Showing papers in "Annals of Surgical Oncology in 2018"

AJCC 8th Edition: Colorectal Cancer.

Abstract: In the 8th edition of the American Joint Committee on Cancer (AJCC) staging manual, the chapter on colorectal cancer provides an extended description of anatomy, followed by rules for clinical and pathologic classification. Although the basic staging structure has remained the same, there have been many updates and clarifications. One of the significant additions in the discussion of pathologic classification is the detailed description of Tis dysplasia. Penetrating into the lamina propria with possible invasion into the muscularis mucosa, Tis lesions are referred to as intramucosal adenocarcinoma. Penetration through the basement membrane at any gastrointestinal site is considered invasive, but in colorectal cancer, only tumors that invade the submucosa metastasize. Due to the potential for sampling errors, Tis lesions are recorded in the cancer registry, while those with other forms of dysplasia, including high-grade, are not. T categories have not changed. As in AJCC 7, T4 is subdivided into T4a and T4b. Tumors that invade the serosal surface (visceral peritoneum) are referred to as T4a. There is further clarification that tumors with perforation, in which the tumor cells are continuous with the serosal surface through inflammation, are also considered T4a. In areas of the colon and rectum without peritoneal covering, such as posterior aspects of the ascending and descending colon and lower rectum, T4a is not applicable. Tumors that directly invade or adhere to adjacent organs or structures are considered T4b. N categories have also not changed; however, there is an extended discussion of isolated tumor cells in lymph nodes and micrometastases. Isolated tumor cells, which generally consist of up to 20 cells within the subcapsular or marginal sinus of a lymph node, are of controversial prognostic value. According to AJCC 8, they should be designated N0 (or N0i?), but their presence does not elevate disease to stage III. Micrometastases are clusters of 20 or more cells or metastases measuring[ 0.2 mm and \\ 2 mm in diameter. A recent meta-analysis demonstrated that micrometastases are associated with poor prognosis. Lymph nodes harboring micrometastases should be considered positive and are denoted N1. AJCC 8 clarifies the interpretation of discrete tumor nodules found within the lymph drainage area of a primary colon or rectal carcinoma. Nodules containing no identifiable lymph node tissue or vascular/neural structures should be considered tumor deposits and designated N1c. The shape, contour, and size of the deposit are not considered in these designations. Tumor deposits within a vessel wall should be considered lymphovascular invasion, with the site-specific designations L? for lymphatic or small-vein invasion and V? for deposits in endothelial-cell-lined spaces with associated red blood cells or smooth muscle cells. If tumor nodules are found around a neural structure, they should be categorized as perineural invasion. N1c elevates disease to stage III, even in the absence of nodal metastases. The number of tumor deposits is recorded with site-specific factors but does not influence the designation (i.e. a patient with one tumor deposit and a patient with four tumor deposits are both staged as N1c). The number of tumor deposits is not added to the number of positive lymph nodes. The M category has been expanded, with the addition of M1c for peritoneal metastases (M1a denotes metastases to one distant site or organ, and M1b denotes metastases to more than one). The rationale for the M1c designation is that patients with peritoneal metastases generally fare worse than those with visceral organ metastases. AJCC 8 provides a fuller discussion of proper colorectal cancer resection, including measurement of the distance Society of Surgical Oncology 2018

8th Edition of the AJCC Cancer Staging Manual: Pancreas and Hepatobiliary Cancers

Abstract: The American Joint Committee on Cancer (AJCC) Staging Manual represents the standard for classifying patients with pancreas and hepatobiliary cancers, predicting prognosis, and guiding treatment decisions. For the new 8th edition, the AJCC Hepatobiliary Task Force, a multidisciplinary team of international experts, conducted two face-to-face meetings. At the first meeting, specialists in individual disease sites presented analysis of the literature and reviewed questions and issues from the 7th edition. Recommendations for revisions were proposed and discussed. At the second meeting, additional data to support the proposed revisions were reviewed, and revisions were approved by the full task force, including representatives from the Union for International Cancer Control (UICC) and the AJCC Editorial Board. Chapters were submitted to the Editorial Board for editing and final approval. The cornerstone of staging of hepatobiliary cancers is high-quality surgery, detailed pathologic analysis, and reliable follow-up, which are not available from large datasets and registries. Owing to the relative rarity of hepatobiliary cancers and the complex anatomy, often requiring technically demanding surgery, the AJCC staging system is largely based on single-institution series from centers of excellence in surgery and pathology. Much of the evidence that forms the basis for the revised 8th edition has been validated at other centers of excellence in hepatobiliary cancer. Importantly, the revisions also drew heavily on international expertise, particularly from Asia, where the incidence of hepatobiliary cancers is high. For the 8th edition, the N category has been harmonized for gallbladder, perihilar bile ducts, distal bile duct, ampulla, and pancreas. For these disease sites, N1 is defined as one to three metastatic lymph nodes, and N2 as four or more metastatic lymph nodes. A number-based categorization of metastatic lymph nodes results in better prognostic stratification. Other key modifications in the AJCC 8th edition are described below.

