Oligoprogression in the Non-small Cell Lung Cancer (NSCLC)

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (15 September 2022) | Viewed by 13791

Special Issue Editors


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Guest Editor
Medical Thoracic Oncology Unit, IRCCS Istituto Tumori “Giovanni Paolo II”, Bari, Italy
Interests: lung cancer; pleural mesothelioma; tobacco control and prevention; immunotherapy

E-Mail Website
Guest Editor
Medical Thoracic Oncology Unit, IRCCS Istituto Tumori “Giovanni Paolo II”, Bari, Italy
Interests: lung cancer; pleural mesothelioma; tobacco control and prevention; immunotherapy; breath analysis
Special Issues, Collections and Topics in MDPI journals
Medical Thoracic Oncology Unit, IRCCS Istituto Tumori “Giovanni Paolo II”, Bari, Italy
Interests: lung cancer; pleural mesothelioma; tobacco control and prevention; immunotherapy; small-cell lung cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Oligoprogressive disease in non-small cell lung cancer (NSCLC) consists of progression at only a few sites of metastasis in patients with otherwise controlled widespread disease. Several genomic studies have revealed a distinct clonal evolution at each site of metastatic disease inducing treatment resistance or increased metastatic potential independent of the primary site of disease or even other metastatic sites. Therefore, these patients with progression limited to only a few sites of disease may warrant treatment with a local approach. In particular, local ablative therapy for oligoprogressive disease may allow for the continuation of systemic treatments by overcoming the few sub-clones that have developed resistance. Of the ablative therapies for oligoprogressive disease, stereotactic body radiotherapy is now frequently used to treat the metastatic site of NSCLC oligoprogression using ablative doses with minimally invasive techniques and acceptable toxicity. However, surgery, transpulmonary chemoembolization, radiofrequency ablation, and cryoablation are also under development. An oligoprogressive state is initially described in patients with oncogene-addicted NSCLC treated due to the clonal heterogeneity and extrinsic selection pressure induced by targeted therapy. Nevertheless, for some years now the concept of oligoprogression has also been under investigation in NSCLC patients treated with immunotherapy, where the use of ablative radiotherapy for oligoprogressive sites can also be associated with an abscopal response in untreated lesions. This Special Issue focuses on the biology of oligoprogressive NSCLC and the multidisciplinary approaches able to treat this condition.

Dr. Domenico Galetta
Dr. Annamaria Catino
Dr. Vito Longo
Guest Editors

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Keywords

  • brain metastasis
  • adrenal metastasis
  • oligoprogression
  • lung metastasis
  • liver metastasis
  • bone metastasis
  • target therapy
  • immunotherapy

Published Papers (5 papers)

