Adjuvant chemotherapy for locally advanced non-small cell lung cancer: still state of the art or an outdated therapy?
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ABSTRACT:
SUBMITTER: Schlachtenberger G
PROVIDER: S-EPMC9989812 | biostudies-literature | 2023 Feb
REPOSITORIES: biostudies-literature
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Adjuvant chemotherapy for locally advanced non-small cell lung cancer: still state of the art or an outdated therapy?
Schlachtenberger Georg G Hekmat Khosro K Wahlers Thorsten T Heldwein Matthias B MB
Translational lung cancer research 20230115 2
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Project description:Adjuvant chemotherapy (AC) plays now a significant role in the treatment of resected non-small cell lung cancer (NSCLC) patients and has become standard in clinical practice. It took more than two decades of clinical research to show its value, but it is has been well established that its benefit translates into a 4-5% absolute increase in 5-year survival according to published meta-analysis. This improvement is obtained with two-drug, Cisplatin-based regimens (multiples choices are acceptable but vinorelbine is the drug with more reported evidence) and usually four courses are recommended. Survival increase is restricted to cases in which there is involvement of lymph nodes (both N1 and N2 levels). For N0 cases AC might be considered, with a lower level of evidence, for tumors larger than 4 cm in diameter. At the present time, molecular predictive factors and gene signatures are investigational. Patient selection is of paramount importance. Proper recovery from surgery and the absence of major comorbidities are essential features. Toxicity is significant, but manageable and transient. Neutropenia is the most relevant side effect due to the risk of febrile neutropenia. The role of timing of administration, adjuvant radiotherapy (RT) and of newer drugs under evaluation is also reviewed.
| S-EPMC4384209 | biostudies-literature
Project description:Lung cancer is the second most common and the deadliest type of cancer worldwide. Clinically, non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer; approximately one-third of affected patients have locally advanced NSCLC (LA-NSCLC, stage III NSCLC) at diagnosis. Because of its heterogeneity, LA-NSCLC often requires multidisciplinary assessment. Moreover, the prognosis of affected patients is much below satisfaction, and the efficacy of traditional therapeutic strategies has reached a plateau. With the emergence of targeted therapies and immunotherapies, as well as the continuous development of novel radiotherapies, we have entered an era of novel treatment paradigm for LA-NSCLC. Here, we reviewed the landscape of relevant therapeutic modalities, including adjuvant, neoadjuvant, and perioperative targeted and immune strategies in patients with resectable LA-NSCLC with/without oncogenic alterations; as well as novel combinations of chemoradiation and immunotherapy/targeted therapy in unresectable LA-NSCLC. We addressed the unresolved challenges that remain in the field, and examined future directions to optimize clinical management and increase the cure rate of LA-NSCLC.
| S-EPMC10794016 | biostudies-literature
Project description:BackgroundStage III or IVA endometrial cancer carries a significant risk of systemic and locoregional recurrence.MethodsIn this randomized phase 3 trial, we tested whether 6 months of platinum-based chemotherapy plus radiation therapy (chemoradiotherapy) is associated with longer relapse-free survival (primary end point) than six cycles of combination chemotherapy alone in patients with stage III or IVA endometrial carcinoma. Secondary end points included overall survival, acute and chronic toxic effects, and quality of life.ResultsOf the 813 patients enrolled, 736 were eligible and were included in the analysis of relapse-free survival; of those patients, 707 received the randomly assigned intervention (346 received chemoradiotherapy and 361 received chemotherapy only). The median follow-up period was 47 months. At 60 months, the Kaplan-Meier estimate of the percentage of patients alive and relapse-free was 59% (95% confidence interval [CI], 53 to 65) in the chemoradiotherapy group and 58% (95% CI, 53 to 64) in the chemotherapy-only group (hazard ratio, 0.90; 90% CI, 0.74 to 1.10). Chemoradiotherapy was associated with a lower 5-year incidence of vaginal recurrence (2% vs. 7%; hazard ratio, 0.36; 95% CI, 0.16 to 0.82) and pelvic and paraaortic lymph-node recurrence (11% vs. 20%; hazard ratio, 0.43; 95% CI, 0.28 to 0.66) than chemotherapy alone, but distant recurrence was more common in association with chemoradiotherapy (27% vs. 21%; hazard ratio, 1.36; 95% CI, 1.00 to 1.86). Grade 3, 4, or 5 adverse events were reported in 202 patients (58%) in the chemoradiotherapy group and 227 patients (63%) in the chemotherapy-only group.ConclusionsChemotherapy plus radiation was not associated with longer relapse-free survival than chemotherapy alone in patients with stage III or IVA endometrial carcinoma. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00942357.).
