Curative-intent Surgical Resection Research Articles

Outcomes in patients undergoing curative surgery for gastric cancer by facility type and socioeconomic factors: An analysis of the National Cancer Database (NCDB).

4066 Background: Surgical and medical treatment for resectable gastric cancer is complex, and multidisciplinary team involvement is essential to provide optimal treatment outcomes. However, socioeconomic disparities influence the quality of medical care patients receive. We hypothesized that facility type, median income, insurance type, and location would impact patients' overall survival (OS). Methods: In a retrospective analysis of NCDB data, we identified patients with stage II and III gastric adenocarcinoma who underwent curative-intent surgical resection and chemotherapy between 2004-2018. Demographic and socioeconomic factors were studied, including treatment facility type, median household income, urban/rural residence, and insurance status. Multivariate Cox proportional hazard model was used to evaluate the impact of these variables on overall survival (OS). The Kaplan-Meier method was used to estimate OS. Log-rank test was used to compare the OS between groups. Results: Based on the criteria listed above, 36,318 patients were identified: 76.3% were Caucasian, 14.4% black, 7.2% Asian, and 2.0% other. 56.4% lived in large metropolitan areas (LM), 29.9% in small/medium metropolitan areas (SM), and 14.2% in rural areas (RA). Patients who were treated in academic/research programs had significantly better OS (mOS 40.5 months) compared to integrated-network cancer programs (mOS 34.0 months, HR 0.897, p < 0.0001), comprehensive community cancer programs (mOS 31.0 months, HR 0.89, p < 0.0001), and community cancer programs (mOS 29.5, HR 0.881, p < 0.0001). Patients from LM had better OS compared to those from SM and RA (mOS 39.0, 32.1, 29.9 months respectively, p < 0.0001). Privately insured patients had improved OS compared to Medicare-insured patients (mOS 40.8 vs 29.7 months, HR 0.758, p < 0.0001). Higher annual income (≥ $63,000) was positively associated with improved OS (p < 0.0001). Conclusions: Outcomes for patients with gastric cancer treated with surgery and chemotherapy are strongly influenced by socioeconomic variables, including place of residence, treatment setting, insurance, and income level. We highlight improved outcomes in patients who resided in LM and were treated at academic/research centers. A potential hypothesis for this trend is increased access to specialized, multidisciplinary care and clinical trials.

Analysis of cathepsin S expression in gastric adenocarcinoma and in Helicobacter pylori infection.

Recent experimental studies have suggested a potential link between cathepsin S (CTTS) and gastric adenocarcinoma progression. Herein, we aimed to evaluate the expression of CTTS in gastric adenocarcinoma in patients who underwent curative-intent surgical resection. This was a cross-sectional study that included two groups: gastric adenocarcinoma (n = 42) and gastritis (n = 50). The gastritis group was then subdivided into H. pylori-positive (n = 25) and H. pylori-negative (n = 25) groups. Gastric tissue samples were analysed to determine CTTS expression through immunohistochemistry. Samples were obtained by oesophagogastroduodenoscopy or surgical specimens. In patients with gastritis, the age ranged from 18 to 78 years. Among them, 34% were male, and 66% were female. In patients with gastric adenocarcinoma, the age ranged from 37 to 85 years. Among them, 50% were male. When comparing the expression of CTTS between the two groups, only 16% of the gastritis samples had an expression higher than 25%. Alternatively, among patients with gastric adenocarcinoma, 19% had expression between 25-50%, 14.3% between 51-75%, and 26.2% had expression higher than 75% (p < 0.001). In the gastritis group, CTTS expression was significantly higher in patients with a positive test for H. pylori than negative test for H. pylori: 87.5% and 38.5%, respectively (p<0.001). There was no statistically significant association between CTTS positivity and clinicopathological variables, including tumour staging, histological type, angiolymphatic invasion, recurrence, current status and death. CTTS expression is higher in gastric adenocarcinoma samples. Patients with gastritis due to H. pylori also show a higher expression of CTTS than patients with negative results for this bacterium.

Utility of Perioperative Measurement of Cell-Free DNA and Circulating Tumor DNA in Informing the Prognosis of GI Cancers: A Systematic Review.