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Research

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14 pages, 1417 KiB  
Article
Role of Radiosurgery and Stereotactic Ablative Radiotherapy for Oligometastatic Non-Oncogene Addicted NSCLC
by Serena Badellino, Mario Levis, Erica Maria Cuffini, Marzia Cerrato, Erika Orlandi, Ilaria Chiovatero, Arianna Aprile, Alessio Gastino, Chiara Cavallin, Giuseppe Carlo Iorio, Ramona Parise, Cristina Mantovani and Umberto Ricardi
Cancers 2022, 14(6), 1465; https://doi.org/10.3390/cancers14061465 - 12 Mar 2022
Viewed by 1766
Abstract
Local ablative therapy (LAT), intended as stereotactic ablative radiotherapy or stereotactic radiosurgery, is a well-recognized effective treatment for selected patients with oligometastatic NSCLC. Current clinical evidence supports LAT alone or in combination with systemic therapies. Our retrospective mono-institutional study aims to assess the [...] Read more.
Local ablative therapy (LAT), intended as stereotactic ablative radiotherapy or stereotactic radiosurgery, is a well-recognized effective treatment for selected patients with oligometastatic NSCLC. Current clinical evidence supports LAT alone or in combination with systemic therapies. Our retrospective mono-institutional study aims to assess the role of LAT with a peculiar focus on the largest series of non-oncogene addicted oligometastatic NSCLC patients to date. We included in this analysis all patients with the mentioned disease characteristics who underwent LAT for intracranial and/or extracranial metastases between 2011 and 2020. The main endpoints were local control (LC), progression free survival (PFS) and overall survival (OS) in the whole population and after stratification for prognostic factors. We identified a series of 245 consecutive patients (314 lesions), included in this analysis (median age 69 years). In 77% of patients, a single metastasis was treated with LAT and intracranial involvement was the most frequent indication (53% of patients) in our series. The overall response rate (ORR) after LAT was 95%. In case of disease progression, 66 patients underwent new local treatments with curative intent. With a median follow-up of 18 months, median PFS was 13 months (1-year PFS 50%) and median OS was 32 months (1-year OS 75%). The median LC was not reached (1-year LC 89%). The presence of brain metastases was the only factor that negatively affected all clinical endpoints, with a 1-year LC, PFS and OS of 82%, 29% and 62% respectively, compared to 95%, 73% and 91%, respectively, for patients without BMs (p < 0.001 for each endpoint). At the multivariate analysis, mediastinal nodal involvement at baseline (p = 0.049), ECOG PS = 1 (p = 0.011), intracranial disease involvement (p = 0.001), administration of chemotherapy in combination with LAT (p = 0.020), and no delivery of further local treatment for progression or delivery of focal treatment for intracranial progression (p < 0.001) were related to a poorer OS. In our retrospective series, which is to our knowledge the largest to date, LAT showed encouraging results and confirmed the safety and effectiveness of focal treatments in non-oncogene addicted oligometastatic NSCLC patients. Full article
(This article belongs to the Special Issue Oligoprogression in the Non-small Cell Lung Cancer (NSCLC))
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24 pages, 2608 KiB  
Article
Prediction of Microscopic Metastases in Patients with Metachronous Oligo-Metastases after Curative Treatment of Non-Small Cell Lung Cancer: A Microsimulation Study
by Henri B. Wolff, Leonie Alberts, Elisabeth A. Kastelijn, Naomi E. Verstegen, Sherif Y. El Sharouni, Franz M. N. H. Schramel, Rein Vos and Veerle M. H. Coupé
Cancers 2021, 13(8), 1884; https://doi.org/10.3390/cancers13081884 - 14 Apr 2021
Cited by 1 | Viewed by 1776
Abstract
Metachronous oligo-metastatic disease is variably defined as one to five metastases detected after a disease-free interval and treatment of the primary tumour with curative intent. Oligo-metastases in non-small cell lung cancer (NSCLC) are often treated with curative intent. However additional metastases are often [...] Read more.
Metachronous oligo-metastatic disease is variably defined as one to five metastases detected after a disease-free interval and treatment of the primary tumour with curative intent. Oligo-metastases in non-small cell lung cancer (NSCLC) are often treated with curative intent. However additional metastases are often detected later in time, and the 5-year survival is low. Burdensome surgical treatment in patients with undetected metastases may be avoided if patients with a high versus low risk of undetected metastases can be separated. Because there is no clinical data on undetected metastases available, a microsimulation model of the development and detection of metastases in 100,000 hypothetical stage I NSCLC patients with a controlled primary tumour was constructed. The model uses data from the literature as well as patient-level data. Calibration was used for the unobservable model parameters. Metastases can be detected by a scheduled scan, or an unplanned scan when the patient develops symptoms. The observable information at time of detection is used to identify subgroups of patients with a different risk of undetectable metastases. We identified the size and number of detected oligo-metastases, as well as the presence of symptoms that are the most important risk predictors. Based on these predictors, patients could be divided into a low-risk and a high-risk group, having a model-based predicted probability of 8.1% and 89.3% to have undetected metastases, respectively. Currently, the model is based on a synthesis of the literature data and individual patient-level data that were not collected for the purpose of this study. Optimization and validation of the model is necessary to allow clinical usability. We describe the type of data that needs to be collected to update our model, as well as the design of such a validation study. Full article
(This article belongs to the Special Issue Oligoprogression in the Non-small Cell Lung Cancer (NSCLC))
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Review

