Oncologist最新文献

Background: Radiation pneumonitis (RP) is a common adverse event related to thoracic radiotherapy in patients with non-small cell lung cancer (NSCLC). The treatment of RP needs to be improved.

Methods: NSCLC patients with grade 2 or higher RP were enrolled and randomly assigned into 2 groups: recombinant human endostatin (Rh-endostatin) group (Rh-endostatin + glucocorticoid) and control group (glucocorticoid only). The primary endpoint was RP relapse rate.

Results: A total of 40 patients were included. The relapse rate of RP was significantly lower in Rh-endostatin group (15% vs 45%, P = .038). Though the remission rate of RP was similar in the two groups, the combined therapy significantly reduced the interval from RP treatment to RP remission (0.92 vs 1.47 months, P = .048). The RP mortality rate was 5% and 35% in the Rh-endostatin group and control group, respectively (P = .044). The incidence of pulmonary fibrosis was numerically lower in Rh-endostatin group (25% vs 45%, P = .185). The circulating lymphocyte levels in Rh-endostatin group significantly increased after treatment, when compared to the control group. The median progression-free survival was 7.8 and 6.0 months, respectively (hazard ratio [HR]: 0.95, 95% confidence interval [CI]: 0.40-2.23, P = .910). The median overall survival was 16.0 and 7.7 months in two groups, respectively (HR: 0.56, 95%CI: 0.27-1.16, P = .119). There was no significant difference between the two groups in adverse events.

Conclusion: This prospective randomized study provides evidence that the combination of Rh-endostatin and glucocorticoids can reduce RP relapse rates and promote remission without increasing adverse events in advanced NSCLC patients.

Discussion: This Discussion can take one of two forms: 350 words and two salient graphics, such as a table, schema, waterfall plot, image or graph; or 450 words with a single salient graphic. This discussion is part of the Abstract and as such needs to be distinct from the extended Discussion at the end of the paper. Citation of references should be done in the extended Discussion at the end of the CTR; references (up to 5) should be cited in the Author Summary only if absolutely necessary.ClinicalTrials.gov Identifier: NCT03796364.

Clinicaltrials.gov identifier: NCT03796364.

Background: Prostate-specific membrane antigen (PSMA; FOLH1) is a cell-surface target for diagnostics and treatment in prostate cancer. We utilized a database of molecularly-profiled prostate tumors to evaluate clinical, genomic, and immunologic correlates of high FOLH1 RNA expression.

Patients and methods: Prostate cancer specimens (N = 7,082) underwent DNA/RNA sequencing and immunohistochemistry at Caris Life Sciences. FOLH1-High/Low expression was defined by upper/lower quartiles or median transcripts per million. Overall survival (OS) was calculated from insurance claims.

Results: Prostate adenocarcinoma had 2.97-fold higher FOLH1 expression compared to high-grade neuroendocrine prostate cancer (q < 0.0001). Of 7,020 adenocarcinomas, 4,464 were primary prostate samples, 828 were lymph node metastases, and 1,686 were distant metastases. FOLH1 expression varied across metastatic sites (highest in lymph node and lowest in liver; 1.2-fold difference, q < 0.05). FOLH1-High tumors were enriched in AR-V7 variants (10.1% vs 4.5%, q < 0.05) and associated with higher androgen receptor (AR) signaling (0.82 vs 0.78, q < 0.05). Conversely, FOLH1-Low tumors were enriched with FOXA1 (12.2% vs 6.4%), APC (11.4% vs 3.0%), PIK3CA (5.8% vs 2.7%), and PIK3R1 (2.6% vs 0.48%) mutations (q < 0.05). FOLH1-High tumors had a lower M1:M2 ratio, fewer Tregs and CD8+ T cells, higher immune checkpoint expression, and lower interferon signature scores. FOLH1-High primary tumors were more frequently microsatellite instability-High, tumor mutational burden-High, and PD-L1-positive. Among patients with metastatic tumors, median OS was improved in the FOLH1-High group (31.9 vs 23.3 months, P < .001).

Conclusions: This enhanced understanding of the distinct molecular and clinical profiles of FOLH1-expressing prostate cancers may inform optimization of PSMA-directed treatments.

