Adherence Rate to Alliance for Clinical Trials in Oncology Z0011 Trial Based on Breast Cancer Subtype.

BACKGROUND: The American College of Surgeons Oncology Group Z0011 (ACOSOG Z0011 or Z11) trial demonstrated no survival advantage with completion axillary lymph node dissection (ALND) for patients with T1-2 breast cancer, 1 to 2 positive SLNs who received adjuvant chemoradiation therapy. More than 70% of the cohort had estrogen receptor (ER)+ tumors. There is paucity of data on the adherence rate to Z11, as well as a dearth of data on the applicability of Z11 for the different subtypes. We conducted a large hospital-based study to evaluate the adherence rate to Z11 based on subtypes. STUDY DESIGN: The National Cancer Database was queried to evaluate 33,859 patients diagnosed with T1-2, N1, and M0 breast cancer treated with lumpectomy with negative margins, and adjuvant chemoradiation therapy between 2012 and 2018. Patients were classified into 3 groups: (1) ER+/HER2-, (2) ER-/HER2-, and (3) HER2+ regardless of ER status. The revised Scope of the Regional Lymph Node Surgery 2012 was used to classify patients into those who underwent an SLN or ALND. Differences in use of ALND by subtypes were compared. The Kaplan-Meier method and log-rank test were used to compare overall survival (OS). A p value of <0.05 was considered statistically significant. RESULTS: For ER+/human epidermal growth factor receptor 2 (HER2)-, ER-/HER2-, and HER2+ tumors, the rate of ALND was 43.6%, 50.2%, and 47.8%, respectively. The 5-year OS for SLN and ALND for the entire cohort was 94.0% and 93.1% (p = 0.0004); for ER+/HER2-, it was 95.4% and 94.7% (p = 0.04); for ER-/HER2-, it was 84.1% and 84.3% (p = 0.41); for HER2+, it was 94.2% and 93.2% (p = 0.20). Multivariable cox proportional hazard regression analysis demonstrated no significant survival differences between SLN and ALND (p = 0.776). CONCLUSIONS: Z11 is applicable for women with early N1 disease, regardless of subtypes. ALND did not confer a survival advantage over SLN. Despite this, up to 50% of patients who fit Z11 criteria continue to undergo ALND.

Timing After Neoadjuvant Therapy Predicts Mortality in Patients Undergoing Esophagectomy: a Propensity Score-Matched Analysis.

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.

Comparative outcomes of transthoracic versus transhiatal esophagectomy.

BACKGROUND: Surgical resection has become a mainstay of therapy for locally advanced esophageal cancer and can increase survival significantly. With the advancement of minimally invasive surgery, there is still debate on the best approach for esophagectomy. We report a modern analysis of outcomes with transthoracic versus transhiatal esophagectomy. METHODS: A prospectively managed esophagectomy database was queried for patients undergoing transthoracic or transhiatal esophagectomy between 1996 and 2016. Continuous variables were compared using the Kruskal-Wallis or the analysis of variance tests as appropriate. Pearson χ2 test was used to compare categorical variables. All statistical tests were 2-sided and an α (type I) error < .05 was considered statistically significant. RESULTS: A total of 846 patients underwent esophagectomy with a median age of 66 (28-86) years. There was no difference in estimated blood loss for transthoracic and transhiatal, but mean operating room times were longer for transthoracic versus transhiatal (P < .001), and the number of retrieved lymph nodes was higher for transthoracic versus transhiatal (P < .002). Postoperative complications occurred in 207 (29%) transthoracic patients vs 59 (44.7%) transhiatal patients, (P < .001). The most common complications in transthoracic versus transhiatal techniques, respectively, were anastomotic leaks: 4.3% vs 9.8%; (P = .01), anastomotic stricture 7% vs 26.5%; (P < .001), and pneumonia 12.6% vs 22.7%; (P < .002). Median survival significantly improved in patients undergoing transthoracic (62 months) vs transhiatal (39 months) P = .03. CONCLUSION: We found that a transthoracic approach was associated with lower pneumonias, anastomotic leaks, wound infections, and strictures, with an improvement in nodal harvest. Survival was also significantly improved in patients who underwent transthoracic esophagectomy.

Multi-agent neoadjuvant chemotherapy improves response and survival in patients with resectable pancreatic cancer.

