Peritoneal metastases from primary appendiceal and colorectal carcinomas demonstrate distinct molecular identities on comprehensive tumor analysis.

BACKGROUND AND OBJECTIVES: Published data comparing peritoneal metastases from appendiceal cancers (pAC) and colorectal cancers (pCRC) remain sparse. We compared pAC and pCRC using comprehensive tumor profiling (CTP). METHODS: CTP was performed, including next-generation sequencing and analysis of copy number variation (CNV), microsatellite instability (MSI) and tumor mutational burden (TMB). RESULTS: One hundred thirty-six pAC and 348 pCRC samples underwent CTP. The cohorts' age and gender were similar. pCRC demonstrated increased pathogenic variants (PATHs) in APC (48% vs. 3%, p < 0.01), ARID1A (12% vs. 2%, p < 0.01), BRAF (12% vs. 2%, p < 0.01), FBXW7 (7% vs. 2%, p < 0.01), KRAS (52% vs. 41%, p < 0.05), PIK3CA (15% vs. 2%, p < 0.01), and TP53 (53% vs. 23%, p < 0.01), and decreased PATHs in GNAS (8% vs. 31%, p < 0.01). There was no difference in CNV, fusion rate, or MSI. Median TMB was higher in pCRC (5.8 vs. 5.0 mutations per megabase, p = 0.0007). Rates of TMB-high tumors were similar (pAC 2.1% vs. pCRC 9.0%, p = 0.1957). pCRC had significantly more TMB-high tumors at lower thresholds. CONCLUSIONS: Despite a reduced overall TMB, pAC demonstrated mutations distinct from those seen in pCRC. These may serve as discrete biomarkers for future study.

Lymph Node Metastases in Gastrointestinal Stromal Tumors: an Uncommon Event.

BACKGROUND: Lymph node (LN) metastases are uncommon among gastrointestinal stromal tumors (GISTs), and their presence has not been utilized in disease prognostication. This study was designed to examine factors associated with GIST nodal metastases and their impact on survival. PATIENTS AND METHODS: Patients undergoing surgical resection of GIST with nodal evaluation were selected from the National Cancer Database. Logistic regression was utilized to evaluate factors associated with LN metastases. Survival was assessed for patients with and without nodal involvement and Cox regression was used to evaluate the impact of LN metastases while adjusting for other prognostic factors. RESULTS: Out of 5018 patients, 301 (6.0%) had LN involvement. Nodal metastases occurred most frequently among tumors of the stomach (49.5%), followed by the small bowel (43.2%), colorectum (6.0%), and esophagus (1.3%). On multivariable analysis, male sex (OR 1.34), high mitotic rate (OR 2.10), tumor size (OR 1.02), and a primary tumor located in the small bowel (OR 1.36) were all significantly associated with nodal metastases. LN metastases were significantly associated with decreased overall survival (OS) for tumors arising in the small bowel (log-rank p < 0.01) and the colorectum (log-rank p < 0.01). Within a multivariable model adjusting for established prognostic factors, LN metastases remained independently associated with decreased survival (HR 1.60, p < 0.001). CONCLUSIONS: For GISTs, LN metastases occur more often in males and were associated with tumor size and mitotic activity. Nodal involvement is associated with decreased survival, independent of other well-established prognostic factors.

Visceral angiosarcoma: A nationwide analysis of treatment factors and outcomes.

BACKGROUND AND OBJECTIVES: Visceral angiosarcoma is rare and aggressive, accounting for 2% of soft tissue sarcomas. Using a national data set, we examine determinants of outcomes for patients presenting with this rare disease. METHODS: The 2004-2015 National Cancer Database was queried for patients with visceral angiosarcoma. Trends in treatment and outcomes were examined. Factors affecting overall survival (OS) were assessed with log-rank and Cox regression. RESULTS: Eight hundred and ninety-three patients with visceral angiosarcoma were identified (median age 65 years, male [63%], Charlson comorbidity index <1 [86%]). Tumor size was <5 cm in 20.7%, and 34.2% were moderate/high grade. Median OS was 3.8 months (95% CI: 3.4-4.4). By multivariate analysis, increased tumor grade and size, and liver/biliary origin demonstrated worse OS while surgery, radiation, and systemic chemotherapy demonstrated improved OS (all p < 0.001). Survival was similar between patients achieving R0 resection and those with R1/2 resection receiving chemotherapy by Kaplan-Meier analysis. CONCLUSIONS: Visceral angiosarcomas are rare tumors with poor outcomes. Liver/biliary origin, higher tumor grade, and larger tumor size demonstrate worse outcomes. While R0 resection remains the mainstay of treatment, patients with R1/R2 resection have improved survival with addition of chemotherapy. Consideration should be made for multimodal therapy in these patients.

