FOLFOXIRI) and for initial treatment with an epidermal growth factor receptor inhibitor (EGFRi) in patients with a RAS wild-type tumour and a left-sided primary tumour. Aim To explore evolving pattern of metastatic colorectal cancer care over time in Australia. Methods We analysed data from the Treatment of Recurrent and Advanced Colorectal Cancer registry. Results From July 2009 to December 2017, 2552 metastatic colorectal cancer patients were entered into the Treatment of Recurrent and Advanced Colorectal Cancer registry. Of 1585 patients who initially underwent chemotherapy, treatment was with a doublet in 76%. FOLFOXIRI was given to 22 patients (1.4%), mostly young patients and those with potentially resectable disease. Along with first-line chemotherapy, 61% received bevacizumab, while 3.3% received an EGFRi, predominantly over the last 2 years. Within the KRAS wild-type left-sided tumour cohort, EGFRi use increased from 9% in 2015 to 37% in 2017. Across treatment sites, there was a wide variation in the utilisation of FOLFOXIRI and EGFRi therapy; bevacizumab use was more consistent. A clear impact on survival outcomes from these regimens is not evident, potentially due to multiple confounders. Conclusion Doublet chemotherapy + bevacizumab remains the dominant initial strategy, with limited uptake of triplet chemotherapy and of EGFRi. Potential explanations include uncertainty about the significance of post hoc analyses for EGFRi and concerns regarding adverse events for both strategies.

Background The true survival benefit of noncurative primary tumor resection in patients with de novo metastatic colorectal cancer (mCRC) remains uncertain. The present study examined the effect of primary tumor resection on systemic inflammation and survival in patients with mCRC. Materials and Methods Consecutive patients with de novo mCRC who had undergone primary tumor resection were identified from a prospective database. Patients were excluded if they had undergone resection of metastases, had undergone delayed primary resection, or if blood samples were unavailable. The neutrophil/lymphocyte ratio (NLR) was used as a biomarker of systemic inflammation. Overall survival (OS) was compared between patient groups according to the pre- and postprimary resection NLR. The associations between the reversal of an elevated NLR and primary tumor bulk or performance status were explored. Results A total of 145 eligible patients were identified from the database, with a median age of 70 years. The baseline NLR was elevated (> 5) in 65 patients, 36 (55%) of whom had a low NLR after surgery. The reversal of an elevated NLR was associated with significantly improved OS (hazard ratio, 0.53; P = .017). A similar benefit was seen after excluding patients undergoing emergency primary resection. NLR reversal was more frequent in patients with larger primary tumors or good performance status. Conclusion The present study is the first to demonstrate a relationship between the reversal of a systemic inflammatory response and the improved survival after primary resection in those with mCRC. A greater effect was seen in patients with large primary tumors. If validated, these observations could guide clinical decision-making in patients with mCRC at presentation.

Objectives The elderly accounts for a large proportion of patients with metastatic colorectal cancer (mCRC). This study reviews patterns of care and outcomes for elderly patients with mCRC in the community setting. Materials and Methods Elderly patients (≥ 65 years) with mCRC on the TRACC (Treatment of Recurrent and Advanced Colorectal Cancer) registry were identified. Treatment, bevacizumab-related adverse events, and overall survival (OS) were analysed by age cohorts, comparing those aged 65–74 vs. 75–84 vs. ≥ 85 years and correlated with potential prognostic factors. Factors affecting chemotherapy and bevacizumab administration were analysed using logistic regression analysis. Results Of 1439 patients, 363, 352, and 106 were aged 65–74, 75–84, and ≥ 85 years, respectively. 584 (71%) patients received first-line chemotherapy, with chemotherapy use declining with advancing age (84%, 69%, and 34% in 65–74-, 75–84- and ≥ 85-year-olds, respectively). Seven (10%) patients aged ≥ 85 years were not treated with chemotherapy on the basis of age alone. Only 10 of 36 very elderly patients who received chemotherapy also received bevacizumab. Factors affecting bevacizumab administration included age, treatment location, and comorbidities. There was no impact of age on bevacizumab-related adverse events. Resection of metastatic disease occurred in 173 (21%) patients overall, with rates declining with age (26% vs. 21% vs. 6%). Conclusion Chemotherapy usage and resection of metastatic disease decline with advancing age. A minority of patients are not treated with systemic therapy due to advanced age alone. Our cohort suggests underutilisation of bevacizumab in older patients, but where given, toxicity rates did not increase with age.

Aims Considerable progress in cancer treatment is leading to better outcomes, but the cost of therapy is placing increasing pressure on the health system. Understanding the real-world cost of therapies for each stage will become increasingly important in informing treatment selection and health policy. Methods To explore the cost of treating colorectal cancer in the modern era, data were entered onto a prospective database at four hospitals. We estimated the impact of bevacizumab by using data from July 2009, and projected the likely impact of the recent listing of cetuximab. The utility of these data for estimating the cost-effectiveness of treatment was explored. Results Cancer stage and age at diagnosis were major determinants of treatment received and the associated cost. The cost of early stage disease has not substantially changed whereas therapies such as oxaliplatin and irinotecan were significant contributors to substantial increases in stage IV disease, now $71 156 per patient. Bevacizumab has added at least $10 247 per patient and we estimate that cetuximab will add a further $12 022. An exploratory analysis of the cost-effectiveness of oxaliplatin for adjuvant therapy of stage III colon cancer suggests that this is well within the accepted range. Conclusion These data suggest that recent progress in the treatment of later stages of colorectal cancer is being achieved at significant financial cost. The increased costs of managing later stages of disease make an investment in prevention and early detection ever more attractive.

