Explore the vast range of titles available.

Purpose Despite clinical guidelines, palliative care is underutilized during advanced stage lung cancer treatment. To inform interventions to increase its use, patient-level barriers and facilitators (i.e., determinants) need to be characterized, especially among patients living in rural areas or those receiving treatment outside academic medical centers. Methods Between 2020 and 2021, advanced stage lung cancer patients ( n  = 77; 62% rural; 58% receiving care in the community) completed a one-time survey assessing palliative care use and its determinants. Univariate and bivariate analyses described palliative care use and determinants and compared scores by patient demographic (e.g., rural vs. urban) and treatment setting (e.g., community vs. academic medical center) factors. Results Roughly half said they had never met with a palliative care doctor (49.4%) or nurse (58.4%) as part of cancer care. Only 18% said they knew what palliative care was and could explain it; 17% thought it was the same as hospice. After palliative care was distinguished from hospice, the most frequently cited reasons patients stated they would not seek palliative care were uncertainty about what it would offer (65%), concerns about insurance coverage (63%), difficulty attending multiple appointments (60%), and lack of discussion with an oncologist (59%). The most common reasons patients stated they would seek palliative care were a desire to control pain (62%), oncologist recommendation (58%), and coping support for family and friends (55%). Conclusion Interventions should address knowledge and misconceptions, assess care needs, and facilitate communication between patients and oncologists about palliative care.

This single‐arm confirmatory study (JCOG1305) aimed to evaluate the utility of interim positron emission tomography (iPET)‐guided therapy for newly diagnosed advanced‐stage classic Hodgkin lymphoma (cHL). Patients aged 16–60 years with cHL received two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and then underwent an iPET scan (PET2), which was centrally reviewed using a five‐point Deauville scale. PET2‐negative patients continued an additional four cycles of ABVD, whereas PET2‐positive patients switched to six cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP). The co‐primary endpoints were 2‐year progression‐free survival (PFS) among all eligible and PET2‐positive patients. Ninety‐three patients were enrolled between January 2016 and December 2019. One patient was ineligible because of a diagnostic error. The median age of the 92 eligible patients was 35 (interquartile range, 28–48) years. Forty (43%) patients had stage III disease, and 43 (47%) had stage IV disease. The remaining nine (10%) patients had stage IIB disease with risk factors. Nineteen PET2‐positive (21%) patients received eBEACOPP, 18 completed six cycles of eBEACOPP, 73 PET2‐negative (79%) patients continued ABVD, and 70 completed an additional four cycles of ABVD. With a median follow‐up period of 41.1 months, the 2‐year PFS of 92 eligible patients and 19 PET2‐positive patients were 84.8% (80% confidence interval [CI], 79.2–88.9) and 84.2% (80% CI, 69.7–92.1), respectively. Both primary endpoints were met at the prespecified threshold. This study demonstrates that iPET‐guided therapy is a useful treatment option for younger patients with newly diagnosed advanced‐stage cHL. Registration number: jRCTs031180218. JCOG1305 demonstrated that interim PET‐guided therapy was useful for younger patients with newly diagnosed advanced‐stage cHL.

Background Current treatment strategies for advanced non‐small cell lung cancer (NSCLC) are highly individualized and subject to ongoing debates. In the era of immunotherapy, surgery assumes a critical role. The aim of this study was to investigate if subsequent surgical intervention, following a favorable response to immunotherapy and chemotherapy, could yield a more favorable prognosis for patients with advanced stage III NSCLC compared to the continuation of immunotherapy and chemotherapy. Methods We included patients whose tumors exhibited a favorable response (including partial response [PR] and complete response [CR]) to immunotherapy and chemotherapy. These patients were categorized into two groups based on their subsequent treatment plans: surgical and nonsurgical (continuation of maintenance immunotherapy and chemotherapy). The efficacy and long‐term prognosis of these groups were compared after matching them in a 1:1 ratio using propensity scores. Results In total, 186 patients (93 in each group) were included in this study after matching via propensity scores. The 1‐ and 3‐year overall survival (OS) and progression‐free survival (PFS) rates were 96.0%, 88.5%, and 93.1%, 80.7% in the surgical group, and 93.2%, 83.1%, and 57.7%, 50.4% in the nonsurgical group, respectively. Patients in the surgical group exhibited significantly superior PFS and OS compared to those in the nonsurgical group (p = 0.025 and p = 0.00086). Univariate and multivariate analyses confirmed ΔBMI, Δtumor size reduction, tumor response, earlier clinical stage (IIIb vs. IIIa), and surgery as independent protective factor for patient prognosis. We further selected 101 patients with CR (39 in the surgical group and 62 in the nonsurgical group) and found that patients in the surgical group were significantly better in both PFS and OS. Our subgroup analysis in postoperative patients demonstrated that different surgical strategies did not significantly affect the long‐term prognosis of patients (PFS and OS) but could impact their perioperative experience. Conclusion Patients with advanced stage III NSCLC, whose tumors achieved PR and CR after 2–4 cycles of immunotherapy combined with chemotherapy, experience a more promising prognosis with subsequent surgical intervention compared with the continued immunotherapy. Despite encountering formidable obstacles, such as protracted surgical procedures and associated trauma, we must rise to the challenge and unleash the power of surgery after immunotherapy in advanced NSCLC. In the era of immunotherapy, surgery presents a promising avenue for the potential cure of non‐small cell lung cancer (NSCLC). Various surgical approaches like minimal invasive surgery and bronchial or vascular sleeve resection, frequently aim to attain R0 resection without significant difference in survival rates. Perspective Statement: The notion of curing cancer patients with medication remains an elusive dream. Despite facing formidable obstacles after neoadjuvant therapy, we must rise to the challenge and unleash the power of surgery for curing cancer.

