12.01 Maintaining Oncologic Integrity with Minimally Invasive Resection of Pediatric Embryonal Tumors

Posted on January 18, 2018

H. M. Phelps1, G. D. Ayers2, J. M. Ndolo3, H. L. Dietrich4, K. D. Watson5, M. A. Hilmes3, H. N. Lovvorn6  1Vanderbilt University Medical Center,School Of Medicine,Nashville, TN, USA 2Vanderbilt University Medical Center,Division Of Cancer Biostatistics,Nashville, TN, USA 3Vanderbilt University Medical Center,Pediatric Radiology,Nashville, TN, USA 4Vanderbilt University Medical Center,School Of Nursing,Nashville, TN, USA 5Vanderbilt University Medical Center,Pediatric Hematology/Oncology,Nashville, TN, USA 6Vanderbilt University Medical Center,Pediatric Surgery,Nashville, TN, USA

Introduction:  Embryonal tumors arise typically in infants and young children and are often massive at presentation. Treatment is multimodal, and while complete resection is a critical element, surgery can interrupt therapy. When appropriate, minimally invasive surgery (MIS) offers a potential means to minimize treatment delays. However, the use of MIS to resect embryonal tumors remains controversial regarding the oncologic integrity of this approach.

Methods:  A retrospective review of embryonal tumors treated at a single institution over a 15-year period was conducted to: 1) assess candidacy of embryonal tumors for MIS, and 2) evaluate outcomes for patients undergoing MIS versus open resection. Query of the institution’s cancer registry identified pediatric patients treated for intracavitary embryonal tumors from 2002 to 2017. To assess amenability for MIS, tumor volume (TV) and image-defined risk factors (IDRF, neuroblastic tumors only) were measured radiographically at time of diagnosis and immediately before resection. Stage, Children’s Oncology Group risk stratification, procedure-related details, delay to next dose of chemotherapy, relapse-free survival (RFS), and overall survival (OS) were evaluated. Wilcoxon, Pearson chi-square, and log-rank tests were performed.

Results: A total of 201 patients were treated for neuroblastic tumors (NBL, n=101), Wilms tumor (WT, n=66), hepatoblastoma (n=23), rhabdomyosarcoma (RMS, n=10), and pancreatoblastoma (n=1). Among these patients, 175 tumors were resected either open (n=151, 86%) or by MIS (n=24, 14%; 20 NBL, 3 WT, 1 RMS). Of the 174 with complete data at time of analysis, the median TV at resection was 84.8 ml [IQR 20.4, 372.5]. For NBL cases, a significantly greater proportion of MIS resections (n=17, 94%) had no IDRF when compared to open resections (n=31, 48%; p<0.001). For the entire cohort, RFS at 5 years was 0.78 [CI 0.71–0.85] for open resection versus 0.90 [CI 0.78–1.00] for MIS (p=0.463). OS at 5 years was 0.87 [CI 0.81–0.93] for open resection versus 1.00 [CI 1.00–1.00] for MIS (p=0.294). The largest TV resected via MIS was 93.4 ml, so subgroup comparisons were adjusted for TV<100 ml. No significant difference in margin status between open resection (n=68) and MIS (n=23) was observed, and MIS was associated with significantly less blood loss, shorter hospital stays, shorter operating time, and quicker return to the next chemotherapy cycle (Table 1).

Conclusion: For appropriately selected patients, MIS resection of pediatric embryonal tumors, particularly NBL, maintains an acceptable oncologic integrity while minimizing treatment delays, but large tumor volume, vascular encasement, and small patient size limit its broader applicability.

12.02 Does Muscle Biopsy change the treatment of Pediatric muscular disease?

Posted on January 18, 2018

N. Le1, J. Sujka1, J. Sobrino1, L. A. Benedict1, R. Rentea1, H. Alemayehu1, T. Oyetunji1, S. St. Peter1  1Children’s Mercy Hospital- University Of Missouri Kansas City,Kansas City, MO, USA

Introduction:
Muscle disease presentation is highly variable. Tissue biopsy is performed to confirm diagnosis and to guide therapy however it is unclear if this changes management. The purpose of our study was to determine if muscle biopsy changed patient diagnosis or treatment, which patients were most likely to benefit from muscle biopsy, and the complications resulting from muscle biopsy.

Methods:

With IRB approval a retrospective chart review of all patients less than 18 years old undergoing muscle biopsy between Jan 2010 and Aug 2016 was performed.  Demographics, patient presentation, change in treatment and diagnosis, hospital course, and follow up were evaluated. T-test and descriptive statistical analysis was performed; all means reported with standard deviation.

Results:

A total of 90 patients underwent a muscle biopsy at our institution during the study period. Mean age at time of biopsy was 6.5 years (±5) with the most common site of biopsy was the vastus lateralis. Of these patients only 37% (n=34) had a definitive diagnosis by muscle biopsy, in the remaining patients 27% (n=25) were normal and 35% (n=31) were non diagnostic. Of all patients biopsied, 39% (n=35) had a change in their diagnosis with only 37% (n=34) having a change in their treatment course from the pathology result.

Among the 34 patients who had a change in their treatment, the most common diagnosis was Inflammatory muscle disease at 44% (n=15) followed by those with muscular dystrophy, 23% (n=8). In the 56 patients who did not have a change in treatment, the most common diagnosis was hypotonia at 30% (n=17) followed by those patients whose diagnosis remained undetermined at 25% (n=14). However, the third most common diagnosis that did not change treatment was inflammatory with 21% (n=12). Two of these patients had definitive diagnosis from their biopsy but the remaining 10 were previously suspected of, and being treated for, myositis.

Using the T-test we compared those who did or did not have a change in treatment based on their pathology. There was no statistically significant difference in the patient’s weight, age, operative duration, or length of follow up post operatively. One patient was found to have a complication from surgery, malignant hypothermia. No patients returned to the operating room secondary to operative complications. Mean length of follow up for all patients was 2.75 years (±2).

Conclusion:

Muscle biopsy could be considered to diagnose patients with symptoms consistent with inflammatory or dystrophic muscular disease though the likelihood of this altering the patient’s treatment course is less than 50%.

11.18 Pancreatic Neuroendocrine Tumor (PNET) Imaging Features are Predictive of Biology

Posted on January 18, 2018

A. Fang1, E. Tashakori1, C. Farinas1, M. Mederos1, A. McElhany1, S. Mohammed1, N. Villifane1, W. E. Fisher1, G. Van Buren1  1Baylor College Of Medicine,Michael E. DeBakey Department Of Surgery, The Elkins Pancreas Center,Houston, TX, USA

Introduction:
Pancreatic neuroendocrine tumors (PNETs) are a heterogeneous group of tumors with variable malignant potential. While most PNETs appear as solid, well-circumscribed, and enhancing masses on computed tomography (CT), their heterogeneous nature can lead to differences in their stereotypical appearance. Therefore, the objective of this study was to test the hypothesis that PNETs with atypical features on CT were associated with more aggressive pathologic features.

