Oncology and Therapy最新文献

Introduction: Venetoclax has demonstrated clinical benefit for newly-diagnosed acute myeloid leukemia (AML), but significant neutropenia is a concern. Data on the time course of neutrophil counts for across treatment cycles in real-world settings remain limited. We report an interim analysis of the VENUS study, which examined neutropenia management in patients with AML receiving venetoclax with azacitidine (VEN/AZA) in Japan.

Methods: This multicenter (10 sites), retrospective, observational study included adults with newly-diagnosed AML ineligible for intensive chemotherapy and initiating venetoclax treatment. Treatment patterns, granulocyte colony-stimulating factor (G-CSF) use, antifungal prophylaxis, and time course of neutrophil counts were analyzed for patients who received > 1 cycle of venetoclax.

Results: Venetoclax was administered for a median 27.0 days in Cycle 1 and then a median 21.0 (range 14.0-22.0) days for subsequent cycles, with median dose holds at the end of each cycle of 8.5-15.0 days. Patients (n = 81) receiving G-CSF were treated with VEN/AZA for a median of 6.0 cycles versus 3.0 in those who did not receive G-CSF (n = 39). In Cycle 1, median neutrophil counts decreased to < 500/µl during Days 8-28 but recovered to > 500/µl by Days 29-35. Median nadir neutrophil count was reached during Days 22-28 in almost all subsequent cycles until Cycle 10. Neutrophil counts decreased to < 500/µl in some cycles but improved to > 500/µl by the next week, suggesting neutrophil levels without higher risk of infection in most patients after Cycle 2 with venetoclax dosing schedule modifications and G-CSF administration. Eighty-eight (73.3%) patients received antifungal prophylaxis, but risk-based antifungal prophylaxis may be considered.

Conclusion: This real-world analysis provides insight into the timing of neutrophil count recovery with dosing schedule modification of venetoclax and G-CSF use in patients with newly-diagnosed AML receiving VEN/AZA, informing timing of the use of antifungal prophylaxis for patients at higher risk.

Introduction: This research sought to identify trends in the patient with lung cancer (LC) care pathway, experiences, and needs, across geographies and healthcare settings.

Methods: Patients living with LC for more than 18 years in nine countries completed an online survey covering these domains-demographic, disease, treatment, and patient preferences for information and support services. Recruitment was primarily from patient with LC communities on online platforms.

Results: A total of 1000 patients with LC completed the survey across Europe (49%), North America (29%), and Asia (22%). Demographics of participants were different to what has been reported in literature-there were a lower proportion of type non-small cell lung cancer (NSCLC), a higher proportion of type small cell lung cancer (SCLC), a higher rate of early-stage diagnosis, and a younger population. There were 56% male participants. Although physicians were the main stakeholders influencing treatment choice and quality of life (QoL) discussions, the patient's family/relatives ranked highly as important stakeholders. The top reasons patients reported choosing a treatment were related to efficacy, and hesitation to start a treatment was related to concerns about side effects. QoL was an important factor in both cases. Patients are impacted physically, socially, and mentally-50% report an impact on employment status, 48% report daily difficulties in mental well-being, and 64% have received psychological support or would like to. Disparities were observed across countries in genetic/biomarker testing completed or planned (30-88%) and being asked to participate in clinical trials (15-49%), which reflects the status of how different patient with LC care pathways have adopted innovation in LC care.

Conclusion: Both medical and external factors impact experiences and outcomes of patients living with LC, including the role of family in treatment and QoL discussions. There are intercountry differences in knowledge and disease management.

Introduction: Laryngeal chondrosarcoma (CS) is a rare indolent malignant tumor. High-grade (G3), dedifferentiated (DD), and myxoid (MY) CSs are considered more aggressive subtypes due to their metastatic potential and relatively poor outcomes. The aim of this systematic review is to evaluate treatment modalities and survival outcomes in patients affected by these rarer CS subtypes.

Methods: Papers published from January 1, 2000, to August 25, 2024, describing cases of laryngeal G3, DD, and MY CS were included.

Results: A total of 38 patients (15 G3, 13 DD, and 10 MY) were selected. Cricoid cartilage was the most common site of origin. Total laryngectomy (TL) was often performed. Primary conservative approaches in 42.8% of patients were followed by loco-regional recurrence.

