Abstract
Background
Currently most surgeons allow 6–12 weeks after neoadjuvant therapy prior to recommending esophagectomy. Given that complete pathologic response correlates to improved survival, some have advocated a longer interval should be entertained to increase the pathologic response. The impact of an expanded neoadjuvant therapy-surgery timing is not currently well understood.
Methods
Utilizing the National Cancer Database, we identified patients with esophageal cancer who underwent neoadjuvant therapy followed by esophagectomy. Patients were divided into 3-time intervals: < 6 weeks, 6–12 weeks, and > 3 months.
Results
We identified 9256 patients who received neoadjuvant therapy followed by esophagectomy. There were 7858 (84.9%) males and 1398 (15.1%) females with a median age of 62. The median lymph nodes harvested decreased as timing increased (p < 0.001) and mean lymph nodes positive decreased as timing increased, p = 0.01. The complete response rate also increased as timing increased, p < 0.001. However, this improvement in pathologic complete response did not translate into an increase in median survival. Ninety-day mortality increased as the timing from neoadjuvant therapy increased: 6.4%, 7.9%, and 10.2%, respectively, p = 0.002.
Conclusion
Our data demonstrates that patients who have a prolonged neoadjuvant therapy- esophagectomy interval will have a substantial increase in 90-day mortality. While there was an increase in pathologic complete response rates, this did not translate into an improvement in survival. The current recommendations of a neoadjuvant therapy-surgery timing of 6–12 weeks should remain.
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References
Bray F, Ferlay J, Soerjomataram I et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68: 394-424.
Dubecz A, Gall I, Solymosi N et al. Temporal trends in long-term survival and cure rates in esophageal cancer: a SEER database analysis. J Thorac Oncol 2012; 7: 443-447.
Ajani JA, D'Amico TA, Almhanna K et al. Esophageal and esophagogastric junction cancers, version 1.2015. J Natl Compr Canc Netw 2015; 13: 194-227.
Cunningham D, Allum WH, Stenning SP et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer.[see comment]. New England Journal of Medicine 2006; 355: 11-20.
van Hagen P, Hulshof MC, van Lanschot JJ et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med 2012; 366: 2074-2084.
Shridhar R, Almhanna K, Meredith KL et al. Radiation therapy and esophageal cancer. Cancer Control 2013; 20: 97-110.
Sjoquist KM, Burmeister BH, Smithers BM et al. Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. Lancet Oncol 2011; 12: 681-692.
Meredith KL, Weber JM, Turaga KK et al. Pathologic response after neoadjuvant therapy is the major determinant of survival in patients with esophageal cancer. Ann Surg Oncol 2010; 17: 1159-1167.
Tiesi G, Park W, Gunder M et al. Long-term survival based on pathologic response to neoadjuvant therapy in esophageal cancer. J Surg Res 2017; 216: 65-72.
Purwar P, Bambarkar S, Jiwnani S et al. Multimodality management of esophageal cancer. Indian J Surg 2014; 76: 494-503.
Biere S, Van Berge Henegouwen M, Maas K, al. e. Minimally invasive versus open oesophagectomy for patients with oesophageal cancer: a multicentre, open-label, randomised controlled trial. Lancet. 2012; May:379(9829): 1887-1892.
Ikebe M, Morita M, Yamamoto M, Toh Y. Neoadjuvant therapy for advanced esophageal cancer: the impact on surgical management. Gen Thorac Cardiovasc Surg 2016; 64: 386-394.
Markar SR, Arya S, Karthikesalingam A, Hanna GB. Technical factors that affect anastomotic integrity following esophagectomy: systematic review and meta-analysis. Ann Surg Oncol 2013; 20: 4274-4281.
Oppedijk V, van der Gaast A, van Lanschot JJ et al. Patterns of recurrence after surgery alone versus preoperative chemoradiotherapy and surgery in the CROSS trials. J Clin Oncol 2014; 32: 385-391.
Tripp P, Malhotra HK, Javle M et al. Cardiac function after chemoradiation for esophageal cancer: comparison of heart dose-volume histogram parameters to multiple gated acquisition scan changes. Dis Esophagus 2005; 18: 400-405.
Lund M, Alexandersson von Döbeln G, Nilsson M et al. Effects on heart function of neoadjuvant chemotherapy and chemoradiotherapy in patients with cancer in the esophagus or gastroesophageal junction - a prospective cohort pilot study within a randomized clinical trial. Radiat Oncol 2015; 10: 16.
Cui Z, Tian Y, He B et al. Associated factors of radiation pneumonitis induced by precise radiotherapy in 186 elderly patients with esophageal cancer. Int J Clin Exp Med 2015; 8: 16646-16651.
Zhao Y, Chen L, Zhang S et al. Predictive factors for acute radiation pneumonitis in postoperative intensity modulated radiation therapy and volumetric modulated arc therapy of esophageal cancer. Thorac Cancer 2015; 6: 49-57.
Shaikh T, Ruth K, Scott WJ et al. Increased time from neoadjuvant chemoradiation to surgery is associated with higher pathologic complete response rates in esophageal cancer. Ann Thorac Surg 2015; 99: 270-276.
Qin Q, Xu H, Liu J et al. Does timing of esophagectomy following neoadjuvant chemoradiation affect outcomes? A meta-analysis. Int J Surg 2018; 59: 11-18.
Markar SR, Johar A, Maisey N et al. Complications during neoadjuvant therapy and prognosis following surgery for esophageal cancer. Dis Esophagus 2018;31(5).
Franko J, McAvoy S. Timing of esophagectomy after neoadjuvant chemoradiation treatment in squamous cell carcinoma. Surgery 2018; 164: 455-459.
Shapiro J, van Hagen P, Lingsma HF et al. Prolonged time to surgery after neoadjuvant chemoradiotherapy increases histopathological response without affecting survival in patients with esophageal or junctional cancer. Ann Surg 2014; 260: 807-813; discussion 813-804.
Ruol A, Rizzetto C, Castoro C et al. Interval between neoadjuvant chemoradiotherapy and surgery for squamous cell carcinoma of the thoracic esophagus: does delayed surgery have an impact on outcome? Ann Surg 2010; 252: 788-796.
Chiu CH, Chao YK, Chang HK et al. Interval between neoadjuvant chemoradiotherapy and surgery for esophageal squamous cell carcinoma: does delayed surgery impact outcome? Ann Surg Oncol 2013; 20: 4245-4251.
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Taylor Maramara: concept and design, data analysis and interpretation, manuscript writing and final approval. Ravi Shridhar: concept and design, data analysis and interpretation, manuscript writing and final approval. Paige Blinn: concept and design, data analysis and interpretation, manuscript writing and final approval. Jamie Huston: data acquisition, analysis and interpretation, manuscript revision and final approval. Kenneth Meredith: concept and design, data analysis and interpretation, manuscript writing and final approval.
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Maramara, T., Shridhar, R., Blinn, P. et al. Timing After Neoadjuvant Therapy Predicts Mortality in Patients Undergoing Esophagectomy: a Propensity Score–Matched Analysis. J Gastrointest Surg 27, 2342–2351 (2023). https://doi.org/10.1007/s11605-023-05851-1
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DOI: https://doi.org/10.1007/s11605-023-05851-1