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Background: Chemotherapy-induced cognitive impairment (CICI) is a well-recognized side effect of breast cancer treatment. However, prospective long-term evaluations of CICI using standardized neuropsychological tests are scarce.

Patients and methods: This prospective longitudinal cohort study investigated cognitive dysfunction and its impact on quality of life and everyday functioning in patients with breast cancer receiving first-line chemotherapy compared to patients with breast cancer without chemotherapy. Assessment occurred prior to chemotherapy, postchemotherapy (median 6 months), and 2-3 years later. We used standardized neuropsychological tests, questionnaires, and scales to assess patients' quality of life and functioning. Additionally, serum analysis for neurodegenerative markers and autoantibodies was conducted.

Results: We included n = 53 patients. Overall cognitive function declined statistically significantly (P = .046) postchemotherapy compared to control patients, mostly driven by a reduced figural memory (P = .011). Patients who received chemotherapy showed a greater reduction in quality of life (increased fatigue symptoms, P = .023; reduced Karnofsky index, P < .001); however, without a statistically significant effect on cognitive decline. The neurodegenerative markers Neurofilament light chain (NfL) and phosphorylated Neurofilament heavy chain (pNfH) increased statistically significantly (P < .001) postchemotherapy and pNfH correlated with overall cognitive function. After 2-3 years, both cognitive performance and quality of life were comparable between chemotherapy-treated and control patients.

Conclusion: Our findings suggest that chemotherapy statistically significantly contributes to overall cognitive dysfunction in patients with breast cancer, which disappears after 2-3 years, indicating a recovery in both objectively measurable cognitive function and subjective quality of life. Future research should examine larger sample sizes and explore screening indicators, particularly pNfH.

Background: GD2 ganglioside, a known specific marker for neuroblastoma (NB), exists in different lipoforms, including C18 and C20, which are distinguished by the length of their fatty acid chains. C18 and C20 GD2 lipoforms can be simultaneously measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). We evaluated the diagnostic and prognostic performance of circulating GD2 levels in children with NB.

Methods: Thirty microliters of peripheral blood (PB) plasma samples from 83 children with NB at diagnosis and 83 age-matched healthy controls were analyzed by LC-MS/MS. From stage M patients, 29 additional PB plasma samples were collected after induction therapy, 7 before and after immunotherapy, and 6 at relapse. For 22 stage M patients, bone marrow (BM) plasma samples were also collected at diagnosis.

Results: C18 and C20 GD2 concentrations were significantly higher in children with NB than in controls. Receiver operating characteristic (ROC) analysis showed a cut-point of 44.1 and 0.47 nM for C18 and C20, respectively, able to discriminate with high specificity and sensitivity in patients with NB from controls. Circulating C18 and C20 levels in PB strongly correlated with those in BM. At diagnosis, C18 and C20 GD2 concentrations were significantly higher in stage M, deceased patients, and in those bearing tumors with MYCN amplification. ROC analysis identified prognostic cut points for the whole population, whereas only C20 concentrations above the cut points were significantly associated with a worse event-free survival of patients with stage M disease or with MYCN-amplified tumors. C18 and C20 plasma concentrations strongly decreased during treatment but increased at relapse.

Conclusions: Measurement of circulating GD2 seems to have prognostic power in the subsets of patients with stage M disease and with MYCN-amplified tumors, and be able to early detect relapse, thus its ability to monitor disease should be prospectively evaluated in future studies.

Background: Penile squamous cell carcinoma (PSCC) is a rare malignancy. However, in developing countries the incidence rate is higher. The understanding of molecular alterations is essential for evaluating possible targets for more effective systemic therapies.

Methods: We retrospectively collected clinical data of metastatic PSCC (mPSCC) patients who had received at least one prior systemic treatment from 3 Brazilian hospitals. Tumor samples were evaluated using the next-generation sequencing (NGS) Foundation One DX and immunohistochemistry (IHC). The objective was to identify and describe somatic genomic alterations known to be functional or pathogenic and their association with survival outcomes.

Results: Twenty-three patients were identified, 22 and 18 patients had tumor samples analyzed by IHC and NGS, respectively. PD-L1 expression (CPS ≥ 1%) was positive in 14 patients (63.6%). Regarding the genomic alterations, 16 patients (88.9%) had some clinically relevant genomic alterations. TP53, TERT, CDKN2A, PIK3CA, NOTCH1, and CDKN2B loss were identified in 66.7%, 50%, 50%, 33.3%, 27.8%, and 22.2% of the patients, respectively. No MSI or TMB high (≥10 mutations/MB) cases were identified. NOTCH1 mutation was identified only in HPV-negative patients and it was associated with worse OS (yes: 5.5 vs no: 12.8 months, P = .049) and progression-free survival (yes: 5.5 vs no: 11.7 months, P = .032).

Conclusion: This study demonstrated that molecular alterations in mPSCC from developing countries are similar to those from developed countries. Predictive biomarkers for immunotherapy response such as TMB high or MSI were not identified. Specific gene mutations may identify patients with worse prognoses and open new avenues for therapeutic development.

