The multidisciplinary management of cholangiocarcinoma.

Cholangiocarcinoma is a lethal malignancy of the biliary epithelium that can arise anywhere along the biliary tract. Surgical resection confers the greatest likelihood of long-term survivability. However, its insidious onset, difficult diagnostics, and resultant advanced presentation render the majority of patients unresectable, highlighting the importance of early detection with novel biomarkers. Developing liver-directed therapies and emerging targeted therapeutics may offer improved survivability for patients with unresectable or advanced disease. In this article, the authors review the current multidisciplinary standards of care in resectable and unresectable cholangiocarcinoma, with an emphasis on novel biomarkers for early detection and nonsurgical locoregional therapy options.

Adjuvant Chemoradiation in Patients with Lymph Node-Positive Biliary Tract Cancers: Secondary Analysis of a Single-Arm Clinical Trial (SWOG 0809).

BACKGROUND: SWOG 0809 is the only prospective study of adjuvant chemotherapy followed by chemoradiation focusing on margin status in patients with extrahepatic cholangiocarcinoma (EHCC) and gallbladder cancer (GBCA); however, the effects of adjuvant therapy by nodal status have never been reported in this population. METHODS: Patients with resected EHCC and GBCA, stage pT2-4, node-positive (N+) or margin-positive (R1) who completed four cycles of chemotherapy followed by radiotherapy were included. Cox regression was used to compare overall survival (OS), disease-free survival (DFS), local recurrence, and distant metastasis by nodal status. DFS rates were compared with historical data via a one-sample t-test. RESULTS: Sixty-nine patients [EHCC, n = 46 (66%); GBCA, n = 23 (33%)] were evaluated, with a median age of 61.7 years and an R0 rate of 66.7% and R1 rate of 33.3%. EHCC versus GBCA was more likely to be N+ (73.9% vs. 47.8%, p = 0.03). Nodal status did not significantly impact OS (hazard ratio [HR] 1.98, 95% confidence interval [CI] 0.86-4.54, p = 0.11) or DFS (HR 1.63, 95% CI 0.77-3.44, p = 0.20). Two-year OS was 70.6% for node-negative (N0) disease and 60.9% for N+ disease, while 2-year DFS was 62.5% for N0 tumors and 49.8% for N+ tumors. N+ versus N0 tumors showed higher rates of distant failure (42.2% vs. 25.0%, p = 0.04). The 2-year DFS rate in N+ tumors was significantly higher than in historical controls (49.8% vs. 29.7%, p = 0.004). CONCLUSIONS: Adjuvant therapy is associated with favorable outcome independent of nodal status and may impact local control in N+ patients. These data could serve as a benchmark for future adjuvant trials, including molecular-targeted agents.

NEO-GAP: A Single-Arm, Phase II Feasibility Trial of Neoadjuvant Gemcitabine, Cisplatin, and Nab-Paclitaxel for Resectable, High-Risk Intrahepatic Cholangiocarcinoma.

PURPOSE: Most patients with intrahepatic cholangiocarcinoma (IHCC) develop recurrence after resection. Adjuvant capecitabine remains the standard of care for resected IHCC. A combination of gemcitabine, cisplatin, and nab-paclitaxel (GAP) was associated with a 45% response rate and 20% conversion rate among patients with unresectable biliary tract cancers. The aim of this study was to evaluate the feasibility of delivering GAP in the neoadjuvant setting for resectable, high-risk IHCC. METHODS: A multi-institutional, single-arm, phase II trial was conducted for patients with resectable, high-risk IHCC, defined as tumor size > 5 cm, multiple tumors, presence of radiographic major vascular invasion, or lymph node involvement. Patients received preoperative GAP (gemcitabine 800 mg/m2, cisplatin 25 mg/m2, and nab-paclitaxel 100 mg/m2 on days 1 and 8 of a 21-day cycle) for a total of 4 cycles prior to an attempt at curative-intent surgical resection. The primary endpoint was completion of both preoperative chemotherapy and surgical resection. Secondary endpoints were adverse events, radiologic response, recurrence-free survival (RFS), and overall survival (OS). RESULTS: Thirty evaluable patients were enrolled. Median age was 60.5 years. Median follow-up for all patients was 17 months. Ten patients (33%) experienced grade ≥ 3 treatment-related adverse events, the most common being neutropenia and diarrhea; 50% required ≥ 1 dose reduction. The disease control rate was 90% (progressive disease: 10%, partial response: 23%, stable disease: 67%). There was zero treatment-related mortality. Twenty-two patients (73%, 90% CI 57-86; p = 0.008) completed all chemotherapy and surgery. Two patients (9%) who successfully underwent resection had minor postoperative complications. Median length of hospital stay was 4 days. Median RFS was 7.1 months. Median OS for the entire cohort was 24 months and was not reached in patients who underwent surgical resection. CONCLUSION: Neoadjuvant treatment with gemcitabine, cisplatin, and nab-paclitaxel is feasible and safe prior to resection of intrahepatic cholangiocarcinoma and does not adversely impact perioperative outcomes.

