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Purpose We recently reported that the mRNA-based, 21-gene Genomic Health recurrence score (GHI-RS) provided additional prognostic information regarding distant recurrence beyond that obtained from classical clinicopathologic factors (age, nodal status, tumor size, grade, endocrine treatment) in women with early breast cancer, confirming earlier reports. The aim of this article is to determine how much of this information is contained in standard immunohistochemical (IHC) markers. Patients and Methods The primary cohort comprised 1,125 estrogen receptor–positive (ER-positive) patients from the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial who did not receive adjuvant chemotherapy, had the GHI-RS computed, and had adequate tissue for the four IHC measurements: ER, progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), and Ki-67. Distant recurrence was the primary end point, and proportional hazards models were used with sample splitting to control for overfitting. A prognostic model that used classical variables and the four IHC markers (IHC4 score) was created and assessed in a separate cohort of 786 patients. Results All four IHC markers provided independent prognostic information in the presence of classical variables. In sample-splitting analyses, the information in the IHC4 score was found to be similar to that in the GHI-RS, and little additional prognostic value was seen in the combined use of both scores. The prognostic value of the IHC4 score was further validated in the second separate cohort. Conclusion This study suggests that the amount of prognostic information contained in four widely performed IHC assays is similar to that in the GHI-RS. Additional studies are needed to determine the general applicability of the IHC4 score., Royal Marsden National Institute for Health Research Biomedical Research Centre, Cancer Research United Kingdom Program Grant, Breakthrough Breast Cancer, AstraZeneca, Depto. de Estadística y Ciencia de los Datos, Fac. de Estudios Estadísticos, TRUE, pub

Background: Concurrent chemoradiotherapy (CRT) with cisplatin is a widely accepted treatment strategy for patients with LA HNSCC. However, some patients are deemed Cisplatin ineligible for a variety of reasons and offered alternative sensitising agents. There is a paucity of data regarding outcomes in patients treated with non-cisplatin chemotherapy. Patients and Methods: We retrospectively analysed all consecutive adult LA HNSCC patients from January 2016-Feb 2020 treated with chemoradiotherapy in the definitive or adjuvant settings.We collected data on patient and tumour characteristics, chemotherapy regimen, toxicity as well as clinical outcomes including locoregional control and survival. Result(s): Over the 4-year period, a total of 194 patients received CRT for LA HNSCC. Median age was 61 years (range: 22-82) with a male/female ratio of 6:1. Primary tumour site was the oropharynx in 161 (83%), hypopharynx in 12 (6%), oral cavity in 11 (6%) and larynx in 9 (5%) patients. P16 positive tumours accounted for 146 (75%) of all tumours. Most patients (174, 90%) had definitive treatment as opposed to adjuvant therapy (20, 10%). Cisplatin based chemotherapy was employed in 154 (80%) of all patients, and non-cisplatin-based treatment in 44 (20%). Carboplatin plus paclitaxel was used in 21 (11%) and Cetuximab in 15 (8%) of the entire patient cohort. Carboplatin alone in the adjuvant setting was used in 3 (1%) patients. Final survival and toxicity data will be reported at the conference. Conclusion(s):Non-cisplatin-based chemotherapy was used in20%of our patient cohort with LA HNSCC. It is important to ascertain the safety and efficacy data in these two groups of patients treated with radical CRT.

Background: The COVID-19 pandemic has resulted in reduced cancer diagnoses. Impacts on existing cancer patients has not been well documented. We report the experience of a large metropolitan multisite cancer service that undertook proactive review of systemic anti-cancer therapy (SACT) of all patients to consider changes in response to the pandemic. The aim was to re-balance the risks and benefits of current treatment strategies in light of the pandemic. Method(s): From March-April 2020, all current SACT orders (excluding those related to clinical trials) were reviewed. Patients on curative therapy, or with large perceived benefit were reviewed but not included in further processing. For all other SACT orders, a documented recommendation regarding planned treatment was sent to the patient's individual clinician for consideration. A categorical assessment of the recommendations is presented. Result(s): 570 SACT orders were reviewed, pertaining to 317 patients. 730 individual recommendations were made. The population consisted of 130 males and 187 females, with an average age 60.6 years. Intentions of treatment were: Curative (n=16), Neoadjuvant (n=30), Adjuvant (n = 74), and Palliative (n = 197). Distribution by tumour types (number) was: Breast (93), Gastrointestinal (76), Thoracic (63), Gynaecological (31), Genitourinary (21), Head andNeck/Melanoma (19),CNS (8), andOther (6). The most commonrecommendations (number)were:NoChange (160), Change route of delivery (e.g. intravenous to subcutaneous) (67), Reduce duration of treatment (68), Consider treatment break (60), Reconsider benefit of current treatment (58), Cease treatment (53), and Refer to HITH (47). Conclusion(s): This is the only dataset known to date of the actual impact of COVID-19 on the recommendations for SACT for patients on treatment at the start of the pandemic in Australia.Most patients had some type of modification in their cancer therapymadein the context of competing risk to their health posed by

Background: Concurrent chemoradiotherapy (CRT) with cisplatin is a widely accepted treatment strategy for patients with LA HNSCC. However, some patients are deemed Cisplatin ineligible for a variety of reasons and offered alternative sensitising agents. There is a paucity of data regarding outcomes in patients treated with non-cisplatin chemotherapy. Patients and Methods: We retrospectively analysed all consecutive adult LA HNSCC patients from January 2016-Feb 2020 treated with chemoradiotherapy in the definitive or adjuvant settings.We collected data on patient and tumour characteristics, chemotherapy regimen, toxicity as well as clinical outcomes including locoregional control and survival. Result(s): Over the 4-year period, a total of 194 patients received CRT for LA HNSCC. Median age was 61 years (range: 22-82) with a male/female ratio of 6:1. Primary tumour site was the oropharynx in 161 (83%), hypopharynx in 12 (6%), oral cavity in 11 (6%) and larynx in 9 (5%) patients. P16 positive tumours accounted for 146 (75%) of all tumours. Most patients (174, 90%) had definitive treatment as opposed to adjuvant therapy (20, 10%). Cisplatin based chemotherapy was employed in 154 (80%) of all patients, and non-cisplatin-based treatment in 44 (20%). Carboplatin plus paclitaxel was used in 21 (11%) and Cetuximab in 15 (8%) of the entire patient cohort. Carboplatin alone in the adjuvant setting was used in 3 (1%) patients. Final survival and toxicity data will be reported at the conference. Conclusion(s):Non-cisplatin-based chemotherapy was used in20%of our patient cohort with LA HNSCC. It is important to ascertain the safety and efficacy data in these two groups of patients treated with radical CRT.

Introduction: Immune checkpoint inhibitors (ICIs) have improved outcomes of patients with advanced non-small cell carcinoma (NSCLC). There is no consensus on the maximum duration of ICIs in metastatic disease. Immune related adverse events (IRAEs) with ICIs, although rare, can have serious and life-long consequences. We aim to describe the real-world data on outcomes of NSCLC patients who stopped ICIs earlier than proposed duration due to IRAEs. Method(s): Patients with stage III or IV NSCLC treated with ICIs at Monash Health (Melbourne, Australia) from 2015 to 2019 were retrospectively reviewed. Patients enrolled to clinical trials were excluded. Baseline clinicopathological factors and anti-cancer treatment details were collected. Immunohistochemistry for PD-L1 staining was performed and scored according to standardised practice. IRAEs and reason for ICI cessation was recorded. Overall survival (OS) from the start of ICI was calculated using Kaplan-Meier method. Result(s): A total of 148 patients received ICI therapy with 97 male (66%) and 51 female (34%) patients. 91% were smokers and ECOG 0 or 1 was found in 95%. PD-L1 expression was known in 53/148 patients; where 19% were scored as low, 43% as intermediate and 20% as high. Stage at commencement of ICI was III in 36/148 (24%), where 32/36 (89%) received adjuvant durvalumab after curative intent chemoradiotherapy, and metastatic in 112/148 (76%), where 99 (88%) received nivolumab and 13 (12%) received pembrolizumab, after first line chemotherapy. Median doses of ICIs were 17 in stage III, and 7 in stage IV cohorts. ICIs were ceased in 93/148 (63%) cases due to disease progression, while 38/148 (26%) stopped due to IRAEs; 17 (12%) in stage III and 21 (14%) in stage IV cohort. Severe IRAEs (grade 3 or higher) were pneumonitis (7/148, 5%), colitis (4/148, 3%), endocrinopathy (2/148, 1%), arthritis (2/148, 1%), rash (2/148, 1%) cardiac (2/148, 1%), liver (1/148, 1%), optic neuritis (1/148, 1%), thrombocytopenia (1/1

