Preoperative Chemoradiotherapy for Resectable Gastric Cancer.

BACKGROUND: In Western countries, the current standard of care for resectable gastric cancer is perioperative chemotherapy. Preoperative chemoradiotherapy has been considered, but data are limited regarding this treatment as compared with perioperative chemotherapy alone. METHODS: We conducted an international, phase 3 trial in which patients with resectable adenocarcinoma of the stomach or gastroesophageal junction were randomly assigned to receive preoperative chemoradiotherapy plus perioperative chemotherapy or perioperative chemotherapy alone (control). In both groups, patients received either epirubicin, cisplatin, and fluorouracil or fluorouracil, leucovorin, oxaliplatin, and docetaxel both before and after surgery; the preoperative-chemoradiotherapy group also received chemoradiotherapy (45 Gy in 25 fractions of radiation, plus fluorouracil infusion). The primary end point was overall survival, and secondary end points included progression-free survival, pathological complete response, toxic effects, and quality of life. RESULTS: A total of 574 patients underwent randomization at 70 sites in Australasia, Canada, and Europe: 286 to the preoperative-chemoradiotherapy group and 288 to the perioperative-chemotherapy group. A higher percentage of patients in the preoperative-chemoradiotherapy group than in the perioperative-chemotherapy group had a pathological complete response (17% vs. 8%) and greater tumor downstaging after resection. At a median follow-up of 67 months, no significant between-group differences in overall survival or progression-free survival were noted. The median overall survival was 46 months with preoperative chemoradiotherapy and 49 months with perioperative chemotherapy (hazard ratio for death, 1.05; 95% confidence interval, 0.83 to 1.31), and the median progression-free survival was 31 months and 32 months, respectively. Treatment-related toxic effects were similar in the two groups. CONCLUSIONS: The addition of preoperative chemoradiotherapy to perioperative chemotherapy did not improve overall survival as compared with perioperative chemotherapy alone among patients with resectable gastric and gastroesophageal junction adenocarcinoma. (Funded by the National Health and Medical Research Council and others; TOPGEAR ClinicalTrials.gov number, NCT01924819.).

Conditional survival in patients with stage IB-IIIA melanoma undergoing sentinel node biopsy in Queensland: A longitudinal study.

BACKGROUND: Tumour characteristics such as thickness and ulceration, along with sentinel lymph node (SLN) status, have been essential in predicting survival in patients with locally invasive melanomas at the time of diagnosis. It is unclear if these prognostic factors are relevant 1, 2 or 5 years after diagnosis. OBJECTIVES: The key aim of this project was to analyse conditional survival in a cohort of Queensland patients with stage IB to IIIA melanomas (American Joint Committee on Cancer's staging system, 8th version) and to test the relevance of clinicopathological prognostic factors for melanoma outcome after varying intervals of survival time. METHODS: Patients with primary invasive cutaneous melanoma who were referred to a tertiary melanoma clinic and underwent SLN biopsy between 1994 and 2011 were ascertained. The effect of patient and tumour characteristics on melanoma survival were calculated using multivariate Cox proportional hazard models at diagnosis and at variable times after diagnosis. RESULTS: The final analysis included 651 patients (average age 49 years, 55.5% male) with stage IB to IIIA melanoma. At diagnosis, and after 1 and 2 years survived, SLN positivity, thickness and ulceration were predictive of 10-year survival since diagnosis. However, once patients survived 5 years, only SLN status was predictive. Overall conditional melanoma survival improved with increasing time survived. Five years after diagnosis, 10-year conditional melanoma survival (MSS) was 91% (95% CI 86%-95%) compared with 85% (82%-88%) predicted at diagnosis. The improvement in MSS was observed mainly for Stage II melanoma patients and not for those with a positive SLN biopsy. CONCLUSIONS: This study confirms the improvement of prognosis according to time survived since diagnosis suggesting that after 5 years survival the classic prognostic indicators may not have the same influence.

Efficacy of laparoscopic fundoplication in patients with chronic cough and gastro-oesophageal reflux.

