Baseline neutrophil-lymphocyte ratio holds no prognostic value for esophageal and junctional adenocarcinoma in patients treated with neoadjuvant chemotherapy

BACKGROUND: Several studies have reported that neutrophil-lymphocyte ratio (NLR) can predict survival in esophageal and gastroesophageal junction adenocarcinoma, as it reflects systemic inflammation. Hence, we aimed to determine whether baseline NLR holds prognostic value for esophageal adenocarcinoma patients treated with neoadjuvant chemotherapy (nCT) followed by surgery. METHODS: We studied the data of 139 patients that received nCT before undergoing esophagectomy with curative intent, all identified from a prospectively maintained database (1998-2016). Pretreatment hematology reports were used to calculate the baseline NLR. A receiver operating characteristic curve (ROC-curve) was plotted to determine an optimal cutoff value. NLR quartiles were used to display possible differences between groups in relation to overall survival (OS) and disease-free survival (DFS) using the method of Kaplan-Meier. Cox regression analysis was performed to assess the prognostic value of NLR. RESULTS: The median OS and DFS times were 46 months (interquartile range [IQR]: 19-166) and 30 months (IQR: 13-166], respectively, for the entire cohort. The ROC-curve showed that NLR has no discriminating power for survival status (area under the curve = 0.462) and therefore no optimal cutoff value could be determined. There were no statistically significant differences in median OS times for NLR quartiles: 65 (Q1), 32 (Q2), 45 (Q3), and 46 months (Q4) (P = 0.926). Similarly, DFS showed no difference between quartile groups, with median survival times of 27 (Q1), 19 (Q2), 36 (Q3), and 20 months (Q4) (P = 0.973). Age, pN, pM, and resection margin were independent prognostic factors for both OS and DFS. On the contrary, NLR was not associated with OS or DFS in univariable and multivariable analyses. CONCLUSION: Baseline NLR holds no prognostic value for esophageal and gastroesophageal junction adenocarcinoma patients treated with nCT in this study, in contrast to other recently published papers. This result questions the validity of NLR as a reliable prognostic indicator and its clinical usefulness in these patients

The Impact of Signet Ring Cell Differentiation on Outcome in Patients with Esophageal and Gastroesophageal Junction Adenocarcinoma

Background. Little is known about the association between signet ring cell (SRC) differentiation and response to neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy (nCRT) in patients with esophageal and junctional adenocarcinoma (EAC). We aimed to assess if SRC differentiation is associated with survival and response to nCT or nCRT in patients with EAC. Methods. Patients who underwent nCT and nCRT followed by surgery for EAC from 2000 until 2016 were identified from two institutional prospectively maintained databases. The pretreatment biopsy report or surgical resection specimen was used to differentiate patients into an SRC or non-SRC group. Results. Overall, 129 (19%) of 689 patients included had SRCs (nCT: n = 64; nCRT: n = 65). The SRC group had a more advanced ypT stage (p = 0.003), a higher number of positive lymph nodes in the resection specimen {median (interquartile range [IQR]) 2 [0–5] vs. 1 [0–3]; p = 0.002} and a higher rate of R1/R2 resections (19.4% vs. 12%; p = 0.026). SRC differentiation was not an independent prognostic factor for overall survival (OS) or disease-free survival (DFS). Following nCT, the SRC group had significantly shorter DFS (median [IQR] 12 [5–50] vs. 23 [8–164]; p = 0.013), but not OS, compared with the nonSRC group. In contrast, no differences according to SRC status for OS or DFS were found in patients who underwent nCRT. Conclusions. SRC differentiation was not independently associated with worse OS in patients with EAC who underwent neoadjuvant therapy and surgery. However, nCRT was associated with greater tumor downstaging and better DFS

Responsiveness and convergent validity of QLU-C10D and EQ-5D-3L in assessing short-term quality of life following esophagectomy

