What's new in thoracic oncology.

Many changes have occurred in the field of thoracic surgery over the last several years. In this review, we will discuss new diagnostic techniques for lung cancer, innovations in surgery, and major updates on latest treatment options including immunotherapy. All these have significantly started to change our approach toward the management of lung cancer and have great potential to improve the lives of our patients afflicted with this disease.

Validation of the Pictorial Fit-Frail Scale in a Thoracic Surgery Clinic.

OBJECTIVE: Examine feasibility and construct validity of Pictorial Fit-Frail scale (PFFS) for the first time in older surgical patients. BACKGROUND: The PFFS uses visual images to measure health state in 14 domains and has been previously validated in outpatient geriatric clinics. METHODS: Patients ≥65 year-old who were evaluated in a multidisciplinary thoracic surgery clinic from November 2020 to May 2021 were prospectively included. Patients completed an in-person PFFS and Vulnerable Elders Survey (VES-13) during their visit, and a frailty index was calculated from the PFFS (PFFStrans). A geriatrician performed a comprehensive geriatric assessment (CGA) either in-person or virtually, from which a Frailty Index (FI-CGA) and Frailty Questionnaire (FRAIL) scale were obtained. To assess the validity of the PFFS in this population, the Spearman rank correlations (r spearman ) between PFFS trans and VES-13, FI-CGA, FRAIL were calculated. RESULTS: All 49 patients invited to participate agreed, of which 46/49 (94%) completed the PFFS so a score could be calculated. The majority of patients (59%) underwent an in-person CGA and the reminder (41%) a virtual CGA. The cohort was mainly female (59.0%), with a median age of 77 (range: 67-90). The median PFFS trans was 0.27 (interquartile range [IQR] 0.12-0.34), PFFS was 11 (IQR 5-14), and 0.24 (IQR 0.13-0.32) for FI-CGA. We observed a strong correlation between the PFFS trans and FI-CGA (r spearman = 0.81, P < 0.001) and a moderate correlation between PFFS trans and VES-13 and FRAIL score (r spearman = 0.68 and 0.64 respectively, P < 0.001). CONCLUSIONS: PFFS had good feasibility and construct validity among older surgical patients when compared to previously validated frailty measurements.

Smoking Cessation, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology.

Although the harmful effects of smoking after a cancer diagnosis have been clearly demonstrated, many patients continue to smoke cigarettes during treatment and beyond. The NCCN Guidelines for Smoking Cessation emphasize the importance of smoking cessation in all patients with cancer and seek to establish evidence-based recommendations tailored to the unique needs and concerns of patients with cancer. The recommendations contained herein describe interventions for cessation of all combustible tobacco products (eg, cigarettes, cigars, hookah), including smokeless tobacco products. However, recommendations are based on studies of cigarette smoking. The NCCN Smoking Cessation Panel recommends that treatment plans for all patients with cancer who smoke include the following 3 tenets that should be done concurrently: (1) evidence-based motivational strategies and behavior therapy (counseling), which can be brief; (2) evidence-based pharmacotherapy; and (3) close follow-up with retreatment as needed.

Lymph node sampling-what are the numbers?

Lung cancer is a deadly disease. Lymph node staging is the most important prognostic factor, and lymphatic drainage of the lung is complex. Major advances have been made in this field over the last several decades, but there is much left to understand and improve upon. Herein, we review the history of the lymphatic system and the creation of lymph node maps, the evolution of tumor, node, and metastasis lung cancer classification, the importance of lung cancer staging, techniques for lymph node dissection, and our recommendations regarding a minimum number of nodes to sample during pulmonary resection.

The evolving landscape of thoracic surgical oncology.

The history of Thoracic Surgical Oncology warrants attribution to the strong foundational contributions of the past. Current surgical approaches and techniques along with newer systemic therapies are the product of iterative modifications to prior successes. Progress also fosters traditional thinking to be challenged and other classic topics to be revisited with a contemporary perspective. Cumulatively, past and present clinical and scientific efforts point toward a promising future in the evolving landscape of Thoracic Surgical Oncology.

Contemporary issues in the surgical management of pleural mesothelioma.

The surgical management of pleural mesothelioma (PM) can be divided into diagnostic, staging, palliation, and cytoreductive surgery. In the cytoreductive surgical setting, the combination of different treatment modalities has led to better outcomes than surgery alone. The scarcity of high-quality studies has led to heterogeneity in management of PM across the mesothelioma treatment centers. Here, we review the literature regarding the most important open questions and ongoing clinical trials.