Background: The COVID-19 pandemic has resulted in reduced cancer diagnoses. Impacts on existing cancer patients has not been well documented. We report the experience of a large metropolitan multisite cancer service that undertook proactive review of systemic anti-cancer therapy (SACT) of all patients to consider changes in response to the pandemic. The aim was to re-balance the risks and benefits of current treatment strategies in light of the pandemic. Method(s): From March-April 2020, all current SACT orders (excluding those related to clinical trials) were reviewed. Patients on curative therapy, or with large perceived benefit were reviewed but not included in further processing. For all other SACT orders, a documented recommendation regarding planned treatment was sent to the patient's individual clinician for consideration. A categorical assessment of the recommendations is presented. Result(s): 570 SACT orders were reviewed, pertaining to 317 patients. 730 individual recommendations were made. The population consisted of 130 males and 187 females, with an average age 60.6 years. Intentions of treatment were: Curative (n=16), Neoadjuvant (n=30), Adjuvant (n = 74), and Palliative (n = 197). Distribution by tumour types (number) was: Breast (93), Gastrointestinal (76), Thoracic (63), Gynaecological (31), Genitourinary (21), Head andNeck/Melanoma (19),CNS (8), andOther (6). The most commonrecommendations (number)were:NoChange (160), Change route of delivery (e.g. intravenous to subcutaneous) (67), Reduce duration of treatment (68), Consider treatment break (60), Reconsider benefit of current treatment (58), Cease treatment (53), and Refer to HITH (47). Conclusion(s): This is the only dataset known to date of the actual impact of COVID-19 on the recommendations for SACT for patients on treatment at the start of the pandemic in Australia.Most patients had some type of modification in their cancer therapymadein the context of competing risk to their health posed by

Although sentinel lymph node biopsy (SLNB) has proved to be able to diagnose axillary lymph node status safely and reliably, there is still not enough evidence to suggest that it can be used in patients who have undergone neoadjuvant chemotherapy (NAC) for lymph node-sparing surgery. The present study used molecular approaches to determine whether SLNB can be reliably used in patients who have been treated with NAC before SLN surgery, and whether the total tumor load of the SLN can be used as a predictive factor in axillary lymphadenectomy (ALD). We used one-step nucleic acid amplification (OSNA) to analyze a total of 111 consecutive patients who presented operable invasive breast carcinomas and who had been treated with NAC. SLN was positive in 55 patients and the identification rate was 100%. In 9 of these 55 patients, ALD showed that other lymph nodes were also involved. In all of the other 46 patients, the only lymph node to be identified as positive was SLN. Metastasis was not found in any of the axillary lymph nodes in the isolated tumor cell group. The total tumor load, defined as the amount of cytokeratin 19 mRNA copy numbers in all positives SLN (copies/mu L), showed three risk groups related to the possibility of positive non-sentinel nodes. OSNA is a diagnostic technique that is highly sensitive, specific, and reproducible and it can be used to analyze sentinel lymph nodes after NAC. Total tumor load may be able to help predict additional metastases in axillary lymphadenectomy.

BACKGROUND: The Victorian Pancreas Cancer summit 2017 analysed state-wide data on management of Victorians with pancreas cancer between 2011 and 2015 to identify variations in care and outcomes. Pancreas cancer remains a formidable disease but systemic therapies are increasingly effective. Surgery remains essential but insufficient alone for cure. Understanding patterns of care and identifying variations in treatment is critical to improving outcomes. METHOD(S): This population-based study analysed data collected prospectively by Department of Health and Human services (Victorian state government). Data were extracted from Victorian Cancer Registry (covering all Victorian cancer diagnoses), Victorian Admitted-Episodes Dataset (all inpatient data), Victorian Radiotherapy Minimum Dataset and Victorian Death Index providing demographics, tumour and treatment characteristics, age-standardized incidence, overall and median survival. RESULT(S): Of 3962 Victorian patients with any form of pancreatic malignancy, 82% were ductal adenocarcinoma (PDAC), of whom 67% had metastases at diagnosis. One-year overall survival for PDAC was 30% (60% non-metastatic, 15% if metastatic). Median survival with metastases increased from 2.7 to 3.9 months, and from 13.3 to 15.9 months for non-metastatic PDAC between 2011 and 2015. Thirty-one percent of non-metastatic patients underwent pancreatectomy. About 1.5% were treated with neoadjuvant chemotherapy/chemoradiation. Of patients undergoing intended curative resection, 77% proceeded to adjuvant therapy. Fifty-one percent of metastatic PDAC patients never received anti-tumour therapy. CONCLUSION(S): Nearly one-fourth of surgically treated patients never received systemic therapy. More than two-thirds of non-metastatic patients never proceeded to surgery. Further consideration of neoadjuvant therapy should be given to borderline resectable patients. Most patients with PDAC still die soon after diagnosis, but median survival is increasing.Copy

Background: Breast cancer survivors are at risk for contralateral breast cancer (CBC), with the consequent burden of further treatment and potentially less favorable prognosis. We aimed to develop and validate a CBC risk prediction model and evaluate its applicability for clinical decision-making. Method(s): We included data of 132,756 invasive non-metastatic breast cancer patients from 20 studies with 4682 CBC events and a median follow-up of 8.8 years. We developed a multivariable Fine and Gray prediction model (PredictCBC-1A) including patient, primary tumor, and treatment characteristics and BRCA1/2 germline mutation status, accounting for the competing risks of death and distant metastasis. We also developed a model without BRCA1/2 mutation status (PredictCBC-1B) since this information was available for only 6% of patients and is routinely unavailable in the general breast cancer population. Prediction performance was evaluated using calibration and discrimination, calculated by a time-dependent area under the curve (AUC) at 5 and 10 years after diagnosis of primary breast cancer, and an internal-external cross-validation procedure. Decision curve analysis was performed to evaluate the net benefit of the model to quantify clinical utility. Result(s): In the multivariable model, BRCA1/2 germline mutation status, family history, and systemic adjuvant treatment showed the strongest associations with CBC risk. The AUC of PredictCBC-1A was 0.63 (95% prediction interval (PI) at 5 years, 0.52-0.74; at 10 years, 0.53-0.72). Calibration-in-the-large was-0.13 (95% PI:-1.62-1.37), and the calibration slope was 0.90 (95% PI: 0.73-1.08). The AUC of Predict-1B at 10 years was 0.59 (95% PI: 0.52-0.66); calibration was slightly lower. Decision curve analysis for preventive contralateral mastectomy showed potential clinical utility of PredictCBC-1A between thresholds of 4-10% 10-year CBC risk for BRCA1/2 mutation carriers and non-carriers. Conclusion(s): We developed a reasonab

Background: Multinational academic trials can pose complex organisational issues. We describe our experience running the phase III ASCOLT trial (NCT00565708), studying the impact of aspirin in resected high-risk colorectal cancer. This is the first large academic adjuvant trial fully conducted in the APAC region. Method(s): ASCOLT is coordinated by the National Cancer Centre Singapore and funded largely by academic grants. The trial opened in 2008 and is nearing full accrual (1480 of 1587) at 58 sites in 12 countries/regions, including 5 middle income countries. Trial conduct logistics were analysed to identify barriers and enablers. Result(s): Diverse regulatory requirements necessitated >100 contracts and 49 ethics board reviews, leading to start up times of ~6 months per site. Consent forms were translated into 13 languages. The enrolment target and period were revised in 2017, and site numbers expanded due to lower than projected accrual and event rates. Other challenges include communication and logistical barriers, patient attrition, recruitment holds due to changes in local laws and limited funding for patient visits, affecting countries where healthcare is not publicly funded. Solutions included engaging local cooperative groups (e.g. the Australasian GastroIntestinal Trials Group in Australia and New Zealand) and 6 contract research organisations to manage sites, developing processes sensitive to local needs, transition to electronic data management, and a centralised drug dispensing system. Measures to overcome disparate experience across sites and to quality control include regular contact with the central team to troubleshoot (e.g. >200 data queries are raised a month) and central and on-site monitoring. 16 sites were closed due to resource or recruitment issues. In response to the COVID-19 pandemic, strategies such as telehealth consults, direct postage of drugs to patients, consent form amendments, and rationalised recruitment and biospecimen collectio

