Registry trials have found radial endobronchial ultrasound (r-EBUS) sensitivity to vary between institutions, suggesting that in clinical practice, r-EBUS sensitivity may be lower than reported in ...clinical trials. We performed a meta-analysis to update the estimates of r-EBUS sensitivity and to explore factors contributing to heterogeneity of results.
A systematic review using PubMed was performed through July 2018 to determine the sensitivity of r-EBUS for lung cancer, and to construct a summary receiver operating characteristic curve. The DerSimonian and Laird method was used to weight results. Subgroup analysis and meta-regression was used to identify sources of heterogeneity. Study quality was assessed using the QUADAS tool, and publication bias was tested using funnel plots.
Fifty-one studies with a total of 7,601 patients were included. r-EBUS pooled sensitivity was 0.72 (95% CI, 0.70-0.75), and area under the sROC curve was 0.96 (95% CI, 0.94-0.97). Significant heterogeneity was observed (I
= 76%; heterogeneity P < .01). We failed to demonstrate an association between sensitivity and air bronchus sign, average nodule size, use of fluoroscopy, virtual bronchoscopy, guide sheath, cancer prevalence, multicenter status, or consecutive enrollment. Rapid onsite cytology was associated with increased sensitivity (P = .01). The pooled pneumothorax rate was 0.7% (95% CI, 0.3%-1.1%). Funnel plots were asymmetrical, demonstrating sample size-related effects and possible publication bias.
r-EBUS has an excellent safety profile, but there is significant between-study heterogeneity. Sample size-related effects and possibly publication bias have led to overly optimistic estimates of the sensitivity of r-EBUS.
It is unclear whether the enhanced dexterity and visualization of the surgical robot lessens morbidity and influences staging or survival. We compared outcomes of robotic-assisted lobectomy (RAL) ...with thoracoscopic video-assisted lobectomy (VAL) or open lobectomy (OL) of non-small cell lung cancer.
Using a prospective surgical database, perioperative and cancer-related outcomes of patients who received a lobectomy for non-small cell lung cancer from 2011 to 2017 were analyzed. Outcomes between each surgical approach were compared using inverse probability of treatment weighting generated from the inverse of the propensity score.
There were 831 patients: 106 RAL, 301 VAL, and 424 OL. More RAL patients than VAL received neoadjuvant therapy (16% vs 6%, P = .001), but less than OL (28% vs 16%, P = .014). After adjustment, RAL was associated with longer operative times, less blood loss, and improved nodal harvest (all P < .02). There were no differences in morbidity, nodal upstaging, or mortality between surgical approaches. Length of stay was shorter with RAL vs OL (P < .01). Unadjusted cost was higher after RAL vs VAL (P = .003), but after adjustment, cost differences disappeared.
Robotic-assisted lobectomy was associated with improved nodal harvest and less blood loss as compared with VAL or OL. Length of stay was shorter with RAL as opposed to OL. Unexpectedly, cost was not higher with RAL. The profile of patients who received RAL more closely approximated OL, suggesting RAL may allow typical thoracotomy patients to receive minimally invasive surgery after adequate training and experience.
T cell-mediated immunotherapies are promising cancer treatments. However, most patients still fail to respond to these therapies. The molecular determinants of immune resistance are poorly ...understood. We show that loss of PTEN in tumor cells in preclinical models of melanoma inhibits T cell-mediated tumor killing and decreases T-cell trafficking into tumors. In patients, PTEN loss correlates with decreased T-cell infiltration at tumor sites, reduced likelihood of successful T-cell expansion from resected tumors, and inferior outcomes with PD-1 inhibitor therapy. PTEN loss in tumor cells increased the expression of immunosuppressive cytokines, resulting in decreased T-cell infiltration in tumors, and inhibited autophagy, which decreased T cell-mediated cell death. Treatment with a selective PI3Kβ inhibitor improved the efficacy of both anti-PD-1 and anti-CTLA-4 antibodies in murine models. Together, these findings demonstrate that PTEN loss promotes immune resistance and support the rationale to explore combinations of immunotherapies and PI3K-AKT pathway inhibitors.
This study adds to the growing evidence that oncogenic pathways in tumors can promote resistance to the antitumor immune response. As PTEN loss and PI3K-AKT pathway activation occur in multiple tumor types, the results support the rationale to further evaluate combinatorial strategies targeting the PI3K-AKT pathway to increase the efficacy of immunotherapy.
