Patterns of Recurrence After Surgery Alone Versus Preoperative Chemoradiotherapy and Surgery in the CROSS Trials

Oppedijk, Vera; Gaast, Ate van der; Lanschot, J. Jan B. van; Hagen, Pieter van; Os, Rob van; Rij, Caroline M. van; Sangen, M.J.C. van der; Beukema, Jannet C.; Rütten, Heidi; Spruit, Patty H.; Reinders, Janny G.; Richel, Dick J.; Henegouwen, Mark I. van Berge; Hulshof, Maarten C.C.M.

doi:10.1200/jco.2013.51.2186

Cited by 424 publications

(335 citation statements)

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“…A positive resection margin did not lead to significantly higher rates of local recurrence, and the majority of these patients died from systemic disease. In contrast to other series11 12, this study did not show a higher rate of local recurrence in the SCC group.…”

Section: Discussioncontrasting

confidence: 99%

“…These nodes are variably included by surgeons and oncologists in lymphadenectomy and radiotherapy fields. Interestingly, the present data showed high rates of coexisting systemic recurrence in patients with coeliac lymph node recurrence, as found elsewhere12. This implies that locoregional control is not the predominant issue in patients with involved coeliac nodes.…”

Section: Discussionsupporting

confidence: 83%

“…Even in patients who might be considered at high risk for isolated locoregional recurrence, such as those with a positive resection margin, recurrence occurs in a predominantly systemic fashion. A previous study12 documented the same finding after NACRT, with isolated locoregional recurrence being found in only 9 and 3 per cent respectively of patients receiving surgery alone and those who had NACRT. Most patients developed systemic recurrence following NACRT.…”

Section: Discussionsupporting

confidence: 59%

“…Most patients developed systemic recurrence following NACRT. In that same study12, lymph node‐positive patients and those who did not receive neoadjuvant treatment had an increased risk of local recurrence, but the benefit of treatment was greatest in the SCC group. Given that the outcomes of most patients with adenocarcinoma will be dictated by the presence of systemic disease, the role for radiotherapy as standard practice in all patients should still be questioned, particularly as this is often accompanied by a reduction in systemic chemotherapy dose.…”

Section: Discussionmentioning

confidence: 86%

“…Intuitively, locoregional recurrences would best be defined as those occurring within an agreed target area of a given locoregional therapy, either a field of surgical resection with lymphadenectomy or radiotherapy. Previous studies 12, 13 have used both criteria but with areas of notable contention such as the inclusion of supraclavicular lymph nodes as locoregional recurrence for SCC 12 . Equally contentious in the context of adenocarcinoma is the status of coeliac lymph nodes, which were traditionally considered M1a disease in the sixth TNM classification.…”

Section: Discussionmentioning

confidence: 99%

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Patterns of recurrence in oesophageal cancer following oesophagectomy in the era of neoadjuvant chemotherapy

Knight

Zylstra²,

Hemelrijck

et al. 2017

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BackgroundTumour recurrence following oesophagectomy for oesophageal cancer is common despite neoadjuvant treatment. Understanding patterns of recurrence and risk factors associated with locoregional and systemic recurrence might influence future treatment strategies.MethodsThis was a cohort study involving patients undergoing resection for adenocarcinoma or squamous cell carcinoma of the oesophagus between 2000 and 2014. Clinicopathological factors associated with locoregional and systemic recurrence were analysed using multivariable logistic regression to determine odds ratios (ORs) and 95 per cent confidence intervals.ResultsSome 698 patients were identified. Lymphovascular invasion (OR 2·09, 95 per cent c.i. 1·18 to 3·71) and preoperative stenting (OR 3·70, 1·34 to 10·23) were independent risk factors for isolated locoregional recurrence. Pathological nodal disease in patients with pT1–2 (pN1: OR 2·72, 1·35 to 5·48; pN2–3: OR 5·00, 2·35 to 10·66) or pT3–4 (pN1: OR 3·03, 1·51 to 6·07; pN2–3: OR 5·75, 3·15 to 10·49) disease predisposed to systemic recurrence. Poor or no response to chemotherapy was also an independent risk factor for isolated systemic recurrence (OR 1·85, 1·05 to 3·26). A positive resection margin (R1 resection) was not associated with a significantly increased risk of isolated locoregional recurrence (OR 1·37, 0·81 to 2·33).ConclusionThese findings confirm that oesophageal adenocarcinoma is frequently a systemic disease. Understanding the key predictors of local and systemic recurrence may facilitate the tailoring of oncological therapies to the individual patient.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 83%