BACKGROUND: The outcome of anti-reflux surgery in patients with suspected gastro-oesophageal reflux-induced cough is frequently uncertain. The aims of this study were to assess the efficacy of laparoscopic fundoplication for controlling cough in patients with chronic cough without asthma, who have pathologic gastro-oesophageal reflux, and to identify predictors of response. METHODS: From a prospective database of 1598 patients who have undergone laparoscopic fundoplication, 66 (4%) with proven gastro-oesophageal reflux disease (GORD) and chronic cough without asthma were studied. All patients underwent gastroscopy and 24-h pH monitoring before operation. Heartburn and regurgitation were assessed using a modified DeMeester score. Severity of cough before and after surgery was self-assessed by the patient using a visual analog scale at a minimum of 12 months post-operatively (median 43 mo; range: 14-104 mo). Patients were considered to have responded to fundoplication if they had no cough or the cough had improved by 50% or more after operation. RESULTS: Cough and heartburn/regurgitation were relieved in 61% (40/66) and 90% (44/49) of the patients, respectively. The presence of typical GORD symptoms or oesophagitis, and pH study variables did not predict the response of the cough to fundoplication. CONCLUSION: Refinement in the aetiological diagnosis of chronic cough due to GORD is necessary for improved outcome. Patients diagnosed with GORD-related chronic cough need to be counseled regarding their expectations from anti-reflux surgery.

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.

Identifying a core symptom set triggering radiological and endoscopic investigations for suspected recurrent esophago-gastric cancer: a modified Delphi consensus process.

BACKGROUND: There is currently a lack of evidence-based guidelines regarding surveillance for recurrence after esophageal and gastric (OG) cancer surgical resection, and which symptoms should prompt endoscopic or radiological investigations for recurrence. The aim of this study was to develop a core symptom set using a modified Delphi consensus process that should guide clinicians to carry out investigations to look for suspected recurrent OG cancer in previously asymptomatic patients. METHODS: A web-based survey of 42 questions was sent to surgeons performing OG cancer resections at high volume centers. The first section evaluated the structure of follow-up and the second, determinants of follow-up. Two rounds of a modified Delphi consensus process and a further consensus workshop were used to determine symptoms warranting further investigations. Symptoms with a 75% consensus agreement as suggestive of recurrent cancer were included in the core symptom set. RESULTS: 27 surgeons completed the questionnaires. A total of 70.3% of centers reported standardized surveillance protocols, whereas 3.7% of surgeons did not undertake any surveillance in asymptomatic patients after OG cancer resection. In asymptomatic patients, 40.1% and 25.9% of centers performed routine imaging and endoscopy, respectively. The core set that reached consensus, consisted of eight symptoms that warranted further investigations included; dysphagia to solid food, dysphagia to liquids, vomiting, abdominal pain, chest pain, regurgitation of foods, unexpected weight loss and progressive hoarseness of voice. CONCLUSION: There is global variation in monitoring patients after OG cancer resection. Eight symptoms were identified by the consensus process as important in prompting radiological or endoscopic investigation for suspected recurrent malignancy. Further randomized controlled trials are necessary to link surveillance strategies to survival outcomes and evaluate prognostic value.

Preoperative Ultrasound Assessment of Regional Lymph Nodes in Melanoma Patients Does not Provide Reliable Nodal Staging: Results From a Large Multicenter Trial.

