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Background: Metastatic adenocarcinomas of foregut origin are aggressive and have limited treatment options, poor quality of life, and a dismal prognosis. A subset of such patients with limited metastatic disease might have favorable outcomes with locoregional metastasis-directed therapies. This study investigates the role of sequential cytoreductive interventions in addition to the standard of care chemotherapy in patients with oligometastatic foregut adenocarcinoma., Methods: This is a single-center, phase II, open-label randomized clinical trial. Eligible patients include adults with synchronous or metachronous oligometastatic (metastasis limited to two sites and amenable for curative/ablative treatment) adenocarcinoma of the foregut without progression after induction chemotherapy and having undetectable ctDNA. These patients will undergo induction chemotherapy and will then be randomized (1:1) to either sequential curative intervention followed by maintenance chemotherapy versus routine continued chemotherapy. The primary endpoint is progression-free survival (PFS), and a total of 48 patients will be enrolled to detect an improvement in the median PFS in the intervention arm with a hazard ratio (HR) of 0.5 with 80% power and a one-sided alpha of 0.1. Secondary endpoints include disease-free survival (DFS) in the intervention arm, overall survival (OS), ctDNA conversion rate pre/post-induction chemotherapy, ctDNA PFS, PFS 2 , adverse events, quality of life, and financial toxicity., Discussion: This is the first randomized study that aims to prospectively evaluate the efficacy and safety of surgical/ablative interventions in patients with ctDNA-negative oligometastatic adenocarcinoma of foregut origin post-induction chemotherapy. The results from this study will likely develop pertinent, timely, and relevant knowledge in oncology., (© 2022. Society of Surgical Oncology.)

Background: The authors hypothesized that cytoreductive surgery (CRS, comprising gastrectomy combined with metastasectomy) in addition to systemic chemotherapy (SC) is associated with a better survival than chemotherapy alone for patients with metastatic gastric adenocarcinoma (MGA)., Methods: Patients with MGA who received SC between 2004 and 2016 were identified using the National Cancer Database (NCDB). Nearest-neighbor 1:1 propensity score-matching was used to create comparable groups. Overall survival (OS) was compared between subgroups using Kaplan-Meier analyses. Immortal bias analysis was performed among those who survived longer than 90 days., Results: The study identified 29,728 chemotherapy-treated patients, who were divided into the following four subgroups: no surgery (NS, n = 25,690), metastasectomy alone (n = 1170), gastrectomy alone (n = 2248), and CRS (n = 620) with median OS periods of 8.6, 10.9, 14.8, and 16.3 months, respectively (p < 0.001). Compared with the patients who underwent NS, the patients who had CRS were younger (58.9 ± 13.4 vs 62.0 ± 13.1 years), had a lower proportion of disease involving multiple sites (4.6% vs 19.1%), and were more likely to be clinically occult (cM0 stage: 59.2% vs 8.3%) (p < 0.001 for all). The median OS for the propensity-matched patients who underwent CRS (n = 615) was longer than for those with NS (16.4 vs 9.3 months; p < 0.001), including in those with clinical M1 stage (n = 210). In the Cox regression model using the matched data, the hazard ratio for CRS versus NS was 0.56 (95% confidence interval [CI], 0.49-0.63). In the immortal-matched cohort, the corresponding median OS was 17.0 versus 9.5 months (p < 0.001)., Conclusions: In addition to SC, CRS may be associated with an OS benefit for a selected group of MGA patients meriting further prospective investigation.

Background: The optimal surgical approach to the resection of gastoesophageal junction cancer is unknown. A comprehensive literature search was conducted to further compare the esophageal and gastric approaches to gastroesophageal junction cancer., Methods: A systematic review of the literature from January 1990 to May 2018 was performed to determine whether an esophageal or gastric surgical approach offers better perioperative and oncologic outcomes., Results: A total of 179 abstracts were identified and after excluding publications for non-English language, primary focus on neoadjuvant and/or adjuvant treatment, lack of comparison of surgical approaches or not addressing morbidity, mortality, or survival-related outcomes, a total of 14 nonrandomized, comparative studies were reviewed in detail., Conclusions: The proximal and distant extent of the tumor based on Siewert type classification greatly influences choice of operation. Overall survival rates and surgical outcomes are comparable, and surgical approach should be dictated by patient factors.

