Therapeutic Advances in Medical Oncology最新文献

Background: Relationships between cancer onset, progression, and inflammation have been reported; yet, the significance of inflammatory markers before and after treatment with nanoliposomal irinotecan and fluorouracil with folic acid (NFF) is unclear.

Objectives: We aimed to (1) investigate whether worsening inflammation is associated with disease progression and whether it can be used as a biomarker by comparing inflammatory markers before and after treatment with NFF and (2) verify which is a superior biomarker.

Design: This was a preplanned analysis of a retrospective cohort of the NAPOLEON-2 study, a multicenter observational study. Patients from 20 institutions were enrolled. Those with unresectable pancreatic cancer who received NFF as a second-line or later-line treatment between June 1, 2020, and May 31, 2021, were included.

Methods: The primary endpoint was overall survival, and the main secondary endpoint was progression-free survival. The following inflammatory markers were assessed: neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, Prognostic Nutrition Index (PNI), C-reactive protein/albumin ratio (CAR), Glasgow prognostic score (GPS), Prognostic Index (PI), and Komori score.

Results: A total of 161 patients were enrolled. The CAR, NLR, GPS (1 vs 2), PI (1 vs 2), PNI, and Komori score were useful pre-NFF biomarkers (hazard ratios (HRs): 2.59, 2.28, 2.76/3.35, 2.16/18.89, 2.13, and 3.39, respectively). The CAR, NLR, GPS (compared with a score of 1/2), and PI (compared with a score of 1/2) were useful post-NFF biomarkers (HRs: 2.63, 1.88, 2.54/3.09, 2.30/5.39, respectively). In terms of the receiver operating characteristic curve and Akaike information criterion, the CAR, GPS, and PI showed favorable trends, and overall, CAR was a useful biomarker.

Conclusion: Inflammatory markers can be used as biomarkers both before and after NFF treatment, and CAR may be useful. We hope these findings will contribute to the selection of appropriate treatment options.

Background: Pancreatic cancer, a frequently fatal disease with severe symptoms, can require high-intensity end-of-life (HI-EOL) care, posing challenges to patients' well-being. The examination of HI-EOL care to develop tailored interventions in the management of pancreatic cancer is a critical, yet underexplored area.

Objectives: The objective of this study was to assess the factors that influence the intensity of end-of-life (EOL) care in France.

Design: A retrospective study of patients registered in the French Nationwide database who were hospitalized in France for pancreatic adenocarcinoma from January 1, 2014 to December 31, 2019, and subsequently died during the follow-up period.

Methods: Data on patient demographics, clinical characteristics, hospitalization details, and palliative care were collected. The primary outcome measure was the evaluation of HI-EOL care, defined by indicators such as death in an intensive care unit (ICU), multiple hospitalizations, and chemotherapy administration within the last 30 days of life. Secondary outcomes included indicators of most-intensive EOL (MI-EOL) care and invasive procedures (IP). Univariate and multivariate logistic regression analyses were conducted to identify factors associated with each outcome measure.

Results: A total of 42,696 patients who died from pancreatic adenocarcinoma were included. Among them, 41.1% experienced HI-EOL, with the most common indicators being multiple hospitalizations and death in an ICU, emergency room, or acute care unit. A smaller proportion (2.8%) received MI-EOL care, while 28.1% underwent IPs in the last 30 days of life. The multivariate analysis revealed that male gender and follow-up in non-cancer specialized care facilities were associated with a higher risk of HI-EOL. Conversely, palliative care involvement and older age at death were identified as protective factors. Male gender, older age at death, and palliative care involvement were associated with lower rates of MI-EOL care and IPs.

Conclusion: These results underscore the importance of palliative care integration and individualized approaches in improving the EOL quality of care and patient outcomes for individuals with advanced pancreatic cancer.

Background: Radiation-associated angiosarcoma of the breast (RAASB) is a rare secondary angiosarcoma that typically develops subsequent to breast-conserving therapy for breast cancer. The parameters of the resection width and depth remain the subject of considerable controversy. More recent data indicate that radical resection of the complete radiation field at the thorax is associated with improved local control and survival.

Objectives: The present study investigates the radical resection technique of the entire radiation field and subsequent defect coverage in RAASB, as well as the medium-term follow-up.

Design: Monocentric, retrospective, and non-comparative study.