Analysis of the Survival Impact of Postoperative Chemotherapy After Preoperative Chemotherapy and Resection for Gastric Cancer.

BACKGROUND: Perioperative chemotherapy is a standard-of-care treatment for patients with gastric cancer. However, the impact of the postoperative chemotherapy (postCTX) component on overall survival (OS) is not well defined. METHODS: The National Cancer Database (NCDB) 2006-2014 was queried for patients who received preoperative chemotherapy (preCTX) and resection for gastric cancer. Analysis was performed to identify factors influencing receipt of postCTX. The impact of postCTX on OS was evaluated in propensity-matched groups. RESULTS: Among 3449 patients who received preCTX and resection for gastric cancer, 1091 (31.6%) received postCTX. Independent predictors of receiving postCTX were diagnosis after 2010 (odds ratio [OR] 1.985), distal tumor location (OR 1.348), and 15 or more lymph nodes examined (OR 1.214). Predictors of not receiving postCTX were older age (OR 0.985), comorbidity score higher than 1 (OR 0.592), and black race (OR 0.791). After propensity-matching (1091 per group), the median OS was 56.8 months for those who did receive postCTX versus 52.5 months for those who did not (p = 0.131). Subset analysis according to tumor grade, lymphovascular invasion, number of lymph nodes evaluated, T and N class, and AJCC stage identified an improvement in OS for the patients with N1 disease who received postCTX compared with those who did not (79.6 vs 41.3 months; p = 0.025). However, no other subgroup had a significant survival benefit. CONCLUSIONS: Additional postCTX was administered to a minority of patients who received preCTX and gastrectomy for gastric cancer, and its influence on OS appeared to be limited. Future trials should aim to define patients who will benefit from postCTX.

Implications of Conversion during Attempted Minimally Invasive Adrenalectomy for Adrenocortical Carcinoma.

BACKGROUND: Although advocated by some, minimally invasive adrenalectomy (MIA) for adrenocortical carcinoma (ACC) is controversial. Moreover, the oncologic implications for patients requiring conversion to an open procedure during attempted MIA for ACC are not extensively reported. PATIENTS AND METHODS: The National Cancer Database was queried for patients undergoing resection for ACC. Overall survival (OS) for patients undergoing successful MIA was compared with those requiring conversion, and additionally evaluated with a multivariable Cox regression analysis including other factors associated with OS. After propensity matching, those experiencing conversion were further compared with patients who underwent planned open resection. RESULTS: Among 196 patients undergoing attempted MIA for ACC, 38 (19.4%) required conversion. Independent of 90-day postoperative mortality, conversion was associated with significantly reduced OS compared with successful MIA (median 27.9 months versus not reached, p = 0.002). Even for tumors confined to the adrenal, conversion was associated with worse median OS compared with successful MIA (median 34.2 months versus not reached, p = 0.003). After propensity matching for clinicopathologic covariates to establish well-balanced cohorts (N = 38 per group), patients requiring conversion during MIA had significantly worse OS than those having planned open resection (27.9 months versus 50.5 months, p = 0.020). On multivariable analysis for predictors of OS, conversion during MIA (HR 2.32, p = 0.003) was independently associated with mortality. CONCLUSIONS: ACC is a rare tumor for which adequate oncologic resection is the only chance for cure. Given the relatively high rate of conversion and its associated inferior survival, open resection should be considered standard of care for known or suspected ACC.

Critical analysis of lymph node examination in patients undergoing curative-intent resection for adrenocortical carcinoma.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare tumor and the role of lymph node dissection remains ill-defined. This study evaluates the effect of nodal examination on prognosis and survival in patients undergoing curative-intent resection of ACC. METHODS: The National Cancer Database (2004-2015) was queried for patients undergoing margin-negative resection for ACC. Patients with distant metastases, neoadjuvant therapy, multivisceral resection and T4 tumors were excluded. RESULTS: Among 897 patients, 147 (16.4%) had lymph nodes examined. Factors associated with lymph node examination included increasing tumor size (P < .001), extra-adrenal extension (P < .001), open operation (P < .001), and resection at an academic facility (P = .003). Lymph node metastasis was significantly associated with extra-adrenal tumor extension (P = .04). Lymph node harvest, regardless of the number of nodes examined, was not associated with a survival benefit. Median overall survival was incrementally worse with increasing number of positive lymph nodes (88.2 months for N0, 34.9 months for 1-3 positive nodes, and 15.6 months for ≥4 positive nodes, P < .001). CONCLUSIONS: Lymph node harvest and lymph node metastasis were associated with more advanced tumors. Although nodal harvest did not offer a survival advantage, stratifying the nodal staging classification may provide important prognostic information.

