Feasibility, acceptability, and preliminary efficacy of a self-directed online psychosocial intervention for women with metastatic breast cancer: Finding My Way-Advanced.

PURPOSE: Few digital interventions target patients with advanced cancer. Hence, we feasibility-tested Finding My Way-Advanced (FMW-A), a self-guided program for women with metastatic breast cancer. METHODS: A single-site randomised controlled pilot trial was conducted. Participants were recruited through clinicians, professional networks, and social media and randomised to intervention or usual-care control. Participants were randomly allocated to either the intervention (FMW-A; a 6-week, 6-module CBT-based online self-directed psychosocial program for women with MBC + usual care resources) or control (usual care resources: BCNA's Hope and Hurdles kit). Feasibility outcomes included rates of recruitment, uptake, engagement, and attrition. Distress, QOL, and unmet needs were evaluated for signals of efficacy, and qualitative feedback was collected to assess acceptability. RESULTS: Due to COVID-19 and funding constraints, the target recruitment of 40 was not reached (n = 60 approached; n = 55 eligible; n = 35 consented). Uptake was high (n = 35/55; 63.6%), engagement modest (median 3/6 modules per user), and attrition acceptable (66% completed post-treatment). Efficacy signals were mixed: compared to controls, FMW-A participants experienced small improvements in fear of progression (d = 0.21) and global QOL (d = 0.22) and demonstrated a trend towards improvements in cancer-specific distress (d = 0.13) and role functioning (d = 0.18). However, FMW-A participants experienced small-to-moderate deteriorations in general distress (d = 0.23), mental QOL (d = 0.51), and social functioning (d = 0.27), whereas controls improved. Qualitatively, participants (n = 4) were satisfied with the program, perceived it as appropriate, but noted some sections could evoke transient distress. CONCLUSION: The study demonstrated feasibility (high uptake and acceptable retention) and generated realistic recruitment estimates. While FMW-A appears promising for targeting cancer-specific distress and fear of progression, the mixed findings in quality of life and general distress warrant further revisions and testing.

Outcomes of patients with gallbladder cancer presenting with acute cholecystitis.

The main purpose of this study is to explore the outcomes of patients found to have gallbladder cancer during investigation and diagnosis of acute cholecystitis. The incidence of primary gallbladder cancer co-existing in acute cholecystitis is not well defined in the literature, with anecdotal reports suggesting that they experience worse outcomes than patients with gallbladder cancer found incidentally. METHODS: A retrospective review of all patients with gallbladder cancer managed at the Canberra Health Service between 1998 and May 2022 were identified and reviewed. RESULTS: A total of 65 patients were diagnosed with primary gallbladder cancer during the study period with a mean age of 70.4 years (SD 11.4, range 59-81.8 years) and a female preponderance (74% versus 26%) with a ratio of 2.8. Twenty (31%) patients presented with acute calculus cholecystitis and were found to have a primary gallbladder cancer. This group of patients were older and predominantly female, but the difference was not statistically significant. The overall 5-year survival in the cohort was 20% (stage 1 63%, stage 2 23%, stage 3 16%, and stage 4 0%). There was no statistically significant difference in survival between those who presented with acute cholecystitis vs other presentations. CONCLUSIONS: A third of the patients with gallbladder cancer presented with acute cholecystitis. There was no statistically significant difference in survival in those with bile spillage during cholecystectomy as well those presenting with acute cholecystitis.

Identifying women at risk of weight gain after a breast cancer diagnosis: Results from a cohort of Australian women.

