Immune checkpoint inhibitors in hepatocellular carcinoma: A review of current clinical trials.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer with a poor prognosis due to advanced disease presentation or recurrence despite curative-intent resection. Since the approval of sorafenib in 2007, few systemic therapies offered a significant improvement in treatment outcomes. Over the last 3 years, however, rapid advancements in the field of immunotherapy have led to approval of checkpoint inhibitors in 2020 for use in advanced HCC. Since then, a few other clinical trials have shown promising results in the adjuvant and neoadjuvant setting. The objective of this review is to summarize data from existing clinical trials evaluating the use of systemic immune checkpoint inhibitors in HCC and to follow the natural evolution of this development across the metastatic, adjuvant, and neoadjuvant landscapes.

Patterns of Unnecessary Insurer Prior Authorization Denials in a Complex Surgical Oncology Practice.

INTRODUCTION: Insurance prior authorization (PA) is a determination of need, required by a health insurer for an ordered test/procedure. If the test/procedure is denied, a peer-to-peer (P2P) discussion between ordering provider and payer is used to appeal the decision. The objective of this study was to measure the number and patterns of unnecessary PA denials. METHODS: This was a retrospective review at a quaternary cancer center from October 2021 to March 2022. Included were all patients with outpatient imaging orders for surgical planning or surveillance of gastrointestinal, endocrine, or skin cancer. Primary outcome was unnecessary initial denial (UID) defined as an order that required preauthorization, was initially denied by the insurer, and subsequently overturned by P2P. RESULTS: Nine hundred fifty seven orders were placed and 419 required PA (44%). Of tests requiring authorization, 55/419 (13.1%) were denied. Variability in the likelihood of initial denial was seen across insurers, ranging from 0% to 57%. Following P2P, 32/55 were overturned (58.2% UID). The insurers most likely to have a UID were Aetna (100%), Anthem (77.8%), and Cigna (50.0%). UID was most common for gastrointestinal (58.9%) and endocrine (58.3%) cancers. Average P2P was 33.5 min (interquartile range 28-40). CONCLUSIONS: The majority of imaging studies initially denied were overturned after P2P. If all UIDs were eliminated, this would represent 108 less P2P discussions with an estimated time-savings of 60.3 h annually within a high-volume surgical oncology practice. Combined personnel costs to the health systems and stress on patients with cancer due to image-associated PAs and P2P appear hard to justify.

Outcomes of plastic surgical reconstruction in extremity and truncal soft tissue sarcoma: Results from the US Sarcoma Collaborative.

BACKGROUND: This study aimed to define how utilization of plastic surgical reconstruction (PSR) affects perioperative outcomes, locoregional recurrence-free survival (LRRFS), and overall survival (OS) after radical resection of extremity and truncal soft tissue sarcoma (ETSTS). The secondary aim was to determine factors associated with PSR. METHODS: Patients who underwent resection of ETSTS between 2000 and 2016 were identified from a multi-institutional database. PSR was defined as complex primary closure requiring a plastic surgeon, skin graft, or tissue-flap reconstruction. Outcomes included PSR utilization, postoperative complications, LRRFS, and OS. RESULTS: Of 2750 distinct operations, 1060 (38.55%) involved PSR. Tissue-flaps (854, 80.57%) were most commonly utilized. PSR was associated with a higher proportion of R0 resections (83.38% vs. 74.42%, p < 0.001). Tissue-flap PSR was associated with local wound complications (odds ratio: 1.81, confidence interval: 1.21-2.72, p = 0.004). Neither PSR nor postoperative complications were independently associated with LRRFS or OS. High-grade tumors (1.60, 1.13-2.26, p = 0.008) and neoadjuvant radiation (1.66, 1.20-2.30, p = 0.002) were associated with the need for PSR. CONCLUSION: Patients with ETSTS undergoing resection with PSR experienced acceptable rates of complications and a higher rate of negative margins, which were associated with improved LRRFS and OS. High tumor grade and neoadjuvant radiation were associated with requirement of PSR.

Facility type is associated with improved perioperative and oncologic outcomes after minimally invasive surgery for pancreatic cancer.