Background: The risk of surgery, particularly for older cancer patients with serious, extensive comorbidities, can make this otherwise curative modality precarious. Leveraging data from the American College of Surgeons Oncology Group, this study sought to characterize age-based comparative demographics, adverse event rates, and study completion rates to define how best to conduct research in older cancer patients., Methods: This study relied on clinical data from 21 completed studies to assess whether older patients experienced more grade 3 or worse adverse events and were more likely to discontinue study participation prematurely than their younger counterparts., Results: The study enrolled 12,367 patients. The median age was 60 years, and 36% of the patients were 65 years of age or older. Among 4008 patients with adverse event data, 1067 (27%) had experienced a grade 3 or worse event. The patients 65 years or older had higher rates of grade 3 or worse adverse events compared to younger patients [32% vs. 24%; odds ratio (OR), 1.5; 95% confidence interval (CI), 1.3-1.7; p < 0.0001]. This association was not observed in multivariate analyses. The study protocol was completed by 97% of the patients. No association was observed between age and trial completion (OR 0.8; 95% CI 0.7-1.1; p = 0.14). Only the older gastrointestinal cancer trial patients were less likely to complete their studies compared to younger patients (OR 0.50; 95% CI 0.30-0.70; p < 0.0001)., Conclusion: Despite higher rates of adverse events, the older patients typically completed the study protocol, thereby contributing relevant data on how best to render care to older cancer patients and affirming the important role of enrolling these patients to surgical trials.

Background: There is considerable interest in a neoadjuvant approach for resectable pancreatic ductal adenocarcinoma (PDAC). This study evaluated perioperative gemcitabine + erlotinib (G+E) for resectable PDAC., Methods: A multicenter, cooperative group, single-arm, phase II trial was conducted between April 2009 and November 2013 (ACOSOG Z5041). Patients with biopsy-confirmed PDAC in the pancreatic head without evidence of involvement of major mesenteric vessels (resectable) were eligible. Patients (n = 123) received an 8-week cycle of G+E before and after surgery. The primary endpoint was 2-year overall survival (OS), and secondary endpoints included toxicity, response, resection rate, and time to progression. Resectability was assessed retrospectively by central review. The study closed early due to slow accrual, and no formal hypothesis testing was performed., Results: Overall, 114 patients were eligible, consented, and initiated protocol treatment. By central radiologic review, 97 (85%) of the 114 patients met the protocol-defined resectability criteria. Grade 3+ toxicity was reported in 60% and 79% of patients during the neoadjuvant phase and overall, respectively. Twenty-two of 114 (19%) patients did not proceed to surgery; 83 patients (73%) were successfully resected. R0 and R1 margins were obtained in 67 (81%) and 16 (19%) resected patients, respectively, and 54 patients completed postoperative G+E (65%). The 2-year OS rate for the entire cohort (n = 114) was 40% (95% confidence interval [CI] 31-50), with a median OS of 21.3 months (95% CI 17.2-25.9). The 2-year OS rate for resected patients (n = 83) was 52% (95% CI 41-63), with a median OS of 25.4 months (95% CI 21.8-29.6)., Conclusions: For resectable PDAC, perioperative G+E is feasible. Further evaluation of neoadjuvant strategies in resectable PDAC is warranted with more active systemic regimens.

The findings and recommendations of the North American Consensus Conference on Training in HPB Surgery held October 2014 are presented. The conference was hosted by the Society for Surgical Oncology (SSO), Americas Hepatopancreaticobiliary Association (AHPBA), and the American Society of Transplant Surgeons (ASTS). The current state of training in HPB surgery in North America was defined through three pathways-HPB, Surgical Oncology, and Solid Organ Transplant fellowships. Consensus regarding programmatic requirements included establishment of minimum case volumes and inclusion of quality metrics. Formative assessment, using milestones as a framework and inclusive of both operative and non-operative skills, must be present. Specific core HPB cases should be defined and used for evaluation of operative skills. The conference concluded with a focus on the optimal means to perform summative assessment to evaluate the individual fellow completing a fellowship in HPB surgery. Presentations from the hospital perspective and the American Board of Surgery led to consensus that summative assessment was desired by the public and the hospital systems, and should occur in a uniform but possibly modular manner for all HPB fellowship pathways. A task force comprised of representatives of the SSO, AHPBA, and ASTS are charged with implementation of the consensus statements emanating from this consensus conference.Copyright © 2016 The American Society of Transplantation, the American Society of Transplant Surgeons, and the Society of Surgical Oncology. All rights reserved. No part of this document may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without written permission by The American Society of Transplantation, the American Society of Transplant Surgeons, or the Society of Surgical Oncology.