ISSUES ADDRESSED: This study aimed to identify risk factors associated with weight gain post a diagnosis of breast cancer in a cohort of Australian women. METHODS: In this retrospective clinical audit, objectively measured weight, age and menopause status, treatment type/s, grade, stage, oestrogen receptor and progesterone receptor (PR) status were extracted for 73 breast cancer patients from an ongoing breast cancer treatment quality assurance project. Weight gain or loss was classified as a body mass increase or decrease of ≥5% of weight at diagnosis. RESULTS: When compared to weight at diagnosis, 57% of patients maintained, 22% gained, and 21% lost weight at 24 months post-diagnosis. Factors associated with weight gain were a diagnosis of grade II (P < .001) or grade III (P < .001) compared to grade I breast cancer, and refusal of radiotherapy (P < .001). Factors associated with weight loss were being postmenopausal compared to premenopausal (P = .033), PR positive compared to PR negative (P < .001), refusal of chemotherapy (P < .001) and radiotherapy recommended (P < .001). CONCLUSIONS: The maintenance of weight in a majority of women in this cohort is a novel finding. Early identification of women at risk of weight gain post a breast cancer diagnosis can assist health professionals identify, and therefore assisting patients in the prevention and management of weight gain and associated sequela. Investigating the weight-related communications between a patient and specialist, their access to allied health professionals and social support may assist in understanding the overall positive changes in this cohort.

Prognostic significance of postsurgery circulating tumor DNA in nonmetastatic colorectal cancer: Individual patient pooled analysis of three cohort studies.

Studies in multiple solid tumor types have demonstrated the prognostic significance of ctDNA analysis after curative intent surgery. A combined analysis of data across completed studies could further our understanding of circulating tumor DNA (ctDNA) as a prognostic marker and inform future trial design. We combined individual patient data from three independent cohort studies of nonmetastatic colorectal cancer (CRC). Plasma samples were collected 4 to 10 weeks after surgery. Mutations in ctDNA were assayed using a massively parallel sequencing technique called SafeSeqS. We analyzed 485 CRC patients (230 Stage II colon, 96 Stage III colon, and 159 locally advanced rectum). ctDNA was detected after surgery in 59 (12%) patients overall (11.0%, 12.5% and 13.8% for samples taken at 4-6, 6-8 and 8-10 weeks; P = .740). ctDNA detection was associated with poorer 5-year recurrence-free (38.6% vs 85.5%; P < .001) and overall survival (64.6% vs 89.4%; P < .001). The predictive accuracy of postsurgery ctDNA for recurrence was higher than that of individual clinicopathologic risk features. Recurrence risk increased exponentially with increasing ctDNA mutant allele frequency (MAF) (hazard ratio, 1.2, 2.5 and 5.8 for MAF of 0.1%, 0.5% and 1%). Postsurgery ctDNA was detected in 3 of 20 (15%) patients with locoregional and 27 of 60 (45%) with distant recurrence (P = .018). This analysis demonstrates a consistent long-term impact of ctDNA as a prognostic marker across nonmetastatic CRC, where ctDNA outperforms other clinicopathologic risk factors and MAF further stratifies recurrence risk. ctDNA is a better predictor of distant vs locoregional recurrence.

How does the gut microbiome influence immune checkpoint blockade therapy?

Immune checkpoint blockade (ICB) therapies are revolutionary cancer treatments; however, they only benefit about a third of patients. Therefore, extensive research is underway to find methods to improve their therapeutic efficacy. One avenue of study that has recently emerged is to consider the role the gut microbiome plays in therapeutic success. Several high-impact studies have repeatedly shown that the presence, composition and level of diversity of the gut flora directly impact cancer treatment outcome in both mice and patients. These studies have also highlighted the danger of using antibiotics shortly before or during cancer treatments. However, there are still several questions that need to be answered, including which bacteria promote the greatest benefit, the mechanisms by which they act and how we can use this information to influence treatment outcome. In this review, we explain how the gut microbiome was realized to be of such importance and propose hypotheses for why gut flora have such a critical impact on ICB therapeutic success. We also describe a hypothetical mechanism involving bacterial translocation out of the gut and into the tumor, whereby the bacteria act in an adjuvant capacity to facilitate an antitumor response. By highlighting key papers in the field, we hope to hasten research on the subject so as to find a means to improve the therapeutic efficacy of these ground-breaking cancer treatments.