Hyperthermic intraoperative chemotherapy (HIOC) for Stage IVa thymic malignancy may improve 5-year disease-free survival.

BACKGROUND AND OBJECTIVES: Stage IVa thymic malignancy has limited treatments. This study evaluated whether hyperthermic intraoperative chemotherapy (HIOC) after radical resection of Stage IVa thymic malignancy improves survival. METHODS: All patients who underwent resection, with or without HIOC, for Stage IVa thymic malignancy at a single center from 1990 to 2021 were reviewed. RESULTS: Thirty-four patients were identified; 22 surgery-only versus 12 surgery and HIOC (60 min cisplatin regimen 175 mg/m2 ). Demographics and comorbidities were similar between groups. Three patients in each group were carcinomas; remainder were thymomas. Thirty-two patients underwent attempted macroscopic complete resection; 22 operations succeeded, 68.8%. Significant complications were similar between groups, 18.2% surgery-only versus 25.0% HIOC, p = 0.68. Median time to recurrence trended longer for HIOC patients (42.9 vs. 32.9 months in surgery-only, p = 0.77). Overall survival, 5-year, was similar (75.8% HIOC vs. 76.2% surgery-only, p = 0.91). On stratified analysis, thymoma patients with macroscopic complete resection and HIOC experienced similar 5-year Overall (80.0% vs. 100.0% surgery-only, p = 0.157) but longer trending 5-year disease-free (85.7% vs. 40.0%, p = 0.18) and 5-year locoregional recurrence-free survival (85.7% vs. 68.6%, p = 0.75). CONCLUSIONS: This retrospective cohort study treating Stage IVa thymic malignancy with radical pleurectomy, with or without HIOC, found addition of HIOC-signaled delayed recurrence and improved disease-free survival.

Pleurectomy Decortication in the Treatment of Malignant Pleural Mesothelioma: Encouraging Results and Novel Prognostic Implications Based on Experience in 355 Consecutive Patients.

OBJECTIVE: We report a series of 355 consecutive patients treated over 9 years in a single institution with intended PDC. BACKGROUND: Surgery for MPM has shifted from extra-pleural pneumonectomy to PDC with the goal of MCR. METHODS: Clinical and outcome data were reviewed. Kaplan-Meier estimators and log rank test were used to compare the overall survival, and logistic regression models were used. RESULTS: MCR was achieved in 304. There were 223 males, median age was 69 and histology was epithelioid in 184. The 30 and 90-day mortality were 3.0% and 4.6%.Most complications were low grade. Prolonged air leak in 141, deep venous thrombosis in 64, Atrial fibrillation in 42, chylothorax in 24, Empyema in 23, pneumonia in 21, Hemothorax in 12 and pulmonary embolus in 8. Median/5-year survival were 20.7 months/17.9% in the intent-to-treat cohort and 23.2months/21.2% in the MCR group. The survivals were best for patients with Tlstage and epithelioid histology (69.8months/54.1%). In a multivariable analysis, factors that were found to be associated with longer patient overall survival included epithelioid histology, T stage, quantitative clinical stage/tumor volume staging, adjuvant chemotherapy, intraoperative heated chemo, female sex, and length of stay shorter than 14 days. CONCLUSIONS: PDC is feasible with low mortality and is associated with manageable complication rates. 5-year survival of patients undergoing PDC with MCR in multi-modality setting is approaching 25% depending on quantitative and clinical stage, sex and histological subtype and is better than PDC without- MCR.

Pre-COVID-19 National Mortality Trends in Open and Video-Assisted Lobectomy for Non-Small Cell Lung Cancer.

INTRODUCTION: In the current era of episode-based hospital reimbursements, it is important to determine the impact of hospital size on contemporary national trends in surgical technique and outcomes of lobectomy. METHODS: Patients aged >18 y undergoing open and video-assisted thoracoscopic surgery (VATS) lobectomy from 2008 to 2014 were identified using insurance claims data from the National Inpatient Sample. The impact of hospital size on surgical approach and outcomes for both open and VATS lobectomy were analyzed. RESULTS: Over the 7-y period, 202,668 lobectomies were performed nationally, including 71,638 VATS and 131,030 open. Although the overall number of lobectomies decreased (30,058 in 2008 versus 27,340 in 2014, P < 0.01), the proportion of VATS lobectomies increased (24.0% versus 46.9%), and open lobectomies decreased (76.0% versus 53.0%, all P < 0.01). When stratified by hospital size, small hospitals had a significant increase in the proportion of open lobectomies (6.4%-12.2%; P = 0.01) and trend toward increased number of VATS lobectomies (2.7%-12.2%). Annual mortality rates for VATS (range: 1.0%-1.9%) and open (range: 1.9%-2.4%) lobectomy did not significantly differ over time (all P > 0.05) but did decrease among small hospitals (4.1%-1.3% and 5.1%-1.1% for VATS and open, respectively; both P < 0.05). After adjusting for confounders, hospital bed size was not a predictor of in-hospital mortality. CONCLUSIONS: Utilization of VATS lobectomies has increased over time, more so among small hospitals. Mortality rates for open lobectomy remain consistently higher than VATS lobectomy (range 0.4%-1.4%) but did not significantly differ over time. This data can help benchmark hospital performance in the future.