Introduction: A multimodal approach in operable early-stage oesophago-gastric (OG) cancer has evolved in the last decade, leading to improvement in overall outcomes. Areas covered: A review of the published literature and conference abstracts was undertaken on the topic of optimal adjunctive chemotherapy or chemoradiotherapy in early-stage OG cancers. This review article focuses on the current evidence pertaining to neoadjuvant and perioperative strategies in curable OG cancers including the evolving landscape of immunotherapy and targeted drugs in this setting. Expert commentary: Adjunctive therapies in the form of preoperative chemo-radiotherapy (CRT) or chemotherapy and perioperative chemotherapy over surgery alone improve outcomes in patients with operable OG cancer. Although there are variations in practice around the world, a multi-disciplinary approach to patient care is of paramount importance. Immunotherapy and on treatment functional imaging are two examples of emerging strategies to improve the outcome for early-stage patients. A better understanding of the molecular biology of this disease may help overcome the problem of tumor heterogeneity and enable more rationally designed and targeted therapeutic interventions in the future.Copyright © 2020, © 2020 Informa UK Limited, trading as Taylor & Francis Group.

BACKGROUND: The Victorian Pancreas Cancer summit 2017 analysed state-wide data on management of Victorians with pancreas cancer between 2011 and 2015 to identify variations in care and outcomes. Pancreas cancer remains a formidable disease but systemic therapies are increasingly effective. Surgery remains essential but insufficient alone for cure. Understanding patterns of care and identifying variations in treatment is critical to improving outcomes. METHOD(S): This population-based study analysed data collected prospectively by Department of Health and Human services (Victorian state government). Data were extracted from Victorian Cancer Registry (covering all Victorian cancer diagnoses), Victorian Admitted-Episodes Dataset (all inpatient data), Victorian Radiotherapy Minimum Dataset and Victorian Death Index providing demographics, tumour and treatment characteristics, age-standardized incidence, overall and median survival. RESULT(S): Of 3962 Victorian patients with any form of pancreatic malignancy, 82% were ductal adenocarcinoma (PDAC), of whom 67% had metastases at diagnosis. One-year overall survival for PDAC was 30% (60% non-metastatic, 15% if metastatic). Median survival with metastases increased from 2.7 to 3.9 months, and from 13.3 to 15.9 months for non-metastatic PDAC between 2011 and 2015. Thirty-one percent of non-metastatic patients underwent pancreatectomy. About 1.5% were treated with neoadjuvant chemotherapy/chemoradiation. Of patients undergoing intended curative resection, 77% proceeded to adjuvant therapy. Fifty-one percent of metastatic PDAC patients never received anti-tumour therapy. CONCLUSION(S): Nearly one-fourth of surgically treated patients never received systemic therapy. More than two-thirds of non-metastatic patients never proceeded to surgery. Further consideration of neoadjuvant therapy should be given to borderline resectable patients. Most patients with PDAC still die soon after diagnosis, but median survival is increasing.Copy

Background: Breast cancer survivors are at risk for contralateral breast cancer (CBC), with the consequent burden of further treatment and potentially less favorable prognosis. We aimed to develop and validate a CBC risk prediction model and evaluate its applicability for clinical decision-making. Method(s): We included data of 132,756 invasive non-metastatic breast cancer patients from 20 studies with 4682 CBC events and a median follow-up of 8.8 years. We developed a multivariable Fine and Gray prediction model (PredictCBC-1A) including patient, primary tumor, and treatment characteristics and BRCA1/2 germline mutation status, accounting for the competing risks of death and distant metastasis. We also developed a model without BRCA1/2 mutation status (PredictCBC-1B) since this information was available for only 6% of patients and is routinely unavailable in the general breast cancer population. Prediction performance was evaluated using calibration and discrimination, calculated by a time-dependent area under the curve (AUC) at 5 and 10 years after diagnosis of primary breast cancer, and an internal-external cross-validation procedure. Decision curve analysis was performed to evaluate the net benefit of the model to quantify clinical utility. Result(s): In the multivariable model, BRCA1/2 germline mutation status, family history, and systemic adjuvant treatment showed the strongest associations with CBC risk. The AUC of PredictCBC-1A was 0.63 (95% prediction interval (PI) at 5 years, 0.52-0.74; at 10 years, 0.53-0.72). Calibration-in-the-large was-0.13 (95% PI:-1.62-1.37), and the calibration slope was 0.90 (95% PI: 0.73-1.08). The AUC of Predict-1B at 10 years was 0.59 (95% PI: 0.52-0.66); calibration was slightly lower. Decision curve analysis for preventive contralateral mastectomy showed potential clinical utility of PredictCBC-1A between thresholds of 4-10% 10-year CBC risk for BRCA1/2 mutation carriers and non-carriers. Conclusion(s): We developed a reasonab

Background: Multinational academic trials can pose complex organisational issues. We describe our experience running the phase III ASCOLT trial (NCT00565708), studying the impact of aspirin in resected high-risk colorectal cancer. This is the first large academic adjuvant trial fully conducted in the APAC region. Method(s): ASCOLT is coordinated by the National Cancer Centre Singapore and funded largely by academic grants. The trial opened in 2008 and is nearing full accrual (1480 of 1587) at 58 sites in 12 countries/regions, including 5 middle income countries. Trial conduct logistics were analysed to identify barriers and enablers. Result(s): Diverse regulatory requirements necessitated >100 contracts and 49 ethics board reviews, leading to start up times of ~6 months per site. Consent forms were translated into 13 languages. The enrolment target and period were revised in 2017, and site numbers expanded due to lower than projected accrual and event rates. Other challenges include communication and logistical barriers, patient attrition, recruitment holds due to changes in local laws and limited funding for patient visits, affecting countries where healthcare is not publicly funded. Solutions included engaging local cooperative groups (e.g. the Australasian GastroIntestinal Trials Group in Australia and New Zealand) and 6 contract research organisations to manage sites, developing processes sensitive to local needs, transition to electronic data management, and a centralised drug dispensing system. Measures to overcome disparate experience across sites and to quality control include regular contact with the central team to troubleshoot (e.g. >200 data queries are raised a month) and central and on-site monitoring. 16 sites were closed due to resource or recruitment issues. In response to the COVID-19 pandemic, strategies such as telehealth consults, direct postage of drugs to patients, consent form amendments, and rationalised recruitment and biospecimen collectio

Introduction: A multimodal approach in operable early-stage oesophago-gastric (OG) cancer has evolved in the last decade, leading to improvement in overall outcomes. Areas covered: A review of the published literature and conference abstracts was undertaken on the topic of optimal adjunctive chemotherapy or chemoradiotherapy in early-stage OG cancers. This review article focuses on the current evidence pertaining to neoadjuvant and perioperative strategies in curable OG cancers including the evolving landscape of immunotherapy and targeted drugs in this setting. Expert commentary: Adjunctive therapies in the form of preoperative chemo-radiotherapy (CRT) or chemotherapy and perioperative chemotherapy over surgery alone improve outcomes in patients with operable OG cancer. Although there are variations in practice around the world, a multi-disciplinary approach to patient care is of paramount importance. Immunotherapy and on treatment functional imaging are two examples of emerging strategies to improve the outcome for early-stage patients. A better understanding of the molecular biology of this disease may help overcome the problem of tumor heterogeneity and enable more rationally designed and targeted therapeutic interventions in the future.Copyright © 2020, © 2020 Informa UK Limited, trading as Taylor & Francis Group.