Background Metastatic lung cancer is a debilitating disease, but with the advances in immunotherapy, therapeutic options have vastly increased. Numerous complete blood count parameters (CBC) have been described as easily accessible biomarkers that might predict response to immunotherapy. However, to date, no comprehensive study has been performed on the longitudinal changes of these parameters during cancer progression. Methods The clinicopathological variables and CBC parameters of 986 advanced stage lung cancer patients were retrospectively analyzed. Blood tests were performed as part of the routine checkup and the results were recorded at the time of the diagnosis of the primary tumor, the diagnosis of brain or bone metastases, and also during the last available follow‐up. Results In the experimental subcohort, 352 and 466 patients were diagnosed with brain and bone metastases, respectively. The control group consisted of 168 patients without clinically detectable or other distant organ metastases. In our longitudinal analyses, we found significantly decreasing absolute lymphocyte count (ALC: P < 0.001), and significantly increasing absolute neutrophil count (ANC: P < 0.001) levels in all patient subgroups, irrespective of histopathological type and metastatic site. Interestingly, patients with brain metastases had significantly descending‐ascending platelet count (PLT) trendlines (P < 0.001), while the bone metastatic subgroup exhibited significantly ascending‐descending trendlines (P = 0.043). Conclusions Significantly decreasing ALC, significantly increasing ANC and fluctuating PLT levels may be found in brain and bone metastatic lung cancer patients during disease progression. Our findings might contribute to improve personalized healthcare in this devastating malignancy. Key points Significant findings of the study Significantly decreasing ALC, and significantly increasing ANC levels can be found in advanced‐stage lung cancer patients during disease progression Patients with brain metastases have descending‐ascending PLT trendlines, while patients with bone metastases exhibit ascending‐descending trendlines during disease progression What this study adds The descending values for ALC, and the ascending mean values for PLT and ANC, might be suggestive of poor response to second‐ or third‐line immunotherapy in advanced‐stage lung cancer patients. The current study might help to improve patient selection and treatment strategies for brain and/or bone metastatic lung cancer patients. In our longitudinal analyses, we found significantly decreasing ALC, and significantly increasing ANC levels in advanced‐stage lung cancer patients during disease progression. Interestingly, patients with brain metastases have descending‐ascending PLT trendlines, while patients with bone metastases exhibit ascending‐descending trendlines during disease progression. The current study might help to improve patient selection and treatment strategies for brain and bone metastatic lung cancer patients.

Geriatric age group patients with poor performance status and advanced stage cancer are often denied chemotherapy. In this series of cases, we demonstrated that systemic anti‐cancer therapy can be considered in these patients after a meticulous modification of the chemo‐protocol.

Progress in ovarian cancer treatment lags behind other tumor types. With diagnosis usually at an advanced stage, there is a high demand for reliable prognostic biomarkers capable of the selection of effective chemo- and targeted therapies. Our goal was to establish a large-scale transcriptomic database and use it to uncover and rank survival-associated genes. Ovarian cancer cohorts with transcriptome-level gene expression data and clinical follow-up were identified from public repositories. All samples were normalized and entered into an integrated database. Cox univariate survival analysis was performed for all genes and was followed by multivariate analysis for selected genes involving clinical and pathological variables. False discovery rate was computed for multiple hypothesis testing and a 1% cutoff was used to determine statistical significance. The complete integrated database comprises 1816 samples from 17 datasets. Altogether, 2468 genes were correlated to progression-free survival (PFS), and 704 genes were correlated with overall survival (OS). The most significant genes were WBP1L, ASAP3, CNNM2, and NCAPH2 for progression-free survival and CSE1L, NUAK1, ALPK2, and SHKBP1 for overall survival. Genes significant for PFS were also preferentially significant for predicting OS as well. All data including HR and p values as well as the used cutoff values for all genes for both PFS and OS are provided to enable the ranking of future biomarker candidates across all genes. Our results help to prioritize genes and to neglect those which are most likely to fail in studies aiming to establish new clinically useful biomarkers and therapeutic targets in serous ovarian cancer.