Conclusions: Aggressive subtypes of CS require a radical approach because of the higher rate of loco-regional and distant recurrences compared to low-grade CS. TL with radical intent is the most common treatment, and adjuvant therapy should be considered after careful multidisciplinary discussion.

Introduction: There is a lack of data on the efficacy, effectiveness, and safety of lanreotide autogel in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) of Chinese ethnicity. This noninterventional, retrospective study evaluated the effectiveness and safety of lanreotide autogel in patients of Chinese ethnicity with GEP-NETs in clinical practice.

Methods: Patients' charts were abstracted from five hospitals in Hong Kong and Taiwan (July-September 2021), where lanreotide autogel is approved for treating GEP-NETs. Included patients were adults with unresectable, metastatic, or locally advanced GEP-NETs who received a first injection (index) of lanreotide autogel 120 mg between 01 January 2017 and 30 June 2020 (planned sample size: N = 30). Follow-up ran from index to a maximum of 48 (± 4) weeks or until disease progression, start of new antitumor treatment, or death. The primary endpoint was progression-free survival (PFS) rate at week 48 (±4), and secondary endpoints included PFS rate at week 24 (±4), estimated using Kaplan-Meier analyses. All analyses were descriptive.

Results: Of 27 patients enrolled, 22 (81.5%) had 48 weeks of follow-up. Tumors of pancreatic origin were the most common (73.9%). PFS rate was 0.96 (95% confidence interval: 0.72 - 0.99) at 24 weeks and 0.82 (0.53-0.94) at 48 weeks. Overall, 74.1% patients experienced ≥ 1 treatment-emergent adverse event; none were serious. No deaths were reported.

Conclusions: Lanreotide autogel was well tolerated and showed good tumor control rate in a real-world setting. These findings align with results from previous studies in Caucasian, Japanese, and Korean patients, thus supporting lanreotide autogel for treating patients with GEP-NETs of Chinese ethnicity.

The systemic treatment landscape for advanced and metastatic chondrosarcoma, a malignancy with limited responsiveness to conventional therapies, has always been notoriously challenging. While standard chemotherapy offers minimal benefits, certain subtypes, such as mesenchymal and dedifferentiated chondrosarcomas, have shown some response to systemic therapies initially developed for other sarcomas. Investigational strategies are focusing on molecular targets, including mutations in the isocitrate dehydrogenase gene (IDH), signaling pathways, such as hedgehog and death receptor 5 (DR5) and immune modulation. IDH mutations, notably found in conventional and dedifferentiated chondrosarcomas, have prompted the evaluation of IDH inhibitors, which have demonstrated promising efficacy in preclinical and early clinical trials, despite limited data in chondrosarcoma. Additionally, the hedgehog pathway, implicated in chondrosarcoma progression, has been targeted with inhibitors, although clinical translation has shown mixed results. Immunotherapy, including programmed cell death 1 (PD-1) checkpoint inhibitors and chimeric antigen receptor-T (CAR-T) cells, is also being investigated but faces challenges due to the immunosuppressive tumour microenvironment. Among new approaches, DR5 agonists such as INBRX-109 have shown single-agent efficacy, with minimal toxicity, opening possibilities for use in combination therapies to improve outcomes. Given the heterogenous and treatment-resistant nature of chondrosarcoma, we highlight the need for multi-omics and genetic profiling to guide personalized, combination therapies that target multiple carcinogenic pathways. The integration of multi-targeted approaches could enhance efficacy, address tumour heterogeneity, and overcome resistance, presenting a hopeful direction for systemic therapy in this challenging cancer. The investigation of combination regimens with IDH inhibitors, immunotherapy and DR5 agonists hold promise for transforming the management of advanced chondrosarcoma.

Introduction: Despite many prostate cancer (PC) treatment options in Japan, physicians' and patients' preferences in metastatic castration-sensitive PC (mCSPC) and castration-resistant PC (CRPC) are unclear.

