Background
The past 20 years have seen advances in colorectal cancer management. We sought to determine whether survival in patients undergoing resection of colorectal liver metastases (CLM) has ...improved in association with three landmark advances: introduction of irinotecan- and/or oxaliplatin-containing regimens, molecular targeted therapy, and multigene alteration testing.
Methods
Patients undergoing CLM resection during 1998–2014 were identified and grouped by resection year. The influence of alterations in
RAS
,
TP53
, and
SMAD4
was evaluated and validated in an external cohort including patients with unresectable metastatic colorectal cancer.
Results
Of 1961 patients, 1599 met the inclusion criteria. Irinotecan- and/or oxaliplatin-containing regimens and molecular targeted therapy were used for more than 50% of patients starting in 2001 and starting in 2006, respectively, so patients were grouped as undergoing resection during 1998–2000, 2001–2005, or 2006–2014. Liver resectability indications expanded over time. The 5-year overall survival (OS) rate was significantly better in 2006–2014, vs. 2001–2005 (56.5% vs. 44.1%,
P
< 0.001).
RAS
alteration was associated with worse 5-year OS than
RAS
wild-type (44.8% vs. 63.3%,
P
< 0.001). However, OS did not differ significantly between patients with
RAS
alteration and wild-type
TP53
and
SMAD4
and patients with
RAS
wild-type in our cohort (
P
= 0.899) or the external cohort (
P
= 0.932). Of 312 patients with genetic sequencing data, 178 (57.1%) had clinically actionable alterations.
Conclusion
OS after CLM resection has improved with advances in medical therapy and surgical technique. Multigene alteration testing is useful for prognostication and identification of potential therapeutic targets.
Current chemotherapy regimens against pancreatic cancer are met with little success as poor tumor vascularization significantly limits the delivery of oncological drugs. High-dose targeted drug ...delivery, through which a drug delivery vehicle releases a large payload upon tumor localization, is thus a promising alternative strategy against this lethal disease. Herein, we synthesize anti-carcinoembryonic antigen (CEA) half-antibody conjugated lipid−polymer hybrid nanoparticles and characterize their ligand conjugation yields, physicochemical properties, and targeting ability against pancreatic cancer cells. Under the same drug loading, the half-antibody targeted nanoparticles show enhanced cancer killing effect compared to the corresponding nontargeted nanoparticles.
Background
The use of the robotic approach is increasing for colorectal cancer operations, but the added cost of the platform has the potential to introduce challenges in its dissemination. We ...hypothesized that adoption of the robot is introducing new disparities in access to minimally invasive surgery (MIS) for colorectal cancer, especially across patient insurance groups.
Methods
This cross-sectional study analyzed surgical cases of stage I–III colorectal cancer from the National Cancer Database (NCDB) between 2010 and 2019. The primary outcome was surgical approach (robotic, laparoscopic, or the composite “MIS”). The predictor was a patient’s primary payor. Potential confounders included sociodemographics, tumor characteristics, and the facility. Hierarchical multivariable models were generated, and sensitivity analyses were performed.
Results
For colorectal cancer operations, the MIS approach increased from 39% in 2010 to 73% in 2019, driven predominantly by an increase in the robotic approach from 2 to 24%. For laparoscopy, the size of the disparity between patients with Private insurance and Medicaid shrank from 11% (2010) to 4% (2019), whereas this disparity increased for the robotic approach from 1% (2010) to 5% (2019). On adjusted analysis, patients with Medicaid (odds ratio OR 0.86 CI 0.79–0.95) and the Uninsured (OR 0.67 CI 0.56–0.79) had lower odds of receiving a robotic operation than those with Private insurance in 2019. This disparity remained consistent across five sensitivity analyses.
Conclusions
As the field of colorectal cancer surgery shifts away from laparoscopy and toward robotics, new inequities across patient insurance are emerging. Proactive efforts are needed to ensure all patients benefit from a minimally invasive approach.
Background
For patients with synchronous liver metastases (LM) from rectal cancer, a consensus on surgical sequencing is lacking. We compared outcomes between the reverse (hepatectomy first), classic ...(primary tumor resection first), and combined (simultaneous hepatectomy and primary tumor resection) approaches.
Methods
A prospectively maintained database was queried for patients with rectal cancer LM diagnosed before primary tumor resection who underwent hepatectomy for LM from January 2004 to April 2021. Clinicopathological factors and survival were compared between the three approaches.