Methods:
Through our prospectively maintained Pancreas Surgery Registry, we retrospectively analyzed the radiologic and pathologic features of resected PNETs between January 2005 and December 2015. After independent verification, the CT characteristics such as size, morphology, and enhancement pattern were compared to their histopathologic findings using Chi square and Fisher’s exact tests. Multivariate logistic regression models were generated with backward selection method and a removal p value of 0.1. 

Results:
We analyzed 52 patients who underwent preoperative CT imaging and PNET resection. 29 lesions demonstrated abnormal imaging characteristics such as hypoenhancement (4), isoenhancement (1) calcifications (7), and cystic appearance (19). On univariate analysis, cystic appearance was significantly associated with lower grade and less lymphovascular invasion (p = 0.02, and 0.04, respectively). Bile duct dilation and lymphadenopathy were significantly associated with higher grade and stage, (p = 0.02 and 0.01, respectively). Tumor size significantly correlated with higher stage, positive margin, and lymphovascular invasion (p = 0.02, 0.03, and 0.02, respectively). On multivariate analysis, when controlling for lymphadenopathy, bile duct dilation, and image size, cystic lesions were a significant predictor of lower staging (p = 0.003, 0.01, and 0.01, respectively) and lower rates of lymphovascular invasion (p = 0.04). Hypoenhancment, isoenhancment, and calcifications did not correlate with aggressive pathologic findings.

Conclusion:

This cohort study demonstrated that PNETs with cystic appearance were less aggressive. Conversely, characteristics such as lymphadenopathy, bile duct dilation, and larger lesion size were predictors of aggressive pathologic characteristics. However, enhancement pattern and the presence of calcifications on CT were not associated with more aggressive features. 

11.19 Smoking and Next Generation Sequencing Mutation Signature in Melanoma

Posted on January 18, 2018

K. Loo1, I. Soliman1, M. Renzetti1, T. Li1, H. Wu1, B. Luo1, A. Olszanski1, S. Movva1, M. Lango1, N. Goel1, S. Reddy1, J. Farma1  1Fox Chase Cancer Center,Philadelphia, PA, USA

Introduction: The use of molecular profiling to characterize tumors is becoming increasingly utilized to guide and tailor therapies for personalized treatment in the setting of malignant melanoma. Furthermore, smoking has been identified as a largely preventable cause of cancer mortality. Yet it remains to be seen whether smoking has a causative or protective effect in the setting of malignant melanoma. Using Next Generation Sequencing (NGS), we investigated a panel of 50 targetable cancer-related gene mutations in melanoma tumors. The principle aim of this study was to investigate the correlations between previous history of smoking with genetic mutations among individual genes, as well as total mutation burden in patients with malignant melanoma.

Methods: A retrospective study was conducted to include both primary and recurrent malignant melanoma tumor samples. Utilizing a prospective database, we identified a cohort of patients whose tumor tissue samples underwent NGS sequencing analysis for somatic mutations of 50 cancer-related genes. Within this cohort, clinical and pathological data were also collected. A univariate analysis was conducted using Fisher’s exact and Wilcoxon tests to compare patients with previous history of smoking to never smokers to investigate differences in each cohort’s molecular profile.  

Results: A total of 173 patients with malignant melanoma whose tumor tissue specimens underwent NGS sequencing were analyzed in this study cohort. Median age at diagnosis was 65 (range 21-94) and 64% were male (n=111). The smoking cohort was divided into never smokers (n=72) versus current or former smokers (n=101). Of the 168 patients with staging data, 9% of patients were Stage I melanoma (n=15), 30% Stage II (n=50), 49% with Stage III (n=83), and 12%with Stage IV (n=20).

In the total cohort, 277 mutations were identified affecting 34 unique genes. No mutations were found in 12% of patients (n=20), while 47% of patients (n=82) had 1 mutation, 24% (n=41) had 2 mutations, 9% (n=16) had 3 mutations, and 8% (n=14) had 4 or more mutations. The most common mutations among patients with a history of smoking were BRAF v600E (27.7%, vs. 19.4% in never smokers) and CDKN2A (12.87%, vs. 9.72% in never smokers) genes. Conversely, the most common genes among never smokers were NRAS (34.72%, vs. 31.7% in smokers) and TP53 (22.22%, vs. 21.8% in smokers). The overall mutation burden in the never smoker cohort was 1.59 versus 1.60 in the current and former smoker cohort (p=0.94).

Conclusion: This study demonstrated no significant association of overall mutational burden or increased incidence of individual gene mutations to smoking status, additional studies are needed to identify the effect of smoking on melanoma tumor characteristics with a larger sample size. Further studies with additional tumor biomarkers are additionally warranted to discern the impact of smoking on malignant melanoma tumors. 

11.20 Postoperative Opioid Consumption in Cancer Patients after Curative-Intent Surgery

Posted on January 18, 2018

J. A. Balch1, J. S. Lee1,2, V. Parashar1,2, J. B. Miller3, S. M. Bremmer1,2, J. V. Vu1,2, L. A. Dossett1,2  1University Of Michigan,Department Of Surgery,Ann Arbor, MI, USA 2University Of Michigan,Center For Health Outcomes And Policy,Ann Arbor, MI, USA 3University Of Michigan,Center For Bioethics & Social Sciences In Medicine,Ann Arbor, MI, USA

Introduction:  

Multiple studies demonstrate that opioid prescriptions far exceed patient consumption after surgery. These excess opioids can be inappropriately used or diverted for nonmedical use, thereby contributing to the national epidemic of opioid-related morbidity and mortality. Cancer patients are at particular risk for chronic pain and opioid use, and have higher rates of persistent opioid use after curative-intent surgery. To more accurately assess the amount of opioid needed postoperatively in cancer patients, we systematically reviewed the literature to evaluate opioid consumption in cancer patients after curative-intent surgery.

Methods:

MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched to identify studies describing opioid consumption in cancer patients after curative-intent surgery. The primary outcome was the amount of opioid consumed within 24 hours after the operation concluded. Reported opioid amounts were converted to oral morphine equivalents (OME) for comparison. Three reviewers independently screened studies for inclusion, extracted data, and assessed study quality.

Results:

Of the 31 studies reviewed in full, sixteen eligible studies reported opioid consumption for five types of curative-intent procedures, including breast, gynecologic, colorectal, renal, and lung cancer. We used 24 hours as a time point as this number represents peak postoperative opioid consumption. The amount of opioid consumed in this time point varied widely across surgical disciplines, ranging from 4 OME for breast cancer to 208 OME for gynecologic cancer (Figure1). Within each discipline, the amount of opioids consumed also varied widely depending on the use of non-opioid analgesics, peripheral nerve blocks, and epidural analgesia. For example, for breast cancer, the study group with the lowest reported opioid consumption (4 OME; Albi-Feldzer 2013) used scheduled acetaminophen and ketoprofen. In contrast, the breast cancer study group with the highest opioid consumption (72 OME; Terkawi 2014) had no standardized protocol for non-opioid analgesics.

Conclusion:

In cancer patients undergoing curative-intent surgery, opioid consumption varies widely depending on the use of non-opioid analgesics, peripheral nerve blocks, and epidural analgesia. Standardized pain management protocols may reduce variation in opioid consumption and minimize excessive opioid prescribing.
 

