Oncologist最新文献

Background: Isocitrate dehydrogenase (IDH)-mutant gliomas represent a distinct category of diffuse gliomas with unique biological behavior and clinical course. Over the past decade, our understanding of these tumors has dramatically evolved, thanks to advances in molecular classification, imaging, and targeted therapies.

Method: This review provides a comprehensive overview of the current landscape in IDH-mutant glioma management.

Results: We highlight key molecular features and recent refinements in WHO tumor classification, along with novel diagnostic tools such as magnetic resonance spectroscopy and liquid biopsy. Surgical strategies have also shifted, with emphasis on maximal safe resection guided by functional mapping and advanced neuroimaging. Therapeutically, IDH inhibitors like vorasidenib are emerging as promising agents in selected patient populations, offering prolonged disease control. Additionally, radiotherapy and chemotherapy remain critical components, with ongoing trials evaluating their integration with targeted approaches. Finally, we explore future directions, including immunotherapy, PARP inhibitors, and CDK4/6 inhibitors especially in recurrent or treatment-resistant cases.

Conclusions: This review underscores the importance of a multidisciplinary, precision medicine approach in optimizing outcomes for patients with IDH-mutant gliomas.

Background: Biliary tract cancer (BTC), as a relatively rare tumor, carries a poor prognosis. While immunotherapy combined with chemotherapy can extend survival, response rates remain low. Targeted therapies tailored to specific genetic mutations may improve outcomes when paired with immune checkpoint inhibitors. This report examines 2 cases of advanced BTC with distinct genetic alterations, treated with targeted therapy and immune checkpoint inhibitors, to assess efficacy and feasibility.

Case presentation: A 45-year-old patient with a BRAF V600E-mutated intrahepatic cholangiocarcinoma received dabrafenib, trametinib, and durvalumab. This led to significant tumor reduction, enabling complete surgical resection with clear margins. Postoperative analysis showed a major pathological response. A 39-year-old patient with MET-amplified gallbladder cancer was treated with tepotinib, durvalumab, and chemotherapy, resulting in metastases regression and successful tumor downstaging. Surgery achieved no evidence of disease.

Conclusions: Combining targeted therapies with immune checkpoint inhibitors showed promising results in 2 patients with advanced BTC driven by specific genetic mutations. Significant tumor reduction and successful surgeries suggest this approach may improve resectability and outcomes. These cases highlight the potential of personalized treatment guided by genetic profiling. Further research is needed to confirm these findings and explore broader applications for this strategy.

Background: Cardiotoxicity is a concern for patients with sarcoma receiving anthracyclines. Dexrazoxane reduces this risk; however, the timing of administration varies in practice. This study evaluated the association between dexrazoxane timing and anthracycline cardiotoxicity risk.

Patients and methods: This retrospective, single-center cohort study included adults with sarcoma treated with anthracyclines from 2010 to 2020 with a baseline and ≥1 follow-up echocardiogram. "Early" dexrazoxane was defined as starting with the first anthracycline dose; "later" as starting with the second or subsequent doses. The primary endpoint was time to cardiotoxicity (decline in left ventricular ejection fraction [LVEF] ≥10%-<50% from baseline). Associations were evaluated using multivariable Cox proportional hazards models.

Results: Among 672 patients, the median doxorubicin-equivalent dose was 300 mg/m2 (interquartile range [IQR]: 200-444 mg/m2); dexrazoxane was administered early in 130 patients (19.3%) and later in 275 (40.9%). Over a median follow-up of 8.6 months (IQR: 3.9-23.1 months), 48 (7.1%) developed cardiotoxicity. Among patients who received a cumulative anthracycline dose >300 mg/m2, those receiving early dexrazoxane had an 85% reduction in cardiotoxicity risk (hazard ratio, 0.15; 95% CI, 0.02-0.99) compared to those who did not receive dexrazoxane, adjusting for age, diabetes, and baseline LVEF. Early dexrazoxane was not significantly associated with cardiotoxicity risk among patients who received a cumulative anthracycline dose ≤300 mg/m2.

Conclusions: Early dexrazoxane is significantly associated with lower cardiotoxicity risk in adults with sarcoma receiving anthracycline doses >300 mg/m2. These findings support the potential benefit of early dexrazoxane use in patients at elevated risk for anthracycline-induced cardiotoxicity; however, further validation is warranted.