Salvage surgery for local recurrence after sublobar surgery in Stages I and II non-small cell lung cancer.

BACKGROUND AND OBJECTIVES: To examine if patients undergoing salvage surgery for local recurrence following sublobar resection (SLR) have similar perioperative complications and overall survival (OS) compared to lobectomy patients for early stage non-small cell lung cancer (NSCLC). METHODS: Patients undergoing lobectomy and SLR (segmentectomy or wedge resection) for Stages I and II NSCLC from 2010 to 2016 were reviewed. Lobectomy patients and those who underwent salvage surgery for local recurrence after SLR were compared. Salvage surgeries were curative-intent resections for recurrence. RESULTS: Cases included 634 lobectomies and 986 SLR. Fifty-nine SLR patients (6.0%) recurred at a local site compared to 11 lobectomy patients (1.7%; p < 0.001). Twenty-three locally recurrent SLR patients (39.0%) went on to salvage surgery. Peri-operative complications after salvage surgeries were similar to lobectomies (34.8% 8/23 vs. 34.7% 220/634, p = 1.00). OS at 5 years for salvage surgery patients was similar to lobectomy patients (79.6% 13/23 vs. 70.6% 227/634, p = 0.23). OS for patients who underwent salvage surgery was significantly better than those who did not have salvage surgery for recurrence (79.6% vs. 53.0%, p = 0.02). CONCLUSIONS: Patients who undergo salvage surgery for local recurrence after SLR had similar perioperative complications and OS compared to lobectomy patients but less than half underwent salvage surgery.

Thoracic surgery with geriatric assessment and collaboration can prepare frail older adults for lung cancer surgery.

BACKGROUND AND OBJECTIVES: We assessed frailty, measured by a comprehensive geriatric assessment-based frailty index (FI-CGA), and its association with postoperative outcomes among older thoracic surgical patients. METHODS: Patients aged ≥65 years evaluated in the geriatric-thoracic clinic between June 2016 through May 2020 who underwent lung surgery were included. Frailty was defined as FI-CGA > 0.2, and "occult frailty", a level not often recognized by surgical teams, as 0.2 < FI-CGA < 0.4. A qualitative analysis of geriatric interventions was performed. RESULTS: Seventy-three patients were included, of which 45 (62%) were nonfrail and 28 (38%) were frail. "Occult frailty" was present in 23/28 (82%). Sixty-one (84%) had lung malignancy. Geriatric interventions included delirium management, geriatric-specific pain and bowel regimens, and frailty optimization. More sublobar resections versus lobectomies (61% vs. 25%) were performed among frail patients. Frailty was not significantly associated with overall complications (odds ratio [OR]: 2.4; 95% confidence interval [CI]: 0.88-6.44; p = 0.087), major complications (OR: 2.33; 95% CI: 0.48-12.69; p = 0.293), discharge disposition (OR: 2.8; 95% CI: 0.71-11.95; p = 0.141), or longer hospital stay (1.3 more days; p = 0.18). CONCLUSION: Frailty and "occult frailty" are prevalent in patients undergoing lung surgery. However, with integrated geriatric management, these patients can safely undergo surgery.

Geographic differences in therapy for stage I non-small-cell lung cancer in older adults.

