Clinical lung cancer最新文献

Background: Disease progression during or after consolidation treatment with durvalumab, an immune-oncology agent (IO) for non-small cell lung cancer, confers a poor prognosis. Systemic therapy is the mainstay. Currently, standard first-line systemic therapy includes IO; however, in the post-durvalumab setting, it remains unclear if IO should be used again.

Methods: We performed an analysis of a nationwide, deidentified database of patients with stage III non-small cell lung cancer who received concurrent chemoradiation, durvalumab consolidation, and salvage systemic therapy. Overall survival, measured from salvage treatment, was compared between salvage IO or IO-based regimens (ie IO regimens) and non-IO regimens. Predictive factor of PD-L1 level was demonstrated by effect modification.

Results: Analyses included 104 patients: 49 patients (47%) received salvage IO regimens and 55 (53%) received non-IO regimens. The median overall survival was 12.7 months: 13.4 months with IO regimens versus 9.5 months with non-IO regimens, P = .27. Among patients with PD-L1 < 1% (n = 41), survival was numerically worse with IO regimens than with non-IO regimens: hazard ratio (HR) 1.88 (95% CI, 0.81-4.39, P = .14). However, among those with PD-L1 ≥ 1% (n = 63), survival was better with IO regimens than non-IO regimens: HR 0.48 (95% CI, 0.25-0.93, P = .03). The association between regimens and survival differed by PD-L1 level, P-interaction =.007. Poor performance status and lower socioeconomic index were significant adverse prognostic factors.

Conclusion: In post-durvalumab setting, this analysis suggests that salvage IO regimens are superior to non-IO regimens, but only among patients with PD-L1 ≥ 1%.

Background: Chronological age alone does not adequately capture inter-individual variability in the health status and treatment outcomes of patients with advanced non-small cell lung cancer (NSCLC). Biological age, calculated using routine clinical biomarkers (BioAge), may offer superior prognostic value.

Patients and methods: A retrospective analysis was conducted on 138 patients treated with immune checkpoint inhibitors (ICIs; ICI cohort) and 154 ICI-naïve patients treated with chemotherapy (chemotherapy cohort). BioAge was calculated using chronological age and seven clinical biomarkers. BioAge acceleration (BioAgeAccel) was defined as the residual derived from the linear regression of BioAge on chronological age. The Kaplan-Meier method and Cox proportional hazards model were used for survival analyses. In the ICI cohort, associations with immune-related adverse events (irAEs) development were evaluated using competing risk regression.

Results: Higher BioAge (≥79.1 years) was independently associated with shorter overall survival (OS) in both cohorts, whereas chronological age (≥75 years) was not. In the ICI cohort, biologically older patients demonstrated significantly worse OS than biologically younger patients, and BioAgeAccel was an independent prognostic factor. However, the BioAgeAccel was not associated with OS in the chemotherapy cohort. No significant associations were observed between BioAge, BioAgeAccel, or chronological age and the risk of irAEs.

Conclusion: Biological age is a robust prognostic factor for advanced NSCLC. BioAgeAccel has additional prognostic value, particularly in the context of immunotherapy. Incorporating biological age metrics into clinical practice may improve patient stratification and support individualized treatment decisions.

Background: Pulmonary sarcomatoid carcinomas (PSCs) are rare, aggressive tumors with a poor prognosis. Conventional chemotherapy shows limited efficacy, whereas immune checkpoint inhibitors and doxorubicin have shown potential. This study evaluated the efficacy and safety of durvalumab, doxorubicin, and ifosfamide in recurrent and/or metastatic PSC.

Patients and methods: Patients with recurrent or metastatic PSC received durvalumab (1500 mg, day 1), doxorubicin (20 mg/m² intravenously, days 1-3), and ifosfamide (1.5 g/m² intravenously with mesna, days 2-4) every 3 weeks for up to four cycles, followed by durvalumab monotherapy until disease progression or unacceptable toxicity, for up to 12 months. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), duration of response (DOR), and toxicity.

Results: The study was prematurely terminated due to low recruitment rates, with 20 patients enrolled (15 male, 5 female; median age: 63.5 years). Among 18 evaluable cases, 16 (88.9%) were programmed death-ligand 1 positive. Six patients (30.0%) had prior palliative chemotherapy. ORR was 35.0% (95% CI, 17.7%-55.8%). The median DOR was 5.3 months (95% CI, 1.7-not estimated). After a median follow-up of 7.0 months (1.2-37.6), the median PFS and OS were 4.8 months (95% CI, 2.0-6.5) and 9.4 months (95% CI, 5.5-26.8), respectively. Adverse events (AEs) occurred in 19 patients, with serious AEs in 10 patients.

Conclusion: Durvalumab combined with doxorubicin and ifosfamide suggested clinical activity in recurrent and/or metastatic PSC. Larger studies are warranted to confirm benefits and refine treatment strategies.

Background: Accurate evaluation of mediastinal and hilar lymph node (LN) is essential in non-small cell lung cancer (NSCLC) management. While PET/CT plays a central role, SUV_max alone is limited by false positives and false negatives. The tumor-to-lymph node SUV_max (T/LN SUV_max) ratio may improve diagnostic accuracy by contextualizing nodal uptake relative to the primary tumor.

Methods: This retrospective single-center study analyzed 2469 LNs from 1408 NSCLC patients who underwent both PET/CT and EBUS-TBNA between 2010 and 2021. Sonographic features, including LN size, presence of coagulative necrosis sign (CNS), absence of central hilar structure (CHS), PET/CT findings and cytology results were recorded. Multivariate logistic regression identified independent predictors of malignancy. ROC analysis determined the optimal cut-off value for T/LN SUV_max ratio.

Results: Malignant LNs (n = 980, 39.7%) were more likely to be larger size, round in shape, with homogeneous texture, distinct margins, CNS, and lacking CHS (all P < .001). Malignant LNs had significantly lower T/LN SUV_max ratios than benign LNs (1.74 ± 1.45 vs. 4.12 ± 2.46; P < .001). Lower T/LN SUV_max ratio, higher SUV_max, larger size, and absence of CHS were independent predictors of malignancy. A cut-off of 2.10 yielded 79.1% sensitivity, 78.9% specificity, 79% diagnostic accuracy (AUC: 0.838).

Conclusions: The T/LN SUV_max ratio is a simple, and reproducible parameter with high diagnostic performance for predicting LN malignancy in PET/CT-guided EBUS-TBNA for NSCLC. Although this was a single-center retrospective study, the large cohort strengthens the reliability of our findings, and a cut-off value ≤ 2.10 may help clinicians prioritize LN sampling.

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.