Introduction
Enhanced recovery after surgery (ERAS) programs provide a format for multidisciplinary care and has been shown to predictably improve short term outcomes associated with surgical ...procedures. Esophagectomy has historically been associated with significant levels of morbidity and mortality and as a result routine application and audit of ERAS guidelines specifically designed for esophageal resection has significant potential to improve outcomes associated with this complex procedure.
Methods
A team of international experts in the surgical management of esophageal cancer was assembled and the existing literature was identified and reviewed prior to the production of the guidelines. Well established procedure specific components of ERAS were reviewed and updated with changes relevant to esophagectomy. Procedure specific, operative and technical sections were produced utilizing the best current level of evidence. All sections were rated regarding the level of evidence and overall recommendation according to the evaluation (GRADE) system.
Results
Thirty-nine sections were ultimately produced and assessed for quality of evidence and recommendations. Some sections were completely new to ERAS programs due to the fact that esophagectomy is the first guideline with a thoracic component to the procedure.
Conclusions
The current ERAS society guidelines should be reviewed and applied in all centers looking to improve outcomes and quality associated with esophageal resection.
Summary Background In a previous meta-analysis, we identified a survival benefit from neoadjuvant chemotherapy or chemoradiotherapy before surgery in patients with resectable oesophageal carcinoma. ...We updated this meta-analysis with results from new or updated randomised trials presented in the past 3 years. We also compared the benefits of preoperative neoadjuvant chemotherapy compared with neoadjuvant chemoradiotherapy. Methods To identify additional studies and published abstracts from major scientific meetings, we searched Medline, Embase, and Central (Cochrane clinical trials database) for studies published since January, 2006, and also manually searched for abstracts from major conferences from the same period. Only randomised studies analysed by intention to treat were included, and searches were restricted to those databases citing articles in English. We used published hazard ratios (HRs) if available or estimates from other survival data. We also investigated treatment effects by tumour histology and relations between risk (survival after surgery alone) and effect size. Findings We included all 17 trials from the previous meta-analysis and seven further studies. 12 were randomised comparisons of neoadjuvant chemoradiotherapy versus surgery alone (n=1854), nine were randomised comparisons of neoadjuvant chemotherapy versus surgery alone (n=1981), and two compared neoadjuvant chemoradiotherapy with neoadjuvant chemotherapy (n=194) in patients with resectable oesophageal carcinoma; one factorial trial included two comparisons and was included in analyses of both neoadjuvant chemoradiotherapy (n=78) and neoadjuvant chemotherapy (n=81). The updated analysis contained 4188 patients whereas the previous publication included 2933 patients. This updated meta-analysis contains about 3500 events compared with about 2230 in the previous meta-analysis (estimated 57% increase). The HR for all-cause mortality for neoadjuvant chemoradiotherapy was 0·78 (95% CI 0·70–0·88; p<0·0001); the HR for squamous-cell carcinoma only was 0·80 (0·68–0·93; p=0·004) and for adenocarcinoma only was 0·75 (0·59–0·95; p=0·02). The HR for all-cause mortality for neoadjuvant chemotherapy was 0·87 (0·79–0·96; p=0·005); the HR for squamous-cell carcinoma only was 0·92 (0·81–1·04; p=0·18) and for adenocarcinoma only was 0·83 (0·71–0·95; p=0·01). The HR for the overall indirect comparison of all-cause mortality for neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy was 0·88 (0·76–1·01; p=0·07). Interpretation This updated meta-analysis provides strong evidence for a survival benefit of neoadjuvant chemoradiotherapy or chemotherapy over surgery alone in patients with oesophageal carcinoma. A clear advantage of neoadjuvant chemoradiotherapy over neoadjuvant chemotherapy has not been established. These results should help inform decisions about patient management and design of future trials. Funding Cancer Australia and the NSW Cancer Institute.
Sentinel-node biopsy followed by lymphadenectomy for tumor-positive nodes improved disease-free survival among patients with intermediate-thickness melanomas (1.2 to 3.5 mm) and those with thick ...melanomas (>3.5 mm).