Background: In early-stage pancreatic cancer, there are currently no biomarkers to guide selection of therapeutic options. This prospective biomarker trial evaluated the feasibility and potential clinical utility of circulating tumor DNA (ctDNA) analysis to inform adjuvant therapy decision making. Material(s) and Method(s): Patients considered by the multidisciplinary team to have resectable pancreatic adenocarcinoma were enrolled. Pre- and post-operative samples for ctDNA analysis were collected. PCR-based-SafeSeqS assays were used to identify mutations at codon 12, 13 and 61 of KRAS in the primary pancreatic tumor and to detect ctDNA. Results of ctDNA analysis were correlated with CA19-9, recurrence-free and overall survival (OS). Patient management was per standard of care, blinded to ctDNA data. Result(s): Of 112 patients consented pre-operatively, 81 (72%) underwent resection. KRAS mutations were identified in 91% (38/42) of available tumor samples. Of available plasma samples (N = 42), KRAS mutated ctDNA was detected in 62% (23/37) pre-operative and 37% (13/35) post-operative cases. At a median follow-up of 38.4 months, ctDNA detection in the pre-operative setting was associated with inferior recurrence-free survival (RFS) [hazard ratio (HR) 4.1; P = 0.002)] and OS (HR 4.1; P = 0.015). Detectable ctDNA following curative intent resection was associated with inferior RFS (HR 5.4; P < 0.0001) and OS (HR 4.0; P = 0.003). Recurrence occurred in 13/13 (100%) patients with detectable ctDNA post-operatively, including in seven that received gemcitabine-based adjuvant chemotherapy. Conclusion(s): ctDNA studies in localized pancreatic cancer are challenging, with a substantial number of patients not able to undergo resection, not having sufficient tumor tissue for analysis or not completing per protocol sample collection. ctDNA analysis, pre- and/or post-surgery, is a promising prognostic marker. Studies of ctDNA guided therapy are justified, including of treatment int

Background: While adjuvant therapy provides a survival benefit for patients (pts) with early-stage pancreatic cancer there are currently no biomarkers that define pts that are more or less likely to benefit from such treatment. This prospective study investigated the use of circulating tumour DNA (ctDNA) as a marker of residual disease, where detection could predict recurrence. Method(s): Patients newly diagnosed with operable pancreatic adenocarcinoma were enrolled. PCR-based-SafeSeqS assays were used to identify mutations at codons 12, 13 and 61 of KRAS in the primary tumor and to detect ctDNA in plasma samples. Patient management was as per standard of care, blinded to ctDNA data. Result(s): From January 2015 to June 2017, 42 pts with matched plasma samples, collected pre- and post-operatively, and tumor tissue available were evaluated. The median time between surgery and post-op blood collection was 6.3 (range:4-8) weeks. RAS mutations were identified in 38 (90.5%) tumor samples. ctDNA was detected in 23/37 (62.2%) pre-op and 13/35 (37.1%) post-op plasma samples. In multivariate analysis including stage, and resection margin, ctDNA status was the only statistically significant variable. Pre-op ctDNA detection was associated with worse median recurrence free survival (RFS), 10.3 months versus not reached, (Hazard Ratio (HR),3.4; 95% confidence interval (CI), 1.5- 7.6; P = 0.005) and 5.4 months versus 17.1 months, (HR, 5.4; 95% CI, 4.7-37.3; P < 0.0001) post-operatively. Similarly, the presence of ctDNA was associated with worse median overall survival (OS), 13.8 months versus not reached pre-operatively, (HR,3.4; 95% CI 1.1 to 8.3; P = 0.04) and 10.6 months versus not reached (HR,4.5; 95% CI 2.4-28.6; P = 0.001) post-operatively. Notably, recurrence occurred in 13 of 13 pts with detectable post-op ctDNA, despite more than half receiving standard adjuvant chemotherapy. Conclusion(s): ctDNA analysis is a promising prognostic marker in early-stage pancreatic cancer

Background: The optimal duration of ACT following surgery for colon cancer remains controversial. SCOT is an international, randomised trial that compared 3 months versus 6 months of ACT in this setting. We sought the survival benefits that patients participating in SCOT judged necessary to make extra 3 months of ACT worthwhile. Method(s): SCOT participants from Australia & New Zealand completed a validated questionnaire 3 and 18 months after randomisation to elicit the minimum survival benefit each participant judged necessary to make it worthwhile having ACT for 6 months rather than 3 months. Standardised hypothetical scenarios used the following baseline survivals with 3 months of ACT: life expectancies (LE) of 5 years (5Y) and 15 years (15Y), and 5-year survival rates (5YS) of 65% and 85%. Comparisons were nonparametric, 2-sided, and considered statistically significant if p < 0.05. Result(s): Questionnaires were completed by 160 participants, 82 allocated 3 months ACT, and 78 allocated 6 months ACT. ACT was FOLFOX in 121 (75%), XELOX in 39 (25%), and the mean age was 64. Preferences varied substantially among participants, and did not differ according to the randomly allocated treatment group. The median survival benefits judged necessary to make the extra 3 months of ACT worthwhile were an extra: 3 years beyond a LE of 5Y; 3 years beyond a LE of 15Y; 15% beyond a 65% 5YS; and 5% beyond an 85% 5YS. Preferences were similar at 3 months and 18 months. Participants with symptomatic peripheral neuropathy (132, 82%) judged a median benefit of an extra 5% beyond a 65% 5YS necessary to warrant their symptoms. Conclusion(s): Participants' preferences varied substantially, and many judged much larger benefits needed to warrant having ACT for 6 months rather than 3 months than the estimates of the benefits based on the IDEA meta-analysis.

Intramedullary spinal cord metastasis (ISCM) is rare and occurs most commonly in the setting of advanced malignancy. The optimal management pathways are not well defined and treatment outcomes from contemporary therapies remain variable. We report a case of a 49-year-old woman with known primary papillary thyroid carcinoma, who presented with rapidly progressive clinical features of Brown-Sequard syndrome. A detailed pooled analysis of the literature was conducted to characterise the clinical and demographic features, management options, and expected survival outcomes for cases of ISCM. We secondarily performed a subgroup analysis on the incidence, clinical and management characteristics of thyroid carcinoma ISCM.Copyright © 2017 Elsevier Ltd

Background: In early-stage pancreatic cancer, there are currently no biomarkers to guide selection of therapeutic options. This prospective biomarker trial evaluated the feasibility and potential clinical utility of circulating tumor DNA (ctDNA) analysis to inform adjuvant therapy decision making. Material(s) and Method(s): Patients considered by the multidisciplinary team to have resectable pancreatic adenocarcinoma were enrolled. Pre- and post-operative samples for ctDNA analysis were collected. PCR-based-SafeSeqS assays were used to identify mutations at codon 12, 13 and 61 of KRAS in the primary pancreatic tumor and to detect ctDNA. Results of ctDNA analysis were correlated with CA19-9, recurrence-free and overall survival (OS). Patient management was per standard of care, blinded to ctDNA data. Result(s): Of 112 patients consented pre-operatively, 81 (72%) underwent resection. KRAS mutations were identified in 91% (38/42) of available tumor samples. Of available plasma samples (N = 42), KRAS mutated ctDNA was detected in 62% (23/37) pre-operative and 37% (13/35) post-operative cases. At a median follow-up of 38.4 months, ctDNA detection in the pre-operative setting was associated with inferior recurrence-free survival (RFS) [hazard ratio (HR) 4.1; P = 0.002)] and OS (HR 4.1; P = 0.015). Detectable ctDNA following curative intent resection was associated with inferior RFS (HR 5.4; P < 0.0001) and OS (HR 4.0; P = 0.003). Recurrence occurred in 13/13 (100%) patients with detectable ctDNA post-operatively, including in seven that received gemcitabine-based adjuvant chemotherapy. Conclusion(s): ctDNA studies in localized pancreatic cancer are challenging, with a substantial number of patients not able to undergo resection, not having sufficient tumor tissue for analysis or not completing per protocol sample collection. ctDNA analysis, pre- and/or post-surgery, is a promising prognostic marker. Studies of ctDNA guided therapy are justified, including of treatment int