Eighth Edition of the AJCC Cancer Staging Manual: Breast Cancer

Abstract: Since its inception in 1977, the American Joint Committee on Cancer (AJCC) has published a staging system based on anatomic findings: tumor size (T), nodal status (N), and metastases (M). This staging system has evolved, not only encompassing a wide spectrum of tumors but also including multiple updates that enable physicians to utilize new information and outcomes for management strategies in different malignancies. The breast cancer staging system has always been based similarly on TNM classification despite the fact that, for several years, clinicians in practice have used a number of biologic factors to describe the patient’s disease, outcomes, and appropriate therapy. The eighth edition of the AJCC staging for breast cancer is conceptually a radical departure from prior editions, because it incorporates contemporary biologic factors (biomarkers) into the traditional anatomic staging system. These biomarkers result in a modification of the TNM stage. These factors—estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), grade, and multigene assays—are widely used in practice to define prognosis and determine therapy. The eighth edition also maintains a firm footing in the past, enabling comparisons of outcomes to prior studies using the traditional TNM system as the basis, especially important in parts of the world where biologic markers are not routinely available. In the AJCC Staging Manual, biomarkers have previously been incorporated into other tumor systems, such as thyroid and prostate cancer; however, until recently, there have been insufficient data to permit incorporation of biomarkers into the staging system for breast cancer. The expert panel for the eighth edition felt that the peer-reviewed literature was now sufficient to permit inclusion of several of the most well-studied biomarkers. These biomarkers, especially hormone-receptor and HER2, have a great impact on treatment and outcomes. Gene expression profiling has identified several molecular subtypes of breast cancer. While gene expression profiling is the defining feature of breast cancer subtypes, it is not often used clinically. Biomarker assays for ER, PR, and HER2 are used as surrogates for gene expression profiling and are measured with immunohistochemical methods or in situ hybridization. These clinically identifiable and well-studied biomarkers as well as histologic grade have been evaluated in prospective, controlled trials and display sufficient prognostic information to justify incorporation into the AJCC staging system. Measures of proliferation, such as Ki67, were also considered. Because of concerns about interobserver reproducibility, the expert panel elected not to incorporate Ki67 until technical issues were resolved. In the United States, virtually all patients’ primary tumors are evaluated for ER, PR, HER2, and grade. The Nottingham grading system is the most commonly used to report tumor grade. The expert panel felt that, when possible, evaluation of these four biomarkers should adhere to guidelines of the American Society of Clinical Oncology and the College of American Pathology. In the AJCC 8th edition, patients are clinically staged using the traditional TNM anatomic information modified by the expression of these four biomarkers, creating a Clinical Prognostic Stage Group. This stage should be used for all patients whose tumors are evaluated for expression Society of Surgical Oncology 2018

Melanoma Staging: American Joint Committee on Cancer (AJCC) 8th Edition and Beyond

Abstract: Departments of Surgical Oncology and Cancer Biology, Unit 1484, The University of Texas MD Anderson Cancer Center, Houston, TX; Melanoma and Skin Center, The University of Texas MD Anderson Cancer Center, Houston, TX; Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia; Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW, Australia

Randomized Trial Comparing Resection of Primary Tumor with No Surgery in Stage IV Breast Cancer at Presentation: Protocol MF07-01

Abstract: The MF07-01 trial is a multicenter, phase III, randomized, controlled study comparing locoregional treatment (LRT) followed by systemic therapy (ST) with ST alone for treatment-naive stage IV breast cancer (BC) patients. At initial diagnosis, patients were randomized 1:1 to either the LRT or ST group. All the patients were given ST either immediately after randomization or after surgical resection of the intact primary tumor. The trial enrolled 274 patients: 138 in the LRT group and 136 in the ST group. Hazard of death was 34% lower in the LRT group than in the ST group (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.49–0.88; p = 0.005). Unplanned subgroup analyses showed that the risk of death was statistically lower in the LRT group than in the ST group with respect to estrogen receptor (ER)/progesterone receptor (PR)(+) (HR 0.64; 95% CI 0.46–0.91; p = 0.01), human epidermal growth factor 2 (HER2)/neu(–) (HR 0.64; 95% CI 0.45–0.91; p = 0.01), patients younger than 55 years (HR 0.57; 95% CI 0.38–0.86; p = 0.007), and patients with solitary bone-only metastases (HR 0.47; 95% CI 0.23–0.98; p = 0.04). In the current trial, improvement in 36-month survival was not observed with upfront surgery for stage IV breast cancer patients. However, a longer follow-up study (median, 40 months) showed statistically significant improvement in median survival. When locoregional treatment in de novo stage IV BC is discussed with the patient as an option, practitioners must consider age, performance status, comorbidities, tumor type, and metastatic disease burden.

Sentinel Lymph Node Biopsy and Management of Regional Lymph Nodes in Melanoma: American Society of Clinical Oncology and Society of Surgical Oncology Clinical Practice Guideline Update

Abstract: To update the American Society of Clinical Oncology (ASCO)-Society of Surgical Oncology (SSO) guideline for sentinel lymph node (SLN) biopsy in melanoma. An ASCO-SSO panel was formed, and a systematic review of the literature was conducted regarding SLN biopsy and completion lymph node dissection (CLND) after a positive sentinel node in patients with melanoma. Nine new observational studies, two systematic reviews and an updated randomized controlled trial (RCT) of SLN biopsy, as well as two randomized controlled trials of CLND after positive SLN biopsy, were included. Routine SLN biopsy is not recommended for patients with thin melanomas that are T1a (non-ulcerated lesions 1.0 to 4.0 mm). SLN biopsy may be recommended for patients with thick melanomas (T4; > 4.0 mm in Breslow thickness), after a discussion of the potential benefits and risks of harm. In the case of a positive SLN biopsy, CLND or careful observation are options for patients with low-risk micrometastatic disease, with due consideration of clinicopathological factors. For higher risk patients, careful observation may be considered only after a thorough discussion with patients about the potential risks and benefits of foregoing CLND. Important qualifying statements outlining relevant clinicopathological factors, and details of the reference patient populations are included within the guideline.

Intraoperative Pancreatic Cancer Detection using Tumor-Specific Multimodality Molecular Imaging

Abstract: Operative management of pancreatic ductal adenocarcinoma (PDAC) is complicated by several key decisions during the procedure. Identification of metastatic disease at the outset and, when none is found, complete (R0) resection of primary tumor are key to optimizing clinical outcomes. The use of tumor-targeted molecular imaging, based on photoacoustic and fluorescence optical imaging, can provide crucial information to the surgeon. The first-in-human use of multimodality molecular imaging for intraoperative detection of pancreatic cancer is reported using cetuximab-IRDye800, a near-infrared fluorescent agent that binds to epidermal growth factor receptor. A dose-escalation study was performed to assess safety and feasibility of targeting and identifying PDAC in a tumor-specific manner using cetuximab-IRDye800 in patients undergoing surgical resection for pancreatic cancer. Patients received a loading dose of 100 mg of unlabeled cetuximab before infusion of cetuximab-IRDye800 (50 mg or 100 mg). Multi-instrument fluorescence imaging was performed throughout the surgery in addition to fluorescence and photoacoustic imaging ex vivo. Seven patients with resectable pancreatic masses suspected to be PDAC were enrolled in this study. Fluorescence imaging successfully identified tumor with a significantly higher mean fluorescence intensity in the tumor (0.09 ± 0.06) versus surrounding normal pancreatic tissue (0.02 ± 0.01), and pancreatitis (0.04 ± 0.01; p < 0.001), with a sensitivity of 96.1% and specificity of 67.0%. The mean photoacoustic signal in the tumor site was 3.7-fold higher than surrounding tissue. The safety and feasibilty of intraoperative, tumor-specific detection of PDAC using cetuximab-IRDye800 with multimodal molecular imaging of the primary tumor and metastases was demonstrated.