Medical Oncology Group of Australia position statement: COVID-19 vaccination in patients with solid tumours.

People with cancer are vulnerable to increased morbidity and mortality from the coronavirus disease 2019 (COVID-19). COVID-19 vaccination is key to protecting the population of people with cancer from adverse outcomes of SARS-CoV-2 infection. The Medical Oncology Group of Australia aimed to address the considerations around COVID-19 vaccination in people with cancer, in particular, safety and efficacy of vaccination. The assessment of patients with generalised allergic reaction to anti-cancer therapy containing vaccine components and practical implementation of vaccination of people on active anti-cancer therapy are also discussed.

Telehealth in cancer care: during and beyond the COVID-19 pandemic.

The COVID-19 pandemic has precipitated the rapid uptake of telehealth in cancer care and in other fields. Many of the changes made in routine clinical practice could be embedded beyond the duration of the pandemic. This is intended as a practical guide to cancer clinicians and others in establishing and improving the quality of consultations performed by telehealth.

Serial circulating tumour DNA analysis during multimodality treatment of locally advanced rectal cancer: a prospective biomarker study.

OBJECTIVE: For patients with locally advanced rectal cancer (LARC), adjuvant chemotherapy selection following surgery remains a major clinical dilemma. Here, we investigated the ability of circulating tumour DNA (ctDNA) to improve risk stratification in patients with LARC. DESIGN: We enrolled patients with LARC (T3/T4 and/or N+) planned for neoadjuvant chemoradiotherapy. Plasma samples were collected pretreatment, postchemoradiotherapy and 4-10 weeks after surgery. Somatic mutations in individual patient's tumour were identified via massively parallel sequencing of 15 genes commonly mutated in colorectal cancer. We then designed personalised assays to quantify ctDNA in plasma samples. Patients received adjuvant therapy at clinician discretion, blinded to the ctDNA results. RESULTS: We analysed 462 serial plasma samples from 159 patients. ctDNA was detectable in 77%, 8.3% and 12% of pretreatment, postchemoradiotherapy and postsurgery plasma samples. Significantly worse recurrence-free survival was seen if ctDNA was detectable after chemoradiotherapy (HR 6.6; P<0.001) or after surgery (HR 13.0; P<0.001). The estimated 3-year recurrence-free survival was 33% for the postoperative ctDNA-positive patients and 87% for the postoperative ctDNA-negative patients. Postoperative ctDNA detection was predictive of recurrence irrespective of adjuvant chemotherapy use (chemotherapy: HR 10.0; P<0.001; without chemotherapy: HR 22.0; P<0.001). Postoperative ctDNA status remained an independent predictor of recurrence-free survival after adjusting for known clinicopathological risk factors (HR 6.0; P<0.001). CONCLUSION: Postoperative ctDNA analysis stratifies patients with LARC into subsets that are either at very high or at low risk of recurrence, independent of conventional clinicopathological risk factors. ctDNA analysis could potentially be used to guide patient selection for adjuvant chemotherapy.

Finding My Way: results of a multicentre RCT evaluating a web-based self-guided psychosocial intervention for newly diagnosed cancer survivors.

