Oncology Research and Treatment最新文献

Introduction: Although different risk factors for oxaliplatin-associated chronic peripheral neuropathy have been identified and the predictive value of neuroinflammatory cytokines has often been emphasized, a clearly accepted predictive biomarker with economical, reproducible, and easily accessible properties has not yet been identified. In this study, we aimed to determine the relationship between serum uric level measured at the time of diagnosis and oxaliplatin-related peripheral neuropathy, based on literature information on the relationship between diabetic neuropathy and serum uric acid level.

Methods: In the study, 166 patients with colon adenocarcinoma, who were clinically thought to have grade 1-2 neuropathy in their follow-up after completing the adjuvant mFOLFOX6 regimen without dose reduction for 6 months, were grouped as those with or without peripheral neuropathy according to electromyography results. Demographic, clinical, laboratory and treatment-related characteristics, as well as serum uric acid levels at diagnosis, were determined as study variables and the groups were compared. Based on the presence of peripheral neuropathy, an ROC curve was drawn for serum uric acid level, cutoff was determined, and multivariable logistic (binary) regression analysis was also applied to determine independent risk factors that may affect peripheral neuropathy. If the p value was below 0.05, it was considered statistically significant.

Results: It was determined that 29% of the patients (n = 48) had peripheral neuropathy proven by electromyography. It was determined that the majority of patients with peripheral neuropathy were women, above 65 years of age, low body mass index, high body surface area, and smokers. While the serum uric acid level of all patients was 5.1 mg/dL (1.9-9.1), it was significantly higher in patients with peripheral neuropathy than in those without neuropathy (p = 0.0012). We found that ORPN may develop in patients with SUA levels higher than 5.96 mg/dL in men and 6.04 mg/dL in women at the time of diagnosis, and these cutoff values ​​had a sensitivity of 40% and a specificity of 95.40% in men, respectively, while the sensitivity in women was 84.6% and the specificity was 83.87%. In multivariable analysis, female gender, smoking, high body surface area, and high serum uric acid level were determined to be independent predictors for all patients.

Conclusion: Despite the limitations of the study, it was concluded that the possibility of developing oxaliplatin-induced peripheral neuropathy may be high in patients with high serum uric acid levels. This study needs to be repeated prospectively and evaluated in larger cohorts.

Background: Adoptive cellular therapy (ACT) is a promising treatment approach aiming at enhancing T-cell antitumor immune response. ACT includes tumor-infiltrating lymphocytes, chimeric antigen receptor (CAR) and T-cell receptor gene-modified T cells. Despite a milestone achievement with CAR-T cells in hematopoietic malignancies, ACT has shown modest clinical responses in refractory solid cancers and durable responses remain limited to a minor fraction of patients.

Summary: In this review, we highlight major advances, limitations and current developments of T-cell therapies for solid cancers. We discuss emerging promising strategies as next-generation ACT, exploring local delivery routes to maximize efficacy and improve safety, integrating predictive biomarkers to optimize selection of patients who most likely would benefit from ACT, using combination therapy to overcome the immunosuppressive tumor microenvironment, targeting multiple tumor antigen to avoid tumor antigen escape, selection of the most potent T-cell product to overcome T-cell dysfunction, and incorporating cutting-edge new technologies, such as gene-editing to further improve antitumor T-cell functions and reduce therapy-related toxicity.

Key messages: Advances made in ACT trials have move the field of immunotherapy for refractory solid cancers to a new stage, by constantly incorporating new strategies to develop next-generation therapies designed to enhance efficacy and improve safety and to allow a broaden access to a large numbers of patients.

Introduction: Despite decades of extensive research, treatment options for pancreatic adenocarcinoma (PAC) patients kept limited, and prognosis remains dismal. For patients with metastatic PAC (mPAC), palliative combination chemotherapy remains the mainstay of treatment. Current treatment standards for mPAC have evolved from 2010 onwards with the introduction of combination chemotherapy protocols, the development of new chemotherapeutic agents, and the establishment of treatment sequences. Within our cohort, we analyzed the impact of different treatment options and sequences over time for mPAC patients in a Swiss academic center in the pre-molecular era between 2010 and 2018.

Methods: This retrospective analysis included 97 patients who received palliative chemotherapy for mPAC between 2010 and 2018 at our institution. Outcome parameters, including median overall survival (mOS) and median progression-free survival (mPFS), were analyzed in the context of chemotherapy regimens and the number of treatment lines received. For comparative analyses, patients were separated into two groups, advancing to stage IV (metastatic) between 2010 and 2012, and between 2013 and 2018, respectively. Univariate analyses were performed via the log-rank test.

