Solid Lung Cancer Research Articles

β-blockers and statins: exploring the potential off-label applications in breast, colorectal, prostate, and lung cancers

Despite advances in cancer treatment, current cancer incidence and prevalence still demand multimodal treatments to enhance survival and clinical outcomes. Drugs used in cardiology, such as β-blockers and statins have gained attention for their potential roles in oncology. This review focused on their possible complementary use in solid tumors, including breast, colorectal, lung, and prostate cancers. The involvement of the autonomic nervous system in promoting tumor growth can be disrupted by β-blockers, potentially hindering cancer progression. Statins, known for their pleiotropic effects, may also inhibit cancer growth by reducing cholesterol availability, a key factor in cell proliferation. We will provide an update on the impact of these therapies on cancer treatment and surveillance, discuss the underlying mechanisms, and explore their effects on the heart, contributing to the growing field of cardio-oncology.

Lung cancer volume doubling time by computed tomography: A systematic review and meta-analysis

AimLung cancer growth rate influences screening strategies and treatment decisions. This review aims to provide an overview of primary lung cancer growth rate, quantified by volume doubling time (VDT) through computed tomography (CT) measurement. MethodsUsing PRISMA-DTA guideline, PubMed, EMBASE, and Web of Science were searched until March 2024 for studies reporting CT-measured VDT of pathologically confirmed primary lung cancer before intervention. Summary data were extracted from published reports by two independent researchers. Primary outcomes were pooled mean VDT of lung cancer by nodule type and histology, distribution of indolent lung cancer (defined as VDT>400 days or negative), and correlated factors. ResultsThirty-three studies were eligible, comprising 3959 patients with primary lung cancer (mean age range:57.6–77.0 years; 60.0 % men). The pooled mean VDT for solid, part-solid, and nonsolid lung cancer were 207, 536, and 669 days, respectively (p < 0.001). When stratified by histology within solid lung cancer, the pooled mean VDT of adenocarcinoma, squamous cell carcinoma, small cell lung cancer, and others were 223, 140, 73, and 178 days, respectively (p < 0.001). Indolent lung cancer was observed in 34.9 % of lung cancer, predominantly in adenocarcinoma (68.9 %). Adenocarcinoma was associated with slower growth, whereas factors such as tumor size, solidity, TNM staging, and smoking history were positively associated with growth rates. ConclusionsPooled mean VDT of solid lung cancer was approximately 207 days, demonstrating significant variability in histology yet remaining under the 400-day referral threshold. Key predictors of growth rate include histology, size, solidity, and smoking history, essential for tailoring early intervention strategies. Trial registration numberCRD42023408069

An Insight into Perfusion Anisotropy within Solid Murine Lung Cancer Tumors.

Blood vessels are essential for maintaining tumor growth, progression, and metastasis, yet the tumor vasculature is under a constant state of remodeling. Since the tumor vasculature is an attractive therapeutic target, there is a need to predict the dynamic changes in intratumoral fluid pressure and velocity that occur across the tumor microenvironment (TME). The goal of this study was to obtain insight into perfusion anisotropy within lung tumors. To achieve this goal, we used the perfusion marker Hoechst 33342 and vascular endothelial marker CD31 to stain tumor sections from C57BL/6 mice harboring Lewis lung carcinoma tumors on their flank. Vasculature, capillary diameter, and permeability distribution were extracted at different time points along the tumor growth curve. A computational model was generated by applying a unique modeling approach based on the smeared physical fields (Kojic Transport Model, KTM). KTM predicts spatial and temporal changes in intratumoral pressure and fluid velocity within the growing tumor. Anisotropic perfusion occurs within two domains: capillary and extracellular space. Anisotropy in tumor structure causes the nonuniform distribution of pressure and fluid velocity. These results provide insights regarding local vascular distribution for optimal drug dosing and delivery to better predict distribution and duration of retention within the TME.