BACKGROUND: Geographic and socioeconomic factors impact patient treatment choices for certain cancers. Whether they impact treatment in older adults with lung cancer is unknown. We investigated geographic differences in treatment for stage I non-small-cell lung cancer (NSCLC) in older adults in the United States. METHODS: Using the Surveillance, Epidemiology and End Results Database 18th submission, a cohort of stage I NSCLC patients ≥60-years-old was created. Treatment differences (surgery or radiation alone) by geographic location and socioeconomic factors were analyzed. RESULTS: Forty-three thousand three hundred and eighty-seven stage I NSCLC patients were analyzed. Demographics and socioeconomic factors varied across all 13 states (p < 0.001). Surgery was the most common treatment in all states (range 58.6% in AK to 86.5% in CT) (all p < 0.001). Our multivariable analysis found older individuals had higher odds of getting radiation as compared to surgery (odds ratio [OR]: 1.22 for 65-69 years-old to OR: 8.95 for 85+ years-old; p < 0.001). Multiple states (LA, HI, IA, MI, WA, NM) were associated with increased odds of radiation use (vs. surgery alone) (all p < 0.05). People with lower education level (OR: 0.98) and median income (OR: 0.99) and non-Black race (OR: 0.52 for "other" to OR: 0.68 for "White" race with respect to Black race) were associated with lower odds of radiation (p < 0.05). CONCLUSIONS: Our study identified treatment differences for stage I NSCLC patients in the United States related to demographics, socioeconomic factors, and geographic location.

Risk of chyle leak after robotic versus video-assisted thoracoscopic esophagectomy.

BACKGROUND: We investigate the incidence and risk factors for post-operative outcomes including chyle leak following minimally invasive esophagectomy (MIE). METHODS: Patients undergoing MIE from May 2016 until August 2020 were prospectively followed. Outcomes of robotic and video-assisted thoracoscopic surgery (VATS) esophagectomy were analyzed. RESULTS: 347 esophagectomies were performed: 70 cases were done robotically by 2 surgeons and 277 by VATS by 14 surgeons. Patients had similar demographics, surgical technique, length of stay (LOS), and re-operation rates. Overall complication rates between robotic and VATS MIE were statistically similar (61% vs. 50%; p = 0.082). The majority of complications for either VATS (41.5%) or robotic-assisted minimally invasive esophagectomy (RAMIE) (51.4%) were grade II. Nineteen patients developed a chyle leak. Patients with a chyle leak were similar in age, gender, and hospital LOS (all p > 0.05), but were more likely to undergo a three-hole or robotic esophagectomy (both p < 0.05) as well as have higher rehabilitation requirements on discharge (26% vs. 10%; p = 0.05). Among the two surgeons who each performed > 20 robotic esophagectomies (n = 70), nine chyle leaks occurred. Rates varied by surgeon (7 vs. 2; p = 0.003). Lower leak rates occurred in the surgeon with more robotic esophagectomy experience (n = 47 vs. 23). Patients were similar in age, and gender (p > 0.05), but those with a chyle leak were more likely to undergo three-hole esophagectomies, prophylactic thoracic duction ligations, undergo the abdominal portion via laparotomy, and not have a prophylactic omental flap (all p < 0.05). CONCLUSION: Robotic and VATS esophagectomy have similar rates of re-operation, length of stay, discharge needs and complications. Differences in outcomes between VATS and Robotic esophagectomy appears to be related to surgeon experience with the robot but may also be associated with techniques such as anastomotic height, omental flap utilization and performance of laparoscopy.

Preserving NLST mortality benefits and acceptable morbidity for lung cancer surgery in a community hospital.

BACKGROUND AND OBJECTIVES: The aim of this study was to demonstrate whether academic thoracic surgeons could achieve morbidity and mortality rates in community hospitals equivalent to those seen in National Lung Screening Trial (NLST). METHODS: This was a retrospective review of community hospital lung cancer procedures for clinical Stage I-III non-small-cell lung cancers from 2007 through 2014. Variables include age, comorbidities, computed tomography (CT) characterization, and operative techniques. RESULTS: There were 177 patients who had lung cancers removed by a minimally invasive approach (79%), including lobectomy in 127 (72%), segmentectomy in 4 (2%), and wedge-resections in 46 (26%). The median patient age was 71 years (interquartile range [IQR], 63-76). The cohort was primarily female (58%), clinical Stage I (82%), with a median tumor size of 2.3 cm (IQR, 1.5-3.3). The median length of stay was 6 days (range: 1-35). Complications were experienced by 78 (44.1%) patients, most commonly atrial fibrillation in 20 (11.3%) followed by air-leak in 19 (10.7%). There were no in-hospital deaths. Tumor location and extent of resection were associated with complications, while larger tumor size, margin contour, and resection method were associated with air-leak (all p < 0.05). Higher clinical stage and larger tumor size were associated with occult Stage III disease (both p < 0.05). CONCLUSIONS: The low morbidity and mortality rates from the NLST were achievable in a community setting for early-stage lung cancer. Characterization of cancers using CT imaging identified factors most commonly associated with postoperative complications and the presence of occult Stage III disease.