Current surveillance imaging and tumor markers lack sensitivity for the early detection of recurrence in GI cancers. This study critically evaluates the current literature on the role of sequential measurement of circulating tumor DNA (ctDNA) before and after curative resection in informing recurrence. A systematic search using a predefined, registered protocol was conducted for studies published between January 2010 and May 2020. Included studies described patients with GI cancers treated with curative-intent surgical resection and measurement of ctDNA both before and after surgery. Patients were divided into three groups on the basis of the presence or absence of ctDNA at these time points. The primary outcome was recurrence-free survival (RFS). The search yielded 3,873 articles; five met the inclusion criteria and collectively evaluated 57 patients. Pooled median RFS was 62 months (interquartile range 19 to not reached). Although median RFS was not reached in group 1 (- to -) or group 2 (+ to -), median RFS in group 3 (+ to +) was 15 months (interquartile range 9.6-60.4 months). Cox hazard ratio was 4.46 (95% CI, 1.17 to 16.99; P = .028) between group 1 and group 2, and 10.47 (95% CI, 2.91 to 37.74; P < .001) between group 2 and group 3. Detectable ctDNA, either preoperatively or postoperatively, and its persistence after curative surgery are associated with a greater risk of recurrence and decreased RFS in GI cancers. Thus, perioperative measurement of ctDNA may be a useful postoperative risk stratification tool and guide additional therapies.

Comparison of clinicopathological characteristics of mucinous adenocarcinoma and conventional adenocarcinoma of gallbladder

BackgroundGallbladder mucinous adenocarcinoma (GBMAC) is a rare type of gallbladder malignant tumor, whereas little is known regarding the clinicopathological features and surgical outcomes of GBMAC. MethodsFrom January 2000 till December 2015, 54 GBMAC patients who underwent curative-intent surgical resection at our institution were retrospectively reviewed. We compared the clinicopathological features and surgical outcomes of these GBMAC patients with a relatively large cohort of surgically resected conventional gallbladder adenocarcinoma (GBAC) patients without existence of mucinous components. ResultsThe clinicopathological features of GBMAC were significantly different from conventional GBAC, including poorer tumor differentiation (P < 0.001), higher CA19-9 levels (P < 0.001), larger tumor sizes (P = 0.020), advanced AJCC tumor stage (P = 0.002), higher frequency of liver parenchyma invasion (P = 0.020), portal vein invasion (P = 0.003), lymph node metastasis (P = 0.016), lympho-vascular invasion (P < 0.001) and perineural invasion (P = 0.025). Relative to conventional GBAC patients, GBMAC patients showed significantly worse overall survival (OS) (29.0 vs 15.0 months; P < 0.001). Multivariate analysis confirmed the surgical margin (P = 0.046), tumor differentiation grade (P = 0.018), lymph node metastasis (P = 0.024), and presence of signet-ring cell component (P = 0.005) as independent prognostic factors influencing OS of patients with GBMAC. ConclusionGBMAC always had more aggressive biological behaviors and poor survival outcomes even after curative surgery. GBMAC patients with the presence of signet-ring cell component showed even worse survival outcome.

Determining Which Patients Require Preoperative Pelvic Radiotherapy Before Curative-Intent Surgery and/or Ablation for Metastatic Rectal Cancer.

The aim of this study is to determine the optimal indications for preoperative pelvic radiotherapy (RT) in patients with metastatic rectal cancer who underwent curative-intent surgical resection and/or ablation. Between January 2000 and October 2019, 246 patients who met our inclusion criteria were enrolled. Preoperative RT was performed in 22 patients (8.9%). Lower margin below the peritoneal reflection (p < 0.001), mesorectal fascia (MRF) invasion (p = 0.02), and lateral pelvic lymph node (LPLN) involvement (p = 0.005) were more frequent in the preoperative RT group. During the median follow-up period of 13.3 months (interquartile range [IQR]: 6.0-36.3 months), local recurrence (LR) was identified in 60 patients (24.4%). It was the first site of recurrence in 45 of them (18.3%). Among them, three patients were in the preoperative RT group. On multivariable analysis, lower margin below the peritoneal reflection, MRF invasion, LPLN involvement, carcinoembryonic antigen (CEA) level ≥ 10 ng/mL before treatment, and preoperative RT were significant prognostic factors for LR-free survival (LRFS). In the patient group without any risk factors, the 2-year LRFS rate was 94.9% without preoperative RT. In the patient group with one or more risk factors, the 2-year LRFS was 64.4% without and 95.2% with preoperative RT. LR developed in about 25% of patients within 2 years. Preoperative RT should be considered, especially in patients with a risk factor for LR, including lower margin below the peritoneal reflection, MRF invasion, LPLN involvement, or CEA ≥ 10 ng/mL before treatment.