Impact of Postmastectomy Radiation Therapy in Prepectoral Versus Subpectoral Implant-Based Breast Reconstruction

Abstract: This study aimed to compare the impact of postmastectomy radiation therapy (PMRT) on outcomes after prepectoral versus subpectoral implant-based breast reconstruction with local deepithelialized dermal flap and acellular dermal matrix (ADM). From 2010 to 2017, 274 patients (426 breasts) underwent prepectoral reconstruction. In this group, 241 patients (370 breasts) were not exposed to PMRT, whereas 45 patients (56 breasts) were exposed to PMRT. Of 100 patients (163 breasts) who underwent partial subpectoral reconstruction, 87 (140 breasts) were not exposed to PMRT, whereas 21 patients (23 breasts) were exposed. The outcomes were assessed by comparing complication rates between the pre- and subpectoral groups. A higher rate of capsular contracture was found for the prepectoral patients with PMRT than for those without PMRT (16.1 vs 3.5%; p = 0.0008) and for the subpectoral patients with PMRT than for those without PMRT (52.2 vs 2.9%; p = 0.0001). The contracture rate was three times higher for the subpectoral patients with PMRT than for the prepectoral patients with PMRT (52.2 vs 16.1%; p = 0.0018). In addition, 10 (83.3%) of 12 cases with capsular contracture in the subpectoral cohort that received PMRT were Baker grades 3 or 4 compared with only 2 (22.2%) of 9 cases of the prepectoral group with PMRT (p = 0.0092). The patients undergoing subpectoral breast reconstruction who received PMRT had a capsular contracture rate three times greater with more severe contractures (Baker grade 3 or 4) than the patients receiving PMRT who underwent prepectoral breast reconstruction.

Cytolytic Activity Score to Assess Anticancer Immunity in Colorectal Cancer.

Abstract: Elevated tumor-infiltrating lymphocytes (TILs) within the tumor microenvironment is a known positive prognostic factor in colorectal cancer (CRC). We hypothesized that since cytotoxic T cells release cytolytic proteins such as perforin (PRF1) and pro-apoptotic granzymes (GZMA) to attack cancer cells, a cytolytic activity score (CYT) would be a useful tool to assess anticancer immunity. Genomic expression data were obtained from 456 patients from The Cancer Genome Atlas (TCGA). CYT was defined by GZMA and PRF1 expression, and CIBERSORT was used to evaluate intratumoral immune cell composition. High CYT was associated with high microsatellite instability (MSI-H), as well as high levels of activated memory CD4+T cells, gamma-delta T cells, and M1 macrophages. CYT-high CRC patients had improved overall survival (p = 0.019) and disease-free survival (p = 0.016) compared with CYT-low CRC patients, especially in TIL-positive tumors. Multivariate analysis demonstrated that CYT- high associates with improved survival independently after controlling for age, lymphovascular invasion, colonic location, microsatellite instability, and TIL positivity. The levels of immune checkpoint molecules (ICMs)—programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), cytotoxic T-lymphocyte-associated protein 4 (CTLA4), lymphocyte-activation gene 3 (LAG3), T cell immunoglobulin and mucin domain 3 (TIM3), and indoleamine 2,3-dioxygenase 1 (IDO1)—correlated significantly with CYT (p < 0.0001); with improved survival in CYT-high and ICM-low patients, and poorer survival in ICM-high patients. High CYT within CRC is associated with improved survival, likely due to increased immunity and cytolytic activity of T cells and M1 macrophages. High CYT is also associated with high expression of ICMs; thus, further studies to elucidate the role of CYT as a predictive biomarker of the efficacy of immune checkpoint blockade are warranted.

Image-Guided Surgery in Patients with Pancreatic Cancer: First Results of a Clinical Trial Using SGM-101, a Novel Carcinoembryonic Antigen-Targeting, Near-Infrared Fluorescent Agent.

Abstract: Near-infrared (NIR) fluorescence is a promising novel imaging technique that can aid in intraoperative demarcation of pancreatic cancer (PDAC) and thus increase radical resection rates. This study investigated SGM-101, a novel, fluorescent-labeled anti-carcinoembryonic antigen (CEA) antibody. The phase 1 study aimed to assess the tolerability and feasibility of intraoperative fluorescence tumor imaging using SGM-101 in patients undergoing a surgical exploration for PDAC. At least 48 h before undergoing surgery for PDAC, 12 patients were injected intravenously with 5, 7.5, or 10 mg of SGM-101. Tolerability assessments were performed at regular intervals after dosing. The surgical field was imaged using the Quest NIR imaging system. Concordance between fluorescence and tumor presence on histopathology was studied. In this study, SGM-101 specifically accumulated in CEA-expressing primary tumors and peritoneal and liver metastases, allowing real-time intraoperative fluorescence imaging. The mean tumor-to-background ratio (TBR) was 1.6 for primary tumors and 1.7 for metastatic lesions. One false-positive lesion was detected (CEA-expressing intraductal papillary mucinous neoplasm). False-negativity was seen twice as a consequence of overlying blood or tissue that blocked the fluorescent signal. The use of a fluorescent-labeled anti-CEA antibody was safe and feasible for the intraoperative detection of both primary PDAC and metastases. These results warrant further research to determine the impact of this technique on clinical decision making and overall survival.

Timing and Delays in Breast Cancer Evaluation and Treatment

Abstract: Even small delays in the treatment of breast cancer are a frequently expressed concern of patients. Knowledge about this subject is important for clinicians to counsel patients appropriately and realistically, while also optimizing care. Although data and quality measures regarding time to chemotherapy and radiotherapy have been present for some time, data regarding surgical care are more recent and no standard exists. This review was written to discuss our current knowledge about the relationship of treatment times to outcomes. The published medical literature addressing delays and optimal times to treatment was reviewed in the context of our current time-dependent standards for chemotherapy and radiotherapy. The surgical literature and the lack of a time-dependent surgical standard also were discussed, suggesting a possible standard. Risk factors for delay are numerous, and tumor doubling times are both difficult to determine and unhelpful to assess the impact of longer treatment times on outcomes. Evaluation components also have a time cost and are inextricable from the patient’s workup. Although the published literature has lack of uniformity, optimal times to each modality are strongly suggested by emerging data, supporting the current quality measures. Times to surgery, chemotherapy, and radiotherapy all have a measurable impact on outcomes, including disease-free survival, disease-specific survival, and overall survival. Delays have less of an impact than often thought but have a measurable impact on outcomes. Optimal times from diagnosis are < 90 days for surgery, < 120 days for chemotherapy, and, where chemotherapy is administered, < 365 days for radiotherapy.