Background: Patients undergoing intersphincteric resection (ISR) for low rectal cancer often experience persistent bowel dysfunction, psychological distress, and compromised quality of life, especially in the context of preventive stoma creation. These challenges can negatively affect recovery, immune function, and long-term prognosis. Psychosocial interventions, such as narrative therapy and resilience training, may mitigate these effects, yet their integrated application in ISR populations remains unexplored.

Methods: In this single-center randomized controlled trial, 178 patients with stage I-III low rectal cancer who underwent ISR between October 2019 and October 2021 at the First Affiliated Hospital of Soochow University were randomized to receive either standard care or a structured 6-month intervention combining narrative therapy and resilience training. Primary outcomes included psychological resilience (CD-RISC), emotional well-being (HADS), sleep quality (PSQI), and nutritional recovery (serum albumin, prealbumin, BMI). Secondary endpoints encompassed postoperative complications, systemic inflammation (CRP, IL-6, TNF-α), and 2-year disease-free survival (DFS) and overall survival (OS). All analyses followed the intention-to-treat principle.

Results: The intervention group demonstrated significantly greater improvements in psychological and nutritional parameters (all P < .01), fewer complications (12.4% vs. 23.6%, P = .035), and reduced inflammatory markers on postoperative day 7. At 24 months, both DFS (89.2% vs. 75.3%, P = .028) and OS (93.1% vs. 81.6%, P = .031) were significantly higher in the intervention group. Effect sizes (Cohen's d) and minimal clinically important differences (MCIDs) were assessed to support the interpretation of clinical relevance.

Conclusion: An integrated psychosocial intervention significantly enhanced functional recovery and long-term oncologic outcomes following ISR. These findings underscore the value of incorporating structured psychological support into postoperative care for low rectal cancer.

Background: Radiation-associated second primary malignancies (SPMs) are a significant risk factor affecting the quality of life in long-term cervical cancer survivors. However, the impact of brachytherapy-boost and advanced radiotherapy techniques on the risk of radiation-related SPMs remains unclear.

Methods: We utilized data from the Surveillance, Epidemiology, and End Results (SEER) database (1975-2019) to assess the risk of radiation-associated SPMs among cervical cancer patients. Radiation-associated second solid and hematologic malignancies were defined as those diagnosed in survivors living for ≥5 and ≥2 years, respectively. The fine-gray sub-distribution hazard model was employed to compare the risk of SPMs across different groups.

Results: External beam radiation therapy (EBRT) was associated with an increased risk of pelvic SPMs (sub-distribution hazard ratio [sHR] = 2.13; P < .001). However, no increased risk was observed for extra-pelvic or hematologic SPMs. For radiotherapy-treated patients, the 15-year cumulative incidence of overall pelvic SPMs significantly declined from 3.92% in 1975-1994 to 2.85% in 1995-2006 (sHR = 0.87; P = .036), further decreasing to 2.27% after 2001 compared to those treated in 1975-2001 (sHR = 0.59; P = .030). Brachytherapy alone increased the risk of pelvic SPMs (sHR = 3.04; P < .001), but the combination of brachytherapy with EBRT did not further elevate the risk of pelvic SPMs (sHR = 1.35; P = .092).

Conclusions: The risk of radiation-associated pelvic SPMs has diminished over the past 40 years, and the combination of brachytherapy with EBRT did not further increase the risk of SPMs among cervical cancer patients.

Background: There is limited evidence regarding the economic burden, treatment patterns, and overall survival (OS) of patients with cholangiocarcinoma (CCA) and cancer of unknown primary (CUP) who initiated the FGFR inhibitor pemigatinib.

Patients and methods: We used the Komodo Healthcare Map to identify patients with CCA who initiated pemigatinib between 4/17/2020 and 5/31/2023. Follow-up began at initiation and lasted ≥ 1 month. Outcomes included health care resource utilization (HCRU), costs, treatment patterns, and OS.