Surgical resection for adrenocortical carcinoma: Current trends affecting survival.

Adrenocortical carcinoma (ACC) is associated with a poor prognosis. We reviewed the National Cancer Database (NCDB) to analyze the prognostic factors in surgically resected ACC patients and the association of surgical approaches with overall survival (OS). A retrospective NCDB (2004-2014) review of patients undergoing curative-intent surgical resection for ACC was performed. Effects of patient demographics, tumor characteristics, histopathology, and perioperative course on OS were analyzed. Log-rank statistics were used to associate clinical variables with OS. The multivariable Cox proportional hazard model included only statistically significant variables. A total of 1599 patients with ACC were included. A majority of patients were female (60.73%) and presented with a Charlson-Deyo score of zero (75.42%). A majority of the ACC cases were Grade 3 (45.69%), and almost a third (30.64%) underwent margin-positive resections. Univariate analysis demonstrated a decrease in OS associated with increasing age and comorbidities. A negative resection margin and lack of lymphovascular invasion predicted better OS. Multivariable analysis showed that age, grade, surgical resection margins, and hospital length of stay were associated with OS. Advanced age, grade, presence of lymphovascular invasion, and positive surgical margins predicted a worse overall survival for adrenocortical cancer in our analysis. Resection with negative margins improves outcomes.

Neoadjuvant Approaches in Hepatocellular Carcinoma: There's No Time Like the Present

Abstract Hepatocellular carcinoma (HCC) remains a lethal malignancy and is an increasingly common cause of cancer death worldwide. Curative-intent surgical resection remains the standard of care for eligible patients, yet outcomes remain poor for many patients, with most patients experiencing recurrence in the 5 years after resection. There is currently significant interest in using locoregional and systemic therapies—in both the neoadjuvant and adjuvant settings—to increase the chance of cure. This review article appraises the existing literature and current clinical trial landscape of neoadjuvant therapies in HCC.

The impact of germline and somatic mutations in the homologous recombination repair pathway in pancreatic cancer patients who undergo perioperative chemotherapy.

602 Background: Limited data is available regarding the effects of germline and somatic mutations in the homologous recombination repair (HRR) pathway in patients with resectable pancreatic cancer and exactly which mutations can be targeted with platinum-based chemotherapy. We aimed to assess the impact of HRR pathway mutations in a large cohort of pancreatic patients who underwent curative intent surgical resection. Methods: Patients with resectable pancreatic cancer who underwent perioperative chemotherapy, diagnosed from 1999-2020 from the participating members of the Oncology Research Information Exchange Network (ORIEN) were included in the study. Patients with germline and somatic whole exome sequencing data were analyzed for known pathogenic and likely pathogenic variants according to ClinVar in the following HRR pathway genes: BRCA1, BRCA2, PALB2, BRIP1, BRAD1, ATM, RAD51C, RAD51, RAD50, CHECK2, FANCC, FANCA, MRE11 and XRCC2. The Kaplan Meier method was used to compare median overall survival (OS) between patients with adenocarcinoma, with and without HRR pathway mutations. Multivariate cox proportional hazard model was used to calculate HR and 95% CI adjusting for age at diagnosis, sex and pathologic stage. Results: During the study period, the ORIEN cohort included 417 patients with resectable pancreatic cancer and whole exome sequencing. Of these 313 (75%) patients had adenocarcinoma and 104 (25%) neuroendocrine tumor. A total of 19 patients (5%) had an HRR pathway mutation - 15 (5%) in the adenocarcinoma group and 4 (4%) in the neuroendocrine group. In the adenocarcinoma group, 97 (31%) patients underwent platinum-based perioperative chemotherapy. Median OS was 2.8 years (IQR 2.5-3.3) in the adenocarcinoma group without HRR pathway mutation and 3.8 years (IQR 3.4-NA) in the group with HRR pathway mutation (HR 0.6: 95% CI 0.3-1.4, p = 0.76). Conclusions: There was a trend towards improved survival in patients with adenocarcinoma receiving perioperative platinum-based chemotherapy with HRR pathway mutations compared to those without a mutation. This finding supports previous data in the literature regarding the prognostic role of HRR pathway alterations in pancreatic cancer. Larger prospective studies are needed to assess the predictive role of these mutations in the perioperative setting in response to platinum-based chemotherapy.