Intraoperative Ultrasound-Guided Excision of Axillary Clip in Patients with Node-Positive Breast Cancer Treated with Neoadjuvant Therapy (ILINA Trial) : A New Tool to Guide the Excision of the Clipped Node After Neoadjuvant Treatment.

Abstract: The accuracy of sentinel lymph node biopsy (SLNB) after neoadjuvant therapy (NAT) has been improved with the placement of a clip in the positive node prior to treatment. Several methods have been described for clipped node excision during SLNB after NAT. We assessed the feasibility of intraoperative ultrasound (IOUS)-guided excision of the clipped node during SLNB and investigated whether the accuracy of SLNB is improved. After approval by the Institutional Ethics Committee, all breast cancer patients undergoing NAT had an US-visible clip placed in the positive node. The ILINA trial consisted of IOUS-guided excision of the clipped node along with SLNB and axillary lymph node dissection (ALND). Forty-six patients had a clip placed in the positive node. In two (4.3%) cases, the clip could not be seen prior to surgery and the patient underwent ALND; however, the clipped node was successfully removed by IOUS-guided excision in 44 patients. Thirty-five patients (79.5%) underwent SLNB along with IOUS-guided excision of the clipped node and ALND, and were subsequently included in the ILINA trial. Nine patients were not included (five patients with SLNB only and four patients with ALND without SLNB). SLNB matched the clipped node in 27 (77%) patients. The false negative rate for the ILINA protocol was 4.1% (95% confidence interval 0.1–21.1%). IOUS-guided excision of the axillary clipped node after NAT was feasible, safe, and successful in 100% of cases. The ILINA trial is accurate in predicting axillary nodal status after NAT.

Intraoperative Margin Management in Breast-Conserving Surgery: A Systematic Review of the Literature

Abstract: Breast surgeons have a wide variety of intraoperative techniques available to help achieve low rates for positive margins of excision, with variable levels of evidence. A systematic review of the medical literature from 1995 to July 2016 was conducted, with 434 abstracts identified and evaluated. The analysis included 106 papers focused on intraoperative management of breast cancer margins and contained actionable data. Ultrasound-guided lumpectomy for palpable tumors, as an alternative to palpation guidance, can lower positive margin rates, but the effect when used as an alternative to wire localization (WL) for nonpalpable tumors is less certain. Localization techniques such as radioactive seed localization and radioguided occult lesion localization were found potentially to lower positive margin rates as alternatives to WL depending on baseline positive margin rates. Intraoperative pathologic methods including gross histology, frozen section analysis, and imprint cytology all have the potential to lower the rates of positive margins. Cavity-shave margins and the Marginprobe device both lower rates of positive margins, with some potential for negative cosmetic effects. Specimen radiography and multiple miscellaneous techniques did not affect positive margin rates or provided too little evidence for formation of a conclusion. A systematic review of the literature showed evidence that several intraoperative techniques and actions can lower the rates of positive margins. These results are presented together with graded recommendations.

Impact of Malnutrition After Gastrectomy for Gastric Cancer on Long-Term Survival

Abstract: Preoperative malnutrition can worsen morbidity and mortality; however, the role of postgastrectomy nutritional status remains unclear. Our purpose was to clarify whether malnutrition after gastrectomy could predict long-term survival. Patients with pathological stage I, II, and III gastric cancer who underwent gastrectomy between 2002 and 2013 were included. The nutrition risk index (NRI) was evaluated before and at 1, 3, 6 and 12 months after gastrectomy. The patients were divided into normal (NRI > 97.5) or malnutrition (NRI ≤ 97.5) groups, and we compared the correlations of clinicopathological characteristics, surgical treatment, and overall survival between the two groups. Among the 760 participants, patients in the malnutrition group were significantly older and had higher incidences of comorbidity and advanced cancer than the patients in the normal group. Multivariate analysis showed that overall survival was poorer in the malnutrition group before gastrectomy [hazard ratio (HR) 1.68] and at 1 month (HR 1.77), 3 months (HR 2.18), 6 months (HR 1.81) and 12 months (HR 2.17) after gastrectomy (all p < 0.01). Malnutrition at 1 and 3 months after gastrectomy was significantly associated with poor cause-specific survival. Total gastrectomy, preoperative malnutrition, older age, and adjuvant chemotherapy were independent risk factors of postoperative malnutrition at 12 months postgastrectomy. Malnutrition before gastrectomy and at 1, 3, 6 and 12 months after gastrectomy significantly and adversely affects overall survival. Nutritional interventions to lessen the impact of postoperative malnutrition offer hope for prolonged survival.

External Beam Radiation Therapy for Resectable Soft Tissue Sarcoma: A Systematic Review and Meta-Analysis.

Abstract: The aim of this study was to evaluate the role of preoperative and postoperative external beam radiation therapy (EBRT) in the treatment of resectable soft tissue sarcomas (STSs) of different tumor locations. A systematic literature search was performed to identify studies investigating the effects of EBRT (versus no EBRT) on local recurrence (LR) and overall survival (OS) or comparing different EBRT sequences. Random effects meta-analyses were calculated and presented as cumulative odds ratios (ORs). Sixteen studies (n = 3958 patients) comparing EBRT versus no EBRT, including one randomized controlled trial (RCT) in extremity sarcoma, were analyzed. EBRT appeared to reduce LR in both retroperitoneal tumors (OR 0.47, p < 0.0001) and other locations (OR 0.49, p = 0.001). OS was improved by EBRT in retroperitoneal STSs (OR 0.37, p < 0.0001) but not in other tumor locations. Eleven studies (n = 2140), including one RCT, compared preoperative and postoperative radiotherapy. LR was less frequent following preoperative EBRT in retroperitoneal STSs (OR 0.03, p = 0.02), as well as in other tumor locations (OR 0.67, p = 0.01), while wound complications in extremity sarcoma were more frequent following preoperative EBRT (OR 2.92, p < 0.0001). Several studies included in this meta-analysis bear a high risk of bias and no RCT has been published for retroperitoneal STS. This meta-analysis supports the use of EBRT for local tumor control in patients with resectable STSs. Based on a small number of non-randomized studies, a positive effect on OS may exist in the subgroup of retroperitoneal STSs.