Aim: This study assessed the responsiveness and convergent validity of two preference-based measures; the newly developed cancer-specifc EORTC Quality of Life Utility Measure-Core 10 dimensions (QLU-C10D) relative to the generic three-level version of the EuroQol 5 dimensions (EQ-5D-3L) in evaluating short-term health related quality of life (HRQoL) outcomes after esophagectomy. Methods: Participants were enrolled in a multicentre randomised controlled trial to determine the impact of preoperative and postoperative immunonutrition versus standard nutrition in patients with esophageal cancer. HRQoL was assessed seven days before and 42 days after esophagectomy. Standardized Response Mean and Efect Size were calculated to assess responsiveness. Ceiling efects for each dimension were calculated as the proportion of the best level responses for that dimension at follow-up/post-operatively. Convergent validity was assessed using Spearman’s correlation and the level of agreement was explored using Bland–Altman plots. Results: Data from 164 respondents (mean age: 63 years, 81% male) were analysed. HRQoL signifcantly reduced on both measures with large efect sizes (>0.80), and a greater mean diference (0.29 compared to 0.16) on QLU-C10D. Both measures had ceiling efects (>15%) on all dimensions at baseline. Following esophagectomy, ceiling efects were observed with self-care (86%), mobility (67%), anxiety/depression (55%) and pain/discomfort (19%) dimensions on EQ-5D-3L. For QLU-C10D ceiling efects were observed with emotional function (53%), physical function (16%), nausea (35%), sleep (31%), bowel problems (21%) and pain (20%). A strong correlation (r=0.71) was observed between EQ-5D-3L anxiety and QLU-C10D emotional function dimensions. Good agreement (3.7% observations outside the limits of agreement) was observed between the utility scores. Conclusion: The QLU-C10D is comparable to the more widely applied generic EQ-5D-3L, however, QLU-C10D was more sensitive to short-term utility changes following esophagectomy. Cognisant of requirements by policy makers to apply generic utility measures in cost efectiveness studies, the disease-specifc QLU-C10D should be used alongside the generic measures like EQ-5D-3L.Norma B. Bulamu, Ravi Vissapragada, Gang Chen, Julie Ratclife, Louise A. Mudge, B. Mark Smithers, Elizabeth A. Isenring, Lorelle Smith, Glyn G. Jamieson, and David I. Watson, on behalf of The Australian Immunonutrition Study Grou

Completion Dissection or Observation for Sentinel-Node Metastasis in Melanoma.

Sentinel-lymph-node biopsy is associated with increased melanoma-specific survival (i.e., survival until death from melanoma) among patients with node-positive intermediate-thickness melanomas (1.2 to 3.5 mm). The value of completion lymph-node dissection for patients with sentinel-node metastases is not clear. In an international trial, we randomly assigned patients with sentinel-node metastases detected by means of standard pathological assessment or a multimarker molecular assay to immediate completion lymph-node dissection (dissection group) or nodal observation with ultrasonography (observation group). The primary end point was melanoma-specific survival. Secondary end points included disease-free survival and the cumulative rate of nonsentinel-node metastasis. Immediate completion lymph-node dissection was not associated with increased melanoma-specific survival among 1934 patients with data that could be evaluated in an intention-to-treat analysis or among 1755 patients in the per-protocol analysis. In the per-protocol analysis, the mean (±SE) 3-year rate of melanoma-specific survival was similar in the dissection group and the observation group (86±1.3% and 86±1.2%, respectively; P=0.42 by the log-rank test) at a median follow-up of 43 months. The rate of disease-free survival was slightly higher in the dissection group than in the observation group (68±1.7% and 63±1.7%, respectively; P=0.05 by the log-rank test) at 3 years, based on an increased rate of disease control in the regional nodes at 3 years (92±1.0% vs. 77±1.5%; P<0.001 by the log-rank test); these results must be interpreted with caution. Nonsentinel-node metastases, identified in 11.5% of the patients in the dissection group, were a strong, independent prognostic factor for recurrence (hazard ratio, 1.78; P=0.005). Lymphedema was observed in 24.1% of the patients in the dissection group and in 6.3% of those in the observation group. Immediate completion lymph-node dissection increased the rate of regional disease control and provided prognostic information but did not increase melanoma-specific survival among patients with melanoma and sentinel-node metastases. (Funded by the National Cancer Institute and others; MSLT-II ClinicalTrials.gov number, NCT00297895 .)

Patient age and risk of recurrence of primary melanoma at high risk of spread

Melanoma is more aggressive with poorer outcomes in older than younger patients. Older age has been associated with greater tumour thickness, higher rates of ulceration, and high mitotic rates, but it is not clear whether poorer outcomes in the elderly are solely due to these tumour-specific features or to additional effects of age-related decline in in immune surveillance, greater comorbidity, and age-related behaviours such as delayed diagnosis

Symptoms, investigations and management of patients with cancer of the oesophagus and gastro-oesophageal junction in Australia

OBJECTIVE: To document presenting symptoms, investigations and management for Australian patients with oesophageal adenocarcinoma (OAC), gastro-oesophageal junction adenocarcinoma (GOJAC) and oesophageal squamous cell carcinoma (OSCC). DESIGN, SETTING AND PARTICIPANTS: Cross-sectional study of a population-based sample of 1100 Australian patients aged 18-79 years with histologically confirmed oesophageal cancer diagnosed in 2002-2005, using data from cancer registries and treatment centres, supplemented with clinical information collected through medical record review in 2006-2007 and mortality information collected in 2008. MAIN OUTCOME MEASURES: Prevalence of primary symptoms, and staging investigations and treatment modalities used. RESULTS: The primary presenting symptom was dysphagia, which was self-reported by 41%, 39% and 48% of patients with OAC, GOJAC and OSCC, respectively. Less common symptoms were reflux, chest pain, bleeding and weight loss. All patients underwent endoscopy, most had a staging computed tomography scan (OAC 93%, GOJAC 95% and OSCC 93%), and about half had positron emission tomography scans (OAC 51%, GOJAC 44% and OSCC 42%). Pretreatment tumour stage was reported in 25% of records, and could be derived from results of investigations in a further 23%, but the remaining half lacked sufficient information to ascribe a pretreatment stage. Curative treatments were attempted for 60% of OAC, 88% of GOJAC and 65% of OSCC patients. Surgery was performed on 52% of OAC, 83% of GOJAC and 41% of OSCC patients. About two-thirds of surgical patients received additional therapies. CONCLUSIONS: With anticipated increases in oesophageal cancer incidence, the resources required to diagnose and manage patients with oesphageal cancer are also likely to rise. Our data provide a baseline from which to plan for the future care of patients with cancers of the oesophagus.Bernard M Smithers, Paul P Fahey, Tracie Corish, David C Gotley, Gregory L Falk, Garett S Smith, George K Kiroff, Andrew D Clouston, David I Watson and David C Whitema