Background: The benefit of adjuvant therapy following resection of early stage, node-negative gastric adenocarcinoma following a margin negative (R0) resection is unclear., Methods: The National Cancer Data Base was used to identify patients with a T2N0 gastric adenocarcinoma (tumor invasion into the muscularis propria) who underwent R0 resection. Patients treated with neoadjuvant therapy and those for whom lymph node count was unavailable were excluded from the analysis. Kaplan-Meier and Cox regression were used to evaluate differences in and predictors of overall survival., Results: A total of 1687 patients underwent R0 resection for T2N0 gastric adenocarcinoma between 2003-2011. Adjuvant chemotherapy treatment was administered to 7.1 and 14.1 % received adjuvant chemoradiation; 65.4 % had <15 lymph nodes examined. Multivariate Cox regression identified higher Charlson score, <15 lymph nodes examined, higher tumor grade, and tumor location in the cardia as factors associated with significantly decreased overall survival. With a median follow-up of 36 months, the 5-year overall survival was 71 % for patients with ≥15 lymph nodes examined and 53 % for those with <15 lymph nodes (p < 0.001). In patients who had <15 lymph nodes examined, there was an overall survival benefit for adjuvant chemoradiation (hazard ratio 0.71, p = 0.043). In patients with ≥15 lymph nodes examined, no survival benefit for adjuvant therapy was identified (p > 0.74)., Conclusions: Adequate lymph node dissection and pathologic staging is critical in directing optimal treatment of patients with early gastric cancer. Understaging as a result of suboptimal lymphadenectomy may explain the perceived benefit of adjuvant chemoradiation after an R0 resection for T2N0 gastric cancer.

Background: Intrahepatic cholangiocarcinoma (ICC) is rare but is increasing in incidence. While hepatectomy can be curative, the benefit of adjuvant therapy (AT) remains unclear. We utilized the National Cancer Data Base (NCDB) to isolate predictors of overall survival, describe the national pattern of AT administration, and identify characteristics of patients who experience a survival benefit from AT following resection for ICC., Methods: Patients who were diagnosed with ICC between 1998 and 2006 and underwent surgical resection were identified through the NCDB. Kaplan-Meier and Cox regression analyses evaluated differences in overall survival between patients who received AT and those who did not., Results: Overall, 638 patients who underwent surgery for ICC were identified. Multivariate Cox regression analysis identified positive lymph nodes, unexamined lymph nodes, positive margins, and lack of AT as predictors of decreased overall survival; 28.1 % of patients had positive margins while 20.1 % had positive nodes. These patients, as well as those who were younger and had fewer co-morbid conditions, were most likely to receive AT. After adjusting for other prognostic variables, patients were found to significantly benefit from AT if they had positive lymph nodes [chemotherapy: hazard ratio (HR) 0.54, p = 0.0365; chemoradiation: HR 0.50, p = 0.005] or positive margins (chemotherapy: HR 0.44, p = 0.0016; chemoradiation: HR 0.57, p = 0.0039)., Conclusions: Positive lymph nodes and positive margins were associated with poor survival after resection for ICC. After controlling for other prognostic factors, AT was associated with significant survival benefits among patients with positive nodes or positive margins.

Background: There is substantial variation in the surgical complexity of hepatectomy. Currently, the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) risk adjusts for hospital quality comparisons using only the primary procedure code. Our objectives were to (1) assess the association between secondary procedures and complications; (2) assess model performance with inclusion of surgical complexity adjustment; and (3) examine whether secondary procedures affect hospital quality rankings., Methods: Using ACS NSQIP (2007-2012), patients undergoing hepatectomy were identified. Secondary procedure codes and total work relative value units (RVUs) were used to approximate procedural complexity. The effect of procedural complexity variables on outcomes and hospital quality rankings were examined using hierarchical models., Results: Among 11,826 patients who underwent hepatectomy at 261 hospitals, 32.8 % underwent at least one secondary procedure. Serious morbidity occurred in 18.0 % of patients. Seven of nine secondary procedures were significantly associated with death or serious morbidity on multivariable analysis. Model performance improved when secondary procedure categories were included, and secondary procedure categories outperformed total RVUs. The C-statistic for death or serious morbidity was 0.689 in the standard NSQIP model, 0.703 when total RVU was included, and 0.718 when secondary procedure categories were included. Of the 26 hospitals that were poor performers for death or serious morbidity using the standard ACS NSQIP model, three became average performers when secondary procedure categories were included in the model., Conclusions: Secondary procedures are associated with an increased risk of postoperative complications. Inclusion of secondary procedure code categories in research and risk prediction models should be considered for hepatectomy.