The impact of race and socioeconomic status on the presentation, management and outcomes for gastric cancer patients: Analysis from a metropolitan area in the southeast United States.

BACKGROUND: Socioeconomic disparities in gastric cancer have been associated with differences in care and inferior outcomes. We evaluated the presentation, treatment, and survival for patients with gastric cancer (GC) in a metropolitan setting with a large African American population. METHODS: Retrospective cohort analysis of patients with GC (2003-2018) across a multi-hospital system was performed. Associations between socioeconomic and clinicopathologic data with the presentation, treatment, and survival were examined. RESULTS: Of 359 patients, 255 (71%) were African American and 104 (29%) Caucasian. African Americans were more likely to present at a younger age (64.0 vs 72.5, P < .001), have state-sponsored or no insurance (19.7% vs 6.9%, P = .02), reside within the lowest 2 quintiles for median income (67.4% vs 32.7%, P < .001), and have higher rates of Helicobacter pylori (14.9% vs 4.8%, P = .02). Receipt of multi-modality therapy was not impacted by race or insurance status. On multivariable analysis, only AJCC T class (HR 1.68) and node positivity (HR 2.43) remained significant predictors of disease-specific survival. CONCLUSION: Despite socioeconomic disparities, African Americans, and Caucasians with GC had similar treatment and outcomes. African Americans presented at a younger age with higher rates of H. pylori positivity, warranting further investigation into differences in risk factors and tumor biology.

Comprehensive tumor profiling reveals unique molecular differences between peritoneal metastases and primary colorectal adenocarcinoma.

BACKGROUND AND OBJECTIVES: Peritoneal metastases (PM) from primary colorectal cancer (pCRC) are associated with poor outcomes; however, molecular differences are not well defined. METHODS: We compared unpaired tumor profiles of patients with pCRC and PM from Caris Life Sciences. Testing included next-generation sequencing of 592 genes, microsatellite instability (MSI) and tumor mutational burden (TMB). Mutations were test-defined as pathogenic (PATH). RESULTS: Six hundred seventeen pCRC and 348 PM patients had similar gender (55% male) and age (median 59). PATHs were similar between PM and pCRC in KRAS, BRAF, SMAD2, SMAD4, and PTEN. pCRC PATHs were increased in APC (76% vs 48%, P < .01), ARID1A (29% vs 12%, P < .05), TP53 (72% vs 53%, P < .01), PIK3CA (22% vs 15%, P < .05), and FBXW7 (13% vs 7%, P < .01) compared with PM. Mucinous PM had more PATHs in GNAS (19% vs 8%, P = .032) while nonmucinous PM had more PATHs in BRAF (13% vs 8%, P = .027). Right-sided PM had decreased PATHs in APC (39% vs 68%, P < .0001), ARID1A (7% vs 38%, P < .004), and TP53 (48% vs 65%, P = .033) while there were no difference for left-sided PM. Nine percent of pCRC and 6% of PM were MSI-high (P = NS). There was no difference in TMB-high, TMB-intermediate, or TMB-low between PM and pCRC. CONCLUSIONS: PM have similar rates of KRAS mutation with increased PATHs in GNAS (mucinous) and BRAF (nonmucinous) compared to pCRC. No differences in MSI or TMB were identified between PM and pCRC tumors. These findings inform future study into the molecular profile of PM.

A Population-Based Study of the Effects of a Regional Guideline for Completion Axillary Lymph Node Dissection on Axillary Surgery in Patients with Breast Cancer.