BACKGROUND: This study sought to evaluate outcome differences by facility type in patients who underwent minimally invasive surgery (MIS) for pancreatic ductal adenocarcinoma (PDAC). METHODS: The National Cancer Database was used to identify patients with clinical stage I-III PDAC who underwent MIS from 2010 to 2019 in academic or community facilities. RESULTS: Of 6806 patients who fulfilled inclusion criteria; 1788 (26.3%) were treated at community facilities and 5018 (74.7%) at academic facilities. Patients treated at academic facilities were more likely to receive care at a high-volume facility (62% vs. 32%, p < 0.001), undergo a Whipple (64% vs. 61%, p < 0.001), and be clinical stage II (42% vs. 38%) and III (5.6% vs. 4.9%, p = 0.001). Treatment at academic facilities was predictive of receiving neoadjuvant therapy (OR 2.08, p < 0.001), negative margin resection (OR 0.80, p = 0.004), lower 90-day mortality (OR 0.72, p = 0.02), decreased length of stay (IRR 0.96, p < 0.001), and longer OS (HR 0.88, p = 0.002). CONCLUSION: Patients who underwent MIS for PDAC at academic facilities experienced an association with improved perioperative and oncologic outcomes than those treated in community facilities.

Palliative Cytoreductive Surgery With or Without Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis: Is It Safe and Effective?

INTRODUCTION: Palliation is a controversial indication for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Patients with peritoneal carcinomatosis (PC) are living longer, and the roles of palliative CRS and HIPEC are increasingly challenged. The purpose of this study is to evaluate indications, morbidity, and symptom improvement from CRS/HIPEC in advanced PC. METHODS: A retrospective review of patients undergoing CRS and/or HIPEC with a palliative intent at a single institution from February 2008 to February 2018 was performed. Main end points included symptom improvement, symptom-free interval, and overall survival. RESULTS: Two hundred and seventy seven patients were referred for CRS/HIPEC during the study period and 17 underwent 20 palliative procedures. Appendiceal (n = 6) and colorectal cancers (n = 6) were the most common malignancies. Ascites (n = 8) and bowel obstruction (n = 8) were the most common indications for intervention. The postoperative complication rate was 50% and major complication rate was 20%. Partial symptom improvement or resolution of symptoms was achieved in 18 (90%) cases. A durable symptom control at 90 d was achieved in 13 (65%) cases. The median time to symptom recurrence was 5.1 mo (interquartile range: 2-11.4), and the median overall survival was 11.6 mo (interquartile range: 3.8-28.5). CONCLUSIONS: Palliative CRS and/or HIPEC achieve symptom improvement in patients with advanced PC. Risk assessment and expected time to recovery from surgery remain paramount for patient selection.

Two-Stage Hepatectomy for Bilateral Colorectal Liver Metastases: A Multi-institutional Analysis.

BACKGROUND: Two-stage hepatectomy (TSH) is an important tool in the management of bilateral colorectal liver metastases (CRLM). This study sought to examine the presentation, management, and outcomes of patients completing TSH in major hepatobiliary centers in the United States (US). METHODS: A retrospective review from five liver centers in the US identified patients who completed a TSH procedure for bilateral CRLM. RESULTS: From December 2000 to March 2016, a total of 196 patients were identified. The majority of procedures were performed using an open technique (n = 194, 99.5%). The median number of tumors was 7 (range 2-33). One-hundred and twenty-eight (65.3%) patients underwent portal vein embolization. More patients received chemotherapy prior to the first stage than chemotherapy administration preceding the second stage (92% vs. 60%, p = 0.308). Median overall survival (OS) was 50 months, with a median follow-up of 28 months (range 2-143). Hepatic artery infusion chemotherapy was administered to 64 (32.7%) patients with similar OS as those managed without an infusion pump (p = 0.848). Postoperative morbidity following the second-stage resection was 47.4%. Chemotherapy prior to the second stage did not demonstrate an increased complication rate (p = 0.202). Readmission following the second stage was 10.3% and was associated with a decrease in disease-free survival (p = 0.003). OS was significantly decreased by positive resection margins and increased estimated blood loss (EBL; p = 0.036 and p = 0.05, respectively). CONCLUSION: This is the largest TSH series in the US and demonstrates evidence of safety and feasibility in the management of bilateral CRLM. Outcomes are influenced by margin status and operative EBL.