Landscape of clinical drug development of ADCs used for the pharmacotherapy of cancers: an overview of clinical trial registry data from 2002 to 2022

BackgroundTo provide reference for clinical development of ADCs in the industry, we analyzed the landscape and characteristics of clinical trials about antibody-drug conjugates (ADCs).MethodClinical trials to study ADCs used for the pharmacotherapy of cancers initiated by the sponsor were searched in the Cite line Pharma Intelligence (Trialtrove database), and the landscape and characteristics of these clinical trials were analyzed from multiple perspectives, such as the number, phases, status, indications, and targets of the clinical trials.ResultAs of December 31, 2022, a total of 431 clinical trials have been initiated to study ADCs used for the pharmacotherapy of cancers, and the number of the last 10 years was 5.5 times as large as the first 11 years. These clinical trials involved 47 indications, including breast cancer, lymphoma (lymphoma, non-Hodgkin’s and lymphoma, Hodgkin’s), unspecified solid tumor, bladder cancer and lung cancer (lung, non-small cell cancer and lung, small cell cancer). As for each of these five indications, 50 + clinical trials have been carried out, accounting for as high as 48.50% (454/936). ADCs involve 38 targets, which are relatively concentrated. Among them, ERBB2 (HER2) and TNFRSF8 (CD30) involve in 100 + registered clinical trials, and TNFRSF17 (BCMA), NECTIN4 and CD19 in 10 + trials. The clinical trials for these five targets account for 79.02% (354/448) of the total number. Up to 93.97% (405/431) of these clinical trials explored the correlation between biomarkers and efficacy. Up to 45.91% (292/636) of Lots (lines of treatment) applied in the clinical trials were the second line. Until December 31, 2022, 54.52% (235/431) of the clinical trials have been completed or terminated.ConclusionADCs are a hotspot of research and development in oncology clinical trials, but the indications, targets, phases, and Lot that have been registered are seemingly relatively concentrated at present. This study provides a comprehensive analysis which can assist researchers/developer quickly grasp relevant knowledge to assess a product and also providing new clues and ideas for future research.

Irinotecan Resistance Mechanisms in Cancer: Challenges and Opportunities

Irinotecan, a topoisomerase I inhibitor, has been widely used in the treatment of various solid tumors, including colorectal, lung, and pancreatic cancers. However, its efficacy is often limited by the development of resistance mechanisms within cancer cells. Understanding these resistance mechanisms is crucial for improving treatment outcomes and developing effective therapeutic strategies. This review article provides a comprehensive overview of the mechanisms underlying irinotecan resistance in cancer. Key resistance mechanisms discussed include the overexpression of drug efflux pumps, activation of DNA repair pathways, altered drug metabolism, and microenvironmental factors. Clinical implications, challenges, and emerging opportunities in overcoming irinotecan resistance are also explored, including the identification of biomarkers predictive of response/resistance, combination therapies targeting multiple resistance pathways, and advancements in drug delivery systems. By elucidating the complexities of irinotecan resistance, this review aims to inform future research directions and facilitate the development of personalized treatment approaches for patients with resistant cancers.

Spectral CT for preoperative diagnosis of N2 station lymph node metastasis in solid T1 non-small cell lung cancer

PurposeTo evaluate the diagnostic value of spectral CT for the preoperative diagnosis of N2 station lymph nodes metastasis in solid T1 non-small cell lung cancer (NSCLC). MethodFor this retrospective study, dual-phase contrast agent-enhanced CT was performed in patients with NSCLC from September 2019 to June 2023. Quantitative spectral CT parameters measurements were performed by 2 radiologists independently. Logistic regression analysis and Delong test were performed. Results60 NSCLC patients (mean age, 62.85 years ± 8.49, 44men) were evaluated. A total of 121 lymph nodes (38 with metastasis) were enrolled. There was no significant difference in the slope of the spectral Hounsfield unit curve (λHu) on arterial phase (AP) or venous phase (VP) between primary lesions and metastatic lymph nodes (P > 0.05), but significant difference in VP λHu between primary lesions and non-metastatic lymph nodes (P < 0.001). The CT40KeV, λHu, normalized iodine concentration (nIC), normalized effective atomic number (nZeff) measured during both AP and VP were lower in metastatic lymph nodes than in non-metastatic lymph nodes (all P < 0.05). Short-axis diameter (S) of metastatic lymph nodes was higher than non-metastatic lymph nodes (P < 0.001). Area under the curve (AUC) for S performed the highest (0.788) in diagnosing metastatic lymph nodes. When combined with VP λHu, VP nZeff, AUC increased to 0.871. ConclusionSpectral CT is a complementary means for the preoperative diagnosis of N2 station lymph nodes metastasis in solid T1 NSCLC. The combined parameters have higher diagnostic efficiency.

Prevention of Brain Metastases: A New Frontier.

