Immunotherapy and Radiation Therapy for Non-Small Cell Lung Cancer—A Stimulating Partnership

2020 ◽  
Vol 41 (03) ◽  
pp. 360-368
Author(s):  
Ritchell van Dams ◽  
Ye Yuan ◽  
Clifford G. Robinson ◽  
Percy Lee
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Metastatic Disease ◽  
Cell Lung Cancer ◽  
Early Stage ◽  
Locally Advanced ◽  
Small Cell ◽  
Standards Of Care ◽  
Small Cell Lung ◽  
Early Stage Disease

AbstractNon-small cell lung cancer (NSCLC) is the most common subtype of lung cancer and the leading cause of cancer-related death. Although durable local control rates are high after surgical resection or definitive radiotherapy for early-stage disease, a substantial proportion of these patients eventually experience regional and/or distant failure and succumb to their metastatic disease. The discovery of immunotherapeutics and targeted biologics has revolutionized the treatment of locally advanced and metastatic disease, improving progression-free and overall survival when incorporated with the current standards of care. Notably, post-hoc analyses and early clinical trials provide a growing body of evidence to support a synergistic effect between radiation and immunotherapy for the treatment of NSCLC from early-stage to metastatic disease. Radiotherapy appears to be capable of not only potentiating the effect of immunotherapy in targeted lesions, but also eliciting an antitumor response in distant lesions without any direct exposure to radiation. This review explores the biologic basis of immunotherapy, targeted biologics, and radiotherapy as well as the preclinical and clinical data that support the combined use of radioimmunotherapy for early-stage, locally advanced, and metastatic NSCLC.

A Review of Treatment in Non-small-cell Lung Cancer

2011 ◽  
Vol 07 (03) ◽  
pp. 174 ◽  
Author(s):  
Athanasios G Pallis ◽  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Early Stage ◽  
Performance Status ◽  
Locally Advanced ◽  
Small Cell ◽  
Small Cell Lung ◽  
Early Stage Disease ◽  
Significant Prolongation

Non-small-cell lung cancer (NSCLC) accounts for approximately 85 % of all lung cancer cases. For patients with early-stage disease, surgery followed by adjuvant chemotherapy is the optimal treatment. For patients with locally advanced disease, the standard approach is chemoradiotherapy, since it offers a small but statistically significant prolongation in survival compared with the sequential approach. It should be noted, however, that this approach is associated with significant toxicity and it only applies to patients with good performance status. For patients with metastatic disease, chemotherapy represents the cornerstone of treatment and results in a median survival of approximately 10 months. Recently, the addition of bevacizumab or cetuximab to chemotherapy doublets and the use of gefitinib and erlotinib has improved the outcome in selected patients with advanced NSCLC. Hopefully, advances in understanding the molecular biology of cancer and mechanisms of tumourigenesis will facilitate the discovery and development of novel ‘targeted agents’ and will further improve outcomes for these patients.

A Review of Treatment in Non-small-cell Lung Cancer

2012 ◽  
Vol 08 (04) ◽  
pp. 208 ◽  
Author(s):  
Athanasios G Pallis ◽  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Early Stage ◽  
Performance Status ◽  
Locally Advanced ◽  
Small Cell ◽  
Small Cell Lung ◽  
Early Stage Disease ◽  
Significant Prolongation

Non-small-cell lung cancer (NSCLC) accounts for approximately 85 % of all lung cancer cases. For patients with early-stage disease, surgery followed by adjuvant chemotherapy is the optimal treatment. For patients with locally advanced disease, the standard approach is chemoradiotherapy, since it offers a small but statistically significant prolongation in survival compared with the sequential approach. It should be noted, however, that this approach is associated with significant toxicity and it only applies to patients with good performance status. For patients with metastatic disease, chemotherapy represents the cornerstone of treatment and results in a median survival of approximately 10 months. Recently, the addition of bevacizumab or cetuximab to chemotherapy doublets and the use of gefitinib and erlotinib has improved the outcome in selected patients with advanced NSCLC. Hopefully, advances in understanding the molecular biology of cancer and mechanisms of tumourigenesis will facilitate the discovery and development of novel ‘targeted agents’ and will further improve outcomes for these patients.