Primary Liver Cancer: An NCDB Analysis of Overall Survival and Margins After Hepatectomy.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) constitute the majority of primary liver cancers. This retrospective review aimed to determine whether site of care is a significant predictor of patient outcome after hepatectomy as measured by overall survival, hazard ratios (HRs), and resection margin status. METHODS: Data regarding patients with a new diagnosis of ICC and HCC who underwent hepatectomy were analyzed from the national cancer database. The patients were divided into two cohorts: those receiving treatment at academic cancer centers (ACCs) and those receiving treatment at community cancer centers (CCCs). The study adjusted for confounding variables and selection bias using propensity score matching. Median overall survival (months), hazard ratios, and resection margin status (R0, R1/R2, unknown) were examined. RESULTS: The inclusion criteria were met by 10,463 patients. After propensity matching, 5600 patients remained, with half receiving treatment at ACCs and half at CCCs. Median overall survival from the date of diagnosis for patients undergoing hepatectomy was longer at ACCs than at CCCs (28.3 vs 24.8 months; p < 0.001). Additionally, multivariable Cox proportional hazards models showed that treatment at CCCs was associated with poorer survival than treatment at ACCs (HR, 1.226; 95% confidence interval [CI], 1.142-1.316; p < 0.0001). Treatment facility designation also was a predictive indicator of resection margin status, with patients at CCCs exhibiting higher odds of R1/R2 resections (odds ratio [OR], 1.41; 95% CI, 1.19-1.67; p < 0.0001). CONCLUSION: Hepatectomy for ICC and HCC performed at ACCs was associated with improved outcomes compared with CCCs. Centralization of care to ACCs may lead to improved patient outcomes.

Optimal Surveillance Frequency After CRS/HIPEC for Appendiceal and Colorectal Neoplasms: A Multi-institutional Analysis of the US HIPEC Collaborative.

BACKGROUND: No guidelines exist for surveillance following cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for appendiceal and colorectal cancer. The primary objective was to define the optimal surveillance frequency after CRS/HIPEC. METHODS: The U.S. HIPEC Collaborative database (2000-2017) was reviewed for patients who underwent a CCR0/1 CRS/HIPEC for appendiceal or colorectal cancer. Radiologic surveillance frequency was divided into two categories: low-frequency surveillance (LFS) at q6-12mos or high-frequency surveillance (HFS) at q2-4mos. Primary outcome was overall survival (OS). RESULTS: Among 975 patients, the median age was 55 year, 41% were male: 31% had non-invasive appendiceal (n = 301), 45% invasive appendiceal (n = 435), and 24% colorectal cancer (CRC; n = 239). With a median follow-up time of 25 mos, the median time to recurrence was 12 mos. Despite less surveillance, LFS patients had no decrease in median OS (non-invasive appendiceal: 106 vs. 65 mos, p < 0.01; invasive appendiceal: 120 vs. 73 mos, p = 0.02; colorectal cancer [CRC]: 35 vs. 30 mos, p = 0.8). LFS patients had lower median PCI scores compared with HFS (non-invasive appendiceal: 10 vs. 19; invasive appendiceal: 10 vs. 14; CRC: 8 vs. 11; all p < 0.01). However, on multivariable analysis, accounting for PCI score, LFS was still not associated with decreased OS for any histologic type (non-invasive appendiceal: hazard ratio [HR]: 0.28, p = 0.1; invasive appendiceal: HR: 0.73, p = 0.42; CRC: HR: 1.14, p = 0.59). When estimating annual incident cases of CRS/HIPEC at 375 for non-invasive appendiceal, 375 invasive appendiceal and 4410 colorectal, LFS compared with HFS for the initial two post-operative years would potentially save $13-19 M/year to the U.S. healthcare system. CONCLUSIONS: Low-frequency surveillance after CRS/HIPEC for appendiceal or colorectal cancer is not associated with decreased survival, and when considering decreased costs, may optimize resource utilization.