This review discusses the topic of prevention of brain metastases from the most frequent solid tumor types, i.e., lung cancer, breast cancer and melanoma. Within each tumor type, the risk of brain metastasis is related to disease status and molecular subtype (i.e., EGFR-mutant non-small cell lung cancer, HER2-positive and triple-negative breast cancer, BRAF and NRAF-mutant melanoma). Prophylactic cranial irradiation is the standard of care in patients in small cell lung cancer responsive to chemotherapy but at the price of late neurocognitive decline. More recently, several molecular agents with the capability to target molecular alterations driving tumor growth have proven as effective in the prevention of secondary relapse into the brain in clinical trials. This is the case for EGFR-mutant or ALK-rearranged non-small cell lung cancer inhibitors, tucatinib and trastuzumab-deruxtecan for HER2-positive breast cancer and BRAF inhibitors for melanoma. The need for screening with an MRI in asymptomatic patients at risk of brain metastases is emphasized.

The novel DNA methylation marker FIBIN suppresses non-small cell lung cancer metastasis by negatively regulating ANXA2

ObjectivesThe clinical T1 stage solid lung cancer with metastasis is a serious threat to human life and health. In this study, we performed RNA sequencing on T1 advanced-stage lung cancer and adjacent tissues to identify a novel biomarker and explore its roles in lung cancer. MethodsQuantitative reversed-transcription PCR, reverse transcription PCR and Western blot, MSP and Methtarget were utilized to evaluate FIBIN expression levels at both the transcriptional and protein levels as well as its methylation status. Differential target protein was evaluated for relative and absolute quantitation by isobaric tags. Co-IP was performed to detect the interactions between target protein. Precise location and expression levels of target proteins were revealed by immunofluorescence staining and component protein extraction using specific kits, respectively. ResultsWe reported that FIBIN was frequently silenced due to promoter hypermethylation in lung cancer. Additionally, both in vitro and in vivo experiments confirmed the significant anti-proliferation and anti-metastasis capabilities of FIBIN. Mechanistically, FIBIN decreased the nuclear accumulation of β-catenin by reducing the binding activity of GSK3β with ANXA2 while promoting interaction between GSK3β and β-catenin. ConclusionOur findings firstly identify FIBIN is a tumor suppressor, frequently silenced due to promoter hypermethylation. FIBIN may serve as a predictive biomarker for progression or metastasis among early-stage lung cancer patients.

Comparison of lifetime mortality risk, incidence risk, and DALYs of baseline cancer rates among countries as a benchmark for radiation-related cancer risk

Statistical benchmark data are necessary when considering the basis for radiation protection criteria based on calculated risks. We herein focused on baseline mortality and incidence cancer rates as benchmark data collected from 33 countries. Furthermore, we calculated the lifetime mortality and incidence risks and disability-adjusted life years (DALYs) for all solid cancers, colon cancer, lung cancer, breast cancer, thyroid cancer, and leukemia using the baseline cancer rates and compared them among the countries. The results showed that the lifetime mortality and incidence risks and DALYs for all solid cancers differed among the countries by a factor of 2–4 for males and 2–3 for females; these were low in less-developed countries. Our study proposed that health risk based on baseline cancer rates should be the benchmark for comparing radiation cancer risks.

Abstract 4086: ABN202 (anti-Trop-2-interferon-beta mutein): A potent antibody-cytokine fusion protein for the treatment of Trop-2 positive solid tumors