Aim As multiple new agents have been added to the treatment options for patients with metastatic colorectal cancer, survival outcomes in clinical trials have continued to improve. Similarly, improved outcomes in routine clinical care would be anticipated, but have yet to be demonstrated. Here, we aim to explore whether survival gains demonstrated in clinical trials are reproducible in routine practice, and whether factors beyond new therapies may be contributing to improved outcomes. Methods Comparison of comprehensive treatment and outcome data for consecutive patients diagnosed in 2003–2006 versus 2007–2010 at four specialist hospitals in Australia. Results Data were available on 965 patients; median age 66.1 years (range 19–93), 572 (59%) were male. For the latter time period, there was an increase in patients receiving any treatment (74% vs 66%, P = 0.014), initial combination chemotherapy (57% vs 44%, P

BACKGROUND AND PURPOSE: Histologic grading of intracranial astrocytomas is affected by sampling error and substantial inter- and intraobserver variability. We proposed that incorporating MR imaging into grading will predict patient survival more accurately than histopathology alone. MATERIALS AND METHODS: Patients with a new diagnosis of World Health Organization grades II–IV astrocytoma or mixed oligoastrocytoma diagnosed between September 2007 and December 2010 were identified. Two hundred forty-five patients met the inclusion criteria. Preoperative MRIs were independently reviewed by 2 readers blinded to the histologic grade, and an MR imaging grade was given. The MR imaging and histopathologic grades were compared with patient survival. RESULTS: Patients with grade II or III astrocytomas on histology but evidence of necrosis on MR imaging (consistent with a grade IV tumor) had significantly worse survival than patients with the same histology but no evidence of necrosis on MR imaging ( P = .002 for grade II histology and P = .029 for grade III). Their survival was not significantly different from that in patients with grade IV tumors on histology ( P = .164 and P = .385, respectively); this outcome suggests that all or most are likely to have truly been grade IV tumors. MR imaging evidence of necrosis was less frequent in grade II and III oligoastrocytomas, preventing adequate subgroup analysis. CONCLUSIONS: MR imaging can improve grading of intracranial astrocytomas by identifying patients suspected of being undergraded by histology, with high interobserver agreement. This finding has the potential to optimize patient management, for example, by encouraging more aggressive treatment earlier in the patient9s course.

In recurrent glioblastoma, health-related quality of life (HRQL) is a crucial trial endpoint. We examined HRQL outcomes as a secondary endpoint for patients in the CABARET randomized phase 2 trial. 122 patients were randomly allocated to bevacizumab monotherapy or bevacizumab plus carboplatin. We calculated change scores from baseline for each HRQL measure on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and the Brain Cancer Module (QLQ-BN20), together with time to deterioration in HRQL, and the proportion of participants with clinically meaningful improvements in specific disease-related symptoms. At baseline, 117 of 122 randomized patients (96%) attempted questionnaires. Questionnaire participation rates were >90% for patients continuing on treatment, however at the end-of-treatment visit only 72 (64% of eligible participants) returned a form. There were no differences between arms in change scores over the treatment period. Time to ≥10 point deterioration in scores from baseline was also similar between arms. HRQL deterioration occurred largely before progression for the domains tested, but scores in HRQL domains specifically relevant to symptoms of recurrent glioblastoma also improved for about 50% of patients with symptoms at baseline. Neither detrimental nor beneficial effects on HRQL were seen with carboplatin added to bevacizumab, with a proportion of patients on both arms experiencing symptomatic benefit. Given the reduced questionnaire completion at end of treatment, time to HRQL deterioration is a feasible and robust clinical trial endpoint in this patient population. Clinical trials registration number: ACTRN12610000915055.

3609 Background: Multiple meta-analyses have demonstrated that routine surveillance following curative intent colorectal cancer surgery improves overall survival. This benefit is largely driven by early detection and curative intent resection of oligometastatic disease. Intuitively, any surveillance benefit should be proportional to recurrence risk, leading some to question the value of surveillance for stage I patients where recurrence rates are low. However, the survival benefit of surveillance has not previously been reported by stage. Methods: We explored data from a multi-site cohort of colorectal cancer patients (pts) diagnosed from 1 January 2001 to 31 December 2016. Pts were followed according to standard protocols with a standardized comprehensive outcome data captured prospectively. Pts with a rectal primary or metastatic disease at presentation were excluded from the analysis. We examined the correlation of stage at diagnosis with tumor recurrence and subsequent outcomes. Results: Of 3608 colon cancer pts, 690 (19%) had stage 1, 1580 (44%) had stage 2, and 1338 (37%) had stage 3 disease. Median follow-up was 7.8 years. Stage at diagnosis impacted recurrence rate (4% stage I vs 12% stage II vs 28% stage III, p < .0001) but not median time to recurrence. Recurrence patterns varied with stage (e.g. distant nodal disease 5% vs 7% vs 16%, p = .003; liver metastases 90% vs 53% vs 42%, p = 0.001). In pts with recurrence, resection of oligometastatic disease varied significantly by stage (58% vs 42% vs 30%, p < .0001) as did post-resection 5 year survival (91% vs 66% vs 43%, p < 0.001). In pts with recurrence treated with palliative intent, stage at diagnosis also impacted post-recurrence 5 year survival (11% vs 7% vs 5%, p < 0.03). Conclusions: Colon cancer stage at diagnosis substantially impacts the proportion of pts able to undergo curative intent surgery for surveillance detected recurrent disease, potentially driven by stage specific metastatic patterns. Stage at diagnosis also has a significant impact on post-resection survival outcomes potentially driven by stage specific biology. Our data indicate a far greater survival impact of surveillance for stage I colon cancer than would be anticipated based on recurrence rate alone.

623 Background: Patients with metastatic colorectal cancer (mCRC) arising from a right sided colorectal cancer (RC) have an inferior survival versus patients with a left sided colorectal cancer (LC). Previous analyses have suggested that multiple factors contribute. Methods: The Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) Registry has prospectively captured comprehensive data on consecutive mCRC patients since 2009. For this analysis LC were defined as primary tumors at or distal to the splenic flexure and included rectal cancers. We analysed patient, tumor, treatment and outcome data. Results: Of 2306 patients enrolled from July 2009–March 2018, median age 67 years (range 18–100), 1559 (67.6%) had a LC. Patients with a RC were older (median 71 vs 65 years, p < 0.001), more likely to be female (50.2% vs 36.9%, p < 0.001) and to have a Charlson score ≥ 3 (67.5% vs 54.6%, p < 0.001). More common in RC, where tested, were BRAF mutations (22.3% vs 7.2%, p < 0.001) and deficient mismatch repair (6.4% vs 1.5%, p < 0.001), but not RAS mutations. Peritoneal metastases were more frequent in RC (29.7% vs 14.9%, p < 0.001). RC patients were more likely to have their primary tumor resected (77.9% vs 70.6%, p < 0.001) and to receive less first-line chemotherapy (72.2% vs 78.7%, p = 0.001). Progression-free survival on first-line systemic therapy was inferior for RC patients (8.1 vs 10.8 months, HR 1.38, p < 0.001). Median overall survival (OS) for all RC patients was inferior (19.6 vs 27.5 months, HR 1.44, p < 0.001). Primary side remained a significant factor for OS in multivariate analysis. Conclusions: Our data confirms the poor prognosis associated with RC, contributed to by multiple factors. However, primary side remains significant even when adjusting for these, indicating the existence of further as yet undefined differences. [Table: see text]