OBJECTIVE: To assess whether preoperative ultrasound (US) assessment of regional lymph nodes in patients who present with primary cutaneous melanoma provides accurate staging. BACKGROUND: It has been suggested that preoperative US could avoid the need for sentinel node (SN) biopsy, but in most single-institution reports, the sensitivity of preoperative US has been low. METHODS: Preoperative US data and SNB results were analyzed for patients enrolled at 20 centers participating in the screening phase of the second Multicenter Selective Lymphadenectomy Trial. Excised SNs were histopathologically assessed and considered positive if any melanoma was seen. RESULTS: SNs were identified and removed from 2859 patients who had preoperative US evaluation. Among those patients, 548 had SN metastases. US was positive (abnormal) in 87 patients (3.0%). Among SN-positive patients, 39 (7.1%) had an abnormal US. When analyzed by lymph node basin, 3302 basins were evaluated, and 38 were true positive (1.2%). By basin, the sensitivity of US was 6.6% (95% confidence interval: 4.6-8.7) and the specificity 98.0% (95% CI: 97.5-98.5). Median cross-sectional area of all SN metastases was 0.13 mm2; in US true-positive nodes, it was 6.8 mm2. US sensitivity increased with increasing Breslow thickness of the primary melanoma (0% for ≤1 mm thickness, 11.9% for >4 mm thickness). US sensitivity was not significantly greater with higher trial center volume or with pre-US lymphoscintigraphy. CONCLUSION: In the MSLT-II screening phase population, SN tumor volume was usually too small to be reliably detected by US. For accurate nodal staging to guide the management of melanoma patients, US is not an effective substitute for SN biopsy.

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-specific 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 Effect Size were calculated to assess responsiveness. Ceiling effects 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 significantly reduced on both measures with large effect sizes (> 0.80), and a greater mean difference (0.29 compared to 0.16) on QLU-C10D. Both measures had ceiling effects (> 15%) on all dimensions at baseline. Following esophagectomy, ceiling effects were observed with self-care (86%), mobility (67%), anxiety/depression (55%) and pain/discomfort (19%) dimensions on EQ-5D-3L. For QLU-C10D ceiling effects 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 effectiveness studies, the disease-specific QLU-C10D should be used alongside the generic measures like EQ-5D-3L. TRIAL REGISTRATION: The trial was registered with the Australian New Zealand Clinical Trial Registry (ACTRN12611000178943) on the 15th of February 2011.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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 .).

Oncologic Outcomes After Isolated Limb Infusion for Advanced Melanoma: An International Comparison of the Procedure and Outcomes Between the United States and Australia.

BACKGROUND: Isolated limb infusion (ILI) is a minimally invasive procedure for delivering high-dose chemotherapy to extremities affected by locally advanced or in-transit melanoma. This study compared the outcomes of melanoma patients treated with ILI in the United States of America (USA) and Australia (AUS). METHODS: Patients with locally recurrent in-transit melanoma treated with ILI at USA or AUS centers between 1992 and 2018 were identified. Demographic and clinicopathologic characteristics were collected. Primary outcomes of treatment response, in-field progression-free survival (IPFS), distant progression-free survival (DPFS), and overall survival (OS) were evaluated by the Kaplan-Meier method. Multivariable analysis evaluated whether availability of new systemic therapies affected outcomes. RESULTS: More ILIs were performed in AUS (n = 411, 60 %) than in the USA (n = 276, 40 %). In AUS, more ILIs were performed for stage 3B disease than in the USA (62 % vs 46 %; p < 0.001). The reported complete response rates were similar (AUS 30 % vs USA 29 %). Among the stage 3B patients, AUS patients had better IPFS (p = 0.001), whereas DPFS and OS were similar between the two countries. Among the stage 3C patients, the USA patients had better OS (p < 0.001), whereas IPFS and DPFS were similar. Availability of new systemic therapies did not affect IPFS or DPFS in either country. However, the USA patients who received ILI after ipilimumab approval in 2011 had significantly improved OS (hazard ratio, 0.62; p = 0.013). CONCLUSIONS: AUS patients were treated at an earlier disease stage than the USA patients with better IPFS for stage 3B disease. The USA patients treated after the availability of new systemic therapies had a better OS.

International Multicenter Experience of Isolated Limb Infusion for In-Transit Melanoma Metastases in Octogenarian and Nonagenarian Patients.