PURPOSE: This multicentre randomised controlled trial examined the efficacy of Finding My Way (FMW), a 6-week/6-module online self-guided psychotherapeutic intervention for newly diagnosed curatively treated cancer survivors, in reducing cancer-related distress and improving quality of life compared to an online attention control. METHODS: Participants were randomised on a 1:1 ratio using a gender-stratified block design to intervention (n = 94) or attention control (n = 97), and were blinded to condition. Assessments were completed at baseline (T0), post-intervention (T1), 3 months (T2), and 6 months (T3) post-intervention. Mixed model repeated measures analyses examined differences between groups for cancer-specific distress (primary outcome) and general distress, quality of life (QoL), coping, and health service utilisation (secondary outcomes). RESULTS: While both groups reported reduced cancer-specific and general distress over time, between-group differences were not significant. Intervention participants reported lower total health service utilisation and supportive care utilisation post-intervention than controls (total HS use: between-group mean difference = - 1.07 (- 1.85 to - 0.28); supportive care use: between-group mean difference = - 0.64 (- 1.21 to - 0.06)) and significantly higher emotional functioning at 3 months (between-group mean difference = 7.04 (0.15 to 13.9)). At 6 months, the supportive care utilisation finding reversed (between-group mean difference = 0.78 points (0.19 to 1.37). Across remaining QoL and coping outcomes, no significant group differences emerged. CONCLUSIONS: While both groups experienced reductions in distress, between-group differences were not significant. This contrasts with the significantly improved emotional functioning observed in FMW participants at 3 months and the short-term reductions in health service utilisation. Long-term increases in supportive care service utilisation suggest FMW only met needs while being actively used. TRIAL REGISTRATION: ACTRN12613000001796;  http://www.ANZCTR.org.au/ACTRN12613000001796.aspx.

Nuclear-Biased DUSP6 Expression is Associated with Cancer Spreading Including Brain Metastasis in Triple-Negative Breast Cancer.

DUSP6 is a dual-specificity phosphatase (DUSP) involved in breast cancer progression, recurrence, and metastasis. DUSP6 is predominantly cytoplasmic in HER2+ primary breast cancer cells, but the expression and subcellular localization of DUSPs, especially DUSP6, in HER2-positive circulating tumor cells (CTCs) is unknown. Here we used the DEPArray system to identify and isolate CTCs from metastatic triple negative breast cancer (TNBC) patients and performed single-cell NanoString analysis to quantify cancer pathway gene expression in HER2-positive and HER2-negative CTC populations. All TNBC patients contained HER2-positive CTCs. HER2-positive CTCs were associated with increased ERK1/ERK2 expression, which are direct DUSP6 targets. DUSP6 protein expression was predominantly nuclear in breast CTCs and the brain metastases but not pleura or lung metastases of TNBC patients. Therefore, nuclear DUSP6 may play a role in the association with cancer spreading in TNBC patients, including brain metastasis.

Optimizing poly (ADP-ribose) polymerase inhibition through combined epigenetic and immunotherapy.

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with poor survival outcomes. Currently, there are no targeted therapies available for TNBCs despite remarkable progress in targeted and immune-directed therapies for other solid organ malignancies. Poly (ADP-ribose) polymerase inhibitors (PARPi) are effective anticancer drugs that produce good initial clinical responses, especially in homologous recombination DNA repair-deficient cancers. However, resistance is the rule rather than the exception, and recurrent tumors tend to have an aggressive phenotype associated with poor survival. Many efforts have been made to overcome PARPi resistance, mostly by targeting genes and effector proteins participating in homologous recombination that are overexpressed during PARPi therapy. Due to many known and unknown compensatory pathways, genes, and effector proteins, overlap and shared resistance are common. Overexpression of programmed cell death-ligand 1 (PD-L1) and cancer stem cell (CSC) sparing are novel PARPi resistance hypotheses. Although adding programmed cell death-1 (PD-1)/PD-L1 inhibitors to PARPi might improve immunogenic cell death and be crucial for durable responses, they are less likely to target the CSC population that drives recurrent tumor growth. Lysine-specific histone demethylase-1A and histone deacetylase inhibitors have shown promising activity against CSCs. Combining epigenetic drugs such as lysine-specific histone demethylase-1A inhibitors or histone deacetylase inhibitors with PARPi/anti-PD-1/PD-L1 is a novel, potentially synergistic strategy for priming tumors and overcoming resistance. Furthermore, such an approach could pave the way for the identification of new upstream epigenetic and genetic signatures.

The survival outcome of patients with metastatic colorectal cancer based on the site of metastases and the impact of molecular markers and site of primary cancer on metastatic pattern.