scholarly journals Surgery in Small-Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 390
Author(s):  
Nicola Martucci ◽  
Alessandro Morabito ◽  
Antonello La Rocca ◽  
Giuseppe De Luca ◽  
Rossella De Cecio ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Early Stage ◽  
Small Cell ◽  
Stage I ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Early Stage Disease ◽  
Stage Disease

Small-cell lung cancer (SCLC) is one of the most aggressive tumors, with a rapid growth and early metastases. Approximately 5% of SCLC patients present with early-stage disease (T1,2 N0M0): these patients have a better prognosis, with a 5-year survival up to 50%. Two randomized phase III studies conducted in the 1960s and the 1980s reported negative results with surgery in SCLC patients with early-stage disease and, thereafter, surgery has been largely discouraged. Instead, several subsequent prospective studies have demonstrated the feasibility of a multimodality approach including surgery before or after chemotherapy and followed in most studies by thoracic radiotherapy, with a 5-year survival probability of 36–63% for patients with completely resected stage I SCLC. These results were substantially confirmed by retrospective studies and by large, population-based studies, conducted in the last 40 years, showing the benefit of surgery, particularly lobectomy, in selected patients with early-stage SCLC. On these bases, the International Guidelines recommend a surgical approach in selected stage I SCLC patients, after adequate staging: in these cases, lobectomy with mediastinal lymphadenectomy is considered the standard approach. In all cases, surgery can be offered only as part of a multimodal treatment, which includes chemotherapy with or without radiotherapy and after a proper multidisciplinary evaluation.

scholarly journals Multimodality Therapy for Limited-Stage Small-Cell Lung Cancer

2016 ◽  
Vol 12 (2) ◽  
pp. 111-117 ◽  
Author(s):  
Daniel Almquist ◽  
Kailash Mosalpuria ◽  
Apar Kishor Ganti
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Early Stage ◽  
Combined Modality Therapy ◽  
Initial Therapy ◽  
Small Cell ◽  
Small Cell Lung ◽  
Early Stage Disease ◽  
Limited Stage

Limited-stage small-cell lung cancer (SCLC) occurs in only one third of patients with SCLC, but it is potentially curable. Combined-modality therapy (chemotherapy and radiotherapy) has long been the mainstay of therapy for this condition, but more recent data suggest a role for surgery in early-stage disease. Prophylactic cranial irradiation seems to improve outcomes in patients who have responded to initial therapy. This review addresses the practical aspects of staging and treatment of patients with limited-stage SCLC.

scholarly journals Differences in Patterns of Recurrence in Early-Stage Versus Locally Advanced Non-Small Cell Lung Cancer

2014 ◽  
Vol 98 (5) ◽  
pp. 1755-1761 ◽  
Author(s):  
Feiran Lou ◽  
Camelia S. Sima ◽  
Valerie W. Rusch ◽  
David R. Jones ◽  
James Huang
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Early Stage ◽  
Locally Advanced ◽  
Small Cell ◽  
Stage Versus ◽  
Small Cell Lung ◽  
Patterns Of Recurrence

scholarly journals New Perspectives in Different Gene Expression Profiles for Early and Locally Advanced Non-Small Cell Lung Cancer Stem Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Valentina Masciale ◽  
Federico Banchelli ◽  
Giulia Grisendi ◽  
Roberto D’Amico ◽  
Antonino Maiorana ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Early Stage ◽  
Locally Advanced ◽  
Small Cell ◽  
Small Cell Lung ◽  
Advanced Stages