Background: While adjuvant therapy provides a survival benefit for patients (pts) with early-stage pancreatic cancer there are currently no biomarkers that define pts that are more or less likely to benefit from such treatment. This prospective study investigated the use of circulating tumour DNA (ctDNA) as a marker of residual disease, where detection could predict recurrence. Method(s): Patients newly diagnosed with operable pancreatic adenocarcinoma were enrolled. PCR-based-SafeSeqS assays were used to identify mutations at codons 12, 13 and 61 of KRAS in the primary tumor and to detect ctDNA in plasma samples. Patient management was as per standard of care, blinded to ctDNA data. Result(s): From January 2015 to June 2017, 42 pts with matched plasma samples, collected pre- and post-operatively, and tumor tissue available were evaluated. The median time between surgery and post-op blood collection was 6.3 (range:4-8) weeks. RAS mutations were identified in 38 (90.5%) tumor samples. ctDNA was detected in 23/37 (62.2%) pre-op and 13/35 (37.1%) post-op plasma samples. In multivariate analysis including stage, and resection margin, ctDNA status was the only statistically significant variable. Pre-op ctDNA detection was associated with worse median recurrence free survival (RFS), 10.3 months versus not reached, (Hazard Ratio (HR),3.4; 95% confidence interval (CI), 1.5- 7.6; P = 0.005) and 5.4 months versus 17.1 months, (HR, 5.4; 95% CI, 4.7-37.3; P < 0.0001) post-operatively. Similarly, the presence of ctDNA was associated with worse median overall survival (OS), 13.8 months versus not reached pre-operatively, (HR,3.4; 95% CI 1.1 to 8.3; P = 0.04) and 10.6 months versus not reached (HR,4.5; 95% CI 2.4-28.6; P = 0.001) post-operatively. Notably, recurrence occurred in 13 of 13 pts with detectable post-op ctDNA, despite more than half receiving standard adjuvant chemotherapy. Conclusion(s): ctDNA analysis is a promising prognostic marker in early-stage pancreatic cancer

Intramedullary spinal cord metastasis (ISCM) is rare and occurs most commonly in the setting of advanced malignancy. The optimal management pathways are not well defined and treatment outcomes from contemporary therapies remain variable. We report a case of a 49-year-old woman with known primary papillary thyroid carcinoma, who presented with rapidly progressive clinical features of Brown-Sequard syndrome. A detailed pooled analysis of the literature was conducted to characterise the clinical and demographic features, management options, and expected survival outcomes for cases of ISCM. We secondarily performed a subgroup analysis on the incidence, clinical and management characteristics of thyroid carcinoma ISCM.Copyright © 2017 Elsevier Ltd

Background: The optimal duration of ACT following surgery for colon cancer remains controversial. SCOT is an international, randomised trial that compared 3 months versus 6 months of ACT in this setting. We sought the survival benefits that patients participating in SCOT judged necessary to make extra 3 months of ACT worthwhile. Method(s): SCOT participants from Australia & New Zealand completed a validated questionnaire 3 and 18 months after randomisation to elicit the minimum survival benefit each participant judged necessary to make it worthwhile having ACT for 6 months rather than 3 months. Standardised hypothetical scenarios used the following baseline survivals with 3 months of ACT: life expectancies (LE) of 5 years (5Y) and 15 years (15Y), and 5-year survival rates (5YS) of 65% and 85%. Comparisons were nonparametric, 2-sided, and considered statistically significant if p < 0.05. Result(s): Questionnaires were completed by 160 participants, 82 allocated 3 months ACT, and 78 allocated 6 months ACT. ACT was FOLFOX in 121 (75%), XELOX in 39 (25%), and the mean age was 64. Preferences varied substantially among participants, and did not differ according to the randomly allocated treatment group. The median survival benefits judged necessary to make the extra 3 months of ACT worthwhile were an extra: 3 years beyond a LE of 5Y; 3 years beyond a LE of 15Y; 15% beyond a 65% 5YS; and 5% beyond an 85% 5YS. Preferences were similar at 3 months and 18 months. Participants with symptomatic peripheral neuropathy (132, 82%) judged a median benefit of an extra 5% beyond a 65% 5YS necessary to warrant their symptoms. Conclusion(s): Participants' preferences varied substantially, and many judged much larger benefits needed to warrant having ACT for 6 months rather than 3 months than the estimates of the benefits based on the IDEA meta-analysis.

Periampullary adenocarcinoma, including pancreatic cancer, is a heterogeneous group of tumors with dismal prognosis, partially due to lack of reliable targetable and predictive biomarkers. RNA-binding motif protein 3 (RBM3) has previously been shown to be an independent prognostic and predictive biomarker in several types of cancer. Herein, we examined the prognostic value of RBM3 in periampullary adenocarcinoma, as well as the effects following RBM3 suppression in pancreatic cancer cells in vitro. RBM3 mRNA levels were examined in 176 pancreatic cancer patients from The Cancer Genome Atlas. Immunohistochemical expression of RBM3 was analyzed in tissue microarrays with primary tumors and paired lymph node metastases from 175 consecutive patients with resected periampullary adenocarcinoma. Pancreatic cancer cells were transfected with anti-RBM3 siRNA in vitro and the influence on cell viability following chemotherapy, transwell migration and invasion was assessed. The results demonstrated that high mRNA-levels of RBM3 were significantly associated with a reduced overall survival (p = 0.026). RBM3 protein expression was significantly higher in lymph node metastases than in primary tumors (p = 0.005). High RBM3 protein expression was an independent predictive factor for the effect of adjuvant chemotherapy and an independent negative prognostic factor in untreated patients (p for interaction = 0.003). After siRNA suppression of RBM3 in vitro, pancreatic cancer cells displayed reduced migration and invasion compared to control, as well as a significantly increased resistance to chemotherapy. In conclusion, the strong indication of a positive response predictive effect of RBM3 expression in pancreatic cancer may be highly relevant in the clinical setting and merits further validation., Export Date: 13 February 2018; Article; Correspondence Address: Jirström, K.; Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Skåne University HospitalSweden; email: karin.jirstrom@med.lu.se. QC 20180228

Background: ASCOLT is an international Phase III randomized control trial (NCT00565708) investigating the impact of adjuvant aspirin on recurrence and survival after curative resection of colorectal cancer (CRC). Retrospective data suggest that COX2 and HLA Class 1 antigen expression may predict for aspirin benefit (Reimers MS, JAMA internal medicine, 2014;174(5):732-739; and Chan AT, JAMA, 2009;302(6):649-658.) Translational studies aim to confirm putative biomarkers of aspirin sensitivity in this prospective trial. This study reports the IHC assessment of COX2 and HLA in representative samples. Method(s): FFPE slides from consenting Australian patients were stained with COX2 and HLA Class 1 antibodies (Chan AT, JAMA, 2009;302(6):649-658.). Digital images were captured using Aperio software. IHC expression was scored by a pathologist (DW) blinded to sample identification. Intensity was assessed semi-quantitatively for each antibody in one area of dominant (primary) intensity and one of secondary intensity in each section. A scale was applied for staining intensity: 0=absent, 1=weak, 2=moderate and 3=strong; and for amount of tumor epithelium stained: 1= 5%-24%, 2= 25%-49%, 3=50%-74% 4= >75%. Normal epithelium, which typically has strong COX2 and HLA staining, was used as internal control. Only tumor epithelium was scored (not inflammatory cells). Result(s): 90 tumors were stained for both COX2 and HLA Class 1. All tumors showed diffuse staining for both markers, mostly strong, but with many tumors having regions with lesser degrees of expression (Table). Conclusion(s): COX2 expression was generally strong and HLA Class 1 was more likely to show regions of weak to moderate expression. No significant correlation was detected between COX2 and HLA expression levels. Further pathological analysis is underway and correlations will be made with outcome once trial data has matured in 2020.

BACKGROUND: The Short Course Oncology Therapy (SCOT) study is an international, multicentre, non-inferiority randomised controlled trial assessing the efficacy, toxicity, and cost-effectiveness of 3 months (3 M) versus the usually given 6 months (6 M) of adjuvant chemotherapy in colorectal cancer. METHOD(S): In total, 6088 patients with fully resected high-risk stage II or stage III colorectal cancer were randomised and followed up for 3-8 years. The within-trial cost-effectiveness analysis from a UK health-care perspective is presented using the resource use data, quality of life (EQ-5D-3L), time on treatment (ToT), disease-free survival after treatment (DFS) and overall survival (OS) data. Quality-adjusted partitioned survival analysis and Kaplan-Meier Sample Average Estimator estimated QALYs and costs. Probabilistic sensitivity and subgroup analysis was undertaken. RESULT(S): The 3 M arm is less costly (-4881; 95% CI: -6269; -3492) and entails (non-significant) QALY gains (0.08; 95% CI: -0.086; 0.230) due to a better significant quality of life. The net monetary benefit was significantly higher in 3 M under a wide range of monetary values of a QALY. The subgroup analysis found similar results for patients in the CAPOX regimen. However, for the FOLFOX regimen, 3 M had lower QALYs than 6 M (not statistically significant). CONCLUSION(S): Overall, 3 M dominates 6 M with no significant detrimental impact on QALYs. The results provide the economic case that a 3 M treatment strategy should be considered a new standard of care.Copyright © 2018, The Author(s).

