Oncology and Therapy最新文献

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: 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: 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: 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.

The incidence of brain metastases is higher in patients with non-small cell lung cancer (NSCLC) than in patients with most other cancers, and the development of brain metastases is associated with poor prognosis. The objective of the podcast is to provide information about current and future treatments for brain metastases that develop in patients with EGFR-mutated NSCLC. The panel discusses surveillance and management of patients with brain metastases, different types of currently used treatments, and recent data on the intracranial efficacy of antibody-drug conjugates (ADCs). The panel also discusses current and future studies of ADCs in patients with EGFR-mutated NSCLC with brain metastases. This podcast discussion, among four oncologists (two thoracic oncologists, one radiation oncologist, and one neurologist/neuro-oncologist), is for healthcare professionals (HCPs) at community practices and research institutions.

Introduction: The introduction of immunotherapy (IT) has transformed clinical care of patients with metastatic melanoma. However, many patients still die as a result of progressive disease. Here we analyzed how IT improved survival in a real-world setting. Additionally, we investigated whether IT alters the dynamics and pattern of metastatic progression in different organs resulting from tissue-specific immune microenvironments.

Methods: We retrospectively compared a group of 61 patients with metastatic melanoma (24 female, 37 male) treated with IT between 2015 and 2018 with a historical control group of 56 patients with metastatic melanoma (21 female, 35 male) treated with chemotherapy between 2005 and 2008 regarding treatment response rates and overall survival as well as the timing and distribution of metastatic progression.

Results: Patients with metastatic melanoma treated with IT showed increased response rates and longer overall survival when compared with patients treated with chemotherapy. In addition, treatment with IT altered the dynamics but not the pattern of metastatic progression when compared with treatment with chemotherapy. Interestingly, patients receiving IT lived significantly longer after metastatic progression to lymph nodes, lungs and brain, but not after metastatic progression to the liver.

Conclusion: Our results confirm the efficacy of IT in a real-world setting. The altered dynamics of metastases supports studies suggesting a unique role of immune privilege in the liver tissue microenvironment that increases resistance to immunotherapy.

Introduction: Niraparib was approved for first-line (1L) maintenance (1LM) treatment of patients with advanced epithelial ovarian cancer (EOC) following the PRIMA/ENGOT-OV26/GOG-3012 (PRIMA) trial. PRIMA was restricted to patients at higher risk of progression (excluded stage III EOC with no visible residual disease [NVRD] after primary cytoreductive surgery [PCS]). This retrospective study evaluated the potential impact of excluding stage III EOC with NVRD from PRIMA by assessing real-world treatment outcomes following 1LM niraparib monotherapy in this patient population.

Methods: Data from a US-nationwide electronic health record-derived deidentified database comprised adult patients diagnosed with stage III/IV EOC who received 1L platinum-based chemotherapy and initiated niraparib 1LM monotherapy (01Jan2017-28Feb2023). Patients were classified as PRIMA-like (EOC with higher-risk prognostic factors for disease progression) or stage III disease with NVRD after PCS. Real-world time to next treatment (rwTTNT) and progression-free survival (rwPFS), assessed from the end date of 1L platinum-based chemotherapy, were measured via Kaplan-Meier methods.

Results: Among 453 patients who received niraparib 1LM (PRIMA-like cohort, n = 390; stage III NVRD cohort, n = 63), median follow-up from index was 14.9 (interquartile range [IQR], 7.3-25.1) and 18.4 (IQR, 9.3-29.1) months in the PRIMA-like and stage III NVRD cohorts, respectively. Median rwTTNT was significantly longer in the stage III NVRD cohort (22.5 [95% confidence interval (CI), 17.3-not reached] months) than in the PRIMA-like cohort (11.7 [95% CI, 10.8-12.9] months; P < 0.001). Median rwPFS in the stage III NVRD cohort (25.2 [95% CI, 12.6-not reached] months) was more than double that in the PRIMA-like cohort (10.1 [95% CI, 9.1-11.9] months; P < 0.001).