Calcifications and Cystic Morphology on Preoperative Imaging Predict Survival After Resection of Pancreatic Neuroendocrine Tumors.

BACKGROUND: Radiographic calcifications and cystic morphology are associated with higher and lower tumor grade, respectively, in pancreatic neuroendocrine tumors (PNETs). Whether calcifications and/or cystic morphology could be used preoperatively to predict post-resection survival in patients with PNETs remains elusive. METHODS: Patients undergoing curative-intent resection of well-differentiated PNETs from 2000 to 2017 at eight academic institutions participating in the US Neuroendocrine Tumor Study Group were identified. Preoperative cross-sectional imaging reports were reviewed to identify the presence of calcifications and of a cystic component occupying >50% of the total tumor area. Clinicopathologic characteristics and recurrence-free survival (RFS) were compared. RESULTS: Of 981 patients studied, 18% had calcifications and 17% had cystic tumors. Tumors with calcifications were more commonly associated with Ki-67 ≥3% (47% vs. 33%; p = 0.029), lymph node metastasis (36% vs. 24%; p = 0.011), and distant metastasis (13% vs. 4%; p < 0.001). In contrast, cystic tumors were less commonly associated with lymph node metastasis (12% vs. 30%; p < 0.001). Five-year RFS after resection was most favorable for cystic tumors without calcifications (91%), intermediate for solid tumors without calcifications (77%), and least favorable for any calcified PNET (solid 69%, cystic 67%; p = 0.043). Calcifications remained an independent predictor of RFS on multivariable analysis (p = 0.043) controlling for nodal (p < 0.001) and distant metastasis (p = 0.001). CONCLUSIONS: Easily detectable radiographic features, such as calcifications and cystic morphology, can be used preoperatively to stratify prognosis in patients with PNETs and possibly inform the decision to operate or not, as well as guide the extent of resection and potential use of neoadjuvant therapy.

Current Practices in Hepatic Artery Infusion (HAI) Chemotherapy: An International Survey of the HAI Consortium Research Network.

BACKGROUND: An increasing number of hepatic artery infusion (HAI) programs have been established worldwide. Practice patterns for this complex therapy across these programs have not been reported. This survey aimed to identify current practice patterns in HAI therapy with the long-term goal of defining best practices and performing prospective studies. METHODS: Using SurveyMonkeyTM, a 28-question survey assessing current practices in HAI was developed by 12 HAI Consortium Research Network (HCRN) surgical oncologists. Content analysis was used to code textual responses, and the frequency of categories was calculated. Scores for rank-order questions were generated by calculating average ranking for each answer choice. RESULTS: Thirty-six (72%) HCRN members responded to the survey. The most common intended initial indications for HAI at new programs were unresectable colorectal liver metastases (uCRLM; 100%) and unresectable intrahepatic cholangiocarcinoma (uIHC; 56%). Practice patterns evolved such that uCRLM (94%) and adjuvant therapy for CRLM (adjCRLM; 72%) have become the most common current indications for HAI at established centers. Referral patterns for pump placement differed between uCRLM and uIHC, with most patients referred while receiving second- and first-line therapy, respectively, with physicians preferring to evaluate patients for HAI while receiving first-line therapy for CRLM. Concern for extrahepatic disease was ranked as the most important factor when considering a patient for HAI. CONCLUSIONS: Indication and patient selection factors for HAI therapy are relatively uniform across most HCRN centers. The increasing use of adjuvant HAI therapy and overall consistency of practice patterns among HCRN centers provides a robust environment for prospective data collection and randomized clinical trials.