Background: Cancer recurrence is a critically important outcome to patients and providers. However, no publicly available cancer registry data contain recurrence information. The National Cancer Data Base (NCDB) collects recurrence data; however, this information is not provided to researchers because of completeness and accuracy concerns. Our objective was to examine completeness of cancer recurrence information in the NCDB., Methods: Stage I-III thyroid/colon/melanoma/pancreas/breast cancers diagnosed in 2002-2005 were identified. Recurrence status, recurrence type, and recurrence date were evaluated for data completeness. Patient, tumor, and hospital factors were examined using generalized linear mixed models. Pseudo-R (2) statistics estimated the relative contribution of patient and hospital factors., Results: Of 702,144 patients with thyroid/colon/melanoma/pancreas/breast cancers treated in 1405 hospitals, recurrence information was incomplete in 21.5/24.0/20.2/34.8/18.2 % of patients, respectively. On average, hospitals had incomplete recurrence information on 56.7-66.7 % of their patients. Patients with incomplete information had more comorbidities, a higher cancer stage, non-private insurance, and lived farther from the hospital. Hospitals with the poorest collection were larger tertiary hospitals serving higher-income patients. However, these patients and hospital factors explained less than 3 %, while unexplained hospital variation accounted for the largest part of the observed variation (%ΔR (2) = 84 %)., Conclusions: The majority of hospitals report incomplete recurrence information for more than half of their patients. The presence of incomplete recurrence information was largely dependent on undefined hospital factors, rather than patient or tumor characteristics. Attempts to improve cancer recurrence information should focus on hospital operational and process factors surrounding how the hospital tumor registries collect recurrence data.

Background: Surgical margin involvement is an important outcome after pancreatic cancer surgery; however, variation in pathologic review practices may limit its use as a quality indicator. Our objectives were to assess variation in hospital performance and the reliability of margin involvement after pancreatic cancer surgery., Methods: From the National Cancer Data Base, patients who underwent pancreatic resection for stage I to III adenocarcinoma were identified. Risk-adjusted surgical margin involvement was evaluated using hierarchical regression methods, and variation in hospital performance and reliability was determined., Results: From 1,002 hospitals, 14,889 patients underwent pancreatic resection for adenocarcinoma, and 3,573 (24.0 %) had an involved surgical margin (R1 22.8 %; R2 1.2 %). The strongest predictors associated with margin involvement were T stage [T3: odds ratio (OR) 2.08, 95 % confidence interval (CI) 1.68-2.59; T4: OR 7.26, 95 % CI 5.50-9.60; vs. T1] and tumor size (2-3.9 cm: OR 1.66, 95 % CI 1.39-1.98, ≥ 4 cm: OR 2.28, 95 % CI 1.90-2.74; vs. <2 cm). Factors associated with a decreased likelihood of margin involvement were the use of neoadjuvant therapy and hospital type (academic and National Cancer Institute-designated comprehensive cancer centers vs. community). At the hospital level, the mean risk-adjusted surgical margin involvement rate was 25.9 % and ranged 10.1 to 50.5 %. Twenty-one (2.1 %) hospitals had lower-than-expected and 17 (1.7 %) had higher-than-expected margin involvement. A minimum acceptable reliability of 0.4 was met after 13 cases and was achieved by 249 hospitals that performed 79 % of pancreatic resections assessed., Conclusions: Despite differences in pathologic evaluation practices, hospitals can be feasibly and reliably provided comparative data on surgical margin status after resection for pancreatic cancer.

