Prognostic and predictive value of non-steroidal anti-inflammatory drugs in the EORTC 1325/KEYNOTE-054 phase III trial of pembrolizumab versus placebo in resected high-risk stage III melanoma.

Background: Pain is common in patients with cancer. The World Health Organisation recommends paracetamol or non-steroidal anti-inflammatory drugs (NSAIDs) for mild pain and combined with other agents for moderate/severe pain. This study estimated associations of NSAIDs with recurrence-free survival (RFS), distant metastasis-free survival (DMFS) and the incidence of immune-related adverse events (irAEs) in high-risk patients with resected melanoma in the EORTC 1325/KEYNOTE-054 phase III clinical trial.

Immune-related adverse events secondary to immunotherapy in oncology: A guide for general practice.

Background: Immunotherapy has reshaped the prognoses for many cancers and is increasingly used in both metastatic and adjuvant settings. There is a high prevalence of immunotherapy side effects, or immune-related adverse events (irAEs), which can affect any organ. Some irAEs can cause permanent or prolonged morbidity and, in rare cases, may be fatal.

Prognostic and predictive value of metformin in the European Organisation for Research and Treatment of Cancer 1325/KEYNOTE-054 phase III trial of pembrolizumab versus placebo in resected high-risk stage III melanoma.

Background: Metformin is a commonly prescribed and well-tolerated medication. In laboratory studies, metformin suppresses BRAF wild-type melanoma cells but accelerates the growth of BRAF-mutated cells. This study investigated the prognostic and predictive value of metformin, including with respect to BRAF mutation status, in the European Organisation for Research and Treatment of Cancer 1325/KEYNOTE-054 randomised controlled trial.

Efficacy of anti-PD-1 and ipilimumab alone or in combination in acral melanoma.

Background: Acral melanoma is a rare melanoma subtype with poor prognosis. Importantly, these patients were not identified as a specific subgroup in the landmark melanoma trials involving ipilimumab and the anti-programmed cell death protein-1 (PD-1) agents nivolumab and pembrolizumab. There is therefore an absence of prospective clinical trial evidence regarding the efficacy of checkpoint inhibitors (CPIs) in this population.

Prognostic and predictive value of β-blockers in the EORTC 1325/KEYNOTE-054 phase III trial of pembrolizumab versus placebo in resected high-risk stage III melanoma.

Background: β-adrenergic receptors are upregulated in melanoma cells and contribute to an immunosuppressive, pro-tumorigenic microenvironment. This study investigated the prognostic and predictive value of β-adrenoreceptor blockade by β-blockers in the EORTC1325/KEYNOTE-054 randomised controlled trial.

Methods: Patients with resected stage IIIA, IIIB or IIIC melanoma and regional lymphadenectomy received 200 mg of adjuvant pembrolizumab (n = 514) or placebo (n = 505) every three weeks for one year or until recurrence or unacceptable toxicity.

Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): health-related quality-of-life results from a double-blind, randomised, controlled, phase 3 trial.

Background: The European Organisation for Research and Treatment of Cancer (EORTC) 1325-MG/KEYNOTE-054 trial in patients with resected, high-risk stage III melanoma demonstrated improved recurrence-free survival with adjuvant pembrolizumab compared with placebo (hazard ratio 0·57 [98·4% CI 0·43-0·74]; p<0·0001). This study reports the results from the health-related quality-of-life (HRQOL) exploratory endpoint.

Methods: This double-blind, randomised, controlled, phase 3 trial was done at 123 academic centres and community hospitals across 23 countries.

Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): distant metastasis-free survival results from a double-blind, randomised, controlled, phase 3 trial.

Background: The European Organisation for Research and Treatment of Cancer (EORTC) 1325/KEYNOTE-054 trial assessed pembrolizumab versus placebo in patients with resected high-risk stage III melanoma. At 15-month median follow-up, pembrolizumab improved recurrence-free survival (hazard ratio [HR] 0·57 [98·4% CI 0·43-0·74], p<0·0001) compared with placebo, leading to its approval in the USA and Europe. This report provides the final results for the secondary efficacy endpoint, distant metastasis-free survival and an update of the recurrence-free survival results.

Diet and risk of gastro-oesophageal reflux disease in the Melbourne Collaborative Cohort Study.

Objective: To examine associations between diet and risk of developing gastro-oesophageal reflux disease (GERD).

Design: Prospective cohort with a median follow-up of 15·8 years. Baseline diet was measured using a FFQ.

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).

Longer Follow-Up Confirms Recurrence-Free Survival Benefit of Adjuvant Pembrolizumab in High-Risk Stage III Melanoma: Updated Results From the EORTC 1325-MG/KEYNOTE-054 Trial.

Purpose: We conducted the phase III double-blind European Organisation for Research and Treatment of Cancer (EORTC) 1325/KEYNOTE-054 trial to evaluate pembrolizumab versus placebo in patients with resected high-risk stage III melanoma. On the basis of 351 recurrence-free survival (RFS) events at a 1.25-year median follow-up, pembrolizumab prolonged RFS (hazard ratio [HR], 0.