Survival Prediction in Pancreatic Ductal Adenocarcinoma by Quantitative Computed Tomography Image Analysis.

Abstract: Pancreatic cancer is a highly lethal cancer with no established a priori markers of survival. Existing nomograms rely mainly on post-resection data and are of limited utility in directing surgical management. This study investigated the use of quantitative computed tomography (CT) features to preoperatively assess survival for pancreatic ductal adenocarcinoma (PDAC) patients. A prospectively maintained database identified consecutive chemotherapy-naive patients with CT angiography and resected PDAC between 2009 and 2012. Variation in CT enhancement patterns was extracted from the tumor region using texture analysis, a quantitative image analysis tool previously described in the literature. Two continuous survival models were constructed, with 70% of the data (training set) using Cox regression, first based only on preoperative serum cancer antigen (CA) 19-9 levels and image features (model A), and then on CA19-9, image features, and the Brennan score (composite pathology score; model B). The remaining 30% of the data (test set) were reserved for independent validation. A total of 161 patients were included in the analysis. Training and test sets contained 113 and 48 patients, respectively. Quantitative image features combined with CA19-9 achieved a c-index of 0.69 [integrated Brier score (IBS) 0.224] on the test data, while combining CA19-9, imaging, and the Brennan score achieved a c-index of 0.74 (IBS 0.200) on the test data. We present two continuous survival prediction models for resected PDAC patients. Quantitative analysis of CT texture features is associated with overall survival. Further work includes applying the model to an external dataset to increase the sample size for training and to determine its applicability.

Is Low-Volume Disease in the Sentinel Node After Neoadjuvant Chemotherapy an Indication for Axillary Dissection?

Abstract: Intraoperative evaluation of sentinel lymph nodes (SLNs) after neoadjuvant chemotherapy (NAC) has a higher false-negative rate than in the primary surgical setting, particularly for small tumor deposits. Additional tumor burden seen with isolated tumor cells (ITCs) and micrometastases following primary surgery is low; however, it is unknown whether the same is true after NAC. We examined the false-negative rate of intraoperative frozen section (FS) after NAC, and the association between SLN metastasis size and residual disease at axillary lymph node dissection (ALND). Patients undergoing SLN biopsy after NAC were identified. The association between SLN metastasis size and residual axillary disease was examined. From July 2008 to July 2017, 702 patients (711 cancers) had SLN biopsy after NAC. On FS, 181 had metastases, 530 were negative; 33 negative cases were positive on final pathology (false-negative rate 6.2%). Among patients with a positive FS, 3 (2%) had ITCs and no further disease on ALND; 41 (23%) had micrometastases and 125 (69%) had macrometastases. Fifty-nine percent of patients with micrometastases and 63% with macrometastases had one or more additional positive nodes at ALND. Among those with a false-negative result, 10 (30%) had ITCs, 15 (46%) had micrometastases, and 8 (24%) had macrometastases; 17 had ALND and 59% had one or more additional positive lymph nodes. Overall, 1/6 (17%) patients with ITCs and 28/44 (64%) patients with micrometastases had additional nodal metastases at ALND. Low-volume SLN disease after NAC is not an indicator of a low risk of additional positive axillary nodes and remains an indication for ALND, even when not detected on intraoperative FS.

Detection of Parathyroid Autofluorescence Using Near-Infrared Imaging: A Multicenter Analysis of Concordance Between Different Surgeons

Abstract: Parathyroid glands (PGs) exhibit autofluorescence (AF) when excited by near-infrared laser. This multicenter study aims to analyze how this imaging could facilitate the detection of PGs during thyroidectomy and parathyroidectomy procedures. This was a retrospective Institutional Review Board-approved analysis of prospectively collected data at three centers. Near-infrared fluorescence imaging (NIFI) was used to detect AF from PGs during thyroidectomy and parathyroidectomy procedures. Logistic regression analysis was performed to assess the utility of NIFI to identify PGs and concordance at these centers. Overall, 210 patients underwent total thyroidectomy (n = 95), thyroid lobectomy (n = 41), and parathyroidectomy (n = 74) (n = 70 per center). Using NIFI, AF was detected from 98% of visually identified PGs. Upon initial exploration, 46% of PGs were not visible to the naked eye due to coverage by soft tissue, but AF from these glands could be detected by NIFI without any further dissection. Overall, a median of one PG per patient was detected by NIFI in this fashion before being identified visually (p = nonsignificant between centers). On logistic regression, smaller PGs were more likely to be missed visually, but localized by AF on NIFI (odds ratio with increasing size, 0.91; p = 0.02). In our experience, NIFI facilitated PG identification by detecting their AF, before conventional recognition by the surgeon, in 37–67% of the time. Despite the variability in this rate across centers, there was a concordance in detecting AF from 97 to 99% of the PGs using NIFI. We suggest the incorporation of AF on NIFI alongside conventional visual cues to aid identification of PGs during neck operations.

Robotic Versus Laparoscopic Right Colectomy with Complete Mesocolic Excision for the Treatment of Colon Cancer: Perioperative Outcomes and 5-Year Survival in a Consecutive Series of 202 Patients.

