Stage III non-small cell lung cancer: escalation matters, but how?
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ABSTRACT:
SUBMITTER: Hegde AM
PROVIDER: S-EPMC5943225 | biostudies-literature | 2018 Apr
REPOSITORIES: biostudies-literature
Publications
Stage III non-small cell lung cancer: escalation matters, but how?
Hegde Aparna Madhukeshwar AM Walker Paul Raymond PR
Translational lung cancer research 20180401 Suppl 2
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Project description:BackgroundTo explore the maximum tolerated dose (MTD) and evaluate the safety of dose escalation using hypofractionated simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) concurrent with chemotherapy for unresectable stage III non-small cell lung cancer (NSCLC).MethodsFour escalating radiation dose levels were used. This study included 25 patients with previously untreated NSCLC who received six concurrent weekly chemotherapy cycles comprising cisplatin and docetaxel. Dose-limiting toxicity (DLT) was defined as any acute toxicity that interrupted radiotherapy for more than 1 week. MTD was defined as the highest dose level that didn't induce DLT or grade 5 toxicity in two patients.ResultsAll 25 patients received the prescribed escalating radiation dose from the start dose up to LEVEL 4. Two patients experienced DLT at dose LEVEL 4. One patient died because of upper gastrointestinal hemorrhage within 6 months after radiotherapy, whereas another patient among the additional five patients died because of grade 5 radiation pneumonitis within 2 months after radiotherapy. Dose LEVEL 3 was defined as MTD. The 1- and 2-year local controls were 82.8 and 67.8%, respectively. The median progression-free survival was 15.4 months, whereas the median overall survival was 27.3 months.ConclusionsDose escalation was safely achieved up to LEVEL 3 [the planning gross target volume (PTVG) 60.5 Gy/22 Fx, 2.75 Gy/Fx; the planning clinical target volume (PTVC) 49.5 Gy/22 Fx] using SIB-IMRT concurrently with chemotherapy for unresectable stage III NSCLC, and the acute toxicities were generally well tolerated. Further prospective studies on long-term outcomes and late toxicities are warranted.Trial registrationRetrospective registration, ChiCTR1900027290 (08/11/2019).
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Project description:Lung cancer remains the leading cause of cancer-related death with an incidence that continues to increase in both sexes and all ages. However, 80% to 90% of lung cancers are non-small cell lung cancer (NSCLC) and the remaining 10% to 20% are small cell lung cancer. Adenocarcinoma is the most common histologic subtype of lung cancer worldwide. More frequently, lung cancer diagnosis is made in advanced stages. Stage III NSCLC refers to locoregionally advanced disease without metastases and represents about 30% NSCLC cases. Despite the absence of metastases at diagnosis, the outcome is generally poor. Stage III comprises a heterogeneous group and optimal management requires the input of a multidisciplinary team. All modalities of oncologic treatment are involved: surgery, chemotherapy, radiotherapy, and more recently, immunotherapy and targeted therapy. We will discuss the different therapeutic options in stage III NSCLC, both in operable and inoperable scenarios, and the role of immunotherapy and targeted therapy.
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Project description:Until recently, the standard treatment in unresectable stage III non-small cell lung cancer was concurrent chemoradiotherapy, but often with dismal outcome. The introduction of consolidation treatment with immune checkpoint inhibitors has shifted the treatment landscape and prognosis of these patients. However, patients whose tumors harbors an epidermal growth factor receptor (EGFR) mutation derived less benefit, with an increased risk of immune-related adverse events. Moreover, current data suggested that patients with oncogenic addicted tumors, mainly EGFR-positive tumors, and also anaplastic lymphoma kinase (ALK)-positive have poorer progression free survival after chemoradiotherapy. Indeed, these tumors have also inferior distant control compared with those who have wild-type disease, especially in the central nervous system, highlighting the need for assessing the role of targeted therapies in this patient population. It is speculated that outcome could probably increase with a consolidation treatment strategy including an EGFR tyrosine kinase inhibitor. However, a personalized treatment approach is not considered standard of care in this setting due to lack of robust evidence, as the majority of trials were performed in unselected patients, number of patients is limited and the majority of these studies were underpowered. In this review we summarize the role of tyrosine kinase inhibitors in unresectable stage III NSCLC, specifically focusing on EGFR-mutant tumors.
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Project description:Lung cancer remains the most common cause of cancer death across the world. Non-small-cell lung cancer (NSCLC) represents the most frequent type of lung cancer and is frequently diagnosed at an advanced stage. Stage III NSCLC, which encompasses 30% of cases, refers to a state between localized and metastatic disease, and is associated with poor prognosis. As highlighted in this review, stage III represents a heterogenous group, whose complex management includes multimodal treatment, discussed below, and requires discussion in multidisciplinary teams. The goal of this approach is a maximalist attitude in these patients with locally advanced and non-metastatic disease. However, many issues remain under debate including the optimal sequences of treatment between different treatment modalities, patient selection particularly for surgery, the duration of perioperative treatments and the identification of biomarkers to determine which patients might benefit of specific treatment like immunotherapy and targeted therapies. This review describes the current landscape of management of stage III NSCLC, discussing the critical issue of resectability, and highlighting the recent advancements in the field, particularly the incorporation of immune-checkpoint inhibitors (ICIs) and targeted therapies in this setting.
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Project description:Lung cancer is a major cause of cancer deaths worldwide. Non-small-cell lung cancer (NSCLC) represents most lung cancer cases, and approximately one-third of patients present with stage III disease at diagnosis. As multiple treatment plans can be adopted for these patients depending on tumor size and nodal staging, stage III NSCLC management is challenging. Over the past decades, multidisciplinary teams (MDTs) have been implemented in healthcare services to coordinate actions among the different health care professionals involved in cancer care. The aim of this review was to discuss real-world evidence of the impact of MDTs on stage III NSCLC management, survival, and quality of life. Here, we performed a literature review to investigate the role of nutrition and navigational nursing in NSCLC care and the influence of MDTs in the choice of treatment plans, including immunotherapy consolidation, and in the management of chemotherapy and radiotherapy-related adverse events. We also performed a mapping review to identify gaps in the implementation of cancer care MDTs in healthcare services around the world.
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