Regional node management in melanoma has remained controversial since Snow
1
recommended elective complete lymphadenectomy for all patients with melanoma, regardless of whether there was clinical evidence of regional nodal metastases. However, routine elective lymphadenectomy exposes all patients to procedure-related complications and cannot benefit the majority, who have no regional nodal metastases. Multiple randomized trials have suggested a benefit of routine lymphadenectomy in at least some groups of patients with melanoma.
2
–
6
Because of dissatisfaction with both elective lymphadenectomy and nodal observation, lymphatic mapping and sentinel-node biopsy were introduced for individualized management of regional lymph nodes.
6
–
9
Sentinel-node biopsy is a . . .
Summary Background Resectable oesophageal cancer is often treated with surgery alone or with preoperative (neoadjuvant) chemoradiotherapy or chemotherapy. We aimed to clarify the benefits of ...neoadjuvant chemoradiotherapy or chemotherapy versus surgery alone by a meta-analysis of randomised trial data. Methods Eligible trials were identified first from earlier published meta-analyses and systematic reviews. We also used MEDLINE, Cancerlit, and EMBASE databases to identify additional studies and published abstracts from major scientific meetings since 1980. Only randomised studies with an analysis by an intention-to-treat principle were included, and searches were restricted to those databases citing articles in English. We used published hazard ratios if available or estimates from other survival data or survival curves. Treatment effects by type of tumour and treatment sequencing were also investigated. Findings Ten randomised comparisons of neoadjuvant chemoradiotherapy versus surgery alone (n=1209) and eight of neoadjuvant chemotherapy versus surgery alone (n=1724) in patients with local operable oesophageal carcinoma were identified. The hazard ratio for all-cause mortality with neoadjuvant chemoradiotherapy versus surgery alone was 0·81 (95% CI 0·70–0·93; p=0·002), corresponding to a 13% absolute difference in survival at 2 years, with similar results for different histological tumour types: 0·84 (0·71–0·99; p=0·04) for squamous-cell carcinoma (SCC), and 0·75 (0·59–0·95; p=0·02) for adenocarcinoma. The hazard ratio for neoadjuvant chemotherapy was 0·90 (0·81–1·00; p=0·05), which indicates a 2-year absolute survival benefit of 7%. There was no significant effect on all-cause mortality of chemotherapy for patients with SCC (hazard ratio 0·88 0·75–1·03; p=0·12), although there was a significant benefit for those with adenocarcinoma (0·78 0·64–0·95; p=0·014). Interpretation A significant survival benefit was evident for preoperative chemoradiotherapy and, to a lesser extent, for chemotherapy in patients with adenocarcinoma of the oesophagus. The findings provide an evidence-based framework for the use of neoadjuvant treatment in management decisions.
The European Organisation for Research and Treatment of Cancer, Quality of Life Questionnaire–30 (EORTC QLQ-30) instrument was used in the other two adjuvant therapy trials, but has not been ...specifically validated to assess immunotherapy and does not address endocrinopathies or dermatological immune-related adverse events, both of which are very relevant to those trials.3,4,6 All of the trials previously described were done with a protocol of timed assessments, including health-related quality of life. The frequency of discontinuation and reversibility of adverse events is likely to be a reason for the apparent lack of effect on the average health-related quality-of-life score when the whole cohort is analysed.1 The high frequency of discontinuation in the two adjuvant immunotherapy trials could have affected reporting of health-related quality of life.4,6 These adjuvant trials were powered to assess survival and recurrence endpoints, not health-related quality of life. Patients might also perceive drug-induced toxicity as being indicative of potential benefit, or could believe they are receiving active treatment; as such, a true assessment of the effect of drug toxicity on quality of life is not recorded.7 In the COMBI-AD trial, for an individual who does not have known metastatic melanoma, the overall conclusion—that treatment with dabrafenib plus trametinib has the same health-related quality-of-life outcome as placebo—does not tell the full story.
Purpose
Enhanced Recovery After Surgery (ERAS) protocols have been effectively expanded to various surgical specialities including oesophagectomy. Despite nutrition being a key component, actual ...nutrition outcomes and specific guidelines are lacking. This cohort comparison study aims to compare nutritional status and adherence during implementation of a standardised post-operative nutritional support protocol, as part of ERAS, compared to those who received usual care.
