Current oncology最新文献

Advanced gastric/gastroesophageal junction (G/GEJ) adenocarcinoma remains a common and deadly form of cancer. Advances in G/GEJ cancer treatment have improved survival outcomes with the claudin-18.2 (CLDN18.2)-targeted agent, zolbetuximab, and immune checkpoint inhibitors (ICIs) targeting the PD-1 receptor. This article offers an evidence-informed opinion on considerations when selecting between these first-line treatments for G/GEJ adenocarcinoma in patients with HER2-negative disease that expresses CLDN18.2 and/or PD-L1, including the reliability of biomarker scoring and interpretation, overall survival (OS) rates, toxicity profiles, and logistical practicalities. Evidence from Phase III trials for zolbetuximab and ICIs suggest similar OS benefits of 14-18 months compared to chemotherapy alone, but there appears to be a gradient of benefit for ICIs with increasing PD-L1 combined positive score (CPS). There is high inter-observer variability in CPS scoring, particularly at lower thresholds. Zolbetuximab is associated with high rates of nausea and vomiting during the initial infusion, whereas ICIs are associated with risk of later-onset immune-related toxicities that can be fatal in rare cases. In considering the available evidence, our opinion is that zolbetuximab is a reasonable option for initial targeted treatment in HER2-/CLDN18.2-positive advanced G/GEJ when PD-L1 CPS score is <10 based on the reliability of biomarker testing, comparable OS, and avoidance of potentially irreversible ICI-induced immune toxicity.

Neurofibromatosis type 1 (NF1) is a complex, multisystem, genetic disorder caused by germline NF1 variants that predispose affected individuals to tumors of the nervous system. With the identification of the NF1 gene in the late 1980s and the elucidation of the role of the encoded protein, neurofibromin, in regulating RAS signaling, considerable research effort has been invested to identify therapeutic treatments for NF1 tumors. Over the past two decades, high-throughput drug screening approaches have been a significant component of these endeavors. However, considerable variability exists among studies in terms of disease models, symptom targets, screening libraries, methods, and outcomes. In this review, we present an overall summary of efforts toward discovering new therapeutic strategies for NF1-related tumors using high-throughput screening and how such findings can be employed for prospective research in the NF1 field.

Background: Glioblastoma (GB) is the most common primary brain tumor, with poor prognosis, significant neurological symptoms, and near-universal recurrence. Biomarker development is often limited by the scarcity of tumor tissue available for study. Noninvasive serum-based profiling offers potential to improve outcomes.

Purpose: This study examined serum proteomic and metabolomic profiles pre- and post-concurrent chemoirradiation (CRT) to identify associations with patient outcomes and molecular classification, and to explore relevant signaling and metabolic pathways.

Methods: Serum samples from 109 GB patients, obtained prior to and following completion of CRT, were analyzed with each patient serving as their own control, using a SOMAScan^® proteomic assay (7289 proteins) and metabolomics (SECIM, 6015 compounds). Clinical data were obtained through chart review. Proteomic and metabolomic changes were examined at baseline (prior to CRT) and in alteration (pre- vs. post-CRT) for their association with overall survival (OS), progression-free survival (PFS), MGMT, and IDH status. Cox models, gene set enrichment analysis (Hallmark, GSEA), and Kaplan-Meier survival analysis were used.

Results: Several hundred proteins and metabolites were associated with OS and PFS. MGMT status was known in 60% and IDH in 38% of patients. Pre-CRT DLST (HR 11.7, p < 0.001, adj p = 0.01) was the only protein significantly associated with OS. Pre-CRT, and higher 7-HOCA was linked to worse OS (HR 1.3) and PFS (HR 1.5), while increased p-cresol was associated with improved OS (HR 0.8) and PFS (HR 0.9). Kaplan-Meier analysis based on signal alteration post-CRT vs. pre-CRT, revealed superior OS with lower DLST and MSR1 and superior PFS with higher PGAM2 and ATG5, and lower 7-HOCA. Pathway analysis linked improved PFS to fatty acid metabolism, citric acid cycle, and purine biosynthesis. MGMT and IDH class comparisons revealed associations primarily with amino acid and fatty acid metabolism. Both MGMT methylation and IDH mutation correlated with increased PLAG12B expression, with significance only for MGMT (p < 0.001). IDH mutation was associated with decreased MSR1 (p = 0.047) and p-cresol (p < 0.001).

Conclusions: Serum-based fatty acid and purine metabolism pathways are associated with OS and PFS in GB. 7-HOCA and p-cresol emerged as potential biomarkers linked to treatment response and molecular subtype. These findings support further investigation of noninvasive biospecimens for clinically actionable biomarkers in GB.