Background: Mutations in TP53 are common in gastroesophageal cancer and portend a poor prognosis. Tumor cells with TP53 mutations increasingly rely on ataxia-telangiectasia and Rad3-related (ATR) protein to respond to and repair DNA damage induced by cytotoxic chemotherapy. We aimed to assess the efficacy of ATR inhibitor, berzosertib, with irinotecan in patients harboring TP53-mutated, metastatic gastroesophageal cancer.

Methods: NCI 10211 is a phase II trial that enrolled patients with TP53-mutated, unresectable or metastatic gastroesophageal adenocarcinoma to receive berzosertib with irinotecan on day 1, 15 in 28-day cycles. Initially, patients who had progressed on at least 1 prior line of therapy were enrolled which was later amended to at least 2 prior lines of therapy. The primary outcome was objective response rate (ORR), and secondary outcomes included progression-free survival (PFS) and overall survival (OS). Nine patients underwent biopsy for correlative studies, which included assay evaluation of γH2AX, NBS1, and KAP1 p-Ser 824 expression.

Results: Of the 17 patients enrolled, 16 were evaluable for the primary endpoint of ORR. The ORR was 0%, disease control rate (DCR) of 56.2%, median PFS (mPFS) of 4.01 months, and median OS (mOS) of 6.21 months. The study did not meet its primary endpoint. The most common treatment-related adverse events were nausea (52.9%), anemia (41.2%), diarrhea (41.2%), and lymphopenia (41.2%) without any unexpected adverse events.

Conclusion: This novel combination of ATR inhibitor berzosertib with irinotecan did not lead to objective responses in patients with TP53-mutated, advanced gastroesophageal adenocarcinoma. The combination regimen was well tolerated without unexpected adverse events. This trial was registered with ClinicalTrials.gov (NCT03641313).

Six months of treatment with dostarlimab followed by nonoperative management in case of clinical complete response (cCR) is the new standard-of-care for patients with microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) locally advanced rectal cancer (LARC). The most recent update of the seminal phase II trial by Cercek et al. shows a cCR rate of 100% that allowed sparing chemoradiation and surgery to all included patients. Here, we present three clinical cases of patients with dMMR and MSI-H LARC treated with neoadjuvant dostarlimab at three Italian institutions with radiological evidence of disease progression while on treatment and discuss potential similarities among them to understand when and how this apparently rare event may occur.

Background: Immune checkpoint inhibitors (ICIs) have revolutionized oncology by enhancing antitumor immune responses. However, their use is frequently associated with immune-mediated adverse events, including colitis (ICIs-colitis). This condition shares clinical and histological features with inflammatory bowel diseases (IBD), such as Crohn's disease (CD) and ulcerative colitis (UC). Emerging evidence highlights the gut microbiota's role in both ICIs-colitis and IBD pathogenesis. This study aimed to determine whether a distinct microbiota profile, assessed via machine learning, could differentiate ICIs-colitis from IBD and healthy controls (HCs).

Methods: A prospective study was conducted with patients diagnosed with ICIs-colitis, alongside historical cohorts of IBD patients (active and inactive UC/CD) and HCs. Stool samples were analyzed using 16S rRNA gene sequencing. Diversity metrics (alpha and beta) and differential abundance at multiple taxonomic levels were evaluated. Machine learning techniques, including supervised and unsupervised algorithms, were employed to identify microbiota patterns and signatures distinguishing the groups.

Results: Nineteen patients with ICIs-colitis, 40 with UC (20 active, 20 inactive), 34 with CD (14 active, 20 inactive), and 36 HCs were analyzed. Alpha diversity differed between ICI-colitis and UC (P = .03) and between ICI-colitis and CD (P = .0002), but not versus healthy controls (P = .94). Beta diversity showed significant disease-associated clustering among ICI-colitis, UC and CD (PERMANOVA P < .001). Differential abundance analyses identified higher Enhydrobacter in ICI-colitis versus IBD and higher Bifidobacterium longum in UC. Machine-learning approaches (sparse partial least squares discriminant analysis, sPLS-DA, and Random Forest) supported group discrimination.