BACKGROUND: Pattern of spread in patients with metastatic colorectal cancer (mCRC) is variable and may reflect different biology in subsets of patients. This is a retrospective study to explore the outcome of patients with mCRC based on their site of metastasis at diagnosis and to explore the association between tumor characteristics [KRAS/RAS, BRAF, mismatch repair (MMR) status, site of primary] and the site of metastasis. METHODS: Patients from two Australian databases were divided into six groups based on site of metastasis at time of diagnosis of metastatic disease; lung-only, liver-only, lymph node-only or any patients with brain, bone or peritoneal metastases. Primary endpoint was overall survival (OS) of each cohort compared with the rest of the population. A Mantel-Haenszel chi-squared test used to explore the association between site of metastasis and selected tumor characteristics. RESULTS: Five thousand nine hundred and sixty-seven patients were included. In a univariate analysis, median OS was significantly higher when metastases were limited to lung or liver and shorter for those with brain, bone or peritoneal metastases (p < .001) in both datasets. BRAF mutation was strongly associated with peritoneal metastases (relative risk = 1.8, p < .001) with lower incidence of lung (RR = 0.3, p = .004) and liver (RR = 0.7, p = .005) limited metastases. Lung-only metastases were more frequent with KRAS/RAS mutation (RR = 1.4, p = .007). Left colon tumors were associated with bone (RR = 1.6, p < .001) and lung-only metastases (RR = 2.3, p = .001) while peritoneal spread was less frequent compared with right colon tumors (RR = 0.6, p < .001). Rectal cancer was associated with brain, bone and lung metastases (RR = 1.7; p = .002, 1.7; p < .001, 2.0; p < .001). Liver-only metastases were less frequent in deficient MMR tumors (RR = 0.7, p = .01). CONCLUSION: Survival duration with mCRC is related to the site of metastases with lung limited disease showing a more favorable survival outcome compared to other single metastatic site disease. The BRAF mutation and primary rectal cancer were associated with poor prognostic metastatic sites.

Chemotherapy and radiotherapy for advanced pancreatic cancer.