Adjuvant therapy following induction therapy and surgery improves survival in N2-positive non-small cell lung cancer.

BACKGROUND: The purpose of this study was to evaluate treatment strategies and factors influencing overall survival (OS) and disease-free survival (DFS) in resectable, non-small cell lung cancer (NSCLC) with mediastinal (N2) lymph node metastasis. METHODS: All patients undergoing surgery for NSCLC with N2 disease between 2006 and 2016 were included. Treatment approaches included surgery only, neoadjuvant therapy followed by surgery, surgery followed by adjuvant therapy, and neoadjuvant therapy followed by surgery and adjuvant therapy (triple therapy). Patient clinical and pathologic data were retrospectively collected. RESULTS: A total of 281 patients were included in the study. In total, 209 patients had neoadjuvant therapy, 47.4% of which went on to received additional adjuvant therapy. The pathologic complete response rate was 12.9%. The treatment strategy which included triple therapy was isolated as a significant contributor to improved OS and DFS. Nodal downstaging (N0) after induction therapy conferred an OS benefit (38.3% vs. 15.6%, p = .03). Patients with single-station N2 disease experienced higher DFS. Video-assisted thoracic surgery (VATS) lobectomy completion rates were higher at the end of the study period compared to the beginning (p < .001). CONCLUSIONS: Patients who undergo neoadjuvant therapy for N2-positive NSCLC may benefit from additional adjuvant therapy. Single-station N2 disease confers higher DFS. VATS completion rates for lobectomy increase as experience increases.

Outcomes of superior segmentectomy versus lower lobectomy for superior segment Stage I non-small-cell lung cancer are equivalent: An analysis of 196 patients at a single, high volume institution.

OBJECTIVES: To determine if superior segmentectomy has equivalent overall (OS), disease-free (DFS), and locoregional-recurrence-free survival (LRFS) to lower lobectomy for early-stage non-small-cell lung cancer (NSCLC) in the superior segment. METHODS: We retrospectively reviewed all Stage 1 lower lobectomies for superior segment lesions and superior segmentectomies at our hospital from 2000 to 2018. Comparison statistics and Cox hazard modeling were performed to determine differences between groups and attempt to identify risk factors for OS, DFS, and LRFS. RESULTS: Superior segmentectomy patients, compared with lower lobectomy patients, had more current smokers, worse forced expiratory volume in 1 s percentage, radiologic emphysema scores, clinically and pathologically smaller tumors, and more occurrences of 0 lymph nodes examined. Outcomes for superior segmentectomy compared with lower lobectomy were equivalent for 5-year OS (67.0% vs. 75.1%, p = 0.70), DFS (56.9% vs. 60.4%, p = 0.59), and LRFS (87.9% vs. 91.3%, p = 0.46). Multivariable Cox modeling lacked utility due to no outcome differences. CONCLUSIONS: In well-selected patients, superior segmentectomies can have equivalent OS, DFS, and LRFS compared with lower lobectomies of superior segment tumors for early stage lung cancer. Further data are needed to provide better risk estimates.

Computed Tomography Scanning for Early Detection of Lung Cancer.

Parallel and often unrelated developments in health care and technology have all been necessary to bring about early detection of lung cancer and the opportunity to decrease mortality from lung cancer through early detection of the disease by computed tomography. Lung cancer screening programs provide education for patients and clinicians, support smoking cessation as primary prevention for lung cancer, and facilitate health care for tobacco-associated diseases, including cardiovascular and chronic lung diseases. Guidelines for lung cancer screening will need to continue to evolve as additional risk factors and screening tests are developed. Data collection from lung cancer screening programs is vital to the further development of fiscally responsible guidelines to increase detection of lung cancer, which may include small groups with elevated risk for reasons other than tobacco exposure.

Image-guided video-assisted thoracoscopic resection (iVATS): Translation to clinical practice-real-world experience.