IntroductionLung cancer is one of the most common cancers in the world, causing over 1.7 million deaths in 2018. Thus far, no effective treatments against lung cancer for advanced stages have been found. For early stages, although surgery is considered the gold standard treatment, 30–55% of patients develop recurrence within the first 5 years of surgery. Our aim is to assess whether cancer stem cells (CSC) display overexpression of a pool of genes that were previously identified for adenocarcinoma recurrence in patients with early and locally advanced stages of non-small cell lung cancer (NSCLC).MethodsThis cross-sectional study was carried out by harvesting surgical tumor specimens obtained from patients harboring early (I-II) and locally advanced (IIIA) stages of NSCLC. For each patient, cell sorting was performed to identify and isolate the ALDHhigh (CSC) and ALDHlow (cancer cells) populations. The mRNA expressions of 31 recurrence-related genes (target genes) in both ALDHhigh and ALDHlow populations were then assessed and compared.ResultsSurgical specimens were obtained from 22 patients harboring NSCLC. Sixteen (51.6%) out of 31 recurrence-related genes were significantly overexpressed in ALDHhigh cells in the early stages and 9 (29.0%) were overexpressed in the locally advanced stages of NSCLC. Overall, the relative mRNA expressions for these recurrence-related genes were higher in early-stage patients. The average fold change, considering all 31 recurrence-related genes together, was 4.5 (95% CI = 3.1-6.3) in early-stage patients and 1.6 (95% CI = 1.2-2.2) in locally advanced-stage patients.ConclusionsOur study represents the first attempt toward identifying genes associated with recurrence that are overexpressed in cancer stem cells in patients with early and locally advanced stages of NSCLC. This finding may contribute to the identification of new target therapies tailored for NSCLC stages.

scholarly journals Combination of Bempegaldesleukin and Anti-CTLA-4 Prevents Metastatic Dissemination After Primary Resection or Radiotherapy in a Preclinical Model of Non-Small Cell Lung Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Amber M. Bates ◽  
Ryan J. Brown ◽  
Alexander A. Pieper ◽  
Luke M. Zangl ◽  
Ian Arthur ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Surgical Resection ◽  
Metastatic Disease ◽  
Cell Lung Cancer ◽  
Primary Tumor ◽  
Early Stage ◽  
Small Cell ◽  
Effective Control ◽  
Small Cell Lung

Surgical resection or hypo-fractionated radiation therapy (RT) in early-stage non-small cell lung cancer (NSCLC) achieves local tumor control, but metastatic relapse remains a challenge. We hypothesized that immunotherapy with anti-CTLA-4 and bempegaldesleukin (BEMPEG; NKTR-214), a CD122-preferential IL2 pathway agonist, after primary tumor RT or resection would reduce metastases in a syngeneic murine NSCLC model. Mice bearing Lewis Lung Carcinoma (LLC) tumors were treated with combinations of BEMPEG, anti-CTLA-4, and primary tumor treatment (surgical resection or RT). Primary tumor size, mouse survival, and metastatic disease at the time of death were assessed. Flow cytometry, qRT-PCR, and cytokine analyses were performed on tumor specimens. All mice treated with RT or surgical resection of primary tumor alone succumbed to metastatic disease, and all mice treated with BEMPEG and/or anti-CTLA-4 succumbed to primary tumor local progression. The combination of primary tumor RT or resection and BEMPEG and anti-CTLA-4 reduced spontaneous metastasis and improved survival without any noted toxicity. Flow cytometric immunoprofiling of primary tumors revealed increased CD8 T and NK cells and decreased T-regulatory cells with the combination of BEMPEG, anti-CTLA-4, and RT compared to RT alone. Increased expression of genes associated with tumor cell immune susceptibility, immune cell recruitment, and cytotoxic T lymphocyte activation were observed in tumors of mice treated with BEMPEG, anti-CTLA-4, and RT. The combination of BEMPEG and anti-CTLA-4 with primary tumor RT or resection enabled effective control of local and metastatic disease in a preclinical murine NSCLC model. This therapeutic combination has important translational potential for patients with early-stage NSCLC and other cancers.

Surgery for Early-Stage Small Cell Lung Cancer

2011 ◽  
Vol 9 (10) ◽  
pp. 1132-1139 ◽  
Author(s):  
Bryan J. Schneider ◽  
Ashish Saxena ◽  
Robert J. Downey
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Early Stage ◽  
Small Cell ◽  
Response To Therapy ◽  
Small Cell Lung ◽  
Early Stage Disease ◽  
Limited Stage ◽  
Thoracic Radiation

Limited-stage small cell lung cancer remains one of the more frustrating malignancies to treat. Current standard of care typically includes platinum-based chemotherapy with thoracic radiation, and although response to therapy is high, most patients will ultimately experience relapse and die of recurrent disease. No high-level data exist supporting surgical resection of early-stage disease; however, several retrospective reviews and small single-arm studies suggest surgery may benefit patients with very limited extent of disease. This article reviews the available literature, and proposes guidelines for including potentially curative resection in the management of patients with limited-stage small cell lung cancer.

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