Trends Over Time in Recurrence Patterns and Survival Outcomes after Neoadjuvant Therapy and Surgery for Pancreatic Cancer.

OBJECTIVE: We aimed to determine if advances in neoadjuvant therapy affected recurrence patterns and survival outcomes after pancreatectomy for pancreatic ductal adenocarcinoma (PDAC). BACKGROUND: Data are limited on how modern multimodality therapy affects PDAC recurrence and post-recurrence survival. METHODS: Patients who received neoadjuvant therapy followed by curative-intent pancreatectomy for PDAC during 1998-2018 were identified. Treatments, recurrence sites and timing, and survival were compared between patients who completed neoadjuvant therapy and pancreatectomy in 1998-2004, 2005-2011, and 2012-2018. RESULTS: The study included 727 patients (203, 251, and 273 in the 1998-2004, 2005-2011, and 2012-2018 cohorts, respectively). Use of neoadjuvant induction chemotherapy increased over time, and regimens changed over time, with >80% of patients treated in 2012-2018 receiving FOLFIRINOX or gemcitabine with nab-paclitaxel. Overall, recurrence sites and incidence (67.5%, 66.1%, and 65.9%) remained stable, and 85% of recurrences occurred within 2 years of surgery. However, compared to earlier cohorts, the 2012-2018 cohort had lower conditional risk of recurrence in postoperative year 1 and higher risk in postoperative year 2. Overall survival increased over time (median, 30.6, 33.6, and 48.7 mo, P < 0.005), driven by improved post-recurrence overall survival (median, 7.8, 12.5, and 12.6 mo; 3-year rate, 7%, 10%, and 20%; P < 0.005). CONCLUSIONS: We observed changes in neoadjuvant therapy regimens over time and an associated shift in the conditional risk of recurrence from postoperative year 1 to postoperative year 2, although recurrence remained common. Overall survival and post-recurrence survival remarkably improved over time, reflecting improved multimodality regimens for recurrent disease.

Gut Microbiome in Patients With Early-Stage and Late-Stage Melanoma.

Importance: The gut microbiome modulates the immune system and responses to immunotherapy in patients with late-stage melanoma. It is unknown whether fecal microbiota profiles differ between healthy individuals and patients with melanoma or if microbiota profiles differ among patients with different stages of melanoma. Defining gut microbiota profiles in individuals without melanoma and those with early-stage and late-stage melanoma may reveal features associated with disease progression. Objective: To characterize and compare gut microbiota profiles between healthy volunteers and patients with melanoma and between patients with early-stage and late-stage melanoma. Design, Setting, and Participants: This single-site case-control study took place at an academic comprehensive cancer center. Fecal samples were collected from systemic treatment-naive patients with stage I to IV melanoma from June 1, 2015, to January 31, 2019, and from healthy volunteers from June 1, 2021, to January 31, 2022. Patients were followed up for disease recurrence until November 30, 2021. Main Outcomes and Measures: Fecal microbiota was profiled by 16S ribosomal RNA sequencing. Clinical and pathologic characteristics, treatment, and disease recurrence were extracted from electronic medical records. Fecal microbiome diversity, taxonomic profiles and inferred functional profiles were compared between groups. Results: A total of 228 participants were enrolled (126 men [55.3%]; median age, 59 [range, 21-90] years), including 49 volunteers without melanoma, 38 patients with early-stage melanoma (29 with stage I or melanoma in situ and 9 with stage II), and 141 with late-stage melanoma (66 with stage III and 75 with stage IV). Community differences were observed between patients with melanoma and volunteers. Patients with melanoma had a higher relative abundance of Fusobacterium compared with controls on univariate analysis (0.19% vs 0.003%; P < .001), but this association was attenuated when adjusted for covariates (log2 fold change of 5.18 vs controls; P = .09). Microbiomes were distinct between patients with early-stage and late-stage melanoma. Early-stage melanoma had a higher alpha diversity (Inverse Simpson Index 14.6 [IQR, 9.8-23.0] vs 10.8 [IQR, 7.2-16.8]; P = .003), and a higher abundance of the genus Roseburia on univariate analysis (2.4% vs 1.2%; P < .001) though statistical significance was lost with covariate adjustment (log2 fold change of 0.86 vs controls; P = .13). Multiple functional pathways were differentially enriched between groups. No associations were observed between the microbial taxa and disease recurrence in patients with stage III melanoma treated with adjuvant immunotherapy. Conclusions and Relevance: The findings of this case-control study suggest that fecal microbiota profiles were significantly different among patients with melanoma and controls and between patients with early-stage and late-stage melanoma. Prospective investigations of the gut microbiome and changes that occur with disease progression may identify future microbial targets for intervention.

Fluoroscopic Intraoperative Breast Neoplasm and Node Detection.