Abstract: During the past decade, the concept of complete mesocolic excision (CME) has emerged as a possible strategy to minimize recurrence for right colon cancers The purpose of this study was to compare robotic versus laparoscopic CME in performing right colectomy for cancer Pertinent data of all patients who underwent robotic or laparoscopic right colectomy with CME using a Pfannenstiel incision and intracorporeal anastomosis performed between October 2005 and November 2015 were entered in a prospectively maintained database A total of 202 patients underwent robotic (n = 101) or laparoscopic (n = 101) right colectomy within the study period Patient characteristics were equivalent between groups The robotic group showed a statistically significant reduction in conversion rate (0% vs 69%, p = 001) but a longer operative time (279 min vs 236 min, p < 0001) compared with the laparoscopic group There were no other differences in perioperative clinical or pathological outcomes Five-years overall survival was 77 versus 73 months for the robotic versus laparoscopic groups (p = 064) The disease-free survival (DFS) rates were 85% and 83% for the robotic versus laparoscopic groups (p = 058) Among UICC stage III patients, there was a slight but not significant difference in 5-year DFS for the robotic group (81 vs 68 months; p = 0122) Both approaches for right colectomy with CME were safe and feasible and resulted in excellent survival Robotic assistance was beneficial for performing intracorporeal anastomosis and dissection as evidenced by the lower conversion rates Further robotic experience may shorten the operative time

Assessment of Computed Tomography (CT)-Defined Muscle and Adipose Tissue Features in Relation to Short-Term Outcomes After Elective Surgery for Colorectal Cancer: A Multicenter Approach

Abstract: Sarcopenia, visceral obesity (VO), and reduced muscle radiodensity (myosteatosis) are suggested risk factors for postoperative morbidity in colorectal cancer (CRC), but usually are not concurrently assessed. Published thresholds used to define these features are not CRC-specific and are defined in relation to mortality, not postoperative outcomes. This study aimed to evaluate body composition in relation to length of hospital stay (LOS) and postoperative outcomes. Pre-surgical computed tomography (CT) images were assessed for total area and radiodensity of skeletal muscle and visceral adipose tissue in a pooled Canadian and UK cohort (n = 2100). Sex- and age-specific values for these features were calculated. For 1139 of 2100 patients, LOS data were available, and sex- and age-specific thresholds for sarcopenia, myosteatosis, and VO were defined on the basis of LOS. Association of CT-defined features with LOS and readmissions was explored using negative binomial and logistic regression models, respectively. In the multivariable analysis, the predictors of LOS (P < 0.001) were age, surgical approach, major complications (incidence rate ratio [IRR] 2.42; 95% confidence interval [CI] 2.18–2.68), study cohort, and three body composition profiles characterized by myosteatosis combined with either sarcopenia (IRR, 1.27; 95% CI 1.12–1.43) or VO (IRR, 1.25; 95% CI 1.10–1.42), and myosteatosis combined with both sarcopenia and VO (IRR, 1.58; 95% CI 1.29–1.93). In the multivariable analysis, risk of readmission was associated with VO alone (odds ratio [OR] 2.66; 95% CI 1.18–6.00); P = 0.018), VO combined with myosteatosis (OR, 2.72; 95% CI 1.36–5.46; P = 0.005), or VO combined with myosteatosis and sarcopenia (OR, 2.98; 95% CI 1.06–5.46; P = 0.038). Importantly, the effect of body composition profiles on LOS and readmission was independent of major complications. The findings showed that CT-defined multidimensional body habitus is independently associated with LOS and hospital readmission.

FOLFIRINOX Versus Gemcitabine/Nab-Paclitaxel for Neoadjuvant Treatment of Resectable and Borderline Resectable Pancreatic Head Adenocarcinoma.

Abstract: Both FOLFIRINOX and gemcitabine/nab-paclitaxel (G-nP) are used increasingly in the neoadjuvant treatment (NAT) of pancreatic ductal adenocarcinoma (PDA). This study aimed to compare neoadjuvant FOLFIRINOX and G-nP in the treatment of resectable (R) and borderline resectable (BR) head PDA. A single-institution retrospective review of R and BR patients undergoing pancreaticoduodenectomy after NAT with FOLFIRINOX or G-nP was performed. Comparative analysis was performed using inverse-probability-weighted (IPW) estimators. The end points of the study were overall survival (OS) and an 80% reduction in CA19-9 with NAT. In this study, 193 patients were analyzed, with 73 patients receiving FOLFIRINOX and 120 patients receiving G-nP. The median OS was 38.7 months for FOLFIRINOX versus 28.6 months for G-nP (p = 0.214). The patients who received FOLFIRINOX were younger and had fewer comorbidities, more BR disease, and larger tumors than those treated with G-nP (all p < 0.05). The two regimens were equally effective in achieving an 80% decline in CA19-9 (p = 0.8). The R0 resection rates were similar (80%), but FOLFIRINOX was associated with a reduction in pN1 disease (56% vs. 72%; p = 0.028). The receipt of adjuvant therapy was similar (74 vs. 75%; p = 0.79). In the Cox regression analysis with adjustment for baseline and treatment-related variables (FOLFIRINOX vs. G-nP, age, gender, computed tomography (CT) tumor size, BR vs. R, pre-NAT CA19-9), regimen type was not associated with a survival benefit. In the IPW analysis of 166 patients, however, the average treatment effect of FOLFIRINOX was to increase OS by 4.9 months compared with G-nP (p = 0.012). Both FOLFIRINOX and G-nP are viable options for neoadjuvant treatment of PDA. In this study, neoadjuvant FOLFIRINOX was associated with a 4.9-month improvement in survival compared with G-nP after adjustment for covariates.

Organ Preservation in Rectal Cancer After Chemoradiation: Should We Extend the Observation Period in Patients with a Clinical Near-Complete Response?

Abstract: To assess whether extending the observation period in patients with a near clinical complete response (near cCR) after chemoradiation (CRT) leads to an impaired oncological outcome. Patients who had a clinical complete response (cCR) 8–10 weeks after CRT restaging with magnetic resonance imaging and endoscopy were offered a watch-and-wait strategy (WW therefore, it seems logical to extend the observation period rather than to proceed to surgery. Although there is a non-significant increase in local regrowth rate in these patients, it does not seem to impact the oncological outcome.

Neoadjuvant Chemotherapy Use in Breast Cancer is Greatest in Excellent Responders: Triple-Negative and HER2+ Subtypes.

Abstract: While breast cancer has historically been treated with surgery followed by adjuvant chemotherapy (AC) and radiation when indicated, neoadjuvant chemotherapy (NAC) use is thought to be increasing; however, the trends of its use in various biological subtypes have not been evaluated. We sought to evaluate the trend of NAC use over time by biological subtype. We identified all patients with invasive breast cancer who underwent curative intent surgery and were treated with chemotherapy from 2010 to 2015 from the National Cancer Database. An unadjusted analysis of trends in proportions over time was performed using Cochran–Armitage trend tests stratified by hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status. Of 315,264 patients who received chemotherapy, 251,726 (79.8%) received AC and 63,538 (20.2%) received NAC. From 2010 to 2015, significant increases in NAC use were seen in all biologic subtypes (all p < 0.001). The highest proportions and greatest increases in proportions of NAC were seen among triple-negative breast cancers (TNBC; 19.5–33.7%) and HER2+ (HR−/HER2+, 21.5–39.8%; HR+/HER2+, 17.0–33.7%) tumors. HR+/HER2− tumors also had a statistically significant increase in use but this increase was less dramatic (13.0–16.8%) and NAC use in recent years was significantly lower than in other subtypes (p < 0.001). Within patients receiving chemotherapy for breast cancer, its receipt in the neoadjuvant setting has been increasing among all biologic subtypes. The highest use of NAC is in TNBC and HER2+ disease, with use in these subgroups being twice as frequent as in HR+/HER2− disease.