Background: The changing treatment landscape for metastatic colorectal cancer creates multiple potential treatment strategies. An Australian-centric database capturing comprehensive information across a range of treatment locations would create a valuable resource enabling multiple important research questions to be addressed. Aims: To establish a collection of a consensus dataset capturing treatment and outcomes at multiple public and private hospitals across Australia. Methods: An electronic database was developed by a panel of clinicians, to capture an agreed dataset for patients with newly diagnosed metastatic colorectal cancer. Of particular interest were clinician decision-making, the impact of comorbidities and the frequency of major adverse events. Results: Since July 2009, data collection has been established at six public and eight private hospitals across three Australian states and territories. Successful linkage and analysis, with support from BioGrid Australia, of selected data on the initial 864 patients demonstrates that data can be captured from diverse sites, including public and private practice, that multiple factors impact on treatment delivered and outcomes achieved and that comprehensive data on rare but important adverse events can be captured. As a clinical research tool, the project has been highly successful, generating multiple presentations at national and international conferences related to a diverse range of research questions. Conclusions: Multistate, project-specific data collection involving large numbers of patients is achievable. Providing invaluable insight into the routine clinical management of metastatic colorectal cancer in the era of targeted therapies, this also creates a significant resource for research, including many questions not being addressed by clinical trials.

Bevacizumab, an anti-angiogenic agent, is FDA-approved for use in patients with recurrent glioblastoma multiforme (rGBM). The radiologic evaluation of tumor response to bevacizumab is complex and there is no validated method of monitoring tumor vascularity during therapy. We evaluated perfusion-weighted MR imaging (PWI) in our cohort of patients enrolled in the CABARET trial, which examined the effectiveness of bevacizumab with or without carboplatin in patients with rGBM. Pre-treatment and early follow-up (4- and 8-week) PWI were used to calculate relative cerebral blood volume (rCBV) histogram statistics of the contrast-enhancing and FLAIR hyperintense tumor volumes. A novel rCBV measurement (load) was developed to estimate the total volume of perfused tumor blood vessels. Changes in all rCBV measures were examined for correlations with progression-free (PFS) and overall survival (OS). All of our 15 patients enrolled in the CABARET trial were included. Median PFS and OS were 23 and 45 weeks respectively. Kaplan-Meier analysis of pre-treatment PWI revealed an 18 week reduction in median OS in patients with high tumor rCBV (p = 0.031). Changes in rCBV measures, especially load, correlated significantly with PFS and OS at both follow-up time-points. Patients with the greatest reduction in rCBVload by 8-weeks of therapy had a significantly increased median OS (30 weeks; p = 0.013). PWI may be of significant clinical utility in managing patients with rGBM, particularly those treated with anti-angiogenic agents such as bevacizumab. These findings need to be confirmed prospectively in larger studies.

With an ever-increasing focus on personalized medicine, all factors known to affect treatment response need to be considered when defining optimal therapy for individual patients. While the prognostic impact of primary tumor site on colorectal cancer (CRC) outcomes is established, emerging data suggest potential differences in response to biologic therapies. We studied the impact of tumor site on bevacizumab efficacy in patients with metastatic CRC.We analyzed data of patients in an Australian prospective multicenter metastatic CRC (mCRC) registry who received first-line chemotherapy. Tumor site was defined as right colon, cecum to transverse; left colon, splenic flexure to rectosigmoid; and rectum. Kaplan-Meier and Cox models were used for survival analyses.Of 926 patients, 297 had right colon, 354 left colon, and 275 rectum primary disease. Median age was 68.6, 65.9, and 63.3 years, respectively (P = .001). Right colon disease was significantly associated with intraperitoneal spread (P .0001), while left colon and rectum disease preferentially metastasized to the liver and lungs, respectively (P .0001 in both settings). A total of 636 patients (68.7%) received bevacizumab. Progression-free survival was superior for bevacizumab-treated patients in all groups but appeared greatest in right colon disease (hazard ratio, 0.46; 95% confidence interval, 0.36-0.60; P ≤ .001). Overall survival was longest in patients with disease of the rectum, followed by left colon and right colon (median, 26.2, 23.6, and 18.2 months, respectively; P = .0004).Tumor site appears to be prognostic in mCRC, with rectum and right colon disease associated with the best and worst outcomes, respectively. Patients who received bevacizumab in addition to chemotherapy had superior outcomes, with the effect appearing greatest in patients with right colon disease.

Colorectal cancer is one of the most common malignancies in the Westernized world. Particularly in the setting of metastatic disease, advances in the use of biomarkers have resulted in “personalized therapy” being an aspect of routine care. However, their role is less clear-cut in the context of adjuvant treatment for early-stage colon cancer. We still largely rely on conventional TNM staging to determine prognosis and treatment options in early-stage disease. Ongoing research is elucidating alternative measures, in the form of prognostic and predictive biomarkers, which may better assist in understanding the wide spectrum of outcomes in early-stage disease; as well as the potential to select and tailor appropriate therapeutic options for an individual rather than simply treating a disease and a “cancer stage”. This review outlines key discoveries and controversies in the application of biomarkers to tailor treatment in early-stage colon cancer.

Background: Lymph node yield (LNY) is a measure of quality of care and a strong prognostic factor for outcome from colorectal cancer (CRC). The main aims of this study were to determine LNY across multiple Australian centres and the clinico-pathologic factors that influence yield. Methods: Analysis of data from prospective CRC databases at 11 Australian centres between January 1988 and May 2008 was undertaken utilizing the linkage and analysis resources of BioGrid Australia. The LNY depending on different clinico-pathologic patient characteristics was evaluated. Results: In total, 10 082 cases (54.1% men, 45.9% women) were identified. Median LNY was 12 (range 0–174). LNY increased significantly (P < 0.001) over time, from a mean of 8.5 in 1988 to 13 in 2008. LNY also varied significantly between surgical centres. Female gender, younger age, right-sided disease, higher T and N stage, specific operation types and absence of preoperative radiotherapy were all significantly associated with higher LNY. Conclusions: While varying across centres, the median LNYs in Australia are acceptable and have improved significantly over recent years. Multiple clinico-pathologic factors significantly influence the number of nodes retrieved.

