Search Results (40)

Oligometastatic non-small cell lung cancer (omNSCLC) is increasingly recognized as a clinically actionable subset, characterized by a limited number of metastatic lesions and the potential to benefit from combined systemic and local treatments. Advances in systemic therapy, particularly immune checkpoint inhibitors (ICI) and molecular targeted agents, have led to prolonged disease control in selected patients. Prospective clinical trials have shown that incorporating local therapy into systemic treatment can improve progression-free and overall survival outcomes in carefully selected patients with metastatic disease. Radiotherapy has increasingly become the preferred modality for local consolidation, especially when surgical options are limited or impractical. Key factors influencing treatment selection include biomarker status, the number and distribution of metastases, and the response to the initial systemic therapy. The optimal timing and modality of local interventions remain under investigation. This review examines the evolving treatment strategies for omNSCLC, primarily from the perspective of systemic therapies. By contextualizing local treatment modalities within the framework of immunotherapy and targeted therapy, we reinterpret current evidence to clarify when and how local therapy contributes to long-term disease control. Full article

Systemic chemotherapy is a standard treatment for patients with stage IV cancer with distant metastases, and there is little evidence of the effectiveness of local treatments for distant metastatic lesions. However, in recent years, randomized phase II trials targeting oligometastases in lung cancer and solid tumors have reported that local therapy combined with systemic chemotherapy improves clinical outcomes. We reviewed previous clinical trials and demonstrated the efficacy of radiotherapy for oligometastatic disease. Stereotactic body radiotherapy (SBRT) is a promising treatment that achieves high local control rates for oligometastatic disease. Although SBRT generally does not cause severe adverse events, the safety of SBRT combined with systemic chemotherapy needs to be carefully considered. We discussed the efficacy and safety of SBRT and summarized the details of SBRT methods and techniques for each metastatic site. Further research and clinical trials are warranted to improve the efficacy of SBRT combined with systemic chemotherapy for oligometastatic non-small cell lung cancer (NSCLC). Full article

Introduction: Radiomics is the extraction of non-invasive and reproducible quantitative imaging features, which may yield mineable information for clinical practice implementation. Quantification of lung function through radiomics could play a role in the management of patients with pulmonary lesions. The aim of this study is to test the capability of radiomic features to predict pulmonary function parameters, focusing on the diffusing capacity of lungs to carbon monoxide (DL_CO). Methods: Retrospective data were retrieved from electronical medical records of patients treated with Stereotactic Body Radiation Therapy (SBRT) at a single institution. Inclusion criteria were as follows: (1) SBRT treatment performed for primary early-stage non-small cell lung cancer (ES-NSCLC) or oligometastatic lung nodules, (2) availability of simulation four-dimensional computed tomography (4DCT) scan, (3) baseline spirometry data availability, (4) availability of baseline clinical data, and (5) written informed consent for the anonymized use of data. The gross tumor volume (GTV) was segmented on 4DCT reconstructed phases representing the moment of maximum inhalation and maximum exhalation (Phase 0 and Phase 50, respectively), and radiomic features were extracted from the lung parenchyma subtracting the lesion/s. An iterative algorithm was clustered based on correlation, while keeping only those most associated with baseline and post-treatment DL_CO. Three models were built to predict DL_CO abnormality: the clinical model—containing clinical information; the radiomic model—containing the radiomic score; the clinical-radiomic model—containing clinical information and the radiomic score. For the models just described, the following were constructed: Model 1 based on the features in Phase 0; Model 2 based on the features in Phase 50; Model 3 based on the difference between the two phases. The AUC was used to compare their performances. Results: A total of 98 patients met the inclusion criteria. The Charlson Comorbidity Index (CCI) scored as the clinical variable most associated with baseline DL_CO (p = 0.014), while the most associated features were mainly texture features and similar among the two phases. Clinical-radiomic models were the best at predicting both baseline and post-treatment abnormal DL_CO. In particular, the performances for the three clinical-radiomic models at predicting baseline abnormal DL_CO were AUC₁ = 0.72, AUC₂ = 0.72, and AUC₃ = 0.75, for Model 1, Model 2, and Model 3, respectively. Regarding the prediction of post-treatment abnormal DL_CO, the performances of the three clinical-radiomic models were AUC₁ = 0.91, AUC₂ = 0.91, and AUC₃ = 0.95, for Model 1, Model 2, and Model 3, respectively. Conclusions: This study demonstrates that radiomic features extracted from healthy lung parenchyma on a 4DCT scan are associated with baseline pulmonary function parameters, showing that radiomics can add a layer of information in surrogate models for lung function assessment. Preliminary results suggest the potential applicability of these models for predicting post-SBRT lung function, warranting validation in larger, prospective cohorts. Full article