Care at high-volume centers is associated with improved outcomes for patients with pancreatic neuroendocrine tumors: A population-level analysis.

BACKGROUND AND OBJECTIVES: Primary resection and debulking of liver metastases have been associated with improved survival in pancreatic neuroendocrine tumors (PNETs). The treatment patterns and outcomes differences between low-volume (LV) institutions and high-volume (HV) institutions remains unstudied. METHODS: A statewide cancer registry was queried for patients with nonfunctional PNET from 1997 to 2018. LV institutions were defined as treating <5 newly diagnosed patients with PNET per year, while HV institutions treated ≥5. RESULTS: We identified 647 patients: 393 with locoregional (n = 236 HV care, n = 157 LV care) and 254 with metastatic disease (n = 116 HV care, n = 138 LV care). Patients with HV care had improved disease-specific survival (DSS) compared to patients with LV care for both locoregional (median 63 vs. 32 months, p < 0.001) and metastatic disease (median 25 vs. 12 months, p < 0.001). In patients with metastatic disease, primary resection (hazard ratio [HR]: 0.55, p = 0.003) and HV institution (HR: 0.63, p = 0.002) were independently associated with improved DSS. Furthermore, diagnosis at a HV center was independently associated with higher odds of receiving primary site surgery (odds ratio [OR]: 2.59, p = 0.01) and metastasectomy (OR: 2.51, p = 0.03). CONCLUSIONS: Care at HV centers is associated with improved DSS in PNET. We recommend referral of all patients with PNETs to HV centers.

Does Caudate Resection Improve Outcomes of Patients Undergoing Curative Resection for Perihilar Cholangiocarcinoma? A Systematic Review and Meta-Analysis.

BACKGROUND: Margin-negative (R0) resection is the strongest positive prognostic factor in perihilar cholangiocarcinoma (PHC). Due to its anatomic location, the caudate lobe is frequently involved in PHC. This review aimed to examine the impact of caudate lobe resection (CLR) in addition to hepatectomy and bile duct resection for patients with PHC. METHODS: The MEDLINE, EMBASE, and Cochrane databases were systematically reviewed from inception to October 2021 to identify studies comparing patients undergoing surgical resection with hepatectomy and bile duct resection with or without CLR for treatment of PHC. Outcomes included the proportion of patients achieving R0 resection, overall survival (OS), and perioperative morbidity. RESULTS: Altogether, 949 studies were screened. The review included eight observational studies reporting on 1137 patients. The patients who underwent CLR had a higher likelihood of R0 resection (odds ratio [OR], 5.85; 95% confidence interval [CI], 2.64-12.95) and a better OS (hazard ratio [HR], 0.65; 95% CI, 0.54-0.79) than those who did not. The use of CLR did not increase the risk of perioperative morbidity (OR, 1.03; 95% CI, 0.65-1.63). CONCLUSIONS: Given the higher likelihood of R0 resection, improved OS, and no apparent increase in perioperative morbidity, this review supports routine caudate lobectomy in the surgical management of PHC. These results should be interpreted with caution given the lack of high-quality prospective data and the high probability of selection bias.

Does Intraoperative Frozen Section and Revision of Margins Lead to Improved Survival in Patients Undergoing Resection of Perihilar Cholangiocarcinoma? A Systematic Review and Meta-analysis.