Long-Term Outcomes of Gastric Cancer Patients with Preoperative Sarcopenia.

Abstract: There are few reports of long-term outcomes of gastric cancer patients with sarcopenia. The purpose of this study was to assess the impact of sarcopenia on long-term outcomes in gastric cancer patients who underwent curative resection. A total of 951 patients aged 65 years or older who underwent R0 resection for gastric cancer were investigated. Sarcopenia was defined as a decreased arm muscle area < 38.05 cm2 in men and < 27.87 cm2 in women combined with a decline in grip strength to < 26 kgf in men and < 18 kgf in women. Of 951 patients, 111 (11.7%) were diagnosed with sarcopenia. Reduced surgery was performed significantly more frequently in patients with sarcopenia (p = 0.006). The incidence of eligible patients who received adjuvant chemotherapy was significantly lower in patients with sarcopenia than in those without sarcopenia (p = 0.030). Mortality due to gastric cancer and aging-associated multiple organ failure rates without obvious diseases were higher in patients with sarcopenia (p = 0.036 and p < 0.001, respectively). Overall survival (OS) and cause-specific survival (CSS) were significantly worse in patients with sarcopenia (p < 0.001 and p = 0.005, respectively). Multivariate analysis for OS and CSS revealed that sarcopenia was an independent prognostic factor in gastric cancer patients (p < 0.001 and p = 0.043, respectively). Sarcopenia is related to poor survival in gastric cancer patients and appears to be a significant negative prognostic factor in patients with gastric cancer who underwent curative resection.

Recurrence of Pancreatic Neuroendocrine Tumors and Survival Predicted by Ki67

Abstract: Despite evidence of different malignant potentials, postoperative follow-up assessment is similar for G1 and G2 pancreatic neuroendocrine tumors (panNETs) and adjuvant treatment currently is not indicated. This study investigated the role of Ki67 with regard to recurrence and survival after curative resection of panNET. Patients with resected non-functioning panNET diagnosed between 1992 and 2016 from three institutions were retrospectively analyzed. Patients who had G1 or G2 tumor without distant metastases or hereditary syndromes were included in the study. The patients were re-categorized into Ki67 0–5 and Ki67 6–20%. Cox regression analysis with log-rank testing for recurrence and survival was performed. The study enrolled 241 patients (86%) with Ki67 0–5% and 39 patients (14%) with Ki67 6–20%. Recurrence was seen in 34 patients (14%) with Ki67 0–5% after a median period of 34 months and in 16 patients (41%) with Ki67 6–20% after a median period of 16 months (p < 0.001). The 5-year recurrence-free and 10-year disease-specific survival periods were respectively 90 and 91% for Ki67 0–5% and respectively 55 and 26% for Ki67 6–20% (p < 0.001). The overall survival period after recurrence was 44.9 months, which was comparable between the two groups (p = 0.283). In addition to a Ki67 rate higher than 5%, tumor larger than 4 cm and lymph node metastases were independently associated with recurrence. Patients at high risk for recurrence after curative resection of G1 or G2 panNET can be identified by a Ki67 rate higher than 5%. These patients should be more closely monitored postoperatively to detect recurrence early and might benefit from adjuvant treatment. A clear postoperative follow-up regimen is proposed.

Neoadjuvant Therapy Versus Upfront Resection for Pancreatic Cancer: The Actual Spectrum and Clinical Burden of Postoperative Complications

Abstract: Neoadjuvant therapy (NAT) is used for borderline-resectable or locally advanced pancreatic cancer (PDAC) and exhibits promising results in terms of pathological outcomes. However, little is known about its effect on surgical complications. We analyzed 445 pancreatic resections for PDAC from 2014 to 2016 at The Pancreas Institute, Verona University Hospital. The Modified Accordion Severity Grading System and average complication burden (ACB) were used to compare patients treated with NAT with patients who underwent upfront surgery (UFS). Of 305 pancreaticoduodenectomies (PD), patients treated with NAT (n = 99) had less pancreatic fistula (POPF, 9.1% vs. 15.6%, p = 0.05) without grade C cases, but grade B ACB was increased (0.28 for NAT vs. 0.24 for UFS, p = 0.05). The postpancreatectomy hemorrhage (PPH) rate was lower in the NAT group (9.1% vs. 14.6%, p = 0.02), but ACB grades B (0.37 for NAT vs. 0.26 for UFS, p = 0.03) and C (0.43 for NAT vs. 0.29 for UFS, p = 0.05) were increased. Delayed gastric emptying (DGE) was increased in NAT cases (15.2% vs. 8.3%, p = 0.04), with higher grade C ACB (0.43 for NAT vs. 0.29 for UFS, p = 0.03). Of 94 distal pancreatectomies (DP), NAT patients (n = 26) developed more grade C POPF (11.5% vs. 1.5%, p = 0.04) and DGE (11.5% vs. 2.9%, p = 0.01) without differences in ACB. Patients undergoing PD for PDAC after NAT exhibited reduced incidence of POPF and PPH but increased incidence of DGE compared with patients treated with UFS. Among patients developing postoperative complications after PD, those receiving NAT were associated with increased clinical burden.

Prognostic Significance of Preoperative Controlling Nutritional Status (CONUT) Score in Patients Undergoing Hepatic Resection for Hepatocellular Carcinoma: A Multi-institutional Study.

