Walter J. Scott

Complete Response to Neoadjuvant Chemoradiotherapy in Esophageal Carcinoma Is Associated With Significantly Improved Survival

PURPOSE Attempts to improve survival of patients with esophageal cancer have been made using induction chemoradiotherapy (CRT) followed by surgery. A large single-center experience was reviewed to determine which treatment-related variables could predict survival and recurrence. PATIENTS AND METHODS All patients undergoing esophagectomy between January 1994 and December 2002 were reviewed. Univariate and multivariate analyses were performed using log-rank and Cox proportional hazards models, and survival curves were estimated using the Kaplan-Meier method. RESULTS Of 171 patients with invasive cancer, 131 (77%) underwent preoperative CRT. The average age was 60 years, and most patients were male (85%). Operations performed included Ivor-Lewis (60%), transhiatal (8%), three-hole (23%), or left thoracoabdominal (8%) esophagectomy. Perioperative mortality rate was 5%. Median overall survival (OS) of the entire group was 33 months, and the 5-year OS rate was 26%. Induction CRT was associated with a 33% 5-year survival rate compared with 11% for surgery alone (P = .43). Patients downstaged to pathologic stage 0 or I had an improved OS and disease-free survival (DFS) compared with those patients who were not downstaged (P = .022). Additionally, the ability to perform an R0 resection was a significant factor for OS and DFS (n = 130; P < .0001 and P <.0002, respectively). CONCLUSION Response to CRT and the ability to perform an R0 resection are associated with significantly improved survival in patients with esophageal carcinoma.

Optimum lymphadenectomy for esophageal cancer.

Objective:Using Worldwide Esophageal Cancer Collaboration data, we sought to (1) characterize the relationship between survival and extent of lymphadenectomy, and (2) from this, define optimum lymphadenectomy. Summary Background Data:What constitutes optimum lymphadenectomy to maximize survival is controversial because of variable goals, analytic methodology, and generalizability of the underpinning data. Methods:A total of 4627 patients who had esophagectomy alone for esophageal cancer were identified from the Worldwide Esophageal Cancer Collaboration database. Patient-specific risk-adjusted survival was estimated using random survival forests. Risk-adjusted 5-year survival was averaged for each number of lymph nodes resected and its relation to cancer characteristics explored. Optimum number of nodes that should be resected to maximize 5-year survival was determined by random forest multivariable regression. Results:For pN0M0 moderately and poorly differentiated cancers, and all node-positive (pN+) cancers, 5-year survival improved with increasing extent of lymphadenectomy. In pN0M0 cancers, no optimum lymphadenectomy was defined for pTis; optimum lymphadenectomy was 10 to 12 nodes for pT1, 15 to 22 for pT2, and 31 to 42 for pT3/T4, depending on histopathologic cell type. In pN+M0 cancers and 1 to 6 nodes positive, optimum lymphadenectomy was 10 for pT1, 15 for pT2, and 29 to 50 for pT3/T4. Conclusions:Greater extent of lymphadenectomy was associated with increased survival for all patients with esophageal cancer except at the extremes (TisN0M0 and ≥7 regional lymph nodes positive for cancer) and well-differentiated pN0M0 cancer. Maximum 5-year survival is modulated by T classification: resecting 10 nodes for pT1, 20 for pT2, and ≥30 for pT3/T4 is recommended.

Video-assisted thoracic surgery versus open lobectomy for lung cancer: a secondary analysis of data from the American College of Surgeons Oncology Group Z0030 randomized clinical trial.