Conclusion: A unique microbiota signature characterizes ICIs-colitis compared to IBD and HCs. These findings underscore the potential of microbiota profiling and machine learning to aid in diagnosing and managing ICIs-colitis. Future studies should validate these findings in larger, multicenter cohorts, and explore therapeutic implications.

Purpose: This observational, prospective study aimed to evaluate the feasibility and usefulness of a person-based care (PbC) digital pathway integrating narrative medicine (NM) and electronic patient-reported outcomes measures (e-PROMs) for patients with metastatic breast cancer; the secondary objective was to assess its perceived impact on quality of life (QoL).

Patients and methods: The study was conducted in Italy from May 2023 to February 2024. Enrolled patients (≥18 years old, life expectancy ≥24 weeks) completed a digital diary with narrative prompts and the EORTC QLQ-C30/+Br23 questionnaire at enrollment and before each treatment cycle. Oncologists reviewed narratives and patient-reported outcomes (PROs), adjusting care accordingly. Feasibility, usefulness, and perceived impact on QoL were assessed through final questionnaires for patients and oncologists. Feasibility was also evaluated via compliance and usefulness through thematic and comparative analysis of narratives and PROs, assessing integration, concordance, and discordance.

Results: Twenty-nine patients and 6 oncologists participated. Study compliance was high; 21 patients and all oncologists completed the final questionnaires. Patients evaluated the digital diary as usable and effective in communication, while oncologists valued its compatibility with clinical workflow and ability to gather details not captured by ePROMs. Concordance and discordance between narratives and PROs were low (4.8% vs. 0.5%), but they provided complementary information (30.5% vs. 64.2%). PROs were more integrative in "problem" items (78.4% vs. 15.5%), whereas narratives were more informative on "resource" items (79% vs. 18.3%). Ten patients reported improved perceived QoL through the PbC pathway, while 6 found it potentially beneficial. Oncologists recognized its role in personalizing care.

Conclusion: Integrating NM and ePROMs in the PbC pathway proved feasible and useful, enhancing the perceived impact on QoL and fostering more personalized and empathetic care.

Overexpression of human epidermal growth factor receptor 2 (HER2) has been implicated as a molecular driver of numerous solid tumor subtypes. An antibody drug conjugate (ADC) directed to HER2, trastuzumab-deruxtecan, recently gained tumor-agnostic FDA approval for the treatment of advanced HER2-positive (IHC 3+) solid tumors. Here, we present a patient with HER2-positive invasive poorly differentiated scrotal carcinoma treated with trastuzumab-deruxtecan. The treatment resulted in a complete response, with a tolerable side effect profile and ongoing treatment-free survival. Our case adds to the literature suggesting clinical benefit of the use of trastuzumab-deruxtecan in HER2-positive tumors, and underscores the importance of molecular testing for patients with rare tumor subtypes.

Background: Evidence on homologous recombination repair (HRR) mutation prevalence in prostate cancer (PC) patients and the diagnostic testing path to guide treatment remains limited outside of clinical trials. The objective of this study was to investigate the DNA source, type of tumor tissue, timing for testing in the patient's disease course, and rate of conclusive results in a real-world population.

Patients and methods: This was an observational, cohort study, involving 20 Italian cancer centers. The study population included consecutive PC patients undergoing germline, tumor, and/or plasma circulating tumor DNA (ctDNA) to profile HRR genes between January 1, 2020 and January 31, 2025.

Results: Among 1400 PC patients included, 248 (17.7%) showed (likely)pathogenic variants (PVs) in the HRR genes. Most HRR testing was conducted during the metastatic castration-resistant PC (mCRPC)(779, 62.8%). The rate of conclusive results was 89.7% and varied widely according to the type of tumor tissue. The prevalence of HRR alterations was 18.1% in the mCRPC and 13.8% in the hormone-sensitive PC (P = .06). The concordance between tumor testing and ctDNA was 83.9%. Interestingly, 4.6% reported ctDNA testing positive but tumor testing negative, leading to important therapeutic implications. The prevalence of positive ctDNA testing was 47.4% vs 10.5%, for testing within 1 month or over 3 months, respectively, from the initiation of a new line of therapy.

Conclusion: This large real-world study, through the workflow adopted by clinicians for HRR genomic testing, provides novel insights into the variables influencing the success rate of genomic testing.