BACKGROUND: Preoperative localization is necessary for nonpalpable breast lesions. A novel procedure, fluoroscopic intraoperative neoplasm and node detection (FIND), obviates the preoperative painful and potentially expensive localization by using intraoperative visualization of the standard clip placed during diagnostic biopsy. We hypothesized FIND would improve negative margin rates. STUDY DESIGN: This is an IRB-approved retrospective study (September 2016 to March 2021). Electronic chart review identified breast and axillary node procedures using wire localization (WL) or FIND. Primary outcome was margin status. Secondary outcomes included re-excision rate, specimen weight, surgery time, and axillary node localization rate. RESULTS: We identified 459 patients, of whom 116 (25.3%) underwent FIND and 343 (74.7%) WL. Of these, 68.1% of FIND and 72.0% of WL procedures were for malignant lesions. Final margin positivity was 5.1% (4 of 79) for FIND and 16.6% (41 of 247) for WL (p = 0.008). This difference lost statistical significance on multivariable logistic regression (p = 0.652). Re-excision rates were 7.6% and 14.6% for FIND and WL (p = 0.125), with an equivalent mean specimen weight (p = 0.502), and mean surgery time of 177.5 ± 81.7 and 157.1 ± 66.8 minutes, respectively (mean ± SD; p = 0.022). FIND identified all (29 of 29) targeted axillary nodes, and WL identified only 80.1% (21 of 26) (p = 0.019). CONCLUSIONS: FIND has lower positive margin rates and a trend towards lower re-excision rates compared with WL, proving its value in localizing nonpalpable breast lesions. It also offers accurate localization of axillary nodes, valuable in the era of targeted axillary dissection. It is a method of visual localization, using a skill and equipment surgeons already have, and saves patients and medical systems an additional schedule-disruptive, painful procedure, especially valuable when using novel localization devices is cost-prohibitive.

Intestinal toxicity to CTLA-4 blockade driven by IL-6 and myeloid infiltration.

Immune checkpoint blockade (ICB) has revolutionized cancer treatment, yet quality of life and continuation of therapy can be constrained by immune-related adverse events (irAEs). Limited understanding of irAE mechanisms hampers development of approaches to mitigate their damage. To address this, we examined whether mice gained sensitivity to anti-CTLA-4 (αCTLA-4)-mediated toxicity upon disruption of gut homeostatic immunity. We found αCTLA-4 drove increased inflammation and colonic tissue damage in mice with genetic predisposition to intestinal inflammation, acute gastrointestinal infection, transplantation with a dysbiotic fecal microbiome, or dextran sodium sulfate administration. We identified an immune signature of αCTLA-4-mediated irAEs, including colonic neutrophil accumulation and systemic interleukin-6 (IL-6) release. IL-6 blockade combined with antibiotic treatment reduced intestinal damage and improved αCTLA-4 therapeutic efficacy in inflammation-prone mice. Intestinal immune signatures were validated in biopsies from patients with ICB colitis. Our work provides new preclinical models of αCTLA-4 intestinal irAEs, mechanistic insights into irAE development, and potential approaches to enhance ICB efficacy while mitigating irAEs.

Extracorporeal Membrane Oxygenation for Adult Patients With Neoplasms: Outcomes and Trend Over the Last 2 Decades.

Extracorporeal membrane oxygenation (ECMO) is utilized in the management of severe respiratory and circulatory failure. Advanced malignancy is a relative contraindication, but the indication for ECMO in the oncologic population has not been clearly established because of the wide spectrum of malignant disease and prognoses. The Extracorporeal Life Support Organization database was queried for patients older than 18 years with an International Classification of Diseases code of neoplasm over the past 2 decades (2000-2019). The data were divided into 2 decades to analyze and compare the trends with background and outcomes. One thousand six-hundred ninety-seven patients met inclusion criteria from the latest decade which is over 15 times the previous decade (n = 110). Compared with the previous decade, ECMO was used more in patients with older age (56 vs . 50.5 years old; p < 0.001), cardiac and extracorporeal cardiopulmonary resuscitation (ECPR) support type ( p = 0.011), and lower oxygenation index (23.0 vs . 35.6; p < 0.001) in the latest decade. Although overall survival did not show significant improvement overall (38.9% vs . 33.6%; p = 0.312), survival in pulmonary ECMO has significantly improved in the latest decade (41.6% vs . 29.1%; p = 0.032). Compared with the previously reported data for all adult ECMO, our patients had a significantly lower survival with pulmonary (41.6% vs . 61.1%; p < 0.001) and cardiac (38.4% vs . 44.3%; p = 0.008) support while not with ECPR.

The Microbiome: the Link to Colorectal Cancer and Research Opportunities.

OPINION STATEMENT: In recent years, we have seen an increase in the study and interest of the role of the microbiome in the development of malignancies, their progression, and evasion of therapies. This has been particularly fruitful in the case of colorectal cancer; multiple investigators have described correlative observations as well as hypotheses strengthened in preclinical studies that have begun to elucidate the critical role the gut and tumoral microbiome plays in carcinogenesis. Furthermore, these landmark studies lay the groundwork in describing the microbiome's role in carcinogenesis and provide a rich field of future study. Here, we review contemporary understandings of these observations and proposed mechanisms behind them.