Results: Two hundred twenty-one patients were included: 78 patients (35.3%) with CUP (median follow-up, 5.9 months) and 143 patients (64.7%) without CUP (median follow-up, 7.3 months). Pemigatinib was similarly well-tolerated in CUP vs non-CUP. Discontinuation was observed in 43.6% vs 49.0% (P = .445). Medication possession ratio ≥ 0.80 was achieved by 71.6% vs 67.2% (P = .504). CUP was associated with significantly higher prevalence of metastatic disease (100.0% vs 63.6%), per patient per month (PPPM) ambulatory HCRU (8.2 vs 5.5), and ambulatory costs ($8584 vs $5308). Medical costs averaged $13 444 vs $9881 PPPM for CUP and non-CUP, respectively (P = .066). Median OS was significantly shorter with CUP (10.2 vs 30.7 months).

Conclusion: Although pemigatinib was similarly well-tolerated regardless of CUP status, patients with CUP incurred greater ambulatory burden and had poorer OS. Patients with CUP were more likely to have evidence of metastatic disease at pemigatinib initiation, which may help explain these results. With the advent of targeted treatments for gene-altered CCA, reflexive genomic testing should be encouraged for all patients with CUP.

Background: Antibody-drug conjugates (ADCs) are an emerging class of therapeutics that combine the specificity of monoclonal antibodies with cytotoxic or immune-stimulatory payloads. In non-small cell lung cancer (NSCLC), they offer a novel strategy with potential in both first-line therapy and in cases to overcome resistance to existing targeted and immune-based therapies.

Objective: To review the clinical development, efficacy, safety, biomarker strategies, and emerging targets of ADCs in NSCLC, with a focus on implications for practice and ongoing challenges.

Methods: We conducted a comprehensive literature review of published trials, conference abstracts, and press releases evaluating ADCs in NSCLC, with attention to target antigens, clinical trial outcomes, and biomarker approaches.

Results: ADCs targeting HER2, TROP2, and c-MET have received regulatory approval in NSCLC, with demonstrated efficacy-particularly in biomarker-selected populations. Bispecific HER3/epidermal growth factor receptor (EGFR)-directed ADCs have shown encouraging activity in early phase studies, with ongoing trials expected to clarify durability and optimal patient selection. Other targets such as ITGB6, B7-H3, and AXL have shown early signals of efficacy. Predictive biomarkers vary in reliability, and mutation, amplification, or protein expression do not uniformly predict response. Toxicity and acquired resistance remain key challenges; improved diagnostics may enhance patient selection.

Conclusion: ADCs are poised to reshape the therapeutic landscape of NSCLC. Their success will hinge on refining biomarker strategies, managing toxicity, and integrating resistance-mitigating approaches such as bispecific constructs or rational combinations. As research advances, ADCs may become essential components of personalized therapy across a range of molecular and histologic NSCLC subtypes.

Background: Despite the increasing approval and ongoing clinical trials of FGFR-targeted therapies, accurately detecting FGFR fusions remains a challenge due to limited research, low incidence rates, complex fusion partner distribution, and unique kinase domain distribution.

Methods: We conducted a multicenter study to comprehensively profile FGFR fusions in the largest Chinese pan-cancer cohort to date, comprising 118 FGFR fusions from 114 individuals. Both DNA- and RNA-based sequencing approaches were utilized to reveal novel and fundamental features of FGFR fusion.

Results: Our research reveals an incidence rate of 0.96% for FGFR rearrangements within this Chinese cohort, including a high incidence rate of FGFR fusions (40%) in parotid gland carcinoma. However, this is based on a small sample size of 5 tumors and should be interpreted cautiously pending validation in larger cohorts. We also uncovered distinct breakpoint distribution patterns across various FGFR rearrangements. For example, a primary breakpoint in intron17 of FGFR2 was predominant (21/22), while FGFR1/3 breakpoints displayed substantial diversity. For the first time, we identified "hot" breakpoints in FGFR1 intron17, exon18, and FGFR3's 3' untranslated region. These findings underline the importance of incorporating these regions in targeted sequencing to ensure comprehensive detection of FGFR1/3 fusions. Notably, we observed a predilection for intrachromosomal distribution in common FGFR1/2/3 fusions. In contrast, most novel fusions (12/15) exhibited an interchromosomal distribution pattern, indicating variations in the fusion formation mechanism. Importantly, our study demonstrates the substantial incremental value of RNA-NGS or other orthogonal methods in confirming the functionality of FGFR rearrangements initially identified by DNA sequencing. In our cohort, 46% (6/13) of rare FGFR1/2/3 fusions lacked detectable RNA transcripts; however, this does not definitively indicate non-functionality as factors such as low RNA quality, expression below detection limits, or nonsense-mediated decay may contribute. Therefore, RNA-based validation is critical for accurately identifying potentially targetable FGFR fusions and guiding therapy.