Background Alzheimer’s disease (AD) is the leading cause of dementia, marked by the accumulation of extracellular amyloid plaques, intraneuronal neurofibrillary tangles, and neuroinflammation, all contributing to cognitive decline. Although disease‐modifying therapies targeting amyloid plaques show promise, eligibility for these treatments is limited, and studies suggest that the risks may outweigh the potential benefits for many patients. Recent preclinical studies suggest that peripheral approaches may influence amyloid (Aβ) and tau deposition, as well as neuroinflammation in the brain. Plasma exchange (PE), where plasma is replaced with albumin, has emerged as a potential treatment for AD. This study investigates the effects of PE on Aβ pathology and neuroinflammation in APP/PS1 mice at an advanced stage of amyloid pathology. Methods Four PE procedures were performed monthly starting at 11 months of age. At 15 months, all animals were euthanized, and brains were processed for histological analysis. Amyloid deposits were assessed with Thioflavin‐S (ThS) and 4G8 immunostaining in the cortex and hippocampus. ELISA was used to measure soluble and insoluble Aβ1–40 and Aβ1–42 in brain homogenates and plasma. Inflammatory responses were quantified using a Luminex bead‐based immunoassay for cytokines (IL‐1β, IL‐6, TNFα, IFN‐γ, IL‐10, IL‐4) in whole‐brain homogenates and plasma. Iba‐1 and GFAP immunostaining assessed microglial and astrocyte areas. Results PE‐treated animals showed significant reductions in amyloid plaque number and area in the cortex compared to untreated APP/PS1 mice. Additionally, Iba‐1+ and GFAP+ areas were significantly smaller in PE‐treated animals. Biochemical analysis confirmed reductions in insoluble Aβ1–40 and Aβ1–42 levels in the brain of PE‐treated animals. PE also modulated the inflammatory response, decreasing IL‐1β, IL‐6, IL‐10, and IL‐4 in the brain compared to untreated mice. Conclusions These findings suggest that PE may reduce amyloid burden and modulate inflammation in the brain. An increase in plasma Aβ1–40 and Aβ1–42 after PE suggests Aβ movement from the brain to the blood. Further studies are needed to elucidate the mechanisms underlying Aβ clearance and inflammation modulation.

Circulating tumor DNA (ctDNA) has demonstrated great potential as a noninvasive biomarker to assess minimal residual disease (MRD) and profile tumor genotypes in patients with non‐small‐cell lung cancer (NSCLC). However, little is known about its dynamics during and after tumor resection, or its potential for predicting clinical outcomes. Here, we applied a targeted‐capture high‐throughput sequencing approach to profile ctDNA at various disease milestones and assessed its predictive value in patients with early‐stage and locally advanced NSCLC. We prospectively enrolled 33 consecutive patients with stage IA to IIIB NSCLC undergoing curative‐intent tumor resection (median follow‐up: 26.2 months). From 21 patients, we serially collected 96 plasma samples before surgery, during surgery, 1–2 weeks postsurgery, and during follow‐up. Deep next‐generation sequencing using unique molecular identifiers was performed to identify and quantify tumor‐specific mutations in ctDNA. Twelve patients (57%) had detectable mutations in ctDNA before tumor resection. Both ctDNA detection rates and ctDNA concentrations were significantly higher in plasma obtained during surgery compared with presurgical specimens (57% versus 19% ctDNA detection rate, and 12.47 versus 6.64 ng·mL−1, respectively). Four patients (19%) remained ctDNA‐positive at 1–2 weeks after surgery, with all of them (100%) experiencing disease progression at later time points. In contrast, only 4 out of 12 ctDNA‐negative patients (33%) after surgery experienced relapse during follow‐up. Positive ctDNA in early postoperative plasma samples was associated with shorter progression‐free survival (P = 0.013) and overall survival (P = 0.004). Our findings suggest that, in early‐stage and locally advanced NSCLC, intraoperative plasma sampling results in high ctDNA detection rates and that ctDNA positivity early after resection identifies patients at risk for relapse. ctDNA profiling in plasma revealed higher levels and detection rates of ctDNA during tumor resection as compared to pretreatment time points in patients with early‐stage or locally advanced NSCLC. Moreover, patients testing positive for ctDNA immediately after tumor resection had worse clinical outcomes than patients with undetectable ctDNA. Our research highlights the role of ctDNA assessment for guiding treatment in patients with respectable NSCLC.