| S-EPMC6948006 | biostudies-literature
Project description: Not available
| S-EPMC6543111 | biostudies-literature
Project description:Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors of the head and neck, and it originates from the mucous epithelium of the nasopharynx. Because it is "hidden", the symptoms of NPC can easily be missed, and more than 70% of patients present with locally advanced disease at diagnosis. Concurrent radiation therapy with chemotherapy can significantly improve regional control of NPC. At present, distant metastasis is the main cause of treatment failure. At the end of the 20th century, clinical trial No. IG0099 in the United States confirmed the effectiveness of adjuvant chemotherapy (AC) for the first time. However, in the past 20 years, various clinical trials and meta-analyses conducted globally have yielded contradictory results regarding the effect of AC on locally advanced NPC. AC has changed from category 1 to the current category 2A in the National Comprehensive Cancer Network (NCCN) guidelines, and it remains controversial whether AC can significantly improve the survival of NPC patients. Here, we comprehensively analyzed the role of AC in locally advanced NPC by comparing some treatment methods. We conclude the role of AC in treating locally advanced NPC, based on the studies presented, remains undefined but is associated with increased toxicity.
| S-EPMC7970762 | biostudies-literature
Project description: Not available
| S-EPMC10087986 | biostudies-literature
Project description:During the past 20 years, treatments for head and neck squamous cell carcinoma (HNSCC) have changed dramatically owing largely to the advent of novel approaches such as combined modality therapy as well as improvements in surgical and radiotherapeutic techniques. Locally advanced disease in particular, which engendered very high recurrence and mortality rates, is now associated with long-term disease-free survival in the majority of cases. This article will focus on locally advanced HNSCC, which frequently remains a clinical challenge, review state-of-the-art therapy, and introduce promising novel therapies. The field continues to evolve rapidly with new evidence during the past year clearly establishing the benefit of adjuvant chemoradiotherapy (CRT), as well as early evidence showing improved survival with the use of an epidermal growth factor receptor inhibitor in combination with radiotherapy. There are varied regimens in use for patients with locally advanced disease, but at the same time the multitude of options can plague the clinician when trying to select the most appropriate one. This article will attempt to put the various approaches into perspective and propose an evidence-based treatment algorithm.
| S-EPMC2361996 | biostudies-other
Project description:Non-small cell lung cancer (NSCLC) is the most abundant type of epithelial lung cancer being diagnosed after 40% of invasions of excrescence in pulmonary tissues. According to WHO, 30% of NSCLC patients can be cured if diagnosed and treated early. Mutations play an important role in advanced stage NSCLC treatment, which includes critical proteins necessary for cellular growth and replication. Restricting such mutations may improve survival in lung cancer patients. Newer technologies include endoscopic bronchial ultrasonography and esophageal ultrasonography. Currently, policymaking or decision-making for treatment regimens merely depends on the genomic alterations and mutations. DNA sequencing, methylation, protein, and fragmented DNA analysis do NSCLC screening. Achievement of these goals requires consideration of available therapeutics in current anticancer approaches for improving quality of life and treatment outcomes for NSCLC patient. The specific goals of this review are to discuss first-line and second-line therapies for advanced-stage NSCLC and molecularly targeted therapy including thoughtful discussion on precise role of treatment strategies in specific tumors. Also, concerned diagnostics, new clinical trial designs, and pursuing appropriate combinations of radiotherapy and/or chemotherapy with biological therapy for exceptional cases considering resistance mechanisms and palliative care will be discussed.