BACKGROUND: Perihilar cholangiocarcinoma (PHC) is a rare malignancy that arises at the biliary confluence. Achieving a margin-negative resection (R0) is challenging given the anatomic location of tumors and remains the most important prognostic indicator of long-term survival. The objective of this study is to review the impact of intraoperative revision of positive biliary margins in PHC on oncologic outcomes. PATIENTS AND METHODS: Electronic databases were searched from inception to October 2021. Studies comparing three types of patients undergoing resection of PHC with intraoperative frozen section of the proximal and/or distal bile ducts were identified: those who were margin-negative (R0), those with an initially positive margin who had revised negative margins (R1R0), and those with a persistently positive margin with or without revision of a positive margin (R1). The primary outcome was overall survival (OS). Secondary outcomes included risk of postoperative complication. RESULTS: A total of 449 studies were screened. Ten retrospective observational studies reporting on 1955 patients were included. Patients undergoing successful revision of a positive proximal and/or distal bile duct margin (R1R0) had similar OS to those with a primary margin-negative resection (R0) [hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.72-1.19, p = 0.56, I2 = 84%], and significantly better OS than patients with a positive final bile duct margin (R1) (HR 0.52, 95% CI 0.34-0.79, p = 0.002, I2 = 0%). There was no increase in the risk of postoperative complications associated with additional resection, although postoperative morbidity was inconsistently reported. CONCLUSIONS: This review supports routine intraoperative biliary margin evaluation during resection of PHC with revision if technically feasible.

Disparities in Electronic Screening for Cancer-Related Psychosocial Distress May Promote Systemic Barriers to Quality Oncologic Care.

BACKGROUND: Screening for cancer-related psychosocial distress is an integral yet laborious component of quality oncologic care. Automated preappointment screening through online patient portals (Portal, MyChart) is efficient compared with paper-based screening, but unstudied. We hypothesized that patient access to and engagement with EHR-based screening would positively correlate with factors associated with digital literacy (eg, age, socioeconomic status). METHODS: Screening-eligible oncology patients seen at our Comprehensive Cancer Center from 2014 through 2019 were identified. Patients with active Portals were offered distress screening. Portal and screening participation were analyzed via multivariable logistic regression. Household income in US dollars and educational attainment were estimated utilizing zip code and census data. RESULTS: Of 17,982 patients, 10,279 (57%) had active Portals and were offered distress screening. On multivariable analysis, older age (odds ratio [OR], 0.97/year; P<.001); male gender (OR, 0.89; P<.001); Black (OR, 0.47; P<.001), Hawaiian/Pacific Islander (OR, 1.54; P=.007), and Native American/Alaskan Native race (OR, 0.67; P=.04); Hispanic ethnicity (OR, 0.76; P<.001); and Medicare (OR, 0.59; P<.001), Veteran's Affairs/military (OR, 0.09; P<.01), Medicaid (OR, 0.34; P<.001), or no insurance coverage (OR, 0.57; P<.001) were independently associated with lower odds of being offered distress screening; increasing income (OR, 1.05/$10,000; P<.001) and educational attainment (OR, 1.03/percent likelihood of bachelor's degree or higher; P<.001) were independently associated with higher odds. In patients offered electronic screening, participation rate was 36.6% (n=3,758). Higher educational attainment (OR, 1.01; P=.03) was independently associated with participation, whereas Black race (OR, 0.58; P=.004), Hispanic ethnicity (OR, 0.68; P=.01), non-English primary language (OR, 0.67; P=.03), and Medicaid insurance (OR, 0.78; P<.001) were independently associated with nonparticipation. CONCLUSIONS: Electronic portal-based screening for cancer-related psychosocial distress leads to underscreening of vulnerable populations. At institutions using electronic distress screening workflows, supplemental screening for patients unable or unwilling to engage with electronic screening is recommended to ensure efficient yet equal-opportunity distress screening.

Surgical timing after preoperative chemotherapy is associated with oncologic outcomes in resectable colorectal liver metastases.