BACKGROUND: Pancreatic cancer (PC) is a highly lethal disease with few effective treatment options. Over the past few decades, many anti-cancer therapies have been tested in the locally advanced and metastatic setting, with mixed results. This review attempts to synthesise all the randomised data available to help better inform patient and clinician decision-making when dealing with this difficult disease. OBJECTIVES: To assess the effect of chemotherapy, radiotherapy or both for first-line treatment of advanced pancreatic cancer. Our primary outcome was overall survival, while secondary outcomes include progression-free survival, grade 3/4 adverse events, therapy response and quality of life. SEARCH METHODS: We searched for published and unpublished studies in CENTRAL (searched 14 June 2017), Embase (1980 to 14 June 2017), MEDLINE (1946 to 14 June 2017) and CANCERLIT (1999 to 2002) databases. We also handsearched all relevant conference abstracts published up until 14 June 2017. SELECTION CRITERIA: All randomised studies assessing overall survival outcomes in patients with advanced pancreatic ductal adenocarcinoma. Chemotherapy and radiotherapy, alone or in combination, were the eligible treatments. DATA COLLECTION AND ANALYSIS: Two review authors independently analysed studies, and a third settled any disputes. We extracted data on overall survival (OS), progression-free survival (PFS), response rates, adverse events (AEs) and quality of life (QoL), and we assessed risk of bias for each study. MAIN RESULTS: We included 42 studies addressing chemotherapy in 9463 patients with advanced pancreatic cancer. We did not identify any eligible studies on radiotherapy.We did not find any benefit for chemotherapy over best supportive care. However, two identified studies did not have sufficient data to be included in the analysis, and many of the chemotherapy regimens studied were outdated.Compared to gemcitabine alone, participants receiving 5FU had worse OS (HR 1.69, 95% CI 1.26 to 2.27, moderate-quality evidence), PFS (HR 1.47, 95% CI 1.12 to 1.92) and QoL. On the other hand, two studies showed FOLFIRINOX was better than gemcitabine for OS (HR 0.51 95% CI 0.43 to 0.60, moderate-quality evidence), PFS (HR 0.46, 95% CI 0.38 to 0.57) and response rates (RR 3.38, 95% CI 2.01 to 5.65), but it increased the rate of side effects. The studies evaluating CO-101, ZD9331 and exatecan did not show benefit or harm when compared with gemcitabine alone.Giving gemcitabine at a fixed dose rate improved OS (HR 0.79, 95% CI 0.66 to 0.94, high-quality evidence) but increased the rate of side effects when compared with bolus dosing.When comparing gemcitabine combinations to gemcitabine alone, gemcitabine plus platinum improved PFS (HR 0.80, 95% CI 0.68 to 0.95) and response rates (RR 1.48, 95% CI 1.11 to 1.98) but not OS (HR 0.94, 95% CI 0.81 to 1.08, low-quality evidence). The rate of side effects increased. Gemcitabine plus fluoropyrimidine improved OS (HR 0.88, 95% CI 0.81 to 0.95), PFS (HR 0.79, 95% CI 0.72 to 0.87) and response rates (RR 1.78, 95% CI 1.29 to 2.47, high-quality evidence), but it also increased side effects. Gemcitabine plus topoisomerase inhibitor did not improve survival outcomes but did increase toxicity. One study demonstrated that gemcitabine plus nab-paclitaxel improved OS (HR 0.72, 95% CI 0.62 to 0.84, high-quality evidence), PFS (HR 0.69, 95% CI 0.58 to 0.82) and response rates (RR 3.29, 95% CI 2.24 to 4.84) but increased side effects. Gemcitabine-containing multi-drug combinations (GEMOXEL or cisplatin/epirubicin/5FU/gemcitabine) improved OS (HR 0.55, 95% CI 0.39 to 0.79, low-quality evidence), PFS (HR 0.43, 95% CI 0.30 to 0.62) and QOL.We did not find any survival advantages when comparing 5FU combinations to 5FU alone. AUTHORS' CONCLUSIONS: Combination chemotherapy has recently overtaken the long-standing gemcitabine as the standard of care. FOLFIRINOX and gemcitabine plus nab-paclitaxel are highly efficacious, but our analysis shows that other combination regimens also offer a benefit. Selection of the most appropriate chemotherapy for individual patients still remains difficult, with clinicopathological stratification remaining elusive. Biomarker development is essential to help rationalise treatment selection for patients.

Metastatic pancreatic ductal adenocarcinoma: diagnosis and treatment with a view to the future.

Metastatic pancreatic ductal adenocarcinoma (mPDAC) is a lethal disease with a poor 5-year survival. Systemic treatments can be used to control symptoms and prolong life. Cytotoxic chemotherapies are commonly administered, with combination treatments, such as fluorouracil, folinic acid, irinotecan and oxaliplatin (FOLFIRINOX) or nab-paclitaxel and gemcitabine showing the largest clinical benefits. Newer genomic classifications of PDAC may provide a rationale for targeted therapies or immunotherapies, although at present these remain largely experimental. This review discusses the evidence behind the currently used regimens, while introducing the potential future of pancreatic cancer care.

Uptake and adherence to an online intervention for cancer-related distress: older age is not a barrier to adherence but may be a barrier to uptake.