Clinical relevance of adjuvant chemotherapy in patients with pancreatic ductal adenocarcinoma who underwent surgery following neoadjuvant modified FOLFIRINOX.

546 Background: The benefit of adjuvant chemotherapy (ACT) following curative-intent surgery in pancreatic ductal adenocarcinoma (PDAC) patients who had received neoadjuvant modified FOLFIRINOX (mFOLFIRINOX) remains unidentified. This retrospective analysis aimed to assess the clinical relevance of ACT in patients who underwent surgery following neoadjuvant mFOLFIRINOX. Methods: Between January 2017 and December 2020, 220 patients received neoadjuvant mFOLFIRINOX and underwent pancreatectomy for localized PDAC at the Asan Medical Center, Seoul, Korea. Patients unable to undergo curative-intent surgical resection (R0 or R1) and those with histological types other than ductal adenocarcinoma were excluded. Survival outcomes were compared according to ACT administration. Disease-free survival (DFS) was defined as the duration between surgery and recurrence or death of any etiology, whichever occurred first; and overall survival (OS) was that between surgery and death from any etiology. Results: ACT was administered to 150 (68.2%) patients. ACT recipients were significantly younger (median age, 61 vs. 64, p = 0.035) and they received significantly fewer cycles of neoadjuvant chemotherapy (median, 7 vs. 9, p = 0.0001) compared to non-recipients. As ACT, mFOLFIRINOX (n = 98, 65.3%), gemcitabine monotherapy (n = 39, 26.0%), and gemcitabine-capecitabine (n = 4, 2.7%) were administered. ACT recipients showed significantly better survival outcomes compared to non-recipients; median DFS 13.4 months (95% CI, 10.7–18.8) vs. 8.3 months (95% CI, 4.9–16.0), respectively (p = 0.0042); and median OS 33.4 months (95% CI, 29.9–NA) vs. 23.8 months (95% CI, 17.9–NA), respectively (p = 0.0021). DFS and OS were significantly better in ACT recipients regardless of the lymph node (LN) status during surgery (p = 0.033 for DFS and p = 0.027 for OS in negative LN; and p = 0.032 for DFS and p = 0.012 for OS in positive LN). There was no significant difference in DFS (p = 0.79) and OS (p = 0.49) between mFOLFIRINOX and gemcitabine-based regimens. In multivariate analysis, ACT remained significant as a favorable prognostic factor (DFS, hazard ratio [HR] 0.43 (95%CI, 0.26–0.71, p = 0.001); OS, HR 0.33 (95%CI, 0.17–0.64, p = 0.001). Conclusions: In PDAC patients who underwent surgery following neoadjuvant mFOLFIRINOX, ACT may be associated with improved survival outcomes. Its benefit was not affected by the LN status and ACT regimens.

Emerging Evidence from Landmark Clinical Trials on Perioperative Immunotherapy in Resectable Non-Small Cell Lung Cancer

Non-small cell lung cancer (NSCLC) remains one of the most prevalent cancers worldwide, with high rates of local and distant recurrence limiting survival even after curative-intent surgical resection. Traditional adjuvant chemotherapy benefits only 5% of patients, and as such additional treatment modalities are urgently needed to improve NSCLC patient outcomes. Systemic therapy with PD1 and PDL1 immune check-point inhibitors (ICIs) has emerged as a promising treatment option in many types of solid malignancies, including lung cancer. Encouraging results from immunotherapy trials in metastatic lung cancer populations, and now newer results from ongoing clinical trials in early stage locally advanced lung cancers, suggested an evolving role for perioperative immune checkpoint inhibition in resectable NSCLC. In this review we examine the latest advances in the landscape of clinical trials on immunotherapy in resectable NSCLC. We discuss the key findings and specific clinical challenges related to neoadjuvant administration of these immune therapies in the CheckMate816, Impower030, AEGEAN and KEYNOTE671 phase III clinical trials. The role of adjuvant ICI is also discussed examining the ANVIL, Impower010, and PEARLS trials. By understanding the remaining unanswered questions and clinical dilemmas that exist in this rapidly evolving field for ICIs in early stage NSCLC, clinicians may provide patients options which may markedly improve survival outcomes for this life-threatening disease.