Abstract: The Controlling Nutritional Status (CONUT) score is an objective tool that is widely used to assess the nutritional status in patients, including those with cancer. The relationship between the CONUT score and prognosis in patients who have undergone hepatic resection has not been evaluated in a multi-institutional study. Data were retrospectively collected for 2461 consecutive patients with hepatocellular carcinoma (HCC) who had undergone hepatic resection with curative intent at 13 institutions between January 2004 and December 2015. Patients were assigned to two groups: preoperative CONUT scores ≤ 3 (low CONUT score) and ≥ 4 (high CONUT score). Clinicopathological characteristics, surgical outcomes, and long-term survival were compared using propensity score matching analysis. Of the 2461 patients, 540 (21.9%) had high (≥ 4) and 1921 (78.1%) had low (≤ 3) preoperative CONUT scores. Overall, a high CONUT score was significantly associated with older age, female sex, low body mass index, low serum albumin, high serum total bilirubin, low lymphocyte count, low serum cholesterol, shorter prothrombin time, higher indocyanine green retention test at 15 min, Child–Pugh B (vs. A), liver cirrhosis, minor resection, shorter operation time, massive blood loss, blood transfusion, and postoperative complications. After propensity score matching, a higher CONUT score was significantly associated with poor overall survival (OS) and recurrence-free survival (RFS) using multivariate analysis. This retrospective, multi-institutional analysis showed that, in patients who undergo curative hepatectomy for HCC, the preoperative CONUT score is predictive of worse OS and RFS, even after propensity score matching analysis.

Circulating Tumor Cells Predict Occult Metastatic Disease and Prognosis in Pancreatic Cancer.

Abstract: Occult metastatic tumors, below imaging thresholds, are a limitation of staging systems that rely on cross-sectional imaging alone and are a cause of the routine understaging of pancreatic ductal adenocarcinomas (PDACs). We investigated circulating tumor cells (CTCs) as a preoperative predictor of occult metastatic disease and as a prognostic biomarker for PDAC patients. A total of 126 patients (100 with cancer, 26 with benign disease) were enrolled in our study and CTCs were identified and enumerated from 4 mL of venous blood using the microfluidic NanoVelcro assay. CTC enumeration was correlated with clinicopathologic variables and outcomes following both surgical and systemic therapies. CTCs were identified in 78% of PDAC patients and CTC counts correlated with increasing stage (ρ = 0.42, p < 0.001). Of the 53 patients taken for potentially curative surgery, 13 (24.5%) had occult metastatic disease intraoperatively. Patients with occult disease had significantly more CTCs than patients with local disease only (median 7 vs. 1 CTC, p < 0.0001). At a cut-off of three or more CTCs/4 mL, CTCs correctly identified patients with occult metastatic disease preoperatively (area under the receiver operating characteristic curve 0.82, 95% confidence interval (CI) 0.76–0.98, p < 0.0001). CTCs were a univariate predictor of recurrence-free survival following surgery [hazard ratio (HR) 2.36, 95% CI 1.17–4.78, p = 0.017], as well as an independent predictor of overall survival on multivariate analysis (HR 1.38, 95% CI 1.01–1.88, p = 0.040). CTCs show promise as a prognostic biomarker for PDAC patients at all stages of disease being treated both medically and surgically. Furthermore, CTCs demonstrate potential as a preoperative biomarker for identifying patients at high risk of occult metastatic disease.

Tumor-Infiltrating NETs Predict Postsurgical Survival in Patients with Pancreatic Ductal Adenocarcinoma

Abstract: Tumor-infiltrating neutrophils (TINs) indicate poor prognosis for patients with pancreatic ductal adenocarcinoma (PDAC). Activated neutrophils can generate neutrophil extracellular traps (NETs). Little is known about the presence and prognostic significance of tumor-infiltrating NETs in PDAC. This study enrolled 317 patients, in two independent sets (training and validation), who underwent curative pancreatectomy for PDAC in Shanghai Cancer Center. TINs and NETs were identified by immunohistochemical staining for CD15 and citrullinated histone H3, respectively. The relationship between clinicopathological features and outcomes was analyzed. Accuracy of prognostic prediction models was evaluated using concordance index (C-index) and Akaike information criterion (AIC). NETs were associated with OS (both, P < 0.001) and RFS (both, P < 0.001) in the training and validation sets. Tumor-infiltrating NETs predicted poor postsurgical survival of patients with PDAC. Moreover, multivariate analysis identified NETs and AJCC TNM stage as two independent prognostic factors for OS and RFS. Combination of NETs with the 8th edition TNM staging system (C-index, 0.6994 and 0.6669, respectively; AIC, 1067 and 1126, respectively) generated a novel model that improved the predictive accuracy for survival in both sets (C-index, 0.7254 and 0.7117, respectively; AIC, 1047 and 1102, respectively). The model combining presence of NETs with the 7th edition AJCC TNM staging system also had improved predictive accuracy. NETs were an independent prognostic factor in PDAC and incorporation of NETs along with the standard TNM stating system refined risk-stratification and predicted survival in PDAC with improved accuracy.

The Impact of Primary Tumor Location on Long-Term Survival in Patients Undergoing Hepatic Resection for Metastatic Colon Cancer.

Abstract: The impact of primary tumor location on overall survival (OS), recurrence-free survival (RFS), and long-term outcomes has not been well established in patients undergoing potentially curative resection of colorectal liver metastases (CRLM). A single-institution database was queried for initial resections for CRLM 1992–2004. Primary tumor location determined by chart review (right = cecum to transverse; left = splenic flexure to sigmoid). Rectal cancer (distal 16 cm), multiple primaries, and unknown location were excluded. Kaplan–Meier and Cox regression methods were used. Cure was defined as actual 10-year survival with either no recurrence or resected recurrence with at least 3 years of disease-free follow-up. A total of 907 patients were included with a median follow-up of 11 years; 578 patients (64%) had left-sided and 329 (36%) right-sided primaries. Median OS for patients with a left-sided primary was 5.2 years (95% confidence interval [CI] 4.6–6.0) versus 3.6 years (95% CI 3.2–4.2) for right-sided (p = 0.004). On multivariable analysis, the hazard ratio for right-sided tumors was 1.22 (95% CI 1.02–1.45, p = 0.028) after adjusting for common clinicopathologic factors. Median RFS was marginally different stratified by primary location (1.3 vs. 1.7 years; p = 0.065). On multivariable analysis, location of primary was not significantly associated with RFS (p = 0.105). Observed cure rates were 22% for left-sided and 20% for right-sided tumors. Among patients undergoing resection of CRLM, left-sided primary tumors were associated with improved median OS. However, long-term survival and recurrence-free survival were not significantly different stratified by primary location. Patients with left-sided primary tumors displayed a prolonged clinical course suggestive of more indolent biology.