11.16 Perioperative Chemoradiation Does Not Influence Incisional Hernia Formation After Cancer Resection

Posted on January 18, 2018

S. Kavalukas1, R. Baucom2, L. Huang1, S. Phillips1, C. Bailey1, R. Pierce1, M. Holzman1, K. Sharp1, B. Poulose1  1Vanderbilt University Medical Center,Department Of Surgery,Nashville, TN, USA 2Baylor University Medical Center,Dallas, TX, USA

Introduction:  The effect of adjuvant therapy on subsequent ventral incisional hernia (VIH) formation after cancer resection is unknown.  This study assessed the impact of adjuvant therapy on long term VIH formation after tumor resection for abdominal malignancy.

Methods:  Patients undergoing resection of abdominal malignancy were retrospectively identified and followed up to 2 years by computed tomography (CT) scan for VIH formation.  Those who received either chemotherapy and/or radiation 6 months before or after resection (adjuvant therapy, AT) were compared to patients without adjuvant therapy (no adjuvant therapy, NAT).  Cox proportional hazards (CPH) regression was used identify factors associated with VIH formation over time while adjusting for multiple confounding factors.

Results: 485 patients underwent abdominal cancer resections (AT n=105; NAT n=380). The median age was 58 yrs for the AT group and 61 for the NAT group. 40% of the AT group and 41% of the NAT group were female. The clinical cancer stage breakdown was statistically significant between the 2 groups (AT had more stage 4 and NAT had more stage 1 cancers). The proportion of patients free of VIH at 24 months was 46% in the AT group and 39% in the NAT group (Figure, p=0.62).  AT was not found to be associated with increased VIH compared to NAT in the CPH model (HR=0.817, 95% CI: (0.567, 1,177).

Conclusion: The rate of incisional hernia formation after resection for abdominal malignancy does not appear to be influenced by adjuvant chemo- or radiotherapy. Continued evaluation of risk factors and the role of hernia prevention is important to maintain quality of life for cancer survivors. 

 

11.17 The Emerging Role of Surgery in Melanoma Patients Treated with Immune Checkpoint Inhibitors (ICI)

Posted on January 18, 2018

C. Puza1, P. Mosca1, A. K. Salama2, H. Howard3, D. Agnese3, A. Terando3, D. G. Blazer1, R. Scheri1, G. Beasley1  1Duke University,Department Of Surgery,Durham, NC, USA 2Duke University,Division Of Medical Oncology,Durham, NC, USA 3Ohio State University,Division Of Surgical Oncology,Columbus, OH, USA

Introduction: The emergence of novel ICI has resulted in dramatic improvements in survival for patients with metastatic melanoma. Relative to traditional chemotherapy, the types of disease response patterns to ICI therapy can be more complex, including mixed responses and pseudoprogression.  Specifically, some lesions may regress while new lesions appear, or tumors may remain stable in size for long periods of time. As the role of surgery in these scenarios is continuing to evolve, the purpose of this study was to explore outcomes associated with surgery following ICI therapy. 

Methods:  A retrospective study was conducted at two centers and included patients with melanoma who underwent surgery following treatment with monotherapy or combination therapy with anti-PD-1 and/or anti CTLA-4 checkpoint blockade.  Data collected included: treatment regimen, toxicities, operative reports, pathology, and clinical plus radiographic follow-up.

Results: Of 17 identified patients, 7 patients had received anti-CTLA-4 therapy, 4 anti-PD-1 therapy, and 6 anti-CTLA-4 therapy plus anti-PD-1 therapy before surgery. Five patients were being treated in the adjuvant setting and developed new lesions while 12 patients were being treated for metastatic disease and underwent surgery for persistent disease on imaging.   Seventeen patients underwent 18 operations including: 4 small bowel resections, 2 splenectomies, 4 wide local excisions, 4 groin dissections, 1 craniectomy, 1 mesenteric mass resection, 1 axillary dissection, and 1 lung nodule resection.  There were no major reported complications from surgery.  Seventeen of 18 masses were confirmed to be persistent melanoma on surgical pathology while 1 was a desmoid tumor.  At median follow up of 10-months, 1 patient has died, 8 are alive with known disease, and 8 continue to have no further evidence of disease since the time of surgery. 

Conclusion: In this small group of patients receiving ICI therapy for melanoma, surgery was well tolerated. Surgery may benefit select patients with mixed responses to ICI therapy. Indications for surgery in this population warrant further exploration.  

 

11.14 RAS Mutation Confers Prognostic Significance in Patients Undergoing CRS-HIPEC for Colorectal Cancer

Posted on January 18, 2018

Z. Morgan1, A. Krepline1, M. Hembrook1, S. Tsai1, K. K. Christians1, H. Mogal1, T. C. Gamblin1, C. N. Clarke1  1Medical College Of Wisconsin,Division Of Surgical Oncology,Milwaukee, WI, USA

Introduction: Approximately 5% of patients with colorectal cancer (CRC) will present with peritoneal carcinomatosis (PC) with a mean overall survival (OS) of 6-months if left untreated. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is an aggressive surgical approach to treat peritoneal carcinomatosis (PC).  The role of this procedure in CRC continues to evolve.  There remains a significant need to further characterize the natural history of CRC carcinomatosis and identify prognostic factors to facilitate better risk stratification for prospective CRS-HIPEC patients. We performed a single institution study of CRC patients undergoing CRS-HIPEC with curative intent to identify prognostic factors associated with recurrence or overall survival.

Methods: Patients with CRC evaluated for CRS-HIPEC at the Regional Therapies Program at the Medical College of Wisconsin from 2010 -2017 were identified. Patients with non-CRC pathology, progression of disease precluding surgical intervention and/or HIPEC for palliation were excluded.  Patients who had CRS only or did not receive at least 60 minutes of HIPEC were excluded. Clinicopathologic data including age, sex, PCI score, completeness of cytoreduction, lymphovascular invasion, neutrophil-lymphocyte ratio, histology, microsatellite stability, BRAF and RAS mutation status were collected and analyzed.

Results: 47 patients underwent CRS- HIPEC with curative intent. Median PCI score was 14 [IQR: 6-21]. 34 (72%) patients had complete (CC0) resection, 11(23%) had CC1 (≤0.25 cm residual tumor) resection, 2 (4%) had CC2 (0.25-2.5 cm) resection.  6 (13%) of CRC were MSI-high.  22 (47%) were RAS mutant, 4 (9%) BRAF mutant.  At median follow-up of 2 years, 23 (48%) died of disease with a median overall survival (OS) of 19 months [IQR: 10-27], 36 (77%) patients developed recurrence with a median disease free survival (DFS) of 7 months [IQR: 5-12].   No factors analyzed reached significance for OS. RAS mutation status and LVI were the only significant predictors of decreased DFS (p= 0.02 and 0.03 respectively) on univariate analysis. On multivariate analysis neither remained significant.  

