Surgical Oncology Insight最新文献

Introduction

Breast cancer among patients under 50 years old accounts for 18% of new cases. Few studies have reported current trends in clinical-pathologic features and treatment patterns for young patients. We evaluated these trends in a modern cohort of breast cancer patients under 50.

Methods

We identified women with breast cancer from the National Cancer Database from 2004–2017. Patients were grouped into 18–29, 30–39, 40–49, and ≥ 50-year cohorts. Proportions and temporal comparisons between demographic, clinicopathologic features, and treatment types were evaluated. Temporal trends across sequential periods were performed.

Results

Of the 2387,902 patients selected, 554,941 (23.3%) were younger than 50. During 2004–2017, the proportions remained stable in the 18–29 (0.5–0.6%) and 30–39 (4.5–5%) age groups, while decreasing in the 40–49 group (absolute difference: −4.8%, p < 0.001). Overall, in those younger than 50, early-stage breast cancer (clinical stage 0-II) increased by 3.9%, while stages III and IV decreased by 2.7% and 1.3% (p < 0.001), respectively. Mastectomy rates and neoadjuvant systemic therapy use increased by 10.4% and 9.8%, respectively (p < 0.001) in all groups under 50.

Conclusions

Despite stable proportions in the youngest age groups (18–29 and 30–39), a noteworthy decrease in the 40–49 age group was observed, suggesting potential shifts in disease detection. The rise in early-stage disease and neoadjuvant systemic therapies should theoretically translate into an increase in the number of breast-conserving candidates. However, the increase in mastectomies highlights the need to better understand the factors influencing treatment decisions in this population.

Background

With the release of the 2015 management guidelines, the American Thyroid Association narrowed the indications for postoperative radioactive iodine (RAI) in well-differentiated thyroid cancer. However, the adoption of new guidelines varies between healthcare entities. The goal of this study was to characterize the appropriateness of RAI use within our health system, before and after the 2015 guideline changes.

Methods

In this retrospective cohort study, we identified patients who were treated for well-differentiated thyroid cancer between 2011–2020. Patients were characterized as “undertreated,” “appropriately treated,” or “overtreated” with RAI. Variation in RAI use was assessed using interrupted time series and multivariable logistic regression analyses.

Results

Among 6310 patients, the mean age was 50 ± 15 years, and 74% were female. There was an immediate drop in the likelihood of receiving RAI after the release of the 2015 guidelines (p = 0.016), and the likelihood of receiving RAI therapy continued to significantly decline over time (OR 0.83, p < 0.001). Despite this trend in the absolute rate of RAI use, there was a significant increase in overtreatment with RAI after the release of the 2015 guidelines (p < 0.001), indicating imperfect uptake of the new criteria. Two hospitals within the health system were identified as disproportionate contributors to overtreatment (Hospital 4: OR 6.50, p < 0.001; Hospital 6: OR 8.63, p < 0.001).

Conclusions

While the use of postoperative RAI was largely appropriate across our health system, rates of guideline adherence differed between hospitals. Efforts to standardize treatment protocols systemwide may enable more rapid and consistent uptake of new management guidelines.

Malignant bowel obstruction (MBO) is defined as a mechanical/functional/radiologic obstruction of the gastrointestinal tract beyond the Ligament of Treitz in the presence of a known primary or metastatic abdominopelvic malignancy. Though numerous retrospective studies have been conducted on the outcomes of various treatment modalities, there is a tremendous heterogeneity of MBO definitions, clinical presentations, and offered treatments. Few prospective studies or randomized trials exist, making it difficult to ascertain generalizable data and develop applicable clinical guidelines. In this review, a systematic computerized search was conducted on PubMed for high quality data on MBO epidemiology, pathophysiology, and treatment modalities, with a particular focus on comprehensive systematic literature reviews. The current standard of care for medical, surgical, and endoscopic treatment of MBO was discussed in detail. Historical data was contextualized and the latest findings of the first randomized-controlled clinical trial (SWOG S1316) studying surgical vs. non-surgical treatment of MBO was critically appraised. These findings give insight on how to optimize future trial design, measure comprehensive quality of life outcomes, and develop clinical practice guidelines in line with patient-specific goals of treatment.

