Summary of 'The current status and future perspectives on the management of stage III NSCLC: a focus on unresectable cancer treatment paradigms'.
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ABSTRACT:
SUBMITTER: Paz-Ares L
PROVIDER: S-EPMC7735210 | biostudies-literature | 2020 Dec
REPOSITORIES: biostudies-literature
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Summary of 'The current status and future perspectives on the management of stage III NSCLC: a focus on unresectable cancer treatment paradigms'.
British journal of cancer 20201201 Suppl 1
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Project description: Not available
| S-EPMC7735209 | biostudies-literature
Project description:BackgroundPatients with unresectable stage III non-small-cell lung cancer constitute a heterogeneous group in which the available treatments may range from radical therapies with radio-chemotherapy to supportive treatments depending on the extent of the disease and comorbidities present. For years the standard treatment based on the combination of chemotherapy and radiotherapy (RT) has remained unchanged and survival outcomes have been poor.AimRecent advances in molecular biology and RT technology have resulted in improved survival. This article reviews the treatments that constitute current standard treatment in unresectable advanced lung cancer and the situations and indications for the management of patients who are not candidates for radical therapy.Relevance for patientsAlthough unresectable lung cancer does not have a good prognosis, new drugs and new technologies in radiation oncology can offer treatment options adapted to the patient's clinical situation, ranging from therapies administered with radical intent to others aimed mainly at improving the patient's quality of life, which, judiciously chosen, will provide optimal management of the patient.
| S-EPMC7837736 | biostudies-literature
Project description:Consolidation anti-programmed death-ligand 1 has become a new standard of care in unresectable stage III non-small cell lung cancer (NSCLC) following chemo-radiotherapy (CTRT), based on the results of two phase III trials. Advances remain however needed, in particular to reduce the risk of distant relapse and for treatment personalization. Newer strategies are currently being tested, including consolidation with dual immune checkpoint inhibitors (ICIs), concurrent chemo-radioimmunotherapy and (chemo)-immunotherapy induction before CTRT. One randomized phase II reported better outcomes with a double ICI consolidation as compared with durvalumab alone. Three nonrandomized phase II trials also suggested that concurrent ICI-CTRT was feasible. Within this review, we summarize the current evidence, highlight ongoing trials and discuss challenges that will ideally lead to a cure for more patients with unresectable stage III NSCLC.
| S-EPMC9340398 | biostudies-literature
Project description:IntroductionIn the placebo-controlled, phase 3 PACIFIC trial, durvalumab significantly prolonged progression-free survival (PFS) (p < 0.0001) and overall survival (OS) (p = 0.00251) in patients with unresectable stage III NSCLC and no progression after platinum-based concurrent chemoradiotherapy (cCRT). Pneumonitis or radiation pneumonitis (PRP) was common in both arms. We report exploratory analyses evaluating the association of symptomatic (grade ≥2) PRP (G2+PRP) with baseline factors and clinical outcomes.MethodsPatients with WHO performance status of 0 or 1 were randomized (2:1) to 12 months of durvalumab or placebo, 1 to 42 days after cCRT. Associations between baseline factors and on-study G2+PRP in durvalumab-treated patients were investigated using univariate and multivariate logistic regression. PFS and OS were analyzed using Cox proportional hazards models adjusted for time-dependent G2+PRP plus covariates for randomization stratification factors without and with additional baseline factors.ResultsOn-study G2+PRP occurred in 94 of 475 (19.8%) and 33 of 234 patients (14.1%) on durvalumab and placebo, respectively (median follow-up, 25.2 mo); grade greater than or equal to 3 PRP was uncommon (4.6% and 4.7%, respectively). Time to onset and resolution of G2+PRP was similar with durvalumab and placebo. Univariate and multivariate analyses identified patients treated in Asia, those with stage IIIA disease, those with performance status of 1, and those who had not received induction chemotherapy as having a higher risk of G2+PRP. PFS and OS benefit favoring durvalumab versus placebo was maintained regardless of time-dependent G2+PRP.ConclusionsFactors associated with higher risk of G2+PRP with durvalumab after cCRT were identified. Clinical benefit was maintained regardless of on-study G2+PRP, suggesting the risk of this event should not deter the use of durvalumab in eligible patients with unresectable stage III NSCLC.
| S-EPMC10918565 | biostudies-literature
Project description:Microglia are the tissue macrophages of the central nervous system (CNS) and the first to respond to CNS dysfunction and disease. Gene expression profiling of microglia during development, under homeostatic conditions and in the diseased CNS provided insight in microglia functions and changes thereof. Single cell sequencing studies further contributed to our understanding of microglia heterogeneity in relation to age, sex and CNS disease. Recently, single nucleus gene expression profiling was performed on (frozen) CNS tissue. Transcriptomic profiling of CNS tissues by (single) nucleus RNA-sequencing has the advantage that it can be applied to archived and well stratified frozen specimens. Here, we give an overview of the significant advances recently made in microglia transcriptional profiling. In addition, we present matched cellular and nuclear microglia RNA-seq datasets we generated from mouse and human CNS tissue to compare cellular versus nuclear transcriptomes from fresh and frozen samples. We demonstrate that microglia can be similarly profiled with cell and nucleus profiling, and importantly also with nuclei isolated from frozen tissue. Nuclear microglia transcriptomes are a reliable proxy for cellular transcriptomes. Interestingly, lipopolysaccharide- (LPS)-induced changes in gene expression were even more pronounced in the nuclear transcriptome. In addition, heterogeneity in microglia observed in fresh samples is similarly detected in frozen nuclei of the same donor. Together, these results show that microglia nuclear RNAs obtained from frozen CNS tissue are a reliable proxy for microglia gene expression and cellular heterogeneity and may prove an effective strategy to study of the role of microglia in neuropathology.