Conclusion: Our findings offer critical novel insights into functional FGFR fusions and bear considerable clinical implications for identifying individuals whose tumors are most likely to respond favorably to FGFR-targeted therapies.

Background: Amplification/overexpression of the human epidermal growth factor receptor 2 (HER2) gene drives cell proliferation, differentiation, and migration of breast cancer. However, HER2-targeted therapies are not standard treatment for HER2-positive non-breast solid tumors currently. This phase II open-label basket trial evaluated pyrotinib's efficacy and safety in patients with non-breast solid tumors.

Methods: Patients with previously treated HER2-positive advanced non-breast solid tumors were enrolled at Zhongshan Hospital, Fudan University. All participants received pyrotinib in 21-day cycles. Primary endpoint was objective response rate (ORR) at 6 weeks, assessed per RECIST version 1.1. Circulating tumor DNA (ctDNA) analysis was conducted to identify biomarkers of efficacy.

Results: Fifty-three patients were enrolled and 51 evaluable for efficacy analysis. The median follow-up was 32.2 months. ORR was 18.9% (95% CI: 10.2%-31.7%) and disease control rate was 73.6% (95% CI: 60.1%-84.2%). Median progression-free survival (mPFS) was 5.1 (95% CI: 4.2-8.1) months and median overall survival (mOS) was 17.2 (95% CI: 16.2-33.2) months. Patients with colorectal cancer had the highest ORR and the longest mOS (33.2 months, 95% CI: 14.9-51.5). Among patients with HER2 overexpression, those with immunohistochemistry 3+ had longer mPFS and mOS. Sixteen patients required dose reductions due to grade 3 adverse events (AEs); no ≥grade 4 AEs occurred. Analysis of ctDNA revealed that patients with progression disease had higher mutation frequency, more diverse mutational profiles, and higher copy number burden.

Conclusion: Pyrotinib demonstrated a favorable safety profile and modest efficacy in patients with previously treated HER2-positive advanced non-breast solid tumors.

Background: Neoadjuvant chemotherapy (NACT) has been widely used in breast cancer patients. The aim of the study was to compare survival outcomes between breast cancer patients receiving NACT, with and without complete pathologic response (pCR), and those receiving adjuvant chemotherapy (ACT).

Methods: Based on the Surveillance, Epidemiology, and End Results database, we conducted a population-based cohort study including 48 350 breast cancer patients, 15 525 of whom with pCR after NACT, and 124 202 patients after ACT during the period of 2010-2021. In comparison with patients in ACT group, we assessed hazard ratios (HRs) of breast cancer-specific and overall mortality among individuals in NACT using Cox regression.

Results: During the period of follow-up (median 5 years), 4800 and 8257 breast cancer-related deaths were identified among patients in NACT and ACT group, respectively. Patients in NACT group had unfavorable molecular type (human epidermal growth factor receptor 2 overexpression, triple negative), more advanced tumor features (higher grade and stage) and was more likely to undergo mastectomy and radiotherapy. Moreover, patients undergoing NACT had higher cumulative mortality rate of breast cancer (19.60% vs 10.46%), compared with those receiving ACT. After controlling for covariates, NACT patients were at increased risk of breast cancer-specific mortality (HR 1.47, 95% CI 1.41-1.53) compared with ACT patients. In contrast, NACT patients with pCR were associated with an improved breast cancer-specific survival (HR 0.59, 95% CI 0.54-0.64). The elevated risk was obviously greater among NACT patients in NACT-disfavored subgroups including lobular/mixed histology, well/moderately differentiated grade, local cancer stage, or HR+/HER2- molecular subtype (HRs 1.63-1.93).

Conclusions: NACT patients have worse survival, compared with their ACT counterparts. Although patients with pCR after NACT derive significant survival benefits, NACT-disfavored subgroups may gain limited benefit from NACT, and alternative approaches should be considered.