Preoperative Risk Score for Predicting Incomplete Cytoreduction: A 12-Institution Study from the US HIPEC Collaborative.

BACKGROUND: For patients with peritoneal carcinomatosis undergoing cytoreductive surgery with heated intraperitoneal chemotherapy (CRS/HIPEC), incomplete cytoreduction (CCR2/3) confers morbidity without survival benefit. The aim of this study is to identify preoperative factors which predict CCR2/3. METHODS: All patients who underwent curative-intent CRS/HIPEC of low/high-grade appendiceal, colorectal, or peritoneal mesothelioma cancers in the 12-institution US HIPEC Collaborative from 2000 to 2017 were included (n = 2027). The primary aim is to create an incomplete-cytoreduction risk score (ICRS) to predict CCR2/3 CRS utilizing preoperative data. ICRS was created from a randomly selected cohort of 50% of patients (derivation cohort) and verified on the remaining patients (validation cohort). RESULTS: Within our derivation cohort (n = 998), histology was low-grade appendiceal neoplasms in 30%, high-grade appendiceal tumor in 41%, colorectal tumor in 22%, and peritoneal mesothelioma in 8%. CCR0/1 was achieved in 816 patients and CCR 2/3 in 116 patients. On multivariable analysis, preoperative factors associated with incomplete cytoreduction were male gender [odds ratio (OR) 3.4, p = 0.007], presence of ascites (OR 2.8, p = 0.028), cancer antigen (CA)-125 ≥ 40 U/mL (OR 3.4, p = 0.012), and carcinoembryonic antigen (CEA) ≥ 4.2 ng/mL (OR 3.2, p = 0.029). Each preoperative factor was assigned a score of 0 or 1 to form an ICRS from 0 to 4. Scores were grouped as zero (0), low (1-2), or high (3-4). Incidence of CCR2/3 progressively increased by risk group from 1.6% in zero to 13% in low and 39% in high. When ICRS was applied to the validation cohort (n = 1029), this relationship was maintained. CONCLUSION: The incomplete cytoreduction risk score incorporates preoperative factors to accurately stratify the risk of CCR2/3 resection in CRS/HIPEC. This score should not be used in isolation, however, to exclude patients from surgery.

Trends in the Use of Adjuvant Chemotherapy for High-Grade Truncal and Extremity Soft Tissue Sarcomas.

BACKGROUND: In the randomized controlled trial (RCT) EORTC 62931, adjuvant chemotherapy failed to show improvement in relapse-free survival (RFS) or overall survival (OS) for patients with resected high-grade soft tissue sarcoma (STS). We evaluated whether the negative results of this 2012 RCT have influenced multidisciplinary treatment patterns for patients with high-grade STS undergoing resection at seven academic referral centers. METHODS: The U.S. Sarcoma Collaborative database was queried to identify patients who underwent curative-intent resection of primary high-grade truncal or extremity STS from 2000 to 2016. Patients with recurrent tumors, metastatic disease, and those receiving neoadjuvant chemotherapy were excluded. Patients were divided by treatment era into early (2000-2011, pre-European Organisation for Research and Treatment of Cancer [EORTC] trial) and late (2012-2016, post-EORTC trial) cohorts for analysis. Rates of adjuvant chemotherapy and clinicopathologic variables were compared between the two cohorts. Univariate and multivariate regression analyses were used to determine factors associated with OS and RFS. RESULTS: 949 patients who met inclusion criteria were identified, with 730 patients in the early cohort and 219 in the late cohort. Adjuvant chemotherapy rates were similar between the early and late cohorts (15.6% versus 14.6%; P = 0.73). Patients within the early and late cohorts demonstrated similar median OS (128 months versus median not reached, P = 0.84) and RFS (107 months versus median not reached, P = 0.94). Receipt of adjuvant chemotherapy was associated with larger tumor size (13.6 versus 8.9 cm, P < 0.001), younger age (53.3 versus 63.7 years, P < 0.001), and receipt of adjuvant radiation (P < 0.001). On multivariate regression analysis, risk factors associated with decreased OS were increasing American Society of Anesthesiologists class (P = 0.02), increasing tumor size (P < 0.001), and margin-positive resection (P = 0.01). Adjuvant chemotherapy was not associated with OS (P = 0.88). Risk factors associated with decreased RFS included increasing tumor size (P < 0.001) and margin-positive resection (P = 0.03); adjuvant chemotherapy was not associated with RFS (P = 0.23). CONCLUSIONS: Rates of adjuvant chemotherapy for resected high-grade truncal or extremity STS have not decreased over time within the U.S. Sarcoma Collaborative, despite RCT data suggesting a lack of efficacy. In this retrospective multi-institutional analysis, adjuvant chemotherapy was not associated with RFS or OS on multivariate analysis, consistent with the results from EORTC 62931. Rates of adjuvant chemotherapy for high-grade STS were low in both cohorts but may be influenced more by selection bias based on clinicopathologic variables such as tumor size, margin status, and patient age than by prospective, randomized data.