Results
Among 274 patients, 141 (51%) underwent the reverse approach; 73 (27%), the classic approach; and 60 (22%), the combined approach. Higher carcinoembryonic antigen level at LM diagnosis and higher number of LM were associated with the reverse approach. Combined approach patients had smaller tumors and underwent less complex hepatectomies. More than eight cycles of pre-hepatectomy chemotherapy and maximum diameter of LM > 5 cm were independently associated with worse overall survival (OS) (
p
= 0.002 and 0.027, respectively). Although 35% of reverse-approach patients did not undergo primary tumor resection, OS did not differ between groups. Additionally, 82% of incomplete reverse-approach patients ultimately did not require diversion during follow-up.
RAS/TP53
co-mutation was independently associated with lack of primary resection with the reverse approach (odds ratio: 0.16, 95% CI 0.038–0.64,
p
= 0.010).
Conclusions
The reverse approach results in survival similar to that of combined and classic approaches and may obviate primary rectal tumor resections and diversions.
RAS/TP53
co-mutation is associated with a lower rate of completion of the reverse approach.
Background
For patients undergoing resection of colorectal liver metastases (CLMs), the prognostic role of somatic gene alterations is increasingly recognized. F-box/WD repeat–containing protein 7 (
...FBXW7
) is a tumor suppressor gene found in approximately 10% of patients with colorectal cancer. The aim of this study is to assess the association of
FBXW7
with overall survival after CLM resection.
Methods
Patients who underwent initial CLM resection during 2001–2016 and had genetic sequencing data were studied. Risk factors for overall survival (OS) were evaluated with Cox proportional hazards models using backward elimination.
Results
Of 2045 patients who underwent CLM resection during the study period, 476 were included. The majority (90.5%) underwent prehepatectomy chemotherapy. A total of 27 patients (5.7%) had
FBXW7
alteration, along with 240 (50.4%)
RAS
, 337 (70.8%)
TP53
, 51 (10.7%)
SMAD4
, and 27 (5.7%)
BRAF
. Cox proportional hazards model analyses including 5 somatic gene alteration status and 12 clinicopathologic factors revealed
FBXW7
(hazard ratio HR 1.99,
P
= 0.015),
BRAF
(HR 2.47,
P
= 0.023),
RAS
(HR 2.42,
P
< 0.001),
TP53
(HR 2.00,
P
< 0.001), and
SMAD4
alterations (HR 1.90,
P
= 0.004) as significantly associated with OS, together with three clinicopathologic factors, prehepatectomy chemotherapy > 6 cycles (HR 1.51,
P
= 0.021), number of CLM (HR 1.05,
P
= 0.007), and largest liver metastasis diameter (HR 1.07,
P
= 0.023). The covariate-adjusted 5-year OS was significantly lower in patients with
FBXW7
alteration than in patients with
FBXW7
wild-type (40.4% vs.59.4%,
P
= 0.015).
Conclusions
FBXW7
alterations are associated with worse survival after CLM resection. The information on multiple somatic gene alterations is imperative for risk stratification and patient selection for CLM resection.
To evaluate the association between staging concordance, treatment sequencing, and response to neoadjuvant therapy (NAT) on the survival of patients with pancreatic ductal adenocarcinoma (PDAC).
NAT ...is increasingly utilized in the management of patients with PDAC, but it is unclear whether its benefit is contingent on tumor down-staging.
This was a cohort study of stage I-III PDAC patients in the National Cancer Database (2006-2015) treated with upfront resection or NAT followed by surgery. We determined staging concordance using patients' clinical and pathological staging data. For NAT patients, we used Bayesian analysis to ascertain staging concordance accounting for down-staging.
Among 16,597 patients treated at 979 hospitals, 13,982 had an upfront resection and 2,615 NAT followed by surgery. Overall survival (OS) at 5-years ranged from 26.0% (95% CI 24.9%-27.1%) among cT1-2N0 patients to 18.6% (17.9%-19.2%) among cT1-3N+ ones. Patients with cT3-4 or cN+ tumors had improved OS after NAT compared to upfront surgery (all p< 0.001), while there was no difference among patients with cT1-2N0 (P = 0.16) disease. Relative to accurately staged cT1-2-3N+ or cT4 patients treated with upfront surgery, NAT was associated with a lower risk of death HR 0.46 (0.37-0.57) for N+; HR 0.56 (0.40-0.77) for T4 disease, even among those without tumor down-staging HR 0.81 (0.73-0.90) for N+; HR 0.48 (0.39-0.60) for T4.
NAT is associated with improved survival for PDAC, particularly for patients with more advanced disease and regardless of down-staging. Consideration should be given to recommending NAT for all PDAC patients.
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