INTRODUCTION: Preoperative chemotherapy (POC) is often employed for patients with resectable colorectal liver metastasis (CRLM). The time to resection (TTR) following the end of chemotherapy may impact oncologic outcomes; this phenomenon has not been studied in CRLM. METHODS: We queried our institutional cancer database for patients with resected CRLM after POC from 2003 to 2019. TTR was calculated from date of last cytotoxic chemotherapy. Kaplan-Meier analysis and multivariable Cox proportional hazards modeling were used to analyze recurrence-free survival (RFS) and overall survival (OS). RESULTS: We identified n = 187 patients. One hundred twenty-four (66%) patients had a TTR of <2 months, while 63 (33%) had a TTR of ≥2 months. Median follow-up was 36 months. On Kaplan-Meier analysis, patients with TTR ≥ 2 months had shorter RFS (median 11 vs. 17 months, p = 0.002) and OS (median 44 vs. 62 months, p < 0.001). On multivariable analysis, TTR ≥ 2 months was independently associated with worse RFS (hazard ratio [HR] = 1.54, 95% confidence interval [CI] = 1.06-2.22, p = 0.02) and OS (HR = 1.75, 95% CI = 1.11-2.77, p = 0.01). CONCLUSION: TTR ≥ 2 months following POC is independently associated with worse oncologic outcomes in patients with resectable CRLM. We therefore recommend consideration for hepatic resection of CRLM within this window whenever feasible.

Considerations and barriers to starting a new HAI pump program: an international survey of the HAI Consortium Research Network.

BACKGROUND: Widespread implementation of HAI pump chemotherapy has been limited by logistic and feasibility concerns. Recent studies demonstrating excellent outcomes have fueled renewed enthusiasm and multiple new programs have emerged. This survey aims to identify barriers critical to establish a successful HAI program. METHODS: Using SurveyMonkey™, a 17-question survey assessing factors required for establishing a successful program was developed by 12 HAI Consortium Research Network (HCRN) surgical oncologists. Content analysis was used to code textual responses. Frequency of categories and average rank scores for each choice were calculated. RESULTS: Twenty-eight HCRN members responded to the survey. Implementation time varied, with 15 institutions requiring less than a year. Most programs (n = 17) became active in the past 5 years. Medical and surgical oncology were ranked most important for building a program (average ranking scores: 7.96 and 6.59/8). Administrative or regulatory approval was required at half of the institutions. The top 3 challenges faced when building a program were related to regulatory approval (6.65/9), device/equipment access (6.33/9), and drug (FUDR) access (6.25/9). CONCLUSION: Development of successful programs outside of historically established centers is feasible and requires a multidisciplinary team. Future collaborative efforts are critical for sustainability of safe/effective new programs.

Landmark Series: Immunotherapy and Targeted Therapy for Pancreatic Cancer.

Pancreatic cancer is one of the most aggressive gastrointestinal malignancies despite multimodality therapy. In the last several years, genomic studies have revealed that carcinogenesis is driven largely by key driver mutations that can be targeted for oncologic therapy. In addition, advances in cancer immunology have identified receptors and monoclonal antibodies that can be manipulated into harnessing the power of the host's immune system for antitumor treatment. These strategies have generated a paradigm shift in the management of several cancer types, including those in the gastrointestinal tract. However, there are several complicating factors when translating the results to pancreatic cancer, including the dense, fibrotic stroma unique to this disease that may shield the cancer cells from both cytotoxic and immunologic agents. Although the majority of trials have been performed in the metastatic setting, this review will focus on both the historic studies that have defined this field as well as the emerging data arising from ongoing efforts to exploit newly discovered mutations and their druggable targets.

Oncoplastic Breast-Conserving Surgery: Can We Reduce Rates of Mastectomy and Chemotherapy Use in Patients with Traditional Indications for Mastectomy?