Multidisciplinary Team (MDT) meetings are critical in the management of complex cancer cases. There are limited data regarding the effectiveness of neuro-oncology MDT meetings and the impact of documenting and disseminating the recommended patient management. We established a weekly neuro-oncology MDT meeting and developed a standard electronic communication process. A survey was issued to participating clinicians to assess their level of satisfaction. The survey revealed that 100% felt the meeting and its documentation was very or extremely important, and 94% (n=15) felt the meeting was effective in documentation and communication of plans. There was a mixed response regarding which patients should be discussed: 44% (n=7) thought all patients should be discussed and 56% (n=9) thought only those patients with complex management issues should be discussed. We have developed an efficient method of documenting and disseminating patient information arising from our neuro-oncology MDT meeting. Clinician satisfaction was high.

Background: Varying amounts of data related to cancer diagnosis, treatment and/or outcome are routinely collected by many disparate groups. Routinely combining data from these sources could improve data quality and utility for audit and research purposes. The aim of this study is to demonstrate the benefits of linkage between oncology databases. Methods: We examined colorectal cancer (CRC) data recorded by the Victorian Cancer Registry and two hospital clinical databases between January 2000 and December 2005. Where data were in common, the completeness and accuracy of each dataset were examined. Where content differed, the potential value of making this additional data available to the other database was examined. Results: Of the 831 cases recorded at the hospitals, 822 (98.9%) were also recorded on the cancer registry. Eight of the 913 cases (0.87%) recorded as having CRC by the registry did not have CRC. Errors in recording of tumour site and tumour or nodal stage were frequent in both databases. Metastasis stage was recorded in only 29 of 822 (3.5%) registry cases examined. Discordance for diagnosis date and death date was also frequent, although the difference was typically minor. Adding additional death data from the registry to the clinical database significantly altered stage-specific and overall survival figures. Conclusion: A multidirectional flow of data between hospital and registry databases provides multiple opportunities to improve data quality and utility. While issues around data ownership and usage need to be considered, the advantages of routine data linkage are readily apparent.

Aim: The aims of this study were to calculate theoretical cost savings of oxaliplatin dose rounding in colorectal cancer (CRC), and to assess clinician attitudes to chemotherapy dose rounding. Methods: Data were obtained from a prospective data repository (BioGrid Australia) from four hospitals regarding the use of oxaliplatin, given at a standard dose of 85 mg/m2. We examined potential cost savings for patients with a body surface area (BSA) between 1.77 m2 and 1.94 m2, resulting in a calculated dose up to 10% above 150 mg (a 100 mg and 50 mg vial). The attitudes of oncologists at these hospitals toward minor dose reductions were assessed. Results: From January 2003 to June 2008, of 676 patients with Stages III or IV CRC, 227 (33.58%) received oxaliplatin. Overall 66 patients (29%) had a calculated BSA between 1.77 m2 and 1.94 m2. The potential cost saving for these hospitals in one year, if oxaliplatin doses were rounded down to 150 mg, is $AU51 898. Extrapolated to the Australian population, estimated savings are over $AU2.5 million per year. Three of nine (33.3%) oncologists were comfortable with an initial dose reduction of up to 10% in the adjuvant disease setting, and seven of nine (77.8%) in the setting of metastatic disease. Conclusion: Minor dose reductions for CRC to accommodate vial sizes would lead to significant cost savings. Oncologists are more comfortable with minor dose reductions when treatment is given in a palliative setting.

3516Background: Adjuvant CT in stage III CC prevents recurrence by eradicating minimal residual disease (MRD) not visible on imaging. However, many patients (pts) will not have MRD and not all pts with MRD will benefit from standard CT. In this study, we determined (i) if the presence of ctDNA following surgery was predictive of recurrence following CT; (ii) if ctDNA could be used to determine the effectiveness of CT during treatment and (iii) if the presence of ctDNA following CT completion was predictive for later recurrence. Methods: Serial plasma samples from stage III CC pts planned for adjuvant CT were collected post-surgery, during CT and at treatment completion. Somatic mutations in individual tumors were identified via massively parallel sequencing of 15 genes commonly mutated in colorectal cancer. Personalized Safe-SeqS assays to quantify ctDNA in plasma samples were designed. Clinicians were blinded to ctDNA results. Results: 95 pts were enrolled from Nov-2014 to May-2017, median age was 64 yea...

Objective The optimal strategy for elective distant staging of colorectal carcinoma (CRC) has yet to be defined, with current guidelines based on small and limited series. One specific issue requiring review is the value of routine computerized tomographic (CT) chest examination. Also lacking is data on current routine clinical practice. Method A retrospective chart review of consecutive cases of elective surgery for CRC from five hospitals. Results Two hundred and fifty-seven cases were reviewed, 128 colon and 129 rectal primaries. 164 (64%) of patients overall, ranging from 45% to 88% across the individual centres, had a preoperative serum CEA level performed. CT abdomen/pelvis was performed in 222 (86%) of cases, ranging from 69% to 98% per centre. CT chest was performed in 95 (37%) of cases, 47% of rectal vs 29% of colon cancers (P = 0.004). In 17 cases (18%) CT chest examinations revealed abnormalities suspicious for metastatic disease, leading to a change in management in six (35%) of these cases. Of the 17 cases with an abnormal CT chest, in only 5 of the 14 (36%) where carcinoembryonic antigen (CEA) levels were also recorded was this increased, and in only three (21%) was this markedly (> 10 μg/l) elevated. Conclusions Substantial variability exists in the preoperative evaluation of patients with CRC. Many patients do not have a CEA and/or abdominal imaging performed. Where performed, CT chest revealed suspicious findings in a significant number of patients, the vast majority of whom had a normal or near normal CEA. Future studies are required to define optimal preoperative staging.