Abstract Trop-2, trophoblast cell-surface antigen 2, is a type 1 transmembrane glycoprotein overexpressed in many solid cancers, including breast, lung, pancreatic, bile duct and bladder cancer. Overexpression of Trop-2 in cancer patients is associated with disease progression and poor prognosis. The antibody-drug conjugate (ADC) targeting Trop-2, Sacituzumab-govitecan (Trodelvy®), is approved for patients with triple-negative breast cancer (TNBC) and bladder cancer. However, Trop-2 targeting ADCs exhibit a high frequency of grade 3/4 adverse events and a short duration of response. Therefore, there is an unmet medical need for new treatment strategies beyond ADCs. In a previous study, we designed ABN202 (αTrop-2) to comprise a Trop-2 targeting antibody (Sacituzumab) and IFN-β mutein (ABN102) for the Trop2-positive tumor-specific delivery of ABN102. We confirmed anti-cancer activities of ABN202 against Trop-2 positive bladder cancer. In this study, we evaluated in vitro and in vivo anti-cancer efficacy of ABN202 (αTrop-2) in Trop-2 positive TNBC, bile duct cancer and bladder cancer cell lines. To identify response biomarkers for ABN202 (αTrop-2), we analyzed cell lines exhibiting both response and non-response to ABN202 (αTrop-2). In conclusion, ABN202 (αTrop-2) demonstrated potent anti-cancer efficacy compared to Trodelvy®. Our results support ABN202 (αTrop-2) as a promising drug candidate against Trop2-positive solid tumors. Citation Format: Hee Geon Park, Hyun Kyung Lee, Myeung Ryun Seo, Daa Eun Kim, Sang Beom Bang, Ji Yang Lee, Sung Youl Hong, Kyoung Song, Chan Gyu Lee, Hae Min Jeong, Sae Hyung Lee, Na Young Kim, Jun Young Choi, Young Kee Shin. ABN202 (anti-Trop-2-interferon-beta mutein): A potent antibody-cytokine fusion protein for the treatment of Trop-2 positive solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4086.

Abstract 6582: Preclinical characterization of IPH45, a novel topoisomerase I inhibitor ADC targeting Nectin-4 for the treatment of Nectin-4 expressing tumors

Abstract Background: Nectin-4 is a cell membrane adhesion protein overexpressed in several solid tumors, including urothelial, breast, lung, ovarian, and pancreatic cancers, with limited expression in normal tissues, making it an ideal target for antibody-drug conjugates (ADC). Enfortumab Vedotin (EV, PADCEV®) is an ADC targeting Nectin-4 with a monomethyl auristatin E (MMAE) payload approved for the treatment of patients with urothelial carcinoma (UC), but with limited clinical activity reported beyond UC. In addition, EV causes peripheral neuropathy and skin toxicity, leading to treatment discontinuation. To overcome these limitations and the mechanism of resistance to EV, IPH45, a novel topoisomerase I inhibitor ADC targeting Nectin-4 with an improved therapeutic index, was developed. Methods: In vitro studies were performed to investigate internalization, tumor cell killing and bystander effect, antibody-dependent cellular cytotoxicity (ADCC) and complement activation. In vivo efficacy studies were performed on cell line-derived xenografts (CDX) of triple negative breast cancer, patient-derived xenografts (PDX) of urothelial carcinoma and syngeneic tumor models expressing human Nectin-4. IPH45 efficacy was compared to EV. Toxicology studies to determine the dose range were conducted in rat and non-human primates (NHP). Results: IPH45 consists of a humanized IgG1 targeting a unique epitope in human Nectin-4, non-overlapping with EV, a cleavable linker, and a topoisomerase I inhibitor with a high drug-to-antibody ratio (DAR). In vitro, IPH45 is internalized upon binding to its target and induces direct killing of Nectin-4 expressing tumor cells as well as bystander killing of Nectin-4 non-expressing tumor cells in mixed culture. IPH45 mediates ADCC and complement-mediated killing. IPH45 demonstrates activity in CDX and PDX models with similar effective dose as EV. Moreover, IPH45 shows anti-tumor efficacy in vitro and in vivo in primary and secondary EV resistant models. In dose-range finding toxicology studies in rats and NHP, IPH45, unlike EV, does not elicit skin toxicity. IPH45 remains well tolerated up to the highest dose tested, suggesting a potentially larger therapeutic index than MMAE-based ADCs. Pharmacokinetic analyses in mice, rats, and NHP show minimal release of free toxin in the serum and half-life compatible with Q2W or less frequent dosing schedules in clinic. Conclusion: IPH45 is a topoisomerase I ADC targeting Nectin-4 with the potential for larger therapeutic index than EV, improved safety and dosing regimen, and ability to overcome primary and secondary resistance to EV or other Nectin-4 ADC in development. IPH45 is progressing to the clinic where the translatability of this unique profile into improved patient outcomes will be assessed across indications. Citation Format: Romain Remark, Cécile Bonnafous, Laura Chiossone, Caroline Soulas, Cyril Perrier, Guillaume Habif, Sivan Bokobza, Aurélie Maguer, Rachel Courtois, Julie Lopez, Grégory Fenaux, Olivier Benac, Barbara Carrette, Robin Letay-Drouet, Raja Bonifay, Séverine Augier, Léa Simon, Benjamin Rossi, Ariane Morel, Agnès Represa, Nicola Beltraminelli, Yannis Morel, Carine Paturel, Eric Vivier. Preclinical characterization of IPH45, a novel topoisomerase I inhibitor ADC targeting Nectin-4 for the treatment of Nectin-4 expressing tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6582.