Methods: From January 2017 to January 2024 a total of 10 patients with RAASB were treated at our hospital. The radical resection technique was employed in the treatment of all patients, encompassing the entire radiation field. Three patients received local flaps (two of whom received vertical and transversal rectus abdominis muscle flaps and one received a local random pattern flap), while the remaining seven were treated with split-thickness skin grafts for defect coverage.

Results: The median age at initial diagnosis of breast cancer was 59.3 ± 9.41 years, while that of RAASB was 66.2 ± 8.32 years. The median latency period between the start of irradiation of the chest wall and the initial presentation of RAASB was 6.5 ± 3.08 years. The cumulative median total radiation dose was 57.23 ± 8.34 Gray (cumulative Gray) in 9 of the 10 patients. The overall survival (OS) was 80% in the cohort, with a median follow-up period of 40.0 ± 27.96 months. Three patients exhibited local relapses following radical resection, with two of these patients ultimately succumbing to their condition.

Conclusion: Patients with RAASB may benefit from a radical resection of the entire radiation field. Despite the relatively mutilating nature of the procedure, the radical resection technique may have the potential to reduce the rate of local recurrence and prolong OS.

Background: Over the past few decades, the gonadotropin-releasing hormone agonist goserelin has been evaluated in ovarian function suppression (OFS) with adjuvant endocrine therapy and ovarian function preservation (OFP) during chemotherapy.

Objective: The goal of this systematic literature review was to assess the efficacy of goserelin in OFS and OFP in combination with endocrine therapies and chemotherapy, respectively, in pre- and perimenopausal women with early-stage breast cancer.

Design: This study is a systematic review.

Data sources and methods: The literature search was conducted using PubMed. Prospective clinical studies evaluating the efficacy of goserelin in OFS or OFP in pre- or perimenopausal breast cancer were identified by four reviewers working in teams of two.

Results: Twenty-nine studies were included in this systematic review. The addition of goserelin as OFS to adjuvant endocrine therapy generally resulted in significant benefits in disease-free survival. Studies have shown better OFP results among women 40 years or younger compared with older patients. Chemotherapy in association with goserelin for OFP resulted in a higher recovery rate of menses within 6-24 months, a shorter time for menstrual recovery, and significantly higher pregnancy rates when compared with cytotoxic therapy without goserelin. Hormonal recovery with higher anti-Müllerian hormone and estradiol levels, and lower follicle-stimulating hormone and luteinizing hormone levels occurred more frequently among women who received goserelin during chemotherapy as compared with those receiving cytotoxic therapy alone. The benefits of goserelin in OFP were more substantial among women 40 years or younger than in older patients.

Conclusion: The findings of this systematic review highlight the benefits of adding goserelin to endocrine therapies for OFS and chemotherapy for OFP in early-stage breast cancer. Additionally, scientific data supporting OFS (including goserelin) in combination with newer agents such as cyclin-dependent kinase 4 and 6 inhibitors and bone-modifying agents are emerging.

Background: Patients with unresectable upper gastrointestinal (UGI) cancers have limited treatment options and poor prognosis. Although phase I trials provide access to novel therapies, their benefits in this population are unclear.

Objectives: We aimed to assess efficacy and survival outcomes of patients with refractory UGI cancers within phase I trials.

Design: We conducted a retrospective pooled analysis of phase I trials enrolling patients with advanced UGI cancers who received at least one dose of the study drug at SCRI UK between 2011 and 2023.

Methods: Efficacy and survival outcomes, including objective response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR), duration of response, progression-free survival (PFS) and overall survival (OS), were assessed. Analyses were conducted for the entire cohort and stratified by trial agent class, molecularly matched therapy allocation and receipt of the recommended phase II dose (RP2D). Patients participating in multiple trials were analysed separately for each study.

Results: From 1796 screened patients, 124 with UGI cancers were included in 37 phase I trials. Most were male (75%), with liver or peritoneal metastases (73%), treated with a median of 2 prior therapy lines. Of these, 60% received immunotherapy, 30% small molecules and 10% antibody-drug conjugates. Molecularly matched therapy was given to 22% and 86% received treatment at RP2D. In response-evaluable patients, ORR was 15%, CBR 40%, DCR 86% and median OS was 9.7 months. Treatment at RP2D was significantly associated with higher CBR (odds ratio 4.75, p = 0.04) and prolonged PFS (p = 0.04). Depth of response and treatment at RP2D were independent prognostic factors.

Conclusions: Participation in phase I trials offers benefits in refractory upper gastrointestinal cancers with compelling results in late-line settings and potential early access to new therapies.