INTRODUCTION: Traditional indications for mastectomy include multiple ipsilateral lesions and/or disease spanning ≥ 5 cm. Neoadjuvant chemotherapy increases breast conservation but does not improve survival. We hypothesized that oncoplastic breast-conserving surgery (OPS) may allow for breast conservation while providing full staging and tumor profiling information to guide systemic therapy decisions, thereby permitting more judicious chemotherapy use. METHODS: This was an observational cohort of patients with invasive breast cancer with multiple lesions and/or disease spanning ≥ 5 cm who underwent OPS from 2012 to 2018. Clinicopathologic features, mastectomy rate, chemotherapy use, and recurrence were evaluated. RESULTS: Overall, 100 patients were identified. Average disease span was 62.8 ± 20.1 mm, with an average of 2.9 lesions (range 1-13). 'No ink on tumor' was achieved at the index operation in 80 patients; 13 patients underwent completion mastectomy to achieve adequate margins. Eighty-one patients completed radiation therapy. Breast conservation was possible in 50/58 (86%) patients who did not receive chemotherapy. Forty-two patients received chemotherapy (8 neoadjuvant, 34 adjuvant), of whom 37 (88%) achieved breast conservation. Twenty-six patients with high-risk features received adjuvant chemotherapy. Oncotype DX testing demonstrated the need for chemotherapy in an additional eight patients. After a median follow-up of 40 months, four patients had a local recurrence, including two who declined radiation therapy. CONCLUSIONS: OPS can facilitate breast conservation in most patients with traditional indications for mastectomy. Additionally, OPS may reduce unnecessary chemotherapy, especially in patients who qualify for Oncotype DX testing. Further study evaluating long-term oncologic and cosmetic outcomes is warranted.

Long-Term Outcomes after Spleen-Preserving Distal Pancreatectomy for Pancreatic Neuroendocrine Tumors: Results from the US Neuroendocrine Study Group.

BACKGROUND: The adoption of spleen-preserving distal pancreatectomy (SPDP) for malignant disease such as pancreatic neuroendocrine tumors (pNETs) has been controversial. The objective of the current study was to assess the impact of SPDP on outcomes of patients with pNETs. METHODS: Patients undergoing a distal pancreatectomy for pNET between 2002 and 2016 were identified in the US Neuroendocrine Tumor Study Group database. Propensity score matching (PSM) was used to compare short- and long-term outcomes of patients undergoing SPDP versus distal pancreatectomy with splenectomy (DPS). RESULTS: Among 621 patients, 103 patients (16.6%) underwent an SPDP. Patients who underwent SPDP were more likely to have lower BMI (median, 27.5 [IQR 24.0-31.2] vs. 28.7 [IQR 25.7-33.6]; p = 0.005) and have undergone minimally invasive surgery (n = 56, 54.4% vs. n = 185, 35.7%; p < 0.001). After PSM, while the median total number of lymph nodes examined among patients who underwent an SPDP was lower compared with DPS (3 [IQR 1-8] vs. 9 [5-13]; p < 0.001), 5-year overall survival (OS) and recurrence-free survival (RFS) were comparable (OS: 96.8 vs. 92.0%, log-rank p = 0.21, RFS: 91.1 vs. 84.7%, log-rank p = 0.93). In addition, patients undergoing SPDP had less intraoperative blood loss (median, 100 mL [IQR 10-250] vs. 150 mL [IQR 100-400]; p = 0.001), lower incidence of serious complications (n = 13, 12.8% vs. n = 28, 27.5%; p = 0.014), and shorter length of stay (median: 5 days [IQR 4-7] vs. 6 days [IQR 5-13]; p = 0.049) compared with patients undergoing DPS. CONCLUSION: SPDP for pNET was associated with acceptable perioperative and long-term outcomes that were comparable to DPS. SPDP should be considered for patients with pNET.

Seminars in surgical oncology-Pancreas cancer adjuvant therapy trials.

Adjuvant therapy for pancreatic cancer has undergone a paradigm shift in the last 30 years. Before the 1990s, surgery was the main treatment with high morbidity and minimal long-term survival. In the mid-1980s, GITSG showed a doubling of overall survival from 11 to 20 months with 5-fluorouracil-based chemoradiation and now the PRODIGE trial showed the benefit of FOLFIRINOX with the longest overall survival to date approaching 5 years. Further investigation on the agents, duration and sequencing of therapy remains ongoing.

A comparison of surgical resection and liver transplantation in the treatment of intrahepatic cholangiocarcinoma in the era of modern chemotherapy: An analysis of the National Cancer Database.