Hypothesised cutaneous sites of origin of stage III melanomas with unknown primary: A multicentre study

Based on molecular evidence that melanomas with unknown primary (MUPs) arise from the skin, we hypothesised that sites of MUPs are disproportionately on trunk and lower limbs, sites that are not readily visible to patients and clinicians. We tested this hypothesis by inferring the anatomic site of origin of MUPs from the corresponding known cutaneous sites of melanoma patients with known primary tumours (MKPs). We analysed data from three separate cohorts of patients from Brisbane, Australia (n = 236); Manchester, UK (n = 51) and Padova, Italy (n = 33), respectively, who first presented with stage III melanoma with lymph node metastases. We matched two MKP patients to each MUP patient based on lymph node dissection (LND) site, age and sex, and imputed cutaneous sites of origin of MUPs from their two matched MKPs for study countries, giving two possible sites for each MUP per centre. Overall, results showed that MUP patients were predominantly male, and trunk was the most likely origin, comprising around a third to a half of MUPs across the three cohorts. The remaining MUP inferred sites varied by country. In the Australian cohort, the legs accounted for a third of imputed sites of MUPs, while in the UK and Italian cohorts, the most frequent site was the arms followed by the legs. Our findings suggest the need for regular and thorough skin examination on trunk and limbs, especially in males, to improve early detection of cutaneous melanoma and reduce the risk of metastatic disease at the time of presentation

Australian multicenter study of isolated limb infusion for melanoma

Purpose: Isolated limb infusion (ILI) offers a less invasive alternative to isolated limb perfusion (ILP) for the treatment of locally advanced extremity melanoma. In Australia, ILI has essentially completely replaced ILP. The aim of this study was to collect and evaluate the results of ILI in an Australian multicenter setting. Patients and Methods: The results of 316 first ILI procedures, performed between 1992 and 2008 in five Australian institutions, were collectively analyzed, with all five institutions using the same protocol. Melphalan was circulated in the isolated limb for 20–30 min (±actinomycin D). Response was determined using the World Health Organization criteria, and limb toxicity was assessed using the Wieberdink scale. Results: The median patient age was 74 years (range 28–100) and 59 % of patients were female. Overall response rate was 75 % (complete response [CR] 33 %; partial response 42 %). Stable disease was seen in 18 % of patients and progressive disease in 7 %. Wieberdink grade III or higher was seen in 30 % of the cases. No toxicity-related amputations occurred, and median survival was 44 months. In patients with a CR, median survival was 80 months (p = 0.014). On multivariate analysis, Breslow thickness, lower-limb ILI, and a procedure performed at the Melanoma Institute Australia remained significant predictors for response, although not for survival. Conclusions: This Australian multicenter study of ILI is the largest reported to date. ILI is a useful technique that can be safely and effectively performed across tertiary referral centers for the successful management of advanced extremity melanoma. Increased optimization of perioperative factors might allow response rates to be raised further, while maintaining acceptable toxicity.Hidde M. Kroon, Brendon J. Coventry, Mitchell H. Giles, Michael A. Henderson, David Speakman, Mark Wall ... et al

Building a sustainable clinical academic workforce to meet the future healthcare needs of Australia and New Zealand: Report from the first summit meeting

The delivery of healthcare that meets the requirements for quality, safety and cost-effectiveness relies on a well-trained medical workforce, including clinical academics whose career includes a specific commitment to research, education and/or leadership. In 2011, the Medical Deans of Australia and New Zealand published a review on the clinical academic workforce and recommended the development of an integrated training pathway for clinical academics. A bi-national Summit on Clinical Academic Training was recently convened to bring together all relevant stakeholders to determine how best to do this. An important part understood the lessons learnt from the UK experience after 10 years since the introduction of an integrated training pathway. The outcome of the summit was to endorse strongly the recommendations of the medical deans. A steering committee has been established to identify further stakeholders, solicit more information from stakeholder organisations, convene a follow-up summit meeting in late 2015, recruit pilot host institutions and engage the government and future funders