OBJECTIVE Video-assisted thoracoscopic lobectomy remains controversial. We compared outcomes from participants in a randomized study comparing lymph node sampling versus dissection for early-stage lung cancer who underwent either video-assisted thoracoscopic or open lobectomy. METHODS Data from 964 participants in the American College of Surgeons Oncology Group Z0030 trial were used to construct propensity scores for video-assisted thoracoscopic versus open lobectomy (based on age, gender, histology, performance status, tumor location, and T1 vs T2). Propensity scores were used to estimate the adjusted risks of short-term outcomes of surgery. Patients were classified into 5 equal-sized groups and compared using conditional logistic regression or repeated measures analysis of variance. RESULTS A total of 752 patients (66 video-assisted and 686 open procedures) were analyzed on the basis of propensity score stratification. Median operative time was shorter for video-assisted thoracoscopic lobectomy (video-assisted thoracoscopy 117.5 minutes vs open 171.5 minutes; P < .001). Median total number of lymph nodes retrieved (dissection group only) was similar (video-assisted thoracoscopy 15 nodes vs open 19 nodes; P = .147), as were instances of R1/R2 resection (video-assisted thoracoscopy 0% vs open 2.3%; P = .368). Patients undergoing video-assisted thoracoscopic lobectomy had less atelectasis requiring bronchoscopy (0% vs 6.3%, P = .035), fewer chest tubes draining greater than 7 days (1.5% vs 10.8%; P = .029), and shorter median length of stay (5 days vs 7 days; P < .001). Operative mortality was similar (video-assisted thoracoscopy 0% vs open 1.6%, P = 1.0). CONCLUSION Patients undergoing video-assisted lobectomy had fewer respiratory complications and shorter length of stay. These data suggest video-assisted thoracoscopic lobectomy is safe in patients with resectable lung cancer. Longer follow-up is needed to determine the oncologic equivalency of video-assisted versus open lobectomy.

Patterns of survival and recurrence after surgical treatment of early stage non-small cell lung carcinoma in the ACOSOG Z0030 (ALLIANCE) trial.

OBJECTIVE Surgical resection has been the mainstay of curative treatment of early stage lung cancer in selected patients. We evaluated survival and patterns of recurrence after surgical resection for early stage lung cancer from the American College of Surgeons Oncology Group Z0030/Alliance trial. METHODS One thousand eighteen patients enrolled in the Z0030 trial were analyzed according to clinical T stage. Differences between groups were compared using the 2-sample rank test or χ(2) test. Log rank test and Cox proportional hazards regression were used to compare survival and recurrence. To compare patients who underwent open versus video-assisted thoracoscopic surgery (VATS) resections, propensity-score matched analysis was performed. Seven hundred fifty-two patients (66 undergoing VATS and 686 undergoing open surgery) were classified into 5 equal-sized propensity-score groups. Proportional hazards regression was used to compare these outcomes. RESULTS There were 578 patients with cT1 tumors and 440 patients with cT2 tumors. Median follow-up was 6.7 years. Median overall survival was 9.1 years (stage T1) and 6.5 years (stage T2). Overall survival at 5 years was 72% (stage T1) and 55% (stage T2). Local recurrence-free survival at 5 years was 95% (stage T1) and 91% (stage T2) (P = .015). Among patients with stage T1 cancer, 4.2% (23 out of 542) had local recurrences, whereas 7.3% (30 out of 409) of those with stage T2 tumors had local failure. There was no difference in the development of new primary tumors between stage T1 and stage T2 groups. In the propensity-score matched analysis of VATS versus open lobectomy patients, there was no difference in overall survival, disease-free survival, and freedom from development of a new primary tumor. CONCLUSIONS Results of patients with resected early stage non-small cell carcinoma from a large-scale, multicenter trial serve as benchmarks against which to compare nonsurgical therapies for early stage lung cancer. Propensity-score matched analysis shows no difference in survival between patients undergoing VATS and open lobectomy.

Comparing cancer patients who enroll in a smoking cessation program at a comprehensive cancer center with those who decline enrollment

Despite the availability of smoking interventions for cancer patients, many eligible patients decline enrollment into such programs. We examined reasons patients provide for declining smoking treatment and compared treatment decliners to enrollees.