Oncologic outcomes of patients with resectable primary gastric squamous cell carcinoma: a systematic review.

BackgroundPrimary gastric squamous cell carcinoma (PGSCC) is an uncommon type of gastric malignancy estimated to comprise around 0.04-0.5% of all gastric malignancies. PGSCC’s long-term survival has been quoted to range from 17-50% depending on stage, with surgery arguably representing the most useful modality for prolonging oncologic survival. Nevertheless, reliable data on its effectiveness are still lacking in the literature.MethodA systematic literature search of the Medline, Cochrane library and Scopus databases was undertaken, to identify cases of surgically managed PGSCC reporting patient-related outcomes.ResultsIn total, 23 case reports and 1 case series incorporating 38 patients were identified. Mean patient age was 61.2 years and the male/female ratio was 18:1. Most tumors were high-stage at the time of diagnosis, with the T4 stage predominating in the patient pool (n=15, 50%) along with a high percentage of lymphatic spread (N positive tumors, n=15, 47%). All patients underwent curative-intent surgical resection and were subsequently followed for an average of 30.7±14 months. Extrapolated survival data revealed a projected 3- and 5-year overall survival of 62.2% and 51.9%, respectively, while the 3-year probability for being disease-free was calculated to be 30.8%. T4 stage and lymphatic spread were found to be predictors of poor survival in univariate but not in multivariate analysis.ConclusionNotwithstanding the methodological limitations inherent to the present review, the obtained results, when superimposed on existing cross-sectional survival data, suggest significantly enhanced patient survival following surgery, solidifying its role in the management of patients with PGSCC.

Association between Timing and Duration of Adjuvant Chemotherapy and Colorectal Cancer Survival in Korea, 2011-2014: A Nationwide Study based on the Health Insurance Review and Assessment Service Database.

Background: Population-based analyses of the treatment outcomes of colorectal cancer (CRC) in Asian countries are limited. Therefore, we conducted a nationwide study to assess the relationship between the timing and duration of adjuvant chemotherapy (AC) and survival in patients with CRC in South Korea.Methods: Data on AC from the Health Insurance Review and Assessment Service Database (HIRA) were analyzed, and the survival of patients who underwent curative-intent surgical resection for CRC between 2011 and 2014 was investigated.Results: From the HIRA data, 45,992 patients with stage II-III CRC were identified. Chemotherapy regimens were administered as follows: 10,640 (23.3%) received 5-fluorouracil and leucovorin/capecitabine (FL/CAP), 13,083 (28.7%) received FL/CAP plus oxaliplatin (FOLFOX/CAPOX), 299 (0.7%) received uracil and tegafur/doxifluridine (UFT/D), and 21,570 (47.3%) underwent surgery alone. Patients who did not receive AC had worse survival than those who received AC in both the colon and rectum groups (HR, 1.96, 95% CI, 1.85-2.07 and HR, 2.18, 95% CI, 2.01-2.37, respectively). Regarding patients with stage II-III CRC, AC initiation ≥ 2 months after surgery was associated with a significant decrease in overall survival (OS) (FL/CAP: HR, 1.82; 95% CI, 1.53-2.17 and FOLFOX/CAPOX: HR, 2.92; 95% CI, 2.47-3.45); however, the effects of UFT/D regimens were not statistically significant. For patients with stage II-III colon cancer, AC <3 months had lower OS (FL/CAP: HR, 3.72, 95% CI, 2.80-4.94; FOLFOX/CAPOX: HR, 2.15, 95% CI, 1.87-2.47; and UFT/D: HR, 1.74, 95% CI, 0.56-5.41). In terms of patients with stage II-III rectal cancer, AC <3 months, regardless of chemotherapy regimens, had a significant lower survival (FL/CAP: HR, 1.91, 95% CI, 1.66-2.20; FOLFOX/CAPOX: HR, 2.20, 95% CI, 1.75-2.77; and UFT/D: HR, 3.71, 95% CI, 1.45-9.44).Conclusions: Postoperative time to initiation and duration of AC were associated with survival. Based on our results, initiating AC within 2 months after surgery and administering AC for >3 months can potentially have an OS benefit in patients with stage II-III CRC.