Background: Methodological limitations of prior studies have prevented progress in the treatment of patients with borderline resectable pancreatic adenocarcinoma. Shortcomings have included an absence of staging and treatment standards and pre-existing biases with regard to the use of neoadjuvant therapy and the role of vascular resection at pancreatectomy., Methods: In this manuscript, we review limitations of studies of borderline resectable PDAC reported to date, highlight important controversies related to this disease stage, emphasize the research infrastructure necessary for its future study, and present a recently-approved Intergroup pilot study (Alliance A021101) that will provide a foundation upon which subsequent well-designed clinical trials can be performed., Results: We identified twenty-three studies published since 2001 which report outcomes of patients with tumors labeled as borderline resectable and who were treated with neoadjuvant therapy prior to planned pancreatectomy. These studies were heterogeneous in terms of the populations studied, the metrics used to characterize therapeutic response, and the indications used to select patients for surgery. Mechanisms used to standardize these and other issues that are incorporated into Alliance A021101 are reviewed., Conclusions: Rigorous standards of clinical trial design incorporated into trials of other disease stages must be adopted in all future studies of borderline resectable pancreatic cancer. The Intergroup trial should serve as a paradigm for such investigations.

Background: Hereditary diffuse gastric cancer (HDGC) represents a minority of gastric cancer (GC) cases. The goal of this study is to use a RAND/University of California Los Angeles (UCLA) appropriateness methodology to examine indications for genetic referral, CDH1 testing, and consideration of prophylactic total gastrectomy (PTG)., Methods: A multidisciplinary expert panel of 16 physicians from six countries scored 47 scenarios. Appropriateness of scenarios was scored from 1 (highly inappropriate) to 9 (highly appropriate). Median appropriateness scores (AS) of 1-3 were considered inappropriate, 4-6 uncertain, and 7-9 appropriate. Agreement was reached when 12 of 16 panelists scored the statement similarly. Appropriate scenarios agreed upon were subsequently scored for necessity., Results: The panel felt that patients with family history of diffuse gastric cancer (DGC), lobular breast cancer, or multiple family members with GC should be referred for genetic assessment and multidisciplinary decision-making. The panel felt that it is appropriate for patients with DGC to have CDH1 mutation testing in a family with (1) ≥2 cases of GC, with at least one case of DGC diagnosed before age of 50 years; (2) ≥3 cases of GC diagnosed at any age, one or more of which is DGC; (3) a patient diagnosed with DGC and lobular breast carcinoma; or (4) patients diagnosed with DGC under age of 35 years. The panel felt that PTG should be offered to CDH1 mutation carriers 20 years or older., Conclusions: Identification of genetic mutations in patients at risk for hereditary GC is important, and criteria for testing are suggested.

Purpose: We designed American College of Surgeons Oncology Group (ACOSOG) Z6041, a prospective, multicenter, single-arm, phase II trial to assess the efficacy and safety of neoadjuvant chemoradiation (CRT) and local excision (LE) for T2N0 rectal cancer. Here, we report tumor response, CRT-related toxicity, and perioperative complications (PCs)., Methods: Clinically staged T2N0 rectal cancer patients were treated with capecitabine and oxaliplatin during radiation followed by LE. Because of toxicity, capecitabine and radiation doses were reduced. LE was performed 6 weeks after CRT. Patients were evaluated for clinical and pathologic response. CRT-related complications and PCs were recorded., Results: Ninety patients were accrued; 6 received nonprotocol treatment. The remaining 84 were 65% male; median age 63 years; 83% Eastern Cooperative Oncology Group performance score 0; 92% white; mean tumor size 2.9 cm; and average distance from anal verge 5.1 cm. Five patients were considered ineligible. Therapy was completed per protocol in 79 patients, but two patients did not undergo LE. Among 77 eligible patients who underwent LE, 34 patients achieved a pathologic complete response (44%) and 49 (64%) tumors were downstaged (ypT0-1), but 4 patients (5%) had ypT3 tumors. Five LE specimens contained lymph nodes; one T3 tumor had a positive node. All but one patient had negative margins. Thirty-three (39%) of 84 patients developed CRT-related grade ≥3 complications. Rectal pain was the most common PC., Conclusions: CRT before LE for T2N0 tumors results in a high pathologic complete response rate and negative resection margins. However, complications during CRT and after LE are high. The true efficacy of this approach will ultimately be assessed by the long-term oncologic outcomes.