2019-08-10 | GSE135618 | GEO
Project description:Colon cancer continues to be one of the leading causes of mortality and morbidity throughout the world despite the availability of reliable screening tools and effective therapies. The majority of patients with colon cancer are diagnosed at an early stage (stages I to III), which provides an opportunity for cure. The current treatment paradigm of early stage colon cancer consists of surgery followed by adjuvant chemotherapy in a select group of patients, which is directed at the eradication of minimal residual disease to achieve a cure. Surgery alone is curative for the vast majority of colon cancer patients. Currently, surgery and adjuvant chemotherapy can achieve long term survival in about two-thirds of colon cancer patients with nodal involvement. Adjuvant chemotherapy is recommended for all patients with stage III colon cancer, while the benefit in stage II patients is not unequivocally established despite several large clinical trials. Contemporary research in early stage colon cancer is focused on minimally invasive surgical techniques, strategies to limit treatment-related toxicities, precise patient selection for adjuvant therapy, utilization of molecular and clinicopathologic information to personalize therapy and exploration of new therapies exploiting the evolving knowledge of tumor biology. In this review, we will discuss the current standard treatment, evolving treatment paradigms, and the emerging biomarkers, that will likely help improve patient selection and personalization of therapy leading to superior outcomes.
| S-EPMC7443846 | biostudies-literature
Project description:Bone sarcomas (BS) are rare mesenchymal tumors usually located in the extremities and pelvis. While surgical resection is the cornerstone of curative treatment, some locally advanced tumors are deemed unresectable and hence not suitable for curative intent. This is often true for pelvic sarcoma due to anatomic complexity and proximity to vital structures, making treatment options for these tumors generally limited and not unanimous, with decisions being made on an individual basis after multidisciplinary discussion. Several studies have been published in recent years focusing on innovative treatment options for patients with locally advanced sarcoma not amenable to local surgery. The present article reviews the evidence regarding the treatment of patients with locally advanced and unresectable pelvic BS, with the goal of providing an overview of treatment options for the main BS histologic subtypes involving this anatomic area and exploring future therapeutic perspectives. The management of unresectable localized pelvic BS represents a major challenge and is hampered by the lack of comprehensive and standardized guidelines. As such, the optimal treatment needs to be individually tailored, weighing a panoply of patient- and tumor-related factors. Despite the bright prospects raised by novel therapeutic approaches, the role of each treatment option in the therapeutic armamentarium of these patients requires solid clinical evidence before becoming fully established.
| S-EPMC9139258 | biostudies-literature
Project description: Not available
| S-EPMC10080321 | biostudies-literature
Project description:BackgroundCurrently, the value of induction chemoimmunotherapy before chemoradiotherapy (CRT) in unresectable stage III non-small cell lung cancer (NSCLC) has not been explored. This study was designed to explore the efficacy and safety of induction chemoimmunotherapy in patients with unresectable stage III NSCLC.MethodsUnresectable stage III NSCLC patients who received CRT with or without induction chemoimmunotherapy between August 2014 and December 2021 were retrospectively enrolled. Progression-free survival (PFS) and overall survival (OS) were assessed from the initiation of treatment and estimated by the Kaplan-Meier method. The potential factors affecting PFS and OS were analyzed by univariate and multivariate Cox regression models. One-to-one propensity score matching (PSM) was used to further minimize confounding.ResultsA total of 279 consecutive patients were enrolled, with 53 (19.0%) receiving induction chemoimmunotherapy followed by CRT (I-CRT group), and the remaining 226 (81.0%) receiving CRT alone (CRT group). After PSM, the median PFS was 24.8 months in the I-CRT group vs. 13.3 months in the CRT group (P=0.035). The median OS was not reached (NR) vs. 36.6 months ((P=0.142). The incidence of treatment-related adverse events (TRAEs) was similar in both groups, except that the incidence of hematological toxicity was higher in the I-CRT group (77.1% vs. 58.3%, P=0.049). Compared to induction chemotherapy, induction chemoimmunotherapy demonstrated a superior objective response rate (60.4% vs. 22.2%, P<0.001) and further prolonged PFS (median NR vs. 13.2 months, P=0.009) and OS (median NR vs. 25.9 months, P=0.106) without increasing the incidence of TRAEs in patients receiving concurrent chemoradiotherapy.ConclusionInduction chemoimmunotherapy is safe and may improve outcomes of CRT in patients with unresectable stage III NSCLC. Moreover, induction chemoimmunotherapy may further improve treatment response and survival outcomes compared to induction chemotherapy before cCRT.
| S-EPMC10711043 | biostudies-literature
Project description:Platinum-based chemotherapy is commonly used as the standard first-line treatment for unresectable malignant pleural mesothelioma (MPM). However, in recent times, immune-checkpoint inhibitors (ICIs) have led to a paradigm shift. Herein, we review relevant literature and ongoing trials of ICIs used as both first-line and salvage therapies. Specifically, in the Japanese single-arm, phase II trial, the MERIT trial, nivolumab, an antiprogrammed cell death 1 (PD-1) antibody showed favorable efficacy when used as a salvage therapy. Currently, multiple ICI monotherapy or combination therapy trials have been conducted, which could provide further evidence. Among available ICIs, the anti-PD-1 antibody is promising for unresectable MPM, despite the limited efficacy of anti-CTLA4 monotherapy. Ongoing studies will further confirm the potential efficacy of ICIs for MPM, as observed across other malignancies. It is also crucial to identify any clinically useful predictive biomarkers that could reveal ICIs with maximal effects in MPM.
| S-EPMC7057421 | biostudies-literature