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What is the role of neoadjuvant chemotherapy, radiation, and adjuvant treatment in resectable esophageal cancer?

ABSTRACT: The majority of patients with operable esophageal cancers present with locally advanced disease, for which surgical resection as a sole treatment modality has been historically associated with poor survival. Even following radical resection, most of these patients will eventually succumb to their disease due to distant metastasis. For this reason, there has been intense interest in the role of neoadjuvant therapy. Neoadjuvant therapy primarily consists of either chemotherapy, radiation therapy, or a combination of the two. Multiple studies of variable scope, design, and patient characteristics have been conducted to determine whether neoadjuvant therapy is warranted, and-if so-what is the best modality of treatment. Despite nearly three decades of study, decisions regarding neoadjuvant therapy for esophageal cancer remain controversial. Regardless, the available evidence provided by large, prospective studies supports preoperative chemotherapy as opposed to surgery alone. Therefore, in our opinion, there is no longer any question as to whether induction therapy is appropriate for locally advanced esophageal cancer. Less clear, however, is the evidence that the addition of radiation to chemotherapy in the preoperative setting is superior to neoadjuvant chemotherapy alone. Our group generally advocates for neoadjuvant chemotherapy alone followed by radical esophageal resection. The data for adjuvant therapy are soft, and particularly troubling is the high rate of treatment drop out in trials studying adjuvant therapy. Therefore, we strongly prefer neoadjuvant chemotherapy and reserve adjuvant chemotherapy for those rare, highly selected patients-patients with T1 tumors, for example-who do not receive neoadjuvant treatment and are found to have occult nodal disease at the time of surgery.

SUBMITTER: Altorki N

PROVIDER: S-EPMC5387137 | biostudies-other | 2017 Mar

REPOSITORIES: biostudies-other

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What is the role of neoadjuvant chemotherapy, radiation, and adjuvant treatment in resectable esophageal cancer?

Altorki Nasser N Harrison Sebron S

Annals of cardiothoracic surgery 20170301 2

The majority of patients with operable esophageal cancers present with locally advanced disease, for which surgical resection as a sole treatment modality has been historically associated with poor survival. Even following radical resection, most of these patients will eventually succumb to their disease due to distant metastasis. For this reason, there has been intense interest in the role of neoadjuvant therapy. Neoadjuvant therapy primarily consists of either chemotherapy, radiation therapy, ...[more]

PMID: 28447006

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Project description:BackgroundCarcinoma of the esophagus is an aggressive malignancy with an increasing incidence. Its virulence, in terms of symptoms and mortality, justifies a continued search for optimal therapy. The large and growing number of patients affected, the high mortality rates, the worldwide geographic variation in practice, and the large body of good quality research warrants a systematic review with meta-analysis.MethodsA systematic review and meta-analysis investigating the impact of neoadjuvant or adjuvant therapy on resectable thoracic esophageal cancer to inform evidence-based practice was produced.MEDLINE, CANCERLIT, Cochrane Library, EMBASE, and abstracts from the American Society of Clinical Oncology and the American Society for Therapeutic Radiology and Oncology were searched for trial reports. Included were randomized trials or meta-analyses of neoadjuvant or adjuvant treatments compared with surgery alone or other treatments in patients with resectable thoracic esophageal cancer. Outcomes of interest were survival, adverse effects, and quality of life. Either one- or three-year mortality data were pooled and reported as relative risk ratios.ResultsThirty-four randomized controlled trials and six meta-analyses were obtained and grouped into 13 basic treatment approaches. Single randomized controlled trials detected no differences in mortality between treatments for the following comparisons:- Preoperative radiotherapy versus postoperative radiotherapy.- Preoperative and postoperative radiotherapy versus postoperative radiotherapy. Preoperative and postoperative radiotherapy was associated with a significantly higher mortality rate.- Postoperative chemotherapy versus postoperative radiotherapy.- Postoperative radiotherapy versus postoperative radiotherapy plus protein-bound polysaccharide versus chemoradiation versus chemoradiation plus protein-bound polysaccharide. Pooling one-year mortality detected no statistically significant differences in mortality between treatments for the following comparisons:- Preoperative radiotherapy compared with surgery alone (five randomized trials).- Postoperative radiotherapy compared with surgery alone (five randomized trials).- Preoperative chemotherapy versus surgery alone (six randomized trials).- Preoperative and postoperative chemotherapy versus surgery alone (two randomized trials).- Preoperative chemoradiation therapy versus surgery alone (six randomized trials). Single randomized controlled trials detected differences in mortality between treatments for the following comparison:- Preoperative hyperthermia and chemoradiotherapy versus preoperative chemoradiotherapy in favour of hyperthermia. Pooling three-year mortality detected no statistically significant difference in mortality between treatments for the following comparison:- Postoperative chemotherapy compared with surgery alone (two randomized trials). Pooling three-year mortality detected statistically significant differences between treatments for the following comparisons:- Preoperative chemoradiation therapy versus surgery alone (six randomized trials) in favour of preoperative chemoradiation with surgery.- Preoperative chemotherapy compared with preoperative radiotherapy (one randomized trial) in favour of preoperative radiotherapy.ConclusionFor adult patients with resectable thoracic esophageal cancer for whom surgery is considered appropriate, surgery alone (i.e., without neoadjuvant or adjuvant therapy) is recommended as the standard practice.