Background: Standardization of surgical and pathologic techniques is crucial to the interpretation of studies evaluating adjuvant therapies for pancreatic cancer (PC)., Methods: To assess the degree to which treatment administered prior to enrollment of patients in trials of adjuvant therapy is quality controlled, the operative and pathology reports of patients in American College of Surgeons Oncology Group (ACOSOG) Z5031-a national trial of chemoradiation following pancreaticoduodenectomy (PD)-were rigorously evaluated. We analyzed variables with the potential to influence staging or outcome., Results: 80 patients reported to have undergone R0 (75%) or R1 (25%) pylorus-preserving (38%) or standard (62%) PD were evaluated. A search for metastases was documented in 96% of cases. The proximity of the tumor to the superior mesenteric vein was reported in 69%; vein resection was required in 9% and lateral venorrhaphy in 14%. The method of dissection along the superior mesenteric artery (SMA) was described in 68%, being ultrasonic dissection (17%), stapler (24%), and clamp and cut (59%). SMA skeletonization was described in 25%, and absence of disease following resection was documented in 24%. The surgeon reported marking the critical SMA margin in 25%; inking was documented in 65% of cases and evaluation of the SMA margin was reported in 47%. A range of 1-49 lymph nodes was evaluated. Only 34% of pathology reports met College of American Pathologists criteria., Conclusions: Trials of adjuvant therapy following PD suffer from a lack of standardization and quality control prior to patient enrollment. These data suggest areas for improvement in the design of multidisciplinary treatment protocols.

Introduction: Systems for assessing surgical trainee competence must be practical, reliable, and valid. We developed a novel system, the Surgical Training and Assessment Tool (STAT), for longitudinal competency assessments of surgical trainees' operative performances. We hypothesized the tool would be both practical and reliable within an academic surgical oncology training program., Methods: Three surgical qualities of our primary interest (knowledge, skill, and independence) and the key technical maneuvers of approximately 200 surgical oncology procedures were defined and organized into hierarchical menus and loaded into a secure, web-based database. After every training case, trainee and attending surgeon electronically submitted evaluations of the trainee's performance, along with comments, and an overall grade. Data on system use and scores were analyzed., Results: Over the first 14 months of use at a university-based surgical oncology fellowship program, 1,029 assessments were recorded (528 attending surgeon, 501 trainee self-assessments). Median time to complete each assessment was 39 s (range 9-532 s, mean 60 s). Knowledge, skill, and independence assessments each demonstrated strong correlation with overall competency grade (Pearson correlations 0.60, 0.76, and 0.69, respectively). Multiple linear regression analysis showed all to be significant predictors of the overall grade (model R (2) = 0.63; test of predictive significance p < 0.001 for each)., Conclusions: STAT is a novel system for tracking and assessing trainee operative performance, which is easily integrated into the workflow of an academic surgical oncology department. Our analysis suggests that it is a practical and reliable instrument; its validity is promising and warrants further study.

Background: Patients with curatively resected colorectal cancer hepatic metastases often harbor occult metastatic disease and are at high risk of experiencing recurrence. This patient cohort is ideally suited to test novel therapies such as immunotherapy. We treated patients-post-hepatic resection-with anti-idiotype monoclonal antibody vaccines to the tumor-associated antigens carcinoembryonic antigen (CeaVac) and human milk fat globule (TriAb), both of which are co-expressed in more than 90% of colorectal cancer patients., Methods: Vaccinations commenced 6-12 weeks post-hepatic resection and consisted of four biweekly treatments of 2 mg CeaVac and TriAb, then monthly treatments for 2 years, then on every other month for 3 years. The primary endpoint was to investigate the proportion of patients recurrence-free at 2 years, and the objective of the study was to demonstrate that at least 58% would be recurrence-free at this time to consider the regimen worthy of further study., Results: Between July 2001 and October 2004, 56 patients were accrued; 52 patients with margin-negative resection were eligible for analysis. Hepatic lobectomy was performed in 56% of patients with a median of one metastasis (range 1-3). Of the 52 eligible patients, 49 were evaluable for the primary end point. Median follow-up was 3.1 years. The proportion of patients recurrence-free at 2 years was 39%, with a lower confidence bound (LCB) of 0.29. Median recurrence-free survival was 16 months. The 2-year overall survival was 94% (95% CI, 0.81, 0.98). Only 10% of patients had documented grade-3 adverse events., Conclusions: Anti-idiotype monoclonal antibody vaccine therapy with CeaVac and TriAb as an adjuvant to curative resection of colorectal cancer hepatic metastases is well tolerated but did not improve 2-year recurrence-free survival when compared with the expected value of 40% reported for hepatic resection alone.