Induction Cisplatin and Paclitaxel Followed by Combination Chemoradiotherapy with 5-Fluorouracil, Cisplatin, and Paclitaxel Before Resection in Localized Esophageal Cancer: A Phase II Report

BackgroundMultimodality therapy for esophageal cancer holds promise for improving outcome in this lethal disease. On the basis of encouraging data from a phase I trial, we conducted a phase II study of preoperative chemotherapy, followed by concurrent chemoradiotherapy and surgery.MethodsPatients with clinically staged resectable esophageal cancer were treated with induction cisplatin and paclitaxel, followed by 45 Gy of external beam radiation with concurrent infusional 5-fluorouracil and weekly cisplatin and paclitaxel. Four to eight weeks after multimodality induction, esophagectomy was performed in suitable patients. Study end points were survival, pathologic complete response, and toxicity.ResultsTwenty-one patients were enrolled with a median age of 58 years, and all patients were clinically staged II or III. Sixteen (76.2%) patients completed the trial, of whom four (25%) had a pathologic complete response. One patient died from postoperative complications. Grade 3 or 4 toxicity was observed in 76% of patients, and dose-limiting toxicity was seen in 6 of the first 14 patients, thus necessitating a planned dose reduction of paclitaxel. At a median follow-up of 30 months, 13 patients remain alive. The 2-year disease-specific survival for the study population was 78%.ConclusionsThis regimen of multimodality therapy before resection resulted in an encouraging 2-year survival rate but a disappointing rate of pathologic complete response and was toxic, necessitating a predetermined paclitaxel dose reduction. The incorporation of taxanes into induction strategies for esophageal cancer seems promising, but the optimal schedule remains undefined.

Symptomatic cardiac toxicity is predicted by dosimetric and patient factors rather than changes in 18F-FDG PET determination of myocardial activity after chemoradiotherapy for esophageal cancer☆

PURPOSE To determine factors associated with symptomatic cardiac toxicity in patients with esophageal cancer treated with chemoradiotherapy. MATERIAL AND METHODS We retrospectively evaluated 102 patients treated with chemoradiotherapy for locally advanced esophageal cancer. Our primary endpoint was symptomatic cardiac toxicity. Radiation dosimetry, patient demographic factors, and myocardial changes seen on (18)F-FDG PET were correlated with subsequent cardiac toxicity. Cardiac toxicity measured by RTOG and CTCAE v3.0 criteria was identified by chart review. RESULTS During the follow up period, 12 patients were identified with treatment related cardiac toxicity, 6 of which were symptomatic. The mean heart V20 (79.7% vs. 67.2%, p=0.05), V30 (75.8% vs. 61.9%, p=0.04), and V40 (69.2% vs. 53.8%, p=0.03) were significantly higher in patients with symptomatic cardiac toxicity than those without. We found the threshold for symptomatic cardiac toxicity to be a V20, V30 and V40 above 70%, 65% and 60%, respectively. There was no correlation between change myocardial SUV on PET and cardiac toxicity, however, a greater proportion of women suffered symptomatic cardiac toxicity compared to men (p=0.005). CONCLUSIONS A correlation did not exist between percent change in myocardial SUV and cardiac toxicity. Patients with symptomatic cardiac toxicity received significantly greater mean V20, 30 and 40 values to the heart compared to asymptomatic patients. These data need validation in a larger independent data set.

A comparison of perioperative outcomes of Video-Assisted Thoracic Surgical (VATS) Lobectomy with open thoracotomy and lobectomy: Results of an analysis using propensity score based weighting