Background: Non-small cell lung cancer (NSCLC) is the most common form of lung cancer and a leading cause of cancer-related death. Despite therapeutic advances, long-term survival in stage IV disease is uncommon. Tumor analyses that combine genomic and functional platforms may provide the opportunity to monitor clonal dynamics and guide therapy selection. Case Presentation: We report a 67-year-old woman with metastatic poorly differentiated lung adenocarcinoma, who achieved four durable remissions and survived nearly 12 years. Serial studies using ex vivo analysis of programmed cell death (EVA/PCD) functional-profiling-guided therapeutic choices were correlated with next-generation sequencing (NGS). Molecular events included the emergence of a BRAF V600E mutation responsive to dabrafenib plus trametinib and the acquisition of an EGFR exon 19 deletion responsive to Osimertinib. EVA/PCD identified activity for targeted agents and revealed synergy for vinorelbine plus Osimertinib not predicted by genomic profiling, which provided additional response. Discussion: This case highlights clonal evolution in NSCLC and illustrates how serial tissue analyses correlating phenotypic and genomic events can offer therapeutic interventions to provide long-term survival. Conclusions: The integration of functional and genomic profiling may improve personalized treatment in NSCLC by interrogating tumor heterogeneity and clonal evolution to inform rational therapeutic selection.

To explore the relationship between magnetic resonance imaging (MRI) parameters, including T2-weighted intensity and apparent diffusion coefficient (ADC), and intraoperative tumor characteristics, particularly consistency, in vestibular schwannomas (VSs). The association between tumor consistency, facial nerve (FN) function, and postoperative outcomes was analyzed. A single-center retrospective analysis included newly diagnosed VS cases (2020-2023) with cisternal involvement (Samii T3a; volume ≥ 0.7 cm³). T2 and ADC maps from the perimetral region of interest were normalized, and tumors were categorized into 3 classes by combining qualitative consistency (soft, fibrous, or fibrous/hard), ultrasonic aspirator power, and adherence to neurovascular structures. FN function was assessed using the House-Brackmann scale at the immediate postoperative period and 12-month follow-up. MRIs of 33 VSs (18 solid and 15 cystic) were analyzed. Normalized values of both T2 (N-T2_mean) and ADC (N-ADC_min) maps predicted the classical radiological differentiation. N-ADC_min may have some role in predicting consistency (value 1.361, p = 0.017, accuracy 0.48) and demonstrated a significant association (p = 0.04) with the FN outcome in the immediate postoperative period. An augmented consistency could impair FN function by increasing the intrameatal pressure related to greater transmission of shocks derived from the dissection maneuvers of the cisternal component of the tumor. The possibility of non-invasively exploring VS consistency with a parameter easily calculable on MRI might be beneficial in surgical planning, modifying the timing of the opening of the meatus with respect to what could be the surgical routine in some centers.

Background: EQ-5D-3L health utilities inform health technology assessments in oncology, often derived from clinical trials enrolling highly selected populations, which may over-estimate real-world health utilities. Little is known about the association between socioeconomic status (SES) and EQ-5D-3L health utilities. Our objective was to examine EQ-5D-3L health utilities across SES in a real-world sample of patients with cancer.

Methods: We conducted a cross-sectional analysis of EQ-5D-3L responses from 170 adult patients with cancer accrued from an Ontario oncology centre. We fitted multivariable linear regression models to estimate associations between covariates and EQ-5D-3L health utilities.

Results: Lower EQ-5D-3L health utilities were significantly associated with the lowest and undisclosed family income categories in models with and without birth sex (p < 0.05). In the model including birth sex, disutility estimates for lowest family income (

Conclusions: Lower EQ-5D-3L health utilities were significantly associated with low income and nondisclosure, highlighting the need to incorporate SES in analyzing health utilities in cancer care.

Background: There is an insufficient knowledge base for optimal parenteral nutrition (PN) use for patients with incurable cancer, leading to vague guidelines and varied practices. The aim of the study is to describe the practices and actual outcomes of PN in patients with incurable cancer at Norwegian hospitals. Methods: This multicentre study retrospectively reviewed 507 deceased patients (>18 years) receiving PN between 2011 and 2017. Data were collected from PN initiation until death, and analyses were descriptive. Results: Fifty-one percent had upper and lower gastrointestinal cancers, and the main PN indications were insufficient intake (75%) and gastrointestinal malfunction (47%). Sixty-seven percent received no anticancer treatment. Forty-three (8%) received PN as temporary bridging to anticancer treatment, of whom fifteen (35%) resumed or initiated treatment. The median PN dose corresponded to 53% of estimated energy requirements, and 94% of the patients had complementary energy intake. The most common reason for discontinuation was expected imminent death (47%). While common symptoms during PN were nausea (52%), vomiting (46%), and oedema (37%), 15% reported improved wellbeing. Conclusions: In this real-world cohort, up to 80% of the patients would not meet the eligibility criteria of previous trials due to cancer diagnosis and treatment, gastrointestinal tract function, weight loss criteria or complications such as ascites. This study highlights the heterogeneity in how patients with incurable cancer receive PN, and emphasises the importance of individualised PN treatment, carefully and safely managed to meet the patients' palliative care situation. Future real-world pragmatic patient-centred protocols bridging the gap between clinical trials and patients in clinical practice are warranted.