Conclusion: CRS HIPEC can achieve improved survival in patient with PC from CRC, however better risk stratification is needed for patient selection.  RAS mutation status is an independent marker of poor prognosis and may provide enhanced prognostic information in these high risk patients.  Larger cohort studies are needed to validate these findings.

 

11.15 Impact of Marital Status on Presentation and Management of Early Stage Melanoma

Posted on January 18, 2018

C. E. Sharon1, A. J. Sinnamon1, M. E. Ming2, E. Y. Chu2, R. R. Kelz1, R. E. Roses1, D. L. Fraker1, G. C. Karakousis1  2Hospital Of The University Of Pennsylvania,Dermatology,Philadelphia, PA, USA 1Hospital Of The University Of Pennsylvania,Endocrine And Oncologic Surgery,Philadelphia, PA, USA

Introduction:
Early detection of melanoma is associated with improved patient outcomes. There is data to suggest that spouses or partners may facilitate detection of melanoma prior to the onset of regional and distant metastases. Less well known is the influence of marital status on the detection of early clinically localized melanoma. We sought to evaluate the impact of marital status on T stage at time of presentation for early stage disease and decision for SLN biopsy in appropriate patients.

Methods:
Patients at least 18 of age without evidence of regional or distant metastases were identified using Surveillance Epidemiology and End Results (SEER 2010-2014). The main independent variable of interest was marital status, categorized as married, never married, divorced, and widowed. Separate analysis dichotomizing patients as married or unmarried was also performed. Chi square test was used to evaluate for significant differences in distribution of T stage at presentation by marital status. Multivariable analysis using ordered logistic regression was performed to adjust for additional patient factors. 

Results:
A total of 56,718 patients were identified for study. Most patients were married (n=39,448, 70%). Others were never married (n=8,374, 15%), divorced (n=4,024, 7%), or widowed (n=4,872, 9%). Distribution of T stage at diagnosis was significantly different by marital status (p<0.001). Forty-three percent of married patients presented with T1a disease, compared to 40% of never married patients, 36% of divorced patients, and 30% of widowed patients (p<0.001). Conversely, 10% of widowed patients presented with T4b disease compared to only 4% of married patients (p<0.001). The association between marital status and higher T stage at presentation remained significant among all non-married groups after adjustment for income, age, gender, state of residence, urban versus rural, and high school education level. There was no observed effect modification between marital status and gender (p=0.17). Independent of T stage and other patient factors, never married and widowed patients were also less likely to undergo sentinel lymph node biopsy (SLNB) in lesions over 1mm in thickness, for which SLNB is routinely recommended (p<0.001).

Conclusion:
Married status is associated with earlier presentation of localized melanoma, which has important implications on prognosis and extent of surgery. Moreover, patients who are never married or widowed are less likely to undergo SLNB for lesions where it is routinely recommended. Marital status should be considered when counseling patients for melanoma procedures and when recommending frequency of screening and follow-up to optimize patient care. 
 

11.13 How Well Does the Surgical Apgar Score Predict Risk of Serious Complications After Cancer Surgery?

Posted on January 18, 2018

S. M. Manstein1, N. Goel1, W. H. Ward1, L. Demora1, E. A. Ross1, S. S. Reddy1, M. C. Smaldone1, J. M. Farma1, C. S. Chu1, A. Kutikov1, D. Y. Chen1, M. N. Lango1, R. Viterbo1, J. A. Ridge1, A. Karachristos1, R. G. Uzzo1, N. F. Esnaola1  1Fox Chase Cancer Center,Surgical Oncology,Philadelphia, PA, USA

Introduction:
Major cancer surgery is associated with significant risks of perioperative morbidity and mortality, resulting in delayed adjuvant therapy, higher recurrence rates, and worse overall survival. Previous retrospective studies have promoted use of the Surgical Apgar Score (SAS) for preoperative risk assessment. This study prospectively evaluated the predictive value of SAS to predict serious complication (SC, as defined by the American College of Surgeons National Surgical Quality Improvement Program) in cancer patients undergoing elective major surgery.

Methods:
Demographic, comorbidity, procedure, and intraoperative data was collected prospectively for 405 cancer patients undergoing elective major surgery at a single NCI-designated comprehensive cancer center between 2014-17. The SAS was calculated immediately postoperative and outcome data was collected prospectively. Rates of SC according to SAS risk category were compared using Cochran-Armitage trend test. As a measure of discrimination, receiver operator characteristic (ROC) curves were generated and area under the ROC curves (AUC) and 95% confidence intervals (CI) were calculated.

Results:
The median age was 64 years of age (range, 23-86); 44.0% of patients were female, 12.8% were non-Caucasian, 2.5 % were Latino. 77.8% of patients were ASA status classification 1-2, while 22.2% were ASA status classification 3 or greater. The distribution of patients who underwent head and neck, upper gastrointestinal/hepatico-pancreatico-biliary, colorectal, gynecologic, urologic, or reconstructive is shown in Table 1. 80.0%, 17.3%, and 2.7% of patients were deemed to be at low (SAS 7-10), intermediate (SAS 5-6), or high risk (SAS 0-4) for SC based on their immediate postoperative SAS. Forty-six patients (11.4%) ultimately experienced a SC within 30 days; 3.7% returned to the operating room, 3.7% experienced a urinary tract infection, 3.2% experienced a respiratory complication, 2.7% experienced a wound complication, and 1.2% experienced a cardiac complication. Overall, 9.3%, 18.6%, and 27.3% of patients with SAS 7-10, 5-6, or 0-4 experienced a SC, respectively (P=.005). The overall discriminatory ability of the SAS, however, was modest (AUC 0.661; 95%CI, 0.582-0.740).

Conclusion:
The majority of patients who underwent elective major cancer surgery in our cohort were deemed to be at low risk for adverse events based on their immediate postoperative SAS. Although there was an overall association between SAS and higher risk of subsequent postoperative SC in our cohort, the ability of the SAS to accurately predict risk of postoperative SC at the patient-level was limited.
 

11.12 Fecal Diversion Is Rarely Necessary In Cytoreduction And Hyperthermic Intraperitoneal Chemotherapy

Posted on January 18, 2018

L. M. Cohen1, J. Baumgartner1, J. Veerapong1, A. Lowy1, K. J. Kelly1  1University Of California – San Diego,Surgical Oncology,San Diego, CA, USA

Introduction: There is currently no consensus on when stoma creation for temporary fecal diversion is indicated during cytoreduction and hyperthermic intrapertioneal chemotherapy (CRS/HIPEC). The aim of this study was to evaluate the indications for and outcomes following fecal diversion in CRS/HIPEC at a high volume center where stoma creation is used infrequently.

Methods:  A retrospective review of a prospectively maintained database of patients with peritoneal surface malignancy was performed to identify those who underwent complete CRS/HIPEC between 2007 and 2017.