Oligometastatic non-small-cell lung cancer (OMD-NSCLC) has emerged as a biologically and clinically distinct subtype of advanced disease, characterized by limited metastatic burden and a more indolent course. In this narrative review, we examine the current definition of OMD-NSCLC, diagnostic tests, possible biomarkers, and current therapeutic strategies. Biological insights highlight the role of microRNAs in differentiating true oligometastatic state from polymetastatic disease. The main local ablative therapies (LAT) include surgery and radiotherapy. The integration of LAT with systemic therapies has been explored in clinical trials, yielding promising but occasionally inconsistent results. As the therapeutic landscape of OMD-NSCLC patients continues to evolve, refining definitions, identifying predictive biomarkers, and individualizing care are essential steps toward achieving the potential of radical-intent therapy. Full article

Purpose/Objective(s): Peritoneal carcinosis can occur in several gastrointestinal or gynecological malignancies and its prognosis is usually poor. With the advent of more effective systemic agents, the overall survival of metastatic patients has been revolutionized and isolated peritoneal or abdominal wall metastases might benefit from local treatments; Stereotactic Body Radiotherapy (SBRT) might be considered in selected patients with oligometastatic presentation. Materials/Methods: Oligometastases were defined according to recent ESTRO/EORTC consensus. Inclusion criteria were as follows: ECOG PS ≤ 2, written informed consent, up to five lesions to be treated at the same time, patients treated with radiotherapy schedules applying minimum 6 Gy per fraction. The primary endpoint of the study was local control (LC); acute and late toxicity, distant progression-free survival (DPFS), time-to-next systemic treatment (TNST), polymetastatic-free survival (PMFS) and overall survival (OS) were secondary endpoints. Toxicity was assessed according to CTCAE criteria v5.0. Statistical associations between clinical variables and outcomes were assessed using Fisher’s exact test, and Kruskal–Wallis test, as appropriate. Survival outcomes were estimated using the Kaplan–Meier method and compared using the log-rank test. Results: Between April 2020 and September 2024 a total of 26 oligometastatic lesions located in the peritoneum or in the abdominal wall detected in 20 patients received SBRT with Helical Tomotherapy. All cases have been assessed by a multidisciplinary team. Only in three patients out of twenty did more than one lesion receive SBRT: two lesions in two patients, and five lesions in a single case of colorectal cancer with ongoing third-line systemic treatment. Median total dose was 30 Gy (27–35 Gy) in five fractions (3–5). The most frequent primary neoplasm was ovarian cancer in 14/20, endometrial in 2/20, while the remaining were colorectal, vaginal, pancreatic and non-small cell lung cancer. Four lesions were located in the abdominal wall, while the remaining twenty-two were located in the peritoneum. Concurrent systemic therapy was administered in 18/20 patients. With a median follow-up of 15 months (range, 6–59), our 1-year LC was 100%, while 1-year DPFS, PMFS, TNTS and OS rates were 54%, 69%, 61% and 83%, respectively. Abdominal wall location and treatment of a subsequent oligometastatic recurrence with a second course of SBRT were both significantly associated with improved OS (p = 0.03 and p = 0.04, respectively). No G ≥ 3 adverse events occurred. Conclusion: Our preliminary data support the use of SBRT in selected cases of oligometastatic disease located in the peritoneum or in the abdominal wall with excellent results in terms of tolerability and promising clinical outcomes. Full article

Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) have shown clinical activity for patients with EGFR-mutated non-small-cell lung cancer (NSCLC). However, the development of resistance to EGFR-TKIs is almost inevitable, posing a significant barrier to long-term survival. Local ablative therapy (LAT) may facilitate the prolonged survival of patients with oligometastatic NSCLC. Therapeutic combinations of EGFR-TKIs and LAT for residual disease have been suggested to be potentially effective in EGFR-mutated NSCLC with induced oligometastatic disease, wherein a few lesions remain following initial EGFR-TKI treatment. Various resistance pathways for third-generation EGFR-TKIs including osimertinib, current standard of care for patients with EGFR-mutated NSCLC, have also been identified. In addition to resistance mechanisms, the disease-progression pattern may be an essential element for achieving long-term response and survival. Oligo-progressive disease is a state in which only a few lesions become resistant, whereas many lesions remain controlled with effective systemic therapy. Previous studies have shown that LAT for all oligo-progressive lesions could provide survival benefits. This review discusses the current treatment options and potential future therapeutic developments for patients with EGFR-mutated NSCLC who have synchronous oligometastatic disease, oligo-residual disease during treatment with EGFR-TKIs, and oligo-progressive disease following resistance to EGFR-TKIs. Full article