BACKGROUND: The main surgical approach to patients with localized intrahepatic cholangiocarcinoma (ICC) is hepatectomy, but transplantation has been described. A comparison of outcomes between these surgical approaches is necessary to determine if one is preferable. METHODS: Patients with ICC were identified using the National Cancer Database (2010-2016). Patients were grouped based on operation and matched 1:1 by propensity score. Pathologic and postoperative outcomes, as well as overall survival were analyzed. RESULTS: There were 1879 hepatectomy and 74 liver transplantation patients. Before matching, transplantation patients were younger and more often treated at academic centers. More patients who underwent a transplantation received neoadjuvant chemotherapy (70.3% vs. 12.8%). Patients who underwent transplantation had more pathologic T0 (7.7% vs. 0.4%) and T1 (47.7% vs. 42.1%) tumors (p < .001). There were no differences in length of stay, unplanned readmissions, 30/90-day mortality, or median survival between groups (36.1 vs. 36.1 months, p = .34). After matching (n = 57/group), there were no differences in postoperative outcomes or survival between transplantation or hepatectomy (36.1 vs. 33.6 months, p = .57). CONCLUSION: Among patients with ICC, hepatectomy and liver transplantation were associated with similar postoperative outcomes and survival. In light of the resources and chronic immunosuppression required for transplantation, hepatectomy seems preferable for localized ICC.

Sustained Carbohydrate Antigen 19-9 Response to Neoadjuvant Chemotherapy in Borderline Resectable Pancreatic Cancer Predicts Progression and Survival.

BACKGROUND: As neoadjuvant therapy of borderline resectable pancreatic cancer (BRPC) is becoming more widely used, better indicators of progression are needed to help guide therapeutic decisions. MATERIALS AND METHODS: A retrospective review was performed on all patients with BRPC who received 24 weeks of neoadjuvant chemotherapy. Patients with chemotoxicity or medical comorbidities limiting treatment completion and nonexpressors of carbohydrate antigen 19-9 (CA19-9) were excluded. Serum CA19-9 response was analyzed as a predictor of disease progression, recurrence, and survival. RESULTS: One hundred four patients were included; 39 (37%) progressed on treatment (18 local and 21 distant) and 65 (63%) were resected (68% R0). Multivariate logistic regression analysis determined that the percent decrease in CA19-9 from baseline to minimum value (odds ratio [OR] 0.947, p ≤ .0001) and the percent increase from minimum value to final restaging CA19-9 (OR 1.030, p ≤ .0001) were predictive of progression. A receiver operating characteristics curve analysis determined cutoff values predictive of progression, which were used to create four prognostic groups. CA19-9 responses were categorized as follows: (1) always normal (n = 6); (2) poor response (n = 31); (3) unsustained response (n = 19); and (4) sustained response (n = 48). Median overall survival for Groups 1-4 was 58, 16, 20, and 38 months, respectively (p ≤ .0001). CONCLUSION: Patients with initially elevated CA19-9 levels who do not have a decline to a sustained low level are at risk for progression, recurrence, and poor survival. Alternative treatment strategies prior to an attempt at curative resection should be considered in this cohort. IMPLICATIONS FOR PRACTICE: This study identified percent changes in carbohydrate antigen 19-9 blood levels while on chemotherapy that predict tumor growth in patients with advanced pancreas cancer. These changes could be used to better select patients who would benefit from surgical removal of their tumors and improve survival.

Evaluating Need for Additional Imaging and Biopsy After Oncoplastic Breast-Conserving Surgery.

INTRODUCTION: Breast-conserving therapy (BCT) using oncoplastic surgery (OPS) allows for larger resections and improved aesthetics though volume redistribution and tissue rearrangement. Data regarding the impact of OPS on surveillance imaging and need for additional biopsies are limited. METHODS: This observational cohort underwent BCT at a single institution from 2009 to 2018; standard breast-conserving surgery (BCS) was the predominant approach until OPS was introduced in 2012. Rates of imaging beyond standard diagnostic views, as well as rates of biopsy following both approaches, are reported. RESULTS: A total of 422 consecutive patients were identified. The OPS group comprised 205 patients and the BCS group included 217 patients. There was no difference in need for additional imaging between groups (BCS: 58 patients [26.7%] vs. OPS: 53 patients [25.9%]; p = 0.91). When additional imaging was required, it was on the ipsilateral side in 35 (60.3%) BCS patients compared with 24 (45.3%) OPS patients (p = 0.21). The need for biopsy was higher in the BCS group (BCS: 41 patients [18.9%] with 47 total biopsies vs. OPS: 20 patients [9.3%] with 22 total biopsies; p < 0.01). Benign findings on biopsy were similar between groups (BCS: 18 [38.3%] vs. OPS: 11 [50.0%]; p = 0.66). CONCLUSIONS: OPS was not associated with an increased need for additional imaging compared with BCS. Concern regarding challenges with follow-up imaging should not impact the decision to offer OPS. Further study and longer-term follow-up is warranted to understand the trends in need for additional imaging, biopsy, and additional procedures following OPS.