Outcomes of palliative-intent surgery in retroperitoneal sarcoma-Results from the US Sarcoma Collaborative.

BACKGROUND AND OBJECTIVES: Outcomes of palliative-intent surgery in retroperitoneal sarcomas (RPS) are not well understood. This study aims to define indications for and outcomes after palliative-intent RPS resection. METHODS: Using a retrospective 8-institution database, patients undergoing resection of primary/recurrent RPS with palliative intent were identified. Logistic regression and Cox-proportional hazards models were constructed to analyze factors associated with postoperative complications and overall survival (OS). RESULTS: Of 3088 patients, 70 underwent 87 palliative-intent procedures. Most common indications were pain (26%) and bowel obstruction (21%). Dedifferentiated liposarcoma (n = 17, 24%), leiomyosarcoma (n = 13, 19%) were predominant subtypes. Median OS was 10.69 months (IQR, 3.91-23.23). R2 resection (OR, 8.60; CI, 1.42-52.15; P = .019), larger tumors (OR, 10.87; CI, 1.44-82.11; P = .021) and low preoperative albumin (OR, 0.14; CI, 0.04-0.57; P = .006) were associated with postoperative complications. Postoperative complications (HR, 1.95; CI, 1.02-3.71; P = .043) and high-grade histology (HR, 6.56; CI, 1.72-25.05; P = .006) rather than resection status were associated with reduced OS. However, in R2-resected patients, development of postoperative complications significantly reduced survival (P = .042). CONCLUSIONS: Postoperative complications and high-grade histology rather than resection status impacts survival in palliative-intent RPS resections. Given the higher incidence of postoperative complications which may diminish survival, palliative-intent R2 resection should be offered only after cautious consideration.

Facility Type is Associated with Margin Status and Overall Survival of Patients with Resected Intrahepatic Cholangiocarcinoma.

BACKGROUND: Many studies have demonstrated associations between surgical resections at academic centers and improved outcomes, particularly for complex operations. However, few studies have examined this relationship in intrahepatic cholangiocarcinoma (ICC). The hypothesis of this study was that facility type is associated with improved postoperative outcomes and survival for patients with ICC who undergo resection. METHODS: Patients with stages 1 to 3 ICC who underwent hepatectomy were identified using the National Cancer Database (NCDB) (2004-2014). Facilities were categorized as academic or community centers per Commission on Cancer designations. High-volume hospitals were those that performed 11 or more hepatectomies per year. Multilevel logistic mixed-effects models to identify predictors of outcomes and parametric survival-time models were used to determine overall survival (OS). RESULTS: The study identified 2256 patients. Of these patients, 423 (18.8%) were treated at community centers, and 1833 (81.3%) were treated at academic centers. Nearly all high-volume centers were academic facilities (98.5% academic vs. 1.5% community centers), whereas low-volume centers were mixed (65.5% academic vs. 34.5% community centers) (p < 0.001). Surgery performed at an academic center was an independent predictor of decreased positive margins (odds ratio [OR], 0.71; 95% confidence interval [CI], 0.51-0.98; p = 0.04), a lower 90-day mortality rate (OR, 0.62; 95% CI, 0.39-0.97; p = 0.03), and improved OS (hazard ratio [HR], 0.78; 95% CI, 0.63-0.96; p = 0.02). Facility hepatectomy volume was not independently associated with any short- or long-term outcomes. CONCLUSIONS: Treatment at an academic center is associated with fewer positive resection margins, a decreased 90-day mortality rate, and improved OS for patients who undergo ICC resection. Facility surgical volume was not shown to be significantly associated with any postoperative outcomes after adjustment for patient and disease characteristics.