Introduction: Oxaliplatin-based adjuvant chemotherapy has been the standard of care for resected early colon cancer for over a decade. Recent results from the IDEA meta-analysis attempt to address the question of whether 3 or 6 months of adjuvant chemotherapy is preferable in Stage III colon cancer. Areas covered: A review of the literature and recent conference presentations was undertaken on the topic of adjuvant therapy for resected early colon cancers. This article reviews the current evidence for adjuvant treatment of Stage II and III colon cancer, as well as up-to-date data regarding optimal duration of therapy. This article reviews the evidence for lifestyle modifications in the management of early colorectal cancer and other future directions for research in early colon cancer. Expert commentary: In recent years, there have been no advances in the development of novel agents for adjuvant therapy in colorectal cancer. Although the IDEA meta-analysis was negative for its primary non-inferiority endpoint, the detailed results provide valuable information that allows personalisation of treatment regimen and duration.Copyright © 2018 Informa UK Limited, trading as Taylor & Francis Group.

Introduction Uterine carcinosarcoma (UC), previously known as malignant mixed mullerian tumour (MMMT), is a rare uterine neoplasm containing both carcinomatous and sarcomatous components. It is an aggressive subtype of endometrial carcinoma associated with late diagnosis and poor prognosis, representing less than 5% of all uterine malignancies while accounting for more than 15% of uterine cancer related deaths. Due to the relatively low incidence of cases, the optimal management of these patients following primary surgical treatment remains uncertain. Objective To review the characteristics, treatment and outcomes of a cohort of cases of UC. Methods 92 cases of UC were identified from a retrospective observational study of patients whose primary operations were performed by four gynaeoncologists at Monash Health from 1994 to 2016 inclusive. Patient characteristics, histopathology reports, type(s) of adjuvant therapy, presence of recurrence and survival status were extracted from patient records. Staging was determined based on histopathology using the International Federation of Gynaecology and Obstetrics (FIGO) staging system. Results 33 (36%) patients were diagnosed with Stage I UC, 15 (16%) with Stage II, 27 (29%) with Stage III and 17 (18%) with Stage IV. The mean age at the time of primary surgery was 69.97 years, and the mean age at death was 73 years. There was an overall recurrence rate of 14% and death rate of 49%. The association between various patient, disease and treatment factors with survival was analysed. Age at diagnosis and stage of disease were both significant predictors of survival odds, with stage IV UC conferring the highest odds of death compared to stage I (OR 12.5, 95% CI 2-79.2), and increasing age at diagnosis demonstrating a small but significant increase in odds ratio for death (OR 1.06, 95% CI 1.005-1.12). However, there were no significant associations between type of adjuvant therapy and recurrence with death following both univariat

BACKGROUND: The Short Course Oncology Therapy (SCOT) study is an international, multicentre, non-inferiority randomised controlled trial assessing the efficacy, toxicity, and cost-effectiveness of 3 months (3 M) versus the usually given 6 months (6 M) of adjuvant chemotherapy in colorectal cancer. METHOD(S): In total, 6088 patients with fully resected high-risk stage II or stage III colorectal cancer were randomised and followed up for 3-8 years. The within-trial cost-effectiveness analysis from a UK health-care perspective is presented using the resource use data, quality of life (EQ-5D-3L), time on treatment (ToT), disease-free survival after treatment (DFS) and overall survival (OS) data. Quality-adjusted partitioned survival analysis and Kaplan-Meier Sample Average Estimator estimated QALYs and costs. Probabilistic sensitivity and subgroup analysis was undertaken. RESULT(S): The 3 M arm is less costly (-4881; 95% CI: -6269; -3492) and entails (non-significant) QALY gains (0.08; 95% CI: -0.086; 0.230) due to a better significant quality of life. The net monetary benefit was significantly higher in 3 M under a wide range of monetary values of a QALY. The subgroup analysis found similar results for patients in the CAPOX regimen. However, for the FOLFOX regimen, 3 M had lower QALYs than 6 M (not statistically significant). CONCLUSION(S): Overall, 3 M dominates 6 M with no significant detrimental impact on QALYs. The results provide the economic case that a 3 M treatment strategy should be considered a new standard of care.Copyright © 2018, The Author(s).

Introduction: Oxaliplatin-based adjuvant chemotherapy has been the standard of care for resected early colon cancer for over a decade. Recent results from the IDEA meta-analysis attempt to address the question of whether 3 or 6 months of adjuvant chemotherapy is preferable in Stage III colon cancer. Areas covered: A review of the literature and recent conference presentations was undertaken on the topic of adjuvant therapy for resected early colon cancers. This article reviews the current evidence for adjuvant treatment of Stage II and III colon cancer, as well as up-to-date data regarding optimal duration of therapy. This article reviews the evidence for lifestyle modifications in the management of early colorectal cancer and other future directions for research in early colon cancer. Expert commentary: In recent years, there have been no advances in the development of novel agents for adjuvant therapy in colorectal cancer. Although the IDEA meta-analysis was negative for its primary non-inferiority endpoint, the detailed results provide valuable information that allows personalisation of treatment regimen and duration.Copyright © 2018 Informa UK Limited, trading as Taylor & Francis Group.

Background: ASCOLT is an international Phase III randomized control trial (NCT00565708) investigating the impact of adjuvant aspirin on recurrence and survival after curative resection of colorectal cancer (CRC). Retrospective data suggest that COX2 and HLA Class 1 antigen expression may predict for aspirin benefit (Reimers MS, JAMA internal medicine, 2014;174(5):732-739; and Chan AT, JAMA, 2009;302(6):649-658.) Translational studies aim to confirm putative biomarkers of aspirin sensitivity in this prospective trial. This study reports the IHC assessment of COX2 and HLA in representative samples. Method(s): FFPE slides from consenting Australian patients were stained with COX2 and HLA Class 1 antibodies (Chan AT, JAMA, 2009;302(6):649-658.). Digital images were captured using Aperio software. IHC expression was scored by a pathologist (DW) blinded to sample identification. Intensity was assessed semi-quantitatively for each antibody in one area of dominant (primary) intensity and one of secondary intensity in each section. A scale was applied for staining intensity: 0=absent, 1=weak, 2=moderate and 3=strong; and for amount of tumor epithelium stained: 1= 5%-24%, 2= 25%-49%, 3=50%-74% 4= >75%. Normal epithelium, which typically has strong COX2 and HLA staining, was used as internal control. Only tumor epithelium was scored (not inflammatory cells). Result(s): 90 tumors were stained for both COX2 and HLA Class 1. All tumors showed diffuse staining for both markers, mostly strong, but with many tumors having regions with lesser degrees of expression (Table). Conclusion(s): COX2 expression was generally strong and HLA Class 1 was more likely to show regions of weak to moderate expression. No significant correlation was detected between COX2 and HLA expression levels. Further pathological analysis is underway and correlations will be made with outcome once trial data has matured in 2020.

Introduction Uterine carcinosarcoma (UC), previously known as malignant mixed mullerian tumour (MMMT), is a rare uterine neoplasm containing both carcinomatous and sarcomatous components. It is an aggressive subtype of endometrial carcinoma associated with late diagnosis and poor prognosis, representing less than 5% of all uterine malignancies while accounting for more than 15% of uterine cancer related deaths. Due to the relatively low incidence of cases, the optimal management of these patients following primary surgical treatment remains uncertain. Objective To review the characteristics, treatment and outcomes of a cohort of cases of UC. Methods 92 cases of UC were identified from a retrospective observational study of patients whose primary operations were performed by four gynaeoncologists at Monash Health from 1994 to 2016 inclusive. Patient characteristics, histopathology reports, type(s) of adjuvant therapy, presence of recurrence and survival status were extracted from patient records. Staging was determined based on histopathology using the International Federation of Gynaecology and Obstetrics (FIGO) staging system. Results 33 (36%) patients were diagnosed with Stage I UC, 15 (16%) with Stage II, 27 (29%) with Stage III and 17 (18%) with Stage IV. The mean age at the time of primary surgery was 69.97 years, and the mean age at death was 73 years. There was an overall recurrence rate of 14% and death rate of 49%. The association between various patient, disease and treatment factors with survival was analysed. Age at diagnosis and stage of disease were both significant predictors of survival odds, with stage IV UC conferring the highest odds of death compared to stage I (OR 12.5, 95% CI 2-79.2), and increasing age at diagnosis demonstrating a small but significant increase in odds ratio for death (OR 1.06, 95% CI 1.005-1.12). However, there were no significant associations between type of adjuvant therapy and recurrence with death following both univariat