Section: Discussionsupporting

confidence: 59%

Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

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Patterns of recurrence in oesophageal cancer following oesophagectomy in the era of neoadjuvant chemotherapy

Knight

Zylstra²,

Hemelrijck

et al. 2017

BJS Open

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Adjuvant Chemotherapy vs Postoperative Observation Following Preoperative Chemoradiotherapy and Resection in Gastroesophageal Cancer

et al. 2018

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Long-term Efficacy of Neoadjuvant Chemoradiotherapy Plus Surgery for the Treatment of Locally Advanced Esophageal Squamous Cell Carcinoma

et al. 2021

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IMPORTANCEThe prognosis of patients with locally advanced esophageal squamous cell carcinoma (ESCC) remains poor after surgery. Neoadjuvant chemoradiotherapy (NCRT) has been shown to potentially improve survival.OBJECTIVE To compare the treatment efficacy of NCRT plus surgery with surgery alone for long-term survival among patients with locally advanced ESCC. DESIGN, SETTING, AND PARTICIPANTSThe Neoadjuvant Chemoradiotherapy for Esophageal Cancer 5010 study was a multicenter open-label randomized phase 3 clinical trial that enrolled patients between June 1, 2007, and December 31, 2014. Follow-up ended on December 31, 2019. The study was conducted at 8 centers in China. A total of 451 patients aged 18 to 70 years with thoracic ESCC stage T1-4N1M0/T4N0M0 were enrolled and randomized. Data were analyzed from December 1, 2019, to June 30, 2020.INTERVENTIONS Patients randomized to receive NCRT plus surgery (NCRT group) received preoperative chemotherapy (25 mg/m 2 of vinorelbine on days 1 and 8 and 75 mg/m 2 of cisplatin on day 1 or 25 mg/m 2 of cisplatin on days 1 to 4) every 3 weeks for 2 cycles and concurrent radiotherapy (40.0 Gy, administered in 20 fractions of 2.0 Gy for 5 days per week) followed by surgery. Patients randomized to receive surgery alone (surgery group) underwent surgery after randomization. MAIN OUTCOMES AND MEASURESThe primary end point was overall survival in the intention-to-treat population. The secondary end point was disease-free survival.RESULTS A total of 451 patients (mean [SD] age, 56.5 [7.0] years; 367 men [81.4%]) were randomized to the NCRT (n = 224) and surgery (n = 227) groups and were eligible for the intention-to-treat analysis. By December 31, 2019, 224 deaths had occurred. The median follow-up was 53.5 months (interquartile range, 18.2-87.4 months). Patients receiving NCRT plus surgery had prolonged overall survival compared with those receiving surgery alone (hazard ratio, 0.74; 95% CI, 0.57-0.97; P = .03), with a 5-year survival rate of 59.9% (95% CI, 52.9%-66.1%) vs 49.1% (95% CI, 42.3%-55.6%), respectively. Patients in the NCRT group compared with the surgery group also had prolonged disease-free survival (hazard ratio, 0.60; 95% CI, 0.45-0.80; P < .001), with a 5-year survival rate of 63.6% (95% CI, 56.0%-70.2%) vs 43.0% (95% CI, 36.0%-49.7%), respectively. CONCLUSIONS AND RELEVANCEIn this randomized clinical trial, treatment with NCRT plus surgery significantly improved long-term overall survival and disease-free survival and therefore may be considered a standard of care for patients with locally advanced ESCC.

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Patterns of Recurrence After Surgery Alone Versus Preoperative Chemoradiotherapy and Surgery in the CROSS Trials

Abstract: Preoperative CRT in patients with esophageal cancer reduced LRR and peritoneal carcinomatosis. Recurrence within the radiation target volume occurred in only 5%, mostly combined with outfield failures.

Cited by 424 publications

References 16 publications

Patterns of recurrence in oesophageal cancer following oesophagectomy in the era of neoadjuvant chemotherapy

Patterns of recurrence in oesophageal cancer following oesophagectomy in the era of neoadjuvant chemotherapy

Adjuvant Chemotherapy vs Postoperative Observation Following Preoperative Chemoradiotherapy and Resection in Gastroesophageal Cancer

Long-term Efficacy of Neoadjuvant Chemoradiotherapy Plus Surgery for the Treatment of Locally Advanced Esophageal Squamous Cell Carcinoma

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