Surgical resectability of multisite metastatic colorectal cancer: Pushing the limits while appropriately selecting patients.

Management of multisite colorectal metastases is expanding to make curative resection possible for more patients who present with advanced disease. Patient selection, tumor biology, meticulous surgical technique, and thoughtful perioperative care are essential to extending the benefit to patients previously treated with palliative goals of care.

Perioperative chemotherapy is not associated with improved survival in high-grade truncal sarcoma.

BACKGROUND: The treatment benefit of perioperative chemotherapy (CTX) for truncal soft tissue sarcoma (STS) is not well established. This study evaluates the association of CTX with survival for patients with resected primary high-grade truncal STS. MATERIALS AND METHODS: Adult patients with high-grade truncal STS who had curative-intent resection from 2000 to 2016 at seven U.S. institutions were evaluated retrospectively. Patients were stratified by receipt of CTX. Kaplan-Meier curves with log-rank tests were used to compare overall survival (OS) and recurrence-free survival. Logistic regression models were used to evaluate characteristics associated with OS. RESULTS: Of patients with primary high-grade truncal STS, 235 underwent curative-intent resections. The most common histology was undifferentiated pleomorphic sarcoma and mean tumor size was 7.8 cm. Thirty percent of the patients received CTX (n = 70). Among patients receiving CTX, 34% (n = 24) had neoadjuvant CTX, 44% (n = 31) adjuvant CTX, and 21% (n = 15) had neoadjuvant and adjuvant CTX. Patients receiving CTX were more likely to receive radiation (51% versus 34%, P = 0.01), have deep tumors (86% versus 73%, P = 0.037) and solid organ invasion (14% versus 3%, P = 0.001). On univariate analysis, patients who received CTX had worse OS (P < 0.01) and a trend toward worse recurrence-free survival (P = 0.08). Margin status was the only variable associated with improved OS on multivariate analysis (odds ratio 4.36, 95% confidence interval 1.56, 12.13, P < 0.01). CONCLUSIONS: In this multi-institutional retrospective analysis of resected high-grade truncal STS, receipt of perioperative CTX was not associated with improved OS, which may be related to selection bias. Microscopically negative margin status was the only independent factor associated with OS.

Ablation approach for primary liver tumors: Peri-operative outcomes.

BACKGROUND AND OBJECTIVES: Ablation is a common treatment modality for malignant primary liver tumors(PLTs), outcomes following laparoscopic (LA) versus open ablation (OA) are ill-defined. This project compares peri-procedural outcomes of LA versus OA for PLTs. MATERIALS AND METHODS: Patients with PLTs undergoing radiofrequency ablation were queried from ACS NSQIP Database (2005-2013) using CPT codes. Patients undergoing percutaneous ablation or hepatic resection were excluded. Multivariable logistic regression analyses determined the association of ablation approach with 30-day morbidity and mortality. RESULTS: Of 5747 with PLTs, 655 (11.4%) ablations were identified: 177 (27.0%) underwent OA, 478 (73.0%) underwent LA. Patients undergoing LA had lower mortality (1.9% vs 5.1%, P = 0.026), lower minor morbidity (2.3% vs 5.7%, P = 0.031), and lower major morbidity (4.2% vs 17.0%, P < 0.001). Adjusting for demographics, disease-specific variables (preoperative ascites, total bilirubin, platelet count, albumin, and INR), 30-day mortality (OR 3.85, 95%CI: 1.38-10.80, P = 0.010), minor morbidity (OR 2.98, 95%CI: 1.16-7.67, P = 0.024), and major morbidity (OR 4.59 95%CI: 2.41-8.76, P < 0.001) were statistically lower in LA. OA demonstrated increased length of stay(LOS) (5 vs 2 days, P < 0.001), and longer operative time (152 vs 112 min, P < 0.001). CONCLUSION: LA offers decreased peri-procedural morbidity, mortality, and reduced LOS. LA should be the preferred method for hepatic ablation.