On behalf of the Australasian Gastro-Intestinal Trials Group (AGITG) Background: The optimal duration of ACT following surgery for colon cancer remains controversial. SCOT is an international, randomized trial that compared 3 versus 6 months ofACT in this setting.We sought the survival benefits that patients participating in SCOT judged necessary to make extra 3 months of ACT worthwhile. Method(s): SCOT participants from Australia and New Zealand completed a validated questionnaire 3 and 18 months after randomization to elicit the minimum survival benefit each participant judged necessary to make it worthwhile having ACT for 6 months rather than 3 months. Standardized hypothetical scenarios used the following baseline survivals with 3 months of ACT: life expectancies (LE) of 5 years (5Y) and 15 years (15Y), and 5-year survival rates (5YS) of 65% and 85%. Comparisons were non-parametric, two-sided and considered statistically significant if P < 0.05. Result(s): Questionnaires were completed by 160 participants, 82 allocated 3 months ACT and 78 allocated 6 months ACT. ACT was FOLFOX in 121 (75%), XELOX in 39 (25%) and the mean age was 64. Preferences varied substantially among participants, and did not dif-Editorialmaterial and organisationc 2018 JohnWiley & Sons Australia, Ltd. Copyright of individual abstracts remains with the authors fer according to the randomly allocated treatment group. The median survival benefits judged necessary to make the extra 3 months of ACT worthwhile were an extra: 3 years beyond an LE of 5Y; 3 years beyond an LE of 15Y; 15% beyond a 65% 5YS; and 5% beyond an 85% 5YS. Preferences were similar at 3 and 18 months. Participants with symptomatic peripheral neuropathy (132, 82%) judged a median benefit of an extra 5% beyond a 65% 5YS necessary to warrant their symptoms. Conclusion(s): Participants' preferences varied substantially, and many judged much larger benefits needed to warrant having ACT for 6 months rather than 3 months than the es

Selecting potential recipient vessel options for free flap anastomosis is an important consideration in microsurgical breast and chest wall reconstruction. In these settings, the most common comprise the internal mammary and thoracodorsal vessels, although alternative anastomotic sites have also been described. On occasion, consideration of these alternatives becomes a necessity. The use of five separate recipient vessels is highlighted in a unique case of recurrent locally advanced breast cancer requiring multiple complex reconstructions using free tissue transfer. A 56-year-old lady presented for delayed breast reconstruction one year after radical mastectomy for locally advanced lobular breast cancer. Despite wide resections, local chest-wall recurrence five times necessitated five microsurgical reconstructions, using separate recipient pedicles: internal mammary vessels, thoracodorsal vessels, serratus branch of thoracodorsal vessels, intercostal vessels and thoracoacromial vessels. All flaps survived completely, without donor or recipient complications. There has not been a subsequent recurrence at 6 months since last reconstruction. The purpose of this report is to present the first reported case of microsurgical chest wall reconstruction using five separate free flaps requiring anastomosis to multiple recipient vessels for anterior chest wall coverage, to present a literature-based and clinical review of the regional vascular anatomy of the anterior chest wall, and to present an operative approach algorithm. In such complex cases, this understanding can facilitate a streamlined approach to management. © 2014 Wiley Periodicals, Inc. Microsurgery 37:66-70, 2017.Copyright © 2015 Wiley Periodicals, Inc.

Aim: Treatment with pertuzumab-trastuzumab-taxane combinations has become the international standard of care for patients with HER2-positive metastatic breast cancer. In this paper we discuss the practicalities of treating patients with this combination with a particular focus on treatment in the Australian setting. Method(s): An expert panel was convened to discuss practical aspects for use of pertuzumab in the Australian clinical setting. The findings of this panel are reported in this article. Result(s): The combination of pertuzumab-trastuzumab-docetaxel has established efficacy in patients with HER2-positive metastatic breast cancer, prolonging progression-free and overall survival compared to trastuzumab-taxane combinations. In Australia, combinations of pertuzumab and trastuzumab with docetaxel or paclitaxel are reimbursed. Management of treatment related side-effects such as diarrhea, febrile neutropenia and neuropathy typically include dose reduction or switching taxane. Specific patients with poorer tolerance of chemotherapy such as the elderly or those from Asian backgrounds may require particular management strategies. Conclusion(s): The advent of targeted therapies for women with metastatic HER2-positive breast cancer has markedly improved survival. Combinations of pertuzumab-trastuzumab and a taxane are the standard of care in patients with good performance status. Given prolongation of survival and the importance of quality of life endpoints, the treatment paradigm for patients with metastatic HER2-positive breast cancer is changing rapidly. Careful management of toxicities is required, and dose reduction or switching taxane may be necessary. Further research is required on the efficacy of pertuzumab combinations in patients with brain metastases, and on those who relapse quickly following adjuvant therapy.Copyright © 2016 Wiley Publishing Asia Pty Ltd.

Aim: Treatment with pertuzumab-trastuzumab-taxane combinations has become the international standard of care for patients with HER2-positive metastatic breast cancer. In this paper we discuss the practicalities of treating patients with this combination with a particular focus on treatment in the Australian setting. Method(s): An expert panel was convened to discuss practical aspects for use of pertuzumab in the Australian clinical setting. The findings of this panel are reported in this article. Result(s): The combination of pertuzumab-trastuzumab-docetaxel has established efficacy in patients with HER2-positive metastatic breast cancer, prolonging progression-free and overall survival compared to trastuzumab-taxane combinations. In Australia, combinations of pertuzumab and trastuzumab with docetaxel or paclitaxel are reimbursed. Management of treatment related side-effects such as diarrhea, febrile neutropenia and neuropathy typically include dose reduction or switching taxane. Specific patients with poorer tolerance of chemotherapy such as the elderly or those from Asian backgrounds may require particular management strategies. Conclusion(s): The advent of targeted therapies for women with metastatic HER2-positive breast cancer has markedly improved survival. Combinations of pertuzumab-trastuzumab and a taxane are the standard of care in patients with good performance status. Given prolongation of survival and the importance of quality of life endpoints, the treatment paradigm for patients with metastatic HER2-positive breast cancer is changing rapidly. Careful management of toxicities is required, and dose reduction or switching taxane may be necessary. Further research is required on the efficacy of pertuzumab combinations in patients with brain metastases, and on those who relapse quickly following adjuvant therapy.Copyright © 2016 Wiley Publishing Asia Pty Ltd.

The purpose of this study was to estimate the influence of adjuvant radiotherapy for primary breast cancer (BC) on the risk of contralateral BC (CBC) in BRCA1 or BRCA2(BRCA1/2) mutation carriers, with special attention to patients irradiated at age younger than 40 years. Additionally, tendencies in locoregional treatments and rates of contralateral risk-reducing mastectomy over time were explored. In this retrospective cohort study, 691 BRCA1/2-associated BC patients treated between 1980 and 2013 were followed from diagnosis until CBC or censoring event including ipsilateral BC recurrence, distant metastasis, contralateral risk-reducing mastectomy, other invasive cancer diagnosis, death, or loss to follow up. Hazard ratios (HR) for CBC associated with radiotherapy were estimated using Cox regression. Median follow-up time was 8.6 years [range 0.3–34.3 years]. No association between radiotherapy for primary BC and risk of CBC was found, neither in the total population (HR 0.82, 95 % CI 0.45–1.49) nor in the subgroup of patients younger than 40 years at primary diagnosis (HR 1.36, 95 % CI 0.60–3.09). During follow-up, the number of patients at risk decreased substantially since a large proportion of patients were censored after contralateral risk-reducing mastectomy or BC recurrence. Over the years, increasing preference for mastectomy without radiotherapy compared to breast-conserving surgery with radiotherapy was found ranging from less than 30 % in 1995 to almost 50 % after 2010. The rate of contralateral risk-reducing mastectomy increased over the years from less than 40 % in 1995 to more than 60 % after 2010. In this cohort of BRCA1/2-associated BC patients, no association between radiotherapy for primary BC and risk of CBC was observed in the total group, nor in the patients irradiated before the age of 40 years. The number of patients at risk after 10 and 15 years of follow-up, however, was too small to definitively exclude harmful effects of adjuvant radiother