BACKGROUND: Isolated limb infusion (ILI) is used to treat in-transit melanoma metastases confined to an extremity. However, little is known about its safety and efficacy in octogenarians and nonagenarians (ON). PATIENTS AND METHODS: ON patients (≥ 80 years) who underwent a first ILI for American Joint Committee on Cancer seventh edition stage IIIB/IIIC melanoma between 1992 and 2018 at nine international centers were included and compared with younger patients (< 80 years). A cytotoxic drug combination of melphalan and actinomycin-D was used. RESULTS: Of the 687 patients undergoing a first ILI, 160 were ON patients (median age 84 years; range 80-100 years). Compared with the younger cohort (n = 527; median age 67 years; range 29-79 years), ON patients were more frequently female (70.0% vs. 56.9%; p = 0.003), had more stage IIIB disease (63.8 vs. 53.3%; p = 0.02), and underwent more upper limb ILIs (16.9% vs. 9.5%; p = 0.009). ON patients experienced similar Wieberdink limb toxicity grades III/IV (25.0% vs. 29.2%; p = 0.45). No toxicity-related limb amputations were performed. Overall response for ON patients was 67.3%, versus 64.6% for younger patients (p = 0.53). Median in-field progression-free survival was 9 months for both groups (p = 0.88). Median distant progression-free survival was 36 versus 23 months (p = 0.16), overall survival was 29 versus 40 months (p < 0.0001), and melanoma-specific survival was 46 versus 78 months (p = 0.0007) for ON patients compared with younger patients, respectively. CONCLUSIONS: ILI in ON patients is safe and effective with similar response and regional control rates compared with younger patients. However, overall and melanoma-specific survival are shorter.

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 non-SRC 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.

A systematic review and meta-analysis of locoregional treatments for in-transit melanoma.

BACKGROUND AND OBJECTIVES: In-transit melanoma (ITM) metastases present a therapeutic challenge and management decisions can be difficult. There are multiple treatments available, with differing efficacy, and supported by different levels of evidence. The primary objective was to perform a systematic review and where suitable, a meta-analysis of the literature reporting on the use of locoregional treatments for the management of ITM. METHODS: An independent review was conducted including a comprehensive search of the National Library of Medicine using PubMed, MEDLINE, Embase, and Cochrane Library databases. Key data were tabulated, synthesized and pooled to calculate relevant weighted effect sizes for each therapy using random-effect models. The statistical heterogeneity was calculated using the Higgins' method. RESULTS: Of the initial 32 612 articles identified, 57 original articles satisfied eligibility criteria. Eight treatment modalities were identified comprising: amputation (7); hyperthermic isolated limb perfusion (15); isolated limb infusion (8); carbon dioxide laser (9); PV-10 intralesional therapy (5); IL-2 intralesional therapy (8); imiquimod (7); diphenylcyclopropenone (3). Only amputation and topical imiquimod were suitable for formal meta-analysis. CONCLUSIONS: All of the assessed therapies have significant selection bias. Variable levels of evidence support the ongoing use of locoregional treatments and these may significantly improve disease-free survival.

Sun protection behavior after diagnosis of high-risk primary melanoma and risk of a subsequent primary.

BACKGROUND: Melanoma survivors are at high risk of further primary melanomas. OBJECTIVE: To assess sun behavior after melanoma diagnosis and in relation to further primary melanomas. METHODS: We applied repeated measures latent class analysis to reported primary prevention behavior at time of diagnosis and every 6 months for 2 years after diagnosis in patients with clinical stage IB or II melanoma. Correlates of behavior trajectories and risk of subsequent primaries were determined by using multivariable logistic and Cox regression analyses, respectively. RESULTS: Among the 448 male and 341 female patients, sunscreen use fell into 3 trajectories: stable never-use (26% of males and 12% of females), stable sometimes-use (35% of males and 29% of females), and increased to often-use (39% of males and 59% of females). Most reduced their weekend sun exposure, but in 82% of males and 69% of females it remained increased. Males, smokers, the less educated, those who tanned, and those not self-checking their skin were more likely to have trajectories of inadequate protection. Patients with a history of melanoma before the study doubled their risk of another primary melanoma in the next 2 years if sunscreen use in that time was inadequate (hazard ratio, 2.45; 95% confidence interval, 1.00-6.06). LIMITATIONS: Patient-reported data are susceptible to recall bias. CONCLUSION: Our results may assist clinicians in identifying patients not using adequate sun protection and providing information for patient counseling.

Generational shift in melanoma incidence and mortality in Queensland, Australia, 1995-2014.