Gallbladder carcinoma: An analysis of the national cancer data base to examine hispanic influence.

BACKGROUND: Gallbladder cancer (GBC) is a lethal disease with high incidence among Hispanics. Overall survival (OS) among races/ethnicities has not been described using the most recent National Cancer Database. This study hypothesized that prognosis is worse for Hispanics compared to similar non-Hispanic populations. METHODS: Patients with GBC were identified from the National Cancer Database and categorized as White, Black, Hispanic, and Other. Descriptive statistics, OS, and Cox regression were examined. RESULTS: The study identified 12 952 patients. Median age was 71 years and 68.8% were female. The study characterized 69.8% White, 13.9% Black, 11.0% Hispanic, and 5.4% other patients. A 5-year OS curves differed, with survival highest in Hispanic patients (27% vs 23% Other, 18% White, and 17% Black, P < 0.001). Hispanics presented at younger ages (67 vs 72 years, P < 0.001), were more likely to be uninsured (17.3% vs 3.9% P < 0.001), had lower income (P < 0.001), and education levels (P < 0.001) compared to Whites. Following multivariable modeling, treatment at an academic facility (HR 0.90, 95%CI 0.84-0.97) and year of diagnosis (HR 0.90, 95%CI 0.88-0.92) related to survival. Hispanic ethnicity did not show significance (P = 0.207). DISCUSSION: Hispanic ethnicity exhibits the highest OS for GBC, but after adjusting for covariates, this influence is not significant.

Morbidity of curative cancer surgery and suicide risk.

IMPORTANCE: Curative cancer operations lead to debility and loss of autonomy in a population vulnerable to suicide death. The extent to which operative intervention impacts suicide risk is not well studied. OBJECTIVE: To examine the effects of morbidity of curative cancer surgeries and prognosis of disease on the risk of suicide in patients with solid tumors. DESIGN: Retrospective cohort study using Surveillance, Epidemiology, and End Results data from 2004 to 2011; multilevel systematic review. SETTING: General US population. PARTICIPANTS: Participants were 482 781 patients diagnosed with malignant neoplasm between 2004 and 2011 who underwent curative cancer surgeries. MAIN OUTCOMES AND MEASURES: Death by suicide or self-inflicted injury. RESULTS: Among 482 781 patients that underwent curative cancer surgery, 231 committed suicide (16.58/100 000 person-years [95% confidence interval, CI, 14.54-18.82]). Factors significantly associated with suicide risk included male sex (incidence rate [IR], 27.62; 95% CI, 23.82-31.86) and age >65 years (IR, 22.54; 95% CI, 18.84-26.76). When stratified by 30-day overall postoperative morbidity, a significantly higher incidence of suicide was found for high-morbidity surgeries (IR, 33.30; 95% CI, 26.50-41.33) vs moderate morbidity (IR, 24.27; 95% CI, 18.92-30.69) and low morbidity (IR, 9.81; 95% CI, 7.90-12.04). Unit increase in morbidity was significantly associated with death by suicide (odds ratio, 1.01; 95% CI, 1.00-1.03; P = .02) and decreased suicide-specific survival (hazards ratio, 1.02; 95% CI, 1.00-1.03, P = .01) in prognosis-adjusted models. CONCLUSIONS: In this sample of cancer patients in the Surveillance, Epidemiology, and End Results database, patients that undergo high-morbidity surgeries appear most vulnerable to death by suicide. The identification of this high-risk cohort should motivate health care providers and particularly surgeons to adopt screening measures during the postoperative follow-up period for these patients.