BackgroundRandomized trials comparing VATS lobectomy to open lobectomy are of small size. We analyzed a case-control series using propensity score-weighting to adjust for important covariates in order to compare the clinical outcomes of the two techniques.MethodsWe compared patients undergoing lobectomy for clinical stage I lung cancer (NSCLC) by either VATS or open (THOR) methods. Inverse probability of treatment weighted estimators, with weights derived from propensity scores, were used to adjust cohorts for determinants of perioperative morbidity and mortality including age, gender, preop FEV1, ASA class, and Charlson Comorbidity Index (CCI). Bootstrap methods provided standard errors. Endpoints were postoperative stay (LOS), chest tube duration, complications, and lymph node retrieval.ResultsWe analyzed 136 consecutive lobectomy patients. Operative mortality was 1/62 (1.6%) for THOR and 1/74 (1.4%) for VATS, P = 1.00. 5/74 (6.7%) VATS were converted to open procedures. Adjusted median LOS was 7 days (THOR) versus 4 days (VATS), P < 0.0001, HR = 0.33. Adjusted median chest tube duration (days) was 5 (THOR) versus 3 (VATS), P < 0.0001, HR = 0.42. Complication rates were 39% (THOR) versus 34% (VATS), P = 0.61. Adjusted mean number of lymph nodes dissected per patient was 18.1 (THOR) versus 14.8 (VATS), p = 0.17.ConclusionsAfter balancing covariates that affect morbidity, mortality and LOS in this case-control series using propensity-weighting, the results confirm that VATS lobectomy is associated with a statistically significant shorter LOS, similar mortality and complication rates and similar rates of lymph node removal in patients with clinical stage I NSCLC.

Increased Time From Neoadjuvant Chemoradiation to Surgery Is Associated With Higher Pathologic Complete Response Rates in Esophageal Cancer

BACKGROUND The interval between neoadjuvant chemoradiation treatment and surgery has been described as an important predictor of pathologic response to therapy in nonesophageal cancer sites. We retrospectively reviewed our experience with patients who underwent neoadjuvant chemoradiation and esophagectomy to better understand the impact of the timing of surgery on pathologic complete response rates in esophageal cancer. METHODS Two hundred thirty-one sequentially treated patients from 2000 to 2011 were identified for this study; 88 of these patients completed neoadjuvant chemoradiation followed by esophagectomy at our institution. The interval between completion of chemoradiation and surgery was calculated for each patient. The patients were categorized into quartiles and also into 3-week interval groups. Treatment factors and surgical morbidity data, including the estimated blood loss and length of operative stay, were also assessed. RESULTS Quartiles for the neoadjuvant chemoradiation to surgery interval were less than 45 days, 46 to 50 days, 51 to 63 days, and 64+ days. Corresponding pathologic complete response rates were 12.5%, 20.0%, 22.7%, and 40.9% (p = 0.03). Results for 3-week intervals were similar (p = 0.02). There was no association between increasing time interval between the ending of neoadjuvant chemoradiation to surgery and length of stay longer than 2 weeks. CONCLUSIONS A longer interval between completion of neoadjuvant chemoradiation and surgery was associated with higher pathologic complete response rates without an impact on surgical morbidity.

Surgical treatment of metastatic disease to the lung.

The presence of distant metastases usually implies disease not amenable to cure through surgical resection. In such cases, chemotherapy is the mainstay of treatment, with surgery or radiation reserved for palliative measures. However, metastases limited to the lung may be resected with resultant prolonged patient survival compared to unresectable, widely disseminated metastases. Isolated pulmonary metastases should therefore not be considered untreatable. In this review, we discuss the pathophysiology of pulmonary metastases. We outline prognostic factors associated with metastases, and propose criteria to help select patients for metastasectomy. Surgical approaches, including various open techniques and video-assisted thoracoscopy, are covered. Surgical issues, including the need for unilateral versus bilateral exploration, the extent of resection to achieve cure, the need for lymph node dissection, and the benefit of repeat operations, are discussed. Finally, we review some of the more common tumors that metastasize to the lungs, and the role of metastasectomy in their treatment. Resection of pulmonary metastases confers a survival benefit to a select group of patients so long as the primary tumor is controlled, metastases are limited to the lungs, the patient can tolerate the operation from a cardiopulmonary standpoint, and the metastases are completely resected.