Background: Oligometastatic non-small cell lung cancer (NSCLC) represents a biologically and clinically distinct state characterized by limited metastatic spread. Increasing evidence suggests that aggressive local therapies, including surgical resection, may confer a survival benefit in this population. The objective of this review is to evaluate the current role of surgery in the management of oligometastatic NSCLC, with emphasis on patient selection, surgical strategy, integration with systemic therapy, and ongoing clinical investigations. Methods: This narrative review synthesizes retrospective and prospective clinical data, meta-analyses, major consensus guidelines, and ongoing trials since 2012. We highlight prognostic factors, staging strategies, and the evolving role of molecular and biomarker-based stratification. Results: Multiple retrospective studies and several randomized trials have demonstrated improved progression-free and overall survival with local consolidative therapy in oligometastatic NSCLC. Prognostic factors associated with favorable outcomes include a limited number of metastases (≤3), good performance status, absence of mediastinal nodal disease, metachronous presentation, and actionable molecular alterations. The integration of surgery with systemic therapies, including targeted agents and immunotherapy, has become increasingly common in selected patients. Ongoing trials such as LONESTAR, NORTHSTAR, and BRIGHTSTAR are expected to further define the role of surgery in this setting. Conclusions: Surgery is emerging as a key component of multimodal treatment for carefully selected patients with oligometastatic NSCLC. Future efforts should focus on refining patient selection through molecular stratification and expanding prospective trial data to guide personalized biology-driven treatment strategies. Full article

Background/Objectives: Lung cancer is the leading cause of cancer-related mortality worldwide. Accurate radiotherapy (RT) planning alongside chemotherapy and immunotherapy is critical for improving treatment outcomes for inoperable non-metastatic cases. Conventional computed tomography (CT)-based planning may be inadequate for accurately identifying tumor margins and the location of nodal disease. We investigated whether ¹⁸F-labeled fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET-CT) imaging can assist in target volume delineation for primary, nodal, and metastatic disease in the RT planning and overall therapeutic planning of patients. Methods: In this single-center, prospective study, we recruited 34 patients with histologically confirmed locally advanced non-small-cell lung carcinoma (NSCLC). All patients underwent ¹⁸F-FDG PET-CT-based RT simulation. Two sequential RT plans were created by the same radiation oncologist: one based on CT alone and the other PET-CT. Planning target volumes (PTVs) and PET-CT-guided adjustments were analyzed to assess their impact. Standardized protocols for immobilization, imaging, target delineation, and dose prescription were applied. Results: A total of 34 patients (31 males and 3 females) were recruited in the study. ¹⁸F-FDG PET-CT detected distant metastases in 7/34 (20.6%) patients, altering the overall therapeutic plan in 4/34 (11.8%) and allowing radical RT in 3 of them who had oligometastatic disease (8.8%). It modified RT planning in 26/34 (76.5%) patients and clarified malignancy in atelectatic areas. Nodal involvement was identified in 3/34 patients (8.8%) and excluded in 3/34 cases, avoiding unnecessary nodal irradiation. Additional involved nodes were revealed in 12/34 (35.3%) patients, requiring dose escalation. Overall, changes to the tumor PTV were made in 23/30 (76.6%) and to the nodal PTV in 19/30 (63.3%) cases (p < 0.0001). Primary tumor and nodal PTVs increased in 20/34 (66.7%) and 13/34 (43.3%), respectively. Conclusions: ¹⁸F-FDG PET-CT significantly improves RT planning by more precisely defining tumor and nodal volumes, identifying undetected lesions, and guiding dose adaptation. Larger long-term studies are required to confirm potential locoregional control and survival improvements. Full article