Epidermal growth factor receptor kinase domain duplication (EGFR-KDD) is a rare, recurrent oncogenic variant that constitutively activates EGFR in non-small-cell lung cancer. Herein, we report the case of a 70-year-old man with resectable colorectal adenocarcinoma who underwent surgery followed by adjuvant therapy. He relapsed with multiple liver metastases and received standard chemotherapy until his disease became refractory. Comprehensive genomic profiling of his postoperative colorectal cancer tissue revealed EGFR-KDD. He was treated with an EGFR tyrosine kinase inhibitor (TKI), afatinib and achieved a partial response (- 55%) after 8 weeks; however, he developed massive malignant ascites after 13 weeks. Osimertinib, another EGFR-TKI, controlled his tumors for 9 months. Patient-derived cancer organoids from his malignant ascites confirmed sensitivity to EGFR-TKIs. The findings suggest that EGFR-TKIs can be a potential treatment option for this molecular subgroup.

Background: The relationship between antibiotic treatment and immunotherapy efficacy is complex.

Methods: This study was a single-center study. History of antibiotic use in gastric cancer (GC) patients within 1 or 3 months prior to immunotherapy was collected. Patients were categorized into 3 groups according to whether they had used antibiotics prior to immunotherapy: none, prophylactic use, and infection.

Results: A total of 252 GC patients received immunotherapy, of which 38.5% (97/252) received antibiotic treatment within 1 month before immunotherapy (prophylactic use in 72.2% of patients) and 48.8% (123/252) received antibiotic treatment within 3 months before immunotherapy (prophylactic use in 74.8% of patients). The prophylactic use of antibiotic within 1 month prior to immunotherapy significantly improved overall survival (OS) compared with patients who received anti-infective therapy and had no history of antibiotic use (prophylactic vs infection: OS, 22.6 vs 9.7 m, HR, 0.53, 95% CI, 0.27-1.07; prophylactic vs none: OS, 22.6 vs 14.7 m, HR, 0.57; 95% CI, 0.39-0.83). The use of antibiotics in infected patients did not increase the risk of death in patients compared with those who did not use antibiotics. Prophylactic antibiotic use within 1 month before immunotherapy is an independent prognostic factor for OS.

Conclusions: Prophylactic use of antibiotics is associated with better prognosis in GC patients receiving immunotherapy. Therefore, there is no necessity to delay the use of immune checkpoint inhibitors in this group of patients.

Background: Healthcare resource utilization (HCRU) and costs are often elevated in patients with polycythemia vera (PV), and this patient population has an increased risk of developing thromboembolic events (TEs). This study describes HCRU, costs, and mortality during TE-related hospitalizations among patients with PV in a contemporary real-world setting in the United States.

Patients and methods: This retrospective cohort study included adult inpatients with PV and TE discharged from 623 hospitals between January 1, 2017, and June 30, 2020 with a 2-year follow-up period after the first TE-related (index) hospitalization. Data were abstracted from the PINC AI Healthcare database, which includes 25% of US inpatient discharges.

Results: Among 3494 patients (index TE: arterial, 69.1%; venous, 27.1%; both, 3.7%), mean (SD) age was 70.7 (14) years, and most patients were male (58.6%), White (81.2%), with Medicare insurance (72.6%). Mean (SD) Charlson Comorbidity Index score was 3.2 (2.3). Mean total hospitalization costs were $24 403 during the index hospitalization (mean [SD] hospital length of stay [LOS], 7 [9] days). A third (n = 1150) of patients were admitted to the intensive care unit (mean cost, $29 342; mean [SD] LOS, 5 [7] days). During 30 days and 2 years of follow-up, the TE-related readmission rate was 6.4% and 20.0%, respectively. All-cause mortality was 6.2% during index hospitalization; an additional 4.7% occurred during the 2-year follow-up period.

Conclusion: Among patients with PV and TE, inpatient hospitalization HCRU, costs, and mortality were substantial. These findings highlight the importance of preventing TEs in the management of PV.

Background: In patients with phyllodes tumors of the breast, the presence of mediator of RNA polymerase II transcription subunit 12 homolog mutations (MED12m) and a history of previous fibroadenoma may predict better outcomes. To aid in the prognostication of malignant phyllodes tumors of the breast (B-MPT), we assessed the prognostic value of fibroadenoma-like areas (supposed to have stemmed from a pre-existing fibroadenoma) and MED12m, in patients with resected primary B-MPTs.

Methods: We conducted a single-center, retrospective, cohort study including all consecutive patients aged ≥18 years old, with non-metastatic B-MPT, who underwent surgery from January 2000 to December 2021. The endpoints were the cumulative incidences of all recurrences, according to the presence of fibroadenoma-like areas, reviewed by 3 reference pathologists. A nested, case-control genomic analysis was performed to evaluate the association between MED12m, the presence of fibroadenoma-like areas, and cancer recurrences.

Results: Eight-nine patients were included, with 47% of tumors exhibiting Fibroadenoma-Like Areas (FLA+). These areas were not significantly associated with local recurrence (5-year cumulative incidence in FLA+ vs FLA-: 13.0, 95%CI [4.6-25.9] vs 23.6, 95%CI [11.9-37.5]; P = .14) or distant recurrence (5-year cumulative incidence in FLA+ vs FLA-: 12.5, 95%CI [4.5-25.0] vs 8.9, 95%CI [2.8-19.5], P = .61), at a median follow-up of 6.7 years. MED12m was not associated with distant recurrences or the presence of fibroadenoma-like areas.

Conclusions: Half of B-MPTs are characterized by the presence of fibroadenoma-like areas. This pathologic feature is not significantly associated with lower distant and local recurrences nor with the presence of MED12 mutations.