Background

Malignant pleural effusions (MPE) and malignant ascites (MA) are serious complications of advanced cancer, marked by debilitating symptoms and limited treatment options. Based on a wealth of previous literature implicating the cytokine IL-6 as a central mediator in the pathogenesis of MPE and MA, the Regional Immuno-Oncology Trial 2 (RIOT-2) clinical protocol was developed to explore intra-cavitary delivery of tocilizumab, an IL-6 receptor antagonist, as treatment for these conditions.

Methods

This phase I clinical trial (NCT 06016179) is being conducted to assess the safety and pharmacokinetics of intra-cavitary tocilizumab administration to patients with MPE and MA. Eligible patients are those with pleural effusion or peritoneal ascites due to metastatic cancer who are scheduled to undergo standard-of-care catheter placement for pleural or peritoneal drainage. Following catheter placement, patients will receive a starting dose of tocilizumab 0.5 µg/mL via intra-pleural or intra-peritoneal implantable catheters. Weekly escalating doses of tocilizumab will be given over four weeks. Primary endpoints are frequency and type of adverse events, while secondary endpoints include pharmacokinetic and immunological parameters. This single-center study will proceed until 12 patients have been treated.

Discussion

Inhibition of the IL-6 signaling pathway with tocilizumab is hypothesized to be a rational mitigating treatment strategy for the maladaptive intra-cavitary immune environment in patients with MPE and MA. The RIOT-2 study aims to assess the safety of intra-cavitary tocilizumab therapy, administered via indwelling catheters. Pharmacologic and translational immunologic findings generated by this study could pave the way for future research into clinical applications of intra-cavitary immunotherapy.

Trial registration

The trial is registered at ClinicalTrials.gov; NCT06016179 (registered on August 29th, 2023).

Background

Intra-tumoral immunotherapy has shown potential in treating advanced cancers. Delivery challenges have limited exploration of these modalities in intra-abdominal tumors. In this study, we explore the safety of injecting intra-abdominal tumors with lipopolysaccharide (LPS) from Escherichia coli 0113. This agonist of toll-like receptor 4 (TLR4) holds promise as an agent to enhance the anti-tumor immune response within the tumor microenvironment.

Methods

This Phase I study will recruit adult patients with peritoneal metastases from gastrointestinal primary malignancies who have at least two suitable intra-abdominal soft tissue tumors for injection. LPS will be administered as a single 1 μg dose during diagnostic laparoscopy in patients in whom a subsequent interval laparotomy is planned. A control injection of saline will be injected into a second lesion. Primary outcome is safety, with secondary outcomes being biomarkers of the tumor immune microenvironment in pre- and post-treatment biopsies.

Results

The primary endpoint is to determine the safety (frequency and nature of adverse events) following intra-tumoral LPS injection. Adverse events will be classified using Common Terminology Criteria for Adverse Events. Secondary endpoints include cellular and molecular biomarkers of immune response. The study will proceed until twelve patients have completed the protocol.

Discussion

Patients undergoing standard-of-care laparoscopy in preparation for interval cytoreductive surgery may be ideal candidates for intra-tumoral immunotherapy. This study seeks to establish the safety of using E. coli LPS for injection into intra-abdominal tumors and to establish precedent for interval tumor immune microenvironment assessment as a window-of-opportunity concept in the context of abdominal metastatic disease.

Trial Registration

The trial is registered at Clinical Trials.gov; NCT05751837 (registered February 28th, 2023).