Methods
Two groups of patients undergoing resection of oesophageal cancer were studied. Group 1 (
n
= 17) underwent oesophagectomy between Oct 2014 and Nov 2016 during implementation of an ERAS protocol. Patients in group 2 (
n
= 16) underwent oesophagectomy between Jan 2011 and Dec 2012 prior to the implementation of ERAS. Demographic, nutritional status, dietary intake and adherence data were collected. Ordinal data was analysed using independent
t
tests, and categorical data using chi-square tests.
Results
There was no significant difference in nutrition status, dietary intake or length of stay following implementation of an ERAS protocol. Malnutrition remained prevalent in both groups at day 42 post surgery (
n
= 10, 83% usual care; and
n
= 9, 60% ERAS). A significant difference was demonstrated in adherence with earlier initiation of oral free fluids (
p
<0.008), transition to soft diet (
p
<0.004) and continuation of jejunostomy feeds on discharge (
p
<0.000) for the ERAS group.
Conclusion
A standardised post-operative nutrition protocol, within an ERAS framework, results in earlier transition to oral intake; however, malnutrition remains prevalent post surgery. Further large-scale studies are warranted to examine individualised decision-making regarding nutrition support within an ERAS protocol.
Background
Isolated limb infusion (ILI) is a minimally invasive procedure for delivering high-dose regional chemotherapy to patients with locally advanced or in-transit melanoma located on a limb. ...The current international multicenter study evaluated the perioperative and long-term oncologic outcomes for patients who underwent ILI for stage 3B or 3C melanoma.
Methods
Patients undergoing a first-time ILI for stage 3B or 3C melanoma (American Joint Committee on Cancer AJCC 7th ed) between 1992 and 2018 at five Australian and four United States of America (USA) tertiary referral centers were identified. The primary outcome measures included treatment response, in-field (IPFS) and distant progression-free survival (DPFS), and overall survival (OS).
Results
A total of 687 first-time ILIs were performed (stage 3B:
n
= 383, 56%; stage 3C;
n
= 304, 44%). Significant limb toxicity (Wieberdink grade 4) developed in 27 patients (3.9%). No amputations (grade 5) were performed. The overall response rate was 64.1% (complete response CR, 28.9%; partial response PR, 35.2%). Stable disease (SD) occurred in 14.5% and progressive disease (PD) in 19.8% of the patients. The median follow-up period was 47 months, with a median OS of 38.2 months. When stratified by response, the patients with a CR or PR had a significantly longer median IPFS (21.9 vs 3.0 months;
p
< 0.0001), DPFS (53.6 vs 12.7 months;
p
< 0.0001), and OS (46.5 vs 24.4 months;
p
< 0.0001) than the nonresponders (SD + PD).
Conclusion
This study is the largest to date reporting long-term outcomes of ILI for locoregionally metastatic melanoma. The findings demonstrate that ILI is effective and safe for patients with stage 3B or 3C melanoma confined to a limb. A favorable response to ILI is associated with significantly longer IFPS, DPFS, and OS.