BACKGROUND: We sought to examine the impact of neoadjuvant chemotherapy (NCT), single agent (SA) or multi-agent (MA) chemotherapy, and chemoradiation (NCRT) on response and survival in pancreatic cancer. METHODS: Utilizing the National Cancer Database, we identified patients who underwent resection of the pancreatic head for adenocarcinoma [2006-2013]. Overall survival (OS) analysis was performed using the Kaplan-Meier method. Multivariable cox proportional hazard models (MVA) and propensity score matching (PSM) were developed to identify predictors of survival. For upfront surgery (UFS), OS was limited to receipt of adjuvant treatment. RESULTS: We identified 26,563 patients who underwent pancreatic head resection: UFS =23,877, NCRT =1,482, and NCT =1,204. MA-NCT was utilized in 77% and after PSM, 52%. There was improved R0 resections and 30-day mortality associated with neoadjuvant therapy compared to UFS. Overall response rate to neoadjuvant therapy was 24%. The highest response rate seen with MA-NCRT. Response rates for SA-NCT, MA-NCT, SA-NCRT, and MA-NCRT were 11.5%, 18.1%, 27.5%, and 33.1% (P=0.01). However, OS was improved with neoadjuvant therapy regardless of response compared to UFS (P=0.03). After PSM, the median OS for UFS, SA-NCT, MA-NCT, SA-NCRT, and MA-NCRT was 21.9, 21.5, 29.8, 25.3, and 25.8 months in all patients (P=0.001). MVA after PSM demonstrated that only MA-NCT was associated with decreased mortality while increasing age, higher Charlson-Deyo index, N1, higher grade, tumor size, and positive margins were associated with higher mortality. CONCLUSIONS: There was improved OS associated with MA-NCT in pancreatic cancer patients compared to UFS with adjuvant therapy. OS was improved regardless of response to therapy.

Comparative Perioperative Outcomes by Esophagectomy Surgical Technique.

INTRODUCTION: Surgical resection is vital in the curative management of patients with esophageal cancer. However, a myriad of surgical procedures exists based on surgeon preference and training. We report on the perioperative outcomes based on esophagectomy surgical technique. METHODS: A prospectively managed esophagectomy database was queried for patients undergoing esophagectomy from 1996 and 2016. Basic demographics, tumor characteristics, operative details, and post-operative outcomes were recorded and analyzed by comparison of transhiatal vs Ivor-lewis and minimally invasive (MIE) vs open procedures. RESULTS: We identified 856 patients who underwent esophagectomy. Neoadjuvant therapy was administered in 543 patients (63.4%). There were 504 (58.8%) open esophagectomies and 302 (35.2%) MIE. There were 13 (1.5%) mortalities and this did not differ among techniques (p = 0.6). While there was no difference in overall complications between MIE and open, complications occurred less frequently in patients undergoing RAIL and MIE IVL compared to other techniques (p = 0.003). Pulmonary complications also occurred less frequently in RAIL and MIE IVL (p < 0.001). Anastomotic leaks were less common in patients who underwent IVL compared to trans-hiatal approaches (p = 0.03). MIE patients were more likely to receive neoadjuvant therapy (p = 0.001), have lower blood loss (p < 0.001), have longer operations (p < 0.001), and higher lymph node harvests (p < 0.001) compared to open patients. CONCLUSION: Minimally invasive and robotic Ivor Lewis techniques demonstrated substantial benefits in post-operative complications. Oncologic outcomes similarly favor MIE IVL and RAIL.

Comparative outcomes of minimally invasive and robotic-assisted esophagectomy.

OBJECTIVE: Minimally invasive esophagectomy (MIE) has demonstrated superior outcomes compared to open approaches. The myriad of techniques has precluded the recommendation of a standard approach. The addition of robotics to esophageal resection has potential benefits. We sought to examine the outcomes with MIE to include robotics. METHODS: Utilizing a prospective esophagectomy database, we identified patients who underwent (MIE) Ivor Lewis via thoracoscopic/laparoscopic (TL), transhiatal (TH), or robotic-assisted Ivor Lewis (RAIL). Patient demographics, tumor characteristics, and complications were analyzed via ANOVA, χ2, and Fisher exact where appropriate. RESULTS: We identified 302 patients who underwent MIE: TL 95 (31.5%), TH 63 (20.8%), and RAIL 144 (47.7%) with a mean age of 65 ± 9.6. The length of operation was longer in the RAIL: TL (299 ± 87), TH (231 ± 65), RAIL (409 ± 104 min), p < 0.001. However, the EBL was lower in the patients undergoing transthoracic approaches (RAIL + TL): TL (189 ± 188 ml), TH (242 ± 380 ml), RAIL (155 ± 107 ml), p = 0.03. Conversion to open was also lower in these patients: TL 7 (7.4%), TH 8 (12.7%), RAIL 0, p < 0.001. The R0 resection rate and lymph node (LN) harvest also favored the RAIL cohort: TL 86 (93.5%), TH 60 (96.8%), and RAIL 144 (100%), p = 0.01; LN: TL 14 ± 7, TH 9 ± 6, and RAIL 20 ± 9, p < 0.001. The overall morbidity was lower in MIE patients that underwent a transthoracic approach vs. transhiatal: TL 29 (30.5%), TH 39 (61.9%), RAIL 34 (23.6%), p < 0.001. CONCLUSIONS: Patients undergoing MIE via thoracoscopic/laparoscopic and robotic transthoracic approaches demonstrated lower EBL, morbidity, and conversion to open compared to the transhiatal approach. Additionally the oncologic outcomes measured by R0 resections and LN harvest also favored the patients who underwent a transthoracic approach.