Background: The ability to infect tumor cells limits the antitumor effects of gene therapy. The addition of radiotherapy to treatment with Ad.Egr.TNF.11D, a replication-deficient adenovirus containing a radiation-inducible promoter, early growth response-1, and the tumor necrosis factor-alpha (TNFalpha) complementary DNA may enhance the therapeutic ratio., Methods: Seg-1 human esophageal adenocarcinoma cells were treated with Ad.Egr.TNF.11D with or without radiation. TNFalpha levels were quantified with enzyme-linked immunosorbent assay. Athymic nude mice bearing Seg-1 tumors were randomized to buffer, ionizing radiation, Ad.Egr.TNF.11D, and combination therapy. Tumor growth delay was used to compare treatment regimens. TNFalpha levels were measured in tumor homogenates and plasma., Results: Seg-1 cells treated with Ad.Egr.TNF.11D and ionizing radiation demonstrated increased TNFalpha levels at 72 hours compared with cells exposed to vector alone (124 +/- 0 pg/mL vs. 31.11 +/- 22 pg/mL; P =.008). In vivo, Ad.Egr.TNF.11D-treated tumors expressed low TNFalpha levels (151.5 +/- 107.11 pg/mg protein) compared with tumors receiving combined treatment (793.92 +/- 489.13 pg/mg protein; P =.067). Increased TNFalpha levels were associated with increased tumor growth delay after combined treatment (P <.05)., Conclusions: Radiotherapy enables focal stimulation of TNFalpha expression in Ad.Egr.TNF.11D-infected cells and thus improves local tumor control.

Background: Controversy exists regarding internal mammary lymph nodes (IMNs) in the staging and treatment of breast cancer. Sentinel lymph node identification with radiocolloid can map drainage to IMNs and directed biopsy can be performed with minimal morbidity. Furthermore, recent studies suggest that IMN drainage of breast tumors may be underestimated. To gain further insight into the prognostic value of IMNs, we reviewed the outcome of patients in whom the IMN status was routinely assessed., Methods: A retrospective review of 286 patients with breast cancer who underwent IMN dissection between 1956 and 1987 was conducted., Results: Median follow-up is 186 months, age was 52 years (range, 21-85 years), tumor size was 2.5 cm, and number of IMNs removed was 5 (range, 1-22); 44% received chemotherapy, 16% endocrine therapy, and 5% radiotherapy. Presence of IMN metastases correlated with primary tumor size (P < .0001) and number of positive axillary nodes (P < .0001) but did not correlate with primary tumor location or age. Overall, the 20-year disease-free survival is significantly worse for the 25% of patients with IMN metastases (P < .0001). In patients with positive axillary nodes and tumors smaller than 2 cm, there was a significantly worse survival (P < .0001) in the patients with IMN metastases. This difference in survival was not seen in women with tumors larger than 2 cm., Conclusions: Patients with IMN metastases, regardless of axillary node status, have a highly significant decrease in 20-year disease-free survival. Treatment strategies based on knowledge of sentinel IMN status may lead to improvement in survival, especially for patients with small tumors. At present, sentinel IMN biopsies should be performed in a clinical trial setting.

Background: The efficacy and therapeutic impact of needle-localized thoracoscopic resection (NLTR) was examined in patients with cancer who present with small indeterminate pulmonary nodules (IPNs)., Methods: Between December 1991 and August 1992, 30 patients underwent needle localization of 33 IPNs under computed tomography (CT) guidance followed by thoracoscopic resection. All previous attempts to characterize these small pulmonary nodules (mean size 7.9 +/- 4.9 mm) had failed. Twenty patients had an established diagnosis of cancer 1 month to 20 years before detection of the lung abnormality, whereas the remaining patients had no prior history of cancer., Results: Histology of NLTR specimens in patients with a previous diagnosis of malignancy included 13 malignant and seven benign lesions. In all patients with cancer, therapeutic decisions were influenced by NLTR results. Thoracoscopic related complications were noted in two patients. Average length of hospital stay for NLTR was 6.7 +/- 3.9 days., Conclusion: NLTR in this series has proven to be a safe, well-tolerated, and accurate method for diagnosing and influencing the management of recently identified IPN. NLTR appears warranted for small pulmonary nodules not amenable to less invasive diagnostic modalities.