Background: This study's objective was to be the first to explore the ethnicity/cultural origins, gender identity, ability/disability, sexual orientation, socioeconomic background, and harassment/discrimination experiences of Canadian radiation oncologists (ROs).

Methods: Following a literature review and input from content experts, an ethics-approved national cross-sectional electronic survey was developed in English and French and electronically distributed to all ROs in Canada (n = 598). Descriptive statistics summarized responses. Comparisons between groups were performed using Chi-square tests, and content analysis was performed on open-ended responses.

Results: The survey was completed in full by 42.5% of ROs (254/598). Most respondents were male (62.9%), 35-44 years old (39.2%), and heterosexual (94.3%). 41.2% identified as belonging to a racialized group, which is higher than the overall Canadian population (27%), but Black, Indigenous, and Southeast Asian ROs were underrepresented (1.9% vs. 4%, <1% vs. 5% and 1.6% compared to 4%, respectively). A significant subset analysis showed that only 20% (21/105) of racialized ROs were women, whereas Caucasian women comprised 49.3% (74/150) of Caucasian respondents (p < 0.001). While 75.4% of respondents reported job satisfaction, 42.1% reported experiencing workplace discrimination/harassment within the past 5 years; most commonly, this was perpetrated by fellow faculty (31.7%; 58/183) or patients or their family members (31.7%; 58/183). Respondents felt that gender, race/ethnicity, and age were the three top reasons for discrimination/harassment, with double the amount of racialized ROs reporting harassment compared to White ROs (p < 0.001). Nearly half (45.2%; 114/252) did not understand how to report, or felt uncomfortable reporting, workplace discrimination/harassment.

Conclusions: This study highlights high harassment and discrimination rates amongst Canadian ROs, especially amongst racialized women, which may affect career satisfaction and attrition rates. Compared to census data, Black, Indigenous, and Southeast Asian ROs were underrepresented, and amongst racialized ROs, racialized women were significantly underrepresented. These findings underscore the need for targeted diversity initiatives, improved mentorship programs, and stronger institutional policies to address harassment and foster an inclusive work environment.

Yukon residents often must travel long distances to access specialized cancer care, which may impact cancer treatment patterns. We conducted a retrospective study to characterize all adult breast, prostate, colorectal, and lung cancer cases from the Yukon, diagnosed from 2009 to 2021 and seen in consultation at BC Cancer. We collected data on demographics, tumour characteristics and treatment, including timepoints for cancer care. A secondary analysis of non-referred cases was conducted. There were a total of 336 breast, 270 prostate, 279 colorectal and 266 lung cancer cases diagnosed in the Yukon from 2009 to 2021, of which 298 (88.7%), 120 (44.4%), 206 (73.8%) and 204 (76.7%) cases were referred to BC Cancer, and 266 (79.2%), 118 (43.7%), 204 (73.1%) and 183 (68.8%) were included in this study, respectively. Most cases were diagnosed at an early stage (breast: 92.9%, prostate: 82.2%, colorectal: 72.1%, lung: 45.9%). Nearly 70% of cases resided in Whitehorse (Yukon's capital), where most Yukon residents live. Compared to available published Canadian timepoints, Yukon patients had similar or shorter wait times in 13 of 22 timepoints along the pathway to diagnosis and treatment. However, time from biopsy to surgery had the longest relative wait times across all tumour groups (range: 26-60% longer). Our study provides baseline data that can help inform cancer care provision for Yukon residents.

Chronic pain significantly impairs functional performance in patients with cancer. Although acupuncture is effective for cancer-related pain, its impact on pain-related functional interference remains unclear. This secondary analysis of the PEACE randomized clinical trial included patients with prior cancer diagnoses and musculoskeletal pain for ≥3 months. Participants were randomized to groups undergoing 10 weeks of electro-acupuncture, auricular acupuncture, or a waitlist control. Functional performance was assessed using the Quick-Disability Arm/Shoulder/Hand (Q-DASH) for upper limbs and the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) subscale for lower limbs (higher scores = worse function). Linear mixed models compared changes over time between groups, with week 12 as the primary endpoint. Functional changes were also compared between pain responders and non-responders in the acupuncture arms. Among 360 patients (mean [SD] age, 62.1 [12.7] years; 69.7% women), mean baseline Q-DASH and WOMAC scores were 33.2 (19.8) and 33.3 (20.3). At week 12, both electro-acupuncture and auricular acupuncture significantly improved function versus waitlist: Q-DASH by -7.18 and -9.64 points, respectively, and WOMAC by -6.89 and -7.61 points (all p < 0.001). No differences were found between the two acupuncture groups. Treatment effects on Q-DASH diminished during follow-up, while improvements on WOMAC persisted. Within the acupuncture groups, pain responders achieved greater functional gains than non-responders (Q-DASH, -6.74; WOMAC, -6.16; both p < 0.001). Electro-acupuncture and auricular acupuncture improved upper and lower extremity function in cancer patients with chronic pain. These findings support acupuncture as a potential adjunct in functional rehabilitation for cancer survivors.