Few data exist regarding the use of complementary and alternative medicine (CAM) by unaffected women at high risk of breast cancer.Self-reported CAM use by women from multiple-case breast cancer families was obtained by questionnaire. Factors associated with CAM use were assessed using multiple logistic regression.Of 892 women, 55% (n=489) used CAM, 6% (n=53) specifically to prevent cancer. CAM use was independently associated with tertiary education level (OR 2.56, 95% CI 1.83-3.58, p0.001), greater physical activity (OR 1.05 per hour of physical activity/week, 95% CI 1.00-1.10, p=0.049), greater anxiety (OR 1.92, 95% CI 1.16-3.16, p=0.01), not currently smoking (OR 0.64, 95% CI 0.42-0.97, p=0.037) and lower perceived BC risk (OR 0.82 per 20 percentage points, 95% CI 0.72-0.94, p=0.005).The majority of high-risk women use CAM, but mostly for reasons other than cancer prevention. Most predictors of CAM use are consistent with the limited literature for women at high risk for cancer.

The liver is fundamentally important in drug metabolism. In oncology, the astute clinician must not only understand the meaning and limitations of commonly ordered liver biochemical tests, but also be aware of which anticancer agents might induce liver dysfunction, and of the strategies for appropriate dosing of patients with pre-existing liver dysfunction. In part I of our Review, we highlighted both the importance and inadequacies of identifying serum biochemical liver abnormalities in oncology; we also discussed a lack of routine formal investigation of liver function. We summarised chemotherapy-related hepatotoxicity and other causes of liver toxic effects in patients with cancer. Here in part II, we discuss trials that have specifically assessed chemotherapy dosing strategies in the setting of overt biochemical liver dysfunction and we note their recommendations. Furthermore, we review other assessments of liver metabolic and excretory function, particularly in the setting of chemotherapy drug handling. We discuss the potential use of these metabolic probes in practice.

The liver has a key role in the metabolism (ie, inactivation or activation) of many commonly used anticancer agents-cytotoxics or new biological agents. Therefore, assessment of liver function is a fundamental part of initial work-up and management of patients with cancer. An understanding of the meaning of conventional serum biochemical testing of liver function and status, what variables they are measuring, and usefulness for chemotherapy dosing is essential. Emerging awareness of the drawbacks of conventional serum biochemical testing and further understanding of the intricacies of liver function is leading to the development of alternative strategies for appropriate chemotherapy regimens and dosing. We present an overview of assessment of liver function and chemotherapy dosing. We consider the use of serum liver biochemical testing to predict liver function, potential causes of biochemical abnormalities in patients with cancer, and chemotherapy drugs that are associated with hepatotoxicity. Part II will overview the current knowledge surrounding chemotherapy dosing in the setting of liver dysfunction; as well as alternative tests of hepatic metabolic function that are beginning to be used as strategies for appropriate individualised chemotherapy administration.

Background: Intensive follow up after surgery for colorectal cancer is associated with a significant survival advantage and is endorsed by expert panels, but are physicians convinced of the benefit? Methods: A questionnaire was mailed to all members of the Medical Oncology Group of Australia, assessing surveillance practices after completion of adjuvant treatments. Results: Responses were obtained from 141 (55%) medical oncologists of which 121 were considered evaluable. Thirteen per cent (n = 16) routinely did not carry out follow-up investigations. Of those carrying out surveillance, 47% (n = 51) nominated identifying potentially resectable metastatic disease as prime consideration. Many (44%) were motivated by patient reassurance and expectation. Carcinoembryonic antigen levels were commonly monitored 3 monthly in years 1 (77%, n = 85) and 2 (57%, n = 63) and 6 monthly thereafter (67%, n = 74). Eighty per cent (n = 88) carried out computed tomography (CT) surveillance 1 year after surgery, 69% (n = 76) at year 2 and 55% (n = 60) at year 3. Twenty-six per cent (n = 29) continued scanning annually up to 5 years. Inclusion of CT chest was routine for 33% (n = 36) and never carried out by 11% (n = 12). Conclusion: A significant minority (13%) of oncologists carry out no follow-up investigations, despite level I evidence of a survival advantage similar to standard adjuvant therapies. Further education and study of physician attitudes and reservations to routine surveillance are required.

Breast cancer is one of the most commonly treated malignancies worldwide, but is rare in males. Less than one percent of all breast cancers occur in men, and breast cancer comprises less than one percent of all male malignancies. Thus, clinical experience in managing this condition is limited. In contrast to female breast cancer, much remains unknown about breast cancer in males. While there are similarities between the two, emerging data suggest that there are perhaps more differences than previously thought. Nevertheless, much of how males with breast cancer are managed continues to be extrapolated from randomised trials performed in females, due to lack of data in the male population alone. Another poorly understood aspect is the psychological impact experienced by male patients when diagnosed with what is generally thought of as a female malignancy. This review will discuss the known epidemiology, demographics, risk factors and genetic predispositions surrounding the development of breast cancer in males; as well as current surgical and radiotherapeutic interventional techniques. Histological profiles and subtypes as well as hormone receptor and HER-2 receptor status are also discussed, with an overview of chemotherapy and hormonal strategies in both the adjuvant and metastatic settings.

Background: The use of indwelling central venous catheters (CVC) for chemotherapy delivery is essential for people receiving therapies by protracted venous infusion and for patients with difficult venous access. Complications include infection and catheter-related thrombosis. Strategies have been suggested to prevent catheter-related thrombosis, however, there is no clear consensus on how to proceed. Guidelines recommend against the use of prophylactic anticoagulation in adult patients with solid organ malignancies and an indwelling CVC. We investigated the practice of Australian medical oncologists. Methods: A written questionnaire was mailed to all members of the Medical Oncology Group of Australia assessing practices of prophylactic anticoagulation in adult patients with solid organ malignancies and CVC. Results: Responses were obtained from 141 (55%) medical oncologists and from 40 advanced trainees. Ten percent (n = 4) of oncology trainees and 18.4% (n = 26) of medical oncologists routinely administered anticoagulants to patients with a CVC without a previous history of line-related thrombus. The most common strategy employed (73% of those using anticoagulation) was to recommend 1 mg of warfarin. Conclusions: The results demonstrate that a significant number of patients in Australia receive routine anticoagulation, the most popular strategy being the use of low-dose warfarin. Based on our results there is a clear need for further education regarding the lack of supporting data and the potential harm that may ensue.