Inpatient outcomes of metastatic epidural spinal cord compression in patients with gastric cancer compared to patients with other solid cancer.

255 Background: Metastatic epidural spinal cord compression (MESCC) is an oncologic emergency which can be associated with poor outcomes for cancer patients. Our aim was to study the differences in outcomes of MESCC in patients with gastric cancer (GC-MESCC) compared to those with other solid malignancies. Methods: Healthcare Cost and Utilization Project-Nationwide Inpatient Sample database (2016-2020) was queried to identify all solid (breast, prostate, lung, gastrointestinal, renal and thyroid) cancer patients admitted with spinal cord compression. Multivariate logistic regression was used to evaluate differences in socio-demographics, medical comorbidities and outcomes between MESCC in gastric cancer patients and those with other solid cancers. The primary outcome included inpatient mortality, length of stay (LOS), and total hospital charges (THC). Results: 78,385 patients with the above solid cancers were admitted for spinal cord compression. Among them, 710 had gastric cancer. Patients with gastric cancer were younger (Mean age: 59.1 vs 66.3 years, p &lt; 0.001). They had higher prevalence of anemia (56 vs 41%), protein energy malnutrition (28.9 vs 18.9%, p &lt; 0.001), and lower prevalence of COPD (8.45 vs 18.5%, p =0.003), smoking (22.5 vs 33.6%, p =0.007) and CKD (9.4 vs 12.3%, p =0.03). On multivariate regression, those with GC-MESCC had two-fold higher odds of all-cause mortality (adjusted odds ratio (aOR): 2.0; 95% CI: 1.05-3.96, p = 0.034). On subgroup analysis, mortality was about four times higher for females with GC-MESCC relative to the other group (aOR = 3.8, 95% CI: 1.69-8.52, p = 0.001). There was a trend towards increased LOS (8.9 vs 7.8 days) and THC ($115, 805 vs $96, 074) but it was not statistically significant. Compared with the other cohort, GC-MESCC patients had higher rates of blood transfusion (16.2 vs 9%, p = 0.003). Conclusions: Metastatic epidural spinal cord compression is associated with increased odds of inpatient mortality in gastric cancer patients compared to those with other solid malignancies. Hence, these patients ought to have urgent intervention and close monitoring to prevent adverse outcomes. [Table: see text]

Is 18F-fluorodeoxyglucose PET recommended for small lung nodules? CT findings of 18F-fluorodeoxyglucose non-avid lung cancer.

To determine the image characteristics associated with low 18F-FDG (18F-fluorodeoxyglucose) avidity among 8-15 mm solid lung cancer. Patients satisfying the following criteria were included: underwent surgery between January 2014 and December 2019 for lung cancer, presented 8-15 mm nodule without measurable ground glass component on preoperative CT, and underwent 18F-FDG PET before resection. Image characteristics, including air bronchogram, concave shape, pleural attachment, and background emphysema, were evaluated by two board-certified radiologists. The Mann-Whitney U test was used to compare maximum standardized uptake (SUVmax) values from 18F-FDG PET images. The analysis included 235 patients. The SUVmax values of lesions with air bronchogram and concave shape were significantly lower than the SUVmax values of lesions without these features (median: 1.55 vs 2.56 and 1.66 vs 2.45, both P < .001), whereas lesions arising from emphysematous lungs had significantly higher SUVmax values than lesions arising from non-emphysematous lungs (2.90 vs 1.69, P < .001). No significant differences were detected between lesions attached and not attached to pleura. The interobserver agreement was almost perfect for air bronchograms and background emphysema (κ = 0.882 and 0.927, respectively), and 89.7% of lesions with air bronchograms and arising from non-emphysematous lungs showed SUVmax values below 2.5. Among 8-15 mm solid lung cancer, the presence of air bronchograms and concave shape and the absence of background emphysema were associated with low 18F-FDG accumulation. 18F-FDG PET can be misleading in differentiating certain type of small solid lung cancer.

Risk and Time to Diagnosis of Lung Cancer in Incidental Pulmonary Nodules.