The Organ Preservation in patients with Rectal Adenocarcinoma (OPRA) trial is a randomized, non-blinded, phase II prospective study that investigated total neoadjuvant therapy (TNT) and a selective “watch-and-wait” (WW) approach in locally advanced rectal cancer (LARC). It compared two TNT regimens: induction chemotherapy-chemoradiotherapy (INCT-CRT) and chemoradiotherapy-consolidation chemotherapy (CRT-CNCT). Depending on tumor response, patients were offered WW or surgery. The primary endpoint was disease-free survival (DFS), hypothesizing that patients who underwent TNT with selective WW would have improved DFS compared to historical rates. Secondary endpoints included organ preservation (OP) and overall survival, hypothesizing that differences between INCT-CRT and CRT-CNCT could indicate a superior regimen. Results demonstrated treatment of LARC with TNT and selective WW allows for OP in approximately half of patients without negatively impacting oncologic outcomes such as DFS. The data show that a CRT-CNCT regimen had higher rates of OP, lower rates of tumor regrowth, and similar DFS compared to INCT-CRT. Lastly, DFS does not differ between patients who undergo immediate TME versus TME after regrowth. Thus, patients treated with TNT who achieve a clinical complete response (cCR) can safely undergo WW with the potential for OP. Current research to improve TNT and enhance cCR will expand the utility of the WW approach, including the intensification of neoadjuvant chemotherapy (Janus trial), comparing short-course and long-course CRT prior to CNCT (ENSEMBLE and German trials), utilizing fluoropyrimidine-chemotherapy with and without oxaliplatin in the context of WW (CHOW trial), and exploring less invasive operative approaches for early-stage tumors (NEO and NEO-RT trials).

Synopsis

The OPRA trial demonstrates treatment of locally advanced rectal cancer using total neoadjuvant therapy with selective “watch-and-wait” allows organ preservation in approximately half of patients without negatively impacting oncologic outcomes. For widespread adoption of “watch-and-wait”, data from accruing prospective trials are needed to demonstrate its viability across diverse clinical settings.

Objective

Growing evidence supports the impact of sociodemographics on cancer outcomes. The objective of this study was to examine the Social Vulnerability Index (SVI) and its association with oncologic presentation and subsequent treatments across 8 major cancers.

Methods

This was a retrospective-cohort study using one institution’s contribution to the National Cancer Database (2011–2021). Patients were grouped into low SVI (<75th percentile) and high SVI (≥75th percentile) cohorts. Un-adjusted comparison between groups was performed followed by multivariable regression to control for the effect of demographic characteristics on oncologic presentation, and for demographic and oncologic characteristics on subsequent treatments. A subgroup analysis was performed comparing cancers that have national screening protocols versus those without.

Results

Of 12,712 cases, 2842 (22.4%) were in the high SVI group and 9870 (77.6%). After risk-adjustment, high SVI patients presented at more advanced T-stage (odds ratio 1.09, 95% confidence interval 1.00–1.19); N-stage (1.11, 1.01–1.23); M stage (1.16, 1.03–1.30); and overall stage (1.14, 1.04–1.24) and were more frequently not recommended for surgery (1.15, 1.01–1.32) or chemotherapy (1.20, 1.07–1.38). Screening protocols tended to increase the association between high SVI and advanced oncologic presentation. After adjustment high SVI remained significantly associated with decreased odds of survival (0.85, 0.79 - 0.91).

Conclusions

High SVI is associated with advanced stage presentation and decreased likelihood of being recommended surgery or chemotherapy even after risk-adjustment. Differences in presentation stage are predominantly driven by cancers with screening protocols and ultimately high SVI is associated with decreased odds of survival.

Objectives

We sought to define the attributable morbidity of multivisceral resection (MVR) during distal/subtotal pancreatectomy (DP) in patients with pancreatic ductal adenocarcinoma (PDAC).

Methods

This retrospective review of patients with PDAC used the 2014–2019 pancreas-targeted American College of Surgeons National Surgical Quality Improvement Program database. Operations DP versus MVR were compared based on demographics, comorbidities, intraoperative variables, and postoperative outcomes. Univariate and multivariable logistic regression models assessed morbidity and mortality.

Results

Of 3353 distal pancreatectomies, 124 (4%) were MVR. MVR patients were more likely male (56% versus 49%) and smokers (24% versus 18%) but less likely obese (18% versus 29%) or diabetic (21% versus 30%). MVR operations were longer (median 4.3 versus 3.8 h) and involved partial colectomy (100%), gastrectomy (28%), adrenalectomy (20%), and enterectomy (13%). MVR patients had higher unadjusted rates of mortality (2.4% versus 1.1%), serious morbidity (30.7% versus 14.1%), and overall morbidity (61% versus 36%). MVR patients had higher adjusted risk for serious morbidity [odds ratio (OR) 2.13, 95% confidence intervals: 1.28–3.43] and infectious complications [OR 2.75 (1.73–4.31)], but not mortality [OR 1.05 (0.04–3.73)], although the mortality analyses were underpowered.