Methods: For this cross-sectional study, an online questionnaire survey based on the best-worst scaling (profile case) approach was designed. Physicians' and patients' questionnaires, comprising six attributes (efficacy, safety, target patients, dosage, administration, and medical expenditures), had 24 and 26 items for mCSPC and CRPC surveys, respectively. Four items were presented during each session; respondents selected the "most important" and "least important" among these. The objective was to elicit attributes important for treatment and their relative importance levels among physicians and patients and to explore similarities and differences in choices. Multinomial logit and hierarchical Bayesian models were applied, and preferences were presented as relative importance and utility values.

Results: Responses of 177 physicians (urologists: 173; oncologists: 4) and 292 patients (mCSPC: 94; CRPC: 198) were analyzed. Most patients with CRPC (63.1%) had no metastases. Efficacy was the most important attribute overall. Physicians considered patient survival the most important among efficacy items (11.1%), whereas patients with mCSPC prioritized prevention of metastases spread (9.7%) and prostate-specific antigen (PSA) elevation (9.3%). In CRPC, both physicians and patients prioritized prevention of metastasis development or its spread (physicians: 9.6%; patients: 8.3%) and PSA elevation (physicians: 9.3%; patients: 7.9%). After efficacy, physicians prioritized items related to target patients (cardiovascular disorders; mCSPC: 4.8%; CRPC: 3.4%), whereas patients prioritized safety (mCSPC: falls or fractures [5.6%]; CRPC: liver dysfunction [4.7%]). Patients with mCSPC were also concerned about rising medical expenditures (5.4%).

Conclusion: Treatment efficacy was the most important attribute for both physicians and patients in Japan in mCSPC and CRPC settings, although their preferences differed in priority based on outcomes. These findings may be useful to improve shared decision-making for PC treatment in Japan.

Introduction: Prostate cancer and its treatment, particularly androgen deprivation therapy (ADT), can profoundly impact patients' quality of life. The aim of the prospective observational study reported here was to evaluate the effects of ADT on various aspects of quality of life in men with prostate cancer at a community-based hospital in Southern Italy.

Methods: Eligible men initiating hormonal therapy were recruited between December 2021 and December 2023. Data were collected at baseline (T₀) and after 3 months (T₁) and 6 months (T₂) of ADT using standardized questionnaires (European Organization for Research and Treatment of Cancer [EORTC] QLQ-C30, EORTC QLQ-PR25) and semi-structured interviews.

Results: Of the 52 participants, 43 completed all three assessments. The EORTC QLQ-C30 showed a statistically significant worsening in physical functioning (mean score decrease from 83.8 at T₀ to 76.7 at T₂; p < 0.001), increased fatigue (from 23.7 to 35.2; p < 0.001), and insomnia (from 23.7 to 31.8; p = 0.048) following ADT initiation. The QLQ-PR25 revealed a significant decline in sexual functioning (from 59 to 26.9; p < 0.001) and sexual activity (from 27.3 to 12; p = 0.001). Interviews revealed a significant rise in the number of patients reporting depressed mood. Interviews also highlighted a worsening in body image perception and sexuality, increased feelings of dependence, and challenges in the social and relational spheres.

Conclusions: ADT significantly impacts various aspects of quality of life in men with prostate cancer, particularly physical functioning, fatigue, sexual function, body image, and emotional well-being. These results underscore the critical importance of a comprehensive, patient-centered approach that addresses both the physical and psychosocial aspects of care.

Introduction: Cancer incidence is rising in Italy, making it harder for researchers to search for innovative and comprehensive treatment strategies. The advancement of precision medicine, the hunt for molecular targets, and the development of drugs that may operate on a specific target have all become increasingly important aspects of the oncological treatment strategy in recent years. The aim of this study is to analyze the activity and performance of the Oncology and Research Center of the Marche Region (CORM) and its Molecular Tumor Board (MTB) in implementing precision medicine to improve cancer treatment.

Methods: CORM was established to provide multidisciplinary diagnostic and therapeutic services, promoting early diagnosis, innovative treatments, and continuous patients support. The MTB, including various specialists, facilitates the interpretation of genomic profiles to identify targeted therapies.

Results: From June 2021 to May 2024, 118 patients were evaluated at the MTB of the Marche Region, with 77 undergoing molecular profiling. This study highlights the efficacy of the MTB in selecting appropriate molecular tests, interpreting results, and recommending personalized treatment strategies, leading to improved patient outcomes.