Results: For the entire cohort, mOS and first-line mPFS were 8.2 months (95% confidence interval [95% CI] 6.3-8.6 months) and 4.8 months (95% CI 3.4-5.8 months), respectively. When comparing between patients advancing to stage IV (metastatic) 2010-2012 and 2013-2018, the most frequent choice of systemic first-line therapy evolved from single-agent gemcitabine (GEM) toward the combination protocols FOLFIRINOX (FFX) and gemcitabine/nab-paclitaxel (GEM/nab-PTX). Moreover, the proportion of patients receiving further-line chemotherapies increased significantly between 2010-2012 and 2013-2018 (20 vs. 49% second-line treatment; p value [p] = 0.0035). Finally, a significant improvement in overall survival (OS) was observed for patients advancing to metastatic disease 2013-2018 compared to 2010-2012 (mOS 8.6 vs. 6.1 months; hazard ratio [HR] = 1.82; 95% CI 1.10-3.02, p = 0.0068). The use of combination regimens (FFX or GEM/nab-PTX) instead of GEM monotherapy as first-line systemic treatment was associated with a significantly improved OS (mOS 9.0 vs. 5.1 months; HR = 0.39; 95% CI 0.19-0.77, p = 0.0001) and first-line progression-free survival (PFS) (mPFS 5.0 vs. 4.7 months; HR = 0.57; 95% CI 0.32-1.03, p = 0.0213).

Conclusions: In summary, systemic treatment of mPAC intensified during the study period with the availability of new first-line combination chemotherapy options and more lines of therapy. In parallel, patient survival improved, suggesting a causal relationship between more effective chemotherapy and improved outcome. Combination chemotherapy is standard of care for mPAC, while the future impact of molecular profiling and precision on

Introduction: Integrative therapeutic approaches are able to improve psychophysiological outcomes in cancer patients. Whether additional beneficial effects can be achieved by combining aromatherapy to sound intervention is unclear.

Methods: Eighty cancer patients were randomized (1:1) to either a 20-min sound intervention ("sound only," classical music via headphones) or a sound intervention combined with aromatherapy ("aroma"). Cardiovascular parameters (measured with VascAssist2.0), visual analogue scales for emotional well-being, anxiety, stress, pain and sadness, and the State Trait Anxiety Inventory were assessed before and after intervention.

Results: Sound only led to a significant reduction in the heart rate, while a trend for a lower heart rate was observed in the aroma group. Both pulse wave velocity (p = 0.04) and vascular resistance (p = 0.04) were reduced by sound only. Psychophysiological outcomes were improved by both interventions with a more pronounced but not significantly different effect on pain reduction by aroma (aroma p < 0.001; sound only p = 0.002).

Conclusion: Both interventions were able to improve psychophysiological outcomes. In terms of cardiovascular parameters, a sound intervention alone achieved greater but not significantly different results compared to aroma, while the addition of aromatherapy yielded no substantial additional effects.

Introduction: The INGE-B trial (NCT02894398) aimed to confirm the efficacy and safety data from the PALOMA trials for patients treated first line (1L) with palbociclib (PAL) and letrozole or 1L and later line with PAL and fulvestrant. In addition, so far lacking evidence for efficacy and safety on the combination of PAL with anastrozole, exemestane (1L), or letrozole (later line) was investigated.

Methods: The prospective, multicenter, multicohort phase 2 trial INGE-B enrolled adult patients with locally advanced, inoperable, or metastatic HR+/HER2- breast cancer in Germany. The primary endpoint was the clinical benefit rate (CBR) in patients with measurable disease according to RECIST v1.1. Secondary endpoints were overall response rate, progression-free survival (PFS), overall survival (OS), safety, and quality of life. Data were analyzed with descriptive statistics.

Results: Between 2016 and 2018, 388 patients were enrolled at 64 German sites. Among patients with measurable disease treated with PAL in 1L (n = 157), the CBR was 63.7% (100/157). Among all patients treated with PAL 1L (n = 219), PFS was 20.1 months (95% CI 14.6-24.0), and OS was 40.9 months (95% CI 35.1-49.2). The most common grade 3/4 adverse event was neutropenia (33.4% n = 77). There were no treatment-related deaths.

Conclusion: The INGE-B trial demonstrated good efficacy and tolerability of PAL with letrozole (1L) or fulvestrant (first and later line) in accordance with the PALOMA trials. In addition, the so far lacking proof of efficacy and safety of PAL in combination with anastrozole or exemestane in 1L and with letrozole in later line was provided by INGE-B.

Introduction: The INGE-B trial (NCT02894398) aimed to confirm the efficacy and safety data from the PALOMA trials for patients treated first line (1L) with palbociclib (PAL) and letrozole or 1L and later line with PAL and fulvestrant. In addition, so far lacking evidence for efficacy and safety on the combination of PAL with anastrozole, exemestane (1L), or letrozole (later line) was investigated.

