Clinical lung cancer最新文献

Objectives: To investigate the association between CT attenuation and zero echo time (ZTE) MRI detectability of subsolid pulmonary nodules (SSNs), and to identify a potential attenuation threshold to inform radiation-free follow-up approaches.

Materials and methods: Patients with SSNs ≤ 2 cm scheduled for surgical resection were prospectively enrolled between July 2022 and June 2023. Two radiologists reviewed nodule type (part-solid nodule [PSN] and ground-glass nodule [GGN]), size, location, and attenuation on preoperative CT, and evaluated detectability on ZTE-MRI. Associations between CT features, pathology, and ZTE-MRI detectability were analyzed using univariable and multivariable methods, and predictive performance was assessed with ROC curve analysis.

Results: Thirty-nine patients with 64 SSNs (median diameter, 6.6 mm) participated in the study. Of these, 43 (67.2%) SSNs were identified on ZTE-MRI, including 11 PSNs (100%) and 32 GGNs (60.4%). CT attenuation was the most significant predictor for ZTE-MRI detectability (AUC, 0.993; P < .001), with an optimal threshold of -637.6 HU (sensitivity, 95.2%; specificity, 100.0%). Interreader agreement for ZTE-MRI measurements was high (intraclass correlation coefficient [ICC], 0.986). The size measurements between CT and ZTE-MRI demonstrated minimal bias, up to 0.3 mm. Surgical resection and pathological confirmation were performed for 47 SSNs. Detectable nodules were more frequently invasive adenocarcinomas (IACs) than undetectable nodules (94.1%, 32/34 vs. 30.8%, 4/13; P < .001).

Conclusion: ZTE-MRI detectability of SSNs was significantly associated with CT attenuation, with a potential threshold of -637.6 HU, and correlated with pathological invasiveness. These results may contribute to individualized follow-up protocols for SSNs initially identified by CT imaging.

Background: Lung cancer screening (LCS) with Low-Dose Computed Tomography (LDCT) significantly reduces cancer mortality but remains substantially underutilized. This study examines how social determinants of health (SDOH), including financial concerns, transportation barriers, and patient-provider trust, influence adherence to annual LCS.

Methods: A prospective cohort study was conducted at an urban, safety-net academic health system. Participants who initially underwent LDCT but failed to adhere to annual follow-up were surveyed, assessing demographics, financial and transportation concerns, patient-provider relationships, and experiences of racial discrimination. Data was analyzed using descriptive statistics, chi-square tests, and Spearman correlations.

Results: Among surveyors (n = 236), cost concerns (54.4%) and access to transportation (13.3%) were significant barriers to LCS adherence. Access to transportation was more limited for non-White (22.2%) and female (18.4%) populations, compared to White (6.5%, P < .01) and male (7.1%, P = .02) populations. However, there was no difference in cost concerns (P = .50, P = .89). Additionally, non-White (4.51/5 vs. 4.26/5, P < .01) and female (4.44/5 vs. 4.31/5, P = .04) patients reported higher levels of trust and comfort with providers comparing to their counter cohorts. Perceived racial discrimination in healthcare remained higher in non-White participants (1.53/5 vs. 1.25/5, P < .01) without effect in gender cohorts (P = .24).

Conclusions: LCS can decrease the chance of lung cancer death among eligible individuals but is drastically underutilized. Most people not adhering to LCS cited cost concerns, despite coverage by insurers. Patient-provider trust can be leveraged to assess and address individual barriers to LCS.

Objective: There is a paucity of pretreatment, noninvasive assessment of tumor characteristics in non-small-cell lung cancer (NSCLC) undergoing stereotactic body radiation therapy (SBRT). Our goal was to determine if Computer Assisted Nodule Analysis and Risk Yield (CANARY) could stratify risk for recurrence in patients undergoing SBRT for clinical stage I NSCLC.

Methods: We performed a retrospective review of NSCLC patients who underwent SBRT from 2016 to 2022. Recurrence dates were collected from the date of therapy to May 2023. Pretreatment imaging was entered into the CANARY software, the correct lesion verified and demarcated, and each lesion was categorized into good, intermediate, and poor Score Indicative of Lung Cancer Aggression (SILA). Kaplan-Meier methodology was used to analyze the recurrence free survival (RFS), and Log-rank test was used for group comparison.

Results: The SBRT cohort included 85 patients. By clinical stage, there were 4 (4.7%) IA1, 41 (48.2%) IA2, 30 (35.3%) IA3, and 10 (11.8%) IB. By histology, 48 (56.5%) patients were adenocarcinoma, 23 (27.1%) were squamous cell carcinoma, and 14 (16.5%) were NSCLC. The 2-year RFS was 68.5%. By CANARY, 11 (12.9%) patients were considered to have good risk, 14 (17.6%) intermediate risk, and 60 (70.6%) poor risk by their SILA scores. Their 2-year RFS was 100.0% (100.0%-100.0%), 80.2% (58.7%-100.0%), and 68.1% (54.4%-85.3%), respectively. Intermediate and poor SILA scores had worse RFS than good SILA score patients (P = .09).