Background: Advances in the treatment of non-small cell lung cancer in the last 5 years (new techniques in radiotherapy, including stereotactic ablative radiotherapy, new targeted therapies and advances in immunotherapy) have increased the survival rates of patients diagnosed with this disease. Methods: Our study refers to a patient diagnosed in July 2017 with stage IV A lung cancer, cT3 N3 M1b (poorly differentiated adenocarcinoma, EGFR, ALK and PDL 1 negative), who underwent five lines of treatment and who has, at the time of writing this article (March 2025), a very good performance status, currently undergoing maintenance chemotherapy. Results: The results obtained confirm the revolutionary role of immunotherapy, but also the importance of chemotherapy and external radiotherapy, suggesting the synergistic effect between these three therapies. We also performed a literature review, highlighting the resistance to immunotherapy, rechallenge with immunotherapy, progression of metastatic NSCLC after first-line chemo-immunotherapy and the role of chemotherapy in line II and III after progression of NSCLC to immunotherapy. Conclusions: Results of studies evaluating new agents and their combinations, along with analysis of the mechanisms of evolution of primary and acquired resistance to immunotherapy are awaited, with the aim of selective and personalized treatment options to improve the survival and the quality of life for this category of patients. Full article

Oligoprogressive disease refers to the setting of a prior or ongoing receipt of systemic therapy, with typically up to three metastatic areas having increased in size and/or avidity compared to the start of the systemic therapy. The role of local ablative therapy (LAT) including radiation has mostly been evaluated in the oligometastatic setting with limited data in oligoprogression. A similar principle of using ablative radiation in the oligometastatic setting may be applied to consolidative therapy for oligoprogressive disease. If systemic therapy can control the majority of the disease, and a few areas of therapy-resistant clones continue to proliferate, then potentially controlling those few resistant clones while maintaining systemic control may be beneficial. Doing so may also extend the duration of benefit of the systemic therapy and reserve next systemic line options at a later point, and potentially improve progression free survival (PFS). Here, we review the current data evaluating the role of radiation in oligoprogressive non-small cell lung cancer (NSCLC) and ongoing trials. Full article

Oligometastatic non-small cell lung cancer (NSCLC) represents a separate entity with a different biology and prognosis compared to stage IV NSCLC. Challenges range from the very definition of oligometastatic disease to the timing and techniques of local treatments, and their benefit in prolonging patient survival. Most of the international consensus and guidelines agree on the need for shared criteria, such as appropriate stadiation and even tissue biopsy if needed, in order to select patients that could really benefit from personalised strategies. Multidisciplinary evaluation is crucial in order to define if every lesion is amenable to radical local treatment, which appears to be the most important criterion across different guidelines. A distinction must be made depending on the time of oligo-disease detection, separating de novo oligometastatic disease from oligorecurrence, oligoprogression and oligoresidual disease. These separate entities imply a different biology and prognosis, and treatment strategies consequently must be tailored. Locoregional approaches are therefore often contemplated in order to ensure the best outcome for the patient. In non-oncogene-addicted disease, the advent of immune checkpoint blockers (ICBs) allows physicians to take into consideration consolidative treatments, but timing, technique and subsequent systemic treatment remain open issues. In oncogene-addicted NSCLC, local treatments are nowadays preferably reserved to cases of oligoprogression, but the advent of new, more potent drugs might challenge that. In this review, we summarised the current knowledge, consensuses and data from retrospective and prospective trials, with the aim of shedding some light on the topic and emphasising the unmet clinical need. Full article

Non-small cell lung cancer (NSCLC) is a major cause of mortality in Canada, with many patients presenting with metastatic disease. The oligometastatic state (OM-NSCLC) may be amenable to cure using aggressive local consolidative therapies. Stereotactic body radiotherapy (SBRT), which entails the utilization of a high dose of radiation in one or few fractions, has many benefits in this setting, including its applicability in varied patient populations to ablate lesions in varied anatomical locations. It has also been demonstrated to prolong the time to next-line systemic therapy, to reduce financial burden, to improve quality-adjusted life years, and reduce adverse events caused by these lesions. This review outlines the published phase II and III trials that have already demonstrated the utility of SBRT in OM-NSCLC, as well as the many ongoing trials aiming to further define its role, including the largest phase II/III trial to date, NRG-LU002. Overall, SBRT appears to improve outcomes when combined with a broad range of standard-of-care therapies and is generally well tolerated; however, careful patient selection is necessary to maximize benefits while minimizing harm. Ongoing trials will help define the optimal patients for SBRT and the best timing for this intervention. Full article