The purpose of this study was in vitro sonographic-pathologic correlation of findings in dissected axillary lymph nodes from breast cancer patients undergoing axillary lymph node dissection and ...classification of the sonographic appearance of the nodes on the basis of cortical morphologic features to facilitate early recognition of metastatic disease.
High-resolution sonography was used for in vitro examination of 171 lymph nodes from 19 axillae in 18 patients with unknown nodal status who underwent axillary lymph node dissection for early infiltrating breast cancer. The images were evaluated by two blinded observers, and discordant readings were referred to a third blinded observer. Each lymph node was classified as one of types 1-6 according to cortical morphologic features. Types 1-4 were considered benign, ranging from hyperechoic with no visible cortex to thickened generalized hypoechoic cortical lobulation. Type 5 (focal hypoechoic cortical lobulation) and type 6 (hypoechoic node with absent hilum) nodes were considered metastatic. The reference standard for metastatic disease was histopathologic evaluation of sectioned nodes by a single pathologist blinded to sonographic findings. Largest nodal diameter also was measured.
Interobserver agreement was 77% for classification of nodal morphology (types 1-6) and 88% for characterization of a node as benign or malignant. Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of cortical shape in prediction of metastatic involvement of axillary nodes were 77%, 80%, 36%, 96%, and 80%. Type 4 nodes had the most false-negative findings (four of 36). Node size ranged from 0.2 to 3.8 cm, and subcentimeter nodes of all types were detected.
In breast cancer, axillary lymph nodes can be classified according to cortical morphologic features. Predominantly hyperechoic nodes (types 1-3) can be considered benign. Generalized cortical lobulation (type 4) is uncommonly a false-negative finding, but metastasis, if present, is invariably detected at sentinel node mapping. The presence of asymmetric focal hypoechoic cortical lobulation (type 5) or a completely hypoechoic node (type 6) should serve as a guideline for universal performance of fine-needle aspiration for preoperative staging of breast cancer. This classification, when verified with larger samples, may serve as a useful clinical guideline if proven with results of in vivo studies.
To determine if the outcomes of patients with ILC co-occurring with LCIS are similar to pure ILC and if the presence of LCIS is a prognostic factor for ILC.
In an observational, population-based ...investigation using data from the MD Anderson breast cancer prospectively collected electronic database, we analyzed patients with a diagnosis of stage I-III ILC. Patients were divided into 2 groups: those with ILC with co-occurring ipsilateral LCIS (ILC+LCIS) and those with pure ILC without a histologically detected co-occurring ipsilateral LCIS (ILC alone). We obtained data on demographics, pathologic tumor size (pT), pathologic lymph node (pN) involvement, estrogen (ER), progesterone (PR) receptor status, HER2 status, Ki67, treatment received, distant recurrence-free and overall survival (DRFS, OS).
We identified 4,217 patients with stage I-III ILC treated at MD Anderson between 1966 and 2021. 45% of cases (n = 1,881) had co-existing LCIS. Statistically and numerically, ILC alone tended to associate with pT4 and pN3 stage (P < 0.001), ER/PR negativity (P = 0.0002), HER2 positivity (P = 0.010), higher Ki67 (P = 0.005), non-classical ILC subtype (P = 0.04) and more exposure to neoadjuvant chemotherapy (P = 0.0002) compared to the ILC+LCIS group. The median follow-up time was 6.5 years. Patients with ILC+LCIS had better median DRFS (16.8 vs 10.1 years, Hazard ratio (HR) 0.55, 95% confidence interval (CI) 0.50 – 0.60, P <0.0001) and better median OS (18.9 vs 13.7 years, HR 0.62, 95% CI 0.56 – 0.69; P <0.0001). Multivariate analysis showed the absence of LCIS to be an independent poor prognostic factor along with a higher pT stage and higher pN stage for DRFS and OS.
The findings of this study suggests that the absence of ipsilateral LCIS with ILC is an independent poor prognostic factor and that further studies are warranted to understand this phenomenon.
The data that support the findings of this study are available from the corresponding author, upon reasonable request.
•LCIS co-occurs with ipsilateral ILC in 45% of the cases at the time of diagnosis.•Pure ILC tend to be associated with higher stages at diagnosis compared to ILC+LCIS.•Absence of LCIS at the time of diagnosis of ILC is a poor prognostic factor.