Conclusions: CANARY can potentially risk stratify recurrence in clinical stage I NSCLC patients undergoing SBRT.

Objective: Occult lymph node (LN) metastasis, indicating pathological LN involvement, is often observed in clinical N0 (cN0) early-stage non-small cell lung cancer (NSCLC). Identifying preoperative predictors of occult LN metastasis (pathologically N1 and N2) is crucial for determining the surgical procedure for cN0 NSCLC. This study aimed to investigate the role of genetic mutations in predicting occult LN metastasis and their influence on surgical strategies.

Materials and methods: We retrospectively reviewed patients who underwent lobectomy or segmentectomy for cN0 NSCLC with pathological stages higher than IB, between May 2017 and April 2024. Clinicopathological characteristics and genetic mutations were analyzed. Occult LN metastasis was not detected by imaging but identified through histopathology.

Results: We evaluated 644 patients, median age 71 years. Occult LN metastases were observed in 179 (27.8%) patients. EGFR mutations and ALK rearrangements were significantly associated with occult LN metastasis (EGFR, P = .04; ALK, P = .007), particularly EGFR exon 19 deletions (P = .006). Multivariate analysis confirmed these as significant predictors (P = .006). Notably, patients with these mutations had longer recurrence-free survival (RFS) than those without (HR 1.27, 95% CI, 0.90-1.80, P = .02). For patients with EGFR mutations and ALK rearrangements, RFS was significantly shorter after segmentectomy (HR 3.18, 95% CI, 1.02-9.99, P = .04) and longer after lobectomy (HR 1.28, 95% CI, 0.87-1.90, P = .01).

Conclusion: Genomic profiles, such as EGFR mutations and ALK rearrangements, are associated with occult LN metastasis and outcomes in cN0 NSCLC. Integrating genetic assessments into preoperative planning may optimize surgical strategies and improve prognosis.

Although the pharmacologic management of non-small cell lung cancer (NSCLC) has advanced substantially in the past 2 decades, disparities in the applicability to different histologic subtypes remain. Several treatment options are not suitable for squamous NSCLC, with use restricted to nonsquamous NSCLC (eg, bevacizumab and pemetrexed) because of safety concerns or comparative activity. Differences in mutational landscapes and a lack of matched targeted therapies specific to squamous NSCLC oncogenic aberrations present additional limitations. In the absence of suitable targeted therapies, immunotherapy with or without chemotherapy is the mainstay of squamous NSCLC treatment; however, survival-related outcomes remain poorer for patients with squamous than with nonsquamous NSCLC. Several studies are investigating promising drug therapies for patients with squamous NSCLC. This review seeks to summarize the current and emerging treatment options for patients with squamous NSCLC.

Introduction: Immune checkpoint inhibitors have limited efficacy in patients with EGFR-mutant (EGFR+) and ALK-rearranged (ALK+) non-small cell lung cancer (NSCLC). We conducted a phase II study to evaluate the efficacy of pembrolizumab with carboplatin and pemetrexed in these patients.

Patients and methods: EGFR+ or ALK+ NSCLC patients, previously treated with targeted therapy, were eligible. Carboplatin, pemetrexed and pembrolizumab were administered every 3 weeks for 4 cycles followed by maintenance pemetrexed and pembrolizumab. The primary endpoint was response rate (RR). Blood for circulating tumor cells (CTCs) was collected prior to the 1st and 3rd cycles. The plan was to enroll 28 evaluable patients in both EGFR+ and ALK+ cohorts.

Results: Of the 33 patients enrolled, 26 had EGFR+ and 7 had ALK+ NSCLC. RR (95% CI,) was 46% (27%, 67%) in EGFR+ and 29% (4%, 71%), in ALK+ patients, respectively. Median progression free survival (PFS) and overall survival (OS) in the EGFR+ cohort were 8.3 months (7.2-16.5) and 22.2 months (20.6-NE), respectively. In the ALK+ cohort, median PFS and OS were both 2.9 months. The median CTC count at baseline in 15 evaluable EGFR+ patients was 4 cells/mL (0-23). OS among EGFR+ patients with decreasing vs. increasing CTC count during treatment was not reached vs. 18.5 months, respectively (P = .52). The most common adverse events were fatigue, nausea, anemia and AST/ALT elevation.

Conclusion: Pembrolizumab in combination with chemotherapy demonstrated encouraging RR of 42% and OS of 22 months among patients with recurrent EGFR+ NSCLC. The efficacy in ALK+ patients was not encouraging.

Introduction: In resected non-small cell lung cancer (NSCLC), molecular testing is currently limited to EGFR mutations and ALK rearrangements, as these guide approved adjuvant therapies. The role of next-generation sequencing (NGS), routinely used in metastatic NSCLC, remains unclear in earlier stages. The prevalence of other driver mutations and their impact on outcomes is not well established.