Objectives To develop a risk prediction model to preoperatively discriminate between benign, borderline, stage I invasive, stage II-IV invasive, and secondary metastatic ovarian tumours.Design Observational diagnostic study using prospectively collected clinical and ultrasound data.Setting 24 ultrasound centres in 10 countries.Participants Women with an ovarian (including para-ovarian and tubal) mass and who underwent a standardised ultrasound examination before surgery. The model was developed on 3506 patients recruited between 1999 and 2007, temporally validated on 2403 patients recruited between 2009 and 2012, and then updated on all 5909 patients.Main outcome measures Histological classification and surgical staging of the mass.Results The Assessment of Different NEoplasias in the adneXa (ADNEX) model contains three clinical and six ultrasound predictors: age, serum CA-125 level, type of centre (oncology centres v other hospitals), maximum diameter of lesion, proportion of solid tissue, more than 10 cyst locules, number of papillary projections, acoustic shadows, and ascites. The area under the receiver operating characteristic curve (AUC) for the classic discrimination between benign and malignant tumours was 0.94 (0.93 to 0.95) on temporal validation. The AUC was 0.85 for benign versus borderline, 0.92 for benign versus stage I cancer, 0.99 for benign versus stage II-IV cancer, and 0.95 for benign versus secondary metastatic. AUCs between malignant subtypes varied between 0.71 and 0.95, with an AUC of 0.75 for borderline versus stage I cancer and 0.82 for stage II-IV versus secondary metastatic. Calibration curves showed that the estimated risks were accurate.Conclusions The ADNEX model discriminates well between benign and malignant tumours and offers fair to excellent discrimination between four types of ovarian malignancy. The use of ADNEX has the potential to improve triage and management decisions and so reduce morbidity and mortality associated with adnexal pathology.

Background Germline depletion of complement C3 has been shown to be protective in a mouse model of tauopathy. Therefore, we asked whether global C3 knockdown at the onset and later in tau pathogenesis would protect against tau aggregation and downstream pathologies later in life. Method We generated PS19;C3iKO mice (PS19+/−; C3fl/fl; Rosa26‐CreERT2+/− ) by crossing P301S tau (PS19) mice with C3fl/fl and C3fl/fl; Rosa26‐CreERT2 mice. We studied two cohorts: Cohort 1 received i.p. tamoxifen (TAM; 75 mg/kg) or corn oil (CO) daily for 5 days at 3.6 months of age. PS19;C3iKO mice received CO (n = 14) or TAM (n = 14). PS19 control mice received CO (n = 8) or TAM (n = 8). Cohort 2 (PS19; C3iKO only) received TAM (n =26) or CO (n =25) daily for 5 days at 7.5 months. Behavioral testing was conducted at 9 months of age for cohort 1 and 12 months for cohort 2, after which the mice were euthanized and brain tissue harvested. ELISA and immunofluorescent staining were performed to evaluate the effects of C3 reduction. Result Serum C3 levels were significantly reduced ∼85% 30‐days post‐TAM and ∼80% at the end of the study in Cohort 1. Similarly, in cohort 2, serum C3 levels were significantly reduced ∼85% 30‐days post‐TAM and ∼78% at end of the study. Serum C1q levels remained unchanged in Cohort 1 but were significantly reduced in Cohort 2 at the endpoint. No significant changes in locomotion, anxiety, or memory were seen in Cohort 1 mice. Locomotion was increased in the Open Field test, but spatial memory (SNYM) remained unaffected in Cohort 2 mice. No significant differences were observed in brain pathology of pTau (AT8), C1q, GFAP, Iba1, CD68, or Iba1+/CD68+ microglia between TAM‐ and CO‐treated mice. Further biochemical, neuroinflammatory, and synaptic analysis are ongoing to evaluate the therapeutic potential of C3 reduction. Conclusion Our data indicates that global C3 lowering in PS19 mice at either the onset or an advanced stage of tauopathy did not alter tau pathology or brain C1q levels. However, late‐stage C3 lowering improved locomotor activity in PS19;C3iKO mice. Funding: NIH/NIA RF1 AG060057 (CAL).