Results: Of 416 patients who underwent complete CRS/HIPEC during the time period, 226 had at least one bowel resection and anastomosis and were included in the analysis. In total, 17 patients (8%) had a stoma created at the time of CRS/HIPEC. Six  (3%) had end colostomy and 11 (5%) had ileostomy meant for temporary fecal diversion. All patients with ileostomy creation underwent proctectomy. Additional factors associated with ileostomy creation included: Body mass index (BMI), prior systemic chemotherapy, operative time, and peritoneal carcinomatosis index (PCI) (Table). In all patients and in the subset that underwent low anterior resection (LAR) (n = 38), there were no differences in anastomotic leak rate (0% vs 3%, p=0.543), inpatient morbidity (64% vs 65%, p=0.945), or length of stay (median 11 days in both groups, p=0.926), but 60-day readmission rate was higher in patients with ileostomy (55% versus 25%, p=0.031). All patients with ileostomy underwent reversal. The median time to reversal was 98 days (range 62 to 567).

Conclusion: The main indication for diverting ileostomy in CRS/HIPEC was LAR. Diverting ileostomy was not associated with decreased anastomotic leak rate when considering all patients or the subset of patients that underwent LAR, but was associated with increased rates of 60-day readmission. These data suggest that the use of temporary fecal diversion in CRS/HIPEC is rarely required, including in patients who undergo LAR. 

 

11.11 A 15-year Experience of Anal Carcinoma in a Veteran Population Comparing HIV vs Non-HIV Patients

Posted on January 18, 2018

E. Vo1, B. A. Kimbrough1, S. S. Awad1,2, N. S. Becker1,2, L. W. Chiu1,2, L. Gillory1,2, D. S. Lee1,2, K. Makris1,2, G. Chen1,2, N. N. Massarweh1,2,3, H. S. Tran Cao1,2, C. Y. Chai1,2  1Baylor College Of Medicine,Houston, TX, USA 2Michael E. DeBakey Veterans Affairs Medical Center,Houston, TX, USA 3VA HSR&D Center For Innovations In Quality, Effectiveness And Safety, Michael E. DeBakey VA Medical Center,Houston, TEXAS, USA

Introduction: The incidence of anal cancer in the US has been steadily increasing since the 1970s. Of the known risk factors for anal carcinoma including HIV, HPV infection, history of anogenital warts, organ transplant, and tobacco use, HIV status poses the greatest risk but has not been clearly defined as a prognostic indicator. The objective of our study was to evaluate the clinical differences between HIV and non-HIV patients with anal carcinoma over the past 15 years at our institution.

Methods: We performed a retrospective review of an institutional tumor registry for all patients with histologically confirmed diagnosis of anal carcinoma from 2000-2015. Baseline demographic and clinical data including gender, age at diagnosis, histologic type, HIV status, treatment history and stage at initial diagnosis were collected. Descriptive and univariate analyses were performed to compare HIV vs non-HIV patients. Cancer-specific survival was calculated using Kaplan-Meier method.

Results: A total of 77 patients were included in our review (43% with HIV). The majority of our patients were male (92%), white (73%), with invasive squamous cell carcinoma (66%). HIV patients were diagnosed at a younger age (51 vs. non-HIV 60 years, p<0.01) and earlier stage 0-1 (63% vs. non-HIV 36%, p=0.01). Local excision was offered at a higher rate for HIV patients (52% vs. non-HIV 30%, p=0.05) with less receiving chemoradiation (42% vs. non-HIV 66%, p=0.04) and salvage APR (6% vs. non-HIV 16%, p=0.29). No statistically significant difference in cancer-specific 5-year survival was noted between HIV vs. non-HIV patients (p=0.64).

Conclusion: Although HIV patients are likely to be diagnosed with anal carcinoma at a younger age and at an earlier stage due to awareness of HIV as a risk factor, there was no difference in cancer-specific 5-year survival between HIV and non-HIV patients. Further study is warranted to examine factors which may influence survival in HIV patients in the era of effective antiviral therapy, and a high suspicion for anal cancer remains key to early detection in patients with anal or perianal lesions or symptoms.

11.09 Patient Characteristics and Outcomes among BRAF-mutated Colorectal Cancers: A Retrospective Review

Posted on January 18, 2018

J. Purchla1, W. H. Ward1, F. Lambreton1, N. Nweze1, T. Li2, N. Goel1, S. Reddy1, E. Sigurdson1, J. M. Farma1  1Fox Chase Cancer Center,Department Of Surgical Oncology,Philadelphia, PA, USA 2Fox Chase Cancer Center,Philadelphia, PA, USA

Introduction: Colorectal adenocarcinoma is a disease with varying causative molecular mechanisms, where chromosomal instability leads to gene specific mutations in proto-oncogenes and tumor suppressors. Among the most well-known mutations, the BRAF gene is associated with decreased disease-free and overall survival. This investigation strives to characterize patient and disease-related outcome measures among patients with BRAF-mutated colorectal adenocarcinoma.

Methods: A retrospective study was performed using molecular profiling (MP) data of 35 colorectal patients of any stage who were treated at our tertiary cancer center between 2006 and 2017. Those who did not undergo molecular profiling or those with incomplete data were excluded. If completed, additional genetic analyses performed within or external to our institution were also included. Demographic, clinical, and pathological data were collected and analyzed. Recurrence free survival was assessed using Kaplan-Meier estimation method.

Results: Out of 481 colorectal patients, 35 (7.3%) were identified as having a BRAF mutation. The median age at diagnosis was 73 years old (range 36-90), 25 (71%) were female, and 29 (82.9%) were white. There were 29 (82.9%) colon primary sites, 16 (55.2%) of those right-sided, and 6 (17.1%) rectal. 9 (25.7%) were stage IV, 15 (42.9%) were stage III, 7 (20.0%) were stage II, and 4 (11.4%) were stage I. A majority of patients (77.1%) exhibited more than just a BRAF mutation, with 15 (42.9%) positive for defective mismatch repair/microsatellite instability (dMMR/MSI), 10 (28.6%) with a P53 mutation, 4 (11.4%) SMAD4, 3 (8.6%) APC, and 3 (8.6%) PIK3CA. A total of 5 (14.3%) patients had a prior history of other cancer types. From this cohort, 29 (82.9%) had surgery, and 23 (79.3%) achieved an R0 resection. A total of 19 (54.3%) patients underwent adjuvant therapy. Targeted therapy with EGFR inhibitor was administered in 10 (28.6%) patients. Recurrence occurred in 10 (28.6%) patients, with the median time to recurrence 22.2 months. The recurrence free survival rate to 1 year was 74.5% and to 2 years was 37.1%. The overall survival rate to 1 year was 89.6%, and to 2 years was 56.8%.

Conclusions: In this cohort, patients with BRAF mutated colorectal cancer were generally older, white and female, and more likely to present with advanced disease. Of those who relapsed, more than 60% of patients did so within 2 years of diagnosis. Overall survival decreased substantially after 1 year. Tumors were primarily in the colon, specifically right-sided colon, with a MP likely to show more than 1 mutation. Our investigation shows that this cohort of BRAF-mutated tumors exhibits a poorer prognosis. To better characterize these patients and their disease-related outcomes, further investigation with a larger cohort is warranted. 