There are few Australian data on the incidence of catheter-associated bloodstream infection (BSI) among patients in hematology-oncology units. We found an increase in catheter-associated BSI rates coincident with the introduction of a mechanical valve connector (2.6 infections vs 5.8 infections per 1,000 catheter-days; incidence rate ratio, 2.2; P = .031).

The survival impact of primary tumor resection in patients with metastatic colorectal cancer (mCRC) treated with palliative intent remains uncertain. In the absence of randomized data, the objectives of the present study were to examine the effect of primary tumor resection (PTR) and major prognostic variables on overall survival (OS) of patients with de novo mCRC.Consecutive patients from the Australian 'Treatment of Recurrent and Advanced Colorectal Cancer' registry were examined from June 2009 to March 2015. Univariate and multivariate Cox proportional hazards regression analyses were used to identify associations between multiple patient or clinical variables and OS. Patients with metachronous mCRC were excluded from the analyses.A total of 690 patients de novo and 373 metachronous mCRC patients treated with palliative intent were identified. The median follow-up period was 30 months. The median age of de novo patients was 66 years; 57% were male; 77% had an Eastern Cooperative Oncology Group performance status of 0 to 1; and 76% had a colon primary. A total of 216 de novo mCRC patients treated with palliative intent underwent PTR at diagnosis and were more likely to have a colon primary (odds ratio [OR], 15.4), a lower carcinoembryonic antigen level (OR, 2.08), and peritoneal involvement (OR, 2.58; P .001). On multivariate analysis, PTR at diagnosis in de novo patients was not associated with significantly improved OS (hazard ratio [HR], 0.82; 99% confidence interval [CI], 0.62-1.09; P = .068). PTR at diagnosis did not correlate with outcome in de novo patients with a colon primary (HR, 0.74; 99% CI, 0.54-1.01; P = .014) or a rectal primary (HR, 0.81; 99% CI, 0.27-2.44; P = .621).For de novo mCRC patients treated with palliative intent, PTR at diagnosis does not significantly improve OS when adjusting for known major prognostic factors. The outcomes of randomized trials examining the survival impact of PTR are awaited.

Diabetes is a risk factor for colorectal cancer and several reports suggest worse cancer-specific outcomes in diabetes patients. Recent studies in multiple tumour types indicate metformin may positively impact on cancer-specific and overall survival. A population-based series of stage II colorectal cancer patients treated and followed from 2000 to 2013 were analysed for baseline characteristics, treatment, and outcomes. 1116 patients with stage II colon cancer were identified, 55.5% were male and median age was 70.9 years (range 20.5–101.2). The diabetes patients (21.6%,n= 241) were older than nondiabetes patients (median 74.0 versus 69.6,p= 0.0001). There was no impact of diabetes on cancer presentation or pathology. Diabetes patients were less likely to receive adjuvant treatment (13.7 versus 24.8%,p= 0.002) but were equally likely to complete treatment (69.7 versus 67.7%,p= 1.00). Diabetes did not significantly impact cancer recurrence (HR = 1.07, 95% CI 0.71–1.63) or overall survival (HR = 1.23, 95% CI 0.88–1.72), adjusted for age. Diabetes medication did not impact cancer recurrence or survival. Cancer presentation and outcomes in diabetes patients are comparable to those of nondiabetes patients in those with stage II colon cancer. The effect of metformin merits further evaluation in patients with colon cancer.

To investigate the safety and efficacy of adding bevacizumab to first-line chemotherapy in metastatic colorectal cancer patients with peritoneal disease.We compared rates of gastrointestinal perforation in patients with metastatic colorectal cancer and peritoneal disease receiving first-line chemotherapy with and without bevacizumab in three distinct cohorts: (1) the AGITG MAX trial (Phase III randomised clinical trial comparing capecitabine vs capecitabine and bevacizumab vs capecitabine, bevacizumab and mitomycinC); (2) the prospective Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry (any first-line regimen ± bevacizumab); and (3) two cancer centres in New South Wales, Australia [Macarthur Cancer Therapy Centre and Liverpool Cancer Therapy Centre (NSWCC) from January 2005 to Decenber 2012, (any first-line regimen ± bevacizumab). For the AGITG MAX trial capecitabine was compared to the other two arms (capecitabine/bevacizumab and capecitabine/bevacizumab/mitomycinC). In the AGITG MAX trial and the TRACC registry rates of gastrointestinal perforation were also collected in patients who did not have peritoneal metastases. Secondary endpoints included progression-free survival, chemotherapy duration, and overall survival. Time-to-event outcomes were estimated using the Kaplan-Meier method and compared using the log-rank test.Eighty-four MAX, 179 TRACC and 69 NSWCC patients had peritoneal disease. There were no gastrointestinal perforations recorded in either the MAX subgroup or the NSWCC cohorts. Of the patients without peritoneal disease in the MAX trial, 4/300 (1.3%) in the bevacizumab arms had gastrointestinal perforations compared to 1/123 (0.8%) in the capecitabine alone arm. In the TRACC registry 3/126 (2.4%) patients who had received bevacizumab had a gastrointestinal perforation compared to 1/53 (1.9%) in the chemotherapy alone arm. In a further analysis of patients without peritoneal metastases in the TRACC registry, the rate of gastrointestinal perforations was 9/369 (2.4%) in the chemotherapy/bevacizumab group and 5/177 (2.8%) in the chemotherapy alone group. The addition of bevacizumab to chemotherapy was associated with improved progression-free survival in all three cohorts: MAX 6.9 m vs 4.9 m, HR = 0.64 (95%CI: 0.42-1.02); P = 0.063; TRACC 9.1 m vs 5.5 m, HR = 0.61 (95%CI: 0.37-0.86); P = 0.009; NSWCC 8.7 m vs 6.8 m, HR = 0.75 (95%CI: 0.43-1.32); P = 0.32. Chemotherapy duration was similar across the groups.Patients with peritoneal disease do not appear to have an increased risk of gastrointestinal perforations when receiving first-line therapy with bevacizumab compared to systemic therapy alone.