Timing of postoperative radiation therapy and survival in resected salivary gland cancers: Long-term results from a single institution

ObjectivesTimely administration of postoperative radiation therapy (PORT) impacts oncologic outcomes in resected squamous cell carcinomas of the head and neck. Salivary gland cancers (SGCs) are uncommon, and timing of PORT has not been extensively explored. We aimed to determine if the interval between surgery and PORT impacts outcomes in SGCs. Materials and MethodsThis is a retrospective study of patients with SGCs who underwent curative intent surgical resection followed by adjuvant PORT. Locoregional recurrence free survival (LRFS), disease free survival (DFS), and overall survival (OS) were estimated using the Kaplan Meier method. A multivariate analysis explored the association between demographics, tumor characteristics, and PORT timing with oncologic outcomes using a stepwise Cox proportional hazards model. Results180 eligible patients were identified. The median time to PORT start was 61 (range 8–121) days. 169 (93.5%) of patients received neutron radiation. With a median follow up of 8.2 years in surviving patients, the 10-year OS and LRFS estimates were 61% and 53%. In a multivariate analysis, nodal involvement, histologic grade, and age at diagnosis were associated with OS, while nodal involvement, tumor size, and age at diagnosis were associated with LRFS and DFS. Time to PORT start or completion was not statistically associated with survival outcomes. ConclusionSGC patients who underwent surgery in our tertiary institution received PORT within a median of 61 days after surgery. With long term follow up, PORT timing in this retrospective series was not associated with worse oncologic outcomes, and support timely administration of PORT.

Prognosis for Poorly Differentiated, High-Grade Rectal Neuroendocrine Carcinomas.

Rectal neuroendocrine carcinomas (rNECs) are poorly characterized and, given their aggressive nature, optimal management is not well-established. We therefore sought to describe clinicopathologic traits, treatment details, and survival patterns for patients with rNECs. Patients captured in the National Cancer Database (NCDB; 2004-2016) with rNECs managed with observation, chemotherapy, or proctectomy ± chemotherapy were considered for analysis. The inclusion criteria were met by 777 patients. Mean age was 62.4 years, 45% were male, 80% were Caucasian, 40% presented with lymph nodes metastases, and 49% presented with distant metastases. Chemotherapy and surgical resection were administered in 72 and 19% of cases, respectively. Median overall survival (OS) was 0.83 years (1year, 41%; 3 years, 13%; 5years, 10%). During the study interval, 659 (85%) patients died, with a median follow-up of 0.79 years. On multivariable analysis, age ≥60years, male sex, and distant metastases were associated with worse survival; surgical resection and administration of chemotherapy were associated with a reduced risk of death. Among non-metastatic patients treated with surgical resection, administration of chemotherapy was protective, while a positive lymph node ratio (LNR) ≥42% (median value) was associated with an increased risk of death. There was no difference in the number of examined lymph nodes between LNR cohorts. Patients with rNECs experience dismal survival outcomes, including those with non-metastatic disease treated with curative-intent surgical resection. Neoadjuvant therapy can serve as a useful biologic test, and surgical resection should be judiciously employed.

Neoadjuvant Chemotherapy Switch in Borderline Resectable/Locally Advanced Pancreatic Cancer