Methods: The prospective, multicenter, multicohort phase 2 trial INGE-B enrolled adult patients with locally advanced, inoperable, or metastatic HR+/HER2- breast cancer in Germany. The primary endpoint was the clinical benefit rate (CBR) in patients with measurable disease according to RECIST v1.1. Secondary endpoints were overall response rate, progression-free survival (PFS), overall survival (OS), safety, and quality of life. Data were analyzed with descriptive statistics.

Results: Between 2016 and 2018, 388 patients were enrolled at 64 German sites. Among patients with measurable disease treated with PAL in 1L (n = 157), the CBR was 63.7% (100/157). Among all patients treated with PAL 1L (n = 219), PFS was 20.1 months (95% CI 14.6-24.0), and OS was 40.9 months (95%

Background: Cell-free DNA (cfDNA) is a fragmented DNA that is released into the blood through necrosis, apoptosis, phagocytosis, or active secretion. cfDNA includes a subclass called circulating tumor DNA (ctDNA) released from cancer cells and constitutes a varied proportion of the total cfDNA. Both cfDNA and ctDNA hold significant potential as diagnostic biomarkers in gastrointestinal cancers.

Summary: cfDNA and ctDNA are promising diagnostic biomarkers for gastrointestinal cancers with varied diagnostic values in different types of cancers. cfDNA offers higher sensitivity that makes it more suitable for screening methods and constant monitoring, particularly in integration with conventional biomarkers or in a multimarker model. On the contrary, ctDNA gives a real-time picture of tumor genetics and is more suitable for definitive diagnosis due to its specificity for tumor-associated alterations. Different types of samples and methods of detection can influence sensitivity, and the amount of cfDNA is higher in serum but plasma is used for cfDNA analysis because it contains less cellular contamination. In summary, cfDNA is more sensitive than ctDNA, although they have comparable or slightly lower specificity.

Key message: Further studies are needed to create common guidelines, minimize the cost of analysis, and perform extensive clinical trials to demonstrate the utility of circulating cfDNA and ctDNA in the vast majority of gastrointestinal cancer stages. Therefore, with the advancement in these technologies, cfDNA and ctDNA will be highly beneficial and evolve cancer diagnostics and therapy.

Introduction: The impact of being diagnosed with a life-threatening illness may influence preferences to participate in treatment decisions. The objective of this analysis was to identify factors that are associated with sarcoma patients wanting to take a more active or passive role.

Methods: Data were obtained as part of a nationwide multicenter study (PROSa) aiming to investigate the structure and quality of medical care of sarcoma patients in Germany and their determinants. The study was conducted between 2017 and 2020 in 39 study centers. For the present analysis, cross-sectional data of adult patients with sarcoma of any entity were analyzed. Control preference was measured with the control preference scale (CPS). Preferences were divided in patient-led, shared, or physician-led-decision-making. Associated factors were analyzed exploratively using multivariable multinominal logistic regression models. We included socio-economical and medical variables with stepwise backward variable selection.

Results: We included 1,081 patients (48.6% female). 402 patients (37.2%) preferred to be in control about treatment decisions, while 400 patients (37.0%) favored shared responsibility. 25.8% (n = 279) wished to rather leave the control to the treating physician. Older patients were more likely to prefer shared decision-making than younger patients aged 18-40 years (age group: >75 years: odds ratio [OR] 0.53, 95% confidence interval [95% CI] 0.28; 0.99). Patients with a metastatic tumor desired shared decision making compared to those without metastases (metastasis: OR 1.61, 95% CI 1.09; 2.38). When comparing the patients who preferred physician-led decision making with those who favored to be in control, older patients also preferred leaving the control to the physician and were less inclined to make the decisions by themselves: (18 to >40 years vs. >75 years: OR 0.28, 95% CI 0.15; 0.55). With secondary school (8/9 years) as reference, patients holding a high school degree were more likely to prefer patient-led decision-making over physician-led decision making (OR 2.00, 95% CI 1.26; 3.09). Patients with sarcoma of the abdomen/retroperitoneum were more predisposed to taking control in treatment decisions compared to those with sarcoma of the back/spine or lower limb (back/spine: OR 0.18, 95% CI 0.06; 0.54, lower limb: OR 0.56, 95% CI 0.37; 0.85). With an income of EUR 1,250/month as reference, patients with a higher income were more likely to take control (>EUR 2,750/month: OR 1.7, 95% CI 1.0; 3.1).

Conclusion: The findings of our study demonstrate that patients with metastatic disease are more likely to seek a joint decision, while those of higher age and lower education level are less likely to actively participate in treatment decisions. The results suggest that the impact of advanced illness may influence preferences to participate.

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