INTRODUCTION: Evidence from the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial suggests completion axillary lymph node dissection (cALND) after positive sentinel lymph node biopsy (+SLNB) does not improve outcomes in select patients, leading to practice variation. A multidisciplinary group of surgeons, oncologists, and pathologists developed a regional guideline for cALND which was disseminated in August 2012. We assessed the impact of Z0011 and the regional guideline on cALND rates. METHODS: Consecutive invasive breast cancer cases undergoing SLNB were reviewed at 12 hospitals. Patient, tumor, and process measures were collected for three time periods: TP1, before publication of Z0011 (May 2009-August 2010); TP2, after publication of Z0011 (March 2011-June 2012); and TP3, after guideline dissemination (January 2013-April 2014). Cases were categorized by whether they met the guideline criteria for cALND (i.e. ≤50 years, mastectomy, T3 tumor, three or more positive sentinel lymph nodes [SLNs]) or not (e.g. age > 50 years, breast-conserving surgery, T1/T2 tumor, and one to two positive SLNs). RESULTS: The SLNB rate increased from 56 % (n = 620), to 70 % (n = 774), to 78 % (n = 844) in TP1, TP2, and TP3, respectively. Among cases not recommended for cALND using the guideline criteria, cALND rates decreased significantly over time (TP1, 71 %; TP2, 43 %; TP3, 17 %) [p < 0.001]. The cALND rate also decreased over time among cases recommended to have cALND using the guideline criteria (TP1, 92 %; TP2, 69 %; TP3, 58 %) [p < 0.001]. Based on multivariable analysis, age and nodal factors appeared to be significant factors for cALND decision making. CONCLUSION: Publication of ACOSOG Z0011 and regional guideline dissemination were associated with a marked decrease in cALND after +SLNB, even among several cases in which the guideline recommended cALND.

A population-based comparison of 30-day readmission after surgery for colon and rectal cancer: How are they different?

BACKGROUND: An implicit assumption in the analysis of colorectal readmission is that colon and rectal cancer patients are similar enough to analyze together. However, no studies have examined this assumption and whether substantial differences exist between colon and rectal cancer patients. METHODS: This was a retrospective analysis of the differences in predictors, diagnoses, and costs of readmission between colon and rectal cancer cohorts for 30-day readmission. This study included all patients aged >18 who received an elective colectomy or low anterior resection for colorectal cancer from April 2008 until March 2012 in the province of Ontario. RESULTS: Overall, 13,571 patients were identified and the readmission rates significantly differed between rectal and colon cancer patients (7.1% colon and 10.7% rectal P = 0.001). Diabetes, age, and discharge to long term care were significantly different among colon and rectal patients in the prediction of readmission. Readmission for renal and stoma causes was more prominent in the rectal cohort. The adjusted cost difference for readmission did not significantly differ between rectal and colon cancer $178 ($1,924-1,568 P = 0.84) CONCLUSION: Several important differences in predictors and diagnoses exist between the two cohorts. Conversely, the costs associated with readmission were homogenous between rectal and colon cancer patients. J. Surg. Oncol. 2016;114:354-360. © 2016 Wiley Periodicals, Inc.

Impact of adjuvant therapies following surgery for anal melanoma.

BACKGROUND: Anal melanoma is rare. Surgery is standard of care for non-metastatic disease. There are limited data supporting adjuvant therapy. We sought to examine the impact of adjuvant radiation, chemotherapy and immunotherapy on survival. METHODS: The National Cancer Database was queried. Factors associated with overall survival were examined by Kaplan-Meier and Cox proportional hazards analyses. Patients were grouped by treatment regimen. RESULTS: 450 patients had complete treatment data: surgery alone (63.8%), surgery + radiation (14.9%), surgery + chemotherapy (7.6%), surgery + immunotherapy (9.6%) and non-surgical treatment (4.2%). Median survival was 27.2 months. Node-positive patients had worse survival than node-negative (22.4 vs. 36.8 months; p = 0.0002). Non-surgical treatment yielded worse survival than any surgery-inclusive regimen (10.4 vs. 27.8 months; p = 0.0002). No adjuvant modality conferred a survival advantage. By multivariate analysis, increasing age (HR/1 year = 1.02, p = 0.012) and node positivity (HR = 2.10, p = 0.0002) negatively impacted survival. CONCLUSION: Adjuvant therapy for non-metastatic anal melanoma does not appear to influence survival.

Tumor Location in the Pancreatic Tail Is Associated with Decreased Likelihood of Receiving Chemotherapy for Pancreatic Adenocarcinoma.

