Oncologist最新文献

Introduction: The development of immune-related adverse events (irAEs) has been associated with improved survival outcomes in non-small cell lung cancer (NSCLC). However, this association's extent across race and ethnicity remains uncertain. We evaluated the association between the development of irAEs and treatment outcomes across racially diverse groups treated at a safety net hospital.

Methods: A retrospective chart review was performed to identify patients with advanced NSCLC treated between 2015 and 2020. The incidence of irAEs across racial subgroups was compared using logistic regression analysis. Cox regression analysis was performed to evaluate the association between the development of irAEs and treatment outcomes.

Results: We identified 138 NSCLC patients treated with immune checkpoint inhibitors (ICIs), of whom 50% identified as non-Hispanic Black (NHB). Incidence of irAEs was 28%, with no significant difference between NHB and other racial groups. However, females [OR 2.3, 95% CI, (1.1-4.8)] and patients with Medicaid or MassHealth insurance had a higher incidence of irAEs [OR 2.7 (1.2-5.7)]. Additionally, patients with irAEs had a lower risk of disease progression (multivariable HR 0.46, 95% CI, 0.23-0.92) compared to those without irAEs. The association between irAEs and improved progression free survival (PFS) in NHB patients was similar to the other racial group [median PFS 246 vs 181 days; HR 0.87 (0.58-1.29)].

Conclusion: We demonstrated a similar incidence of irAEs in NHB patients with NSCLC as compared to other racial groups. Patients who developed irAEs experienced significantly improved survival outcomes. This association remained independent of race and ethnicity, underscoring the importance of providing unbiased treatment recommendations.

Objective: DNA methylation is a promising biomarker for cervical cancer screening. This study aimed to validate the triage performance of cytological DNA methylation for detecting cervical intraepithelial neoplasia of grade 3 or worse (CIN3+) in women with high-risk human papillomavirus (hrHPV) infection from a large prospective cohort undergoing opportunistic screening in China (METHY3).

Methods: The triage performance for detecting CIN3+ lesions was compared between HPV16/18 genotyping, a liquid-based cytology (LBC) test, and the PAX1 and JAM3 methylation (PAX1m/JAM3m) test according to cervical pathologic outcomes. Among the 4394 women infected with hrHPV, 1105 had definitive cervical histological findings that were analyzed.

Results: For detecting CIN3+, the specificity of HPV16/18(+), the LBC result of ≥atypical squamous cells of undetermined significance (ASCUS), and PAX1m/JAM3m(+) was 66.4%, 23.9%, and 89.6%, respectively, with odds ratios of 4.24 (95% confidence interval [CI], 2.85-6.40), 4.44 (2.27-10.1), and 18.5 (12.1-28.7) (P < .001), respectively. PAX1m/JAM3m(+) had the highest area under the receiver operating characteristic curve (0.790, 95% CI, 0.747-0.832) in the whole cohort and in women of various ages. PAX1m/JAM3m (+) was detected in all patients with cancer (n = 28). Compared with HPV16/18 genotyping and the LBC test, PAX1m/JAM3m testing reduced referrals to colposcopy by 20.64 percentage points and 61.18 percentage points, respectively.

Conclusions: PAX1 m /JAM3 m testing is highly specific for detecting CIN3+. As a triage biomarker, it is superior to HPV 16/18 genotyping and LBC testing for women with hrHPV infection.

Despite being an important goal, the preservation of quality of life of patients with metastatic castration-resistant prostate cancer (mCRPC) is poorly characterized across lines of therapy. In this review, a systematic literature review and meta-analysis were conducted to synthesize EuroQoL 5-Dimension (EQ-5D) data among adult men with asymptomatic or mildly symptomatic mCRPC in both first line (1L) and second line and later (2L+) therapy. MEDLINE, Embase, and Cochrane CENTRAL were searched from inception to October 2022 using Ovid. Supplemental searches of other data sources were also conducted (PROSPERO registration: CRD42021283512). Meta-analyses were conducted to estimate pooled EQ-5D index utility values and EQ visual analog scale (VAS) scores in both 1L and 2L+. Various sensitivity analyses were also conducted. Forty-five unique publications met the inclusion criteria. In primary studies, baseline EQ-5D index utility values ranged from 0.7 to 0.9 in 1L and 0.63 to 0.7 in 2L+. Twelve trials and observational studies were feasible for inclusion in the meta-analysis. The pooled mean baseline EQ-5D index utility value was estimated as 0.79 (95% CI, 0.70-0.84) and 0.69 (95% CI, 0.67-0.71) for 1L (n = 7 studies) and 2L + (n = 4 studies), respectively. The pooled mean baseline EQ VAS score was estimated as 74.63 (95% CI, 70.97-78.29) and 65.82 (95% CI, 64.53-67.11) in 1L and 2L+, respectively. Limitations include hampered comparability between studies due to heterogeneity in study design and geographical regions. This study provides a comprehensive synthesis of EQ-5D data presently available in adults with mCRPC in both 1L and 2L + therapy.