Project description:BackgroundThe 5-year survival rate of patients with locally advanced esophageal cancer is still low after neoadjuvant therapy plus esophagectomy, and additional adjuvant treatment may be required. Some studies have shown that patients can still benefit from adjuvant chemotherapy (AC) despite its toxic and side effects. This study was designed to explore which patients could benefit from AC.MethodsA retrospective cohort study based on patients who received neoadjuvant therapy plus esophagectomy with complete survival information between December 2014 and November 2020 was conducted. The inclusion criteria were as follows: esophageal cancer was diagnosed by pathological biopsy; neoadjuvant chemotherapy; neoadjuvant chemoradiotherapy; R0 resection. The exclusion criteria were as follows: neoadjuvant chemotherapy combined with targeted therapy or immunotherapy; adjuvant radiotherapy, adjuvant chemoradiotherapy, immunotherapy, or targeted therapy; dead within 90 days of surgery; nonradical (R1/R2) resection; one cycle of postoperative chemotherapy. Patients were divided into AC group (AC) and non-AC group [AC(-)] according to whether AC was performed. We obtained the tumor recurrence and survival status of the patients through inpatient medical records, outpatient electronic medical records, and telephone follow-up of the First Affiliated Hospital of Zhengzhou University. Overall survival (OS) and recurrence-free survival (RFS) were investigated as the outcome measures via Kaplan-Meier curves and Cox analyses.ResultsIn total, 318 patients were enrolled, among which 214 patients received AC while the other 104 patients did not [AC(-)]. There were significant differences in age and lymph nodes dissected between patients who received AC and those who did not receive AC (P<0.05). Survival curves were plotted using the Kaplan-Meier method, and in the overall group and subgroup, AC was beneficial for OS but not for RFS. In the overall group, sex (P=0.027) and age (P=0.027) were independent prognostic factors for OS. Subgroup multivariate Cox proportional hazards analysis showed that age (P=0.026) and AC (P=0.023) were independent prognostic factors for patients.ConclusionsFor patients with locally advanced esophageal cancer who have residual disease after surgery, adjuvant therapy after neoadjuvant chemoradiotherapy and surgery may be a better treatment.

Project description:BackgroundNeoadjuvant or adjuvant chemotherapy confers a modest benefit over surgery alone for resectable non-small-cell lung cancer (NSCLC). In early-phase trials, nivolumab-based neoadjuvant regimens have shown promising clinical activity; however, data from phase 3 trials are needed to confirm these findings.MethodsIn this open-label, phase 3 trial, we randomly assigned patients with stage IB to IIIA resectable NSCLC to receive nivolumab plus platinum-based chemotherapy or platinum-based chemotherapy alone, followed by resection. The primary end points were event-free survival and pathological complete response (0% viable tumor in resected lung and lymph nodes), both evaluated by blinded independent review. Overall survival was a key secondary end point. Safety was assessed in all treated patients.ResultsThe median event-free survival was 31.6 months (95% confidence interval [CI], 30.2 to not reached) with nivolumab plus chemotherapy and 20.8 months (95% CI, 14.0 to 26.7) with chemotherapy alone (hazard ratio for disease progression, disease recurrence, or death, 0.63; 97.38% CI, 0.43 to 0.91; P = 0.005). The percentage of patients with a pathological complete response was 24.0% (95% CI, 18.0 to 31.0) and 2.2% (95% CI, 0.6 to 5.6), respectively (odds ratio, 13.94; 99% CI, 3.49 to 55.75; P<0.001). Results for event-free survival and pathological complete response across most subgroups favored nivolumab plus chemotherapy over chemotherapy alone. At the first prespecified interim analysis, the hazard ratio for death was 0.57 (99.67% CI, 0.30 to 1.07) and did not meet the criterion for significance. Of the patients who underwent randomization, 83.2% of those in the nivolumab-plus-chemotherapy group and 75.4% of those in the chemotherapy-alone group underwent surgery. Grade 3 or 4 treatment-related adverse events occurred in 33.5% of the patients in the nivolumab-plus-chemotherapy group and in 36.9% of those in the chemotherapy-alone group.ConclusionsIn patients with resectable NSCLC, neoadjuvant nivolumab plus chemotherapy resulted in significantly longer event-free survival and a higher percentage of patients with a pathological complete response than chemotherapy alone. The addition of nivolumab to neoadjuvant chemotherapy did not increase the incidence of adverse events or impede the feasibility of surgery. (Funded by Bristol Myers Squibb; CheckMate 816 ClinicalTrials.gov number, NCT02998528.).

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What is the role of neoadjuvant chemotherapy, radiation, and adjuvant treatment in resectable esophageal cancer?

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What is the role of neoadjuvant chemotherapy, radiation, and adjuvant treatment in resectable esophageal cancer?

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