Breast cancer (BC) is the most common malignancy among women. Among 5%-10% of diagnoses are correlated with hereditary cancer syndromes, while the remaining cases are sporadic and linked to multiple factors. When a pathogenetic variant in one of the genes commonly associated with BC is detected, the patient is referred to a tailored surveillance program; otherwise, the standard follow-up guidelines are applied. We present a unique case of BC diagnosed in two monozygotic twins at the same age apparently unrelated to a hereditary syndrome known to date. Notably, despite comparable clinical-pathological features, the two neoplasms behaved differently to neoadjuvant chemo-immunotherapy, showing different outcomes and toxicities. Very little is known about the predictive mechanisms of response and toxicity to immunotherapy and this clinical case might be a starting point for further investigations.

Background: The clinical impact of hypomagnesemia induced by necitumumab plus gemcitabine and cisplatin (GCN) as a second-line or later therapy is unclear.

Objective: We aimed to evaluate the clinical characteristics and survival impact of hypomagnesemia induced by this therapy.

Design: This was a sub-analysis of the retrospective multicenter NINJA study.

Methods: Among the 93 patients enrolled in the NINJA study, this subanalysis included 75 patients with baseline serum magnesium concentrations.

Results: The incidence of grade ⩾2 hypomagnesemia was 18.0% in the patients with normal baseline serum magnesium concentrations and 42.8% in those with low concentrations (p = 0.073). The discontinuation rates of GCN treatment owing to hypomagnesemia in each group were 0% and 7.1%, respectively (p = 0.187). The number of necitumumab doses and severity of hypomagnesemia were positively correlated (r = 0.389, p < 0.001). Patients who developed hypomagnesemia in fewer than 21 days after the first dose of GCN (n = 12) had significantly poorer progression-free survival (PFS) than those without the condition (n = 63; median: 4.1 vs 4.4 months, p = 0.048). A similar trend was observed for OS (median: 9.7 vs 15.7 months, p = 0.062). These results were maintained after multivariate analyses (PFS: hazard ratio (HR) 2.46, p = 0.014; OS: HR 2.78, p = 0.021).

Conclusion: GCN as a second-line or later therapy may be tolerable regardless of the patient's baseline serum magnesium concentration. On the other hand, early serum magnesium reduction with this therapy is associated with a poor prognosis. However, caution should be needed because our results lacked sufficient information for confounding variables other than those analyzed here that may influence the correlation between hypomagnesemia and survival.

Background: Neoadjuvant chemoradiotherapy (NCRT) combined with surgery is the standard treatment option for patients with locally advanced esophageal squamous cell carcinoma (ESCC). However, whether adjuvant chemotherapy (AC) administered postoperatively has a survival benefit remains inconclusive.

Objectives: To investigate whether AC is necessary after NCRT and esophagectomy and determine which patients might benefit from it.

Design: A retrospective study.

Methods: This retrospective study examined patients with ESCC treated with NCRT followed by radical esophagectomy at three hospitals between March 2016 and December 2022. Patients were assigned into the adjuvant and non-adjuvant therapy groups based on whether they received postoperative AC, allowing the comparison of disease-free survival (DFS) and overall survival (OS) between the two groups. In addition, based on whether postoperative pathology indicated pathological complete response (pCR), patients were classified into the pCR and non-pCR populations, with DFS and OS separately analyzed for each subgroup.

Results: Overall, 218 eligible patients were enrolled. No significant advantage was found in DFS (p = 0.540) and OS (p = 0.058) between the adjuvant and non-adjuvant therapy groups. In the non-pCR population, the adjuvant therapy groups had a significant advantage in DFS (p = 0.046) and OS (p = 0.011) compared to the non-adjuvant therapy group. However, in the pCR population, no significant advantage was found in DFS (p = 0.490) and OS (p = 0.110) analyses between the adjuvant and non-adjuvant therapy groups.

Conclusion: In the real world, patients with ESCC who underwent NCRT combined with radical esophagectomy and whose postoperative pathology was pCR did not benefit from AC. However, AC significantly improved DFS and OS in patients whose postoperative pathology did not reach pCR.

Background: Immune checkpoint inhibitors (ICIs) have become the mainstay treatment of metastatic kidney cancer, demonstrating enhanced outcomes and durable responses in select patient subgroups. However, identifying reliable prognostic biomarkers for treatment outcomes remains challenging.

Objectives: This study aimed to assess the correlation between baseline inflammatory markers and overall survival (OS), progression-free survival (PFS), and clinical benefit (CB) in metastatic kidney cancer patients receiving ICIs. CB was defined as patients achieving stable disease, partial response, or complete response.