Background: In a convenience sample of women scheduled for chemotherapy for early-stage breast cancer, we investigated associations of the Center for Disease Control and Prevention's neighborhood-level social vulnerability index (SVI) with pretreatment demographics and patient-reported outcome (PRO) measures (health behavior, function and quality of life, treatment toxicities during chemotherapy).

Methods: The SVI Overall score is comprised of 4 themes: socioeconomic, household composition, minority status/language, and household type/transportation, with scores ranging from 0 = lowest to 1 = highest vulnerability neighborhoods. Participant SVI scores were derived from zip codes listed in the patient's address within the electronic medical record (EMR). Associations of study variables with SVI were evaluated using Spearman correlation for continuous variables and Kruskal-Wallis tests for categorical variables.

Results: In a sample of 309 women, the mean age was 56 years (range 23-83) and 75% White. Greater vulnerability SVI Overall score was associated with lower education (P =.02), nonmarriage (P ≤.0001), higher body mass index (P =.03), and prechemotherapy PRO measures such as fewer self-reported walking minutes/week (P ≤.001), history of smoking (P =.02) and alcohol use (P < .001), depression (P =.01), and lower emotional social support (P =.008). During chemotherapy, moderate, severe, or very severe symptoms were associated with greater vulnerability SVI Overall scores for hot flashes (P =.03), arthralgia (P =.02), myalgia (P =.02), peripheral neuropathy (P =.01), edema of limbs (P =.04), and nausea (P <.001).

Conclusions: SVI scores derived from addresses in the patient's EMR can be used to generate information that adds to the patient's social history in ways that are informative for anticipating and monitoring chemotherapy-related toxicities.

Background: Early screening of hepatocellular carcinoma (HCC) is strongly recommended for hepatitis B virus (HBV)-infected patients. We aimed to develop and validate a predictive nomogram based on HCC occurrence trajectory for screening precancerous patients with HCC.

Methods: Peripheral blood mononuclear cells (PBMC) samples from 22 patients with HCC with their precancerous stage (n = 55) and 18 healthy controls were measured using HumanMethylation EPIC BeadChip assay. HCC trajectory was assessed by pseudotime based on TimeAx algorithm and chronological time. The 43 candidate CpG sites were selected from the methylation signature and measured using multiplex bisulfite sequencing in a retrospective cohort of HBV-infected patients (n = 604). A 5-CpG-classifier was built using the LASSO Cox regression model, based on the association between the methylation level of every CpG and the duration from enrollment to HCC occurrence of individual patient. We validated the risk stratification and predictive accuracy of this classifier in both the primary cohort (n = 300) and independent validation cohort (n = 304).

Results: Pseudotime and chronological time of HCC trajectory analysis revealed that the PD-1/PD-L1 pathway underwent changes in the precancerous stage. Based on the trajectory of methylation signature, we built a 5-CpG-classifier which remained powerful and independent predictive efficiency after stratified analysis by clinicopathological risk factors in both primary cohort and independent validation cohort. A predicting nomogram including the 5-CpG-classifier was constructed after multivariate analysis. One-year cumulative hazard of HCC in low- and high-risk groups of HBV-infected patients was 3.0% (0.1%-5.8%) and 17.90% (11.00%-24.3%) (P < .0001) in primary cohort, 4.5% (1.20%-7.80%) and 27.3 (18.90-34.90) (P < .0001) in the independent validation cohort.

Conclusions: One-year before HCC was a critical period of transitional time when parts of the methylation profile underwent shifting toward HCC like. The nomogram could identify precancerous stage patients with HCC who should be screened for early diagnosis and intervention.

Background: As an extended analysis of the COVID-DELAY study, we aimed to assess the impact of the COVID-19 pandemic on diagnosis, staging, and survival outcomes among patients with colorectal cancer (CRC) diagnosis performed from 2019 to 2022.