Stereotactic body radiotherapy has been established as a viable treatment option for inoperable early-stage non-small cell lung cancer or secondary lesions mainly in oligoprogressive/oligometastatic scenarios. Treating lesions in the so-called “no flight zone” has always been challenging and conflicting data never cleared how to safely treat these lesions. This is truer considering ultra-central lesions, i.e., directly abutting or whose PTV is overlapping critical mediastinal organs. While historical retrospective data are abundant but mostly heterogenous in terms of the definition of ultra-central lesions, dosing regimens and outcomes, prospective data remain scarce, even though recently published studies have given new encouraging results for such delicate treatment scenarios. For this reason, we aimed to review and summarize current knowledge on stereotactic radiation treatment for ultra-central thoracic lesions, highlighting the most recent advances and the messages that can be taken from them. Lastly, we propose a workflow of the necessary steps to identify and treat such patients, therefore helping in elucidating the advantages and caveats of such treatment options. Full article

In the era of immune checkpoint inhibitors (ICI), managing non-oncogene driven non-small cell lung cancer (NSCLC) with brain metastases (BM) is challenging, especially when brain involvement is the initial sign. Patients with newly diagnosed brain metastatic NSCLC without epidermal growth factor receptor (EFGR) nor anaplastic lymphoma kinase (ALK) alterations were retrospectively included. Twenty-five patients were analyzed; 15 (60%) had symptomatic BM as the first sign (group 1), while 10 (40%) had BM discovered during complementary examinations (group 2). Fourteen patients (56%) had concomitant extracerebral metastases, primarily in group 2. Eight (32%) had oligometastatic disease, with seven in group 1. Over half received chemotherapy and pembrolizumab as first-line treatment. BM surgical resection occurred in twelve (80%) patients in group 1 and one in group 2. Median cerebral progression-free survival was 10 months: 12 in group 1 and 5 in group 2. Median overall survival was 25 months: not reached in group 1 and 6 months in group 2. This case series highlights survival outcomes for patients with inaugural BM, a demographic underrepresented in pivotal trials. Oligometastatic disease and symptomatic BM as initial signs seem associated with better prognosis due to increased use of multimodal local approaches. Combining local approaches with first-line ICI+/− chemotherapy appears to improve survival in brain metastatic NSCLC. A literature review was conducted to explore key questions regarding upfront ICI alone or in combination with systemic drugs or local approaches in brain metastatic NSCLC. Full article

Background: Platinum-based chemotherapy is the current standard treatment option in patients with EGFR-mutant non-small-cell lung cancer (NSCLC) who progress on osimertinib. However, outcomes with chemotherapy are dismal, and the treatment of central nervous system (CNS) disease is an unmet need in this setting. Methods: Patients with EGFR-mutant NSCLC who were candidates to receive osimertinib in the metastatic setting at our Center from 2015 to 2022 were retrospectively evaluated to identify patients who received standard platinum-based chemotherapy post-osimertinib. Data were collected on treatment outcomes, with a focus on brain metastases and progression patterns. Results: A total of 220 patients received indication for osimertinib in the study period; n = 176 had adequate follow-up data. Overall, n = 117 patients experienced disease progression on osimertinib. The median time to osimertinib progressive disease (PD) was 15 months (95% confidence interval CI 13–18). Of them, 51 patients (45%) had no access to further treatments. Of the remaining patients, n = 8 received experimental treatments, and n = 55 received standard platinum-based chemotherapy and were considered for this study. Median duration of chemotherapy was 3 months (95% CI 2–5); the best responses among 53 evaluable patients were observed as follows: 15% partial response/complete response (PR/CR), 40% stable disease (SD), 45% PD. Median progression-free survival (PFS) and overall survival (OS) were 3 (95% CI 2–5) and 10 (95% CI 6–15) months, respectively. All patients had baseline and follow-up brain radiologic assessments, and n = 23 had brain metastases at the start of chemotherapy. With a median follow-up of 13 months, intracranial PD occurred in 47% patients, being the first site of PD in 59% of cases. The median time for intracranial (IC) PD was 2 months (95% CI 2–7). IC PD occurred as oligometastatic in 29%, whereas in 71% of cases, it was associated with systemic PD. Conclusions: Access to subsequent treatments and CNS progression are confirmed unmet needs in EGFR-mutant NSCLC patients. Clinical and CNS-specific outcomes in patients receiving standard chemotherapy after the failure of osimertinib are dismal. Novel upfront treatment options with demonstrated prolonged PFS and better CNS outcomes may help address this important issue. Full article