Factors associated with palliative care use in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Peritoneal carcinomatosis represents widespread metastatic disease throughout the abdomen and/or pelvis. Cytoreductive surgery/hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) improves the overall survival compared to standard therapy alone. The role palliative care (PC) plays however, remains poorly studied among these patients. METHODS: Patients who had previously undergone HIPEC and who underwent an inpatient admission from 7/1/2013 to 6/30/2014 were identified to determine which patients were referred for inpatient or outpatient palliative consultation. Multivariable logistic regression analysis was performed to identify risk factors associated with the use of PC. RESULTS: Of the 60 patients analyzed, 23 (38.3%) had a PC consultation with a median time to PC referral of 310 (IQR: 151-484 days). Patients who were prescribed opioids (no PC referral versus PC referral: 46.0% versus 91.3%, P < 0.001), patients who reported the use of a cancer-related emetic (35.1% versus 87.0%, P < 0.001), patients reporting the use of total parenteral nutrition (16.2% versus 39.1%, P = 0.046), and patients dependent on a gastric tube for nutrition (5.4% versus 43.5%, P < 0.001) were more likely to be referred to a PC consultation. On multivariable analysis, use of opioids, use of a cancer-related antiemetic, and the use of a G-tube were independently associated with a greater odds for being referred to PC (all P < 0.05). CONCLUSIONS: Approximately one-third of patients were referred to PC following cytoreductive surgery/hyperthermic intraperitoneal chemotherapy. Palliative care referrals were most commonly used for patients with chronic symptoms, which are difficult to manage, especially toward the end of life.

The prognostic utility of baseline alpha-fetoprotein for hepatocellular carcinoma patients.

INTRODUCTION: Alpha-fetoprotein (AFP) has a valuable role in postoperative surveillance for hepatocellular carcinoma (HCC) recurrence. The utility of pretreatment or baseline AFP remains controversial. The present study hypothesized that elevated baseline AFP levels are associated with worse overall survival in HCC patients. METHODS: Adult HCC patients were identified using the National Cancer Database (2004-2013). Patients were stratified according to baseline AFP measurements into the following groups: Negative (<20), Borderline (20-199), Elevated (200-1999), and Highly Elevated (>2000). The primary outcome was overall survival (OS), which was analyzed by log-rank test and graphed using Kaplan-Meier method. Multivariate regression modeling was used to determine hazard ratios (HR) for OS. RESULTS: Of 41 107 patients identified, 15 809 (33.6%) were Negative. Median overall survival was highest in the Negative group, followed by Borderline, Elevated, and Highly Elevated (28.7 vs 18.9 vs 8.8 vs 3.2 months; P < 0.001). On multivariate analysis, overall survival hazard ratios for the Borderline, Elevated, and Highly Elevated groups were 1.18 (P = 0.267), 1.94 (P < 0.001), and 1.77 (P = 0.007), respectively (reference Negative). CONCLUSION: Baseline AFP independently predicted overall survival in HCC patients regardless of treatment plan. A baseline AFP value is a simple and effective method to assist in expected survival for HCC patients.

External radiation or ablation for solitary hepatocellular carcinoma: A survival analysis of the SEER database.

BACKGROUND AND OBJECTIVES: Hepatocellular carcinoma (HCC) patients are often not candidates for resection. This study hypothesized that external beam radiation (XRT) could be equally effective compared to ablation therapy (AT) for selected HCC patients. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify HCC patients (2004-2012) undergoing XRT or AT for solitary HCC lesions. Propensity score modeling was utilized to adjust for baseline characteristics. RESULTS: Propensity matching identified 784 patients: 157 (20%) XRT and 627 (80%) AT. Median OS for XRT and AT was 22, and 32 months (P < 0.001), respectively. AT demonstrated improved OS for tumors 3-5 cm (30 vs 16 m, P < 0.001) and >5 cm (25 vs 9 m, P < 0.001). Similar survival was found in patients with tumor size <3 cm (37 vs 47 m P = 0.508). Following multivariate analyses, XRT was associated with an increased hazard ratio (HR = 1.64, P < 0.001). Elevated AFP at diagnosis (HR = 1.54, P = 0.001) and tumor size >3 were identified as negative predictors of survival. CONCLUSIONS: Similar survival for solitary HCC lesions <3 cm exists between XRT and AT. However, AT demonstrates improved survival rates compared to XRT for lesions >3 cm. This 3 cm reference point may serve as a valuable metric to guide treatment decisions and future investigations.