Solitary fibrous tumor represents a spectrum of mesenchymal tumors, encompassing tumors previously termed hemangiopericytoma, which are classified as having intermediate biological potential (rarely ...metastasizing) in the 2002 World Health Organization classification scheme. Few series have reported on clinicopathological predictors with outcome data and formal statistical analysis in a large series of primary tumors as a single unified entity. Institutional pathology records were reviewed to identify primary solitary fibrous tumor cases, and histological sections and clinical records reviewed for canonical prognostic indicators, including patient age, tumor size, mitotic index, tumor cellularity, nuclear pleomorphism, and tumor necrosis. Patients (n=103) with resected primary solitary fibrous tumor were identified (excluding meningeal tumors). The most common sites of occurrence were abdomen and pleura; these tumors were larger than those occurring in the extremities, head and neck or trunk, but did not demonstrate significant outcome differences. Overall 5- and 10-year metastasis-free rates were 74 and 55%, respectively, while 5- and 10-year disease-specific survival rates were 89 and 73%. Patient age, tumor size, and mitotic index predicted both time to metastasis and disease-specific mortality, while necrosis predicted metastasis only. A risk stratification model based on age, size, and mitotic index clearly delineated patients at high risk for poor outcomes. While small tumors with low mitotic rates are highly unlikely to metastasize, large tumors ≥15 cm, which occur in patients ≥55 years, with mitotic figures ≥4/10 high-power fields require close follow-up and have a high risk of both metastasis and death.
Immune-related enterocolitis (irEC) is the most common serious complication from checkpoint inhibitors (CPIs). The current front-line treatment for irEC, high-dose corticosteroids (CS), have ...significant side effects and prolonged therapy may reduce CPI-anti-tumor activity. Early addition of TNF-α inhibitors such as infliximab (IFX) may expedite symptom resolution and shorten CS duration. Thus, we conducted the first retrospective study, to our knowledge, evaluating symptom resolution in patients with irEC treated with and without IFX.
Data were collected from the medical records of patients diagnosed with irEC. The primary endpoint was time to symptom resolution for irEC for cases managed with IFX plus CS (IFX group) versus CS alone (CS group). Duration of CS, overall survival (OS), and time to treatment failure (TTF) were secondary endpoints.
Among 75 patients with irEC, 52% received CS alone, and 48% received IFX. Despite higher grade colitis in the IFX group (grade 3/4: 86% vs. 34%; p < 0.001), median times to diarrhea resolution (3 vs. 9 days; p < 0.001) and to steroid titration (4 vs. 13 days; p < 0.001) were shorter in the IFX group than in the CS group without a negative impact on TTF or OS. Total steroid duration (median 35 vs. 51 days; p = 0.150) was numerically lower in the IFX group.
Despite higher incidence of grade 3/4 colitis, IFX added to CS for the treatment of patients with irEC was associated with a significantly shorter time to symptom resolution. The data suggest that early introduction of IFX should be considered for patients with irEC until definitive prospective clinical trials are conducted.
Summary
Objective
Pancreatic neuroendocrine tumours (PNETs) are the major source of disease‐specific mortality in multiple endocrine neoplasia type 1 (MEN1) patients. Chromogranin A (CgA), pancreatic ...polypeptide (PP), glucagon and gastrin have some diagnostic value in sporadic PNETs, but there is very little evidence for their efficacy in diagnosing PNETs in MEN1 patients.
Design
We performed a retrospective chart review of the existing MEN1 database in our institution.
Patients
One hundred and thirteen patients were eligible for diagnostic value analysis of tumour markers. Patients were excluded if measurement of tumour markers was missing, either 3 months prior to PNET diagnosis (PNET patients) or prior to abdominal imaging (non‐PNET patients).
Measurements
Clinicopathologic characteristics and of tumour marker measurements were analysed.
Results
Of 293 confirmed MEN1 cases, 55 PNETs and 58 non‐PNETs met inclusion criteria. The area under the curve (AUC) for CgA, PP, glucagon and gastrin in MEN1 cases was 59·5%, 64·1%, 77·0% and 75·9%, respectively. The AUC for the combination of CgA, PP and gastrin was 59·6%. PP, but not CgA, glucagon or gastrin was significantly associated with both age and PNET functional status (P = 0·0485 and 0·0188, respectively). No markers were significantly associated with sex, PNET size, tumour number, tumour location, American Joint Committee on Cancer (AJCC) stage, presence of lymph node metastasis, lymphovascular invasion or overall survival. CgA values were not significantly lower following PNET resection than pre‐operatively (P = 0·554).
Conclusions
The value of blood markers for diagnosing PNETs in MEN1 patients is relatively low, even when used in combination.
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