OBJECTIVE: We developed a novel approach for localization and resection of lung nodules, using image-guided video-assisted thoracoscopic surgery (iVATS). We report our experience of translating iVATS into clinical care. METHODS: Methodology and workflow for iVATS developed as part of the Phase I/II trial were used to train surgeons, radiologists, anesthesiologists, and radiology technologists. Radiation dose, time from induction to incision, placement of T-bar to incision and incision to closure, hospital stay, and complication rates were recorded. RESULTS: Fifty patients underwent iVATS for resection of 54 nodules in a clinical hybrid operating room (OR) by six surgeons. Fifty-two (97%) nodules were successfully resected. Forty-two (84%) patients underwent wedge resection, four (7%) lobectomies, and two (4%) segmentectomy all with lymph node dissection. Median time from induction to incision was 89 minutes (range: 13-256 minutes); T-bar placement was 14 minutes (10-29 minutes); and incision to closure, 107 minutes (41-302 minutes). Average and total procedure radiation dose were: median = 6 mSieverts (range: 2.9-35 mSieverts). No deaths were reported and median length of stay was 3 days (range: 1-12 days). CONCLUSIONS: Translation of iVATS into clinical practice has been initiated using a safe step-wise process, combining intraoperative C-arm computed tomography scanning and thoracoscopic surgery in a hybrid OR.

Risk factors for delirium after esophagectomy.

INTRODUCTION: Postoperative delirium is a common complication after major surgical procedures and affects outcomes and long-term survival. We identified factors associated with postoperative delirium in patients undergoing esophagectomy. METHODS: Retrospective cohort analysis of 378 patients undergoing esophagectomy. We examined the association between postoperative delirium (DSM-V) criteria with respect to baseline variables and postoperative complications. RESULTS: Postoperative delirium was diagnosed in 64 (16.93%) patients and associated with increasing age (P < .05), chronic obstructive pulmonary disease (P = .07), pneumonia (P = .01), transfusion intraoperatively or within 72 hours of surgery (P < .001), and sepsis (P = .001). Unplanned intubation and increased length of stay (median, 14 days) were significant in patients with delirium (P = .001 and P < .001, respectively). In a secondary analysis, surgical technique and operative approach were associated with delirium. Modified McKeown (three-hole) esophagectomy was twice more likely to develop delirium compared with Ivor Lewis (odds ratio [OR], 2.09; 95% confidence interval [CI], 1.03-4.23). The strongest association was found between delirium and open techniques (thoracotomy and laparotomy) as compared with minimally invasive techniques (thoracoscopy and laparoscopy) (OR, 2.66; 95% CI, 1.22-5.76). Survival was similar between both groups. CONCLUSIONS: Postoperative delirium is common and associated with complications following esophagectomy. Identification of predisposing factors such as age and pre-existing pulmonary diseases and proper selection of surgical treatment may reduce delirium and improve surgical outcomes.

Neoadjuvant irinotecan, cisplatin, and concurrent radiation therapy with celecoxib for patients with locally advanced esophageal cancer.

BACKGROUND: Patients with locally advanced esophageal cancer who are treated with trimodality therapy have a high recurrence rate. Preclinical evidence suggests that inhibition of cyclooxygenase 2 (COX2) increases the effectiveness of chemoradiation, and observational studies in humans suggest that COX-2 inhibition may reduce esophageal cancer risk. This trial tested the safety and efficacy of combining a COX2 inhibitor, celecoxib, with neoadjuvant irinotecan/cisplatin chemoradiation. METHODS: This single arm phase 2 trial combined irinotecan, cisplatin, and celecoxib with concurrent radiation therapy. Patients with stage IIA-IVA esophageal cancer received weekly cisplatin 30 mg/m(2) plus irinotecan 65 mg/m(2) on weeks 1, 2, 4, and 5 concurrently with 5040 cGy of radiation therapy. Celecoxib 400 mg was taken orally twice daily during chemoradiation, up to 1 week before surgery, and for 6 months following surgery. RESULTS: Forty patients were enrolled with stage IIa (30 %), stage IIb (20 %), stage III (22.5 %), and stage IVA (27.5 %) esophageal or gastroesophageal junction cancer (AJCC, 5th Edition). During chemoradiation, grade 3-4 treatment-related toxicity included dysphagia (20 %), anorexia (17.5 %), dehydration (17.5 %), nausea (15 %), neutropenia (12.5 %), diarrhea (10 %), fatigue (7.5 %), and febrile neutropenia (7.5 %). The pathological complete response rate was 32.5 %. The median progression free survival was 15.7 months and the median overall survival was 34.7 months. 15 % (n = 6) of patients treated on this study developed brain metastases. CONCLUSIONS: The addition of celecoxib to neoadjuvant cisplatin-irinotecan chemoradiation was tolerable; however, overall survival appeared comparable to prior studies using neoadjuvant cisplatin-irinotecan chemoradiation alone. Further studies adding celecoxib to neoadjuvant chemoradiation in esophageal cancer are not warranted. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00137852 , registered August 29, 2005.