BackgroundNeoadjuvant chemotherapy (NAC) is an integral part of preoperative treatment for patients with borderline resectable/locally advanced (BR/LA) pancreatic ductal adenocarcinoma (PDAC). The identification of a chemotherapeutic regimen that is both effective and tolerable is critical for NAC to be of oncologic benefit. After initial first-line (FL) NAC, some patients have lack of response or therapeutic toxicities precluding further treatment with the same regimen; optimal decision making regarding this patient population is unclear. Chemotherapy switch (CS) may allow for a larger proportion of patients to undergo curative-intent resection after NAC.MethodsWe reviewed our surgical database for patients undergoing combinatorial NAC for BR/LA PDAC. Variant histologic exocrine carcinomas, intraductal papillary mucinous neoplasm-associated PDAC, and patients without research consent were excluded.ResultsOverall, 468 patients with BR/LA PDAC receiving FL chemotherapy were reviewed, of whom 70% (329/468) continued with FL chemotherapy followed by surgical resection. The remaining 30% (139/468) underwent CS, with 72% (100/139) of CS patients going on to curative-intent surgical resection. Recurrence-free survival (RFS) and overall survival (OS) were not significantly different between the resected FL and CS cohorts (30.0 vs. 19.1 months, p = 0.13, and 41.4 vs. 36.4 months, p = 0.94, respectively) and OS was significantly worse in those undergoing CS without subsequent resection (19 months, p < 0.0001). On multivariable analysis, carbohydrate antigen (CA) 19-9 and pathologic treatment responses were predictors of RFS and OS.ConclusionCS in patients undergoing NAC for BR/LA pancreatic cancer does not incur oncologic detriment. The incorporation of CS into NAC treatment sequencing may allow a greater proportion of patients to proceed to curative-intent surgery.

Intrahepatic Cholangiocarcinoma: A Summative Review of Biomarkers and Targeted Therapies.

Simple SummaryIntrahepatic cholangiocarcinoma is the second most common primary liver malignancy. Among patients with operable disease, surgical resection is the cornerstone of therapy. Among the majority of patients who present with advanced disease treatment, systemic or targeted therapy is indicated. Recent advancements have provided more novel therapeutic approaches to a subset of patients with intrahepatic cholangiocarcinoma. Although rare, intrahepatic cholangiocarcinoma (ICC) is the second most common primary hepatic malignancy and the incidence of ICC has increased 14% per year in recent decades. Treatment of ICC remains difficult as most people present with advanced disease not amenable to curative-intent surgical resection. Even among patients with operable disease, margin-negative surgical resection can be difficult to achieve and the incidence of recurrence remains high. As such, there has been considerable interest in systemic chemotherapy and targeted therapy for ICC. Over the last decade, the understanding of the molecular and genetic foundations of ICC has reshaped treatment approaches and strategies. Next-generation sequencing has revealed that most ICC tumors have at least one targetable mutation. These advancements have led to multiple clinical trials to examine the safety and efficacy of novel therapeutics that target tumor-specific molecular and genetic aberrations. While these advancements have demonstrated survival benefit in early phase clinical trials, continued investigation in randomized larger-scale trials is needed to further define the potential clinical impact of such therapy.

Association of Medicaid Expansion with Pancreatic Cancer Treatment and Outcomes: Evidence from the National Cancer Database.

Socioeconomic- and demographic-based disparities exist in the treatment of pancreatic adenocarcinoma (PDAC). Medicaid expansion (ME) may have an impact on these disparities. Analyses of patients with PDAC from the National Cancer Database (NCDB) were performed to examine the impact of ME on access to treatment and outcomes. Patients with non-metastatic PDAC diagnosed between 2006 and 2016 were identified. Multiple logistic regression analyses were performed to evaluate factors associated with curative-intent surgical resection, multimodal therapy, treatment at a high-volume facility (HVF), and survival. The study identified 41,876 patients who met the criteria. Medicaid expansion was independently associated with curative-intent resection (odds ratio [OR] 1.54; 95 % confidence interval [CI] 1.43-1.67; p < 0.001). In a multivariable analysis, ME was independently associated with multimodal therapy (OR 1.60; 95 % CI 1.44-1.76; p < 0.001) and treatment at an HVF (OR 1.57; 95 % CI 1.42-1.74; p < 0.001). Medicaid expansion was independently associated with improved 30-day mortality (OR 0.49; 95 % CI 0.34-0.79) and 90-day mortality (OR 0.48 95 % CI 0.35-0.59). Cox regression analysis demonstrated that after adjustment for other variables, ME status was associated with improved overall survival (hazard ratio [HR], 0.82; 95 % CI 0.73-0.90; p < 0.001). Medicaid expansion is associated with increased use of care processes that improve outcomes in PDAC, operative outcomes, and overall survival. The study data suggest that ME has helped to improve disparities in PDAC in ME states.

The Presence of Small Nerve Fibers in the Tumor Microenvironment as Predictive Biomarker of Oncological Outcome Following Partial Hepatectomy for Intrahepatic Cholangiocarcinoma.