Design: Retrospective, single-center study.

Methods: A retrospective analysis was conducted on 401 adult patients with advanced kidney cancer treated with ICIs at Emory Winship Cancer Institute between 2018 and 2023. Modified Glasgow Prognostic Score (mGPS), neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), platelet-to-lymphocyte (PLR), and neutrophil-to-eosinophil ratios (NER) were collected from baseline blood samples.

Results: Among 401 patients (median age, 66; 71% male; 21% Black/African American), median follow-up was 43.0 months (95% CI, 36.6-51.4). Patients with mGPS scores of 0 had longer OS than those with a score of 1 (hazard ratio (HR), 0.38; 95% CI, 0.23-0.62; p < 0.001) and 2 (HR, 0.37; 95% CI, 0.20-0.67; p = 0.001), and longer PFS compared to patients with mGPS scores of 1 (HR, 0.66; 95% CI, 0.44-0.98; p = 0.039) and 2 (HR, 0.44; 95% CI, 0.29-0.67; p < 0.001). Low baseline NLR was associated with longer PFS (HR, 0.73; 95% CI, 0.54-0.97; p = 0.032). Low baseline MLR correlated with improved OS (HR, 0.60; 95% CI, 0.44-0.83; p = 0.002) and PFS (HR, 0.73; 95% CI, 0.55-0.97; p = 0.031). Similarly, low baseline PLR was associated with higher CB likelihood (odds ratio (OR), 2.20; 95% CI, 1.31-3.69; p = 0.003), and low baseline NER was linked to improved OS (HR, 0.63; 95% CI, 0.46-0.87; p = 0.004), PFS (HR, 0.67; 95% CI, 0.51-0.88; p = 0.003), and higher CB (OR, 2.04; 95% CI, 1.20-3.46; p = 0.008).

Conclusion: Lower levels of systemic inflammatory markers are associated with more favorable clinical outcomes with ICI treatment. Prospective studies are needed for further validation.

Background: The evidence base for the management of oligoprogression in metastatic melanoma (MM) is limited. To our knowledge, this study presents the first analysis of the local benefit (LB) of radiotherapy combined with hyperthermia during systemic treatment in this diagnosis.

Methods: Patients with oligoprogressive MM who were treated with radiotherapy (RTH) combined with hyperthermia (HT) at a melanoma center between 2019 and 2023 were evaluated. Oligoprogression was defined as up to five progressive metastases. Inclusion criteria was the availability of dimensions assessment of the lesion subjected to RTH before and after treatment, patients without follow-up imaging after radiotherapy were excluded. The benefit of RTH + HT was evaluated in terms of local control (LC) rates and LB rates. LC was defined as the percentage of patients who met the Response Evaluation Criteria In Solid Tumors (RECIST 1.1) criteria for stable disease (SD), partial response (PR), and complete response (CR). LB was defined as the proportion of patients who met the PR and CR criteria. In addition, overall survival (OS) rates were estimated. The association between BRAF status, age, concomitant systemic treatment, radiation total dose, and biologically effective dose and LC was estimated. Data regarding adverse effects associated with RTH + HT were compiled. Survival analyses were performed using the Kaplan-Meier estimator and log-rank tests and were used to compare between groups.

Results: In total, 101 patients were included in the study, the median follow-up was 15.3 months (14-18 months). There were 56.4% BRAF(-) and 43.6% BRAF(+) patients. Most patients (71.3%) were irradiated during immunotherapy, 10.9% received concomitant BRAF and MEK inhibitors, and 3.9% had chemotherapy. LC and LB medians were not reached at the time of analysis. The 1- and 2-year LC rates were 93.5% (95% confidence interval (CI): 88.1%-99.3%) and 88.3% (95% CI: 79.9%-97.6%), respectively. The 1- and 2-year LB rates were 87.5% (95% CI: 80.5%-95.2%) and 78.1% (95% CI: 67.9%-89.9%), respectively. The mean reduction in irradiated tumor size across the entire cohort was 72%. The mOS from radiotherapy was not achieved at the time of our analysis, accordingly 1- and 2-year OS rates were 100% and 95% (95% CI: 90.4%-99.9%). None of the evaluated factors influenced LC among patients.

Conclusion: Hyperthermia with radiotherapy is an effective treatment for patients with oligoprogressive melanoma. This approach has resulted in excellent LC.