11.10 Postoperative Morbidity and Mortality of Neoadjuvant Therapy after Pancreaticoduodenectomy

Posted on January 18, 2018

K. S. Cools2, H. J. Kim2, J. J. Yeh2, H. K. Sanoff3, K. B. Stitzenberg2  2University Of North Carolina At Chapel Hill,Department Of Surgery,Chapel Hill, NC, USA 3University Of North Carolina At Chapel Hill,Department Of Medicine,Chapel Hill, NC, USA

Introduction:
Although surgical resection remains the only potentially curative treatment for pancreas cancer, neoadjuvant chemotherapy and/or radiation therapy has been increasingly employed to try to downstage patients with borderline resectable tumors. Still, there is a paucity of literature examining outcomes at the population level, for patients who do and do not receive neoadjuvant therapy. The existing studies highlight single/few center experiences, with mixed results. The aim of this study was to compare on a population level, the postoperative morbidity and mortality after pancreaticoduodenectomy (PD) in patients undergoing neoadjuvant therapy versus initial surgery for pancreatic ductal adenocarcinoma (PDA).

Methods:
Using the American College of Surgeons National Surgical Quality Improvement Project (NSQIP) Targeted Pancreatectomy data, we identified patients who underwent a PD for PDA between 2014 and 2015. This database consists of pancreas-specific outcomes from 106 centers in the United States. Patients were grouped based on having received neoadjuvant therapy within 90-days of PD. We used bivariable and multivariable analyses to compare postoperative outcomes between the groups.

Results:
A total of 3,758 patients with PDA underwent PD; 930 (24.7%) received neoadjuvant therapy (13.5% chemotherapy only, 0.8% radiation only, and 10.4% chemoradiation). Those in the neoadjuvant group were more likely to have preoperative biliary stenting (66.2% vs 61.8%, p=0.015), a major vein resection (35.8% vs 17.5%, p<0.001), and longer operating time (413 min vs 364 min, p<0.001). At the time of surgery, those in the neoadjuvant group also had more T1 tumors (10.9% vs 5.1%, p<0.001) and fewer nodes positive (N0 49% vs 28%, p<0.001). There were no differences in 30-day postoperative mortality (1.7% vs 2%, p=0.616) or overall complications (55.9% vs 55.2%, p=0.689). On multivariate analysis, patients who received neoadjuvant therapy had a lower likelihood of pancreatic fistula (OR 0.67, 95% CI 0.49-0.92, p<0.001). On multivariate analysis to identify factors associated with pancreatic fistulas, independent predictors included having initial surgery (OR 1.44, 95% CI 1.07-1.95), preoperative biliary stenting (OR 1.3, 95% CI 1.02-1.7), soft pancreatic tissue (OR 2.96, 95% CI 2.32-3.78), longer operative times (OR 1.06, 95% CI 1.0-1.12), and a normal preoperative albumin (OR 1.41, 95% CI 1.08-1.85).

Conclusion:
Using the robust NSQIP database of over 100 centers, we found that neoadjuvant therapy does not increase the overall postoperative morbidity or mortality of a PD for PDA. There is a decreased likelihood of pancreatic fistulas in patients that receive neoadjuvant therapy.

11.07 Mesoappendix Based Vascularized Lymph Node Transfer for the Surgical Treatment of Lymphedema

Posted on January 18, 2018

D. Ruter1, W. Chen4, R. Garza5, D. Eiferman3, R. Skoracki2  1The Ohio State University College Of Medicine,Columbus, OH, USA 2The Ohio State University College Of Medicine,Department Of Plastic Surgery,Columbus, OH, USA 3The Ohio State University College Of Medicine,Department Of General Surgery,Columbus, OH, USA 4The Ohio State University College Of Medicine,Department Of Pathology,Columbus, OH, USA 5PRMA Plastic Surgery,San Antonio, TX, USA

Introduction: Lymphedema is an accumulation of lymph fluid in the interstitial space that is most commonly due to surgical resection of lymph nodes secondary to malignancy. Standard of care compression and mechanical drainage based treatments are time intensive and provide limited long term relief. Autologous lymph node transfer (ALNT) is a microsurgical treatment in which a vascularized lymph node flap is harvested with its blood supply and transferred to the affected extremity to improve clearance of lymph fluid. A number of donor sites, including the groin, axilla, submental, and supraclavicular regions have been described as potential donor sites for vascularized lymph node containing free flaps. An ideal donor site minimizes the risk of iatrogenic lymphedema while being easily accessible with few potential complications. Previously, our group has utilized intraabdominal jejunal mesentery lymph nodes and omentum flaps for ALNT. We hypothesized that the mesoappendix could be harvested minimally invasively as an expendable "spare part" and would be ideal for transplantation if vessel size is adequate and a reliable number of vascularized lymph nodes can be included.

Methods: In this IRB approved study, 25 mesoappendix specimens (22 appendectomy and 3 right hemicolectomy) resected for benign disease underwent gross pathologic examination for determination of the presence of lymph nodes and measurement of the appendicular artery and vein caliber and length.

Results: A single lymph node was present in two of twenty-five (8%) specimens. Mean artery and vein calibers at the point of ligation were 0.87 and 0.86 mm, with mean lengths, as measured from the appendix mesentery to the ligated vessel end, of 1.70 and 1.84 cm, respectively. The two measurable right hemicolectomy specimens had an artery diameter of 1.2 mm, and vein diameters of 1.1 and 2.2 mm.

Conclusion: Mesoappendiceal lymph nodes were inconsistently present. The artery and vein calibers of 46% of the specimens were greater than 0.8 mm, the minimum caliber we prefer for microsurgical anastomosis. Maximal vessel caliber determination was limited by the site of vessel ligation chosen by the operating surgeon, and thus may be underestimated by our study. The exact role of the lymph node itself is not exactly delineated in the treatment of lymphedema, but evidence suggests that greater numbers of lymph nodes transplanted seem to have greater efficacy in removing lymph fluid. The mesoappendix, while it contains few or no lymph nodes is attached to the appendix, which contains a great number of lymphoid follicles in the submucosa. The uncertain role of this tissue in the treatment of lymphedema will require further investigation as a potential solution. However, for patients suffering from lymphedema, the mesoappendix can easily be explored and evaluated for the presence of lymph nodes and sufficiency of the vascular pedicle if planning to do an abdominal based lymph node transfer. 

11.08 Neutrophil To Lymphocyte Ratio Predicts Outcomes After Chemoembolization for Neuroendocrine Tumors

Posted on January 18, 2018

S. M. McDermott1, N. Saunders3, E. M. Schneider2, D. Strosberg2, J. Onesti4, G. Davidson2, M. Bloomston5, M. Dillhoff2, C. R. Schmidt2, L. A. Shirley2  1Ohio State University,College Of Medicine,Columbus, OH, USA 2Ohio State University,Department Of Surgery,Columbus, OH, USA 3Emory University School Of Medicine,Department Of Surgery,Atlanta, GA, USA 4Mercy Health,Department Of Surgery,Grand Rapids, MI, USA 521st Century Oncology,Ft Myers, FL, USA

Introduction: The neutrophil to lymphocyte ratio (NLR) is predictive of outcomes in various cancers, including neuroendocrine tumors (NETs), as well as response to cancer related treatments, including transarterial chemoembolization (TACE). However, the role of NLR in patients with NET treated with TACE is incompletely understood. We hypothesized that, in patients with liver metastases from NETs, a lower NLR value pre-TACE, as well as post-procedure, would correlate with improved long-term outcomes.