Conclusions: In the stage III NVRD cohort, rwTTNT and rwPFS were significantly longer than in the PRIMA-like cohort, consistent with clinical expectation. Results suggest niraparib clinical benefit may have been underestimated in PRIMA because of the exclusion of patients with stage III EOC with NVRD after PCS.

Chimeric antigen receptor (CAR) T-cell therapy is effective in the treatment of patients with diffuse large B cell lymphoma (DLBCL), even those with high-grade disease. However, it has a unique safety profile, including cytokine-release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), and robust management of these events are important to maximize benefits. The aim of this vodcast is to outline the management of a patient receiving CAR T-cell therapy for relapsed/refractory (r/r) DLBCL. In January 2005, the patient was diagnosed with atypical chronic lymphocytic leukemia (CLL) and treated with two cycles of fludarabine and cyclophosphamide before stopping due to skin toxicity. In 2007, the patient progressed and received alemtuzumab. In January 2018, the patient was diagnosed with DLBCL (nongerminal center, stage IV-A, bone marrow infiltration); a clonality analysis with the previous CLL provided a negative result. In March 2018, the patient received first-line treatment with rituximab-cyclophosphamide-doxorubicin-vincristine-prednisolone (R-CHOP)) for six cycles. At this point, a positron emission tomography (PET) scan showed complete remission. Unfortunately, in December 2018, they experienced a relapse and second-line therapy with rituximab, etoposide, cytarabine, cisplatin, and prednisone (R-ESHAP) was started. Following the second cycle of R-ESHAP in February 2019, the patient progressed, and third-line treatment was provided by rituximab plus ifosfamide, gemcitabine, vinorelbine, and prednisone (R-IGEV) for four cycles. The last cycle of R-IGEV was received in May 2019, but the patient progressed. In July 2019, the patient received a tisagenlecleucel infusion. The authors describe the effectiveness of the CAR T-cell therapy and how the adverse events (AEs) encountered, including CRS and ICANS, were managed. Results from real-world evidence studies of tisagenlecleucel in DLBCL are similar to those observed in the pivotal clinical trials. In conclusion, CAR T-cell therapy can be effective and achieve long-lasting, durable responses in patients with high-risk r/r DLBCL. However, long-term follow up is key to watch out for late AEs and potential lymphoma relapse.

Introduction: Myelofibrosis (MF) is often characterized by a multifactorial anemia determined, in part, by bone marrow (BM) fibrosis, extramedullary erythropoiesis and splenomegaly. Ruxolitinib (RUX) is the first-in-class janus kinase 2 (JAK2) inhibitor approved for treatment of MF, proved to reduce spleen volume and decrease symptom burden. The red cell distribution width (RDW) is the measure of erythrocyte volume variability (anisocytosis). RDW has been recognized as a marker of clinical and subclinical systemic inflammation, and its elevation has also been associated with poor outcome in a wide spectrum of benign disorders and in different types of neoplasms.

Methods: We retrospectively evaluated RDW in a single-center series of 200 consecutive patients with primary and secondary MF at RUX treatment initiation and examined any possible correlation with adverse MF features or drug-related anemia and any prognostic impact.

Results: We suggested 20.5% as the optimal cutoff point in RDW values at start of RUX to dichotomize patients in receiver operating characteristic (ROC) analysis for spleen response and for survival. Higher RDW values at RUX start were associated with clinical and laboratory features of an aggressive MF phenotype. Lower spleen response (p < 0.001) and greater odds of drug-related anemia at 3 (p = 0.006) and 6 months (p < 0.001) were also seen in patients with higher RDW. Both increased RDW (considered as a continuous variable) and RDW ≥ 20.5% were associated with shorter overall survival (OS) from RUX initiation in univariate and multivariate analysis: HR 1.25 (95% confidence interval [CI], 1.12-1.40) (p < 0.001) and HR 3.01 (95% CI 1.81-4.99) (p < 0.001), respectively. RDW ≥ 20.5% at RUX start seems to possibly improve patients' sub-stratification along with anemia and conventional prognostic scoring systems.

Conclusions: RDW at RUX start might represent a good indirect measure of MF features and might have prognostic significance for RUX-treated patients affected by MF, aiding in the rapid detection of patients with poor prognosis.