Conclusion: Challenges such as the complexity of genomic data interpretation and the need for more computational tools to assist clinicians were also identified. Still, constant multidisciplinary collaboration between experts and the finest possible innovative technological support are required to achieve the best outcomes in cancer treatment.

Introduction: Personalized medicine has revolutionized the clinical management of patients with solid tumors. However, the large volumes of molecular data derived from next-generation sequencing (NGS) and the lack of harmonized bioinformatics pipelines drastically impact the clinical management of patients with solid tumors. A possible solution to streamline the molecular interpretation and reporting of NGS data would be to adopt automated data analysis software. In this study, we tested the clinical efficiency of the Navify Mutation Profiler (nMP) software in improving the interpretation of NGS data analysis in diagnostic routine samples from patients with solid tumors.

Methods: This study included one coordinating institution (Federico II University of Naples) and five other Italian institutions. Variant call format (VCF) files from reference standard samples previously tested by the coordinating institution and from n = 8 diagnostic routine samples (n = 2 from colorectal carcinoma; n = 2 from non-small cell lung cancer; n = 2 from advanced melanoma; and n = 2 from patients with gastrointestinal stromal tumors) and previously analyzed by each participating institution (n = 5) with standardized internal analysis workflows were uploaded onto the Navify^® Mutation Profiler (nMP) system (Roche Sequencing Solutions, Pleasanton, CA, USA) for automated analysis and interpretation of DNA and RNA molecular alterations analytical parameters, molecular profiling, and clinical interpretation were carried out by the nMP system and compared with the standard workflow data analyzed by the participating institutions.

Results: Overall, all VCF files were successfully submitted and interpreted by the nMP system. A concordance agreement rate of 89.6% was observed between the automated and standard workflow systems. In particular, DNA and RNA molecular profiles obtained with the nMP system matched those obtained with standardized approaches in 44 out of 48 patients (91.7%) and in 11 out of 12 (91.7%) cases, respectively. In addition, the nMP system evidenced wild-type variants in 6 out of 7 (85.7%) cases.

Conclusions: The nMP system represents a valid, easily manageable, and clinically useful system to interpret NGS data on diagnostic routine samples from patients with solid tumors.

Introduction: Real-world data on patients with early breast cancer (EBC) with high-risk features remains limited. This population-based study determined the incidence, outcomes and characteristics of patients with hormone receptor (HR)-positive, human epidermal growth factor 2 receptor (HER2)-negative EBC with high-risk features treated in everyday clinical care in two Finnish hospital districts which represent approximately 40% (2.5 million) of the total Finnish population (5.5 million).

Methods: Adult female patients with BC (ICD-10 C50*) diagnosed between January 2012-June 2019 were indexed at the first BC diagnosis and followed until December 2019 or death. EBC was defined as having no records of metastasis within 90 days of index. High-risk status was defined as ≥ 4 positive axillary lymph nodes (ALNs) or 1-3 ALNs with either grade 3 tumor or tumor size ≥ 5 cm. Outcomes included invasive disease-free survival (IDFS), distant relapse-free survival (DRFS) and overall survival (OS) and were assessed using Kaplan-Meier methods and Cox regression models.

Results: Among the 8678 patients with HR+/HER2- EBC, risk classification was feasible in 8081 (93.1%) individuals. Of these, 1407 (17.4%) were defined as high-risk and the remaining 6674 (82.6%) as low-risk patients. The average annual incidence of high-risk HR+/HER2- EBC in 2012-2018 was 21.8/100,000 women. Five-year invasive disease-free survival (IDFS) and distant recurrence-free survival (DRFS) showed higher risk of recurrence for the high-risk group: IDFS 79.7% (95% CI 77.0-82.2) vs 89.3% (88.3-90.2) in the low-risk group; DRFS 82.4% (79.7-84.7) vs 92.9% (92.1-93.7) in the low-risk. Five-year overall survival (OS) in the high-risk group was 89.5% (87.3-91.4) and was 95.4% (94.7-96.0) in the low-risk group.

Conclusions: This study showed that high-risk patients account for 17% of newly diagnosed HR+/HER2- EBC in Finland. The high-risk profile was associated with increased risk of recurrence, distant relapse and death compared to low-risk patients. The poorer outcomes of high-risk HR+/HER2- EBC emphasizes a clear unmet need in improving the identification and treatment of these patients.