Specific Growth Rate as a Predictor of Survival in Pancreatic Neuroendocrine Tumors: A Multi-institutional Study from the United States Neuroendocrine Study Group.

BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) are often indolent; however, identifying patients at risk for rapidly progressing variants is critical, particularly for those with small tumors who may be candidates for expectant management. Specific growth rate (SGR) has been predictive of survival in other malignancies but has not been examined in PNETs. METHODS: A retrospective cohort study of adult patients who underwent PNET resection from 2000 to 2016 was performed utilizing the multi-institutional United States Neuroendocrine Study Group database. Patients with ≥ 2 preoperative cross-sectional imaging studies at least 30 days apart were included in our analysis (N = 288). Patients were grouped as "high SGR" or "low SGR." Demographic and clinical factors were compared between the groups. Kaplan-Meier and log-rank analysis were used for survival analysis. Cox proportional hazard analysis was used to assess the impact of various clinical factors on overall survival (OS). RESULTS: High SGR was associated with higher T stage at resection, shorter doubling time, and elevated HbA1c (all P ≤ 0.01). Patients with high SGR had significantly decreased 5-year OS (63 vs 80%, P = 0.01) and disease-specific survival (72 vs 91%, P = 0.03) compared to those with low SGR. In patients with small (≤ 2 cm) tumors (N = 106), high SGR predicted lower 5-year OS (79 vs 96%, P = 0.01). On multivariate analysis, high SGR was independently associated with worse OS (hazard ratio 2.67, 95% confidence interval 1.05-6.84, P = 0.04). CONCLUSION: High SGR is associated with worse survival in PNET patients. Evaluating PNET SGR may enhance clinical decision-making, particularly when weighing expectant management versus surgery in patients with small tumors.

Impact of Insurance Status on Survival in Gastroenteropancreatic Neuroendocrine Tumors.

BACKGROUND: Insurance status predicts access to medical care in the USA. Previous studies have shown uninsured patients with some malignancies have worse outcomes than insured patients. The impact of insurance status on patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is unclear. PATIENTS AND METHODS: A retrospective cohort study of adult patients with resected GEP-NETs was performed using the US Neuroendocrine Tumor Study Group (USNETSG) database (2000-2016). Demographic and clinical factors were compared by insurance status. Patients ≥ 65 years were excluded, as these patients are almost universally covered by Medicare. Kaplan-Meier and log-rank analyses were used for survival analysis. Logistic regression was used to assess factors associated with overall survival (OS). RESULTS: The USNETSG database included 2022 patients. Of those, 1425 were aged 18-64 years at index operation and were included in our analysis. Uninsured patients were more likely to have an emergent operation (7.9% versus 2.5%, p = 0.01) and less likely to receive postoperative somatostatin analog therapy (1.6% versus 9.9%, p = 0.03). OS at 1, 5, and 10 years was significantly higher for insured patients (96.3%, 88.2%, and 73.8%, respectively) than uninsured patients (87.7%, 71.9%, and 44.0%, respectively) (p < 0.01). On Cox multivariate regression analysis controlling for T/M stage, tumor grade, ASA class, and income level, being uninsured was independently associated with worse OS [hazard ratio (HR) 2.69, 95% confidence interval (CI) 1.32-5.48, p = 0.006]. CONCLUSIONS: Insurance status is an independent predictor of survival in patients with GEP-NETs. Our study highlights the importance of access to medical care, disparities related to insurance status, and the need to mitigate these disparities.