Summary Background Adjuvant radiotherapy is recommended for patients with melanoma after lymphadenectomy. We previously showed this treatment reduced risk of repeat lymph-node field cancer in ...patients with a high risk of recurrence but had no effect on overall survival. Here, we aim to update the relapse and survival data from that trial and assess quality of life and toxic effects. Methods In the ANZMTG 01.02/TROG 02.01 randomised controlled trial, we enrolled patients who had undergone lymphadenectomy for a palpable lymph-node field relapse and were at high risk of recurrence at 16 hospitals (11 in Australia, three in New Zealand, one in Netherlands, and one in Brazil). We randomly assigned patients (1:1) to adjuvant radiotherapy (48 Gy in 20 fractions, given over a maximum of 30 days) or observation, stratified by institution, areas of lymph-node field (parotid and cervical, axilla, or groin), number of involved nodes (≤3 vs >3), maximum involved node diameter (≤4 cm vs >4 cm), and extent of extracapsular extension (none, limited, or extensive). Participants, those giving treatment, and those assessing outcomes were not masked to treatment allocation, but participants were unaware of each other's treatment allocation. In this follow-up, we assessed outcomes every 3 months from randomisation for the first 2 years, then every 6 months up to 5 years, then annually. The primary endpoint was lymph-node field relapse as a first relapse, assessed in patients without major eligibility infringements (determined by an independent data monitoring committee). We assessed late adverse effects (occurring >90 days after surgery or start of radiotherapy) with standard criteria in the as-treated population. This study is registered with ClinicalTrials.gov , number NCT00287196. Findings Between March 21, 2003, and Nov 15, 2007, we randomly assigned 123 patients to adjuvant radiotherapy (109 eligible for efficacy assessments) and 127 to observation (108 eligible). The final follow-up date was Nov 15, 2011. Median follow-up was 73 months (IQR 61–91). 23 (21%) relapses occurred in the adjuvant radiotherapy group compared with 39 (36%) in the observation group (adjusted hazard ratio HR 0·52 95% CI 0·31–0·88, p=0·023). Overall survival (HR 1·27 95% CI 0·89–1·79, p=0·21) and relapse-free survival (0·89 0·65–1·22, p=0·51) did not differ between groups. Minor, long-term toxic effects from radiotherapy (predominantly pain, and fibrosis of the skin or subcutaneous tissue) were common, and 20 (22%) of 90 patients receiving adjuvant radiotherapy developed grade 3–4 toxic effects. 18 (20%) of 90 patients had grade 3 toxic effects, mainly affecting skin (nine 10% patients) and subcutaneous tissue (six 7% patients). Over 5 years, a significant increase in lower limb volumes was noted after adjuvant radiotherapy (mean volume ratio 15·0%) compared with observation (7·7%; difference 7·3% 95% CI 1·5–13·1, p=0·014). No significant differences in upper limb volume were noted between groups. Interpretation Long-term follow-up supports our previous findings. Adjuvant radiotherapy could be useful for patients for whom lymph-node field control is a major issue, but entry to an adjuvant systemic therapy trial might be a preferable first option. Alternatively, observation, reserving surgery and radiotherapy for a further recurrence, might be an acceptable strategy. Funding National Health and Medical Research Council of Australia, Cancer Council Australia, Melanoma Institute Australia, and the Cancer Council South Australia.
Background
For stage IV melanoma, systemic medical therapy (SMT) is used most frequently; surgery is considered an adjunct in selected patients. We retrospectively compared survival after surgery ...with or without SMT versus SMT alone for melanoma patients developing distant metastases while enrolled in the first Multicenter Selective Lymphadenectomy Trial.
Methods
Patients were randomized to wide excision and sentinel node biopsy, or wide excision and nodal observation. We evaluated recurrence site, therapy (selected by treating clinician), and survival after stage IV diagnosis.
Results
Of 291 patients with complete data for stage IV recurrence, 161 (55 %) underwent surgery with or without SMT. Median survival was 15.8 versus 6.9 months, and 4-year survival was 20.8 versus 7.0 % for patients receiving surgery with or without SMT versus SMT alone (
p
< 0.0001; hazard ratio 0.406). Surgery with or without SMT conferred a survival advantage for patients with M1a (median > 60 months vs. 12.4 months; 4-year survival 69.3 % vs. 0;
p
= 0.0106), M1b (median 17.9 vs. 9.1 months; 4-year survival 24.1 vs. 14.3 %;
p
= 0.1143), and M1c (median 15.0 vs. 6.3 months; 4-year survival 10.5 vs. 4.6 %;
p
= 0.0001) disease. Patients with multiple metastases treated surgically had a survival advantage, and number of operations did not reduce survival in the 67 patients (42 %) who had multiple surgeries for distant melanoma.
Conclusions
Our findings suggest that over half of stage IV patients are candidates for resection and exhibit improved survival over patients receiving SMT alone, regardless of site and number of metastases. We have begun a multicenter randomized phase III trial comparing surgery versus SMT as initial treatment for resectable distant melanoma.
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