Conclusions

Concurrent MVR during DP doubled the risk of postoperative complications. This should be considered during the sequencing of cancer-directed care and preoperative planning.

Purpose

Pediatric oncology patients are at increased risk of unplanned readmissions, but factors associated with readmissions are largely unknown. We aimed to identify patients at increased risk for readmission and characterize unplanned readmissions for pediatric surgical oncology patients.

Methods

Patients < 20 years with a first primary solid organ cancer who underwent definitive oncologic surgery from 2005–2017 were identified in the California Cancer Registry linked to statewide hospitalization data. Unplanned 30-day readmissions from their definitive surgery were defined as acute medical problems and/or surgical complications not related to planned admissions for chemotherapy, radiation, or rehabilitation. Multivariable logistic regression identified factors associated with unplanned 30-day readmission.

Results

2507 pediatric oncology patients were identified. Median age was 10 years. 49.2% had a 30-day readmission (n = 1233), and 36.7% (n = 452) of these readmissions were unplanned. In multivariable models, those at highest risk of unplanned readmission were < 1 year old (OR 2.72, CI 1.72–4.29) and 1–5 years (OR 1.64, CI 1.20–2.24) vs. ages 13–19; had metastatic disease at diagnosis (OR 1.6, CI 1.1–2.1); and had central nervous system (CNS) tumors (OR 2.5, CI 1.6–3.9), hepatic tumors (OR 2.3, 95% CI 1.2–4.2), or soft tissue/extraosseous sarcomas (OR 2.2, CI 1.3–3.9). Longer initial hospitalizations were associated with a higher likelihood of unplanned readmission (10 days vs. 7 days, p < 0.0001).

Conclusion

Unplanned readmissions after surgery for pediatric oncology patients are prevalent. Younger children and those with more advanced/complex disease are at highest risk of unplanned readmissions. Interventions should focus on preventing readmissions in these patients, specifically.

Introduction

Due to the watershed vasculature and lymphatic drainage of splenic flexure (SF) neoplasms, and their exclusion from large clinical trials, optimal management remains debated. This study evaluated extent of resection and surgical approach for SF adenocarcinoma and their respective outcomes.

Methods

Adults with stage I-III splenic flexure adenocarcinoma were identified in the National Cancer Database (2004–2020) and categorized by surgical management.

Results

Of 7412 patients, 4264 (58%) underwent extended colectomy (EC). The cohorts were overall similar, though more patients with stage I disease were managed with segmental colectomy (SC) (24% vs. 20%, p < 0.01). Those undergoing EC had longer hospital stays (LOS) and greater odds of readmission. Use of robotic-assisted surgery was higher in SC (9% vs. 7%, p < 0.01) and increased from 1% in 2010 to 24% in 2020. This approach was independently associated with a shorter LOS than open surgery. Despite a higher number of lymph nodes examined (median 18 vs. 16), EC and SC had similar nodal (both 37%, p = 0.95) and margin involvement (both 4%, p = 0.39). Five-year survival after EC and SC was similar (75% vs. 76%, p = 0.6). Patients undergoing robotic surgery had significantly lower odds of positive surgical margins and experienced an improved prognosis.

Conclusions

EC and SC were performed at similar rates for SF adenocarcinoma, while the use of robotic surgery increased over time. Neither extent of resection nor surgical approach significantly impacted oncologic outcomes. These data indicate that surgical decision-making should be balanced between tumor- and patient-specific considerations, morbidity of extended colectomy, and surgeon preference.

Synopsis

In a national cohort of splenic flexure cancers, segmental and extended colectomy were associated with comparable rates of negative margins, nodal involvement, and survival. Robotic assist increased over time without impacting oncologic outcomes. Surgical procedure and approach should thus be tailored to clinical condition and surgeon preference.