| S-EPMC9376330 | biostudies-literature
Project description:BackgroundSurvival with locally advanced bladder cancer (LABC) following radical cystectomy (RC) remains poor. Although adjuvant chemotherapy (AC) is standard of care, one small, randomized trial has suggested a potential survival benefit when combined with post-operative radiotherapy (PORT).ObjectiveWe examined the association of AC + PORT with overall survival (OS) in patients with LABC after RC.MethodsUsing a prior phase 2 trial to inform design, we conducted observational analyses to emulate a hypothetical target trial of patients aged 18-79 years with pT3-4 Nany M0 or pTany N1-3 M0 urothelial bladder carcinoma following RC who were treated with AC (multiagent chemotherapy within 3 months of RC) with or without PORT (≥45 Gy to the pelvis) from 2006-2015 in the NCDB. Patients who received preoperative chemotherapy or radiotherapy were excluded. The associations of treatment with OS were evaluated using multivariable Cox regression.Results1,684 patients were included, with 66 receiving AC + PORT and 1,618 AC alone. Compared to patients treated with AC alone, those treated with AC + PORT were more likely to have pT4 disease (52% vs 26%; p < 0.01), positive surgical margins (44% vs 17%; p < 0.01), and be treated at a non-academic facility (75% vs 53%; p < 0.01). Crude 5-year OS was 19% for AC + PORT versus 36% for AC alone (p = 0.01). Adjusted 5-year OS was 33% for AC + PORT versus 36% for AC alone (p = 0.49). After adjusting for baseline characteristics including pathologic features, AC + PORT was not associated with improved OS compared to AC alone (HR 1.11; 95% CI 0.82-1.51).ConclusionsAlthough infrequently utilized, the addition of radiotherapy to AC is not associated with improved OS in LABC. These results highlight the need for prospective trials to better define the potential benefits from PORT with regard to symptomatic progression and oncologic outcomes.
| S-EPMC11181795 | biostudies-literature
Project description:BackgroundThe optimal timing of radiotherapy (RT) with respect to surgery remains controversial for locally advanced non-small cell lung cancer (LA NSCLC) undergoing surgery and the long-term effect of neoadjuvant RT, adjuvant RT, and chemotherapy-only on survival is unknown.MethodsA retrospective study with Greedy 5 → 1 Digit propensity score matching technique was performed for locally advanced NSCLC patients identified from the Surveillance, Epidemiology, and End Results (SEER) database during 2004 to 2012. Kaplan-Meier and the log-rank test were conducted to compare NSCLC-specific survival. Cox proportional hazards multivariable regression was performed to assess the impact of different treatment regimens on cancer-specific mortality after adjustment for demographic factors, histology type, tumor grade, tumor size, nodal stage, and extent of resection.ResultsOne thousand, two hundred and seventy-eight locally advanced NSCLC patients undergoing surgery were identified after propensity matching. Cox regression analyses showed the risk of cancer-specific mortality is not significantly different among neoadjuvant RT, adjuvant RT, and chemotherapy-only. Subgroup analyses showed that for patients with T1/2 & N2/3, the surgery plus chemotherapy-only group showed markedly higher mortality risk (HR = 1.42, 95%CI:1.10-1.83) than the neoadjuvant RT group. Other risk factors include older age, higher tumor grade, larger tumor size, and greater lymph node involvement.ConclusionsThe findings of this study suggest that the benefit of additional neoadjuvant or adjuvant RT to chemotherapy may be linked to a proper selection of LA NSCLC patients who undergo surgery. The timing of radiotherapy should be decided on the premise of fully considering patients' condition and the quality of life after treatment.
| S-EPMC6219254 | biostudies-literature