Aim: To evaluate the efficacy and safety of bevacizumab in the adjuvant cancer therapy setting within different subset of patients. Methods & Design/Results: PubMed, EMBASE, Cochrane and Clinical trials.gov databases were searched for English language studies of randomized controlled trials comparing bevacizumab and adjuvant therapy with adjuvant therapy alone published from January 1966 to 7thof May 2014. Progression free survival, overall survival, overall response rate, safety and quality of life were analyzed using random- or fixed-effects models according to the PRISMA guidelines. We obtained data from 44 randomized controlled trials (30,828 patients). Combining bevacizumab with different adjuvant therapies resulted in significant improvement of progression free survival (log hazard ratio, 0.87; 95% confidence interval (CI), 0.84-0.89), overall survival (log hazard ratio, 0.96; 95% CI, 0.94-0.98) and overall response rate (relative risk, 1.46; 95% CI: 1.33-1.59) compared to adjuvant therapy alone in all studied tumor types. In subgroup analyses, there were no interactions of bevacizumab with baseline characteristics on progression free survival and overall survival, while overall response rate was influenced by tumor type and bevacizumab dose (p-value: 0.02). Although bevacizumab use resulted in additional expected adverse drug reactions except anemia and fatigue, it was not associated with a significant decline in quality of life. There was a trend towards a higher risk of several side effects in patients treated by high-dose bevacizumab compared to the lowdose e.g. all grade proteinuria (9.24; 95% CI: 6.60-12.94 vs. 2.64; 95% CI: 1.29-5.40). Conclusions: Combining bevacizumab with different adjuvant therapies provides a survival benefit across all major subsets of patients, including by tumor type, type of adjuvant therapy, and duration and dose of bevacizumab therapy. Though bevacizumab was associated with increased risks of some adverse drug reactions s

Increasing breast cancer incidence and decreasing mortality have highlighted the importance of survivorship issues related to breast cancer. A consideration of the issues related to menopause is therefore of great importance to both women and clinicians. Menopause/menopausal symptoms, with significant negative effects on quality of life and potential long-term health impacts, may in women with breast cancer be associated with: (1) natural menopause occurring concurrently with a breast cancer diagnosis; (2) recurrence of menopausal symptoms following cessation of hormone replacement therapy; (3) treatment-induced menopause (chemotherapy, ovarian ablation/suppression) and adjuvant endocrine therapy. A variety of non-hormonal pharmacological and non-pharmacological therapies have been investigated as therapeutic options for menopausal symptoms with mixed results, and ongoing research is required. This review presents a summary of the causes, common problematic symptoms of menopause (vasomotor, genitourinary and sexual dysfunction), and longer-term consequences (cardiovascular disease and osteoporosis) related to menopause. It proposes an evidenced-based multidisciplinary approach to the management of menopause/menopausal symptoms in women with breast cancer.Copyright © 2015 © 2015 International Menopause Society.

Increasing breast cancer incidence and decreasing mortality have highlighted the importance of survivorship issues related to breast cancer. A consideration of the issues related to menopause is therefore of great importance to both women and clinicians. Menopause/menopausal symptoms, with significant negative effects on quality of life and potential long-term health impacts, may in women with breast cancer be associated with: (1) natural menopause occurring concurrently with a breast cancer diagnosis; (2) recurrence of menopausal symptoms following cessation of hormone replacement therapy; (3) treatment-induced menopause (chemotherapy, ovarian ablation/suppression) and adjuvant endocrine therapy. A variety of non-hormonal pharmacological and non-pharmacological therapies have been investigated as therapeutic options for menopausal symptoms with mixed results, and ongoing research is required. This review presents a summary of the causes, common problematic symptoms of menopause (vasomotor, genitourinary and sexual dysfunction), and longer-term consequences (cardiovascular disease and osteoporosis) related to menopause. It proposes an evidenced-based multidisciplinary approach to the management of menopause/menopausal symptoms in women with breast cancer.Copyright © 2015 © 2015 International Menopause Society.

Purpose Neoadjuvant chemotherapy before cystectomy is recommended. To our knowledge the subset of patients likely to benefit has not been identified. We validate emmprin and survivin as markers of chemotherapy response. Materials and Methods Tumor specimens were obtained before therapy from a total of 250 patients with T1-T4 bladder cancer enrolled in 2 randomized trials comparing neoadjuvant chemotherapy before cystectomy with a surgery only arm. Protein expression was determined by immunohistochemistry. Results Expression was categorized according to predefined cutoffs reported in the literature. Data were analyzed with the Kaplan-Meier method and Cox models. Patients in the chemotherapy cohort with negative emmprin expression had significantly higher down staging overall survival than those with positive expression (71% vs 38%, p <0.001). The values for cancer specific survival were 76% and 56%, respectively (p <0.027). In the cystectomy only cohort emmprin expression was not associated with overall survival (46% vs 35%, p = 0.23) or cancer specific survival (55% vs 51%, p = 0.64). Emmprin negative patients had an absolute risk reduction of 25% in overall survival (95% CI 11-40) and a number needed to treat of 4 (95% CI 2.5-9.3). Survivin expression was not useful as a biomarker in this study. Limitations were the retrospective design and heterogeneity coupled with the time difference between the trials. Conclusions Patients with emmprin negative tumors have a better response to neoadjuvant chemotherapy before cystectomy than those with positive expression. © 2015 American Urological Association Education and Research, Inc.

Objectives To test the hypothesis that observation with early salvage radiotherapy (SRT) is not inferior to 'standard' treatment with adjuvant RT (ART) with respect to biochemical failure in patients with pT3 disease and/or positive surgical margins (SMs) after radical prostatectomy (RP). To compare the following secondary endpoints between the two arms: patient-reported outcomes, adverse events, biochemical failure-free survival, overall survival, disease-specific survival, time to distant failure, time to local failure, cost utility analysis, quality adjusted life years and time to androgen deprivation. Patients and Methods The Radiotherapy - Adjuvant Versus Early Salvage (RAVES) trial is a phase III multicentre randomised controlled trial led by the Trans Tasman Radiation Oncology Group (TROG), in collaboration with the Urological Society of Australia and New Zealand (USANZ), and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP). In all, 470 patients are planned to be randomised 1:1 to either ART commenced at <=4 months of RP (standard of care) or close observation with early SRT triggered by a PSA level of >0.20 ng/mL (experimental arm). Eligible patients have had a RP for adenocarcinoma of the prostate with at least one of the following risk factors: positive SMs +/- extraprostatic extension +/- seminal vesicle involvement. The postoperative PSA level must be <=0.10 ng/mL. Rigorous investigator credentialing and a quality assurance programme are designed to promote consistent RT delivery among patients. Results Trial is currently underway, with 258 patients randomised as of 31 October 2013. International collaborations have developed, including a planned meta-analysis to be undertaken with the UK Medical Research Council/National Cancer Institute of Canada Clinical Trials Group RADICALS (Radiotherapy and Androgen Deprivation In Combination with Local Surgery) trial and an innovative psycho-oncology sub-study to investigate a pat

Androgen deprivation therapy (ADT) is increasingly used to treat advanced prostate cancer and is also utilised as adjuvant or neo-adjuvant treatment for high-risk disease. The resulting suppression of endogenous testosterone production has deleterious effects on quality of life, including hot flushes, reduced mood and cognition and diminished sexual function. Cross-sectional and longitudinal studies show that ADT has adverse bone and cardiometabolic effects. The rate of bone loss is accelerated, increasing the risk of osteoporosis and subsequent fracture. Fat mass is increased and lean mass reduced, and adverse effects on lipid levels and insulin resistance are observed, the latter increasing the risk of developing type 2 diabetes. ADT also appears to increase the risk of incident cardiovascular events, although whether it increases cardiovascular mortality is not certain from the observational evidence published to date. Until high-quality evidence is available to guide management, it is reasonable to consider men undergoing ADT to be at a higher risk of psychosexual dysfunction, osteoporotic fracture, diabetes and cardiovascular disease, especially when treated for extended periods of time and therefore subjected to profound and prolonged hypoandrogenism. Health professionals caring for men undergoing treatment for prostate cancer should be aware of the potential risks of ADT and ensure appropriate monitoring and clinical management. © 2014 Society for Endocrinology. Published by Bioscientifica Ltd.

Early diagnosis of muscle-invasive bladder cancer can be life saving. Treatment will depend on the staging of the cancer.