Prognosis associated with cutaneous melanoma metastases.

Background/objective: Information on the prognosis for patients with regional cutaneous melanoma metastases has been sparse and difficult to establish. In 2009 the American Joint Committee on Cancer (AJCC) melanoma staging has for the first time provided survival rates for patients who manifest intralymphatic metastases. We sought to validate the new staging system in this contemporary, prospectively collected cohort of patients following the development of cutaneous metastases as the first evidence of metastatic disease and explored the factors that influenced their prognosis.

Expression of MUC2, MUC5AC, MUC5B, and MUC6 mucins in colorectal cancers and their association with the CpG island methylator phenotype.

Mucinous differentiation is associated with both CpG island methylator phenotype and microsatellite instability in colorectal cancer. The mucinous phenotype derives from abundant expression of the colonic goblet cell mucin, MUC2, and de novo expression of gastric foveolar mucin, MUC5AC. We, therefore, investigated the protein expression levels of MUC2 and MUC5AC, as well as MUC5B and MUC6, in molecular subtypes of colorectal cancer.

The effect of socioeconomic status on survival from colorectal cancer in the Melbourne Collaborative Cohort Study.

Previous research relating lower socioeconomic status (SES) with poorer survival from colorectal cancer has varied in adjustment for confounding factors and in the use of individual-level or aggregate-level indicators of SES. We investigated the effect of SES and country of birth on survival from colorectal cancers diagnosed in participants of the Melbourne Collaborative Cohort Study. A total of 526 colorectal cancer cases diagnosed since baseline were followed from diagnosis to 1 June 2006 or death.

Ethnicity and risk for colorectal cancers showing somatic BRAF V600E mutation or CpG island methylator phenotype.

Colorectal cancers arising from serrated polyps are characterized by the CpG island methylator phenotype (CIMP) and somatic mutation (V600E) in the BRAF proto-oncogene. Few epidemiologic studies have investigated risk factors for these tumors. We conducted a cohort study of 41,328 residents of Melbourne, Australia that included 9,939 participants of southern European origin and 31,389 of Anglo-Celtic origin.

A phase II study of the heparanase inhibitor PI-88 in patients with advanced melanoma.

Treatment options for advanced melanoma are limited. PI-88, a potent inhibitor of heparanase, demonstrates anitangiogenic properties and has shown activity against melanoma in phase I studies. This was an open-label, multicenter, phase II study of PI-88 in patients with advanced melanoma.

Incidence of malignancies in heart and/or lung transplant recipients: a single-institution experience.

Background: The purpose of this study was to determine the incidence and type of malignancies in heart and/or lung transplant recipients at a single institution in Victoria, Australia, and to compare these findings with the non-transplant general Victorian population.

Methods: Recipients of heart and/or lung transplants at the Alfred Hospital between February 1989 and January 2004 were cross-referenced with the Victorian Cancer Registry. The medical records of all patients with a cancer diagnosis by January 1, 2005 were reviewed.

Body size and composition and risk of rectal cancer (Australia).

Background: Although body mass index has been shown to be associated with colon cancer, studies of rectal cancer risk have generally reported no association. The relationship between rectal cancer risk and central adiposity, overall fat mass, and fat-free mass is unknown.

Methods: In a prospective cohort study of people aged 27-75 years, body measurements were taken directly; fat mass and fat-free mass being estimated by bioelectrical impedance analysis and central adiposity by waist circumference and waist-to-hip ratio.

Body size and composition and colon cancer risk in women.

Studies of colon cancer risk in males have reported strong positive associations with obesity, particularly with central adiposity. The association has been weaker and less consistent for women. In a prospective cohort study of women, body measurements were taken directly; fat mass and fat-free mass being estimated by bioelectrical impedance analysis and central adiposity by waist circumference and waist-to-hip ratio (WHR).

Red meat, chicken, and fish consumption and risk of colorectal cancer.

Background: Red meat and processed meat consumption have been associated with increased risk of colorectal cancer in some, but not all, relevant cohort studies. Evidence on the relationship between risk of colorectal cancer and poultry and fish consumption is inconsistent.

Methods: We conducted a prospective cohort study of 37,112 residents of Melbourne, Australia recruited from 1990 to 1994.

Body size and composition and colon cancer risk in men.

Background: Several studies of male colon cancer have found positive associations with body size and composition. It is uncertain whether this relationship is due to non-adipose mass, adipose mass, distribution of adipose mass such as central adiposity, or all three.

Methods: In a prospective cohort study of men aged 27-75 at recruitment in 1990-1994, body measurements were taken by interviewers.

Emerging pathways in colorectal-cancer development.

The past decade has seen the emergence of new pathways in the development of colorectal cancer. There is now clear evidence that subsets of these tumours do not show chromosomal instability and do not follow the suppressor pathway. Instead, about 15% of colorectal cancers are characterised by microsatellite instability (MSI).