To determine the risk of lung cancer in incidental pulmonary nodules, as well as the time until cancer growth is detected. This retrospective study examined patients with incidental nodules detected on chest computed tomography (CT) in 2017. Characteristics of the dominant nodule were automatically extracted from CT reports, and cancer diagnoses were manually verified by a thoracic radiologist. Nodules were categorized per Fleischner Society guideline categories: solid <6mm, solid 6 to 8mm, solid >8mm, subsolid <6mm, ground glass nodules ≥6mm, and part-solid nodules ≥6mm. The time to nodule growth was determined by CT reports. A total of 3180 patients (nodules) were included, of which 155 (5%) were diagnosed with lung cancer. By category, 7/1601 (0.4%) solid nodules <6mm, 11/713 (1.5%) solid nodules 6 to 8mm, 71/446 (15.9%) solid nodules >8mm, 1/124 (0.8%) subsolid nodules <6mm, 29/202 (14.4%) ground glass nodules ≥6mm, and 36/94 (37.9%) part-solid nodules ≥6mm were malignant. Of solid lung cancers <6mm, growth was observed in 1/4 imaged by 1 year and 2/5 by 2 years; of solid lung cancers 6 to 8mm, growth was observed in 3/10 imaged by 1 year and 6/10 by 2 years. Solid nodules <6mm have a very low risk of malignancy and may not require routine follow-up. However, when malignant, growth is often not observed until 2 or more years later; therefore, stability at 1 to 2 years does not imply benignity.

Segmentectomy for patients with early-stage pure-solid non-small cell lung cancer.

For decades, lobectomy has been the recommended surgical procedure for non-small cell lung cancer (NSCLC), including for small-sized lesions. However, two recent pivotal clinical trials conducted by the Japanese Clinical Oncology Group/West Japan Oncology Group (JCOG0802/WJOG4607L) and the Cancer and Leukemia Group B (CALGB140503), which compared the survival outcomes between lobectomy and sublobar resection (the JCOG0802/WJOG4607L included only segmentectomy, not wedge resection), demonstrated the efficacy of sublobar resection in patients with early-stage peripheral lung cancer measuring ≤ 2 cm. The JCOG0802/WJOG4607L demonstrated the superiority of segmentectomy over lobectomy with respect to overall survival, implying the survival benefit conferred by preservation of the lung parenchyma. Subsequently, the JCOG1211 also demonstrated the efficacy of segmentectomy, even for NSCLC, measuring up to 3 cm with the predominant ground-glass opacity phenotype. Segmentectomy has become the standard of care for early-stage NSCLC and its indications are expected to be further expanded to include solid lung cancers > 2 cm. However, local control is still a major concern for segmentectomy for higher-grade malignant tumors. Thus, the indications of segmentectomy, especially for patients with radiologically pure-solid NSCLC, remain controversial due to the aggressive nature of the malignancy. In this study, we reviewed previous studies and discussed the efficacy of segmentectomy for patients with such tumors.

Percutaneous core-needle biopsy before and immediately after coaxial microwave ablation in solid non-small cell lung cancer: the comparison of genomic testing from specimens

PurposeTo compare the genomic testing based on specimens obtained from percutaneous core-needle biopsy (CNB) before and immediately after coaxial microwave ablation (MWA) in solid non-small cell lung cancer (NSCLC), and to investigate the diagnostic performance of CNB immediately after coaxial MWA in solid NSCLC.MethodsCoaxial MWA and CNB were performed for NSCLC patients, with a power of 30 or 40 watts (W) in MWA between the pre- and post-ablation CNB, followed by continuous ablation after the second CNB on demand. The paired specimens derived from the same patient were compared for pathological diagnosis and genomic testing. DNA/RNA extracted from the paired specimens were also compared.ResultsA total of 33 NSCLC patients with solid lesions were included. There were two patients (6.1%) without atypical cells and three patients (9.1%) who had the technical failure of genomic testing in post-ablation CNB. The concordance rate of pathological diagnosis between the twice CNB was 93.9% (kappa = 0.852), while that of genomic testing was 90.9% (kappa = 0.891). For the comparisons of DNA/RNA extracted from pre- and post-ablation CNB in 30 patients, no significant difference was found when the MWA between twice CNB has a power of 30 or 40 W and ablation time within five minutes (P = 0.174).ConclusionsIf the pre-ablation CNB presented with a high risk of pneumothorax or hemorrhage, the post-ablation CNB could be performed to achieve accurate pathological diagnosis and genomic testing and the maximum effect of ablation, which might allow for the diagnosis of genomic testing in 90.9% of solid NSCLC.