Public campaigns encouraging sun protection for skin cancer prevention began in Queensland, Australia, in the early 1980s. We examined recent trends to assess whether earlier evidence of stabilizing melanoma incidence in young people has persisted. Anonymized incidence and mortality data for in situ and invasive melanoma for the 20 years 1995-2014 were obtained from the Queensland Cancer Registry. Time trends were analyzed using JoinPoint regression. Birth cohort patterns were assessed using age-period-cohort models. Melanoma incidence in Queensland remains the highest recorded in the world (age-standardized incidence of invasive melanoma (2010-2014) = 72/100,000/annum). Over the 20-year period, incidence of in situ melanoma increased in all age groups. Incidence of both thin (≤1 mm) and thick (>1 mm) invasive melanoma was either stable or decreased in people under 60, while it increased in those aged 60 and above, particularly in men. Age-period-cohort analysis revealed decreasing age-specific incidence of invasive melanoma under 40 years of age, beginning with the birth cohort born around the mid-1960s, with steepest falls for those born around 1980 and later. Age-specific incidence was stable between 40 and 59 years of age from the 1945 birth cohort onwards. Melanoma mortality over the period was stable or decreased in all groups except in men aged 60 or over. These findings are evidence of real advances in the prevention and early detection of invasive melanoma in this very high-risk population. They make a compelling case for continued public health efforts to reduce the burden of melanoma in susceptible populations.

Clustering of prevention behaviours in patients with high-risk primary melanoma.

OBJECTIVE: Because melanoma patients are at high risk of further disease, we aimed to study their melanoma prevention behaviours. METHODS: In a large cohort of patients newly diagnosed with high-risk melanoma in Queensland, Australia, we assessed clustering of preventive behaviours using latent class analysis. We assessed associated factors with prevalence proportion ratios (PPRs) and 95% confidence intervals (CIs) estimated by Poisson regression and also if preventive behaviour was associated with better tumour prognosis at diagnosis. RESULTS: Among 789 primary melanoma patients (57% male; 21% with previous melanoma), we identified 4 different behaviour clusters: "no/ low prevention" (34% of cohort), "sun protection only" (25%), "skin checks only" (25%), and "sun protection and skin checks" (17%). Prevalence of clusters differed between males and females and also the component behaviours. Preventive behaviours were associated with having skin that burned and past cutaneous cancer, and for males, combined sun protective and skin checking behaviour was associated with higher education and non-smoking. In patients with no past history of cutaneous cancer, males in the "skin checks only" cluster had significantly reduced chances of a thick (poor prognosis) melanoma (PPR = 0.79, 95% CI 0.68, 0.91) and females in the "sun protection and skin checks" cluster were significantly less likely to have an ulcerated melanoma (PPR = 0.85, 95% CI 0.74, 0.98) compared with the "no/ low prevention" cluster. CONCLUSION: These findings allow tailoring of preventive advice to melanoma patients to reduce their risk of future primary and recurrent disease.

Intralesional PV-10 for the treatment of in-transit melanoma metastases-Results of a prospective, non-randomized, single center study.

BACKGROUND: Patients with in-transit melanoma metastases frequently experience high rates of recurrence, limited overall survival and reduced quality of life. After promising results within a Phase II, multi-center study, PV-10 treatment was continued at our institution for patients with in-transit disease. METHODOLOGY: An open-label, non-randomized, prospective study was performed at the Princess Alexandra Hospital, Queensland, Australia. Patients were treated with PV-10 in accordance with the treatment protocol established during a previous Phase II study. The primary outcome was the complete response of treated lesions. RESULTS: Forty-five patients were enrolled over a total of 82 treatment episodes from July 2008 to December 2015. With sequential PV-10 treatments the complete response rate was 42% and overall response rate 87% on an intention to treat analysis. The median follow-up duration was 22 months and the median overall survival was 25 months from first PV-10 treatment. Having fewer than 15 metastases at the time of treatment was associated with a complete response (P = 0.03). CONCLUSIONS: Intralesional PV-10 provided rapid lesion-specific ablation of melanoma metastases with well-tolerated local effects and minimal systemic adverse events. This therapy should be considered for patients with multiple accessible deposits within the spectrum of low to moderate disease volume.