PURPOSE: While online interventions are increasingly explored as an alternative to therapist-based interventions for cancer-related distress, limitations to efficacy potentially include low uptake and adherence. Few predictors of uptake or adherence to online interventions have been consistently identified, particularly in individuals with cancer. This study examined rates and predictors of uptake and adherence to Finding My Way, a RCT of an online intervention versus an information-only online control for cancer-related distress. METHODS: Participants were adults with cancer treated with curative intent. Adherence was assessed by login frequency, duration and activity level; analyses examined demographic, medical and psychological predictors of uptake and adherence. RESULTS: The study enrolled 191 adults (aged 26-94 years) undergoing active treatment for cancer of any type. Uptake was highest for females and for individuals with ovarian (80%) and breast cancer (49.8%), and lowest for those with melanoma (26.5%). Adherence was predicted by older age and control-group allocation. Baseline distress levels did not predict adherence. High adherers to the full intervention had better emotion regulation and quality of life than low adherers. CONCLUSIONS: Uptake of online intervention varies according to age, gender and cancer type. While uptake was higher amongst younger individuals, once enrolled, older individuals were more likely to adhere to online interventions for cancer-related distress.

Patterns of care for metastatic renal cell carcinoma in Australia.

OBJECTIVE: To examine the patterns of care and outcomes for metastatic renal cell carcinoma (mRCC) in Australia, where there are limited reimbursed treatment options. In particular, we aim to explore prescribing patterns for first-line systemic treatment, the practice of an initial watchful-waiting approach, and the use of systemic treatments in elderly patients. SUBJECTS/PATIENTS AND METHODS: Patients with mRCC undergoing treatment between 2006 and 2012 were identified from four academic hospitals in Victoria and Australian Capital Territory. Demographic, clinicopathological, treatment, and survival data were recorded by chart review. Descriptive statistics were used to report findings. Survival was estimated by the Kaplan-Meier method and compared using the log-rank test. The study was supported by a grant from Pfizer Australia. RESULTS: Our study identified 212 patients with mRCC for analysis. Patients were predominantly of clear cell histology (75%), Eastern Cooperative Oncology Group performance status <2 (67%) and with favourable/intermediate Memorial Sloan-Kettering Cancer Center risk (68%). The median age at diagnosis was 61 years. In all, 163 (77%) patients received first-line systemic therapy, while 49 (23%) received best supportive care (BSC). The most frequently used first-line treatment was sunitinib (125 patients, 77%). Patients who received sunitinib had a median overall survival (OS) of 27.6 months. In all, 43% of patients who received sunitinib underwent a watchful-waiting period of >90 days before initiating treatment; these patients had a median OS of 56.3 months. Elderly patients (50 patients aged ≥70 years) were more likely to receive BSC alone than younger patients (46% vs 16%, P < 0.001). Of those who received systemic therapy, elderly patients were also more likely to have upfront dose reductions (30% vs 8%, P = 0.03). CONCLUSION: Our study of patients with mRCC treated in Australian centres showed that sunitinib was the most commonly prescribed systemic treatment between 2006 and 2012, associated with survival outcomes similar to pivotal studies. We also found that an initial watchful-waiting approach is commonly adopted without apparent detriment to survival. And finally, we found that age has an impact on the prescribing of systemic therapy.

The relationship between rash, tumour KRAS mutation status and clinical and quality of life outcomes in patients with advanced colorectal cancer treated with cetuximab in the NCIC CTG/AGITG CO.17.