BACKGROUND: Chemotherapy (CTX) is associated with improved survival for patients undergoing resection for pancreatic ductal adenocarcinoma (PDAC). The current study evaluated the influence of tumor location on receipt of CTX. METHODS: The NCDB (2006-2017) was queried to identify patients with clinical stage I-III PDAC. Predictors of receipt of CTX, sequencing of CTX, and overall survival (OS) were analyzed. RESULTS: Among 14,557 patients who underwent resection for PDAC 3,453 (24%) did not receive CTX. On multivariable analysis, patients with tail tumors were 15% less likely to receive CTX (OR 0.85, 95% CI 0.747-0.968) and 58% less likely to receive neoadjuvant CTX (OR 0.42, 95% CI 0.351-0.509) relative to patients with head/neck tumors. For patients with body tumors, there was no difference in rates of administration or sequence of CTX. For patients with resected tail tumors, median OS was 29.9 vs 18.9 months (p < 0.001) between those who did and did not receive CTX. For patients with tail tumors, independent predictors of not receiving CTX, regardless of sequence, were increasing age (OR 0.95, 95% CI 0.935-0.965), increasing post-op length of stay (OR 0.95, 95% CI 0.932-0.968), and 30-day post-op readmission (OR 0.46, 95% CI 0.315-0.670). CONCLUSIONS: In patients with clinical stage I-III PDAC, tumor location within the tail was independently associated with not receiving CTX. Given the marked improvement in OS when CTX is administered, strategies aimed at increasing the number of these patients who receive CTX are necessary.

The Association of Race With Adequate Lymph Node Evaluation for Gastric Cancer.

BACKGROUND: National studies have reported racial and socioeconomic disparities in gastric cancer (GC) care. The current study evaluated adequate lymph node (LN) assessment (≥16 LNs) during resection for GC within a healthcare system servicing a socioeconomically disparate, mostly non-White population in the Southeast United States. METHODS: A retrospective cohort study of patients undergoing resection for GC between 2003-2019 was performed. Factors associated with adequate LN assessment including patient and tumor characteristics were analyzed. RESULTS: Among 202 patients, adequate LN assessment was performed in 97 (48%) patients. On univariable analysis, younger age, non-White race, lower Charlson Comorbidity Index (CCI), Medicaid or no insurance, D1+/D2 lymphadenectomy, clinical evidence of regional LN metastases, total gastrectomy, and receipt of neoadjuvant therapy were associated with adequate LN assessment. On multivariable analysis, non-White race (OR 2.79, 95% CI 1.38-5.65), CCI <4 (OR 2.14, 95% CI 1.15-3.96), and D1+/D2 lymphadenectomy (OR 3.63, 95% CI 1.96-6.74) were the only factors independently associated with adequate LN evaluation. CONCLUSIONS: In the current study, non-White race, independent of socioeconomics, was significantly associated with adequate LN assessment. Future work is necessary to improve standardization and achieve higher rates of adequate LN assessment for all patients during resection for GC.

Effects of a regional guideline for completion axillary lymph node dissection in women with breast cancer to reduce variation in surgical practice: A qualitative study of physicians' views.

BACKGROUND: Recently the impact of completion axillary lymph node dissection (cALND) after positive sentinel lymph node biopsy on significant outcomes has been questioned, leading to variation in surgical practice. To address this variation, a multidisciplinary working group created a regional guideline for cALND. We explored the views and experiences of surgeons, medical oncologists (MOs), radiation oncologists (ROs) in a qualitative study that examined guideline implementation in practice. METHODS: The Pathman framework (awareness, agreement, adoption and adherence) informed the interview guide design and analysis. Semi-structured interviews were conducted with MOs, ROs and surgeons and transcribed. Transcripts were coded independently by 2 members of the study team and analyzed. Disagreements were resolved through consensus. RESULTS: Twenty-eight physicians (5 MO; 6RO; 17S) of 41 (68% of those approached) were interviewed. Ten of 11 (91%) hospital sites (54% community; 46% academic) and all 4 cancer clinics within the region were represented. Twenty-seven physicians (96%) were aware of the guideline, with all physicians reporting agreement and general adherence to the guideline. Most physicians indicated nodal factors, age and patient preference were key components of cALND decision-making. Physicians from all disciplines perceived that the guideline helped reduce variation in practice across the region. There were concerns that the guideline could be applied rigidly and not permit individual decision-making. CONCLUSIONS: Physicians identified breast cancer as an increasingly complex and multidisciplinary issue. Facilitators to guideline implementation included perceived flexibility and buy-in from all disciplines, while individual patient factors and controversial supporting evidence may hinder its implementation.