Neoadjuvant chemotherapy or chemoradiotherapy for adenocarcinoma of the esophagus.

BACKGROUND: The optimal treatment strategy for patients with esophageal adenocarcinoma (EAC) remains undetermined. This study compared outcomes in patients undergoing neoadjuvant chemotherapy (nCT) and neoadjuvant chemoradiotherapy (nCRT) for EAC. METHODS: Patients who underwent nCT or nCRT followed by surgery for EAC were identified from a prospective database (2000-2017) and included. After propensity score matching, the impact of the treatments on postoperative complications, in-hospital mortality, pathological outcomes, and survival rates were compared. RESULTS: Of the 396 eligible patients, 262 patients were analysed following matching with 131 patients in both groups. There were no significant differences between the nCT and nCRT groups for overall complications (59% vs 57%, P = 0.802) or in-hospital mortality (2% vs 0%, P = 0.156). Patients who had nCRT had more R0 resections (93% vs 83%, P = 0.013), and higher pathological complete response rates (15% vs 5%, P < 0.001). No differences in 5-year overall survival rates (nCT vs nCRT; 44% vs 33%, P = 0.645) were found. CONCLUSION: In this study no differences between nCT and nCRT were seen in postoperative complications and in-hospital mortality in patients treated for EAC. Inspite of improved complete resection and pathological response there was no difference in the overall survival between the treatment modalities.

Final trial report of sentinel-node biopsy versus nodal observation in melanoma.

BACKGROUND: Sentinel-node biopsy, a minimally invasive procedure for regional melanoma staging, was evaluated in a phase 3 trial. METHODS: We evaluated outcomes in 2001 patients with primary cutaneous melanomas randomly assigned to undergo wide excision and nodal observation, with lymphadenectomy for nodal relapse (observation group), or wide excision and sentinel-node biopsy, with immediate lymphadenectomy for nodal metastases detected on biopsy (biopsy group). Results No significant treatment-related difference in the 10-year melanoma-specific survival rate was seen in the overall study population (20.8% with and 79.2% without nodal metastases). Mean (± SE) 10-year disease-free survival rates were significantly improved in the biopsy group, as compared with the observation group, among patients with intermediate-thickness melanomas, defined as 1.20 to 3.50 mm (71.3 ± 1.8% vs. 64.7 ± 2.3%; hazard ratio for recurrence or metastasis, 0.76; P=0.01), and those with thick melanomas, defined as >3.50 mm (50.7 ± 4.0% vs. 40.5 ± 4.7%; hazard ratio, 0.70; P=0.03). Among patients with intermediate-thickness melanomas, the 10-year melanoma-specific survival rate was 62.1 ± 4.8% among those with metastasis versus 85.1 ± 1.5% for those without metastasis (hazard ratio for death from melanoma, 3.09; P<0.001); among patients with thick melanomas, the respective rates were 48.0 ± 7.0% and 64.6 ± 4.9% (hazard ratio, 1.75; P=0.03). Biopsy-based management improved the 10-year rate of distant disease-free survival (hazard ratio for distant metastasis, 0.62; P=0.02) and the 10-year rate of melanoma-specific survival (hazard ratio for death from melanoma, 0.56; P=0.006) for patients with intermediate-thickness melanomas and nodal metastases. Accelerated-failure-time latent-subgroup analysis was performed to account for the fact that nodal status was initially known only in the biopsy group, and a significant treatment benefit persisted. CONCLUSIONS: Biopsy-based staging of intermediate-thickness or thick primary melanomas provides important prognostic information and identifies patients with nodal metastases who may benefit from immediate complete lymphadenectomy. Biopsy-based management prolongs disease-free survival for all patients and prolongs distant disease-free survival and melanoma-specific survival for patients with nodal metastases from intermediate-thickness melanomas. (Funded by the National Cancer Institute, National Institutes of Health, and the Australia and New Zealand Melanoma Trials Group; ClinicalTrials.gov number, NCT00275496.).