Methods:

After IRB approval, we reviewed 262 patients who underwent TACE for metastatic NET at a single institution. NLR was calculated from the pre-TACE CBC drawn the day of the procedure and the post-TACE CBC drawn approximately one day, one week, and six months after initial treatment. NLR levels were then correlated with overall survival from the time of TACE.

Results:The median post-TACE survival of the entire cohort was 30.1 months. Mean NLR for patients who survived less than 3 years was 4.4 while the mean NLR for patients who survived more than 3 years was 3.3. Median overall survival of patients with a pre-TACE NLR < 4 was 33.3 months vs 21.1 months for patients with a pre-TACE NLR > 4 (p = 0.005). The median survival for patients with post-TACE NLR higher than pre-TACE NLR was 21.4 months vs 25.8 months for patients with post-TACE NLR less than or equal to pre-TACE NLR (p = 0.007) (Figure). NLR values from one day and one week post-TACE did not correlate with outcome.

Conclusion:

An elevated NLR pre-TACE, as well as an NLR value that has not returned to its pre-TACE value several months after the TACE, are associated with worse survival in patients with NET and liver metastases. This value can easily be calculated from the CBC routinely obtained from patients as part of their pre-procedural and post-procedural care. Calculating and trending NLR values for these patients may impact treatment strategies.

11.05 High Mitotic Rate Predicts Sentinel Lymph Node Involvement in Thin Melanomas

Posted on January 18, 2018

K. E. Engelhardt1,2, O. Kutlu3, W. Lancaster1, K. Staveley-O’Carroll4, E. Kimchi4, A. M. Abbott1, E. R. Camp1  1Medical University Of South Carolina,Charleston, Sc, USA 2Northwestern University,Chicago, IL, USA 3University Of Miami,Miami, FL, USA 4University Of Missouri,Columbia, MO, USA

Introduction:
Current recommendations by the National Comprehensive Cancer Network are for consideration of sentinel lymph node biopsy (SLNB) for patients with melanoma <1mm. Clinicians may use presence of ulceration, mitotic rate (MR), and tumor depth to aid in decision making. Low MR has been associated with high false positive rates, however, it is unknown at what value MR becomes a significant predictor of SLN positivity. We hypothesized that higher MR would strongly predict tumor biology in thin melanomas and, therefore, predict SLN involvement.

Methods:
We queried the Surveillance Epidemiology and End Results database for all patients diagnosed with trunk and extremity cutaneous melanoma ≤1mm depth from 2010 to 2013 who underwent SLNB to determine whether MR was an independent predictor of SLN. Patient demographics and tumor characteristics (depth, mitotic rate, ulceration, and tumor location were evaluated). MR was dichotomized at multiple cut-points and estimated multiple stratified logistic regression models were used to identify the ideal cut point for MR as a predictor of SLN status. After determination of the ideal cut-point, we then estimated a hierarchical multivariable logistic regression model to determine the association between high MR and SLN+. We also performed a subset analysis for melanoma at the upper limit of thin categorization (0.75-1mm).

Results:
patient cohort was 51.7% male (n=2,246) with mean patient age of 55.6 years (range 18-85). We identified 4 or more mitosis per high power field as the ideal cut point for dichotomization of MR into high and low risk groups. In our final regression model, MR≥4 (OR 3.67 95%CI 2.66-5.05; p<0.001) and ulceration (OR 2.32 95%CI 1.62-3.31; p<0.001) were significantly associated with SLN+. In a subset analysis of 0.75-1mm melanomas, MR≥4 (OR 4.61 95%CI 2.77-7.66; p<0.001) and ulceration (OR 2.29 95%CI 1.37-3.82 p=0.002) were associated with SLN+. The SLN+ rate of the entire cohort of 0.75-1mm patients was 5.6% (n=122/2184); this number increased to 14.4% (n = 20/139) when the cohort was sub-selected for MR ≥4. Interestingly, depth was not an independent predictor of SLN+ rate in the overall cohort or the 0.75-1mm subset.

Conclusion:
In our analysis, MR≥4 was the strongest independent predictor of SLN+ in thin melanoma. In patients with thin melanoma we found that MR and ulceration, not tumor depth, were independent predictors of SLN involvement. When evaluating patients with thin melanoma for SLNB, MR and ulceration may aid in decision-making analysis more than tumor depth alone.
 

11.06 Timing of Radiation Improves Margin Status but Not Limb-Salvage Rates in Deep Extremity Sarcoma

Posted on January 18, 2018

R. D. Shelby1, L. Suarez-Kelly1, P. Y. Yu1, T. M. Hughes1, C. G. Ethun2, T. B. Tran3, G. Poultsides3, D. M. King7, M. Bedi7, T. C. Gamblin7, J. Tseng4, K. K. Roggin4, K. Chouliaras5, K. Votanopoulos5, B. A. Krasnick6, R. C. Fields6, R. E. Pollock1, J. H. Howard1, K. Cardona2, V. P. Grignol1  1Ohio State University,Columbus, OH, USA 2Emory University School Of Medicine,Atlanta, GA, USA 3Stanford University,Palo Alto, CA, USA 4University Of Chicago,Chicago, IL, USA 5Wake Forest University School Of Medicine,Winston-Salem, NC, USA 6Washington University,St. Louis, MO, USA 7Medical College Of Wisconsin,Milwaukee, WI, USA

Introduction:  The addition of radiation to surgery has improved limb-salvage rates for deep extremity sarcomas. Timing of delivery in a neo-adjuvant (NA) vs adjuvant strategy remains an area of study.  We sought to evaluate the effect of NA radiation on patients with deep extremity sarcomas from a multi-institutional database. 

Methods:  A retrospective review of all adult patients with deep extremity sarcomas who underwent surgical resection at 7 U.S institutions from 2000-2016 was performed. Categorical variables were compared using chi-square test. Continuous variables were compared using two-sample t-tests. To assess the impact of radiation on recurrence free survival (RFS) and overall survival (OS) Cox proportional hazard regression models were used. Multivariate analysis was performed for all statistically significant categories to evaluate association with OS and RFS. 