Objective The aim of this study is to determine the frequency of geriatric assessment in patients aged over 70 years in Australian medical oncology clinics. Material and Methods This was a multicentre audit in two parts: a retrospective file review of initial consultations with an oncologist and prospective audit of case presentations at multidisciplinary meetings (MDMs). Patients aged over 70 years presenting to a medical oncology clinic or being discussed at an MDM were eligible. Data was collected at six oncology centres in Victoria, NSW and Canberra from October 2009 to March 2010. Results Data was collected from 251 file reviews and 108 MDM discussions in a total of 304 patients. Median age was 76 years (range 70–95). The geriatric assessment (GA) domains most frequently assessed during an initial consultation were the presence of comorbidities (92%), social situation—living alone or with someone (80%), social supports (63%), any mention of at least one Activity of Daily Living (ADL) (50%) and performance status (49%). Less frequently assessed were any Instrumental Activity of Daily Living (IADL) (26%), presence of a geriatric syndrome (24%), polypharmacy (29%) and creatinine clearance (11%). Only one patient had all components of ADLs and IADLs assessed. During MDMs all the geriatric domains were comparatively less frequently assessed. No patients had all ADL and IADL components discussed formally in an MDM. Conclusion This is the first multicentre audit that reveals the low rates of GA in Australian medical oncology practice and describes the GA domains considered important by oncology clinicians.

e15106 Background: Multiple studies have indicated the prognostic and potential predictive significance of primary tumor side in metastatic CRC. To date, the few studies examining its impact in early stage disease have either combined data across multiple stages or restricted analysis to overall survival (OS) data. A by stage analysis of the impact of tumor side on recurrence risk is critical if it is to impact adjuvant therapy decisions. Methods: We examined data from a multi-site Australian registry of consecutive patients diagnosed from 2003-2016. Tumors at and distal to the splenic flexure, including the rectum, were considered a left primary (LP). Rectal patients treated with initial chemoradiation were excluded. Clinico-pathologic and outcome data were examined. Data analysis was provided by the healthcare group at IBM Research Australia. Results: A total of 6123 patients were identified, of which 1046 (17.1%) had initial stage I, 1892 (30.9%) had stage II, 1708 (27.9%) had stage III, and 1477 (24.1%) had stage IV disease. Most patients were male (55.2%), and had a LP (n = 3818, 62.4%). Median age at diagnosis was 68.8 years, was higher in patients with a right primary (RP) (71.6 versus 67.0 years for LP, p < 0.001), with more females in the RP group (51.1% vs 41.0% for LP, p < 0.001). The proportion of RP varied by stage, highest in stage II (44.9%), lowest in stage IV (31.5%). For all stage IV disease, including metachronous cases, OS was worse with a RP (HR 1.32, 95% CI 1.14-1.53). For early stage cases, distant recurrence free survival (DRFS) was similar for RP vs LP for stage I (HR 0.63, 95% CI 0.32-1.23), better for stage II RP (HR 0.72, 95% CI 0.55-0.95) and worse for stage III RP disease (HR 1.22, 1.01-1.48). OS did not differ for RP vs LP for stage I or II disease, but was worse for stage III disease with a RP (HR 1.39, 95% CI 1.13-1.70). Furthermore, post recurrence survival was poorer in stage III RP disease (HR 1.61, 95% CI 1.33-1.96). Conclusions: Primary tumor side has potential as an important prognostic marker in early stage CRC. Our novel finding of a variable impact by stage indicate that an assessment of cohorts where recurrence data is available is critical to fully understanding the implications of tumor side for adjuvant therapy decision making.

Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumour. Having a second or subsequent operation at recurrence may be a positive prognostic factor for survival. Recent studies suggest that socio-demographic variables may influence survival, raising the question whether surgical care differs based on these variables. We examined the relationship between selected socio-demographic variables and the number of repeat operations undergone by patients with recurrent GBM. Data from all patients diagnosed with GBM between 2001 and 2011 was obtained from a clinical database maintained across two institutions (one public, one private). The clinical and socio-demographic factors for patients who received one operation were compared to those who had two or more operations, using chi-squared analyses to determine statistical differences between groups. Socioeconomic status was measured using the Index of Relative Socioeconomic Advantage and Disadvantage scores. Of 553 patients, 449 (81%) had one operation and 104 (19%) had ≥2 operations. Patients who had ≥2 operations were significantly younger (median 55 years versus 64 years, p

e15131Background: In pts with metastatic colorectal cancer (mCRC), the resection of isolated CLM is potentially curative. Previous studies have shown that ctDNA can be detected in a high proportion...

742 Background: The liver is the dominant site of metastasis in patients (pts) with mCRC. Radioembolisation is a potential option in the multidisciplinary management of these patients. Recently initial analysis of a randomised controlled trial (RCT) in the 1st line setting demonstrated no overall progression free survival (PFS) benefit from adding SIRT, but prolongation of liver PFS (HR 0.69, p=0.002) was seen. Methods: Consecutive pts with mCRC enrolled from January 2009 were identified from a prospective multi-site Australian registry. Characteristics and outcomes for pts selected for treatment with SIRT were analysed. Results: Of 1,694 pts with mCRC, 580 (34.2%) had liver only disease at diagnosis, 409/580 (70.5%) with synchronous vs 166/580 (28.6%) with metachronous disease. Of pts with liver only disease, 187 (32.2%) were considered resectable at diagnosis, 100 (17%) as potentially resectable and 293 (51%) were treated with palliative intent. Overall 47 pts received SIRT with 1stline chemotherapy (CT). SIRT treated pts were more likely to have a synchronous presentation (85% vs 68%, p=0.01), liver only disease (83.0% vs 27.3%, p=st line treatment of mCRC in routine practice. The available data suggests that OS gains can be seen in the absence of differences in PFS. However, this observed differential effect on survival maybe due to selection biases. SIRT treated patients were significantly younger and fitter than the CT alone group. Future analyses will include a multivariate analysis and examine the impact of the recently presented SIRFLOX trial data on the use of SIRT in clinical practice.