Outcome of Extracorporeal Membrane Oxygenation for Pediatric Patients With Neoplasm: An Extracorporeal Life Support Organization Database Study (2000-2019).

OBJECTIVES: This study update in usage and outcomes of pediatric extracorporeal membrane oxygenation (ECMO) for patients with neoplasm analyzed according to demographics, clinical variables, and complications. DESIGN: Retrospective database review of the Extracorporeal Life Support Organization registry from the last 2 decades (2000-2019). The data were divided between two decades in order to compare patients' backgrounds and outcomes over time. SETTING: ECMO centers reporting to Extracorporeal Life Support Organization. PATIENTS: Patients equal to or younger than 18 years old with International Classification of Diseases, 9th Revision and International Classification of Diseases, 10th Revision codes that referred to neoplasms who were managed with ECMO. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographics, cancer subtype, clinical variables, and ECMO complications were assessed in relation to the primary study outcome of survival to hospital discharge. Nine-hundred two patients met inclusion criteria; 699 patients were in the latest decade, which is more than three times the number from the previous decade (203 patients). On univariate analysis, compared with the previous decade, in the later decade, ECMO was more frequently applied in patients with pre-ECMO cardiac arrest (31.3% vs 17.1%; p < 0.001), and/or lower oxygenation index (38.0 vs 48.1; p < 0.001). We failed to identify a difference in survival between the 2 decades (42.8% vs 37.9%; p = 0.218). On multivariable analysis, diagnosis of hematologic malignancy, post-cardiopulmonary resuscitation support type, hematopoietic stem cell transplant, and age older than seven were each associated with greater odds of mortality. CONCLUSIONS: The use of ECMO in children with neoplasm has expanded over the latest decade with changes in patient selection. Mortality remains unchanged. Hence, although the clinician still should stay cautious in its application, ECMO can be considered as an option to rescue pediatric oncologic patients in the setting of worsening cardiopulmonary status in the PICU.

A large national comparative study of clinicopathological features and long-term survivals between esophageal gastrointestinal stromal tumor and leiomyosarcoma.

BACKGROUND: Esophageal gastrointestinal stromal tumors (E-GIST) and leiomyosarcoma (E-LMS) are rare tumors. Previous studies are limited to small number of patients. We sought to study these two tumors using a large national database. METHODS: The National Cancer Data Base 2004-2014 was queried for patients with E-GIST and E-LMS. The primary outcome was overall survival (OS). Univariate and multivariable Cox regression models were used to investigate OS predictors. RESULTS: We found 141 E-GIST and 38 E-LMS patients, with esophagectomy and systemic treatment rate of 55% and 49% for E-GIST and 50% and 26% for E-LMS. The 5-year OS of E-GIST and E-LMS were 62% and 23%, respectively, p < 0.001. In multivariable analysis, young age, tumor <10 cm, esophagectomy, and E-GIST were associated with superior OS. There was a higher median and mean OS with neoadjuvant vs. upfront surgery for E-GIST group (98 and 111 vs 79 and 80 months). CONCLUSION: E E-GIST has superior OS compared to E-LMS. Esophagectomy is the cornerstone treatment modality. Further studies are needed to evaluate the role of neoadjuvant therapy in E-GIST patients.

Use of a Mobile Intraoperative Computed Tomography Scanner for Navigation Registration During Laser Interstitial Thermal Therapy of Brain Tumors.

OBJECTIVE: In recent years laser interstitial thermal therapy (LITT) has become the ablative neurosurgical procedure of choice. Multiple methods for registration and laser fiber verification have been described, with each method requiring multiple steps and significant time expenditure. We evaluated the use of a commercially available mobile computed tomography (CT) scanner for stereotactic registration during LITT for brain tumors in an attempt to simplify the procedure and improve intraoperative awareness of laser position. METHODS: This is a retrospective chart review comparing LITT of brain tumors in 23 patients undergoing a standard protocol requiring skull pins and transport of the patient to a CT suite to obtain a reference scan compared with 14 patients in whom the Medtronic O-arm was used intraoperatively for navigation registration and confirmation of laser position. RESULTS: Total ablation of the target was achieved in all patients with no surgical complications. Total surgery time was shorter for the O-arm group than for the standard protocol group, once experience was gained with bringing the O-arm in and out of the surgical field. Return from the magnetic resonance imaging suite to the operating room for repositioning of the laser was required for 1 patient in the standard protocol group, but for no patients in the O-arm group. Once experience was gained with using the O-arm, estimated surgical costs were lower for this group. CONCLUSIONS: Use of a mobile intraoperative CT scanner for navigation registration and confirmation of laser position during LITT may play a role in streamlining the procedure and improving patient safety and comfort.