Simple SummaryNerve fibers in the microenvironment of malignant tumors have been shown to be an important prognostic factor for long-term survival in various cancer types; however, their role in intrahepatic cholangiocarcinoma remains to be determined. Therefore, the impact of nerve fibers on long-term survival was investigated in a large European cohort of patients with intrahepatic cholangiocarcinoma who were treated by curative-intent surgical resection. By univariate and multivariate statistics, the absence of nerve fibers was determined to be an independent predictor of impaired long-term survival. A group comparison between patients with and without nerve fibers showed a statically significant difference with a cancer-specific 5-year-survival of 47% in patients with nerve fibers compared to 21% in patients without nerve fibers. Thus, the presence of nerve fibers in the microenvironment of intrahepatic cholangiocarcinoma is revealed as a novel and important prognostic biomarker in these patients.The oncological role of the density of nerve fibers (NFs) in the tumor microenvironment (TME) in intrahepatic cholangiocarcinoma (iCCA) remains to be determined. Therefore, data of 95 iCCA patients who underwent hepatectomy between 2010 and 2019 was analyzed regarding NFs and long-term outcome. Extensive group comparisons were carried out and the association of cancer-specific survival (CSS) and recurrence-free survival (RFS) with NFs were assessed using Cox regression models. Patients with iCCA and NFs showed a median CSS of 51 months (5-year-CSS = 47%) compared to 27 months (5-year-CSS = 21%) in patients without NFs (p = 0.043 log rank). Further, NFs (hazard ratio (HR) = 0.39, p = 0.002) and N-category (HR = 2.36, p = 0.010) were identified as independent predictors of CSS. Patients with NFs and without nodal metastases displayed a mean CSS of 89 months (5-year-CSS = 62%), while patients without NFs or with nodal metastases but not both showed a median CCS of 27 months (5-year-CSS = 25%) and patients with both positive lymph nodes and without NFs showed a median CCS of 10 months (5-year-CSS = 0%, p = 0.001 log rank). NFs in the TME are, therefore, a novel and important prognostic biomarker in iCCA patients. NFs alone and in combination with nodal status is suitable to identify iCCA patients at risk of poor oncological outcomes following curative-intent surgery.

Trends in Accuracy and Comprehensiveness of Pathology Reports for Resected NSCLC in a High Mortality Area of the United States

IntroductionComplete and accurate pathology reports are vital to postoperative prognostication and management. We evaluated the impact of three interventions across a diverse group of hospitals on pathology reports of postresection NSCLC. MethodsWe evaluated pathology reports for patients who underwent curative-intent surgical resection for NSCLC, at 11 institutions within four contiguous Dartmouth Hospital Referral Regions in Arkansas, Mississippi, and Tennessee from 2004 to 2020, for completeness and accuracy, before and after the following three quality improvement interventions: education (feedback to heighten awareness); synoptic reporting; and a lymph node specimen collection kit. We compared the proportion of pathology reports with the six most important items for postoperative management (specimen type, tumor size, histologic type, pathologic [p] T-category, pN-category, margin status) across the following six patient cohorts: preintervention control, postintervention with four different combinations of interventions, and a contemporaneous nonintervention external control. ResultsIn the postintervention era, the odds of reporting all key items were eight times higher than those in the preintervention era (OR = 8.3, 95 % confidence interval [CI]: 6.7–10.2, p < 0.0001). There were sixfold and eightfold increases in the odds of accurate pT- and pN-category reporting in the postintervention era compared with the preintervention era (pT OR = 5.7, 95 % CI: 4.7–6.9; pN OR = 8.0, 95 % CI: 6.5–10.0, both p < 0.0001). Within the intervention groups, the odds of reporting all six key items, accurate pT category, and accurate pN-category were highest in patients who received all three interventions. ConclusionsGaps in the quality of NSCLC pathologic reportage can be identified, quantified, and corrected by rationally designed interventions.

Novel Strategies in Locally Advanced Kidney Cancer - Highlights from KEYNOTE-564.

With upwards of 30% recurrence rates in patients with locally advanced kidney cancer undergoing curative-intent surgical resection, there is a critical need to develop multimodal strategies to improve outcomes in these patients. The first pre-specified interim results from the phase III KEYNOTE-564 study were presented at the 2021 ASCO Annual Meeting as an encouraging approach to address this need.