685 Background: The FIRE3 study reported that cetuximab added to first line combination chemotherapy versus the addition of bevacizumab to the same chemotherapy backbone, with a planned switch to the alternative biologic in second line therapy, resulted in improved overall survival. One possible explanation is that the sequence of biologic administration in mCRC impacts on treatment benefit. Examination of the efficacy of anti-EGFR therapy in cohorts where patients have and have not received prior bevacizumab will inform this. Methods: We interrogated our prospective database (ACCORD), which records comprehensive detail on demographics, treatments received and patient outcomes for consecutive mCRC patients in real world practice across multiple institutions in Australia. We included patients receiving 2nd and subsequent line anti-EGFR monotherapy. Disease control rate (DCR) (partial response plus stable disease), progression free survival (PFS) and overall survival (OS) from the start of anti-EGFR were determined as a function of prior bevacizumab use. Results: From a total of 1511 patients treated between 01/10/2002 and 31/12/2014,129 patients treated with single agent anti- EGFR were identified, 75 had received prior bevacizumab. Demographics, performance status and tumour characteristics were similar between the 2 groups. 84% were confirmed KRAS exon 2 wild type. Prior treatment with bevacizumab did not impact DCR (35% vs 40%, p = 0.5065), median PFS (3.0 vs 3.0 months, p = 0.9460) or OS (8.6 vs 8.4 months, HR 0.95, p = 0.8073). Similarly, for bevacizumab treated patients, the time since last dose of bevacizumab to start of anti-EGFR ( < 3 months (n = 26) vs 3-6 months (n = 17) vs > 6 months (n = 32)) did not impact PFS (2.3 vs 3.6 vs 3 months) or OS (8.9 vs 10.1 vs 7.1 months, HR: 0.88, p = 0.82). Conclusions: There was no evident impact of previous bevacizumab treatment, or time from previous bevacizumab treatment, on the efficacy of single agent anti-EGFR therapy in a routine clinical practice cohort. Our data do not support the notion that prior bevacizumab renders tumors more or less sensitive to subsequent anti EGFR therapy.

The current growth in the cost of cancer care is unsustainable. The authors provide data-driven proposals that have the potential to save money without compromising patient care.

Purpose: The optimal regimen for the treatment of metastatic colorectal cancer (CRC) remains uncertain. We sought to document clinicians' treatment recommendations and determine the motivation behind them. Materials and Methods: A postal questionnaire was sent to all members of the Medical Oncology Group of Australia concerning chemotherapy treatment options in the setting of metastatic CRC. Results: The response rate was 59.7% (n = 188). One hundred sixty-two physicians (86%) treated patients with CRC. Of the 162 physicians, 92.6% (n = 150) recommended oxaliplatin-based regimens as first-line treatment for CRC due to perceived superior efficacy (66.9%; n = 107) or toxicity profile (17%; n = 27). Fluorouracil (FU), leucovorin (LV), and oxaliplatin (FOLFOX6) was the most popular regimen (59.3%; n = 98). Calcium and magnesium to prevent oxaliplatin-related neurotoxicity was routinely used by 34.6% of physicians (n = 56) from cycle 1. Despite the lack of phase III data at the time, 8.6% of physicians (n = 14) selected capecitabine and oxaliplatin (XELOX) a preferred first-line regimen; 61.7% of physicians (n = 100) recommended FU, LV, and irinotecan (FOLFIRI) second-line treatment. Concerning LV dose, one third of physicians (33.3%; n = 54) selected 20 mg/m2 and one third of physicians (32.7%, n = 53) selected 200 mg/m2, with 25.3% of physicians (n = 41) using a fixed 50 mg bolus. Conclusion: This survey demonstrated considerable variation regarding recommended chemotherapy for patients with metastatic CRC. Of considerable concern is the use of calcium and magnesium based on retrospective data alone. Given that this variation in practice may significantly impact patient outcomes, additional studies are required to improve understanding of physician attitudes and the motivations behind treatment decision making.

Metastatic colorectal cancer is one of the most common malignancies in the Western world. Moreover, as this text so ably demonstrates, the optimal management of patients with rectal cancer at any stage of the disease truly requires a multidisciplinary effort that, depending on the stage of illness, can involve colorectal, hepatobiliary, and thoracic surgeons, pathologists, radiologists, radiation oncologists, medical oncologists, and palliative care physicians, all playing important roles. The management of metastatic rectal cancer has become more challenging over the past decade, with treatment strategies in locally advanced and sometimes metastatic disease aimed at cure rather than palliation. Additionally, the number of active anticancer agents including both chemotherapeutics and targeted therapies which have demonstrated efficacy in managing this disease has expanded considerably. Increasingly, treatment strategies are now able to be more tailored toward an individual rather than the disease itself. In this chapter, we will briefly provide an overview of the epidemiology of metastatic rectal cancer, discuss past, present and future anticancer agents used to treat this disease, and provide some perspectives into the optimal management of metastatic rectal cancer, both now and in the future.

The management of gastric cancer remains a challenge. In recent years, the most important advances have been achieved in the adjuvant setting for patients with locally advanced disease, where significant survival benefits have been demonstrated for both perioperative chemotherapy and adjuvant chemoradiotherapy. These findings have changed the standard of care for patients with resectable disease. In the setting of metastatic gastric cancer, the development of new cytotoxic regimens must consider the balance between efficacy and toxicity in patients whose overall prognosis is poor. Major advances in recent years include the development of orally administered fluoropyrimidine analogues, which can be used in place of intravenous fluorouracil, and the addition of newer agents such as oxaliplatin and docetaxel, which have demonstrated efficacy in patients with advanced disease. Targeted therapies have had a major impact on the management of certain malignancies, and while their evaluation in the treatment of advanced gastric cancer remains early, it is likely that these agents will continue to be developed and studied in combination with chemotherapy. This article reviews recent advances in the use of chemotherapy for advanced gastric cancer. Targeted therapies, their mechanisms of action and emerging data supporting their use in gastric cancer are also discussed. The two randomized phase III trials supporting adjuvant therapy for locally advanced, resectable gastric cancer are discussed in detail, together with strategies for future trials in this area. Overall, there remains optimism that further incremental gains will be achieved with future studies combining chemotherapy, radiotherapy and targeted therapies, both in the adjuvant and metastatic disease settings.

e14637 Background: There is a growing body of epidemiological evidence that T2DM is associated with increased incidence of, and poorer survival in CRC, while metformin use in CRC pts with T2DM has ...

e14648 Background: Colorectal cancer, typically a disease of aging, is increasing in incidence amongst YP. Potential differences in clinicopathological features, treatment response, and survival be...

3557 Background: Resection of isolated liver and/or lung metastases in patients (pts) with metastatic colorectal cancer (mCRC) offers a chance at long-term survival. Multiple prognostic models have...