Results: 1483 patients with surgically resected deep extremity sarcomas were identified. Average tumor size was 15cm; the most common histology was undifferentiated pleomorphic sarcoma. 723 (50%) patients had surgery only, 419 (29%) had NA radiation and 311(21%) had adjuvant radiation. Most patients who received radiotherapy had grade 3 tumors (82% NA vs 81% adjuvant vs 60% surgery, p<0.0001). Patients receiving NA radiation were more likely to have a history of radiation (7% NA vs 2% adjuvant vs 4% surgery, p=.0060) and undergo core biopsy for diagnosis (67% NA vs 31% adjuvant vs 34% surgery, p<0.0001) than those who had surgery first. More patients in the NA and surgery alone group underwent radical resection (92% NA vs 83% surgery vs 78% adjuvant p<0.0001). The radiotherapy groups had significantly more limb-sparing operations (98% adjuvant vs 94% NA vs 87% surgery, p<0.0001). NA radiation increased post-operative complications (34% NA vs 24% surgery vs 16% adjuvant, p<0.0001) and the need for tissue flap reconstruction (38% NA vs 24% surgery vs 22% adjuvant, p<0.0001). NA radiotherapy led to more negative margins on frozen (87%% NA vs 79% surgery vs 72% adjuvant, p<.0001) and final pathology (90% NA vs 79% surgery vs 75% adjuvant, p<.0001). There were significantly fewer local recurrences in the NA group (14% vs 17% adjuvant vs 27% surgery, p=0.001). The surgery only group had the fewest metastatic recurrences (52% vs 72% NA vs 62% adjuvant, p=0.001). OS and RFS were better in the groups receiving radiation, although not statistically significant. On multivariate analysis there was no factor independently associated with survival. 

Conclusion: In this large multi-institutional study, radiotherapy (adjuvant and NA) improves limb salvage rates. NA radiation improves margin status and local recurrence rates, however with increased post-operative complications. There were no other differences related to timing of radiotherapy. Our findings are consistent with other smaller studies. 

11.04 Soft Tissue Sarcomas in the Elderly: Are we Overtreating or Undertreating this Patient Population?

Posted on January 18, 2018

A. Gingrich1, S. Bateni1, R. Bold1, A. Kirane1, A. Monjazeb3, M. Darrow4, S. Thorpe2, R. Canter1  1University Of California – Davis,Surgery,Sacramento, CA, USA 2University Of California – Davis,Orthopedics,Sacramento, CA, USA 3University Of California – Davis,Radiation Oncology,Sacramento, CA, USA 4University Of California – Davis,Pathology,Sacramento, CA, USA

Background: The surgical management of elderly cancer patients is a topic of increasing attention, especially as the population ages. Although disparities in access to care and outcomes are a key focus of health services research, few studies have examined differences in patterns of care and outcomes among elderly cancer patients, especially in soft tissue sarcoma (STS).  Our objective was to analyze and compare the clinical, pathologic, and treatment characteristics for elderly STS patients to younger patients, hypothesizing that elderly STS patients represent a distinct cohort of patients for whom more age-specific algorithms are indicated.

Methods: Using the National Cancer Database (2004-2012), we identified 33,859 adult patients (18 -99 years) with non-metastatic STS. We defined “elderly” patients as ≥ 74 years (top quartile of age, n=8,504). We compared patient demographics, tumor characteristics, types of treatment and outcomes among the “elderly” to the non-elderly cohort. We also analyzed survival in the elderly undergoing surgery versus no surgery. Cox proportional hazard analysis was used to analyze multivariate predictors of overall survival among elderly patients.

Results: Age, tumor size, geographic location, rural/urban, and receipt of radiotherapy (RT) were similar between non-elderly and elderly patients. However, significant differences were observed in histologic grade, histologic subtype, and facility type (P<0.05). Elderly patients were less likely to be black (5.8 vs 12.3%, P = 0.001), more likely to have higher comorbidity scores (26.5 vs. 15.2%, P=0.001), and less likely to undergo R0 resection (59.7 vs. 70%, P = 0.001). 90-day mortality was also 3.5 times greater in elderly patients (4.3% vs. 1.2%, P = 0.001). Yet, among elderly patients undergoing surgery, median survival was 43.8 months versus 15.4 months in those who did not undergo surgery (P = 0.001). On Cox proportional hazard analysis of the elderly cohort, predictors of superior survival were comparable to non-elderly patients, including younger age, female sex, lower Charlson-Deyo score, histologic subtype, lower grade, smaller tumor size, surgical resection, R0 resection and receipt of radiation therapy (p<0.05). Chemotherapy did not offer survival benefit (p>0.05).  

Conclusions: Key clinical, pathologic, and treatment differences exist in elderly patients with STS. Although elderly patients have worse rates of R0 resection and 90-day mortality, surgery remains associated with superior long term survival. Better understanding of these important differences in the presentation and management of STS in the elderly are important in the context of the aging population, including the narrower benefit to risk ratio with surgical management of localized disease. 

11.03 A Phase II Trial of Cytoreduction and HIPEC for Advanced Adrenocortical Carcinoma

Posted on January 18, 2018

W. Lo1, T. Beresnev1, M. Merino3, M. Mulquin1, Y. Shutack1, D. Zlott1, J. Hernandez1, J. Davis1, M. Hughes2  1National Cancer Institute,Thoracic And GI Oncology Branch,Bethesda, MD, USA 2Eastern Virginia Medical School,Surgical Oncology,Norfolk, VA, USA 3National Cancer Institute,Pathology,Bethesda, MD, USA

Introduction:  Adrenocortical carcinoma (ACC) is an aggressive disease with 5-year survival estimated at 10-15%. While definitive therapy is complete surgical resection, recurrence occurs in up to 85% of patients. Systemic chemotherapy and molecular-targeted therapy have had minimal benefit for patients with advanced disease. The purpose of this study is to evaluate cytoreduction and HIPEC for safety in patients with advanced ACC confined to the peritoneal cavity, as well as evaluate the strategy for peritoneal progression-free survival.

Methods:  This single-institution, phase 2 clinical trial enrolled patients from April 2013 through September 2016. Eligible patients had histologically confirmed ACC and peritoneal disease deemed resectable by the operating surgeon and preoperative imaging. Comprehensive cytoreductive surgical resection was performed. Patients achieving CCR 0 or 1 proceeded with HIPEC using the closed-abdomen technique. Intraperitoneal cisplatin at 250 mg/m2 was circulated at 40°C for 90 minutes. Primary outcome was peritoneal progression-free survival (PFS). Secondary outcomes included overall survival (OS), adverse events, and treatment toxicity.

Results: Nine patients underwent cytoreduction and HIPEC. Mean operative time was 689 minutes (range 577 – 894 min). Median estimated blood loss was 500 mL (range 100 – 2000 mL). Median length of hospital stay after resection was 11 days. There were no perioperative mortalities or immediate reoperations. No treatment-related toxicities, grade 3 or 4 complications were observed. Thirty percent (n = 3) experienced infection-related complications. During a median follow-up period of 23.2 months, seven patients experienced peritoneal progression of disease and two patients died due to ACC. Median peritoneal PFS was 18.9 months from cytoreductive surgery and HIPEC. Median OS from date of initial diagnosis was 4.23 years. On univariate analysis, prior treatment with mitotane was associated with improved peritoneal PFS and OS. Tumor stage, initial disease-free interval after index resection, tumor functional status, type of initial resection, and prior treatment with etoposide, doxorubicin, and cisplatin (EDP) had no impact on peritoneal PFS or OS.

Conclusion: Recurrent ACC is an aggressive disease, and effective treatment strategies remain undefined. This study demonstrates that cytoreduction and HIPEC can be safely performed for patients with advanced ACC, and may result in a survival advantage for patients with disease confined to the peritoneum after receipt of adjuvant mitotane.  

 

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