Segmentectomy for partially solid non-small cell lung cancer: what counts—the resection or the patient?

Segmentectomy for partially solid non-small cell lung cancer: what counts—the resection or the patient?

Cytopathological differential diagnosis of malignant tumor cells in the cerebrospinal fluid: A retrospective analysis.

Leptomeningeal metastasis is the spread of cancer to the leptomeninges and subarachnoid space and represents a dreadful complication of cancer. The most commonly responsible neoplasms are high-grade lymphomas, leukemias, and some solid tumors, chiefly breast and lung cancer as well as melanoma. Herein we report our ten-year retrospective experience on 715 cases of cerebrospinal fluid cytology, 21 (2.9%) of which were positive for leptomeningeal metastasis. Sample collection and processing, clinical history, interdisciplinary dialog, and ancillary techniques such as immunocytochemistry and flow cytometry are all fundamental in reaching the correct diagnosis and thus optimally caring for patients with leptomeningeal metastasis.

Antibody-Drug Conjugates in Solid Tumor Oncology: An Effectiveness Payday with a Targeted Payload.

Antibody-drug conjugates (ADCs) are at the forefront of the drug development revolution occurring in oncology. Formed from three main components-an antibody, a linker molecule, and a cytotoxic agent ("payload"), ADCs have the unique ability to deliver cytotoxic agents to cells expressing a specific antigen, a great leap forward from traditional chemotherapeutic approaches that cause widespread effects without specificity. A variety of payloads can be used, including most frequently microtubular inhibitors (auristatins and maytansinoids), as well as topoisomerase inhibitors and alkylating agents. Finally, linkers play a critical role in the ADCs' effect, as cleavable moieties that serve as linkers impact site-specific activation as well as bystander killing effects, an upshot that is especially important in solid tumors that often express a variety of antigens. While ADCs were initially used in hematologic malignancies, their utility has been demonstrated in multiple solid tumor malignancies, including breast, gastrointestinal, lung, cervical, ovarian, and urothelial cancers. Currently, six ADCs are FDA-approved for the treatment of solid tumors: ado-trastuzumab emtansine and trastuzumab deruxtecan, both anti-HER2; enfortumab-vedotin, targeting nectin-4; sacituzuzmab govitecan, targeting Trop2; tisotumab vedotin, targeting tissue factor; and mirvetuximab soravtansine, targeting folate receptor-alpha. Although they demonstrate utility and tolerable safety profiles, ADCs may become ineffective as tumor cells undergo evolution to avoid expressing the specific antigen being targeted. Furthermore, the current cost of ADCs can be limiting their reach. Here, we review the structure and functions of ADCs, as well as ongoing clinical investigations into novel ADCs and their potential as treatments of solid malignancies.

Successful ex vivo expansion of tumor infiltrating lymphocytes with systemic chemotherapy prior to surgical resection.

Tumor infiltrating lymphocytes (TIL) have demonstrated efficacious clinical outcomes for many patients with various types of solid cancers, including melanoma, gastrointestinal cancer, lung cancer, and head and neck cancer. Currently, the majority of clinical trials require that patients did not receive systemic therapy right before tumor tissue resection to avoid the interference of chemotherapy in the ex vivo TIL expansion. The primary disadvantage of this strategy is limiting the accessibility of TIL therapy for many eligible cancer patients. Over the past decade, substantial progress has been made for ex vivo expansion technologies in T cells. In this study, we investigated the possibility of enrolling patients who underwent chemotherapy prior to surgical resection. We collected seventeen tumor tissues from treatment naive cases, and five from cases that underwent chemotherapies. Cancer indications enrolled in this study were colorectal and lung cancers from both primary and metastatic sites, such as liver and brain. TILs from these tumors were expanded ex vivo to 2.1E8 (total viable lymphocytes counts) on average, with an overall success rate of 90.9%. Subsequently, TIL phenotypes and cytokine production were analyzed using flow cytometry and ELISA, respectively. We demonstrated functional TIL expansion from tumor tissues despite chemotherapy prior to surgical resection. We observed no significant phenotypic or functional differences between groups with and without chemotherapy. TIL expansion rate and characteristics were similar regardless of chemotherapy prior to resection, thereby providing a possibility to recruit patients with the most recent chemotherapy history in TIL therapy trials.