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11 pages, 569 KiB  
Review
Systemic Therapy for Oligoprogression in Patients with Metastatic NSCLC Harboring Activating EGFR Mutations
by Antonio Rossi and Domenico Galetta
Cancers 2022, 14(3), 832; https://doi.org/10.3390/cancers14030832 - 6 Feb 2022
Cited by 6 | Viewed by 2719
Abstract
After a variable period of activity of the epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment, patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR mutations develop resistance to these TKIs. In some cases, an oligoprogression is diagnosed, and its management [...] Read more.
After a variable period of activity of the epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment, patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR mutations develop resistance to these TKIs. In some cases, an oligoprogression is diagnosed, and its management is still controversial. The oligoprogression represents an intermediate stage of metastatic NSCLC between localized and widely disseminated disease, and is characterized by a limited number and/or sites of metastases in which a disease progression appears, together with a more indolent tumor biology. Currently, the management of oligoprogressed NSCLC involves local treatment, including radiotherapy and/or surgery, to control the progressive lesions. Systemic therapy should also be a potential approach to boost the activity of EGFR-TKIs. However, considering the lack of large trials addressing this topic, the optimal therapeutic strategies remain undefined and should be evaluated on an individualized basis. In this paper, we review the most relevant scientific evidence of continuing the systemic therapy with the same EGFR-TKI for the management of patients with NSCLC harboring EGFR mutations and oligoprogressed to first-line EGFR-TKIs, also discussing the controversies and potential future directions. Full article
(This article belongs to the Special Issue Oligoprogression in the Non-small Cell Lung Cancer (NSCLC))
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14 pages, 464 KiB  
Review
Management of Oligoprogression in Patients with Metastatic NSCLC Harboring ALK Rearrangements
by Chiara Pisano, Marco De Filippis, Francesca Jacobs, Silvia Novello and Maria Lucia Reale
Cancers 2022, 14(3), 718; https://doi.org/10.3390/cancers14030718 - 30 Jan 2022
Cited by 6 | Viewed by 3455
Abstract
Personalized treatment based on driver molecular alterations, such as ALK rearrangement, has revolutionized the therapeutic management of advanced oncogene-addicted NSCLC patients. Multiple effective ALK tyrosine kinase inhibitors (TKIs), with the amelioration of the activity at central nervous system level, are now available, leading [...] Read more.
Personalized treatment based on driver molecular alterations, such as ALK rearrangement, has revolutionized the therapeutic management of advanced oncogene-addicted NSCLC patients. Multiple effective ALK tyrosine kinase inhibitors (TKIs), with the amelioration of the activity at central nervous system level, are now available, leading to substantial prognosis improvement. The exposure to TKIs triggers resistance mechanisms and the sequential administration of other TKIs and chemotherapy is, for the most part, not targeted. In this context, extending the benefit deriving from precision medicine is paramount, above all, when disease progression occurs in a limited number of sites. Retrospective data indicate that, in oligoprogressive disease, targeted therapy beyond progression combined with definitive local treatment of the progressing site(s) is an effective alternative. In these cases, a multidisciplinary approach becomes essential for an integrated treatment strategy, depending on the site of disease progression, in order to improve not only survival, but also quality of life. In this review we provide an updated and comprehensive overview of the main treatment strategies in cases of ALK rearranged oligoprogression, including systemic treatment as well as local therapy, and report a real-world clinical story, with the final aim of identifying the most promising management for this subset of patients. Full article
(This article belongs to the Special Issue Oligoprogression in the Non-small Cell Lung Cancer (NSCLC))
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12 pages, 268 KiB  
Review
Oligoprogression in Non-Small Cell Lung Cancer
by Daijiro Harada and Nagio Takigawa
Cancers 2021, 13(22), 5823; https://doi.org/10.3390/cancers13225823 - 20 Nov 2021
Cited by 12 | Viewed by 2794
Abstract
We reviewed the literature on oligoprogressive disease (OPD) and local ablative therapy (LAT) in patients with advanced non-small cell lung cancer (NSCLC). The frequency of OPD varies depending on its definition and is estimated to be between 15–47%. The implications of the strategy [...] Read more.
We reviewed the literature on oligoprogressive disease (OPD) and local ablative therapy (LAT) in patients with advanced non-small cell lung cancer (NSCLC). The frequency of OPD varies depending on its definition and is estimated to be between 15–47%. The implications of the strategy of continuing the same anticancer agents beyond progressive disease after LAT with radiation therapy for OPD are based on the concept of progression in which only a small number of lesions, not more than about four, proliferate after chemotherapy. In the case of OPD harboring driver mutations such as EGFR, prospective studies are underway. However, evidence from retrospective studies support this strategy, which is currently recommended in some guidelines. The prognosis in OPD cases during the administration of an immune checkpoint inhibitor (ICI) is relatively promising. Additionally, LAT with radiation for OPD after the first-line treatment of ICI with cytotoxic chemotherapy may overcome the resistance to the combination drug therapy due to an abscopal effect. To achieve long-term survival in advanced-stage NSCLC, it is important to verify the optimal method and timing of the therapy through prospective comparative studies as well as patient selection based on patient characteristics and biomarker levels. Full article
(This article belongs to the Special Issue Oligoprogression in the Non-small Cell Lung Cancer (NSCLC))
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