Methods: All consecutive newly diagnosed CRC patients referred to 11 Italian Oncology Departments between March and December 2019, 2020, 2021, and 2022 were enrolled. Access rate, demographics, diagnostic-therapeutic temporal intervals, and first-line progression-free survival (PFS) and OS among metastatic patients were assessed.

Results: Compared to 2019 (n = 690), an initial global reduction in new CRC cases in 2020 (n = 564, -18.3%) was observed, followed by a progressive increase in new CRC diagnoses in 2021 (n = 748, + 8.4%) and 2022 (n = 756, + 9.6%); a higher rate of TNM stage IV tumors was diagnosed in 2020 (35.4%) and 2021 (31.0%) compared to 2019 (29.6%), with normalization in 2022 (26.4%) (P < .001). Not clinically relevant differences between histological diagnosis and first oncological examination, cytohistological diagnosis and systemic treatment start, first oncological appointment and systemic treatment start, treatment start and first radiological assessment between 2020 and 2021-2022 years were found. After propensity score matching according to the year of diagnosis, median OS was significantly worse in 2020, 2021, and 2022 compared to 2019 (27.6 vs 24.8 vs not reached vs 38.9 months, respectively) (P < .001). Concordantly, the median PFS was significantly worse with each passing year: 13.0 vs 11.1 vs 9.2 vs 7.2 months in 2019, 2020, 2021, and 2022, respectively (P = .00027).

Conclusions: A progressive normalization in the rate of new CRC diagnosis as well as TNM stages at diagnosis, in 2021 and 2022 compared to 2020 and 2019, was found. The increase in new CRC cases might have affected some diagnostic-therapeutic time intervals in 2021-2022 years compared to 2020. Significantly, compared to the pre-pandemic phase, pandemic years were independently associated with worse PFS and OS outcomes in patients affected by metastatic disease.

Background: Previous results of our trial demonstrated that the addition of induction chemotherapy (IC) prior to definitive chemoradiotherapy (CRT) failed to significantly improve the response rate or 3-year survival in patients with locally advanced esophageal squamous cell carcinoma (ESCC). Here, we report long-term results and exploratory analyses to further evaluate the therapeutic value of IC.

Methods: Patients with previously untreated, unresectable, stage II-IVA ESCC were randomly assigned to receive IC followed by CRT or CRT alone. The relationship between tumor response to IC and long-term survival was analyzed. Baseline tumor biopsies were collected for RNA-Seq to identify patients who may benefit from IC.

Results: Eligible patients were randomized to either the IC + CRT group (n = 55) or the CRT group (n = 55). With a median follow-up of 74.9 months, the 5-year overall survival rate was 31.8% in the IC + CRT group and 29.1% in the CRT group (P =.675; HR, 0.91; 95% CI, 0.58-1.43). Similarly, no significant differences were identified in 5-year progression-free survival between groups (30.5% vs 25.5%, P =.508; HR, 0.86; 95% CI, 0.56-1.34). Patients who responded to IC had significantly better survival than nonresponders. A risk-score model incorporating 6 key genes to predict IC efficacy was also constructed.

Conclusions: Compared with definitive CRT alone, the addition of IC before CRT still failed to demonstrate superior survival in patients with unselected ESCC, based on long-term follow-up. However, because IC responders were associated with more favorable survival, potential molecular biomarkers were identified for selection of benefit population from IC.

Clinical trials registration: NCT02403531.

Background: Biliary tract cancer (BTC) is an aggressive biliary tract cancer, arising from the bile ducts and gallbladder, with a poor prognosis. The TOPAZ-1 trial of durvalumab plus first-line chemotherapy (gemcitabine plus cisplatin) showed improved survival vs chemotherapy alone. This real-world study aimed to confirm the effectiveness of this regimen.

Methods: This retrospective, multicenter study included patients with advanced BTC treated with first-line durvalumab plus platinum chemotherapy at the Linkou, Taoyuan, and Tucheng branches of Chang Gung Memorial Hospital as well as at Taipei Veterans General Hospital between August 2021 and June 2023.

Results: Among the 45 patients with advanced biliary tree cancer treated with durvalumab plus cisplatin and gemcitabine as first-line treatment, the objective response rate was 31.1% (14 partial responses). An additional 40% (18 patients) had stable disease. The median progression-free survival was 5.6 months (95%CI, 4.4-6.9) and median overall survival was 15.8 months (95%CI, 7.9-23.8). Responders had significantly longer survival than non-responders (15.8 vs 3.3 months). Although higher durvalumab doses (1000-1500 mg) appeared to have improved efficacy compared to lower doses (<1000 mg), the difference was not statistically significant. On multivariate analysis, poor ECOG performance status (≥2) and a high neutrophil-lymphocyte ratio were independent prognostic factors for shorter overall survival.