Methods: We retrospectively analyzed clinical, molecular, and survival data from patients (pts) with stage IA-IIIB NSCLC (AJCC 8th) who underwent surgery and NGS at our Institute from January 2020 to December 2023. The primary endpoint was the prevalence of driver alterations. Exploratory analyses assessed recurrence, disease-free survival (DFS), overall survival (OS), and correlation with mutation status.

Results: Of 221 pts, 216 were eligible. Oncogenic alterations were found in 71% (73% in stage I), most commonly KRAS (30%) and EGFR (26%), followed by MET exon 14 skipping (6%), BRAF (4%), HER2 exon 20 mutations (3%), and ALK and RET rearrangements (1%). Alteration distribution differed by sex and smoking status. With a median follow-up of 20 months, 36% of pts experienced recurrence, including 10 stage I cases. Median time to recurrence was 14 months. Recurrence rates were higher in pts with driver mutant NSCLC (39.6%) versus wild-type (29.6%). Highest recurrence was seen in pts with oncogenic fusion positive NSCLC and EGFR exon 20 insertions.

Conclusions: Driver mutations were detected in 70% of resected NSCLC, including stage I. The recurrence patterns observed support integrating NGS into early-stage management and exploring tailored adjuvant therapies, even for stage I tumors.

Objectives: Lung cancer may require complex interventions such as pneumonectomy. This study investigates late survival after pneumonectomy and assesses the need for late rehospitalizations.

Methods: We performed a retrospective analysis of 479 consecutive patients with lung cancer undergoing pneumonectomy at our institution between 2005 and 2015. Survival was assessed at 3, 5, and 8 years and Cox multivariate analysis was used to identify independent predictors. The National anonymized medico-economic database (PMSI) was used to study early and late (up to 10 years after surgery) postpneumonectomy hospital trajectories (excluding routine follow-up visits) of patients in the last 2 years of the study period (n = 179).

Results: The mean age of patients was 62.7 ± 9.9 years and 74.9% were men; 56.18% had FEV1 below 80% of predicted. Stage III accounted for 62.84% of patients. Overall survival at 3, 5 and 8 years was 58.9%, 47.6% and 39.6%, respectively. Male sex, active tobacco smoking, Charlson Comorbidity Index >5, stage III-IV, and occurrence of Clavien Dindo≥3 postoperative complications were independent predictors of worse survival. After pneumonectomy, a total of 4845 hospitalisations were recorded in 179 patients, 886 for postoperative adjuvant treatments. Forty-five out of the 179 patients had a late hospitalisation for lung cancer recurrence, with an average delay of 23.3 months. There were 25 readmissions, involving 20/179 patients, for respiratory failure, whereas 15/179 patients were readmitted for cardiac failure. In addition, 9/179 patients were readmitted for a new nonpulmonary cancer.

Conclusions: Despite the strong physiological impact, pneumonectomy has satisfactory short and long-term results.

Background: ERBB2 mutations are oncogenic drivers in 2% to 4% of lung cancers and potentially actionable using HER2 tyrosine kinase inhibitors.

Patients and methods: Patients with advanced ERBB2-mutant lung cancer entered 2 phase 2 studies (PUMA-NER-4201 [4201]; PUMA-NER-5201 [SUMMIT]). Patients received neratinib (monotherapy 4201; monotherapy SUMMIT), or neratinib with weekly temsirolimus (combination 4201), or trastuzumab every 3 weeks (combination SUMMIT). Protocol-defined endpoints common to both studies were analyzed. Exploratory genomic analyses were conducted.

Clinicaltrials: gov: NCT01827267; NCT01953926.

Results: Sixty patients in 4201 (neratinib, n = 17; neratinib plus temsirolimus, n = 43) and 78 in SUMMIT (neratinib, n = 26; neratinib plus trastuzumab, n = 52) received study treatment. Objective response rates were 0% (95% confidence interval [CI], 0.0-19.5; 4201) and 3.8% (95% CI, 0.1-19.6; SUMMIT) with neratinib, 14.0% (95% CI, 5.3-27.9) with neratinib plus temsirolimus, and 9.6% (95% CI, 3.2-21.0) with neratinib plus trastuzumab. Five patients whose tumors harbored ERBB2 exon 20 insertion, L755P and D769Y missense mutations, and a novel ERBB2-SHC1 fusion had responses ≥ 1 year (neratinib monotherapy, n = 1; SUMMIT; neratinib plus temsirolimus, n = 2; neratinib plus trastuzumab, n = 2). Grade ≥ 3 treatment-related adverse events occurred in 23.5% (4201) and 34.6% (SUMMIT) of neratinib-treated patients, 37.2% of patients treated with neratinib plus temsirolimus, and 48.1% of patients treated with neratinib plus trastuzumab.

Conclusion: Single-agent neratinib has limited activity in ERBB2-mutated lung cancers. Combinations with temsirolimus or trastuzumab did not markedly improve overall outcomes, producing durable responses in a limited subset of patients.