BACKGROUND: The NCIC CTG/AGITG CO.17 trial demonstrated that cetuximab monotherapy improved overall and progression-free survival (OS and PFS) in patients previously treated for advanced colorectal cancer. A strong relationship was observed between benefit from cetuximab and development of rash. In this analysis, the association of rash and benefit from cetuximab is explored and presented by KRAS mutation status. MATERIAL AND METHODS: Rash was graded by NCI CTC 2.0 criteria. Landmark analysis was performed by excluding patients who died or dropped out within 28 days and then grouping by worst grade of rash experienced by day 28. Multivariate Cox models were conducted separately for patients with KRAS wild-type (WT) tumours and KRAS mutated (MUT) tumours. CO.17 primary outcome was OS. RESULTS: Development of grade 2 + rash on cetuximab was associated with a trend towards increased OS (HR 0.61 with 95% CI 0.36-1.02 and p = 0.06) and PFS (HR 0.68 with 95% CI 0.45-1.03 and p = 0.07) as compared to grade 0/1 rash in patients with WT tumours. In patients with WT tumours on cetuximab both grade 0/1 and grade 2 + rash were associated with increased PFS (HR 0.57 95% CI 0.38-0.86; p = 0.008; and HR 0.32 95% CI 0.21-0.49; p < 0.0001) respectively, in comparison with best supportive care (BSC). Only development of grade 2 + rash on cetuximab was associated with increased OS (HR 0.52 with 95% CI 0.34-0.80 and p = 0.003) in comparison with BSC. No significant difference was found in OS or PFS among patients on cetuximab with MUT tumours with either rash grade as compared to BSC. No consistent trend was observed for the association of severity of rash and quality of life (QoL). CONCLUSION: As all patients with WT tumours benefitted to some extent from cetuximab regardless of the grade of rash, grade of rash was not a useful predictive marker.

How well informed is the informed consent for cancer clinical trials?

AIMS: The purpose of this study was to analyze the content of informed consent forms for clinical trials in medical oncology to assess readability, determine their completeness, and identify any shortcomings. METHODS: Informed consent forms for Phase I-III studies that were conducted at two tertiary care cancer centers over a 3-year period were reviewed. Information pertaining to length of the informed consent form, research regimen/methods, treatment agent, potential risks, and benefits was extracted. The reading level was assessed by Flesch-Kincaid and Gunning-Fog index readability tests. RESULTS: All of the 112 informed consent forms clearly stated the voluntary nature of participation. Nearly one half of the forms (51.8%) were of Phase I studies. The median length of informed consent form was 20 pages (range: 8-28). A detailed estimation of the frequency or intensity of risks (range: 3-8 pages) was provided. The average reading level of the informed consent forms was high (Flesch-Kincaid Grade Level of 9.8), which corresponds roughly to 10th-grade reading level. Less than 15% of all consent forms were written at the recommended eighth-grade reading level. A substantial number of forms did not report a potential risk to pregnant/lactating women (16.9%), mechanism of action of the investigational agent (34.8%), study schema (77.6%), a possibility of receiving sub-therapeutic dose (37%), or death (12.5%). Nearly one half of the forms (49.1%) stated clearly that individual participants may not benefit. CONCLUSION: Overall, these informed consent forms provided a detailed description of the trials in accordance to international guidelines. However, there remains room for improvement, particularly in areas of readability and document length.

External Validation of Risk Scores for Predicting Venous Thromboembolism in Ambulatory Patients with Lung Cancer.

BACKGROUND: The purpose of this study was to evaluate the discriminatory capability of the Khorana, PROTECHT, CONKO, and COMPASS-CAT scores in ambulatory patients with lung cancer. METHODS: This retrospective cohort study included 591 patients with newly diagnosed lung cancer. A symptomatic or incidental VTE occurred in 108 patients. RESULTS: The Khorana score at a 2-point threshold had a discriminatory capability with an odds ratio (OR) of 1.80 and an AUC of 0.57 for 6 months, and an OR of 1.51 and an AUC of 0.55 for 12 months. The CONKO score at a 2-point threshold had a stronger discriminatory capability for both 6 months and 12 months with ORs of 3.00 and 2.13, and AUCs of 0.63 and 0.59, respectively. Additionally, higher white blood cell counts, higher neutrophil counts, hypoalbuminaemia, and not undergoing lung surgery were related to VTE occurrence (p < 0.05). CONCLUSIONS: The Khorana score with the 2-point threshold was validated in ambulatory patients with lung cancer, with the results indicating a decline in its discriminatory capability over time (at 12 months vs. 6 months from diagnosis). The CONKO score at the original 2-point threshold showed a stronger discriminatory capability but further validation with a larger sample size is recommended. The identified predictors should be further investigated in future research.