Conclusion: This real-world study demonstrated the comparable efficacy of durvalumab plus chemotherapy to the TOPAZ-1 trial for patients with advanced BTC and identified prognostic factors. There was a trend toward improved efficacy with higher durvalumab dosing (1000-1500 mg) vs lower dosing, though further research is needed to confirm this relationship.

Background: Immune checkpoint inhibitors (ICIs) are associated with severe immune-related adverse events (s-irAEs) that result in hospitalization, emergency department (ED) visits, treatment discontinuation, or death. This study examined the impact of s-irAEs and their earliest management strategies on clinical outcomes in advanced non-small cell lung cancer (NSCLC).

Methods: Data were derived from ConcertAI Patient360 NSCLC, a US-based electronic medical record database, between January 2012 and May 2021. Eligible patients had advanced NSCLC and received ICI-containing therapy. s-irAEs and management actions were abstracted from unstructured EHR data from ICI initiation through the earliest of 100 days after ICI discontinuation, start of a non-ICI-containing regimen, loss to follow up, end of study period, or death. Multivariable Cox regression analysis was used to evaluate the association between s-irAEs and their earliest management strategies, and real-world progression-free survival (rwPFS) and real-world overall survival (rwOS).

Results: The study included 3211 patients. Median (IQR) age was 67 (60-73) years, and 44.9% were female. Most patients (61.6%) initiated ICIs as first-line therapy; half (50.1%) initiated ICIs as monotherapy, with nivolumab monotherapy (29.5%) as the most common initial ICI-containing regimen in any line. Overall, 8.6% of patients experienced s-irAEs, most often diarrhea (3.5%), pneumonitis (1.4%), and rash (1.3%). Among patients who experienced at least one s-irAEs, over half (57.4%) were hospitalized, and 71.8% were treated with corticosteroids, any time after the occurrence of their first s-irAEs. Median rwPFS was 4.9 (95%CI, 4.6-5.2) months, and median rwOS was 13.6 (12.6-14.7) months from ICI initiation. rwPFS and rwOS were comparable between patients with s-irAEs vs patients without s-irAEs when s-irAEs were first managed with anti-cancer treatment interruptions. Patients with s-irAEs had a 53% (22.3%-91.4%) higher risk of death than patients without s-irAEs when s-irAEs initially required corticosteroids or other immunosuppressants, and a 61% (37.9%-87.9%) higher risk of death when s-irAEs first required hospitalization or ED admission.

Conclusion: The impact of s-irAEs on clinical outcomes may depend on the initial intervention required to manage the adverse event. s-irAEs were associated with worse outcomes when they initially required hospital/ED admission, corticosteroids, or other immunosuppression.

Background: Despite the increasing integration of wearable technology in oncology, its application in the care of older adults, representing most patients with cancer, is poorly defined.

Objective: This systematic review aimed to summarize the current use of wearables in studies in older adults with cancer.

Methods: This systematic review was conducted following the PRISMA guidelines. A systematic search was conducted in PubMed, Embase, Emcare, Web of Science, and Cochrane Library on May 1, 2024. Studies involving wearable devices and patients aged ≥60 years diagnosed with cancer were included. Outcomes reported were study characteristics, wearable outcomes, feasibility and adherence. The mixed method appraisal tool was used to assess the quality of included studies.

Results: A total of 31 publications were included, comprising 1298 older patients. Of these, 12 were pilot/feasibility studies, 12 were observational studies, 6 were randomized controlled trials, and 1 was a cross-sectional study. Most studies used wearable data to measure recovery (19 studies, 61%). Physical activity was the most studied wearable outcome (27 studies, 87%). Adherence to the wearable device was documented in 11 of the 31 studies (35%), with adherence ranging from 74% to 100%.

Conclusions: Our systematic review found wearables were mostly used to measure physical activity, with the most common primary aim of measuring recovery. Most studies reported high adherence, although definitions of adherence were diverse. Our results highlight the need for more and larger studies on wearable technology in older cancer patients, the use of standardized reporting frameworks, and increased participation in research in low- and middle-income countries.